A 34-year-old, previously healthy woman comes to the office due to irregular menstruation and a 4.5 kg (10-lb) weight gain over the past 6 months. The patient also reports muscle weakness causing difficulty climbing stairs or lifting her child. Blood pressure is 152/86 mm Hg and pulse is 72/min. BMI is 31 kg/m². Physical examination shows excessive fat accumulation in the abdomen and supraclavicular area. Sun-exposed areas and skin creases are hyperpigmented and there are wide striae over the abdomen. Coarse hair is present on the face, chest, and abdomen. Which of the following sets of laboratory findings are most likely to be seen in this patient?

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11ec160b_3ab4_a0b4_9249_3b331cabd541_MD0001_00 This patient with central obesity, proximal muscle weakness, striae, and hypertension has common features of cortisol excess (ie, Cushing syndrome). Other possible findings include hyperglycemia, dermal atrophy, and easy bruisability. Hypercortisolism can be confirmed on finding an elevated late-night salivary cortisol concentration or increased 24-hour urine cortisol excretion. Cushing syndrome can be categorized as ACTH-dependent (ie, ↑ACTH stimulating excess cortisol production) or ACTH-independent (ie, glucocorticoid excess not caused by ACTH). Excess ACTH secretion causes identifiable clinical findings: Hyperpigmentation: Both ACTH and alpha-melanocyte-stimulating hormone (MSH) are derived from pro-opiomelanocortin, leading to cosecretion of alpha-MSH. ACTH also directly stimulates the MC2R receptor on melanocytes. Androgenization: ACTH stimulates production of adrenal androgens (eg, ↑DHEAS [dehydroepiandrosterone sulfate], androstenedione). This leads to hirsutism, menstrual abnormalities, and oily skin. This patient's hyperpigmentation and hirsutism are consistent with ACTH-dependent hypercortisolism, likely due to a corticotroph pituitary adenoma (Cushing disease). (Choice B) Primary adrenal insufficiency leads to decreased cortisol levels (and decreased urinary cortisol excretion) with a compensatory rise in ACTH. Hyperpigmentation may be present, but adrenal androgen production is often diminished (due to loss of androgen-producing adrenocortical cells) and hirsutism is not present. (Choices C and E) ACTH-independent Cushing syndrome due to a cortisol-producing adrenal adenoma is characterized by increased urinary cortisol excretion with suppressed ACTH levels. Exogenous glucocorticoids also cause suppression of ACTH, but with decreased production (and urinary excretion) of cortisol. Low cortisol excretion and ACTH levels are also seen in central adrenal insufficiency. Because ACTH is low in these states, patients do not have hyperpigmentation or hyperandrogenic features (eg, hirsutism). (Choice D) Polycystic ovary syndrome is characterized by excessive ovarian production of androgens. Common clinical features include oligo/amenorrhea, obesity, and hirsutism. However, ACTH and cortisol production are unaffected, and hyperpigmentation is not seen. Educational objective: Cushing syndrome can be categorized as ACTH-dependent or ACTH-independent. Excess ACTH secretion in ACTH-dependent Cushing syndrome leads to hyperpigmentation. In addition to increased cortisol production, ACTH stimulates production of adrenal androgens (eg, testosterone, dehydroepiandrosterone sulfate) leading to hirsutism and menstrual irregularities. __________ References: Cushing's disease. (http://www.ncbi.nlm.nih.gov/pubmed/22710101)

A 34-Year-Old, Previously Healthy Woman Comes to the Office Due