Primary Hyperparathyroidism
Elevated serum calcium + inappropriately elevated or normal intact PTH; 85% single parathyroid adenoma; osteitis fibrosa cystica.
Hypercalcemia of Malignancy
Very high calcium (> 13 mg/dL) with suppressed PTH (< 10 pg/mL); mediated by PTHrP (Squamous cell lung cancer, RCC) or osteolytic bone metastases.
Prolactinoma
Most common functioning pituitary adenoma; galactorrhea, amenorrhea, bitemporal hemianopsia; first-line therapy is Dopamine agonists (Cabergoline).
MEN 1 vs. MEN 2A/2B
MEN 1: 3 Ps (Pituitary, Parathyroid, Pancreas). MEN 2A: Medullary thyroid, Pheo, Parathyroid. MEN 2B: Medullary thyroid, Pheo, Mucosal neuromas (RET proto-oncogene).
Hypercalcemia vs. Hypocalcemia Diagnostic Algorithm
| Condition | PTH Level | Serum Calcium & Phosphate | Clinical Hallmarks & Acute Treatment |
|---|---|---|---|
| Primary Hyperparathyroidism | Elevated or inappropriately normal | High Ca2+, Low PO43- (phosphaturia), High 1,25-OH2-Vit D | 'Stones, Bones, Groans, Moans, and Psychiatric Overtones'; Subperiosteal bone resorption on hand X-ray; Parathyroidectomy |
| Hypercalcemia of Malignancy | Suppressed (< 10 pg/mL) | Severe High Ca2+, Low or normal PO43-, High PTHrP | Rapid onset, severe dehydration; Acute treatment: Aggressive IV normal saline hydration + IV Bisphosphonates (Zoledronic acid) / Calcitonin |
| Hypocalcemia (Hypoparathyroidism) | Low (post-thyroidectomy) or High (Pseudohypoparathyroidism / Vit D def) | Low Ca2+, High PO43- | Neuromuscular excitability: Chvostek sign (facial nerve tap produces twitch), Trousseau sign (carpopedal spasm with BP cuff), prolonged QT interval; IV Calcium gluconate |
Multiple Endocrine Neoplasia (MEN) Master Matrix
| Syndrome | Genetic Defect | Endocrine Manifestations | Pathognomonic Pearls |
|---|---|---|---|
| MEN Type 1 (Wermer Syndrome) | Autosomal dominant; MEN1 gene mutation (tumor suppressor encoding Menin on chromosome 11q13) | 3 Ps: 1. Pituitary adenomas (prolactinoma, GH), 2. Parathyroid hyperplasia (hypercalcemia), 3. Pancreatic islet cell tumors (Gastrinoma/ZES, Insulinoma) | Recurrent kidney stones + severe peptic ulcerations; check serum calcium and gastrin |
| MEN Type 2A (Sipple Syndrome) | Autosomal dominant; RET proto-oncogene gain-of-function mutation on chromosome 10 | 1. Medullary Thyroid Carcinoma (100%), 2. Pheochromocytoma (50%), 3. Parathyroid hyperplasia (20%) | Elevated serum calcitonin; prophylactic thyroidectomy in early childhood |
| MEN Type 2B | Autosomal dominant; RET proto-oncogene (M918T codon mutation) | 1. Medullary Thyroid Carcinoma (aggressive, early childhood), 2. Pheochromocytoma, 3. Mucosal neuromas & Marfanoid habitus | Mucosal neuromas of lips/tongue, intestinal ganglioneuromatosis; NO parathyroid hyperplasia |
OMM Board Correlate: Sphenoid Bone & Pituitary Fossa
- Sella Turcica Biomechanics: The pituitary gland sits within the sella turcica of the sphenoid bone, roofed by the diaphragma sellae. Cranial sphenobasilar synchondrosis (SBS) compression or torsion alters reciprocal tension membrane equilibrium.
- Thyroid & Parathyroid Autonomics: Sympathetics derive from T1–T4 and cervical ganglia (superior, middle, inferior). C5–T1 somatic dysfunction frequently accompanies thyroid/parathyroid pathology.
Board Traps & Common Distractors
- In patients with MEN 2A or 2B who have both Medullary Thyroid Carcinoma and Pheochromocytoma, ALWAYS perform adrenalectomy for the Pheochromocytoma BEFORE thyroidectomy; intraoperative catecholamine release during neck dissection without prior alpha-blockade will trigger a fatal hypertensive crisis.
- Pituitary apoplexy is an acute neurosurgical emergency caused by sudden infarction or hemorrhage into a preexisting pituitary macroadenoma; presents with severe 'thunderclap' headache, visual loss, ophthalmoplegia, and acute secondary adrenal crisis (hypotension); administer high-dose stress corticosteroids immediately.
- Severe acute hypercalcemia (> 14 mg/dL) produces profound hypovolemia and cardiac conduction blocks; initial resuscitation requires aggressive IV normal saline (3–4 L over 24 hours) BEFORE administering bisphosphonates.