Endocrinology Flashcards

A 34-year-old woman with a history of lithium therapy for bipolar disorder presents with polyuria, polydipsia, and a serum sodium of 148 mEq/L. Water deprivation test shows urine osmolality of 180 mOsm/kg after 8 hours, rising to 195 mOsm/kg after exogenous desmopressin (DDAVP). Which mechanism best explains her condition?

Answer: Lithium-induced downregulation of aquaporin-2 channels in the collecting duct, causing nephrogenic diabetes insipidus refractory to ADH

Lithium is the classic cause of nephrogenic diabetes insipidus (NDI). It enters principal cells via ENaC and accumulates intracellularly, blocking adenylyl cyclase activation downstream of the V2 receptor and causing degradation of aquaporin-2 water channels. In NDI, urine osmolality fails to rise appropriately after both water deprivation AND exogenous DDAVP ( 50% rise) and primary polydipsia (which typically concentrates urine partially during deprivation).

A 52-year-old man with type 2 diabetes on metformin and sitagliptin presents with recurrent hypoglycemia. He is not on sulfonylureas or insulin. Supervised 72-hour fast reproduces hypoglycemia at hour 18: glucose 41 mg/dL, insulin 22 µU/mL, C-peptide 4.8 ng/mL, proinsulin 22 pmol/L (elevated), beta-hydroxybutyrate 0.1 mmol/L (suppressed), and insulin secretagogue screen is negative. What is the most likely diagnosis?

Answer: Insulinoma

The classic biochemical fingerprint of insulinoma is hypoglycemia with endogenously elevated insulin, C-peptide, and proinsulin, suppressed beta-hydroxybutyrate (indicating insulin-mediated inhibition of lipolysis), and a negative secretagogue screen. Exogenous insulin would suppress C-peptide and proinsulin. Insulin autoimmune syndrome (Hirata disease) is associated with extremely high total insulin levels (often >100 µU/mL) due to insulin-antibody complexes and is more common in Japanese patients or those exposed to thiol compounds; the free/total insulin ratio is key. Non-islet cell tumor hypoglycemia is mediated by IGF-2, causing suppressed insulin and C-peptide.

A 28-year-old woman presents with secondary amenorrhea, galactorrhea, and a serum prolactin of 340 ng/mL. MRI reveals a 12 mm pituitary macroadenoma. She is started on cabergoline 0.5 mg twice weekly. After 6 months, prolactin normalizes and menses resume, but repeat MRI shows only 10% tumor reduction. Cabergoline dose is maximized. At 12 months, she desires pregnancy. What is the most appropriate next step?

Answer: Perform transsphenoidal surgery before attempting conception given inadequate tumor shrinkage

For macroprolactinomas that show poor radiological response to dopamine agonists (< 50% volume reduction), transsphenoidal surgery before conception is the preferred strategy. Macroprolactinomas carry a clinically significant risk (~20–30%) of symptomatic tumor enlargement during pregnancy due to estrogen-driven lactotroph stimulation. In well-shrunk macroadenomas, cabergoline is typically stopped once pregnancy is confirmed and close monitoring suffices; however, when shrinkage is inadequate, surgery pre-conception reduces the tumor bulk, lowering the risk of visual compromise during pregnancy. Continuing cabergoline throughout pregnancy remains an option only if surgery fails or is contraindicated.

A 45-year-old man with MEN1 undergoes resection of a gastrinoma. Post-operatively, he develops hypocalcemia with Ca 7.1 mg/dL, phosphorus 3.0 mg/dL, PTH 890 pg/mL (markedly elevated), and 25-OH vitamin D 8 ng/mL. He is on proton pump inhibitor therapy. Which of the following best explains his biochemical picture?

Answer: Vitamin D deficiency causing secondary hyperparathyroidism with PTH-resistance at the skeletal level

This patient has profound vitamin D deficiency (25-OH vitamin D 8 ng/mL), likely worsened by PPI-associated malabsorption and possibly prior achlorhydria from the gastrinoma itself. Severe vitamin D deficiency impairs intestinal calcium absorption, leading to hypocalcemia that drives compensatory secondary hyperparathyroidism — hence the markedly elevated PTH. The normal-to-low phosphorus (not high, as seen in hypoparathyroidism) confirms PTH is biologically active. Hungry bone syndrome occurs post-parathyroidectomy in the setting of pre-existing hyperparathyroidism; the PTH here is elevated, not suppressed. Hypomagnesemia causes functional hypoparathyroidism (low PTH despite hypocalcemia). Pseudohypoparathyroidism presents with high PTH AND high phosphorus.

A 61-year-old woman with a 6-cm right adrenal mass found incidentally on CT for renal colic. She has well-controlled hypertension on amlodipine. Biochemical workup: 1-mg overnight DST cortisol 4.2 µg/dL, plasma metanephrines normal, aldosterone/renin ratio normal, DHEA-S low-normal. Her ACTH is 8 pg/mL (low-normal). Repeat DST with 8 mg dexamethasone shows cortisol 3.8 µg/dL. What is the most appropriate next management step?

Answer: Adrenalectomy is indicated because the 6-cm size and autonomous cortisol secretion together meet criteria for surgical resection

This lesion meets two independent indications for adrenalectomy: (1) size ≥ 4 cm, which raises concern for adrenocortical carcinoma (ACC risk increases substantially above 4 cm, and ACC is the primary size-based surgical indication for adrenal incidentalomas); and (2) autonomous cortisol secretion (ACS), confirmed by post-1-mg DST cortisol > 1.8 µg/dL — here 4.2 µg/dL with a suppressed ACTH of 8 pg/mL. The high-dose 8-mg DST is used for Cushing's disease (pituitary origin), not adrenal lesions; failure to suppress on high-dose DST in an adrenal source is expected and does not add diagnostic value. Medical therapy is not a definitive treatment for ACS with a resectable lesion, and adrenal vein sampling is used for primary aldosteronism lateralization, not cortisol-producing adenomas.

A 38-year-old woman with Hashimoto's thyroiditis on stable levothyroxine 125 mcg/day for 5 years presents with fatigue, weight gain, and constipation over 4 months. TSH is 11.2 mIU/L, free T4 is 0.7 ng/dL. She reports starting a new medication 6 months ago. Which drug class is most likely responsible for her levothyroxine requirement increase?

Answer: Proton pump inhibitor (pantoprazole) impairing levothyroxine absorption in the proximal small bowel

PPIs (e.g., pantoprazole, omeprazole) raise gastric pH, which impairs dissolution of levothyroxine tablets — absorption is pH-dependent and optimal in an acidic environment. Multiple studies confirm PPIs can require levothyroxine dose increases of 20–30%. While calcium carbonate is a classic culprit when co-administered with levothyroxine, the question specifies a drug started 6 months ago with chronic, progressive hypothyroidism rather than acute malabsorption; also, the clinical vignette does not frame this as a co-administration timing issue. SSRIs do not meaningfully induce CYP enzymes relevant to T4 clearance. Sunitinib causes hypothyroidism through destructive thyroiditis and increased clearance but is used for RCC/GIST, making it a less likely new medication in this context without that history — and sunitinib would not cause the stable-then-worsening pattern seen here.