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)
- 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.
- The test should be performed 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]
Case confirmation: Once primary aldosteronism is suspected, case confirmation is recommended using one of the following well-validated tests (1 – 4):
- Fludrocortisone suppression test (FST) (upright plasma aldosterone levels measured at 10:00 hours after four days administration of the synthetic mineralocorticoid 9-[alpha]-fludrocortisone acetate (0.1 mg every six hours) and sodium chloride [slow-release sodium 30 mmol (1.75 g) thrice daily], with a value of > 6 ng / dl and concomitant PRA levels < than 1.0 ng / ml / hour, confirming primary hyperaldosteronism).[94]
- Intravenous saline load test (SLT) (infusion of two liters of NaCl 0.9% fours hours with PAC more than 10 ng / dl is diagnostic, normally aldosterone suppresses to below 5 ng / dl. It is contraindicated in patients with severe hypertension, chronic kidney failure, heart failure, cardiac dysrhythmias, or severe hypokalemia)[26,95]
- Oral sodium loading test (High sodium diet, of approximately 218 mmol / day, for three days. On the last day of the high-salt diet, patients are required to collect a 24-hour urine sample. Normal suppression is defined as post-test 24-hour urinary aldosterone excretion less than 12 μg / day, with concomitant urinary sodium excretion of more than 200 mmol / day, to document adequate sodium repletion. It has > 90% sensitivity and specificity).[94]
- Captopril challenge test (PAC / PRA > 30, measured two hours after the administration of 25 mg or 50 mg of captopril with patients in the sitting position, has been proposed as a diagnostic cut-off value for primary aldosteronism)[26,94,96] Other less validated tests
- Frusemide upright posture test
- 24-hour urinary aldosterone
- Losartan test
The fludrocortisone suppression test is regarded as the gold standard test for the confirmation of primary aldosteronism. When SLT was compared with the efficacy of FST, SLT was found to have a high positive predictive value (92%) with high sensitivity and specificity (90 and 84%, respectively) and could be considered an effective option to the FST.[95]
Three hundred and seventeen patients were prospectively studied, to assess the efficacy of the captopril test over SLT, and it was found that the accuracy of the SLT surpassed that of the capropril test in patients with a sodium intake < = 130 mEq per day; both the captopril test and the SLT were equally safe and moderately accurate for excluding primary aldosteronism (APA) in patients with a sodium intake > 7.6 g per day. The optimal aldosterone cutoff value for identifying APA was 13.9 and 6.75 ng/dL for the captopril test and SLT, respectively.[96]
A number of false-positive and false-negative diagnoses have been found with the captopril test, and therefore, they are reserved for patients with reduced cardiac or renal function.[97]
Subtype Classification: Once the diagnosis is confirmed a subtype classification is required as the treatment strategies vary depending on the etiology. Young age (< 50 years old), severe hypokalemia (< 3.0 mmol / L), high plasma aldosterone concentrations (> 25 ng / dl), and high urinary aldosterone excretion (> 30 ug / 24 hours) favor the diagnosis of APA versus bilateral adrenal hyperplasia. Although useful they lack specificity, and therefore, cannot be relied on.[26,33,90]
Tests useful in assessing subtypes are:
- Computed Tomography (CT) — A high-resolution CT (HRCT) scan with contrast, with fine cuts (2.5 – 3 mm), is the imaging technique that displays the best sensitivity and specificity in identifying adrenal nodules. CT alone is inadequate for the differential diagnosis between APA and bilateral adrenal hyperplasia. The diagnostic performance of CT (sensitivity 40 to 100%) depends on the size of the APA lesion, being greatest for lesions > 2 cm. The yield for detecting APA less than 1 cm in diameter is lower, and is reported to be around 25%. It cannot distinguish between a functional APA and a non-secreting adrenal adenoma (incidentaloma). A unilateral lesion exceeding 4 cm suggests possible carcinoma.[94,98,99]
- 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.