Screening for Endocrine Hypertension

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The most reliable screening test for primary aldosterone is the ARR, although false-negative and false-positive results are possible.11 False-negative results can be caused by dietary salt restriction, hypokalemia, and use of medications including diuretics, calcium channel blockers, ACE inhibitors, and angiotensin receptor antagonists. Use of ß-adrenergic blockers, α-methyldopa, or NSAIDs can cause false-positive results.15 Patients should be encouraged to follow a liberal sodium diet before ARR testing, and efforts to correct hypokalemia should be implemented. Before ARR is measured, diuretics (specifically spironolactone) should be stopped for at least 4 weeks; other possible interfering medications should be stopped for at least 2 weeks.16

The ARR should be obtained multiple times to confirm elevated readings.16 Reference ranges vary, but generally plasma aldosterone concentrations > 20 ng/dL and plasma renin activity < 1 ng/mL/h indicate whether confirmatory testing should be completed.14 Further confirmatory testing can be achieved with efforts to suppress plasma aldosterone to < 10 ng/dL after an IV infusion of 2 L isotonic saline over 4 hours.12 Oral sodium load is used as well and usually before IV infusion.


Cushing syndrome is caused by excess circulating levels of glucocorticoids and affects < 0.1% of the world population.17 Signs and symptoms include centripetal obesity, moon facies, facial plethora, easy bruising, buffalo hump (or posterior cervical fat pad), hirsutism, and wide-purple striae.18 Up to 80% of these patients also have hypertension.19 If these patients have chronic exposure to high levels of glucocorticoid (the most common source being therapeutic administration of exogenous glucocorticoids), multiple complications can occur.6,20

The Endocrine Society Clinical Practice Guideline recommends the following patient groups be tested for Cushing syndrome:

  1. Young patients with unusual medical conditions, such as osteoporosis and resistant hypertension
  2. Patients with classic signs and symptoms, such as easy bruising, weight gain, facial plethora, and purple striae
  3. Children with decreasing height percentile and increasing weight
  4. Patients with adrenal incidentaloma compatible with adenoma.18

If Cushing syndrome is suspected, 1 of the following 3 initial tests can be completed: 24-hour, urine-free cortisol and creatinine; late-night salivary cortisol; or 1-mg overnight dexamethasone suppression test. Two of these tests must have abnormal results for confirmation before appropriate pituitary or adrenal imaging. If a patient has clinical features indicating Cushing syndrome but test results are normal, he or she should be referred to an endocrinologist. If a patient has ≥ 2 normal tests and probability of Cushing syndrome is unlikely, patients should be recommended for follow-up in 6 months to evaluate for any worsening of symptoms.18


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