A 52-year-old man comes to the office due to easy bruisibility and muscle weakness. Medical history is unremarkable, but the patient has smoked a pack of cigarettes daily for 30 years. Blood pressure is 160/110 mm Hg, and pulse is 80/min. BMI is 29 kg/m². Physical examination shows facial plethora, slight centripetal distribution of body fat, diffuse skin pigmentation, and bilateral peripheral edema. Fasting blood glucose is 160 mg/dL and creatinine is 1.2 mg/dL. Chest x-ray reveals a lung mass. Which of the following is the most likely cause of this patient's elevated blood pressure?

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11ec160b_3bab_f8e0_9249_8b3622bc8dc5_MD0001_00 This patient has Cushing syndrome (CS) presenting with hypertension, facial plethora, easy bruising, centripetal obesity (ie, trunk, abdomen), and hyperglycemia. In light of the associated hyperpigmentation (due to the cosecretion of ACTH and melanocyte-stimulating hormone) and lung mass, this is likely due to an ACTH-secreting small cell lung cancer. Paraneoplastic CS often develops rapidly, and the characteristic facial features may not be present at the time of diagnosis. High levels of cortisol, as seen in patients with CS, frequently cause hypertension due to a combination of the following: Activation of renal mineralocorticoid receptors usually occurs in patients with severe hypercortisolism, which is often due to ectopic ACTH secretion. This receptor activation induces sodium reabsorption and potassium wasting in the renal collecting tubules. (Choice B) Elevated plasma catecholamine levels occur with pheochromocytoma. Hypertension is common, although it is often severe (eg, systolic blood pressure >180 mm Hg), paroxysmal, and associated with tachypalpitations. However, hyperpigmentation and edema would not be expected. (Choice C) Impaired filtration of sodium and water is a major cause of hypertension and peripheral edema in patients with glomerulonephritis and/or other causes of kidney injury; in such cases, creatinine would be elevated. Given this patient's hyperpigmentation, hyperglycemia, and lung mass, CS is more likely. (Choice D) Marked urinary loss of albumin and other proteins is characteristic of nephrotic syndrome. Peripheral edema is usually present due to reduced intravascular oncotic pressure, but hypertension is unusual unless the glomerular filtration rate is impaired (eg, elevated creatinine). Also, hyperpigmentation is not seen. (Choice E) Renal resistance to antidiuretic hormone occurs in nephrogenic diabetes insipidus. Patients are either euvolemic or hypovolemic (if they cannot obtain drinking water as needed) and do not have hypertension or peripheral edema. Educational objective: High levels of cortisol, as seen in patients with Cushing syndrome, frequently cause hypertension due to the increased production of angiotensinogen, adrenergic hypersensitivity, and activation of renal mineralocorticoid receptors, which induces sodium reabsorption. The combined effect leads to expanded blood volume and increased systemic vascular resistance. __________ References: The pathophysiology and treatment of hypertension in patients with Cushing's syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/31164868)

A 52-Year-Old Man Comes to the Office Due to Easy