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Endocrine Pathology Overview

Jul 16, 2025

Overview

This lecture covers endocrine pathology, focusing on parathyroid gland disorders, adrenal gland disorders, and multiple endocrine neoplasia (MEN) syndromes, highlighting their functions, clinical features, diagnostic points, and key pathologies.

Parathyroid Gland: Anatomy & Physiology

  • Humans have four parathyroid glands: two superior (from the 4th pharyngeal pouch) and two inferior (from the 3rd pouch).
  • Chief cells in the parathyroid secrete parathyroid hormone (PTH).
  • PTH function: increases blood calcium, decreases blood phosphate ("phosphate trashing hormone").
  • PTH raises calcium by: activating vitamin D (via alpha-1-hydroxylase in kidney), increasing renal calcium reabsorption, and stimulating bone resorption (via osteoclasts).
  • PTH receptors are on osteoblasts; osteoblasts activate osteoclasts by producing RANK ligand.

Parathyroid Disorders

Hyperparathyroidism

  • Primary hyperparathyroidism: excess PTH due to parathyroid adenoma (most common), hyperplasia, or MEN syndromes.
  • Most common adenoma site: right inferior gland; associated with cyclin D1 overactivity, MEN1 gene mutations.
  • Clinical features: "bones, stones, groans, and moans" — bone pain/fractures (osteitis fibrosa cystica/brown tumors), kidney stones, abdominal symptoms (constipation, pancreatitis), psychiatric symptoms (depression, memory loss), and band keratopathy in eyes.
  • Labs: ↑PTH, ↑calcium, ↓phosphate.
  • X-ray: salt and pepper skull, subperiosteal bone resorption.

Secondary Hyperparathyroidism

  • Caused by chronic renal failure → ↓vitamin D activation, ↑PTH due to hypocalcemia.
  • Features: renal osteodystrophy, "rugger jersey spine" on X-ray.
  • Labs: ↑PTH, ↓calcium, ↓phosphate.

Hypoparathyroidism

  • Causes: surgical removal/blood supply disruption, autoimmune destruction, DiGeorge syndrome (22q11.2 deletion), hypomagnesemia.
  • DiGeorge: absence of 3rd/4th pharyngeal pouches, thymic aplasia, recurrent infections, hypocalcemia.
  • Clinical: hypocalcemia leads to neuromuscular irritability, tetany, Chvostek's sign, Trousseau's sign.
  • Labs: ↓PTH, ↓calcium, ↑phosphate.

Pseudohypoparathyroidism

  • PTH present but target organs (kidney/bone) resistant due to GNAS mutation.
  • Features: hypocalcemia, Albright hereditary osteodystrophy (short stature, shortened 4th/5th metacarpals), knuckle-knuckle-dimple-dimple sign.
  • Labs: ↑PTH, ↓calcium.

Adrenal Pathologies

Hyperaldosteronism

  • Causes: adrenal cortical hyperplasia (most common), adrenal adenoma (Conn syndrome).
  • Features: hypertension, hypokalemia, metabolic alkalosis.

Adrenal Insufficiency (Addison's Disease)

  • Causes: autoimmune destruction (most common worldwide), tuberculosis, Waterhouse-Friderichsen syndrome (adrenal hemorrhage due to meningococcemia).
  • Features: hypotension, hyponatremia, hyperkalemia, metabolic acidosis, hyperpigmentation.

Adrenal Tumors

Pheochromocytoma

  • Tumor of adrenal medulla chromaffin cells; produces excessive catecholamines (epinephrine/norepinephrine).
  • Clinical: episodic hypertension, headache, palpitations, sweating, tachycardia, anxiety.
  • Diagnosis: increased urine/metanephrine, vanillylmandelic acid (VMA).
  • Histology: Zellballen (nest) pattern, sustentacular (S100+) cells; positive for chromogranin, synaptophysin.
  • "Rule of 10s": 10% extra-adrenal (paragangliomas), bilateral, malignant, familial, in children.
  • Chromaffin reaction: tumor turns brown with potassium dichromate due to oxidized catecholamines.

Neuroblastoma

  • Most common adrenal medulla tumor in children; associated with N-myc amplification.
  • Features: abdominal mass (distension); rarely causes hypertension.
  • Histology: Homer-Wright pseudorosettes (tumor cells around pink fibrillary center).

Multiple Endocrine Neoplasia (MEN)

  • MEN1 (Wermer syndrome): parathyroid, pituitary, pancreatic tumors; MEN1 gene mutation, autosomal dominant.
  • MEN2A (Sipple syndrome): medullary thyroid carcinoma, pheochromocytoma, parathyroid tumors; RET gene mutation.
  • MEN2B: medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, marfanoid habitus.

Key Terms & Definitions

  • Parathyroid hormone (PTH) — increases blood calcium, decreases phosphate.
  • Osteitis fibrosa cystica — bone changes from excessive PTH ("brown tumor").
  • Chvostek's sign — facial spasm with cheek tapping (hypocalcemia).
  • Trousseau's sign — carpopedal spasm with BP cuff inflation (hypocalcemia).
  • Zellballen pattern — nests of cells on histology (pheochromocytoma).
  • Conn syndrome — adrenal adenoma causing primary hyperaldosteronism.
  • Albright hereditary osteodystrophy — skeletal findings in pseudohypoparathyroidism.

Action Items / Next Steps

  • Review parathyroid, adrenal, and MEN syndromes for exams.
  • Study diagrams/X-rays of key findings (e.g., salt & pepper skull, Brown tumors, Zellballen).
  • Prepare for next class on lung pathology/respiratory system.

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