PA Endocrinology Bootcamp — Complete Syllabus

By the end of this bootcamp, you must be able to:

Mastery Contract · 15 Objectives

01Diagnose diabetes and prediabetes from A1c, fasting, OGTT, and random glucose thresholds, and know who to screen.

02Choose the second diabetes drug by comorbidity (SGLT2i for HF/CKD, GLP-1 RA for ASCVD/obesity, insulin when catabolic or A1c >10%).

03Manage DKA and HHS in the correct order: fluids → potassium check → insulin → dextrose → gap closure with basal overlap.

04Treat hypoglycemia by route and cause, and separate insulinoma from factitious hypoglycemia with C-peptide.

05Read the TSH/free T4 pair to localize thyroid disease as primary, central, or subclinical.

06Use radioiodine uptake and antibodies to separate Graves, toxic nodules, and thyroiditis — and treat each differently.

07Recognize thyroid storm and myxedema coma and give the first drugs in the right order.

08Work up a thyroid nodule from TSH to ultrasound to FNA by size and TI-RADS features.

09Diagnose and treat adrenal insufficiency and adrenal crisis — hydrocortisone before the cortisol result.

10Run the Cushing algorithm: exclude exogenous steroids, screen twice, then ACTH, then image.

11Screen for primary aldosteronism and pheochromocytoma from the right clues and order alpha before beta blockade.

12Use the calcium/PTH pair to separate primary hyperparathyroidism from malignancy and treat severe hypercalcemia in sequence.

13Recognize hypocalcemia, osteoporosis treatment thresholds, and the bisphosphonate rules.

14Interpret hyperprolactinemia, acromegaly, hypopituitarism, and pituitary apoplexy, and know when the pituitary rule for adenomas applies.

15Distinguish diabetes insipidus from SIADH with the water table and correct sodium at a safe rate.

Before You Begin

How to Use This Syllabus

Teaching Philosophy

Every important disease is taught in one sequence: Recognize → First test → Confirm → First-line treatment → Don't miss. Know the classic patient, the trigger clues, the first test, the confirmatory test, the first drug, the emergency, and the trap.
Commit before you reveal. Every question block — Before you begin, Read the labs, Two-step, Code Blue, Lightning — locks the explanation until you submit. Getting it wrong first is what makes it stick.
Tier 1 (diabetes, DKA/HHS, hypoglycemia, thyroid, adrenal, calcium, pituitary adenomas) gets the most time and questions. Tier 2 covers the tested decision points. Tier 3 is pattern recognition only.
⚠️ Board trap boxes mark the distractors written to fool you. Read them twice.
Endocrinology in 10 Algorithms is the backbone: learn the ten decision pathways first and hang every topic on one of them. Variation blocks change one variable after a teaching point; the Lab Pattern Challenge trains three-second recognition.
Learning labels: Memorize know exactly · Recognize know the pattern · Reference look up, do not memorize for the live session.
Suggested full-day timing: Framework 10 min · Diabetes 90 · DKA/HHS/hypoglycemia 45 · Thyroid 70 · Adrenal 55 · Calcium 35 · Pituitary 40 · Tier 2 25 · Tier 3 10 · Code Blue 15 · One-Page Review 15. The Lab Pattern Challenge, Lightning Round, Integrated Cases, and the 25-question Gauntlet are pre-work or post-class self-assessment.

Before You Begin · The Endocrine Operating System

Two Rules That Solve Half the Exam

Tier 1

Topic F-1

The Endocrine Operating System

Primary vs Secondary · Suppression vs Stimulation · Screening vs Confirmation

★★★ Framework for every question

Rule 1 — Localize the lesion from the hormone pair

Every axis has a trophic hormone (TSH, ACTH, LH/FSH, GH) and a target hormone (T4, cortisol, testosterone/estradiol, IGF-1). Read them as a pair and the gland that failed names itself.

Pattern	Target hormone	Trophic hormone	Lesion	Example
Primary failure	↓	↑	End organ	Hashimoto (TSH↑ FT4↓) · Addison (ACTH↑ cortisol↓)
Secondary failure	↓	↓ or inappropriately normal	Pituitary / hypothalamus	Central hypothyroidism · Secondary AI after steroid withdrawal
Primary excess	↑	↓ (suppressed)	Autonomous end organ	Graves (TSH↓ FT4↑) · Adrenal adenoma (ACTH↓ cortisol↑)
Secondary excess	↑	↑ or inappropriately normal	Pituitary (or ectopic)	Cushing disease · TSH-oma (rare)

🩺 Board rule: a trophic hormone that is "normal" while the target hormone is clearly abnormal is inappropriately normal — that is a central lesion until proven otherwise.

Rule 2 — Suppress to prove excess · Stimulate to prove deficiency

You suspect…	Dynamic test	Normal response	Abnormal = disease
Cortisol excess	1 mg overnight dexamethasone	AM cortisol suppresses (<1.8 µg/dL)	Fails to suppress
GH excess (acromegaly)	75 g oral glucose	GH suppresses to <1 ng/mL	GH fails to suppress
Aldosterone excess	Saline infusion / oral salt load	Aldosterone suppresses	Fails to suppress
Cortisol deficiency	Cosyntropin (ACTH) 250 µg	Cortisol rises to ≥18–20 µg/dL	Blunted rise
ADH deficiency vs resistance	Water deprivation → desmopressin	Urine concentrates	Central: concentrates only after DDAVP · Nephrogenic: never

🩺 Screening ≠ confirmation. Screening tests are cheap and sensitive (TSH, IGF-1, metanephrines, ARR); confirmation is the dynamic test. Boards ask for the first test far more often than the confirmatory one.

★ Memory Trick

Trophic ↑ + target ↓ = the gland is broken (primary). Trophic ↓ + target ↓ = the boss is broken (secondary). Suppress the loud ones, stimulate the quiet ones.

Read the labsFramework check1 lab read

Commit to an answer before you reveal. This is how every READ THE LABS block in the syllabus works: labs first, diagnosis second, reasoning last.

Read the labsQ1 of 1 · Medium · Localize the lesion

TSH 18.4 mIU/L (↑)
Free T4 0.5 ng/dL (↓)

A 41-year-old woman has fatigue and weight gain. Commit to a diagnosis before reading on. Which best explains this pattern?

APrimary hypothyroidism (thyroid gland failure) BCentral hypothyroidism from a pituitary lesion CSubclinical hyperthyroidism from a toxic nodule DEuthyroid sick syndrome during acute illness ELaboratory interference from biotin supplementation

Click to Reveal Answer

Correct answer: A — Primary hypothyroidism (thyroid gland failure)

TSH is high because the pituitary is working and is shouting at a thyroid that cannot answer (FT4 low). High trophic + low target = primary end-organ failure. In an iodine-sufficient country that is Hashimoto thyroiditis until proven otherwise.

Why the other choices are wrong

Central hypothyroidism from a pituitary lesion — Central disease gives a low or inappropriately normal TSH with low FT4. A frankly elevated TSH means the pituitary is intact.
Subclinical hyperthyroidism from a toxic nodule — Any hyperthyroid state suppresses TSH. TSH↑ excludes it.
Euthyroid sick syndrome during acute illness — Nonthyroidal illness classically shows low T3 with normal or low TSH — not a TSH of 18.
Laboratory interference from biotin supplementation — Biotin interference typically makes TSH read falsely low and FT4 falsely high (mimicking Graves), the opposite pattern.

Board pearlThe first lab read of the day: TSH↑ + FT4↓ = primary hypothyroidism. Add anti-TPO if you want the cause; add nothing if you just want to treat.

Covered under Topic F-1 and Topic T-1 — Hypothyroidism

The Backbone · Learn These Ten, Hang Everything Else On Them

Endocrinology in 10 Algorithms

Every endocrine question enters through one of these ten doors. Short enough to say aloud; the detail lives in the domain each one links to.

TSH abnormal

Thyroid Function Test Reading

TSH first; add free T4 (and T3 if TSH is low)
TSH ↑ + FT4 ↓ = primary hypothyroidism (Hashimoto) → levothyroxine 1.6 µg/kg; recheck TSH in 6–8 weeks
TSH ↑ + FT4 normal = subclinical; treat if TSH >10, pregnant, or symptomatic with antibodies
TSH ↓/normal + FT4 ↓ = central: check cortisol and give steroids BEFORE levothyroxine
TSH ↓ + FT4/T3 ↑ = thyrotoxicosis → RAIU (or TRAb): high = Graves/toxic nodule; low = thyroiditis, exogenous, iodine
Sick patient with odd values = nonthyroidal illness; biotin = falsely low TSH, high FT4 — repeat off supplement

TSH FIRST · READ THE PAIR · CORTISOL BEFORE T4Go deeper → Domain 3

Thyroid nodule

Thyroid Nodule & Cancer

TSH first: low → RAIU scan; hot nodule = almost never cancer, treat hyperthyroidism
Normal/high TSH → ultrasound with TI-RADS features (hypoechoic, microcalcifications, irregular margins, taller-than-wide, extrathyroidal extension)
FNA by size and suspicion: ≥1 cm suspicious, ≥1.5 cm intermediate, ≥2–2.5 cm low suspicion; purely cystic = no FNA
Bethesda result drives surgery vs surveillance; molecular testing for indeterminate
Red flags: rapid growth, hoarseness, fixed mass, cervical nodes, radiation history, family history of MTC/MEN2
Cancer types: papillary (most common, best prognosis, nodes) · follicular (hematogenous) · medullary (calcitonin, RET, MEN2) · anaplastic (rapid, fatal)

TSH → ULTRASOUND → FNA BY SIZEGo deeper → Domain 3

Glucose ↑↑ + sick

DKA & HHS

Confirm: DKA = glucose >250, pH <7.3, HCO₃ <18, ketones, gap; HHS = >600, osm >320, pH >7.3, obtunded
Isotonic fluids first (1–1.5 L in hour 1); find the trigger (infection, insulin omission, MI, SGLT2i)
Check potassium before insulin: <3.3 = hold insulin and replace; 3.3–5.2 = add K to fluids; >5.2 = no K yet
Insulin 0.1 U/kg/h; when glucose ~200–250 add dextrose, do not stop insulin
Replace K, consider phosphate <1.0; bicarbonate only if pH <6.9
Resolved when gap closes (DKA) or osm/mentation normalize (HHS); overlap SC basal 1–2 h before stopping the drip

FLUIDS → POTASSIUM → INSULIN → DEXTROSEGo deeper → Domain 2

Glucose ↓

Hypoglycemia

Whipple triad: symptoms + glucose <70 (<55 in non-diabetics) + relief with glucose
Conscious and swallowing: 15 g carbohydrate, recheck in 15 min (rule of 15); IV dextrose if a line; IM/nasal glucagon if not
Sulfonylurea overdose: admit, dextrose plus octreotide; recurrence risk for 24–72 h
Non-diabetic: draw glucose, insulin, C-peptide, proinsulin, sulfonylurea screen, β-hydroxybutyrate DURING hypoglycemia (72-h fast if needed)
High insulin + high C-peptide = insulinoma or sulfonylurea; high insulin + LOW C-peptide = exogenous insulin
Insulinoma: localize (CT/MRI/EUS), resect; think MEN1. Also: adrenal insufficiency, alcohol, sepsis, liver failure

RULE OF 15 · C-PEPTIDE DECIDESGo deeper → Domain 2

Calcium ↑

Hypercalcemia

Confirm: correct for albumin (+0.8 per g/dL below 4) or measure ionized calcium
PTH: high or inappropriately normal = primary hyperparathyroidism (or lithium, FHH — check urine calcium)
PTH low → PTHrP (squamous cancers), 1,25-D (lymphoma, granulomas), 25-D (vitamin D excess), SPEP (myeloma), TSH, vitamin A
Severe (>14 or symptomatic): saline first, then calcitonin (fast, 48 h), then zoledronate (denosumab if CKD); steroids for granuloma/lymphoma; dialysis if refractory
Never thiazides; loop diuretics only after volume repletion
Primary hyperpara surgery: symptoms, Ca >1 above normal, age <50, eGFR <60, T-score ≤−2.5, stones; cinacalcet if not a surgical candidate

ALBUMIN → PTH → SALINE → CALCITONIN → BISPHOSPHONATEGo deeper → Domain 5

Cushingoid patient

Suspected Cushing Syndrome

Step 0: exclude exogenous glucocorticoids (including inhaled, topical, injected) — the most common cause
Screen with two of: 1-mg overnight dexamethasone (cortisol >1.8), late-night salivary cortisol ×2, 24-h urine free cortisol ×2
Confirm hypercortisolism before any imaging
ACTH: suppressed = adrenal source → adrenal CT; normal/high = ACTH-dependent
ACTH-dependent: high-dose dexamethasone suppresses / CRH stimulates = pituitary (Cushing disease) → MRI; no suppression = ectopic (small-cell) → chest CT; inferior petrosal sinus sampling when MRI is unclear
Treat: transsphenoidal surgery (disease), adrenalectomy (adenoma), resect ectopic source; ketoconazole/osilodrostat as bridges

EXOGENOUS? → SCREEN ×2 → ACTH → IMAGEGo deeper → Domain 4

Fatigue + hypotension + hyponatremia

Suspected Adrenal Insufficiency

Unstable? Draw cortisol/ACTH, then hydrocortisone 100 mg IV and saline NOW — do not wait for results
Stable: 8 AM cortisol <3 confirms, >15–18 excludes; in between → cosyntropin stimulation (cortisol <18 at 30–60 min = insufficiency)
ACTH high = primary (Addison: hyperpigmentation, hyperkalemia, salt craving; autoimmune, TB, hemorrhage, HIV) → hydrocortisone + fludrocortisone
ACTH low/normal = secondary (steroid withdrawal is the most common cause; pituitary disease) → hydrocortisone only; check the other axes
Sick-day rules: double or triple the dose; stress-dose steroids for surgery/illness; medical alert bracelet
Trap: hypoglycemia, eosinophilia, and hypercalcemia are supporting clues; hyperkalemia only in primary disease

STEROIDS BEFORE THE RESULT · ACTH LOCALIZESGo deeper → Domain 4

Hypertension + endocrine clue

Adrenal Hypertension

Hypokalemia, resistant HTN, adrenal incidentaloma, HTN <40 → primary aldosteronism: aldosterone/renin ratio (stop MRAs 4–6 wk; correct K)
Confirm with saline suppression / oral salt load; adrenal CT then adrenal vein sampling if surgery is considered
Adenoma = adrenalectomy; bilateral hyperplasia = spironolactone or eplerenone
Paroxysmal headache, sweating, palpitations → plasma free metanephrines (or 24-h urine) BEFORE imaging
Pheochromocytoma: localize (CT/MRI, MIBG), alpha-block (phenoxybenzamine/doxazosin) 10–14 days, salt-load, THEN beta-block, then surgery; never beta first
Incidentaloma: two questions — is it functioning (DST, metanephrines, ARR if hypertensive) and could it be cancer (>4 cm, >10 HU, delayed washout)?

LOW K → ARR · PAROXYSMS → METANEPHRINES · ALPHA BEFORE BETAGo deeper → Domain 4

Polyuria or sodium abnormal

Diabetes Insipidus vs SIADH

Polyuria >3 L/day + high/normal Na + dilute urine (osm <300) = diabetes insipidus; exclude glucose, diuretics, hypercalcemia, hypokalemia
Water deprivation: urine osm stays low → DI; desmopressin raises urine osm >50% = central (give desmopressin), no response = nephrogenic (lithium, hypercalcemia → thiazide, amiloride)
Hyponatremia + urine osm >100 + urine Na >30 + euvolemic + normal TSH/cortisol = SIADH (CNS, lung, SSRIs, carbamazepine, small-cell)
Severe symptoms: 3% saline 100–150 mL bolus; otherwise fluid restriction, salt + loop, urea, tolvaptan
Correction limits: hyponatremia ≤8 mEq/L per 24 h (rescue with D5W + desmopressin); hypernatremia ≤10–12 per day
Post-pituitary surgery: triphasic response (DI → SIADH → DI)

URINE OSM DECIDES · 8 IN 24Go deeper → Domain 6

Pituitary mass or hormone excess

Pituitary Adenoma Workup

Incidentaloma: screen prolactin, IGF-1, and cortisol excess; assess hypopituitarism if ≥1 cm; visual fields if it touches the chiasm
Prolactin high: exclude pregnancy, hypothyroidism, renal failure, antipsychotics/metoclopramide, and stalk effect (modest rise) before calling it a prolactinoma
Prolactinoma is the one adenoma treated medically first: cabergoline (dopamine agonist), even for macroadenomas
Acromegaly: IGF-1 screen → OGTT fails to suppress GH → MRI → transsphenoidal surgery; octreotide/pegvisomant
All other functioning or mass-effect adenomas: transsphenoidal surgery; replace deficient axes (cortisol before thyroxine)
Apoplexy: sudden headache, visual loss, ophthalmoplegia → hydrocortisone immediately, urgent MRI, neurosurgery

PROLACTIN = PILLS · EVERYTHING ELSE = SURGERY · CORTISOL FIRSTGo deeper → Domain 6

Domain 1 · Diabetes Mellitus — Largest Section on the Endocrine Blueprint

Diabetes Mellitus: Diagnosis, Drug Decisions, Complications

Tier 1

Topic DM-1

Diabetes — Diagnosis, Classification & Screening

A1c · FPG · OGTT · Type 1 vs LADA vs Type 2 vs MODY · Who to Screen

★★★ PANCE Core

Why It Matters for Boards

Diabetes is the single most tested endocrine topic on the PANCE. Questions cluster on four decisions: is it diabetes, which type, which drug for this comorbidity, and which complication is being screened.

