Primary hyperaldosteronism laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Laboratory findings consistent with the diagnosis of primary hyperaldosteronism include plasma aldosterone to renin activity ratio (PAC/PRA) of >30, serum aldosterone value of > 6 ng / dl and simultaneous PRA levels < than 1.0 ng / ml / hour after fludrocortisone supression test, or a plasma aldosterone more than 10 ng / dl on saline infusion test or on oral sodium loading test, the post-test 24-hour urinary aldosterone excretion less than 12 μg / day and a urinary sodium excretion of more than 200 mmol / day. the adrenal venous sampling test is gold standard for subtype classification of primary hyperaldosteronism.

Laboratory Findings

Plasma Aldosterone to Renin Ratio (PAC/PRA)

Protocol

• Drugs that affect the renin–angiotensin-aldosterone axis should be stopped before testing, such as: beta-blockers, ACE inhibitors, ARBs (angiotensin receptor blockers), renin inhibitors, dihydropyridine calcium channel blockers, and central alpha2-agonists, for about fourteen days, and spironolactone, eplerenone, amiloride, and triamterene, and loop diuretics for about twenty eight days.
• The test should be conducted between 8 a.m. and 10 a. m. The patient is advised to stay upright for 2 hours prior to testing, and then sit for about 10 minutes before testing.

Interpretation

• Primary hyperaldosteronism (Conn's syndrome) is associated with an increased aldosterone levels (PAC) in plasma along with suppressed renin concentration (PRA) due to feedback inhibition of aldosterone on renin levels in the plasma.
• A PAC/PRA ratio of >30 is a strong evidence of primary hyperladosteronism and value >50 is considered diagnostic in the presence of resistant hypertension, hypokalemia and metabolic alkalosis.

Confirmatory Tests

After preliminary testing for primary hyperaldosteronism via PAC/PRA ratio, any one of the following tests may be performed in order to confirm the diagnosis:

1. Fludrocortisone suppression test (FST) 

• This is the gold standard test for confirmation of primary hyperaldosteronism.

• Patient is given a synthetic mineralocorticoid (9-[alpha]-fludrocortisone acetate 0.1 mg every six hours) and sodium chloride [slow-release sodium 30 mmol (1.75 g) three times daily].
• Plasma aldosterone level is measured in the a.m. after four days of administration.
• A value of > 6 ng / dl and simultaneous PRA levels < than 1.0 ng / ml / hour, confirm primary hyperaldosteronism.

2. Intravenous saline load test (SLT) 

• Patient is infused with two liters of NaCl 0.9% for fours hours.
• Plasma aldosterone more than 10 ng / dl is confirmatory, normally aldosterone would be suppressed to below 5 ng / dl.

3. Oral sodium loading test 

• This test has a sensitivity and specificity of >90%

• Patient is fed a high sodium diet, of approximately 218 mmol / day, for three days.
• On the third day, a 24-hour urine sample is collected.
• Normal suppression is defined as post-test 24-hour urinary aldosterone excretion less than 12 μg / day and a urinary sodium excretion of more than 200 mmol / day.

4. Captopril challenge test 

• Positive test for primary hyperaldosteronism is defined as a PAC / PRA > 30, measured two hours after the administration of 25 mg or 50 mg of captopril with patients in the sitting position.
• Reserved for patients with reduced cardiac or renal function.

Less Common Tests

• Frusemide upright posture test
• 24-hour urinary aldosterone
• Losartan test

Subtype Classification

Once the diagnosis of primary hyperaldosteronism is confirmed, a subtype classification is required as the management may vary based on the etiology.

Tests useful in assessing subtypes are:

1. Computed Tomography (CT) 

• A high-resolution CT (HRCT) scan with contrast, has a high sensitivity (78%) and specificity (75%) for detection of adrenal masses (inluding aldosterone producing adenomas-APAs)
• CT scan is best when used for adrenal adenomas > 2cm but accuracy decreases if the mass is < 1cm.
• A unilateral lesion exceeding 4 cm suggests possible carcinoma
• Moreover, it cannot distinguish between a functional APA and a non-secreting adrenal adenoma (incidentaloma).

2. Magnetic Resonance Imaging (MRI)

• Sensitivity of 70 to 100% in detecting APA, depending on the size of the lesion, being greatest for lesions > 2 cm.
• Limitations are similar to that of CT scan.

3. Adrenal venous sampling (AVS) 

• Gold standard test for subtype classification.

• It has a high sensitivity (95%) and specificity (100%) for the detection of unilateral aldosterone excess but is highly expertise dependent.
• AVS can be performed using any of the three protocols:
  • (a) Unstimulated sequential or simultaneous bilateral AVS
  • (b) Unstimulated sequential or simultaneous bilateral AVS followed by bolus cosyntropin-stimulated sequential or simultaneous bilateral AVS
  • (c) Continuous cosyntropin infusion with sequential bilateral AVS.
• Plasma aldosterone collected from the adrenal veins is corrected to its respective plasma cortisol, measured as a ratio (PAC / cortisol ratio)
• A gradient of > 4:1, points towards unilateral aldosterone secreting adenoma and < 3 : 1 suggests bilateral adrenal hyperplasia.

4. Posture stimulation test

• May be used when AVS is equivocal.
• It is based on the principal that PAC in patients with aldosterone producing adenoma (APA) there is a diurnal variation and is relatively unchanged by changes in the angiotensin II levels being under ACTH control, whereas, bilateral adrenal hyperplasia (IHA) is affected heavily by a small change in the angiotensin II, due to standing.

5. Iodocholesterol scintigraphy (NP-59 scan)

• 6 beta- 131I iodomethyl-19-norcholesterol (NP-59), was introduced in 1977 for the diagnosis for primary aldosteronism.
• The NP-59 scan is performed with dexamethasone suppression.
• It is not very useful in identifying micro adenomas of the adrenals (<1.5cm).

6. 18-Hydroxycorticosterone levels

• Less accurate than other tests.

• Hydroxylation of corticosterone leads to the formation of 18-hydroxycorticosterone.
• Historically, it was used to differentiate APA from bilateral adrenal hyperplasia.
• Supine plasma 18-hydroxycorticosterone levels > 100 ng/dl at 8 a.m., suggest aldosterone producing adenoma (APA).