Primary hyperaldosteronism laboratory findings
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
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.[1]
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 and specificity 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. It shares the same problems as encountered in the CT scan.
- Adrenal venous sampling (AVS) — The endocrine society recommends this as the gold standard test. The sensitivity and specificity of AVS (95 and 100%, respectively) for detecting unilateral aldosterone excess is superior to that of the adrenal CT (78 and 75%, respectively). The procedure although very useful, is expertise-dependant. The right adrenal vein (smaller than the left and usually empties directly into the IVC rather than the renal vein) is more difficult to cannulated, with success rates for cannulating the right adrenal vein ranging from 74[100] to 90 – 96%,[26] increasing with experience. The risk of adrenal hemorrhage is very rare and the complication rate is 2.5% or lower. AVS can be performed using any of the three protocols, (1) unstimulated sequential or simultaneous bilateral AVS, (2) unstimulated sequential or simultaneous bilateral AVS followed by bolus cosyntropin-stimulated sequential or simultaneous bilateral AVS, and (3) 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), in order to counter the possible dilutional effect of the samples. A gradient of > 4:1, from the high to the low side suggests unilateral aldosterone secreting pathology and < 3 : 1 suggests bilateral adrenal hyperplasia.[26,95,98,101] Using these criteria, AVS has a sensitivity of 95% and a specificity of 100% to detect unilateral disease. The minimum gradient suggested by one study was 2.75.[102]
- Posture stimulation test — can be used when AVS is unrewarding. Developed in the 1970s, it was based on the principal that PAC in patients with APA showed diurnal variation and was relatively unaffected by changes in the angiotensin II levels being under ACTH control, whereas, IHA was characterized by enhanced sensitivity to a small change in the angiotensin II, which occurred with standing. A review of 16 published reports demonstrated an accuracy of 85% for APA.[26,100,103]
- Iodocholesterol scintigraphy — [6[beta]- 131I]iodomethyl-19-norcholesterol (NP-59), was introduced in 1977 for the diagnosis for primary aldosteronism. The NP-59 scan, performed with dexamethasone suppression, had the putative advantage of correlating function with anatomical abnormalities. However, because the tracer uptake was poor in adenomas smaller than 1.5 cm in diameter, this method was often not helpful in interpreting micronodular findings and is currently no longer used in most centers.[104]
- 18-Hydroxycorticosterone levels — Formed from 18-hydroxylation of corticosterone it was traditionally used to differentiate APA from bilateral adrenal hyperplasia. Recumbent plasma 18-hydroxycorticosterone levels greater than 100 ng/dl at 8 a.m., suggested APA. However, it lacked accuracy.[105]
References
- ↑ Stowasser M, Gordon RD, Rutherford JC, Nikwan NZ, Daunt N, Slater GJ (2001). "Diagnosis and management of primary aldosteronism". J Renin Angiotensin Aldosterone Syst. 2 (3): 156–69. doi:10.3317/jraas.2001.022. PMID 11881117.