Diagnostic Thresholds — Know the Numbers ColdMemorize

Test	Normal	Prediabetes	Diabetes	Notes
Hemoglobin A1c	<5.7%	5.7–6.4%	≥6.5%	Unreliable with hemoglobinopathy, hemolysis, iron deficiency, pregnancy, transfusion, advanced CKD
Fasting plasma glucose (≥8 h)	<100	100–125 (IFG)	≥126 mg/dL	Most reproducible; repeat to confirm if asymptomatic
2-h plasma glucose, 75-g OGTT	<140	140–199 (IGT)	≥200 mg/dL	Most sensitive; used in pregnancy and when A1c is unreliable
Random plasma glucose	—	—	≥200 mg/dL + symptoms	Polyuria, polydipsia, weight loss, or hyperglycemic crisis — no confirmation needed

🩺 Confirmation rule: asymptomatic patients need two abnormal results (same test repeated, or two different tests from the same sample). Symptomatic + random ≥200 or hyperglycemic crisis = diagnosed on the spot.

Classification — Type 1 vs Type 2 vs LADA vs MODYRecognize

	Type 1	LADA	Type 2	MODY
Mechanism	Autoimmune β-cell destruction	Slow autoimmune destruction in adults	Insulin resistance + relative deficiency	Monogenic β-cell defect (autosomal dominant)
Typical patient	Lean child/young adult, abrupt onset, weight loss	Adult >30, lean, "type 2" that fails oral agents in a few years	Overweight adult, insidious, acanthosis, family history	Lean, <25 y, 3 generations affected, no antibodies
Ketosis-prone	Yes	Eventually	Rare (except SGLT2i, illness)	No
Autoantibodies	GAD65, IA-2, ZnT8, insulin	GAD65 positive	Negative	Negative
C-peptide	Low / absent	Low-normal, falling	Normal / high	Preserved
Initial therapy	Insulin (basal-bolus or pump)	Early insulin	Metformin ± comorbidity-driven agent	Sulfonylurea (HNF1A/HNF4A) or none (GCK)

Screening — Who Gets Tested

All adults ≥35 years, regardless of weight; repeat every 3 years if normal
Any adult with BMI ≥25 kg/m² (≥23 Asian American) plus ≥1 risk factor: first-degree relative, high-risk ethnicity, prior GDM, hypertension, HDL <35 or TG >250, PCOS, physical inactivity, acanthosis nigricans, HIV
Prediabetes → annual testing; refer to a Diabetes Prevention Program; consider metformin for BMI ≥35, age <60, or prior GDM
Prior GDM → lifelong screening every 1–3 years
Type 1 relatives → autoantibody screening is now offered; a person with ≥2 antibodies has stage 1 disease

⚠️ BOARD TRAP — Board Traps

A1c 6.4% + FPG 128 mg/dL on the same sample → this is diabetes (two different tests both abnormal is acceptable); do not call it prediabetes because one test fell short.
A lean 26-year-old with new diabetes → check antibodies and C-peptide before you reach for metformin. Ketones are not required for type 1.
A1c in sickle cell trait, iron deficiency, hemolysis, pregnancy, or CKD → unreliable; use glucose criteria.
"Pancreatogenic" (type 3c) diabetes after chronic pancreatitis or pancreatectomy behaves like type 1 (insulin-requiring, brittle) with exocrine insufficiency — steatorrhea in the stem is the clue.

★ Memory Trick

The four doors: 6.5 / 126 / 200 / 200-plus-symptoms. Prediabetes: 5.7 / 100 / 140. Screen at 35 — or at 25 (BMI) with any risk factor.

Tier 1

Topic DM-2

Diabetes Pharmacology — Choose the Drug by the Comorbidity

Metformin · SGLT2i · GLP-1 RA · Tirzepatide · DPP-4i · Sulfonylurea · TZD · Insulin · Dawn vs Somogyi

★★★ PANCE Core

Why It Matters for Boards

The exam no longer asks "which drug lowers A1c the most." It asks which drug this patient with heart failure / CKD / obesity / ASCVD should receive — comorbidity first, glucose second. The 2026 ADA Standards make cardiorenal protection a co-primary goal independent of A1c.

The Drug Decision TableMemorize

Class	Example	Weight	Hypoglycemia	Major benefit	Major adverse effect	Avoid / Warning
Biguanide	Metformin	Neutral / ↓	No	First-line, cheap, durable, CV-neutral	GI upset, B12 deficiency	Contraindicated eGFR <30; don't initiate 30–45; hold with iodinated contrast; lactic acidosis (rare)
SGLT2 inhibitor	Empagliflozin, dapagliflozin, canagliflozin	↓	No	HF (any EF) and CKD progression; ASCVD (empa/cana)	Genital mycotic infection, UTI, volume depletion, euglycemic DKA, Fournier gangrene	Hold 3–4 days pre-op and during acute illness; not for type 1; limited glucose effect at eGFR <30 (still renal-protective to ~20)
GLP-1 receptor agonist	Semaglutide, liraglutide, dulaglutide	↓↓	No	ASCVD events; weight; CKD (semaglutide)	Nausea/vomiting, delayed gastric emptying, pancreatitis, gallbladder disease	Personal/family MTC or MEN2; gastroparesis; hold before anesthesia (aspiration)
Dual GIP/GLP-1 RA	Tirzepatide	↓↓↓	No	Greatest weight and A1c reduction; HFpEF symptoms/events (ADA 2026)	Same GI profile	Same MTC/MEN2 warning
DPP-4 inhibitor	Sitagliptin, linagliptin	Neutral	No	Well tolerated, oral, usable in CKD (linagliptin needs no dose change)	Nasopharyngitis, pancreatitis, arthralgia	Saxagliptin/alogliptin ↑ HF hospitalization; never combine with a GLP-1 RA (same pathway)
Sulfonylurea	Glipizide, glimepiride, glyburide	↑	Yes — highest of orals	Cheap, fast A1c drop	Hypoglycemia, weight gain	Glyburide in elderly (Beers) or CKD; avoid in sulfa allergy (relative)
Thiazolidinedione	Pioglitazone	↑	No	Durable, helps MASLD, cheap	Fluid retention, HF exacerbation, fractures, bladder cancer signal, macular edema	Contraindicated NYHA III–IV HF
Insulin	Basal (glargine, detemir, degludec); prandial (lispro, aspart)	↑	Yes	Unlimited efficacy; required in type 1, catabolism, A1c >10%	Hypoglycemia, weight gain, hypokalemia, lipohypertrophy	Basal analogs preferred over NPH (less nocturnal hypoglycemia)

🩺 2026 note: oral semaglutide (Wegovy pill, Dec 2025) and orforglipron (Foundayo, Apr 2026) are FDA-approved for obesity; orforglipron is not yet approved for diabetes. The class rules above are unchanged.

Choose by Comorbidity — The Questions the Exam Actually Asks

Patient has…	Add this class (independent of A1c)	Why
Heart failure (HFrEF or HFpEF)	SGLT2 inhibitor	Reduces HF hospitalization and CV death across the EF spectrum; tirzepatide also improves HFpEF outcomes
CKD (eGFR 20–60 or albuminuria)	SGLT2 inhibitor (GLP-1 RA if not tolerated)	Slows eGFR decline and albuminuria; continue until dialysis
Established ASCVD or high risk	GLP-1 RA or SGLT2 inhibitor with proven benefit	MACE reduction (semaglutide, liraglutide, dulaglutide; empagliflozin, canagliflozin)
Obesity / weight is the priority	Tirzepatide or semaglutide	Greatest weight loss; avoid sulfonylureas, TZDs, insulin if possible
MASLD / MASH	GLP-1 RA, tirzepatide, or pioglitazone	Histologic improvement
Cost is the barrier	Metformin → sulfonylurea or pioglitazone	Cheapest effective options; counsel on hypoglycemia / fluid
Hypoglycemia must be avoided (elderly, driver, CKD)	Metformin, DPP-4i, GLP-1 RA, SGLT2i	All non-hypoglycemic as monotherapy; avoid sulfonylurea and insulin
A1c >10%, glucose >300, or symptomatic / catabolic	Insulin now (basal ± prandial)	Glucotoxicity; oral agents cannot catch up; reassess after control
First injectable needed, no catabolism	GLP-1 RA or tirzepatide before insulin	Less hypoglycemia, weight loss, comparable A1c effect

Targets

A1c <7% for most non-pregnant adults; <6.5% if achievable without hypoglycemia; <8% for limited life expectancy, frailty, hypoglycemia unawareness
Preprandial 80–130 mg/dL; peak postprandial <180 mg/dL; CGM time-in-range >70% with <4% below 70
A1c every 3 months until at goal, then every 6 months
Blood pressure: <130/80 (ADA 2026 encourages a systolic <120 target when safely achievable); statin for all with diabetes age 40–75; ACEi/ARB for albuminuria or hypertension

Insulin — Types, Timing, and the Two Morning Hyperglycemia PatternsRecognize

Insulin	Onset	Peak	Duration	Role
Rapid (lispro, aspart, glulisine)	10–15 min	1–2 h	3–5 h	Prandial / correction; give 0–15 min before meals; used in pumps
Short (regular)	30–60 min	2–4 h	5–8 h	IV infusion in DKA; prandial if cost matters (30 min before meals)
Intermediate (NPH)	1–2 h	4–12 h	12–18 h	Twice-daily basal; more nocturnal hypoglycemia; used in pregnancy and for cost
Long (glargine, detemir)	1–2 h	Minimal	~24 h	Once-daily basal; preferred over NPH
Ultra-long (degludec)	1–2 h	None	>42 h	Least hypoglycemia; flexible timing

Starting basal in type 2: 10 units or 0.1–0.2 U/kg at bedtime; titrate 2 units every 3 days to fasting 80–130. If fasting is at goal but A1c is not → add prandial insulin (or GLP-1 RA) before the largest meal, not more basal.
Type 1: total daily dose ~0.4–1.0 U/kg; 50% basal, 50% prandial divided by meals; carbohydrate ratio and correction factor; CGM preferred; automated insulin delivery increasingly standard.

Morning hyperglycemia	Mechanism	3 AM glucose	Fix
Dawn phenomenon	Early-morning GH/cortisol surge → insulin resistance	Normal or high	Move basal to bedtime or increase the dose; consider pump
Somogyi effect	Nocturnal hypoglycemia → counter-regulatory rebound	Low	Decrease evening basal / add bedtime snack
Waning insulin	NPH given at dinner runs out before morning	Rising steadily	Move NPH to bedtime or switch to a long-acting analog

🩺 The board move: the vignette says "fasting hyperglycemia despite increasing insulin" — check a 3 AM glucose. If it is low, the answer is to reduce insulin, never to raise it.

⚠️ BOARD TRAP — Board Traps

Diabetes + heart failure → SGLT2 inhibitor. Not pioglitazone (fluid retention), not saxagliptin (HF hospitalization).
Diabetes + CKD with eGFR 25 → SGLT2 inhibitor for renal protection is still correct even though its glucose-lowering effect is minimal; metformin is contraindicated at eGFR <30.
Diabetes + obesity + prior medullary thyroid cancer in a parent → GLP-1 RA/tirzepatide are contraindicated; pick an SGLT2 inhibitor.
A1c 11% with weight loss and polyuria → start insulin now. Adding a second oral agent is the tempting wrong answer.
Patient on an SGLT2 inhibitor with nausea, malaise, and glucose 190 → check ketones and an anion gap. Euglycemic DKA is real; the normal-ish glucose is the trap.
Metformin and iodinated contrast → per labeling, hold at the time of contrast when eGFR is 30–60 (or with AKI/unstable function) and restart 48 h later once renal function is confirmed stable; current radiology guidance is more permissive above eGFR 30, but the board answer is still “hold.”
GLP-1 RA before surgery → delayed gastric emptying raises aspiration risk; hold weekly agents ~1 week before elective anesthesia per current perioperative guidance.

★ Memory Trick

HF or CKD → "SGLT-2" (2 organs, 1 drug). ASCVD or weight → GLP-1 ("1 heart, lots of weight"). Sick, catabolic, >10% → insulin — no debate. Somogyi = low at 3 AM → less insulin.

Tier 1

Topic DM-3

Diabetes — Complications, Screening & Special Populations

Retinopathy · Nephropathy · Neuropathy · Foot · Cardiovascular · Gestational Diabetes

★★★ PANCE Core

Why It Matters for Boards

Health-maintenance items are cheap points: the exam asks when to screen, what test, and the first-line treatment for each complication.

Screening Schedule — Type 1 vs Type 2

Complication	Screening test	Start	Frequency	First-line management
Retinopathy	Dilated fundoscopy or retinal photography	T1: 5 yr after dx (≥age 11) · T2: at diagnosis	Annually (q1–2 yr if normal)	Glycemic/BP control; anti-VEGF (aflibercept, ranibizumab) for macular edema or proliferative disease; laser photocoagulation
Nephropathy	Urine albumin-to-creatinine ratio + eGFR	T1: 5 yr after dx · T2: at diagnosis	Annually (twice yearly if abnormal)	ACEi/ARB for albuminuria (UACR ≥30) or HTN; SGLT2i (eGFR ≥20); finerenone; BP <130/80
Neuropathy	10-g monofilament + vibration (128 Hz) + pinprick/temperature	T1: 5 yr · T2: at diagnosis	Annually	Glycemic control; pain: duloxetine, pregabalin/gabapentin, TCAs (avoid in elderly/cardiac), topical capsaicin
Foot	Comprehensive foot exam; pulses; ulcer risk	At diagnosis	Annually; every visit if high risk	Offloading, wound care, vascular assessment; probe-to-bone + X-ray/MRI for osteomyelitis
Cardiovascular	BP every visit; lipids at dx then annually	At diagnosis	Annually	Statin for age 40–75 (high-intensity if ASCVD or risk factors); aspirin only for secondary prevention
Autonomic	History: orthostasis, gastroparesis, ED, hypoglycemia unawareness	As symptoms arise	—	Gastroparesis: small low-fat meals, metoclopramide (short course); orthostasis: midodrine, fludrocortisone

Chronic Complication PearlsRecognize

Retinopathy: nonproliferative (microaneurysms, dot-blot hemorrhages, hard exudates, cotton-wool spots) → proliferative (neovascularization = the board word) → vitreous hemorrhage, tractional detachment. Diabetes is the leading cause of new blindness in working-age adults. Pregnancy accelerates retinopathy — exam each trimester.
Nephropathy: earliest sign is albuminuria (30–299 mg/g = moderately increased; ≥300 = severely). Kimmelstiel-Wilson nodules on biopsy. ACEi/ARB even when normotensive if UACR ≥300; never combine ACEi + ARB.
Peripheral neuropathy: symmetric distal "stocking" sensory loss, ↓ ankle reflexes; loss of protective sensation → Charcot foot (warm, swollen, deformed, painless — do not mistake for cellulitis).
Mononeuropathy: CN III palsy with pupil-sparing ptosis and diplopia — ischemic, resolves in weeks. A pupil-involving CN III palsy is an aneurysm until proven otherwise.
Amyotrophy: asymmetric proximal thigh pain and weakness with weight loss in older type 2 patients; self-limited.
Infections: malignant otitis externa (Pseudomonas), mucormycosis (rhinocerebral, especially with DKA), emphysematous pyelonephritis, necrotizing fasciitis, Fournier gangrene.

Gestational Diabetes & Diabetes in PregnancyReference

Screen at 24–28 weeks (earlier if high risk): one-step 75-g fasting OGTT (any one of fasting ≥92, 1-h ≥180, 2-h ≥153 mg/dL) or two-step 50-g challenge (positive ≥130–140) → 100-g 3-h OGTT (≥2 abnormal values)
Treatment: nutrition + exercise first; insulin is first-line pharmacotherapy (does not cross the placenta); metformin and glyburide are alternatives with placental transfer
Targets: fasting <95, 1-h postprandial <140, 2-h <120 mg/dL
Fetal risks: macrosomia, shoulder dystocia, neonatal hypoglycemia, hyperbilirubinemia, polycythemia; pre-existing diabetes with poor early control → congenital heart and neural tube defects, caudal regression
Postpartum: 75-g OGTT at 4–12 weeks, then screening every 1–3 years (~50% develop type 2 within 10 years)
Pre-existing diabetes: preconception A1c <6.5%, folate, stop SGLT2i/GLP-1 RA/statins/ACEi-ARB; retinal exam each trimester; low-dose aspirin from 12 weeks for preeclampsia prevention

Clinical Vignette

A 61-year-old man with 12 years of type 2 diabetes presents with a warm, swollen, erythematous right midfoot. He denies pain. Temperature 37.1 °C, WBC 7,800. Radiograph shows fragmentation of the tarsal bones and joint subluxation. The foot pulses are bounding.

Answer: Charcot neuroarthropathy. Painless (neuropathic), warm, bounding pulses, and bony fragmentation without systemic signs. Treat with immobilization and total-contact casting — not antibiotics. Osteomyelitis is the distractor: it needs an ulcer or a probe-to-bone positive wound, and elevated inflammatory markers.

⚠️ BOARD TRAP — Board Traps

Type 1 diagnosed at age 8 → retinal and renal screening begin at age 11 or 5 years after diagnosis, whichever is later — not at diagnosis.
Type 2 at diagnosis → screen everything on day one; the disease has usually been present for years.
Albuminuria in a normotensive patient → still start an ACEi/ARB.
Third-nerve palsy in a diabetic with a normal pupil → ischemic microvascular palsy; a dilated pupil means aneurysm → emergent CTA.
Aspirin for primary prevention in diabetes is no longer routine — only for established ASCVD or selected high-risk patients.

Domain 2 · Hyperglycemic Crises & Hypoglycemia

DKA · HHS · Hypoglycemia

Tier 1

Topic DK-1

DKA & HHS — Recognition and the Management Algorithm

Comparison Table · Fluids → Potassium → Insulin → Dextrose → Close the Gap · Cerebral Edema · Euglycemic DKA

★★★ PANCE Core

Why It Matters for Boards

DKA/HHS questions test sequence: what first, what before insulin, when to add dextrose, when you are done. The potassium rule alone accounts for a reliable item every exam cycle.

