A 29-year-old woman comes to the emergency department due to worsening generalized weakness and lightheadedness, causing her difficulty ambulating. The patient has had fatigue, nausea, diffuse abdominal pain, and a 10-kg (22-lb) weight loss over the past 3 months. She has a history of hypothyroidism and takes levothyroxine. The patient works as a flight attendant. Temperature is 37.4 C (99.3 F), blood pressure is 80/50 mm Hg, and pulse is 110/min. Orthostatic changes are present. BMI is 19 kg/m². Physical examination shows dry and pigmented buccal mucous membranes. Lungs are clear to auscultation and heart sounds are normal. The abdomen is soft with mild generalized tenderness. Laboratory results are as follows: Which of the following is the most likely cause of this patient's current condition?

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11ec25c8_d39d_21f9_bc81_5fc507764ca0_MD0003_00 This patient likely has primary adrenal insufficiency (PAI) (also known as Addison disease), which most commonly results from an autoimmune response against the bilateral adrenal cortex. It often occurs in conjunction with other autoimmune disease (eg, primary hypothyroidism, vitiligo). The clinical manifestations of PAI result from a deficiency of hormone production in all 3 layers of the adrenal cortex. Reduced mineralocorticoid (mainly aldosterone) production leads to renal sodium wasting with consequent hypovolemia (and weight loss), hypotension, and orthostasis. Reduced glucocorticoid (eg, cortisol) production causes fatigue and contributes to hypotension. There is also decreased negative feedback on ACTH, which leads to high levels of both ACTH and its precursor, proopiomelanocortin (POMC); this causes hyperpigmentation of the skin and mucous membranes due to increased levels of melanocyte-stimulating hormone, which is also derived from POMC. A peripheral eosinophilia is common, likely due to reduced migration of eosinophils from the bloodstream into the tissues in the setting of low cortisol. For unclear reasons, abdominal pain/tenderness and normocytic anemia are often present as well. adrenal cortex Reduced production of adrenal androgens (eg, dehydroepiandrosterone) can lead to decreased libido and secondary sexual characteristics (eg, pubic hair); these effects are typically only seen in women because testicular androgen production continues in men. (Choice B) Anorexia nervosa can present with weight loss and amenorrhea; however, it would not explain hyperpigmented mucous membranes and requires a BMI ≤18.5 kg/m² for diagnosis. ² (Choice C) Diuretic overuse can lead to hypovolemia, hypotension, and orthostatic symptoms; however, it would not explain this patient's hyperpigmented mucous membranes, peripheral eosinophilia, and abdominal pain. (Choice D) Small cell lung cancer can cause weight loss and sometimes presents with ectopic production of ACTH; however, this leads to hypercortisolism (eg, weight gain, hypertension) rather than adrenal insufficiency. (Choice E) Peripheral eosinophilia is common with parasitic infection (eg, strongyloidiasis); however, parasitic infection is less likely in the absence of fever and would not explain hyperpigmented mucous membranes. (Choice F) Viral gastroenteritis can cause fatigue, weight loss, and gastrointestinal distress, but the symptoms typically resolve on their own within about a week. The several-month duration of this patient's symptoms, combined with hyperpigmented mucous membranes, makes PAI more likely. Educational objective: Primary adrenal insufficiency most commonly results from an autoimmune response against the bilateral adrenal cortex and often occurs in conjunction with other autoimmune disease (eg, primary hypothyroidism, vitiligo). Clinical manifestations result from deficiency of mineralocorticoids, glucocorticoids, and androgens and include fatigue, weight loss, hypotension, and hyperpigmentation of the skin and mucous membranes.

A 29-Year-Old Woman Comes to the Emergency Department Due to Worsening