From the Guidelines
For patients with resistant hypertension, I recommend adding a 1 mg dexamethasone suppression test (DST) as the preferred screening test for identifying autonomous cortisol secretion, as well as a plasma aldosterone-to-renin ratio (ARR) test to evaluate for primary aldosteronism. This approach is based on the most recent and highest quality evidence from the study published in 2023 1, which suggests that the 1 mg DST is the preferred screening test for identifying autonomous cortisol secretion. The ARR test is also recommended as the initial test for patients with hypertension and/or hypokalemia in whom primary aldosteronism is suspected, as stated in the same study 1. Additionally, the 2018 guideline from the American College of Cardiology/American Heart Association task force on clinical practice guidelines also supports the use of the ARR test for screening primary aldosteronism in patients with resistant hypertension 1. It is essential to ensure that the patient has adequate potassium levels and has discontinued medications that can interfere with results, such as spironolactone, eplerenone, and other diuretics, for at least 2-4 weeks when possible. The rationale for these tests is that excess mineralocorticoids or glucocorticoids can cause resistant hypertension through increased sodium retention, volume expansion, and vascular sensitivity to catecholamines. Some key points to consider when interpreting the results of these tests include:
- A serum cortisol level of >138 nmol/L after the 1 mg DST indicates evidence of cortisol hypersecretion, while a level of 51-138 nmol/L suggests possible autonomous cortisol secretion 1.
- An ARR of 20 ng/dL per ng/mL/hr has excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism 1. If these initial tests are abnormal, additional confirmatory tests such as a 24-hour urinary free cortisol test and/or late-night salivary cortisol may be needed before proceeding to imaging studies to localize the source of hormone excess.
From the Research
Resistant Hypertension and Cortisol Laboratory Tests
To diagnose the underlying cause of resistant hypertension, several laboratory tests can be considered.
- The 24-hour urine free cortisol (UFC) test is a reliable method for establishing the diagnosis of Cushing's syndrome, a condition that can cause resistant hypertension 2.
- The low-dose dexamethasone suppression test is another test used to diagnose Cushing's syndrome 2.
- Plasma aldosterone to renin ratio is a useful screening tool for primary aldosteronism, a common cause of resistant hypertension 3.
Cortisol Laboratory Tests
The following cortisol laboratory tests can be added if a patient has resistant hypertension:
- 24-hour urine free cortisol (UFC) test, which can be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) or immunoassay 4
- Low-dose dexamethasone suppression test 2
- Plasma cortisol measurement 2
Rationale
These tests can help identify underlying causes of resistant hypertension, such as Cushing's syndrome or primary aldosteronism, which can inform treatment decisions 5, 6, 3.