DKA vs HHS — The Comparison Table

	DKA	HHS
Typical patient	Type 1 (or ketosis-prone type 2, SGLT2i); younger; hours–days	Type 2; older; days–weeks; impaired thirst/access to water
Precipitants	Insulin omission, infection, new-onset T1, MI, drugs (SGLT2i, steroids, antipsychotics)	Infection (UTI, pneumonia), stroke, MI, dehydration, steroids, diuretics
Glucose	>250 mg/dL (often 300–600; may be <250 in euglycemic DKA)	>600 mg/dL (often >1,000)
Ketones	Positive (β-hydroxybutyrate ≥3 mmol/L)	Negative or trace
pH	<7.30 (severe <7.0)	>7.30
Bicarbonate	<18 mEq/L (severe <10)	>18 mEq/L
Anion gap	>12 (elevated)	Normal or mildly elevated
Serum osmolality	Variable (often <320)	>320 mOsm/kg
Neurologic symptoms	Mild; obtundation only when severe	Prominent — obtundation, seizures, focal deficits
Exam clues	Kussmaul respirations, fruity breath, abdominal pain, vomiting	Profound dehydration, hypotension, altered mental status
Fluid deficit	~6 L (100 mL/kg)	~9 L (100–200 mL/kg)
Mortality	<1% (higher with cerebral edema in children)	10–20%
Treatment differences	Insulin 0.1 U/kg/h (bolus optional); dextrose at glucose ~200–250	Fluids dominate; insulin 0.05–0.1 U/kg/h once perfusion restored; dextrose at ~250–300; target osmolality fall ≤3 mOsm/kg/h

The Management Algorithm — Same Skeleton for BothMemorize

1. Recognize. Glucose + ketones/β-hydroxybutyrate + VBG/BMP (anion gap) + osmolality. Find the precipitant (ECG for MI, cultures, urinalysis, pregnancy test).

↓

2. IV fluids. 1–1.5 L isotonic crystalloid in the first hour (15–20 mL/kg), then 250–500 mL/h. Switch to ½NS if corrected Na is normal/high. Fluids alone drop glucose 35–70 mg/dL/h.

↓

3. CHECK POTASSIUM before insulin. K <3.3 → hold insulin, give KCl 20–30 mEq/h. K 3.3–5.2 → insulin + 20–30 mEq K per liter. K >5.2 → insulin, recheck in 2 h.

↓

4. Insulin. Regular insulin 0.1 U/kg/h IV (bolus 0.1 U/kg optional). Goal: glucose falls 50–75 mg/dL/h. If it does not fall ≥10% in the first hour, double the rate.

↓

5. Potassium management. Target K 4–5 mEq/L; check every 2–4 h. Replace phosphate only if <1 mg/dL or with cardiac/respiratory compromise. Magnesium if low (refractory hypokalemia).

↓

6. Add dextrose (D5 or D10 with ½NS) when glucose reaches ~200–250 (DKA) or ~250–300 (HHS) — so insulin can continue.

↓

7. Close the gap. DKA resolved: gap ≤12, HCO₃ ≥15–18, pH >7.3, glucose <200. HHS resolved: osmolality <320, mental status normal. Give SC basal insulin, overlap 1–2 h, then stop the drip. Feed the patient.

Special SituationsReference

Bicarbonate: only if pH <6.9 (100 mEq in 400 mL sterile water with 20 mEq KCl over 2 h). It worsens hypokalemia, shifts the oxygen curve, and can cause paradoxical CNS acidosis.
Cerebral edema (children): headache, bradycardia, altered mental status 4–12 h into treatment. Risk rises with rapid osmolality correction and early bolus insulin. Treat with mannitol or 3% saline; slow the fluids.
Corrected sodium: measured Na + 1.6 mEq/L for every 100 mg/dL glucose above 100 (some use 2.4). Guides tonicity of fluids; a normal measured Na with glucose of 900 is actually hypernatremia.
Hyperchloremic non-gap acidosis late in treatment is expected from saline and ketone excretion — it does not mean ongoing DKA. Follow the gap, not the bicarbonate alone.
Euglycemic DKA: SGLT2 inhibitors, pregnancy, starvation, alcohol. Glucose <250 with ketoacidosis. Same treatment, plus dextrose from the start.
Abdominal pain + leukocytosis + amylase elevation are common in DKA itself; pancreatitis is a distractor unless lipase is markedly high and pain persists after acidosis resolves.
Mucormycosis: DKA + black nasal eschar or facial pain → emergent ENT debridement + amphotericin B.

⚠️ BOARD TRAP — Board Traps

Insulin before fluids → hypotension worsens as water follows glucose into cells.
Insulin with K <3.3 → arrhythmia. Hold and replete.
Stopping insulin because glucose is 180 → the gap reopens. Add dextrose; continue insulin until the gap closes.
Stopping the drip without SC basal overlap → rebound DKA in 2–4 hours.
Bicarbonate for pH 7.1 → not indicated; threshold is 6.9.
Normal potassium on the first BMP → still total-body depleted; plan replacement.
Glucose 200 with an anion gap in a patient on empagliflozin → euglycemic DKA, not gastroenteritis.

★ Memory Trick

F-K-I-K-D-G: Fluids → K check → Insulin → K replete → Dextrose → Gap closed. "No K, no insulin" — 3.3 is the line. Dextrose at 200 (DKA) / 250 (HHS). Done when the GAP closes, not the glucose.

Tier 1

Topic DK-2

Hypoglycemia — Treatment Sequence and the Non-Diabetic Workup

Levels 1–3 · Rule of 15 · Glucagon · Sulfonylurea Overdose · Insulinoma vs Factitious (C-peptide)

★★★ PANCE Core

Why It Matters for Boards

Hypoglycemia is tested three ways: the treatment sequence in a diabetic, the insulinoma vs factitious workup in a non-diabetic, and the drug most likely to have caused it.

Definitions and Recognition

Level	Glucose	Meaning
Level 1	54–69 mg/dL	Alert value — treat and adjust regimen
Level 2	<54 mg/dL	Clinically important; neuroglycopenia likely
Level 3	Any value with altered mental/physical state requiring assistance	Severe — glucagon or IV dextrose

Adrenergic symptoms (glucose ~55–70): tremor, palpitations, diaphoresis, anxiety, hunger — blunted by β-blockers (sweating persists) and by hypoglycemia unawareness after recurrent episodes
Neuroglycopenic symptoms (<50): confusion, behavioral change, focal deficits, seizure, coma
Whipple triad (required to pursue hypoglycemia in a non-diabetic): symptoms + documented low glucose + relief with glucose

Treatment — The Rule of 15 and When to Use GlucagonMemorize

Conscious and able to swallow: 15–20 g fast-acting carbohydrate (4 oz juice, glucose tablets). Recheck in 15 min; repeat if still <70. Then eat a meal/snack.

↓

Unable or unwilling to take oral carbohydrate (out of hospital): glucagon 1 mg IM/SC or 3 mg intranasal; repeat once at 15 min if no response. Roll on the side (vomiting). Glucagon needs hepatic glycogen — less effective after prolonged fasting, alcohol, or liver disease.

↓

In hospital / IV access: dextrose 50% 25 g (or D10 100–250 mL) IV; then D10 infusion if the cause is long-acting (sulfonylurea, long-acting insulin).

↓

Sulfonylurea overdose: hypoglycemia recurs for 24–72 h — admit, D10 infusion, and octreotide to suppress insulin release.

Hypoglycemia in the Non-Diabetic — Insulinoma vs Factitious vs OtherRecognize

During hypoglycemia (72-h fast)	Insulin	C-peptide	Proinsulin	Sulfonylurea screen	Diagnosis
Insulinoma	↑	↑	↑	Negative	Endogenous hyperinsulinism → CT/MRI, endoscopic US → surgical resection; diazoxide/octreotide to bridge. Think MEN1.
Exogenous insulin (factitious)	↑↑	↓ (suppressed)	↓	Negative	Injected insulin has no C-peptide — health-care worker, access to insulin
Sulfonylurea (factitious or accidental)	↑	↑	↑	Positive	Looks exactly like insulinoma until the drug screen
Non-insulin causes	↓	↓	↓	Negative	Adrenal insufficiency, alcohol (blocks gluconeogenesis), sepsis, liver failure, non-islet tumors (IGF-2), post-bariatric dumping

⚠️ BOARD TRAP — Board Traps

Glucagon in a chronic alcoholic or after a 3-day fast → may fail (no glycogen); give IV dextrose (and thiamine before or with it).
Sulfonylurea hypoglycemia treated with one amp of D50 and discharged → recurs; admit for 24–72 h with D10 ± octreotide.
High insulin + high C-peptide → insulinoma or sulfonylurea; the drug screen decides.
Hypoglycemia unawareness → relax the glycemic target for several weeks to restore awareness; CGM with alarms.
β-blockers mask tremor and palpitations but not sweating.

★ Memory Trick

Rule of 15: 15 g → 15 min → recheck. C-peptide is the receipt for home-made insulin. No receipt = injected. Sulfonylurea = insulinoma labs + positive drug screen → octreotide.

Domain 3 · Thyroid — Second-Largest Endocrine Domain

Thyroid: TSH-First Testing, Hypo, Hyper, Thyroiditis, Nodules, Emergencies

Tier 1

Topic T-1

Hypothyroidism & the TSH-First Strategy

TSH → FT4 · Hashimoto · Primary vs Central · Levothyroxine Dosing · Subclinical Disease · Myxedema Coma

★★★ PANCE Core

Testing Strategy — TSH FirstMemorize

Serum TSH — best single screen (log-linear inverse relation to FT4). Normal TSH ends the workup unless pituitary disease is suspected.

↓

Abnormal TSH → add free T4. T3 is useful only in suspected T3 toxicosis; it has no role in diagnosing hypothyroidism.

↓

Antibodies: anti-TPO (Hashimoto), TRAb/TSI (Graves). RAIU/scan for the cause of hyperthyroidism. Ultrasound for nodules.

TSH	Free T4	Interpretation	Next
↑	↓	Primary (overt) hypothyroidism	Levothyroxine; anti-TPO optional
↑	Normal	Subclinical hypothyroidism	Repeat in 6–8 wk; treat if TSH ≥10 or indicated
↓ or inappropriately normal	↓	Central (secondary) hypothyroidism	Pituitary MRI; check cortisol before starting levothyroxine
↓	↑	Primary hyperthyroidism / thyrotoxicosis	RAIU or TRAb
↓	Normal	Subclinical hyperthyroidism (check T3 for T3 toxicosis)	Treat if TSH <0.1 with age ≥65, osteoporosis, or AF
Normal or ↑	↑	TSH-oma or thyroid hormone resistance (rare); assay interference (biotin)	Repeat off biotin; α-subunit; MRI
Normal / ↓	↓ T3, normal/↓ T4	Euthyroid sick (nonthyroidal illness)	Do not treat; recheck after recovery

Hypothyroidism — Recognize → Test → Confirm → Treat → Don't Miss

Recognize

Fatigue, weight gain, cold intolerance, constipation, dry skin, brittle hair, menorrhagia, depression, bradycardia, delayed relaxation of reflexes, periorbital edema, hoarseness; hyperlipidemia, hyponatremia, macrocytosis, ↑CK

First test

TSH

Confirm

TSH ↑ + free T4 ↓ (anti-TPO positive in Hashimoto)

First-line treatment

Levothyroxine 1.6 µg/kg/day (12.5–25 µg start if elderly/CAD); recheck TSH 6–8 wk; empty stomach

Don't miss

Myxedema coma · central hypothyroidism (give steroids first) · overtreatment in the elderly (AF, fractures)

Cause	Clue	Key point
Hashimoto (chronic lymphocytic) thyroiditis	Most common cause in iodine-sufficient regions; women 30–50; painless goiter; anti-TPO +	Increased risk of primary thyroid lymphoma; associated with other autoimmune disease (T1DM, celiac, Addison, pernicious anemia)
Iatrogenic	Post-RAI, post-thyroidectomy, neck irradiation	Most common cause overall in treated Graves patients
Drugs	Amiodarone, lithium, interferon-α, immune checkpoint inhibitors, tyrosine kinase inhibitors	Amiodarone can cause hypo- or hyperthyroidism (iodine load)
Iodine deficiency	Most common cause worldwide; goiter	Rare in the US
Central (secondary/tertiary)	Low/normal TSH with low FT4; other pituitary deficits; headache, visual field cut	Replace cortisol before thyroid hormone; follow FT4, not TSH
Congenital	Newborn screening (TSH) mandatory; treat by 2 weeks to prevent intellectual disability	Most common preventable cause of intellectual disability

🩺 Pregnancy: increase levothyroxine 25–30% as soon as pregnancy is confirmed; target trimester-specific TSH (roughly <2.5 in the first trimester). Untreated maternal hypothyroidism impairs fetal neurodevelopment.

Primary vs Secondary Hypothyroidism

	Primary	Secondary (central)
TSH	↑	↓ or inappropriately normal
Free T4	↓	↓
Cause	Thyroid gland (Hashimoto, ablation, drugs, iodine)	Pituitary/hypothalamic (adenoma, surgery, radiation, Sheehan, apoplexy, infiltration)
Associated findings	Goiter, anti-TPO, other autoimmune disease	Hypogonadism, adrenal insufficiency, GH deficiency, headache, bitemporal hemianopsia
Monitoring	TSH	Free T4 (TSH is useless)
Trap	—	Start hydrocortisone before levothyroxine or you precipitate adrenal crisis

Myxedema Coma — EmergencyRecognize

Recognize: elderly woman with untreated hypothyroidism + precipitant (infection, cold, sedatives, MI) → hypothermia, bradycardia, hypotension, hypoventilation with hypercapnia, hyponatremia, hypoglycemia, altered mental status ("coma" is a misnomer — usually lethargy/confusion)
Labs: TSH markedly ↑ (unless central), FT4 ↓; check cortisol; ECG (bradycardia, low voltage); treat empirically — do not wait
Treatment: ICU; IV levothyroxine (200–400 µg load, then 50–100 µg daily; ± IV liothyronine); stress-dose hydrocortisone (100 mg q8h) until adrenal insufficiency is excluded; passive rewarming; treat the precipitant; supportive ventilation; cautious fluids (hyponatremia)
Mortality 30–60% — highest of the endocrine emergencies

⚠️ BOARD TRAP — Board Traps

Central hypothyroidism + levothyroxine alone → adrenal crisis. Give hydrocortisone first, thyroid hormone second.
Low T3 in an ICU patient → euthyroid sick syndrome; do not treat.
Elderly patient started on full-dose levothyroxine → angina, AF. Start at 12.5–25 µg.
Rechecking TSH 2 weeks after a dose change → too early; wait 6–8 weeks.
Amiodarone patient with new hypothyroidism → continue amiodarone if needed, add levothyroxine.
Hashimoto patient with a rapidly enlarging, firm goiter → thyroid lymphoma; biopsy.

★ Memory Trick

TSH is the thermostat. High TSH = the furnace (thyroid) is broken. Low TSH + low T4 = the thermostat (pituitary) is broken → check the rest of the house (cortisol). Myxedema coma: cold, slow, low (Na, glucose, BP) → warm, T4, steroids.

Tier 1

Topic T-2

Thyrotoxicosis — Graves, Toxic Nodules, Thionamides, Thyroid Storm

Five-Way Comparison · RAIU Pattern · Methimazole vs PTU · RAI Contraindications · Storm Sequence (Iodine AFTER Thionamide)

★★★ PANCE Core

Thyrotoxicosis — Recognize → Test → Confirm → Treat → Don't Miss

Recognize

Weight loss with good appetite, heat intolerance, palpitations, tremor, anxiety, insomnia, diarrhea, oligomenorrhea, proximal weakness, lid lag/stare, warm moist skin, AF in the elderly (may be "apathetic")

First test

TSH (suppressed) → free T4 (± T3)

Confirm

RAIU/scan pattern or TRAb/TSI

First-line treatment

β-blocker for symptoms + definitive therapy by cause (methimazole / RAI / surgery; NSAIDs-steroids for thyroiditis)

Don't miss

Thyroid storm · agranulocytosis on thionamides · RAI in pregnancy or active eye disease · AF/osteoporosis in the elderly

The Five-Way Thyrotoxicosis TableMemorize

	Graves disease	Toxic adenoma	Toxic multinodular goiter	Thyroiditis (subacute / painless / postpartum)	Exogenous thyroid hormone
TSH	↓	↓	↓	↓	↓
Free T4 / T3	↑ (T3 often disproportionately ↑)	↑ (T3 toxicosis common)	↑	↑ (transient)	↑ T4 (LT4) or ↑ T3 with low T4 (liothyronine)
RAI uptake	Diffusely ↑	↑ in nodule	Patchy ↑	↓ / absent	↓ / absent
Uptake pattern	Homogeneous, whole gland	Single hot nodule, rest suppressed	Multiple hot and cold areas	Near-zero uptake	Near-zero uptake
Antibodies	TRAb / TSI positive	Negative	Negative	Anti-TPO ± (painless/postpartum); negative (subacute)	Negative
Clinical clues	Young woman; diffuse goiter with bruit; ophthalmopathy (proptosis, diplopia); pretibial myxedema; acropachy	Solitary nodule; older; no eye signs	Elderly; long-standing nodular goiter; iodine load (amiodarone, contrast) unmasks it (Jod-Basedow)	Painful tender gland after viral URI + ↑ESR (subacute); painless postpartum; triphasic course	Weight-loss supplements, factitious use; low thyroglobulin; small gland
Treatment	Methimazole (PTU 1st trimester) · RAI (not in pregnancy/eye disease) · thyroidectomy	RAI or lobectomy	RAI or thyroidectomy (large goiter/compression)	β-blocker + NSAIDs/steroids for pain; thionamides do NOT work	Stop the hormone

Graves Disease — Specifics

Autoimmune: TSH-receptor stimulating antibodies (TRAb/TSI); most common cause of hyperthyroidism; women 20–40; HLA-DR3
Extrathyroidal signs occur ONLY in Graves: ophthalmopathy (proptosis, periorbital edema, diplopia, lid retraction — lid lag alone occurs in any thyrotoxicosis), pretibial myxedema (infiltrative dermopathy), thyroid acropachy
Methimazole first-line (once daily; less hepatotoxic); 12–18 months then attempt withdrawal (remission ~30–50%). PTU first trimester (methimazole causes aplasia cutis, choanal/esophageal atresia) and in thyroid storm; switch to methimazole after the first trimester (PTU hepatotoxicity)
Both thionamides: agranulocytosis (~0.3%; stop immediately and check CBC for fever/sore throat — do not monitor routinely), hepatotoxicity, rash, arthralgia, ANCA vasculitis (PTU)
Radioactive iodine (I-131): definitive; causes permanent hypothyroidism (expected); contraindicated in pregnancy, lactation, and severe/active ophthalmopathy (or cover with steroids); pretreat elderly/cardiac patients with methimazole; pregnancy test first; avoid pregnancy 6 months
Thyroidectomy: large goiter, compressive symptoms, coexisting nodule/cancer, pregnancy intolerant of thionamides, severe eye disease; render euthyroid first; risks: recurrent laryngeal nerve injury, hypoparathyroidism
Ophthalmopathy: stop smoking; selenium (mild); glucocorticoids or teprotumumab (moderate–severe active); orbital decompression for optic neuropathy

Thyroid Storm — EmergencyMemorize

Recognize: known or undiagnosed hyperthyroidism + precipitant (infection, surgery, RAI, iodine load, DKA, trauma, thionamide withdrawal) → fever (often >40 °C), tachycardia/AF out of proportion, agitation → delirium → coma, vomiting/diarrhea, jaundice, heart failure. Burch-Wartofsky score ≥45 supports. Hormone levels do not differ from uncomplicated thyrotoxicosis — it is a clinical diagnosis.
Treatment in this order:

1. β-blocker — propranolol (also blocks T4→T3 conversion) or esmolol; controls HR, tremor, agitation. Caution in decompensated HF.

