A 34-year-old woman comes to the office with progressive weight gain over the past year. She also has weakness, easy bruising, and irregular menstrual periods. The patient takes no medications and has no drug allergies. Blood pressure is 150/90 mm Hg and pulse is 78/min. Laboratory studies reveal an elevated serum cortisol level that is not suppressed following administration of low-dose dexamethasone. Her 24-hour urine free-cortisol concentration and plasma ACTH are elevated. Which of the following histopathologic findings are most likely to be present in this patient's adrenal glands?

Question

A 34-year-old woman comes to the office with progressive weight gain over the past year.  She also has weakness, easy bruising, and irregular menstrual periods.  The patient takes no medications and has no drug allergies.  Blood pressure is 150/90 mm Hg and pulse is 78/min.  Laboratory studies reveal an elevated serum cortisol level that is not suppressed following administration of low-dose dexamethasone.  Her 24-hour urine free-cortisol concentration and plasma ACTH are elevated.  Which of the following histopathologic findings are most likely to be present in this patient's adrenal glands?

Quizplus · Accepted Answer

11ec160b_3ab4_0472_9249_2fb261f2e8ab_MD0001_00 This patient has symptoms of hypercortisolism, including weight gain, weakness, and easy bruising. She also has increased 24-hour urine excretion of cortisol and an elevated serum cortisol level that is not suppressed by low-dose dexamethasone, which confirm the diagnosis of Cushing syndrome. In addition, her ACTH level is elevated (ACTH-dependent Cushing syndrome), which is most commonly due to an ACTH-secreting corticotroph pituitary adenoma (Cushing disease). Initially, excess ACTH rapidly acts to increase adrenal blood flow and metabolic activity, primarily within the zona fasciculata and reticularis. ACTH stimulates the transfer of cholesterol to the inner mitochondrial membrane by steroidogenic acute regulatory protein (the rate limiting step in steroid production) and its conversion to pregnenolone by cholesterol side-chain cleavage enzyme. Increased pregnenolone availability results in increased cortisol synthesis within the zona fasciculata and increased androgen production within the zona reticularis (can lead to irregular menstruation, hirsutism). ACTH also has a trophic (growth) effect on the zona fasciculata and reticularis; as time passes, high levels of ACTH upregulate RNA and protein synthesis and induce cellular proliferation (hyperplasia). (Choice A) Although increased ACTH can have a transient effect on aldosterone production, angiotensin II is the primary trophic hormone for the zona glomerulosa. Adenoma or nodular hyperplasia of the zona glomerulosa can be associated with increased secretion of mineralocorticoids (primary hyperaldosteronism [Conn syndrome]), which presents with hypertension and hypokalemia (muscle weakness). (Choice B) Atrophy of the entire adrenal cortex is most commonly caused by autoimmune adrenalitis and presents with chronic adrenal insufficiency (Addison disease). There is a compensatory rise in ACTH secretion, but, unlike in this patient, urine cortisol excretion is not elevated. (Choices C and E) Pheochromocytoma is a catecholamine-secreting tumor derived from the chromaffin cells of the adrenal medulla. Adrenal medullary hyperplasia is a rare disorder that may be a precursor to pheochromocytoma. These disorders typically present with symptoms of catecholamine excess (eg, palpitations, diaphoresis) and episodic hypertension. Patients have elevated blood and urine levels of catecholamines rather than cortisol. Educational objective: ACTH is the major trophic hormone of the zona fasciculata and reticularis, whereas the zona glomerulosa is primarily regulated by angiotensin II. Excess production of ACTH causes increased cortisol synthesis within the zona fasciculata (Cushing's manifestations) and increased androgen production within the zona reticularis (irregular menstruation, hirsutism in women).

A 34-Year-Old Woman Comes to the Office with Progressive Weight