endocrine pathology · core

Thyroid · Parathyroid · Adrenal · Pituitary · DM

High‑yield notes for clinical reasoning & board review

🧠 Thyroid goiter · hyper/hypo · neoplasia

Goiter – enlarged thyroid with multiple colloid nodules

most often euthyroid (normal T4/T3/TSH)
Plummer syndrome = late hyperthyroidism (toxic multinodular)
endemic goiter: iodine deficiency (rare in US)
micro: nodules of varying size, colloid follicles, calcification, hemorrhage, fibrosis

Hyperthyroidism – ↑ metabolic rate due to ↑ T4/T3

symptoms: tachycardia, heat intolerance, tremor, diarrhea, weight loss with appetite
primary hyperthyroidism: ↓ TSH, ↑ free T4
secondary/tertiary: ↑ TSH, ↑ free T4

Graves disease – autoimmune (TSI antibodies to TSH receptor)

female >> male, peak 20–40
features: hyperthyroidism, diffuse goiter, ophthalmopathy (exophthalmos), pretibial myxedema
micro: hyperplastic follicles, scalloped colloid

Hypothyroidism – ↓ metabolic rate due to ↓ T4/T3

symptoms: fatigue, cold intolerance, myxedema, macroglossia, constipation, anovulation
primary: ↑ TSH, ↓ free T4
secondary/tertiary: ↓ TSH, ↓ free T4
most common cause in US: iatrogenic (post-thyroidectomy / radioactive iodine)

Thyroiditis

Hashimoto – autoimmune, most common non-iatrogenic hypothyroidism; female 40–65; painless goiter; risk of B-cell lymphoma; micro: lymphocytic infiltrate, germinal centers, Hürthle cells
Subacute (de Quervain) – post-viral, tender goiter, transient hyperthyroidism; granulomatous
Riedel – rare, dense fibrosis, hard thyroid adherent to trachea/esophagus; associated with retroperitoneal fibrosis

Thyroid neoplasia

Papillary carcinoma (80%): female 20–50, radiation exposure; RET rearrangements; psammoma bodies, Orphan Annie nuclei, grooves; excellent prognosis
Follicular carcinoma (15%): female 40–60; hematogenous spread (bone/lung); capsular invasion distinguishes from adenoma
Medullary carcinoma (5%): C-cell origin, secretes calcitonin; amyloid stroma; 25% familial (MEN2); RET mutations
Anaplastic – aggressive, >60, rapidly fatal

TSH is the most sensitive test – normal TSH = euthyroid

🦴 Parathyroid hyper · hypo · brown tumors

Primary hyperparathyroidism – excess PTH

causes: adenoma (80%), hyperplasia (15%), carcinoma (rare)
↑ serum calcium, ↑ PTH
manifestations: kidney stones, osteoporosis, osteitis fibrosa cystica (brown tumors), neuropsychiatric

Secondary hyperparathyroidism – due to hypocalcemia (chronic renal failure, vitamin D deficiency, malabsorption) → compensatory ↑ PTH
Hypoparathyroidism – low PTH

causes: surgical removal, DiGeorge, autoimmune (AIRE mutations)
symptoms: muscle spasms, tingling, prolonged QT, psychiatric
treatment: vitamin D + calcium

Osteitis fibrosa cystica = bone resorption, cystic lesions, brown tumors – classic in primary hyperparathyroidism

🧬 Pituitary & Pineal adenomas · DI · SIADH

Pituitary adenomas – micro (<1cm) vs macro (>1cm); macroadenomas cause visual field defects

Prolactinoma – most common; galactorrhea, amenorrhea, impotence
Nonfunctional – hypopituitarism
GH-producing – gigantism (children) / acromegaly (adults); ↑ IGF-1

Sheehan syndrome – ischemic necrosis postpartum hemorrhage → panhypopituitarism
Diabetes insipidus – ADH deficiency (central) or renal resistance (nephrogenic)

central: head trauma, tumors → hypotonic polyuria, hypernatremia
nephrogenic: lack of renal response

SIADH – excess ADH → water retention, hyponatremia, cerebral edema

common causes: small cell lung cancer, drugs (carbamazepine, SSRIs, cyclophosphamide)

Craniopharyngioma – Rathke pouch remnant, most common hypopituitarism in children
Pineal – calcification (landmark); germ cell tumors (rare)

75% pituitary destruction → panhypopituitarism (thyroid, adrenal, gonadal axes)

⚡ Adrenal Cushing · aldosterone · insufficiency · pheo

Cushing syndrome – glucocorticoid excess

most common: exogenous steroids
endogenous: Cushing disease (pituitary ACTH), ectopic ACTH (small cell lung), adrenal neoplasm
clinical: truncal obesity, buffalo hump, moon facies, striae, hypertension, hirsutism

Hyperaldosteronism – hypertension, hypokalemia

primary (↓ renin): Conn syndrome (adenoma), bilateral hyperplasia
secondary (↑ renin): renal artery stenosis

Adrenogenital syndromes – androgen excess, virilization

congenital adrenal hyperplasia (21-hydroxylase deficiency most common) or adrenocortical tumor

Adrenal insufficiency

Waterhouse-Friderichsen – acute, bilateral hemorrhage, sepsis (N. meningitidis), DIC, shock
Addison disease – chronic autoimmune destruction; weakness, hyperpigmentation, hypotension, hypoglycemia
secondary (hypothalamic/pituitary) – no hyperpigmentation (low ACTH)

Pheochromocytoma – catecholamine-producing tumor (adrenal medulla)

sustained or episodic hypertension, headache, palpitations, diaphoresis
rule of 10s: 10% children, bilateral, malignant, familial, extra-adrenal
elevated urinary VMA & catecholamines; Zellballen pattern

Dexamethasone suppression test: in Cushing disease (pituitary) → ↓ cortisol; in ectopic/neoplasia → no suppression

🧩 MEN Syndromes MEN1 · MEN2A · MEN2B

MEN1 (Werner) – pituitary, parathyroid, pancreatic tumors; Zollinger-Ellison; MEN1 gene (menin)
MEN2A (Sipple) – medullary thyroid carcinoma, pheochromocytoma, parathyroid hyperplasia; RET mutation
MEN2B – medullary thyroid carcinoma, pheochromocytoma, mucocutaneous neuromas; RET mutation

Autosomal dominant, incomplete penetrance; tumors occur at young age

🩸 Diabetes Mellitus type 1 · type 2 · complications

Diagnosis – fasting glucose ≥126 mg/dL (two occasions), or HbA1c ≥6.5%
Type 1 (10%) – young, autoimmune β-cell destruction (coxsackie B trigger, HLA DR3/DR4)

absolute insulin deficiency; 3Ps, DKA; insulitis (lymphocytic); treatment: insulin

Type 2 (90%) – obesity, insulin resistance, relative deficiency

often asymptomatic; hyperosmolar coma possible; amyloid deposition in islets
treatment: diet, oral agents, insulin

Vascular complications – atherosclerosis → MI, stroke, PVD

nephropathy: glomerular lesions, arteriolosclerosis
retinopathy: nonproliferative (microaneurysms, exudates) → proliferative (neovascularization)
neuropathy: peripheral, autonomic (bladder, impotence)

Myocardial infarction is the most common cause of death in DM

Type 1
• HLA DR3/DR4
• Islet lymphocytic infiltrate
• Ketoacidosis prone
• Insulin dependent

Type 2
• Obesity association
• Amyloid in islets
• Non-ketotic hyperosmolar coma
• May be managed without insulin