↓

2. Thionamide — PTU preferred (blocks synthesis and peripheral T4→T3 conversion); methimazole acceptable. Give before iodine.

↓

3. Iodine — SSKI or Lugol solution ≥1 hour after the thionamide (Wolff-Chaikoff: blocks release). Given first, iodine feeds synthesis → worse storm.

↓

4. Glucocorticoid — hydrocortisone 100 mg IV q8h: blocks T4→T3 conversion and treats possible relative adrenal insufficiency.

↓

5. Supportive + precipitant — cooling (acetaminophen, not aspirin — displaces T4 from TBG), fluids, treat infection; cholestyramine to bind enterohepatic T4; plasmapheresis if refractory. Definitive therapy once stable.

⚠️ BOARD TRAP — Board Traps

Iodine before the thionamide in thyroid storm → fuels hormone synthesis. Thionamide first, iodine ≥1 hour later.
Aspirin for fever in thyroid storm → displaces T4 from binding proteins; use acetaminophen and cooling.
Methimazole in the first trimester → aplasia cutis, choanal atresia. PTU first trimester, then switch.
Thyrotoxicosis with low RAIU → thyroiditis or exogenous. Thionamides and RAI will not help.
Routine CBC monitoring on methimazole → not done; instruct the patient to stop and get a CBC for fever/sore throat.
Elderly patient with weight loss, AF, depression, and no tremor → apathetic thyrotoxicosis; check TSH.
Amiodarone-induced thyrotoxicosis: type 1 (iodine load, underlying nodular disease → thionamide) vs type 2 (destructive thyroiditis → steroids).

★ Memory Trick

Storm sequence: Beta → Block → (wait an hour) → Iodine → Steroids. "B-B-I-S." Eye + shin + finger clubbing = Graves only. Low uptake = leak or pills.

Tier 1

Topic T-3

Thyroiditis — Subacute, Painless, Postpartum, Drug-Induced

Triphasic Course · Low Uptake · NSAIDs/Steroids, Not Thionamides

★★★ PANCE Core

Thyroiditis — Compare the CausesRecognize

Type	Clue	Pain	Labs	RAIU	Course	Treatment
Subacute granulomatous (de Quervain)	Weeks after viral URI; middle-aged woman; malaise, fever	Exquisitely tender gland; pain radiates to jaw/ear	↑ESR, ↑CRP, low thyroglobulin release ↑; antibodies negative	↓	Thyrotoxic (2–8 wk) → hypothyroid (weeks–months) → recovery; ~10–15% permanent hypothyroidism	NSAIDs/aspirin; prednisone if severe; β-blocker for symptoms; levothyroxine for symptomatic hypothyroid phase (temporary)
Painless (silent) lymphocytic	Variant of Hashimoto; anti-TPO +	None	Anti-TPO +	↓	Same triphasic course; higher rate of permanent hypothyroidism	β-blocker; observe
Postpartum	Within 12 months of delivery (or miscarriage); anti-TPO +; ↑ in T1DM	None	Anti-TPO +	↓ (RAI contraindicated if breastfeeding anyway)	Thyrotoxic 1–4 mo → hypothyroid 4–8 mo → recovery; ~20–30% permanent; recurs in later pregnancies	β-blocker; levothyroxine for hypothyroid phase; annual TSH
Hashimoto (chronic)	Most common; goiter; hypothyroidism	None	Anti-TPO +, anti-Tg +	Variable	Progressive hypothyroidism; rare transient "Hashitoxicosis"	Levothyroxine
Drug-induced	Amiodarone (type 2 = destructive), lithium, interferon, checkpoint inhibitors (nivolumab, pembrolizumab)	None	Varies	↓	Hypo or hyper; checkpoint inhibitors → thyroiditis then hypothyroidism (also hypophysitis)	Steroids (amio type 2); stop drug if possible; replace
Acute suppurative (infectious)	Bacterial (Staph, Strep); child with pyriform sinus fistula; immunocompromised	Tender, erythema, fever, fluctuance	↑WBC; thyroid function usually normal	Normal	Abscess	IV antibiotics; drainage
Riedel (fibrous)	Rock-hard, fixed, painless goiter with compression; IgG4-related	None	Hypothyroid in 30%	↓	Fibrosis extends into neck	Steroids, tamoxifen; surgery for airway

⚠️ BOARD TRAP — Board Traps

Painful thyroid + thyrotoxicosis + ↑ESR → subacute thyroiditis. NSAIDs, not methimazole. The uptake is low because hormone is leaking, not being made.
Postpartum "depression" with fatigue and weight gain 6 months after delivery → check TSH; postpartum thyroiditis hypothyroid phase.
Giving RAI to a thyroiditis patient → nothing happens (uptake is zero) — and it is the wrong answer.
Thyrotoxic phase of thyroiditis treated with levothyroxine for the later hypothyroid phase → reassess at 6–12 months; most recover and do not need lifelong therapy.

★ Memory Trick

Painful + viral + high ESR = de Quervain ("quer-PAIN"). Every thyroiditis: hyper → hypo → (usually) normal. Treat the phase, not the gland.

Tier 1

Topic T-4

Thyroid Nodules & Thyroid Cancer

TSH → Scan or Ultrasound → FNA Thresholds · Bethesda · Papillary / Follicular / Medullary / Anaplastic

★★★ PANCE Core

Thyroid Nodule AlgorithmMemorize

Nodule found (palpation or incidental imaging) → history for risk: childhood neck radiation, family history of thyroid cancer/MEN2, rapid growth, hoarseness, fixed/hard nodule, cervical adenopathy, age <20 or >60, male.

↓

Serum TSH.

↓

TSH low → RAIU/scan. Hot (functioning) nodule → essentially never malignant → treat hyperthyroidism (RAI/surgery); no FNA. Cold nodule → proceed as below.

↓

TSH normal or high → thyroid ultrasound (first-line imaging): size, composition, echogenicity, margins, calcifications, shape, lymph nodes → TI-RADS/ATA risk category.

↓

Ultrasound-guided FNA if ≥1 cm with high/intermediate suspicion (hypoechoic solid, microcalcifications, irregular margins, taller-than-wide, extrathyroidal extension), ≥1.5 cm low suspicion, ≥2 cm very low suspicion. No routine FNA of nodules <1 cm (unless suspicious nodes/extension). Purely cystic → no FNA.

↓

Bethesda cytology: I nondiagnostic → repeat · II benign → US follow-up · III/IV indeterminate → molecular testing or lobectomy · V suspicious / VI malignant → surgery.

Thyroid Cancer — The Four TypesRecognize

Type	Frequency	Origin	Clue	Spread	Marker	Prognosis / treatment
Papillary	~80–85% (most common)	Follicular cell	Prior radiation; young woman; psammoma bodies, "Orphan Annie" nuclei; often multifocal	Lymphatic (cervical nodes) — still excellent prognosis	Thyroglobulin (post-op)	Excellent (>95% 10-yr). Lobectomy or total thyroidectomy ± RAI; TSH suppression
Follicular	~10%	Follicular cell	Iodine-deficient regions; FNA cannot distinguish adenoma from carcinoma (needs capsular/vascular invasion on histology)	Hematogenous (lung, bone)	Thyroglobulin	Good. Total thyroidectomy + RAI; Hürthle cell is a variant
Medullary	~2–5%	Parafollicular C cells	MEN 2A/2B (RET); calcitonin ↑; may cause diarrhea/flushing; amyloid stroma	Lymphatic and hematogenous	Calcitonin, CEA	Intermediate. Total thyroidectomy; screen for pheochromocytoma before surgery; prophylactic thyroidectomy in RET carriers; RAI useless (no iodine uptake)
Anaplastic	<2%	Dedifferentiated follicular cell	Elderly; rapidly enlarging, rock-hard mass; dysphagia, stridor, hoarseness; may arise from long-standing goiter/papillary	Local invasion, distant	—	Dismal (months). Tracheostomy/airway, palliative radiation/chemo; BRAF-targeted therapy in selected
Lymphoma	<2%	Lymphocytes	Hashimoto patient with rapidly enlarging goiter	—	—	Chemotherapy/radiation; core biopsy

⚠️ BOARD TRAP — Board Traps

Hot nodule → no FNA; it is functional, not cancer.
Nodule 0.8 cm with no suspicious features → surveillance, not FNA.
Follicular neoplasm on FNA → cannot be called benign or malignant by cytology; needs lobectomy for histology.
Medullary thyroid cancer → rule out pheochromocytoma (plasma metanephrines) and hyperparathyroidism before thyroidectomy; test RET; screen family.
Rising thyroglobulin after total thyroidectomy → recurrence (check anti-Tg antibodies, which invalidate the assay).
Hoarseness + fixed hard mass + rapid growth → anaplastic; secure the airway.

★ Memory Trick

Papillary = Popular, Psammoma, Positive prognosis, lymPh nodes. Follicular = Far away (blood → lung/bone). Medullary = MEN, calcitonin, Marker. Anaplastic = Aggressive, Airway.

Tier 1

Topic T-5

The Definitive Thyroid Matrix

Every Thyroid Diagnosis on One Grid · TSH / FT4 / Uptake / Antibody / Clue / First MoveMemorize

★★★ Highest YieldUptake Traps

Disease	TSH	FT4	RAIU	Antibody / Test	Classic Clue	First Move
Hashimoto	↑	↓	N/A	Anti-TPO	Woman, painless goiter, fatigue, weight gain; most common hypothyroidism	Levothyroxine 1.6 µg/kg; TSH at 6–8 wk
Central hypothyroidism	↓/normal	↓	N/A	Other pituitary axes, MRI	Headache, other deficiencies, prior surgery/radiation	Cortisol BEFORE levothyroxine
Subclinical hypothyroidism	↑	Normal	N/A	Anti-TPO	Incidental; pregnancy planning	Treat if TSH >10, pregnant, symptomatic + antibodies
Graves	↓	↑	↑ diffuse	TRAb / TSI	Young woman, diffuse goiter, bruit, ophthalmopathy, pretibial myxedema	Methimazole (PTU 1st trimester) or RAI or surgery; beta-blocker; steroids with RAI if eye disease
Toxic multinodular goiter	↓	↑	↑ patchy	None	Older patient, long-standing nodular goiter, iodine load	RAI or surgery; methimazole to bridge
Toxic adenoma	↓	↑	↑ single hot nodule	None	Solitary nodule; hot = benign	RAI or lobectomy; no FNA needed for a hot nodule
Subacute (de Quervain)	↓ then ↑	↑ then ↓	↓ (<5%)	ESR ↑	Painful tender gland after viral illness	NSAIDs/prednisone + beta-blocker; no thionamide
Painless / postpartum thyroiditis	↓ then ↑	↑ then ↓	↓	Anti-TPO	Painless; 1–6 months postpartum; triphasic; recurs	Beta-blocker; levothyroxine in the hypo phase; 20–30% permanent
Factitious thyrotoxicosis	↓	↑	↓	Thyroglobulin low	Health-care worker, weight-loss pills, no goiter	Stop the hormone; beta-blocker
Amiodarone / iodine	Variable	Variable	↓	IL-6, color Doppler	Amiodarone: type 1 (iodine-induced synthesis) vs type 2 (destructive thyroiditis)	Type 1 methimazole; type 2 prednisone; hypothyroidism from amiodarone = levothyroxine, continue drug
Thyroid storm	↓	↑	—	Burch-Wartofsky ≥45	Fever, HR >140, delirium, vomiting after stress in Graves	PTU/methimazole → iodine 1 h later → propranolol → hydrocortisone
Myxedema coma	↑↑	↓↓	—	Cortisol	Elderly, hypothermia, bradycardia, hyponatremia, obtunded, winter	IV levothyroxine + hydrocortisone (before or with); passive warming

TSH Shortcut

TSH HIGH: Hashimoto · subclinical hypothyroidism · recovery phase of thyroiditis · iodine deficiency · drugs (amiodarone, lithium, checkpoint inhibitors) · TSH-secreting adenoma (with high FT4 — rare)
TSH LOW + high uptake: Graves · toxic MNG · toxic adenoma | TSH LOW + low uptake: subacute/painless/postpartum thyroiditis · factitious · amiodarone type 2 · iodine load · struma ovarii
TSH LOW/NORMAL + low FT4: central hypothyroidism — check cortisol first

Interactive · Recognize It in Three Seconds

Endocrine Lab Pattern Challenge

Nine lab panels. Read the pair, name the pattern, then the diagnosis. Values are illustrative teaching panels, not patient data.

Domain 4 · Adrenal Disorders

Adrenal: Insufficiency, Crisis, Cushing, Aldosteronism, Pheochromocytoma, Incidentaloma

Tier 1

Topic A-1

Adrenal Insufficiency & Adrenal Crisis

Primary vs Secondary Table · Cosyntropin Test · Hydrocortisone Immediately · Fludrocortisone for Primary Only · Sick-Day Rules

★★★ PANCE Core

Adrenal Insufficiency — Recognize → Test → Confirm → Treat → Don't Miss

Recognize

Fatigue, anorexia, weight loss, nausea, abdominal pain, salt craving, orthostasis; hyperpigmentation (palmar creases, buccal mucosa, scars) in primary; hyponatremia, hyperkalemia (primary only), hypoglycemia, eosinophilia, mild hypercalcemia

First test

8 AM serum cortisol (<3 µg/dL diagnostic; >15–18 excludes) + simultaneous ACTH

Confirm

Cosyntropin (250 µg) stimulation test: cortisol <18–20 µg/dL at 30–60 min = insufficiency

First-line treatment

Hydrocortisone 15–25 mg/day divided (or prednisone); fludrocortisone 0.05–0.2 mg/day for primary only; sick-day rules; medical alert ID

Don't miss

Adrenal crisis · starting levothyroxine before cortisol in hypopituitarism · missing the diagnosis in a septic patient with refractory hypotension

Primary vs Secondary Adrenal InsufficiencyRecognize

	Primary (Addison disease)	Secondary / tertiary (central)
Site	Adrenal cortex destroyed (all three zones)	Pituitary ACTH deficiency or hypothalamic CRH suppression
Most common cause	Autoimmune adrenalitis (US; often with other autoimmune disease — APS-1/2); TB worldwide; also hemorrhage (meningococcemia, anticoagulation), metastasis, HIV/CMV, adrenoleukodystrophy, drugs (ketoconazole, etomidate, mitotane, checkpoint inhibitors)	Abrupt withdrawal of chronic glucocorticoids (most common); pituitary tumor/surgery/radiation, Sheehan, apoplexy, hypophysitis (checkpoint inhibitors), opioids
ACTH	↑↑	↓ or inappropriately normal
Cortisol	↓	↓
Aldosterone	↓ (renin ↑)	Normal (RAAS intact)
Sodium	↓ (aldosterone loss + ADH)	↓ (cortisol deficiency → ADH release)
Potassium	↑	Normal
Hyperpigmentation	Yes (↑ ACTH/MSH from POMC)	No
Cosyntropin response	Blunted (gland cannot respond)	Blunted if chronic (atrophy); may be normal in acute/recent onset — use insulin tolerance or metyrapone test
Other clues	Vitiligo, T1DM, Hashimoto, pernicious anemia, celiac (autoimmune polyglandular)	Other pituitary deficits (hypogonadism, hypothyroidism), headache, visual fields, prior steroid use
Treatment	Hydrocortisone + fludrocortisone	Hydrocortisone only (no fludrocortisone)

Adrenal Crisis — EmergencyMemorize

Recognize: shock refractory to fluids/pressors + hyponatremia ± hyperkalemia ± hypoglycemia, in a patient with known AI, on chronic steroids, or with a precipitant (infection, surgery, trauma, vomiting, steroid withdrawal). Also: bilateral adrenal hemorrhage (Waterhouse-Friderichsen — meningococcemia, anticoagulants, antiphospholipid).

↓

Treat immediately — do not wait for labs: hydrocortisone 100 mg IV bolus, then 50 mg q6h (or 200 mg/24 h infusion). If the diagnosis is unknown and time allows, draw cortisol + ACTH first, or use dexamethasone 4 mg (does not interfere with the cortisol assay).

↓

Fluids: 1–3 L isotonic saline with dextrose over the first hours. Treat hypoglycemia, hyperkalemia (usually resolves with cortisol and fluids), and the precipitant.

↓

Taper to maintenance over 2–3 days; add fludrocortisone once hydrocortisone <50 mg/day in primary AI. Educate: sick-day rules (double/triple dose for fever, injectable hydrocortisone kit), medical alert bracelet, stress-dose steroids for surgery.

