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MKSAP Quiz: drug-resistant hypertension

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A 43-year-old man is evaluated for drug-resistant hypertension. Hypertension was diagnosed 1 year ago and has been difficult to control despite maximum dosages of lisinopril, metoprolol, and nifedipine. The patient reports feeling well.

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On physical examination, temperature is 36.5 °C (97.7 °F), blood pressure is 146/92 mm Hg, pulse rate is 88/min, respiration rate is 17/min, and BMI is 27. The general physical examination and funduscopic examination are unremarkable.

Laboratory studies:

Which of the following is the most appropriate next diagnostic test for this patient?

A. CT of the adrenal glands
B. Determination of serum aldosterone to plasma renin activity ratio
C. Digital subtraction renal angiography
D. Measurement of plasma metanephrine and normetanephrine levels

Reveal the Answer

MKSAP Answer and Critique

The correct answer is B) Determination of serum aldosterone to plasma renin activity ratio. This item is available to MKSAP 15 subscribers as item 63 in the Endocrinology and Metabolism section.

This patient has drug-resistant hypertension, unprovoked hypokalemia, and probable metabolic alkalosis; he also has an inappropriately high urine potassium level. In this setting, primary hyperaldosteronism is a very likely cause of his hypertension and hypokalemia, especially given his age. The best screening test for primary hyperaldosteronism is a determination of the ratio of serum aldosterone (in ng/dL) to plasma renin activity (in ng/mL/min). A ratio greater than 20, particularly when the serum aldosterone level is greater than 15 ng/dL (414 pmol/L), is consistent with the diagnosis of primary hyperaldosteronism.

After biochemical confirmation of hyperaldosteronism, localization procedures are appropriate to differentiate aldosterone-producing adenomas, which are amenable to surgical resection, from bilateral hyperplasia, which is medically treated. Given the high incidence of incidental adrenal lesions, however, imaging studies, such as CT of the adrenal glands, should not be performed before autonomous production of aldosterone is confirmed through biochemical testing.

This patient does not fit the demographic or clinical profile of a patient with renovascular hypertension, and thus evaluating the renal arteries with digital subtraction renal angiography is not indicated. Renovascular hypertension due to fibromuscular disease of the renal arteries usually presents in patients younger than 35 years, and azotemia is rarely present. Atherosclerotic renovascular hypertension is more common in patients older than 55 years and is frequently associated with vascular disease in other vessels; azotemia is often present.

This patient did not have any symptoms or signs suggestive of a pheochromocytoma (palpitations, headache, tremor, diaphoresis). Therefore, screening for a pheochromocytoma with measurement of the plasma metanephrine and normetanephrine levels is inappropriate, especially when there is a more likely cause suggested by the electrolyte abnormalities.

Key Point

  • Patients with hypertension should be screened for primary hyperaldosteronism if they are young, have hypokalemia, or have difficult-to-control blood pressure; such screening includes determination of the serum aldosterone to plasma renin activity ratio, with a ratio greater than 20 strongly suggesting the diagnosis.