Endocrinology Flashcards

A 45-year-old woman is found to have an incidental serum calcium of 10.9 mg/dL on routine labs, confirmed on repeat fasting testing. PTH is 68 pg/mL (normal 15–65 pg/mL). Her 24-hour urine calcium is 92 mg/day. Her brother has similar asymptomatic hypercalcemia. Urine creatinine is 1.2 g/day and serum creatinine is 0.9 mg/dL. Which finding most reliably differentiates her condition from primary hyperparathyroidism and argues against parathyroidectomy?

Answer: Calcium-to-creatinine clearance ratio less than 0.01

A calcium-to-creatinine clearance ratio (CaCCR) 0.02. The positive family history and low urine calcium in this case are classic for FHH. Surgery is not indicated because the condition is benign and PTX will not correct it.

A 22-year-old man presents with a palpable neck mass, marfanoid habitus, multiple mucosal neuromas on the lips and tongue, and episodic hypertension. His mother died of thyroid cancer and a suspected cardiac event. Genetic testing confirms a RET proto-oncogene mutation. Compared to a patient with MEN2A, which of the following manifestations is most likely ABSENT in this patient?

Answer: Primary hyperparathyroidism

MEN2B (RET codon 918 mutation) comprises medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuromas, marfanoid habitus, and intestinal ganglioneuromatosis — but does NOT include primary hyperparathyroidism. MEN2A (codons 634, 609, etc.) includes MTC + pheochromocytoma + primary hyperparathyroidism. Both syndromes carry RET mutations. MEN2B has the most aggressive MTC phenotype and prophylactic thyroidectomy is recommended in the first 6 months of life.

A 55-year-old woman undergoes laparoscopic right adrenalectomy for a 3.4 cm adrenal incidentaloma. Preoperative workup showed post-1 mg DST cortisol of 4.1 mcg/dL (subclinical autonomous cortisol secretion), normal urine metanephrines, and normal aldosterone/renin ratio. On postoperative day 1 she develops fatigue, nausea, and hypotension unresponsive to 2L IV normal saline. Her plasma ACTH is undetectable. What is the most appropriate immediate next step?

Answer: Administer IV hydrocortisone 100 mg immediately

This patient is in adrenal crisis due to HPA axis suppression by the chronically autonomous cortisol production of the resected adenoma. Even subclinical hypercortisolism suppresses the contralateral adrenal cortex and the hypothalamic-pituitary axis. Postoperative hypotension, nausea, and undetectable ACTH in this context represent an endocrine emergency. Treatment must not be delayed for diagnostic testing — IV hydrocortisone should be given immediately. After stabilization, a cosyntropin stimulation test can assess recovery of the contralateral adrenal.

A 26-year-old normotensive woman presents with recurrent muscle cramps and fatigue. Labs: K+ 2.8 mEq/L, HCO3- 31 mEq/L, Mg2+ 1.2 mg/dL (low), spot urine Ca/Cr ratio 0.04 (hypocalciuria). She takes no medications. Urine chloride and potassium are inappropriately elevated. Which molecular defect best explains this constellation of findings?

Answer: Inactivating mutation in NCC in the distal convoluted tubule

This is Gitelman syndrome, caused by loss-of-function mutations in SLC12A3 encoding NCC (the thiazide-sensitive Na-Cl cotransporter) in the distal convoluted tubule. The DCT is responsible for Mg reabsorption via TRPM6 channels and calcium reabsorption — NCC dysfunction causes hypomagnesemia and hypocalciuria (the same effect as chronic thiazide use). Bartter syndrome (types 1/2/3 affecting NKCC2, ROMK, or CLCNKB in the TAL) causes hypercalciuria, not hypocalciuria. The triad of hypokalemic metabolic alkalosis + hypomagnesemia + hypocalciuria is pathognomonic for Gitelman.

A 17-year-old girl with obesity, short stature, and shortened 4th and 5th metacarpals has labs showing Ca2+ 7.1 mg/dL, PO4 6.3 mg/dL, PTH 310 pg/mL, and TSH 9.1 mIU/L with normal free T4. Exogenous PTH infusion fails to raise urinary cAMP or phosphate excretion. Her father has the same body habitus but has normal calcium, PTH, and TSH. A GNAS mutation is found in the family. Which mechanism explains why the father is phenotypically similar but metabolically normal?

Answer: Tissue-specific maternal imprinting of GNAS means only the maternally inherited allele is expressed in kidney and pituitary

Pseudohypoparathyroidism type 1a (PHP1a) requires a maternally inherited GNAS mutation because Gsα is expressed only from the maternal allele in the kidney, pituitary, and other key tissues due to genomic imprinting. The father carries the same GNAS mutation and has Albright's hereditary osteodystrophy (AHO) phenotype — short stature, brachydactyly, subcutaneous ossifications — but because the paternal GNAS allele is silenced in hormone-responsive tissues, he has no PTH or TSH resistance. This paternal inheritance pattern is called pseudopseudohypoparathyroidism (PPHP).

A 39-year-old woman presents with progressive weight gain, hypertension, and new-onset diabetes. Laboratory evaluation confirms hypercortisolism (elevated UFC 3x ULN, failed 1 mg overnight DST). Morning plasma ACTH is 52 pg/mL (normal 7–63 pg/mL). MRI of the pituitary with gadolinium at a tertiary center shows no discrete lesion. What is the most appropriate next diagnostic step to localize the source of ACTH?

Answer: Bilateral inferior petrosal sinus sampling (BIPSS) with CRH stimulation

In ACTH-dependent Cushing's syndrome with a negative pituitary MRI, BIPSS is the gold standard for distinguishing Cushing's disease (pituitary source) from ectopic ACTH secretion. Up to 40–50% of pituitary corticotroph microadenomas are missed on MRI. BIPSS measures ACTH in the inferior petrosal sinuses (draining the pituitary) versus a peripheral vein; a central-to-peripheral gradient ≥2.0 at baseline or ≥3.0 after CRH stimulation localizes to the pituitary with >95% sensitivity and specificity. High-dose DST and CRH stimulation testing have insufficient discriminatory power when MRI is non-diagnostic.