⚠️ BOARD TRAP — Board Traps

Waiting for the cortisol result before treating a hypotensive Addisonian → death. Treat, then test.
Refractory hypotension in a patient on chronic prednisone who was NPO for surgery → adrenal crisis; give stress-dose hydrocortisone.
Hyperkalemia in secondary AI → does not happen; if K is high, think primary.
Normal cosyntropin test 2 weeks after pituitary surgery → does not exclude secondary AI (adrenals have not yet atrophied).
Fludrocortisone for secondary AI → unnecessary; aldosterone is intact.
Hypopituitarism: levothyroxine started before hydrocortisone → precipitates crisis.
Etomidate for intubation in septic shock → transient adrenal suppression; ketoconazole, mitotane, checkpoint inhibitors also cause AI.

★ Memory Trick

Primary = Pigmented, Potassium up, Pressure down. Secondary = Steroids stopped, Sodium low, Skin normal. Crisis: "Hydrocortisone first, hunt second." Sick-day rule: double the dose; can't keep it down → inject.

Tier 1

Topic A-2

Cushing Syndrome vs Cushing Disease — The Algorithm

Exclude Exogenous → Screen → ACTH → Dependent vs Independent → Localize → Treat

★★★ PANCE Core

Cushing Syndrome vs Cushing Disease — Get the Words Right

Term	Meaning	Share of endogenous cases
Cushing syndrome	Any state of cortisol excess — exogenous (most common overall) or endogenous	—
Cushing disease	ACTH-secreting pituitary adenoma (usually microadenoma); women 3–8:1	~65–70%
Ectopic ACTH	Small cell lung cancer, bronchial/thymic carcinoid, medullary thyroid, pheochromocytoma; rapid course, hypokalemia, weight loss, hyperpigmentation	~10–15%
Adrenal (ACTH-independent)	Adrenal adenoma (benign, cortisol only), adrenal carcinoma (large, virilizing, rapid), bilateral nodular hyperplasia	~15–20%
Pseudo-Cushing	Alcohol use disorder, depression, obesity, poorly controlled diabetes, pregnancy — mild biochemical hypercortisolism without the disease	—

Recognize the Cushingoid PatientRecognize

Most specific findings: proximal muscle weakness, wide (>1 cm) violaceous striae, easy bruising, facial plethora, osteoporosis in the young — these separate Cushing from simple obesity
Classic but nonspecific: central obesity, moon facies, dorsocervical and supraclavicular fat pads, hirsutism, acne, oligomenorrhea, hypertension, hyperglycemia, hypokalemia (ectopic), depression/psychosis, infections, poor wound healing, nephrolithiasis
Exogenous: any oral, injected, inhaled, or high-potency topical glucocorticoid — including "herbal" preparations; ask before you test

The Cushing AlgorithmMemorize

Suspected Cushing syndrome

↓

Exclude exogenous glucocorticoids (history, medication review, including inhaled/topical/joint injections). If exogenous → taper; no further testing.

↓

Screen for hypercortisolism — any of: 1-mg overnight DST (AM cortisol ≥1.8 µg/dL abnormal) · late-night salivary cortisol ×2 · 24-h urinary free cortisol ×2 (>3–4× ULN). Two concordant abnormal tests = confirmed. (DST false positives: estrogen/OCPs ↑CBG, CYP3A4 inducers; use salivary/UFC in those.)

↓

Plasma ACTH (8–9 AM)

↓

ACTH suppressed (<5–10 pg/mL) → ACTH-independent → adrenal CT (adenoma vs carcinoma vs bilateral hyperplasia) → adrenalectomy. ▸ ACTH normal/high (>20) → ACTH-dependent → pituitary vs ectopic.

↓

Localize ACTH-dependent disease: pituitary MRI (adenoma ≥6 mm supports); high-dose 8-mg DST (pituitary suppresses >50%; ectopic does not); CRH stimulation; inferior petrosal sinus sampling is the gold standard when MRI is equivocal (central:peripheral ACTH gradient ≥2–3). Ectopic → CT chest/abdomen, octreotide/DOTATATE scan.

↓

Treat the source: Cushing disease → transsphenoidal surgery (first-line); radiation or bilateral adrenalectomy if it fails (watch for Nelson syndrome). Adrenal → adrenalectomy. Ectopic → resect tumor. Medical bridge: ketoconazole, metyrapone, osilodrostat, mifepristone, cabergoline/pasireotide. Post-op: stress-dose steroids, taper slowly — the axis is suppressed.

⚠️ BOARD TRAP — Board Traps

Ordering a pituitary MRI first → 10% of people have an incidental pituitary lesion; biochemistry must come first.
Random cortisol to diagnose Cushing → useless.
DST in a woman on oral contraceptives → false positive from ↑ cortisol-binding globulin; use salivary or urinary cortisol.
Hypokalemia + rapid weight loss + hyperpigmentation + smoker → ectopic ACTH (small cell), not Cushing disease.
Alcoholic with moon facies and elevated UFC → pseudo-Cushing; repeat after abstinence (dexamethasone-CRH test).
After curative pituitary surgery the patient becomes hypotensive and nauseated → expected postoperative adrenal insufficiency; give hydrocortisone.

★ Memory Trick

Syndrome = the state. Disease = the pituitary. Step order: Steroids? → Screen (DST/saliva/urine) → ACTH → Scan. Low ACTH = adrenal (CT belly). High ACTH = pituitary or ectopic (MRI head, high-dose DST, IPSS).

Tier 1

Topic A-3

Primary Aldosteronism, Pheochromocytoma & the Adrenal Incidentaloma

ARR → Salt Load → AVS · Metanephrines → Imaging → α Then β → Surgery · Incidentaloma: Functional? Malignant?

★★★ PANCE Core

Primary Aldosteronism (Conn Syndrome) — Most Common Secondary Hypertension

Recognize

Hypertension (often resistant or early-onset) ± hypokalemia (only ~30–40% have low K), muscle cramps/weakness, metabolic alkalosis, mild hypernatremia; adrenal incidentaloma with HTN; family history; OSA

First test

Plasma aldosterone concentration / plasma renin activity ratio (ARR) — aldosterone >15 ng/dL with suppressed renin; correct K first; stop spironolactone/eplerenone ≥4 wk (most other antihypertensives can continue for the screen)

Confirm

Saline infusion test (aldosterone fails to suppress <10 ng/dL) or oral salt loading (24-h urine aldosterone >12 µg); then adrenal CT; adrenal vein sampling to lateralize if surgery is considered (age >35)

First-line treatment

Unilateral adenoma → laparoscopic adrenalectomy. Bilateral hyperplasia (more common) or non-surgical → spironolactone (or eplerenone if gynecomastia)

Don't miss

Screening every resistant hypertensive · attributing hypokalemia to a diuretic · CT alone (nonfunctioning nodules are common) · secondary hyperaldosteronism (renin HIGH: renal artery stenosis, CHF, cirrhosis, diuretics)

	Primary aldosteronism	Secondary hyperaldosteronism	Apparent mineralocorticoid excess / licorice
Aldosterone	↑	↑	↓
Renin	↓ (suppressed)	↑	↓
Cause	Adenoma / bilateral hyperplasia	Renal artery stenosis, CHF, cirrhosis, nephrotic, diuretics	Licorice (glycyrrhizic acid inhibits 11β-HSD2), Liddle syndrome (ENaC), Cushing, CAH (11β/17α)
Edema	No (aldosterone escape)	Yes	No

Pheochromocytoma — Recognize → Test → Localize → Alpha → Beta → Surgery

Recognize

Episodic headache, sweating, palpitations (classic triad) with paroxysmal or sustained hypertension; pallor (not flushing), tremor, anxiety, weight loss, orthostasis, hyperglycemia; crises with anesthesia, β-blockers, contrast, metoclopramide, TCAs; young patient, refractory HTN, or hereditary syndrome (MEN2, VHL, NF1, SDH mutations)

First test

Plasma free metanephrines (highest sensitivity; best in high-risk/hereditary) or 24-h urine fractionated metanephrines and catecholamines (better specificity for low-risk); avoid TCAs, levodopa, decongestants, acetaminophen (assay), caffeine before testing

Confirm

CT or MRI abdomen/pelvis (90% adrenal; 10% extra-adrenal paraganglioma); MIBG or DOTATATE scan if CT negative or metastatic/extra-adrenal suspected; genetic testing (30–40% hereditary)

First-line treatment

α-blockade first (phenoxybenzamine, or doxazosin) for 10–14 days with liberal salt/fluids → then β-blocker if tachycardic → laparoscopic adrenalectomy; expect post-op hypotension and hypoglycemia

Don't miss

β-blocker before α-blockade (unopposed α → hypertensive crisis) · FNA/biopsy of an unblocked pheo · undiagnosed pheo going to surgery · medullary thyroid cancer patient going to thyroidectomy without pheo screen

Classic symptoms — episodic headache, diaphoresis, palpitations + hypertension

↓

Plasma free metanephrines or 24-h urine fractionated metanephrines

↓

Imaging / localization — CT or MRI abdomen; MIBG/DOTATATE if needed

↓

ALPHA BLOCKADE — phenoxybenzamine (irreversible) or doxazosin; 10–14 days; salt + fluid loading; calcium channel blocker as add-on

↓

Then beta blockade only if reflex tachycardia — never first

↓

Surgery — laparoscopic adrenalectomy; anesthesia team aware; post-op watch for hypotension/hypoglycemia; lifelong follow-up (10% malignant, recurrence)

🩺 Rule of 10s (approximate): 10% bilateral, 10% extra-adrenal, 10% malignant, 10% in children, 10% not hypertensive — and now ~30–40% hereditary. Hereditary or bilateral disease → consider cortical-sparing surgery.

Adrenal Incidentaloma — Two QuestionsRecognize

Question	Test	Action threshold
Is it functional?	1-mg DST (all) · plasma/urine metanephrines (all) · ARR (if HTN or hypokalemia) · DHEA-S/androgens (if virilization or suspected carcinoma)	Any hormone excess → surgery (or medical therapy for aldosteronism/subclinical Cushing per patient)
Is it malignant?	Unenhanced CT attenuation (≤10 HU = lipid-rich adenoma), size, homogeneity, contrast washout (>60% absolute at 15 min = adenoma), growth on 6–12-month repeat	>4 cm, >10 HU with poor washout, heterogeneous, irregular, or growing → adrenalectomy; known extra-adrenal cancer → possible metastasis (biopsy only after pheo excluded)

⚠️ BOARD TRAP — Board Traps

Propranolol for a tachycardic hypertensive patient with headaches and sweating → unopposed α-stimulation → hypertensive crisis. Alpha first.
Ordering CT before metanephrines → wrong order; biochemistry first (except in the incidentaloma, where the mass is already found).
Hypokalemia blamed on hydrochlorothiazide in a resistant hypertensive → screen ARR anyway.
Hypertension + hypokalemia + edema → secondary hyperaldosteronism (high renin), not Conn.
Metanephrines drawn while on a TCA or after acetaminophen → false positive; repeat off interfering drugs, seated and rested.

★ Memory Trick

Pheo: the 3 P's — Pressure, Pain (head), Perspiration, Palpitations → Plasma metanephrines → Phenoxybenzamine (α) before Propranolol (β). Conn: high aldo, LOW renin, no edema. Secondary: high aldo, HIGH renin, edema.

Tier 3

Topic A-4

Congenital Adrenal Hyperplasia

21-OH (salt-wasting + virilization) · 11β-OH (HTN + virilization) · 17α-OH (HTN + no sex steroids)

★ Rapid review

Congenital Adrenal Hyperplasia — Rapid ReviewReference

Enzyme deficiency	Cortisol	Aldosterone / BP	Sex steroids	Marker	Presentation
21-hydroxylase (>90%)	↓	↓ → salt wasting, hypotension, hyperkalemia	↑ androgens	↑ 17-hydroxyprogesterone	Virilized XX infant; salt-wasting crisis week 1–3; nonclassic → hirsutism, acne, irregular menses (PCOS mimic)
11β-hydroxylase	↓	↑ 11-deoxycorticosterone → HTN, hypokalemia	↑ androgens	↑ 11-deoxycortisol	Virilization + hypertension
17α-hydroxylase	↓	↑ mineralocorticoids → HTN, hypokalemia	↓ (both androgens and estrogens)	↓ 17-OHP, ↑ corticosterone	XY: ambiguous/female external genitalia; XX: primary amenorrhea, no puberty; hypertension

Treatment: hydrocortisone (suppresses ACTH-driven androgen excess) + fludrocortisone + salt for salt-wasters; stress dosing; nonclassic — glucocorticoid only if symptomatic, or OCP/antiandrogen for hirsutism
Newborn screen measures 17-OHP; false positives in preterm/stressed infants
Mnemonic: "1" in the first digit (21, 11) → hypertension if the second digit is 1 (11β); "1" in the second digit only (17, 11) → hypertension. 21 = the only one with low BP.

Domain 5 · Calcium, Parathyroid & Bone

Calcium & PTH: Hypercalcemia Workup, Hypocalcemia, Osteoporosis, Paget, Osteomalacia

Tier 1

Topic C-1

Hypercalcemia, Primary Hyperparathyroidism & the PTH Pattern Table

Correct the Calcium · PTH Pivot · Primary / Secondary / Tertiary / Malignancy / Vitamin D / FHH · Hypercalcemic Crisis

★★★ PANCE Core

First, Confirm the Calcium

Corrected calcium = measured Ca + 0.8 × (4.0 − albumin). Low albumin lowers total calcium without changing ionized calcium; high albumin (dehydration) or myeloma paraproteins raise it. When in doubt, measure ionized calcium.
Alkalosis (hyperventilation) lowers ionized calcium without changing total calcium → tetany with a "normal" calcium.
Repeat any unexpected value before working it up.

The Calcium/PTH Lab-Pattern TableMemorize

	Ca	PTH	Phosphate	25-OH vitamin D	Major clinical clue	Treatment
Primary hyperparathyroidism	↑	↑ or inappropriately normal	↓	Normal / ↓	Asymptomatic outpatient; stones, osteoporosis, ↑ urine Ca; single adenoma 85%; ↑ chloride, ↑ alk phos, ↓ bicarbonate	Parathyroidectomy if indicated; otherwise monitor; cinacalcet if not surgical
Secondary hyperparathyroidism (CKD)	↓ or normal	↑↑	↑	↓ (↓ 1,25-D)	CKD stage 4–5; renal osteodystrophy; vitamin D deficiency also causes it (with low phosphate)	Phosphate binders, calcitriol/analog, cinacalcet; treat vitamin D deficiency
Tertiary hyperparathyroidism	↑	↑↑↑ (autonomous)	↑	Variable	Long-standing CKD/dialysis or after transplant; glands became autonomous	Parathyroidectomy
Hypercalcemia of malignancy	↑↑ (often >13)	↓ (suppressed)	↓ (PTHrP) or ↑ (lytic)	Normal (↑ 1,25-D in lymphoma)	Inpatient, symptomatic, rapid; PTHrP (squamous lung, renal, breast) · lytic mets (breast, myeloma) · 1,25-D (lymphoma)	Saline → calcitonin + bisphosphonate; denosumab; steroids for lymphoma; treat cancer
Vitamin D deficiency	↓ or normal	↑	↓	↓↓	Osteomalacia/rickets; bone pain, proximal weakness, pseudofractures (Looser zones); ↑ alk phos; malabsorption, CKD, little sun, anticonvulsants	Vitamin D₃ (or D₂ 50,000 IU weekly ×8) + calcium
Familial hypocalciuric hypercalcemia	↑ (mild, lifelong)	Normal / mildly ↑	Normal	Normal	24-h urine Ca LOW (Ca/Cr clearance ratio <0.01); family history; CaSR mutation; asymptomatic	No surgery — benign
Hypoparathyroidism	↓	↓	↑	Normal	Post-thyroidectomy (most common), autoimmune (APS-1), DiGeorge, hypomagnesemia, radiation	Calcium + calcitriol (± thiazide); rhPTH if refractory
Pseudohypoparathyroidism	↓	↑ (resistance)	↑	Normal	Albright hereditary osteodystrophy: short stature, round face, short 4th/5th metacarpals, obesity	Calcium + calcitriol

Primary Hyperparathyroidism — Recognize → Test → Confirm → Treat → Don't Miss

Recognize

Most common cause of outpatient hypercalcemia; women >50; usually asymptomatic on screening labs; "stones (kidney), bones (osteoporosis, osteitis fibrosa cystica, subperiosteal resorption), abdominal groans (constipation, pancreatitis, PUD), psychiatric moans (depression, fatigue, confusion)"; polyuria; short QT

First test

Serum calcium (corrected/ionized) + intact PTH

Confirm

High/inappropriately normal PTH with high Ca; 24-h urine calcium (to exclude FHH and assess stone risk); 25-OH D; creatinine/eGFR; DEXA (include distal radius); renal imaging for stones

First-line treatment

Parathyroidectomy (single adenoma 85%, four-gland hyperplasia 15% — MEN1/2A; carcinoma <1%) — sestamibi/ultrasound/4D-CT localize after the biochemical diagnosis; medical: hydration, avoid thiazides/lithium, bisphosphonate for bone, cinacalcet for calcium

Don't miss

FHH masquerading (check urine Ca before surgery) · MEN syndromes (young, multigland) · hungry bone syndrome after surgery (profound hypocalcemia) · thiazide/lithium-induced hypercalcemia

Surgical indication (asymptomatic primary HPT)	Threshold
Serum calcium	>1.0 mg/dL above the upper limit of normal
Bone	T-score ≤ −2.5 at any site or vertebral fracture
Kidney	eGFR <60 · 24-h urine Ca >400 mg with increased stone risk · nephrolithiasis/nephrocalcinosis on imaging
Age	<50 years
Any symptomatic patient	Surgery

Hypercalcemia — Other Causes to RecognizeRecognize

Granulomatous disease (sarcoidosis, TB): macrophage 1α-hydroxylase → ↑1,25-D; PTH suppressed; treat with steroids
Vitamin D or A toxicity; milk-alkali syndrome (calcium carbonate + antacids → hypercalcemia, alkalosis, AKI)
Drugs: thiazides (↓ renal Ca excretion — often unmasks mild primary HPT), lithium (↑ PTH set point), teriparatide
Hyperthyroidism (bone turnover), immobilization (Paget, young), adrenal insufficiency, pheochromocytoma, MEN

⚠️ BOARD TRAP — Board Traps

Mild hypercalcemia with normal PTH → still primary HPT until proven otherwise (PTH should be suppressed when calcium is high); rule out FHH with urine calcium.
Sestamibi ordered to diagnose hyperparathyroidism → wrong; it localizes for surgery after the biochemical diagnosis; a negative scan does not exclude disease.
Low urine calcium + hypercalcemia + family history → FHH; parathyroidectomy will not help.
Hypercalcemia in a patient on a thiazide → stop it and recheck before the workup.
Furosemide as first-line for hypercalcemia → only after saline repletion.
Hypercalcemia + normal PTH + normal PTHrP + lymphoma → check 1,25-D; treat with steroids.

