Hypertension is one of the most common reasons for patient visits.1 According to the US Preventive Services Task Force, more than 70 million individuals older than 20 have hypertension, which is defined as a blood pressure (BP) of ≥ 130/85 mm Hg.2 Essential hypertension is the most common form of this condition; most affected patients will show improvement with evidence-based pharmacologic treatment, lifestyle modifications, and risk factor reductions.
For patients with refractory hypertension, however, identifying what steps to take in screening and diagnosis can be daunting for clinicians. It is important to identify cases of secondary hypertension, because if it is left undiagnosed and untreated, serious complications—such as cardiovascular and renal disease—are likely to occur.3,4
Secondary hypertension can be caused by myriad disease states and disorders, including endocrine disorders, renal disease, neurologic disorders, acute stress, and drug-induced hypertension.5 Endocrine hypertension is most commonly caused by adrenal gland disorders, including primary aldosteronism, Cushing syndrome, and pheochromocytoma. (Of note, Cushing syndrome is caused by glucocorticoid-secreting adrenal tumors, while Cushing disease is a condition in which there is glucocorticoid excess caused by oversecretion of pituitary adrenocorticotropic hormone.6 Cushing disease is more common than Cushing syndrome, which is rare.7) While nonadrenal endocrine disorders are not as common, they pose significant health issues, including growth hormone excess or deficiency, thyroid disorders, testosterone deficiency, obesity, insulin resistance, and metabolic syndrome.8
Understanding the endocrine causes of hypertension is a valuable resource for clinicians to have in their toolbox. Although the negative consequences of endocrine disorders are significant, these conditions are often recognizable, and pharmacologic treatment and/or surgical interventions can potentially resolve or improve hypertension and reduce risk for other comorbidities. This article summarizes screening and diagnosis guidelines for several possible causes of endocrine hypertension: primary aldosteronism, Cushing syndrome, and pheochromocytoma.
Primary aldosteronism occurs in 5% to 10% of all hypertensive patients and is a common cause of secondary and endocrine hypertension (although in younger—particularly female—patients, it most commonly causes renal artery stenosis).9,10 Historically, primary aldosteronism was considered rare and not generally included in a differential diagnosis for patients presenting with resistant hypertension. However, clinical investigations have indicated that primary aldosteronism is more prevalent than previously thought.11
Patients develop this condition when there is increased aldosterone production independent of the renin-angiotensin system. The resulting sodium retention can lead to hypertension, hypokalemia, and high plasma aldosterone/renin ratio (ARR).12 Clinical findings and symptoms can be vague, increasing the difficulty in identifying primary aldosteronism as the diagnosis. Patients may be asymptomatic, with the only abnormal lab finding being hypokalemia (an infrequent finding, affecting < 25% of patients).13 If hypokalemia is present, symptoms can include nocturia, polyuria, muscle weakness, cramps, paresthesias, and palpitations.11
The Endocrine Society has identified 8 characteristics that increase the likelihood of primary aldosteronism. Patients require further screening if they
- Have a sustained elevated BP (≥ 150 mm Hg [systolic] and/or 100 mm Hg [diastolic])
- Have hypertension (BP > 140/90 mm Hg) that is resistant to 3 conventional antihypertensive drugs, including a diuretic
- Have controlled BP (BP < 140/90 mm Hg) with ≥ 4 antihypertensive drugs
- Have hypertension and spontaneous or diuretic-induced hypokalemia
- Have hypertension and adrenal incidentaloma
- Have hypertension and obstructive sleep apnea
- Have hypertension and a family history of early-onset hypertension or a cerebrovascular accident at a young age (< 40 years)
- Are hypertensive and a first-degree relative of a patient with primary aldosteronism.14
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