Laboratory Testing Instructions for Diagnosing Endocrine Hypertension
For primary aldosteronism, you must temporarily discontinue interfering antihypertensive medications 2-4 weeks before testing if initial screening is borderline or negative in high-suspicion cases; for pheochromocytoma, measure plasma and/or urinary fractionated metanephrines; for Cushing disease, use the 1-mg overnight dexamethasone suppression test; for primary hyperparathyroidism, measure serum calcium and PTH without special preparation; and for renal artery stenosis, no specific lab preparation is required as diagnosis relies on imaging.
Primary Aldosteronism
Medication Management Before Testing
The aldosterone-renin ratio (ARR) screening can typically be interpreted while patients remain on most antihypertensive medications 1. However, if initial screening is negative or borderline in patients with high clinical suspicion, you must temporarily substitute interfering medications with non-interfering agents for at least 2-4 weeks before repeat testing 1.
Interfering medications:
- Beta blockers and central-alpha agonists: suppress both renin and aldosterone
- ACE inhibitors and ARBs: stimulate renin and suppress aldosterone
- Thiazide-type, loop, MRA, and potassium-sparing diuretics: stimulate both renin and aldosterone 1
Non-interfering medications you can use:
- Non-dihydropyridine calcium channel blockers
- Vasodilators
- Peripheral alpha-blockers
- Potentially dihydropyridine calcium channel blockers 1
Confirmatory Testing
After a positive ARR screen, you must perform an aldosterone suppression test such as IV saline infusion or oral salt-loading 1, 2. The Endocrine Society mandates confirmatory testing except when patients present with spontaneous hypokalemia AND plasma aldosterone >20 ng/dL AND renin below assay detection limits 2.
Important Caveat for Concurrent Renal Artery Stenosis
Be aware that renal artery stenosis can mask primary aldosteronism by preventing renin suppression, leading to a false-negative ARR 3, 4. If hypertension remains uncontrolled after treating renal artery stenosis, with persistent hypokalemia and metabolic alkalosis, you must reconsider primary aldosteronism and proceed directly to adrenal venous sampling 4.
Pheochromocytoma
Measure plasma and/or urinary fractionated metanephrines and normetanephrines 5, 6. This is the most reliable biochemical test and should precede any imaging studies 6. The choice between plasma versus urinary testing depends on pre-test probability 5.
Key point: Biochemical documentation must always come before imaging to avoid false-positive incidentalomas 6.
Cushing Disease/Syndrome
Use the 1-mg overnight dexamethasone suppression test as your primary screening tool 7, 5. Administer 1 mg dexamethasone orally at 23:00-24:00, then measure serum cortisol at 08:00-09:00 the next morning. A serum cortisol >1.8 μg/dL (50 nmol/L) suggests autonomous cortisol secretion 7.
Alternative screening options include:
- 24-hour urinary free cortisol excretion
- Late evening salivary cortisol 5
Special consideration: If evaluating a patient with primary aldosteronism and an adrenal adenoma, the Endocrine Society suggests performing a dexamethasone suppression test to exclude concurrent autonomous cortisol secretion 7.
Primary Hyperparathyroidism
No special preparation is required. Simply measure serum calcium and PTH levels 8, 9. The diagnosis depends on demonstrating hypercalcemia (mean plasma calcium near or above the upper normal limit) with elevated or inappropriately normal PTH 8.
For normocalcemic hyperparathyroidism: This newer phenotype requires persistently normal serum calcium with elevated PTH, but you must rigorously exclude all secondary causes of hyperparathyroidism first—it is a diagnosis of exclusion 9.
Genetic testing consideration: Order genetic testing in patients <30 years old and/or those with urinary calcium-to-creatinine ratios between 0.01-0.02 to differentiate from familial hypocalciuric hypercalcemia 9.
Renal Artery Stenosis
No specific laboratory preparation instructions exist for renal artery stenosis, as diagnosis primarily relies on imaging studies 1. However, be aware that atherosclerotic renovascular disease may be present in 14-40% of hypertensive adults, though only 0.1-5% is hemodynamically significant 1.
Critical diagnostic pitfall: When renal artery stenosis coexists with primary aldosteronism, the elevated renin from RAS can normalize the ARR, masking the aldosterone excess 3, 4. In such cases, adrenal venous sampling remains the definitive diagnostic approach despite the non-suppressed renin 3.