★ Memory Trick

PTH is the switch: HIGH-Ca/HIGH-PTH = parathyroid (or FHH — check the urine). HIGH-Ca/LOW-PTH = cancer, D, granuloma, thyroid, drugs. Crisis: "Saline, then calcitonin now, bisphosphonate for later." Surgery for HPT: Ca >1 over, bone ≤ −2.5, kidney <60/stones, age <50.

Tier 1

Topic C-2

Hypocalcemia & Hypoparathyroidism

Chvostek/Trousseau · QT Prolongation · Magnesium First · Calcium + Calcitriol · DiGeorge · Pseudohypoparathyroidism

★★★ PANCE Core

Hypocalcemia — Recognize → Test → Confirm → Treat → Don't Miss

Recognize

Perioral and acral paresthesias, muscle cramps, tetany, carpopedal spasm, laryngospasm, seizures; Chvostek (facial nerve tap → twitch) and Trousseau (cuff inflation → carpal spasm — more specific); prolonged QT; chronic: cataracts, basal ganglia calcification, dry skin, dental defects

First test

Ionized calcium (or albumin-corrected), phosphate, magnesium, PTH, creatinine, 25-OH D

Confirm

Low PTH → hypoparathyroidism (surgical, autoimmune, DiGeorge, hypomagnesemia, infiltrative). High PTH → vitamin D deficiency/CKD (low phosphate = D deficiency; high phosphate = CKD or pseudohypoparathyroidism), pancreatitis, tumor lysis, rhabdomyolysis, citrate, loop diuretics, bisphosphonate/denosumab

First-line treatment

Symptomatic or Ca <7.5: IV calcium gluconate 1–2 g over 10–20 min then infusion; correct magnesium; chronic: oral calcium carbonate/citrate + calcitriol (hypoparathyroidism) or vitamin D₃ (deficiency); thiazide to reduce hypercalciuria

Don't miss

Hypomagnesemia (PPIs, alcohol, diuretics, cisplatin) causing refractory hypocalcemia — replace Mg first · hungry bone syndrome after parathyroidectomy · calcium infusion through the same line as bicarbonate/phosphate (precipitates) · digoxin toxicity potentiated by calcium

Cause	Ca	Phosphate	PTH	Clue
Hypoparathyroidism (surgical, autoimmune, DiGeorge)	↓	↑	↓	Neck surgery; APS-1 (candidiasis, Addison); DiGeorge (22q11: cardiac defects, thymic aplasia, cleft palate)
Hypomagnesemia	↓	Variable	↓ or inappropriately normal (impaired secretion and action)	Alcohol, PPIs, diuretics, diarrhea; calcium will not correct until Mg is replaced
Vitamin D deficiency / osteomalacia	↓	↓	↑	Malabsorption, minimal sun, anticonvulsants, CKD; ↑ alk phos; bone pain
CKD	↓	↑	↑	Low 1,25-D, phosphate retention
Pseudohypoparathyroidism	↓	↑	↑	End-organ PTH resistance; Albright phenotype
Acute pancreatitis / rhabdomyolysis / tumor lysis	↓	↑ (TLS, rhabdo)	↑	Saponification (pancreatitis); phosphate release (TLS/rhabdo)
Massive transfusion / citrate	↓ ionized	Normal	↑	Chelation; total Ca may be normal

⚠️ BOARD TRAP — Board Traps

Hypocalcemia that will not correct with IV calcium → check and replace magnesium.
Low total calcium with low albumin → correct it (or check ionized) before treating.
Post-thyroidectomy hypocalcemia treated with vitamin D₂/D₃ → inactive; use calcitriol (no PTH → no 1α-hydroxylation).
Chronic hypoparathyroidism calcium target → low-normal (8–8.5); higher targets cause hypercalciuria and nephrocalcinosis.
Tetany with a normal calcium after hyperventilation → alkalosis lowers ionized calcium; treat the anxiety, not the calcium.

★ Memory Trick

Chvostek = Cheek. Trousseau = Tourniquet (more specific). Low Ca + high phos = parathyroid or kidney problem. Low Ca + low phos = vitamin D problem. No PTH → no active D → give calcitriol.

Tier 2

Topic C-3

Osteoporosis

DEXA T-score ≤ −2.5 · FRAX · Secondary Causes · Bisphosphonate → Denosumab → Anabolic · Drug Holiday

★★ Frequently tested

Osteoporosis — Screening, Diagnosis, Treatment

Screen with DEXA: all women ≥65; postmenopausal women <65 with risk factors (FRAX ≥ age-65 equivalent risk, low weight, prior fracture, smoking, glucocorticoids, RA, parental hip fracture, alcohol ≥3/day); men ≥70 (Endocrine Society; USPSTF: insufficient evidence for men); anyone with a fragility fracture or on chronic glucocorticoids (≥7.5 mg prednisone ≥3 months)
Diagnosis: T-score ≤ −2.5 at lumbar spine, femoral neck, total hip, or distal radius; or a hip or vertebral fragility fracture regardless of T-score; or osteopenia (T −1 to −2.5) with FRAX 10-year hip ≥3% or major osteoporotic ≥20%. Z-score (age-matched) ≤ −2.0 in premenopausal women/young men → look for a secondary cause
Secondary causes to exclude: hyperparathyroidism, hyperthyroidism, Cushing/glucocorticoids, hypogonadism, vitamin D deficiency, celiac, myeloma, CKD, anticonvulsants, PPIs, aromatase inhibitors/androgen deprivation, anorexia, immobilization — check CBC, CMP, 25-OH D, PTH, TSH, testosterone (men), ± SPEP, celiac serology, 24-h urine Ca
Universal measures: calcium 1,000–1,200 mg/day (diet preferred), vitamin D 800–1,000 IU/day (target 25-OH D ≥30), weight-bearing and resistance exercise, fall prevention, stop smoking, limit alcohol, review sedatives/antihypertensives

Drug	Mechanism	Fracture benefit	Key adverse effects / rules
Alendronate, risedronate (oral); zoledronic acid (IV yearly); ibandronate (vertebral only)	Antiresorptive (osteoclast apoptosis)	Vertebral + hip + non-vertebral	Esophagitis (take upright, empty stomach, water only, wait 30 min); avoid if eGFR <30–35; osteonecrosis of the jaw (dental exam first); atypical femoral fracture with long use (thigh pain → X-ray); flu-like reaction after IV; drug holiday after 5 yr oral / 3 yr IV if low risk
Denosumab (SC q6 months)	RANKL antibody	Vertebral + hip + non-vertebral	Hypocalcemia (correct vitamin D first; caution in CKD); ONJ, atypical fracture; rebound vertebral fractures if stopped without transition to a bisphosphonate; usable in renal impairment
Teriparatide, abaloparatide (daily SC, ≤2 yr)	Anabolic (PTH/PTHrP analog)	Vertebral + non-vertebral (greatest BMD gain)	Hypercalcemia, orthostasis, leg cramps; avoid with Paget, prior radiation, open epiphyses, bone malignancy; follow with an antiresorptive
Romosozumab (monthly SC, 12 months)	Anabolic + antiresorptive (sclerostin antibody)	Vertebral + hip	Boxed warning: MI, stroke — avoid within 1 yr of CV event; follow with an antiresorptive
Raloxifene	SERM	Vertebral only	VTE, hot flashes; ↓ breast cancer risk
Estrogen	Antiresorptive	Vertebral + hip	VTE, stroke, breast cancer; for menopausal symptoms in women <60 / <10 yr from menopause
Calcitonin	Weak antiresorptive	Vertebral (weak)	Malignancy signal; last resort; useful for acute vertebral fracture pain

🩺 Who gets an anabolic first? Very high risk — T-score ≤ −3.0, multiple or recent vertebral fractures, fracture on therapy. Anabolic → then bisphosphonate/denosumab to lock in gains. Glucocorticoid-induced: start a bisphosphonate at prednisone ≥7.5 mg for ≥3 months in moderate/high-risk patients.

⚠️ BOARD TRAP — Board Traps

Stopping denosumab without transitioning to a bisphosphonate → multiple vertebral fractures within a year.
Bisphosphonate with eGFR 25 → contraindicated; use denosumab (with careful calcium/vitamin D).
New thigh/groin pain on a bisphosphonate for 8 years → atypical femoral fracture; X-ray both femurs, stop the drug.
Vertebral fracture with a T-score of −1.8 → this is osteoporosis; treat.
Premenopausal woman with low bone density → use Z-score; look for a cause (anorexia, celiac, Cushing, hyperparathyroidism) before drugs.
Teriparatide in a patient with Paget disease or prior skeletal radiation → osteosarcoma concern; avoid.

★ Memory Trick

−2.5 = the number. Hip/spine fracture = the diagnosis regardless of number. Bisphosphonate: "Sit up, stomach empty, kidneys ≥35." Denosumab: never just stop. Romosozumab: bones up, heart risk up.

Tier 3

Topic C-4

Paget Disease & Osteomalacia

Isolated ↑ Alk Phos = Paget · Low D / Low Phos / High PTH = Osteomalacia · Bisphosphonate vs Vitamin D

★ Rapid review

Paget Disease of Bone vs Osteomalacia — Rapid ReviewReference

	Paget disease	Osteomalacia / rickets
Mechanism	Disordered, accelerated remodeling (osteoclast → chaotic woven bone); possibly paramyxovirus; age >55; men	Defective mineralization of osteoid — vitamin D deficiency (most), phosphate wasting (FGF23 tumors, XLH), renal tubular acidosis, aluminum, anticonvulsants, malabsorption/gastric bypass
Presentation	Often asymptomatic; bone pain, bowing of tibia, skull enlargement (hat no longer fits), hearing loss (CN VIII), warmth over bone (↑ vascularity), high-output HF (rare), kyphosis, fractures	Diffuse bone pain and tenderness, proximal muscle weakness (waddling gait), fractures; rickets in children: bowed legs, rachitic rosary, widened wrists, delayed fontanelle closure
Labs	Isolated ↑ alkaline phosphatase (bone-specific) with normal Ca, phosphate, PTH; ↑ urine hydroxyproline/NTx; hypercalcemia only with immobilization	↓ or normal Ca, ↓ phosphate, ↑ alk phos, ↑ PTH (secondary), ↓ 25-OH D (<10–12 ng/mL)
Imaging	Lytic then sclerotic, thickened cortex, "cotton-wool" skull, "picture-frame" vertebrae; bone scan shows extent	Looser zones (pseudofractures — symmetric radiolucent lines), osteopenia; children: cupped, frayed metaphyses
Complications	Osteosarcoma (<1%) — new pain/swelling or rising alk phos; nerve compression; osteoarthritis	Fractures, hypocalcemic tetany (rare)
Treatment	Zoledronic acid (single IV) or oral bisphosphonate for symptoms, involvement of weight-bearing bone/skull/spine, or before orthopedic surgery; calcitonin if bisphosphonate contraindicated; analgesics	Vitamin D₃ (or D₂ 50,000 IU weekly × 8 weeks then maintenance) + calcium; phosphate + calcitriol for phosphate-wasting forms; burosumab for XLH

⚠️ BOARD TRAP — Board Traps

Elevated alkaline phosphatase with normal GGT and normal calcium in an older man → bone source → Paget; do not chase the liver.
Bone pain + proximal weakness + low phosphate + high PTH → osteomalacia from vitamin D deficiency, not primary hyperparathyroidism (calcium is low/normal).
Paget patient with sudden increase in pain and alk phos → osteosarcoma; image.

Domain 6 · Pituitary & Hypothalamic Disorders

Pituitary: Adenomas, Prolactinoma, Acromegaly, Hypopituitarism, Apoplexy, DI vs SIADH

Tier 1

Topic P-1

Pituitary Adenomas & Prolactinoma

Functioning vs Nonfunctioning · Mass Effect · Hyperprolactinemia Differential · Dopamine Agonist First

★★★ PANCE Core

Pituitary Adenoma Framework — The Rule, Stated CorrectlyMemorize

Adenoma	Presentation	Diagnosis	First-line treatment
Prolactinoma (most common functioning, ~40%)	Women: amenorrhea/oligomenorrhea, galactorrhea, infertility. Men: low libido, ED, gynecomastia, often large tumors with mass effect (diagnosed late). Both: bone loss	Prolactin (level scales with size); exclude pregnancy, drugs, hypothyroidism, renal failure, stalk effect; MRI	Dopamine agonist — cabergoline (or bromocriptine in pregnancy planning) — regardless of size; surgery only for resistance, intolerance, apoplexy, CSF leak
GH-secreting (acromegaly)	Acral growth, coarse features, sweating, OSA, diabetes, HTN, arthropathy, carpal tunnel, colon polyps	IGF-1 → OGTT GH suppression → MRI	Transsphenoidal surgery; then somatostatin analog / pegvisomant / cabergoline
ACTH-secreting (Cushing disease)	Cushing syndrome	Screen for hypercortisolism → ACTH → MRI / IPSS	Transsphenoidal surgery
TSH-secreting (rare)	Hyperthyroidism with a non-suppressed TSH	TSH normal/↑ with FT4 ↑; α-subunit; MRI	Transsphenoidal surgery ± somatostatin analog
Nonfunctioning (~30–40%; often gonadotroph)	Mass effect: headache, bitemporal hemianopsia, CN III/IV/VI palsies (cavernous sinus), hypopituitarism, mild stalk-effect hyperprolactinemia; or incidental	Full hormone panel (exclude secretion; assess deficiencies) + formal visual fields for any lesion near the chiasm	Depends on size, symptoms, hormone deficits, and mass effect: microadenoma → observe with MRI; macroadenoma with visual/neurologic compromise or growth → transsphenoidal surgery; hypopituitarism → replace

🩺 The rule: prolactinoma → dopamine agonist first. Symptomatic functioning non-prolactin adenomas → transsphenoidal surgery. Nonfunctioning/incidental lesions → decision by size, symptoms, hormone abnormalities, and mass effect. "Everything but prolactinoma gets surgery" is an oversimplification that fails the incidentaloma question.

Pituitary Incidentaloma & Mass Effect

Microadenoma (<10 mm): hormone screen (prolactin, IGF-1, ± cortisol screen); if nonfunctioning, MRI at 1 year then less often; no visual fields needed unless near the chiasm
Macroadenoma (≥10 mm): full anterior pituitary panel for hypersecretion and hypopituitarism; formal visual field testing if abutting the chiasm; surgery for visual compromise, apoplexy, or growth
Bitemporal hemianopsia = chiasm compression from below; lateral extension into the cavernous sinus → CN III, IV, VI, V1/V2 palsies
Craniopharyngioma: child (or bimodal adult) with a calcified, cystic suprasellar mass; growth failure, DI, visual loss; surgery ± radiation
Empty sella: CSF fills the sella (often after infarction/surgery or idiopathic); usually normal function — evaluate, do not operate

Hyperprolactinemia — Before You Call It a TumorRecognize

Cause	Typical prolactin	Clue
Pregnancy / lactation	Up to ~200–300	Pregnancy test first — always
Medications (antipsychotics, metoclopramide, domperidone, methyldopa, verapamil, SSRIs, opioids, estrogens)	25–100 (risperidone can exceed)	Timing with the drug; do not add a dopamine agonist to an antipsychotic
Primary hypothyroidism	Mild	TRH stimulates lactotrophs; check TSH
Renal failure	Mild–moderate	Reduced clearance
Stalk effect (any sellar/suprasellar mass, hypophysitis)	<100–150	Loss of dopamine inhibition; prolactin does not match tumor size
Microprolactinoma	100–250	—
Macroprolactinoma	>250, often >1,000	Prolactin roughly proportional to size; beware hook effect
Physiologic	Mild	Stress, exercise, chest-wall/nipple stimulation, seizure

⚠️ BOARD TRAP — Board Traps

Macroprolactinoma with visual loss → dopamine agonist, not surgery.
Prolactin 60 in a woman on risperidone → the drug; do not order surgery, do not give cabergoline.
Hyperprolactinemia + high TSH → treat the hypothyroidism; prolactin normalizes.
Huge sellar mass with a mildly elevated prolactin → either stalk effect (nonfunctioning tumor) or hook effect (giant prolactinoma with saturated assay) — ask for a diluted sample; the treatment differs completely.
Prolactinoma in a woman who becomes pregnant → stop the dopamine agonist for a microadenoma; for a macroadenoma continue bromocriptine or monitor visual fields each trimester (no serial prolactin — it rises anyway).
Cabergoline in high cumulative doses → echocardiographic monitoring for valvular fibrosis.

★ Memory Trick

Prolactin: PILLS (antipsychotics), PREGNANCY, PITUITARY, low thyroid (TRH), kidney. Level tells size: <100 drug/stalk, >250 tumor. Pro-LACTIN → dopamine agonist. Everything else that's SECRETING → scalpel. Nonfunctioning → size, sight, hormones.

