A Man With Hypokalemia, Sleep Apnea, and Resistant Hypertension

Minh Chung; Eric Warren, DO; Darshan Rola; Brian Zacharias; Jennifer Broyles, MD


July 20, 2022


Hypertension is a worldwide pandemic. In 2010, 31.1% of adults had a systolic pressure ≥ 140 mm Hg and/or a diastolic pressure ≥ 90 mm Hg.[1] The prevalence continues to rise, along with the burden on patients and the healthcare system to prevent the complications of long-standing, uncontrolled disease.

Perhaps the most feared complication of hypertension is the associated cardiovascular morbidity and mortality. CVD continues to be the leading cause of mortality worldwide, and approximately half of CVD events are ascribed to hypertension.[2] This is an important public health issue because the evidence suggests that the risks and complications are largely preventable. When hypertension is treated and well controlled, the risk of all-cause and CVD-specific mortality is not significantly (or at all) increased. Therefore, hypertension must be promptly identified and managed in patients to prevent negative outcomes.

Hypertension is categorized as primary or secondary, based on whether the cause of the elevated blood pressure is identifiable. Primary hypertension, which accounts for about 90% of adult patients with high blood pressure, has an idiopathic etiology.[3] It is managed with nonpharmacologic and pharmacologic interventions, such as weight loss, increased physical activity, reduction in salt intake and, if necessary, antihypertensive agents, such as dihydropyridine calcium channel blockers, thiazide diuretics, ACE inhibitors, and angiotensin II receptor blockers.[4]

Although secondary causes should routinely be considered in patients with a new diagnosis of hypertension, certain clinical scenarios warrant further investigation. Some of these circumstances include resistant hypertension (defined as a blood pressure ≥ 140/90 mm Hg despite concurrent use of three antihypertensive medications from different classes, including a diuretic), onset at an age younger than 30 years, and acute worsening of blood pressure control.[3]

Secondary hypertension encompasses all potential causes of chronically elevated blood pressure, including renal artery stenosis, medications, renal parenchymal disease, obstructive sleep apnea, primary hyperaldosteronism, coarctation of the aorta, pheochromocytoma, Cushing syndrome, hypothyroidism, and hyperthyroidism.[3] Primary hyperaldosteronism is the most common cause of secondary hypertension, accounting for about 20% of all cases of resistant hypertension.[5]

Renal artery stenosis was considered as part of the differential diagnosis for this patient. Primary hyperaldosteronism and renal artery stenosis have many similarities, but key differences in the workup can distinguish the two conditions. Both involve hypertension that is usually refractory to typical blood pressure management, as well as hypokalemia and metabolic alkalosis. The key difference arises when the plasma aldosterone-to-renin ratio is measured. In renal artery stenosis, the renin-angiotensin-aldosterone system becomes activated secondary to the decreased afferent arteriole flow. In turn, the juxtaglomerular cells activate the renin cascade, leading to high levels of renin and aldosterone. This causes a low plasma aldosterone-to-renin ratio. In primary hyperaldosteronism, the ratio is high owing to the direct production of aldosterone, which provides negative feedback and reduces the levels of renin. A CT angiogram would reveal the stenosed renal artery, which could produce an audible bruit. A CT in a patient with primary hyperaldosteronism would show an adrenal adenoma rather than impairment of the renal artery. Moreover, an audible bruit would not be present.

Cushing syndrome was also considered in the differential diagnosis for this patient. Cushing syndrome can cause hypertension secondary to an increase in cortisol, which leads to suppression of the vasodilatory systems as well as some minor mineralocorticoid activity. Patients with this syndrome typically have distinct physical features, which were not present in this patient. Cushing syndrome can cause weight gain as well as fatty deposits in areas such as the face and interscapular area, leading to the typical moon facies and buffalo hump appearance. Striae would be present on the flanks, arms, and thighs as well. Thin, fragile skin that bruises easily is also present in some cases. Patients may experience muscle weakness and severe fatigue. To make a definitive diagnosis, a 24-hour urine cortisol sample or a late-night saliva cortisol sample can be obtained. Follow-up with a low-dose dexamethasone suppression test can help confirm the diagnosis if needed.

Pheochromocytomas are tumors that consist of chromaffin tissue and secrete catecholamines. These tumors can occur in the adrenal medulla or other extra-adrenal sites, such as the organ of Zuckerkandl. The symptoms that result from the excess of catecholamines are typically episodic. Patients can experience episodes of tachycardia, palpitations, chest pain, diaphoresis, hypertension, headache, tremor, and anxiety. The patient in this case was not experiencing episodic hypertension; instead, his hypertension was constant. Furthermore, he reported no chest pain, palpitations, or headache, which helped exclude this diagnosis. To confirm the diagnosis of pheochromocytoma, 24-hour urine levels of metanephrines and catecholamines or plasma-fractionated metanephrines levels can be measured. Elevated levels, in conjunction with the typical episodic physical symptoms, can help to make the final diagnosis.


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