Study guide
Endocrinology High-Yield PANCE Review
The endocrine system is a heavily weighted PANCE domain (~7-8% of the blueprint), dominated by diabetes mellitus, thyroid, adrenal, parathyroid/calcium, and pituitary disorders. Master diagnostic thresholds, first-line pharmacotherapy, and the recognition of life-threatening emergencies (DKA/HHS, thyroid storm, myxedema coma, adrenal crisis).
Diabetes Mellitus: Diagnosis & Management
- ◆Diagnostic thresholds (ADA): A1c >=6.5%, fasting glucose >=126 mg/dL, 2-hr OGTT >=200, or random >=200 with symptoms; prediabetes A1c 5.7-6.4% or fasting 100-125.
- ◆Type 1 = autoimmune beta-cell destruction (anti-GAD65/islet antibodies, low or undetectable C-peptide), prone to DKA; Type 2 = insulin resistance, obesity, acanthosis nigricans.
- ◆Metformin remains first-line for glycemic control in most T2DM (reduce/hold if eGFR <30; do not initiate if eGFR <45; lactic acidosis risk). Per ADA 2025-2026, a GLP-1 agonist and/or SGLT2 inhibitor is recommended independent of metformin or A1c when ASCVD, HF, or CKD is present; for diabetic CKD an SGLT2 inhibitor (eGFR >=20) is now first-line for cardiorenal protection.
- ◆A1c goal generally <7% (individualize; <8% in elderly/comorbid); check A1c every 3 months until stable, then every 6 months.
- ◆Screen for complications: annual dilated retinal exam, urine albumin-to-creatinine ratio, monofilament foot exam; ACE-I/ARB for albuminuria or HTN; statin therapy per risk.
- ◆USPSTF: screen adults 35-70 with overweight/obesity for prediabetes/T2DM.
Diabetic Emergencies: DKA vs HHS
- ◆DKA (2024 ADA/EASD consensus): glucose >=200 mg/dL (or known diabetes), bicarbonate <18 and/or pH <7.3, plus ketosis (beta-hydroxybutyrate >=3.0 mmol/L or moderate/large urine ketones). The anion gap was removed as a required criterion, though an elevated anion gap remains classic PANCE teaching (older cutoff glucose >250). Classically Type 1, precipitated by infection or missed insulin (5 I's).
- ◆HHS: glucose >=600, effective serum osm >320 (or effective osm >300), beta-hydroxybutyrate <3.0 (minimal/no ketosis), pH >=7.3; Type 2, profound dehydration and altered mental status, higher mortality.
- ◆Treatment order: IV isotonic fluids FIRST, then insulin infusion, then potassium once K <5.2 and urine output present. Never start insulin if K <3.3 (correct K first to avoid fatal hypokalemia).
- ◆Add dextrose to fluids when glucose reaches ~200-250 (DKA) or ~250-300 (HHS) to allow continued insulin closing the anion gap/clearing ketones.
- ◆Resolve DKA by clearing ketosis (beta-hydroxybutyrate <0.6, or normalized gap/pH), NOT by glucose alone; overlap SC insulin 1-2 hrs before stopping the drip.
Thyroid Disorders
- ◆Hyperthyroidism: low TSH, high free T4; Graves (diffuse goiter, exophthalmos, pretibial myxedema, TSI/TRAb antibodies, diffuse uptake on RAIU). First-line methimazole (PTU only in 1st trimester and thyroid storm); beta-blocker for symptoms.
- ◆Hypothyroidism: high TSH, low free T4; Hashimoto (anti-TPO) most common cause. Treat with levothyroxine; recheck TSH in 6-8 weeks.
- ◆Thyroid storm: fever, tachycardia/AF, agitation, delirium. Give beta-blocker (propranolol), PTU/methimazole, then iodine (>=1 hr after thionamide via Wolff-Chaikoff), plus glucocorticoids.
- ◆Myxedema coma: hypothermia, bradycardia, hyponatremia, altered mental status; treat with IV levothyroxine + IV hydrocortisone (cover adrenal insufficiency before/with thyroid replacement).
- ◆Thyroid nodule workup: check TSH; if normal/high get ultrasound and FNA per size/features; if low, get radioiodine scan (hot nodules rarely malignant). Papillary carcinoma is the most common thyroid cancer.
Adrenal Disorders
- ◆Primary adrenal insufficiency (Addison): hyperpigmentation, hyponatremia + hyperkalemia, hypotension; low cortisol with high ACTH; confirm with cosyntropin (ACTH) stimulation test. Autoimmune is most common cause in developed world.
- ◆Adrenal crisis: hypotension refractory to fluids; give IV hydrocortisone immediately plus aggressive saline/dextrose (do not delay for testing).
- ◆Cushing syndrome: central obesity, moon facies, purple striae, proximal weakness, HTN, hyperglycemia. Most common cause is exogenous steroids. Screen with late-night salivary cortisol, 24-hr urine free cortisol, or 1-mg overnight dexamethasone suppression; then ACTH to localize.
- ◆Pheochromocytoma: episodic headache, palpitations, diaphoresis, HTN; diagnose with plasma free or 24-hr urine fractionated metanephrines. Alpha-blockade (phenoxybenzamine) FIRST, then beta-blockade before surgery (never beta first-unopposed alpha crisis).
- ◆Primary hyperaldosteronism (Conn): HTN + hypokalemia; elevated aldosterone-to-renin ratio; treat with spironolactone/eplerenone or adrenalectomy for adenoma.
Calcium, Parathyroid & Pituitary
- ◆Primary hyperparathyroidism: hypercalcemia + high/inappropriately normal PTH, low phosphate; most often a parathyroid adenoma; 'stones, bones, groans, psychiatric moans.' Parathyroidectomy is definitive.
- ◆Acute severe hypercalcemia: IV normal saline first, then calcitonin (fast, short) and IV bisphosphonate (zoledronic acid, durable); malignancy is the top inpatient cause.
- ◆Hypoparathyroidism (often post-thyroidectomy): low calcium, high phosphate; Chvostek and Trousseau signs, tetany, prolonged QT; treat with calcium + calcitriol.
- ◆Prolactinoma: most common pituitary adenoma; galactorrhea, amenorrhea, low libido, bitemporal hemianopsia if large. First-line is a dopamine agonist (cabergoline/bromocriptine), not surgery.
- ◆Acromegaly (adult GH excess): enlarged hands/feet/jaw, glucose intolerance; screen with IGF-1, confirm with oral glucose GH suppression; treat surgically (transsphenoidal) +/- somatostatin analog.
- ◆Diabetes insipidus (now termed AVP deficiency [central] or AVP resistance [nephrogenic]): polyuria with dilute urine; central (low ADH, responds to desmopressin) vs nephrogenic (ADH-resistant); water deprivation test differentiates, with copeptin measurement increasingly used.