Tier 2

Topic P-2

Acromegaly

IGF-1 First, Not Random GH · OGTT Suppression · Transsphenoidal Surgery · Somatostatin Analogs · Pegvisomant

★★ Frequently tested

Acromegaly — Recognize → Test → Confirm → Treat → Don't Miss

Recognize

Insidious (mean 8–10 yr delay): enlarging hands/feet (ring/shoe size), coarse facies, frontal bossing, prognathism, macroglossia, widened tooth spacing, oily sweaty skin, skin tags, deep voice, carpal tunnel, arthropathy, OSA, hypertension, diabetes, cardiomyopathy, headache, visual field loss, colon polyps; gigantism if before epiphyseal closure

First test

Serum IGF-1 (age/sex-adjusted)

Confirm

GH fails to suppress below 1 ng/mL after 75-g oral glucose; then pituitary MRI (macroadenoma in >75%)

First-line treatment

Transsphenoidal surgery; persistent disease → somatostatin analogs (octreotide, lanreotide, pasireotide), pegvisomant (GH-receptor antagonist; normalizes IGF-1, GH stays high), cabergoline (mild); radiation if refractory

Don't miss

Random GH is worthless · cardiovascular disease (leading cause of death) · colonoscopy at diagnosis · OSA · hypopituitarism after treatment · diabetes worsened by somatostatin analogs (pasireotide)

Monitoring: IGF-1 (and OGTT-GH after surgery); remission = normal IGF-1 and GH <1 ng/mL post-glucose
Somatostatin analog effects: gallstones, GI upset, hyperglycemia (pasireotide), bradycardia
Pegvisomant: blocks the GH receptor — IGF-1 falls but GH rises; monitor liver enzymes; tumor does not shrink

⚠️ BOARD TRAP — Board Traps

Ordering a random GH → pulsatile; use IGF-1 to screen and glucose-suppressed GH to confirm.
IGF-1 mildly elevated in pregnancy or adolescence → physiologic; interpret with age/sex norms.
Acromegaly patient with rectal bleeding → colonoscopy; increased colon polyps/cancer.
Pegvisomant patient with a rising GH → expected; follow IGF-1.

Tier 1

Topic P-3

Hypopituitarism, Sheehan Syndrome & Pituitary Apoplexy

Order of Loss · Cortisol Before Thyroid · Lactation Failure · Thunderclap Headache + Ophthalmoplegia → Steroids + Surgeon

★★★ PANCE Core

Hypopituitarism — Causes and the Order of Loss

Causes: pituitary adenoma (mass or post-treatment), surgery, radiation (years later), apoplexy, Sheehan syndrome, traumatic brain injury, infiltrative (sarcoid, hemochromatosis, Langerhans histiocytosis), hypophysitis (lymphocytic peripartum; immune checkpoint inhibitors — ipilimumab), infection, empty sella, congenital
Order of loss (typical): GH → LH/FSH → TSH → ACTH ("Go Look For The Adenoma"); prolactin is usually the last to fall except in Sheehan, where lactation failure is first
Presentation by axis: GH — fatigue, ↓ muscle, central adiposity, growth failure in children · LH/FSH — amenorrhea, ED, ↓ libido, infertility, ↓ body hair · TSH — central hypothyroidism (low FT4, TSH low/normal) · ACTH — secondary AI (no pigmentation, normal K) · ADH (posterior) — DI (only with stalk/hypothalamic involvement)
Evaluation: 8 AM cortisol + ACTH (cosyntropin may be falsely normal early), free T4 + TSH, LH/FSH + estradiol/testosterone, IGF-1 (GH stimulation testing if replacement considered), prolactin, serum/urine osmolality if polyuric; MRI; visual fields
Replacement order: hydrocortisone first → levothyroxine (titrate to mid-normal free T4) → sex steroids → GH (selected adults) → desmopressin if DI; stress-dose steroids for illness/surgery

Sheehan SyndromeRecognize

Postpartum pituitary infarction after obstetric hemorrhage/hypotension (the gland is hyperplastic and vulnerable in pregnancy)
Earliest clue: inability to lactate; then amenorrhea, fatigue, hypothyroidism, adrenal insufficiency (hypotension, hyponatremia, hypoglycemia); may present months–years later; DI uncommon
MRI: empty sella. Treat: hydrocortisone first, then levothyroxine, estrogen/progestin

Pituitary Apoplexy — EmergencyRecognize

Recognize: sudden severe headache (thunderclap), nausea/vomiting, visual field loss or acuity loss, ophthalmoplegia (CN III most common — ptosis, "down and out"), meningismus, altered consciousness; hypotension and hyponatremia from acute ACTH loss; usually a pre-existing (often undiagnosed) macroadenoma; precipitants: anticoagulants, surgery, hypertension, dopamine agonists, pregnancy, dynamic testing

↓

First action: stress-dose glucocorticoids (hydrocortisone 100 mg IV) + IV fluids — do not wait for cortisol. Draw pituitary panel, electrolytes, coagulation.

↓

Imaging: MRI (CT can miss it; useful to exclude SAH). Emergent neurosurgical evaluation — transsphenoidal decompression for visual loss, deteriorating consciousness, or progressive ophthalmoplegia; stable patients with mild deficits may be managed conservatively with steroids and close monitoring.

↓

Aftermath: most develop permanent hypopituitarism — full replacement and follow-up; watch for DI.

⚠️ BOARD TRAP — Board Traps

Thunderclap headache + CN III palsy + normal CT → do not stop at "SAH excluded"; look at the sella.
Apoplexy patient given levothyroxine for a low T4 → precipitates crisis; steroids first.
Normal cosyntropin test 3 weeks after apoplexy or pituitary surgery → adrenals have not yet atrophied; do not use it to exclude secondary AI early.
Ipilimumab patient with headache, fatigue, and hyponatremia → hypophysitis; hydrocortisone.
Sheehan diagnosed by a high TSH → wrong; central hypothyroidism has low/normal TSH.

★ Memory Trick

Sheehan: "She can't feed, she can't bleed" (no lactation, no menses). Apoplexy: sudden headache + eye palsy + collapse → steroids + surgeon. Replace: Cortisol → T4 → sex → GH ("Cool The Sick Gland").

Tier 2

Topic P-4

Diabetes Insipidus vs SIADH

Water Deprivation → Desmopressin · Central vs Nephrogenic · SIADH: Fluid Restriction, Correct ≤8 mEq/L per Day · Triphasic Post-Op Response

★★ Frequently tested

Diabetes Insipidus vs SIADH — The Water TableMemorize

Terminology note: the 2022 international consensus renamed central DI arginine vasopressin deficiency (AVP-D) and nephrogenic DI AVP resistance (AVP-R). The PANCE blueprint still says diabetes insipidus; know both.

	Central DI (AVP deficiency)	Nephrogenic DI (AVP resistance)	SIADH	Primary polydipsia
Problem	No ADH (pituitary/hypothalamic: surgery, trauma, tumor, infiltrative, idiopathic)	Kidney ignores ADH (lithium, hypercalcemia, hypokalemia, demeclocycline, CKD, congenital V2/aquaporin)	Too much ADH (SCLC, CNS disease, pulmonary disease, drugs — SSRIs, carbamazepine, cyclophosphamide, NSAIDs; pain, nausea, post-op)	Excess water intake (psychiatric, thiazide-related thirst)
Serum sodium	↑ (if thirst impaired or no water access) — often normal-high	↑ / high-normal	↓	↓ / low-normal
Serum osmolality	↑ (>295)	↑	↓ (<275)	↓
Urine osmolality	↓ (<300; often <100)	↓	↑ (>100, inappropriately concentrated; usually >300)	↓ (appropriately dilute)
Urine sodium	Variable	Variable	↑ (>40)	↓
Urine volume	↑↑ (>3 L/day; can exceed 10 L)	↑↑	↓ / normal	↑↑
Volume status	Euvolemic → dry if no access to water	Euvolemic → dry	Euvolemic (no edema, no orthostasis)	Euvolemic
Diagnostic test	Water deprivation: urine stays dilute → desmopressin → urine osm rises >50%	Water deprivation: urine stays dilute → desmopressin → no response	Diagnosis of exclusion: euvolemic hypotonic hyponatremia, urine osm >100, urine Na >40, normal thyroid and adrenal function, no diuretics	Water deprivation → urine concentrates normally; low urine osm at baseline
Treatment	Desmopressin (intranasal/oral/SC); treat cause; free water access	Treat cause (stop lithium if possible — amiloride helps lithium DI); thiazide + low-salt/low-protein diet (paradoxical); NSAIDs	Fluid restriction (first) → salt tablets/urea → loop diuretic → tolvaptan/conivaptan (vaptan; not in hypovolemia); severe symptomatic (seizure, coma): 3% saline 100–150 mL bolus; correct ≤8 mEq/L per 24 h	Water restriction; treat psychiatric cause

Rules That Get Tested

Copeptin (ADH surrogate) is increasingly used instead of water deprivation: high in nephrogenic, low in central
Post-pituitary-surgery triphasic response: DI (days 1–5) → SIADH (days 5–10, from dying neurons dumping ADH) → permanent DI or recovery — watch sodium closely
Osmotic demyelination: correcting chronic hyponatremia faster than 8–10 mEq/L in 24 h → pontine/extrapontine demyelination days later (quadriparesis, dysarthria, locked-in); highest risk with alcohol, malnutrition, hypokalemia, Na <105; if overcorrected, relower with D5W/desmopressin
Severe symptomatic hyponatremia (seizures, coma): 3% saline bolus regardless of cause — then figure out why
Hypernatremia correction: chronic → ≤10–12 mEq/L per 24 h (cerebral edema if too fast); replace the free-water deficit = TBW × (Na/140 − 1)
Before diagnosing SIADH: exclude hypothyroidism and adrenal insufficiency (both cause euvolemic hyponatremia), diuretics, and pseudohyponatremia (hyperglycemia, hyperlipidemia, paraproteins)

⚠️ BOARD TRAP — Board Traps

Hyponatremia + lung mass + concentrated urine → SIADH from small cell; fluid restriction first, not normal saline (saline can worsen it — the kidney keeps the water and excretes the salt).
Correcting sodium from 108 to 128 in 12 hours → osmotic demyelination; cap at 8/24 h.
Polyuria after transsphenoidal surgery with Na 150 → central DI → desmopressin; but recheck — the SIADH phase follows.
Polyuria on lithium → nephrogenic DI; desmopressin does nothing; amiloride/thiazide.
Hyponatremia labeled SIADH without checking cortisol and TSH → missed adrenal insufficiency or hypothyroidism.
Glucose 900 with Na 128 → corrected Na is normal/high; this is not SIADH.

★ Memory Trick

DI: DRY and DILUTE urine, HIGH serum. SIADH: SOAKED serum (low Na), SALTY concentrated urine. DDAVP fixes central, not nephrogenic. Lithium → amiloride. Eight in a day — or the pons pays.

Domain 7 · Reproductive, Lipid & Metabolic Endocrinology — Tier 2

PCOS, Amenorrhea, Hypogonadism, Dyslipidemia, Metabolic Syndrome, Obesity

Tier 2

Topic R-1

PCOS, Amenorrhea & Hyperandrogenism

Rotterdam · Exclude Mimics (17-OHP, DHEA-S, Testosterone) · OCP / Letrozole / Metformin · hCG First · Turner · Müllerian Agenesis · AIS

★★ Frequently tested

PCOS — Rotterdam Criteria and Management by GoalRecognize

Diagnosis (2 of 3): oligo/anovulation (<8 cycles/yr or cycles >35 days); clinical (hirsutism, acne, androgenic alopecia) or biochemical hyperandrogenism; polycystic ovarian morphology (≥20 follicles or volume ≥10 mL per ovary) — after excluding mimics
Exclude: pregnancy, thyroid disease, hyperprolactinemia, nonclassic CAH (8 AM 17-OHP >200 ng/dL → cosyntropin test), androgen-secreting tumor (rapid virilization, testosterone >150–200, DHEA-S >700), Cushing, acromegaly
Pathophysiology: insulin resistance → ↑ ovarian androgens, ↑ LH:FSH (often >2:1 — not diagnostic), ↓ SHBG; elevated free testosterone; anovulation → unopposed estrogen
Comorbidities to screen: 2-h OGTT for diabetes (A1c less sensitive), lipids, blood pressure, OSA, MASLD, depression/anxiety, endometrial hyperplasia if prolonged amenorrhea

Goal	First-line	Alternatives / adjuncts
Menstrual regulation, hirsutism, acne, endometrial protection	Combined hormonal contraceptive + lifestyle/weight loss	Cyclic progestin (endometrial protection only); spironolactone for hirsutism after 6 months of OCP (contraception required — teratogenic); eflornithine cream; laser
Fertility	Letrozole (aromatase inhibitor) for ovulation induction	Clomiphene; metformin adjunct; gonadotropins; IVF; weight loss improves ovulation
Insulin resistance / prediabetes / OCP contraindicated	Metformin	GLP-1 RA for obesity; lifestyle

Amenorrhea — The Algorithm

Primary (no menses by 15, or 13 without breasts) or secondary (no menses ≥3 months if previously regular, ≥6 months if irregular)

↓

hCG — pregnancy first, always

↓

TSH, prolactin, FSH (+ estradiol); testosterone/DHEA-S/17-OHP if hirsute; history: weight loss, exercise, stress, eating disorder, D&C, chemo, radiation, anosmia, galactorrhea

↓

FSH high → primary ovarian insufficiency (<40 y: karyotype for Turner/mosaicism, FMR1 premutation, autoimmune — adrenal antibodies; treat with HRT until ~51 for bone/CV) ▸ FSH low/normal → hypothalamic (functional: low weight/exercise/stress — the "female athlete triad"; Kallmann; infiltrative), pituitary (prolactinoma, Sheehan, mass), PCOS, or outflow tract

↓

Outflow/uterine: Asherman (post-D&C — hysteroscopy), cervical stenosis; primary: imperforate hymen (cyclic pain, bulging membrane), transverse septum, Müllerian agenesis (46,XX, normal ovaries/breasts/pubic hair, absent uterus — renal anomalies), androgen insensitivity (46,XY, breasts present, absent pubic/axillary hair, blind vaginal pouch, testes in canal — remove after puberty)

Menopause & Hormone Therapy — Decision PointsReference

Diagnosis is clinical (12 months amenorrhea, ~51 y); FSH >30–40 supports but is unnecessary; premature (<40) = primary ovarian insufficiency
Hormone therapy is the most effective treatment for vasomotor symptoms and genitourinary syndrome; safest when started <60 y or <10 y from menopause; add a progestin if the uterus is present (unopposed estrogen → endometrial cancer); transdermal estrogen carries less VTE risk
Contraindications: breast/endometrial cancer, VTE/stroke/CAD history, unexplained vaginal bleeding, active liver disease
Non-hormonal: fezolinetant (NK3 antagonist), SSRIs/SNRIs (paroxetine, venlafaxine), gabapentin; vaginal estrogen for GSM is safe in most
Bone: HT prevents loss but is not first-line for established osteoporosis

⚠️ BOARD TRAP — Board Traps

PCOS diagnosed by ultrasound alone → morphology is one criterion, not the diagnosis; and not used in adolescents.
Spironolactone without contraception → feminizes a male fetus.
Amenorrhea workup started with FSH → hCG first.
Breasts present, no pubic hair, no uterus, 46,XY → androgen insensitivity (do not call it Müllerian agenesis, which has normal pubic hair and 46,XX).
Estrogen alone in a woman with a uterus → endometrial hyperplasia/cancer; add progestin.
Runner with amenorrhea, low BMI, stress fracture → functional hypothalamic amenorrhea; treat with nutrition/weight restoration, not OCPs alone (they mask the problem and do not restore bone).

★ Memory Trick

PCOS: 2 of 3 — Periods, Pilosity, Polycystic. OCP for cycles, letrozole for babies, metformin for sugar. Amenorrhea: hCG → TSH → PRL → FSH.

Tier 2

Topic R-2

Hypogonadism, Gynecomastia & Puberty

LH/FSH Localize · Klinefelter vs Kallmann · Two 8 AM Testosterones · Testosterone Risks · Precocious vs Delayed

★★ Frequently tested

Male Hypogonadism — Primary vs Secondary

	Primary (hypergonadotropic)	Secondary (hypogonadotropic)
Testosterone	↓	↓
LH / FSH	↑	↓ or inappropriately normal
Causes	Klinefelter (47,XXY; most common congenital), cryptorchidism, orchitis (mumps), torsion, chemotherapy/radiation, trauma, aging (partial)	Prolactinoma, pituitary mass/surgery/radiation, Kallmann (GnRH deficiency + anosmia), hemochromatosis, opioids, anabolic steroids/exogenous testosterone, glucocorticoids, obesity, OSA, severe illness, eating disorders
Workup	Karyotype; semen analysis	Prolactin, iron studies, other pituitary axes, MRI if prolactin high or testosterone <150 or other deficits
Treatment	Testosterone replacement	Treat the cause (stop opioids/steroids, cabergoline for prolactinoma); testosterone if not seeking fertility; hCG ± FSH/clomiphene to preserve spermatogenesis

Diagnosis: symptoms (↓ libido, ED, fatigue, ↓ muscle, gynecomastia, hot flashes, infertility, osteoporosis) + two 8 AM total testosterone levels below normal (~<300 ng/dL); free testosterone if SHBG abnormal (obesity ↓, aging/liver ↑)
Gynecomastia: ↑ estrogen:androgen ratio — puberty (physiologic, resolves), Klinefelter, testicular tumor (check hCG, AFP, estradiol), cirrhosis, hyperthyroidism, CKD, drugs (spironolactone, ketoconazole, cimetidine, antiandrogens, anabolic steroids, marijuana). Unilateral hard eccentric mass → mammogram/biopsy (male breast cancer, BRCA2)
Puberty: delayed = no testicular enlargement by 14 (boys) / no breasts by 13 (girls) — constitutional delay most common (bone age delayed, family history); precocious = <9 (boys) / <8 (girls) — central (GnRH-dependent; idiopathic in girls, CNS lesion more likely in boys; GnRH agonist) vs peripheral (CAH, tumors, McCune-Albright, exogenous)

⚠️ BOARD TRAP — Board Traps

Low testosterone drawn at 4 PM in an obese man → repeat at 8 AM, fasting, twice; check SHBG/free T.
Starting testosterone in a man who wants children → suppresses spermatogenesis; use hCG/clomiphene.
Low testosterone + low LH + headache → prolactin and MRI before treating.
Anosmia + delayed puberty → Kallmann.
Gynecomastia in a 16-year-old → reassure; in a 25-year-old with a testicular mass → hCG-secreting tumor.

