A 34-year-old woman comes to the office due to a 6-month history of easy bruising with minimal or no trauma. She also has had difficulty climbing stairs due to muscle weakness and frequent nocturnal muscle cramps. The patient has experienced a 7-kg (15-lb) weight gain despite following a restricted-calorie vegan diet. Her medical history is notable for an uncomplicated root canal procedure 6 months ago but is otherwise unremarkable. She takes no prescription or over-the-counter medications. The patient is not currently sexually active and has never been pregnant. Her last menstrual period was 3 months ago. There is no family history of bleeding disorders. Her blood pressure is 146/94 mm Hg and pulse is 78/min. BMI is 29 kg/m². Examination shows facial plethora with dark terminal hair on her upper lip and chin. There is inflammatory acne on her face and back, extensive tinea versicolor on the trunk, and scattered bruises over the extremities. Fasting laboratory results are as follows: Which of the following is the most likely cause of this patient's symptoms?

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11ec25c8_d3a1_dcf4_bc81_59d339e366e9_MD0003_00 This patient has several features suggesting Cushing syndrome (hypercortisolism). Weight gain, proximal muscle weakness, and hypertension are common presenting findings. Patients can experience easy bruisability, dermal atrophy, and wide purple striae due to the catabolic effects of cortisol on connective tissue; however, platelet function and coagulation proteins are normal. Dermatologic signs may include hyperpigmentation (in ACTH-dependent Cushing syndrome) and increased incidence of cutaneous fungal infections (eg, tinea versicolor, onychomycosis). Women can have features of hyperandrogenism (eg, menstrual irregularities, acne, hirsutism) due to co-secretion of adrenal androgens with cortisol. Hyperglycemia is common (due to peripheral insulin resistance and hypercortisolism-induced gluconeogenesis). Hypokalemia and alkalosis may be present (due to the partial mineralocorticoid effects of cortisol) if cortisol levels are very high. Once there is laboratory confirmation of hypercortisolism (eg, late-night salivary cortisol assay, 24-hour urine free cortisol measurement, overnight low-dose dexamethasone suppression test), ACTH levels are measured to differentiate ACTH-dependent (eg, ACTH-secreting pituitary tumor, ectopic ACTH) from ACTH-independent (eg, adrenal adenoma) causes. (Choice B) Cutaneous small-vessel vasculitis can be triggered by infections, medications, inflammatory conditions, or malignancy. It presents with nonblanching violaceous petechiae that can coalesce into palpable purpura. Weight gain, hyperglycemia, and hyperandrogenic symptoms would not be common. Cutaneous small-vessel vasculitis (Choice C) Polycystic ovary syndrome shares a number of features with Cushing syndrome, including obesity, irregular menstrual periods, and hyperandrogenism. However, skin atrophy, muscle weakness, and bruisability are not characteristic. (Choices D, E, and F) Vitamin C deficiency causes microvascular bleeding due to impaired synthesis of collagen. Vitamin K deficiency also causes bleeding, due to reduced levels of coagulation factors II, VII, IX, and X. Von Willebrand disease is an autosomal dominant disorder characterized by impaired platelet function and excessive bleeding. However, none of these conditions would explain this patient's weight gain, muscle weakness, hyperandrogenism, hyperglycemia, and metabolic alkalosis. In addition, vitamin C or K deficiencies are not common in vegans. Educational objective: Cushing syndrome is characterized by weight gain, muscle weakness, and hypertension. Patients can experience easy bruisability, dermal atrophy, and striae due to the catabolic effects of cortisol on connective tissue. Women can have features of hyperandrogenism due to co-secretion of adrenal androgens with cortisol. References: The diagnosis of Cushing's syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/20821267)

A 34-Year-Old Woman Comes to the Office Due to a 6-Month