A 45-year-old man comes to the office for blood pressure follow-up. He has hypertension that has been difficult to control over the last 2 years. The patient has been following a low-salt diet and exercising to lose weight. He occasionally gets muscle cramps while exercising, but otherwise has excellent exercise tolerance and generally feels well. Current medications are lisinopril, hydrochlorothiazide, amlodipine, potassium chloride, and carvedilol. The patient is compliant with clinic visits and regularly fills his prescriptions. He has no other medical conditions, no significant family history of cardiovascular disease, and does not use tobacco, alcohol, or illicit drugs. Blood pressure is 162/94 mm Hg and pulse is 64/min. BMI is 27 kg/m². After 30 minutes, blood pressure is 160/95 mm Hg. During the previous visit, blood pressure was also in this range. The remainder of the physical examination is unremarkable. Laboratory results are as follows: An echocardiogram performed 6 months ago revealed mild left atrial dilation, left ventricular hypertrophy, and a left ventricular ejection fraction of 65%. Which of the following is the most likely cause of this patient's hypertension?

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11ec193a_97a3_937d_853d_d16cb295bda3_MD0002_00 This patient has resistant hypertension (persistently elevated blood pressure >140/90 mm Hg despite an appropriate regimen of >3 drugs), suggesting a secondary cause of hypertension. Primary hyperaldosteronism (PH) is characterized by resistant hypertension, hypokalemia, and metabolic alkalosis. However, hypokalemia is present in <50% of patients and is often masked by potassium-sparing diuretics or potassium supplementation (as is likely in this patient); unopposed thiazide or loop diuretics may rapidly cause severe hypokalemia. Hypokalemia may also be intermittent (eg, muscle cramps while exercising, as in this patient) and may be missed on laboratory testing. In addition, patients may have mild hypomagnesemia (as seen in this patient), possibly due to urinary wasting of magnesium. Primary hyperaldosteronism (PH) < A plasma aldosterone concentration to plasma renin activity (PAC/PRA) ratio of >20 indicates aldosterone secretion independent of renin-angiotensin stimulation and suggests PH. The diagnosis can be confirmed with aldosterone suppression tests (eg, sodium chloride, captopril, fludrocortisone). (Choice A) Coarctation of the aorta is characterized by congenital focal narrowing of the descending aorta and is usually diagnosed in childhood. It may occasionally present in adults with hypertension, usually with blood pressure that is >20 mm Hg higher in the arms than in the legs, and is classically associated with a "to-and-fro" machinery murmur. This patient's echocardiogram findings make coarctation less likely. (Choice B) Cushing syndrome can cause secondary hypertension, but this patient has no other features (eg, facial plethora, Cushingoid habitus, hyperglycemia) to raise suspicion for this disorder. Cushingoid habitus (Choice C) Clinical features that would suggest obstructive sleep apnea as a cause of resistant hypertension include obesity, daytime somnolence, excessive snoring, neck circumference >43 cm (17 in), and witnessed apneic spells. PH is more likely in this patient, but a sleep study could be considered if PH is ruled out. (Choice E) Renal parenchymal and renovascular (eg, renal artery stenosis [RAS]) disease are common causes of resistant hypertension. RAS is highly correlated with atherosclerosis and often presents with rapid-onset hypertension in patients age >55 with additional risk factors (eg, smoking) for atherosclerosis. Other features that suggest RAS include an abrupt rise in creatinine when on an ACE inhibitor (eg, lisinopril), recurrent flash pulmonary edema, abdominal bruit, and asymmetry in renal size on imaging. None of these features are seen in this young patient. Educational objective: Primary hyperaldosteronism (PH) is characterized by hypertension, metabolic alkalosis, and hypokalemia. Potassium may be normal at baseline, but thiazide or loop diuretics may trigger hypokalemia. An elevated plasma aldosterone concentration to plasma renin activity ratio >20 suggests PH. __________ References: Secondary hypertension: a condition not to be missed. (http://www.ncbi.nlm.nih.gov/pubmed/21746730) The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. (http://www.ncbi.nlm.nih.gov/pubmed/26934393)

A 45-Year-Old Man Comes to the Office for Blood Pressure