Tier 2

Topic R-3

Dyslipidemia, Metabolic Syndrome & Obesity

Four Statin Groups · Intensity · TG ≥500 → Fibrate · FH · 3-of-5 Criteria · Pharmacotherapy ≥30 / ≥27 · Surgery ≥40 / ≥35

★★ Frequently tested

Dyslipidemia — Screening, Statin Groups, Drugs

Screening: USPSTF — adults 40–75 for ASCVD risk assessment; lipid panel every 4–6 years from age 20 (ACC/AHA); earlier with family history of premature ASCVD or FH; children: once at 9–11 and 17–21
Risk estimation: Pooled Cohort Equations (or PREVENT) 10-year ASCVD risk; risk enhancers (family history, CKD, metabolic syndrome, inflammatory disease, South Asian ancestry, LDL ≥160, Lp(a), hs-CRP); coronary artery calcium score when the decision is uncertain (CAC 0 → may defer statin)

Statin-benefit group	Intensity	LDL goal / marker
Clinical ASCVD (MI, stroke, PAD, revascularization)	High-intensity (atorvastatin 40–80, rosuvastatin 20–40)	≥50% reduction; very high risk → LDL <55–70; add ezetimibe then PCSK9i if above
LDL ≥190 mg/dL (probable familial hypercholesterolemia)	High-intensity	≥50% reduction; screen and treat relatives; ezetimibe/PCSK9i often required
Diabetes, age 40–75	Moderate; high if multiple risk factors or risk ≥20%	≥30–50% reduction
Primary prevention, age 40–75, 10-yr risk ≥7.5% (discuss 5–7.5%)	Moderate (≥20%: high)	≥30% reduction

Drug	Effect	Key facts
Statins	↓ LDL 30–60%	First-line for all groups; myalgia (check CK if severe; try lower dose/alternate statin), transaminitis (no routine monitoring after baseline), new diabetes (small); contraindicated in pregnancy and active liver disease; simvastatin interacts with CYP3A4 inhibitors
Ezetimibe	↓ LDL ~20%	Add-on to statin (IMPROVE-IT); well tolerated
PCSK9 inhibitors (evolocumab, alirocumab); inclisiran (siRNA)	↓ LDL 50–60%	Injectable; ASCVD or FH not at goal on statin + ezetimibe
Bempedoic acid	↓ LDL ~20%	Statin-intolerant; gout, tendon rupture
Fibrates (fenofibrate)	↓ TG 30–50%	TG ≥500 to prevent pancreatitis; gemfibrozil + statin → myopathy (use fenofibrate); gallstones
Omega-3 (icosapent ethyl)	↓ TG	REDUCE-IT CV benefit in high-risk with TG 150–499 on statin; AF, bleeding
Niacin	↑ HDL, ↓ TG/LDL	Flushing, hyperglycemia, gout, hepatotoxicity; no outcome benefit — rarely used
Bile-acid sequestrants	↓ LDL 15–20%	↑ TG; GI; bind other drugs (levothyroxine); safe in pregnancy

Metabolic Syndrome — 3 of 5Reference

Criterion	Threshold
Waist circumference	≥40 in (102 cm) men · ≥35 in (88 cm) women (lower in Asian populations)
Triglycerides	≥150 mg/dL (or on treatment)
HDL	<40 men · <50 women (or on treatment)
Blood pressure	≥130/85 (or on treatment)
Fasting glucose	≥100 mg/dL (or on treatment)

🩺 Doubles ASCVD risk and quintuples diabetes risk. Treat each component; the unifying therapy is weight loss and activity.

Obesity — Classification and Treatment ThresholdsReference

BMI: overweight 25–29.9; class I 30–34.9; class II 35–39.9; class III ≥40 (Asian cutoffs ~2.5 lower); waist circumference adds risk; 2025 Lancet Commission distinguishes preclinical from clinical obesity (organ dysfunction)
Lifestyle (≥5–10% loss improves everything) is the foundation for all
Pharmacotherapy: BMI ≥30, or ≥27 with a comorbidity — semaglutide 2.4 mg SC weekly or oral 25 mg daily (~15%), tirzepatide (~20%), liraglutide 3 mg, orforglipron (oral, 2026), phentermine-topiramate (glaucoma, pregnancy — teratogenic), naltrexone-bupropion (seizures, opioids), orlistat (fat-soluble vitamin malabsorption); avoid GLP-1/GIP agents with MTC/MEN2 or pancreatitis history
Metabolic/bariatric surgery: BMI ≥40, or ≥35 with comorbidity (ASMBS 2022; ≥30 with uncontrolled type 2 diabetes considered); sleeve gastrectomy most common; Roux-en-Y best for GERD/diabetes; post-op: B12, iron, folate, vitamin D/calcium, thiamine deficiency; dumping syndrome; marginal ulcers (no NSAIDs); alcohol use disorder risk
Weight-promoting drugs to reconsider: insulin, sulfonylureas, TZDs, glucocorticoids, antipsychotics (olanzapine), mirtazapine, paroxetine, valproate, gabapentin, β-blockers

⚠️ BOARD TRAP — Board Traps

TG 1,100 with abdominal pain → pancreatitis; treat with fibrate/insulin infusion, not a statin first.
Gemfibrozil + statin → rhabdomyolysis; use fenofibrate.
LDL 210 in a 30-year-old with a father who had an MI at 42 → familial hypercholesterolemia; high-intensity statin now, screen family.
Statin stopped for mild myalgia with normal CK → rechallenge at a lower dose or alternate-day rosuvastatin; most "intolerance" is nocebo.
Phentermine-topiramate in a woman not on contraception → cleft lip/palate; monthly pregnancy tests.
Post-gastric-bypass confusion, ataxia, ophthalmoplegia → thiamine (Wernicke).

Domain 8 · Neuroendocrine & Multiglandular Syndromes — Tier 3 Rapid Review

MEN 1 · MEN 2A · MEN 2B · Carcinoid · Autoimmune Polyglandular Syndromes

Tier 3

Topic M-1

MEN Syndromes, Carcinoid & Autoimmune Polyglandular Syndromes

MEN 1 (3 P's) · MEN 2A (MTC + Pheo + Parathyroid) · MEN 2B (MTC + Pheo + Neuromas) · 5-HIAA · Octreotide · APS-1 vs APS-2

★ Rapid review

MEN Syndromes — The Visual ComparisonReference

	MEN 1 (Wermer)	MEN 2A (Sipple)	MEN 2B
Gene	MEN1 (menin) — tumor suppressor	RET proto-oncogene (activating)	RET (M918T)
Inheritance	Autosomal dominant	Autosomal dominant	Autosomal dominant (often de novo)
The triad	3 P's: Parathyroid (hyperplasia, ~95%) · Pituitary (prolactinoma most) · Pancreas/duodenum (gastrinoma most common functional → Zollinger-Ellison; insulinoma; VIPoma; nonfunctioning)	Medullary thyroid carcinoma (~100%) · Pheochromocytoma (~50%) · Parathyroid hyperplasia (~20–30%)	Medullary thyroid carcinoma (earliest, most aggressive) · Pheochromocytoma (~50%) · Mucosal neuromas (lips, tongue, eyelids) · Marfanoid habitus · intestinal ganglioneuromatosis · NO parathyroid disease
Presentation	Hypercalcemia in a young adult (most common first sign); recurrent PUD/diarrhea (gastrinoma); hypoglycemia; galactorrhea	Thyroid nodule/neck mass + ↑ calcitonin; pheo symptoms; hypercalcemia	Childhood MTC; bumpy lips; tall thin; GI dysmotility
Other tumors	Carcinoid (bronchial/thymic), adrenal adenomas, lipomas, angiofibromas, collagenomas	Cutaneous lichen amyloidosis, Hirschsprung	—
Screening / management	Annual Ca/PTH, prolactin, IGF-1, gastrin, fasting glucose/insulin, chromogranin A; MRI pituitary, pancreas imaging; subtotal parathyroidectomy (3.5 glands); PPIs for ZES	RET testing of all first-degree relatives; prophylactic thyroidectomy by age 5 (or based on codon); annual calcitonin, metanephrines, Ca; remove pheo before thyroid surgery	Prophylactic thyroidectomy in the first year of life; annual metanephrines

★ Memory Trick

MEN 1 = 3 P's (Parathyroid, Pituitary, Pancreas). MEN 2A = 2 P's + M (Pheo, Parathyroid, Medullary). MEN 2B = 1 P + 2 M's (Pheo, Medullary, Mucosal neuromas) + Marfanoid — no parathyroid. RET for 2; Menin for 1.

Carcinoid SyndromeReference

Recognize

Episodic flushing (face/neck, minutes, triggered by alcohol, stress, foods), secretory diarrhea, wheezing/bronchospasm, abdominal cramps; right-sided valvular disease (tricuspid regurgitation, pulmonic stenosis — fibrous plaques); pellagra (niacin diverted to serotonin: dermatitis, diarrhea, dementia). Syndrome requires hepatic metastases (or a bronchial/ovarian primary) — the liver otherwise inactivates serotonin from midgut tumors

First test

24-h urine 5-HIAA (serotonin metabolite); avoid serotonin-rich foods (bananas, walnuts, tomatoes) and certain drugs before collection; chromogranin A

Confirm

CT/MRI abdomen; somatostatin-receptor imaging (Ga-68 DOTATATE PET, or octreotide scan); echocardiogram for carcinoid heart; biopsy

First-line treatment

Octreotide/lanreotide (control symptoms and slow growth); telotristat (tryptophan hydroxylase inhibitor) for refractory diarrhea; surgical resection when localized/debulking; PRRT (Lu-177 DOTATATE) for progressive disease; niacin supplementation

Don't miss

Carcinoid crisis (hypotension/hypertension, bronchospasm, flushing) with anesthesia, biopsy, or tumor manipulation → pretreat with octreotide; avoid catecholamines. Small-bowel obstruction/mesenteric fibrosis. Appendiceal carcinoid <2 cm at the tip → appendectomy alone

Autoimmune Polyglandular SyndromesReference

	APS-1 (APECED)	APS-2 (Schmidt)
Genetics	AIRE mutation; autosomal recessive; childhood onset	Polygenic (HLA-DR3/DR4); adults; women; most common
Classic triad	Chronic mucocutaneous candidiasis · hypoparathyroidism · Addison disease	Addison disease · autoimmune thyroid disease · type 1 diabetes
Others	Hypogonadism, pernicious anemia, alopecia, vitiligo, hepatitis, malabsorption	Celiac, vitiligo, pernicious anemia, hypogonadism, myasthenia
Teaching point	Child with recurrent thrush + hypocalcemia → screen adrenal antibodies	New Addison → check TSH and glucose; new T1DM with fatigue and hyponatremia → check cortisol

⚠️ BOARD TRAP — Board Traps

Pheo in a patient with medullary thyroid cancer → resect the pheo first (α-blockade) or the thyroidectomy will trigger a crisis.
Hypercalcemia + PUD + galactorrhea in a 28-year-old → MEN 1; check gastrin, prolactin.
Flushing + diarrhea with a normal liver → unlikely carcinoid syndrome unless the primary is bronchial/ovarian; consider medullary thyroid cancer, VIPoma, mastocytosis, pheo, menopause.
Carcinoid patient going to surgery without octreotide → carcinoid crisis.
Addison patient started on levothyroxine before hydrocortisone (APS-2 both present) → adrenal crisis; steroids first — and Hashimoto's high TSH may partly normalize once cortisol is replaced.

Domain 9 · ENDOCRINE CODE BLUE

Eight Emergencies — Diagnosis + First Action in 30–45 Seconds

1. DKA

Kussmaul + fruity breath + gap acidosis. Isotonic fluids first; check K before insulin (hold if <3.3). Dextrose at 200–250; done when the gap closes; overlap SC basal 1–2 h.

2. HHS

Older, type 2, obtunded, glucose >600, osm >320, no acidosis. Aggressive isotonic fluids; insulin more cautiously; dextrose at 250–300; find the precipitant.

3. Thyroid storm

Graves + trigger → fever, AF/tachycardia, delirium. β-blocker → thionamide (PTU) → iodine ≥1 h later → hydrocortisone. Acetaminophen, not aspirin.

4. Myxedema coma

Hypothermia, bradycardia, hypoventilation, hyponatremia, hypoglycemia, lethargy. IV levothyroxine + stress-dose hydrocortisone (before/with T4); passive rewarming; ICU.

5. Adrenal crisis

Shock refractory to fluids + hyponatremia ± hyperkalemia ± hypoglycemia. Hydrocortisone 100 mg IV now — do not wait for cortisol. Fluids with dextrose.

6. Hypercalcemic crisis

Ca >14 or symptomatic: confusion, polyuria, AKI, short QT. IV isotonic saline first; calcitonin (bridge) + zoledronic acid (definitive); steroids if vitamin D–mediated; no furosemide until repleted.

7. Severe hypoglycemia

Confusion/seizure/coma, unable to swallow. IV D50 (or D10) if access; glucagon IM/intranasal if not. Sulfonylurea → admit, D10, octreotide. Thiamine with dextrose in alcohol use.

8. Pituitary apoplexy

Thunderclap headache + ophthalmoplegia (CN III) + visual loss ± collapse in a macroadenoma. Stress-dose glucocorticoids + emergent neurosurgical evaluation; MRI; expect hypopituitarism.

Final Review

Endocrine Lightning Round — 12 Cases, 15 Seconds Each

Final Review

Five Integrated PANCE-Style Cases

Cumulative · Mixed · Untimed

The Endocrine Gauntlet — 25 Questions

Every domain, shuffled, written the way the PANCE writes them. Each explanation names the strongest distractor and why it fails.

Endocrinology on One Page · Screenshot This

The 20 Things to Know Before Your PANCE

Endocrinology · PA Clinical Bootcamp

01Diabetes numbers. A1c ≥6.5 · FPG ≥126 · OGTT ≥200 · random ≥200 + symptoms. Prediabetes 5.7 / 100 / 140. Screen at 35.

02Drug by comorbidity. HF or CKD → SGLT2i. ASCVD or obesity → GLP-1 RA / tirzepatide. A1c >10 or catabolic → insulin. Pioglitazone never in HF.

03DKA order. Fluids → K (hold insulin if <3.3) → insulin → dextrose at ~200–250 → stop the drip only after the gap closes with basal overlap.

04HHS. Glucose >600, osm >320, pH >7.3, obtunded. Fluids are the treatment.

05Morning hyperglycemia. 3 AM low = Somogyi → less insulin. 3 AM normal/high = dawn → more or later basal.

06Hypoglycemia. Rule of 15; glucagon if not swallowing; sulfonylurea → admit + octreotide. High insulin + low C-peptide = injected insulin.

07TSH first. TSH↑ FT4↓ = Hashimoto. TSH↓ FT4↑ = thyrotoxicosis → RAIU/TRAb. Low/normal TSH + low FT4 = central → cortisol before levothyroxine.

08Uptake decides. High uptake = Graves/toxic nodule → thionamide, RAI, surgery. Low uptake = thyroiditis/factitious → NSAID + beta-blocker, no thionamide.

09Thyroid emergencies. Storm: thionamide → iodine 1 h later → propranolol → steroids. Myxedema coma: IV T4 + hydrocortisone + passive warming.

10Thyroid nodule. TSH low → scan (hot = benign). Normal TSH → ultrasound → FNA ≥1 cm if suspicious. MTC = calcitonin, RET, MEN 2.

11Thionamide rules. Methimazole first-line; PTU in the first trimester and storm. Fever + sore throat = stop and CBC. Never RAI in pregnancy.

12Adrenal insufficiency. Unstable: draw cortisol/ACTH, give hydrocortisone and saline NOW. Stable: AM cortisol → cosyntropin. ACTH↑ + K↑ + pigment = primary; steroid withdrawal = most common secondary.

13Cushing algorithm. Exclude exogenous → screen ×2 (1-mg DST, salivary, urine) → ACTH (low = adrenal; high = pituitary/ectopic → high-dose DST/IPSS) → image last.

14Adrenal hypertension. Low K + resistant HTN → aldosterone/renin ratio; AVS before surgery. Paroxysms → metanephrines; alpha before beta before surgery.

15Incidentaloma. Two questions: functioning (DST, metanephrines, ARR) and malignant (>4 cm, >10 HU, slow washout).

16Calcium / PTH. Ca↑ PTH↑ = primary hyperpara (surgery: symptoms, Ca >1 above normal, <50, eGFR <60, T ≤−2.5, stones; low urine Ca = FHH). Ca↑ PTH↓ = cancer/granuloma/vitamin D.

17Severe hypercalcemia. Saline → calcitonin → zoledronate (denosumab if CKD); steroids for lymphoma/granuloma; no thiazides.

18Hypocalcemia & bone. Tetany/QT = IV calcium; hypoparathyroidism needs calcitriol. Osteoporosis: T ≤−2.5 or fragility fracture = bisphosphonate (eGFR ≥35), denosumab if not.

19Pituitary rule. Prolactinoma = cabergoline (even macro). Everything else = transsphenoidal surgery. Acromegaly: IGF-1 → OGTT → MRI. Apoplexy: steroids first.

20Water. DI: dilute urine + high Na; DDAVP response = central. SIADH: urine osm >100, urine Na >30, euvolemic, normal TSH/cortisol; restrict; 3% for seizures; ≤8 in 24 h.

paclinicalbootcamp.comRajiv Choudhary, MD, MPH

⬡ Closing Statement

"Endocrinology on the PANCE is a small number of decisions asked many ways: which test first, which drug for this patient, what must happen before insulin, before iodine, before beta-blockade, before levothyroxine. Learn the sequence and the trap disappears."

— Rajiv Choudhary, MD, MPH

PA EndocrinologyBootcamp Syllabus

By the end of this bootcamp, you must be able to:

The 20 Things to Know Before Your PANCE

PA Endocrinology
Bootcamp Syllabus