The diagnosis and treatment of primary hyperaldosteronism in Germany: results on 555 patients from the German Conn Registry.

BACKGROUND: Primary hyperaldosteronism (Conn's syndrome) is being diagnosed increasingly often. As many as 12% of patients with hypertension have the characteristic laboratory constellation of Conn's syndrome. Its diagnosis and treatment have not been standardized. METHODS: The authors retrospectively analyzed data of 555 patients (327 men and 228 women, aged 55 +/- 13 years) who were treated for primary hyperaldosteronism in 5 different centers from 1990 to 2006. The objective was to determine center-specific features of diagnosis and treatment. RESULTS: 353 (63%) of the patients had the hypokalemic variant of primary hyperaldosteronism; 202 never had documented hypokalemia. The centers differed markedly with respect to the patients' clinical presentation, diagnostic testing of endocrine function, and diagnostic imaging techniques, including adrenal venous sampling. The adrenalectomy rate ranged from 15% to 46%. CONCLUSIONS: The registry data reveal an unexpected heterogeneity in the diagnostic evaluation and treatment of primary hyperaldosteronism. National or international guidelines are needed so that these can be standardized.

Risk factors associated with a low glomerular filtration rate in primary aldosteronism.

CONTEXT: Primary aldosteronism (PA) is associated with vascular end organ damage. OBJECTIVE: We evaluated the newly established German Conn's Registry for evidence of renal impairment and compared the data with those from hypertensive subjects of a population-based survey. DESIGN: We conducted a case-control study. PATIENTS AND CONTROLS: A total of 408 patients with PA from the Conn's registry treated in five German centers were matched for age, sex, and body mass index in a 1:1 ratio with 408 hypertensive control subjects from the population-based F3 survey of the Kooperative Gesundheitsforschung in the region of Augsburg (KORA). MAIN OUTCOME MEASURES: We measured serum creatinine and calculated glomerular filtration rate (GFR). RESULTS: The percentage of patients with a serum creatinine concentration above the normal range of 1.25 mg/dl was higher in patients with PA than in hypertensive controls (29 vs. 10%; P < 0.001). Regression analysis showed that age, male sex, low potassium, and high aldosterone concentrations were independent predictors of a lower GFR. Adrenalectomy reduced systolic blood pressure from a mean of 160 to 144 mm Hg. In parallel, we observed an increase in serum creatinine and a decrease of GFR from 71 to 64 ml/min (P < 0.001). A similar trend was seen after spironolactone treatment. CONCLUSIONS: In a large cohort of patients with PA, markers of disease activity such as plasma aldosterone and serum potassium are independent predictors of a lower GFR. Specific interventions, such as adrenalectomy or spironolactone treatment, are associated with a further decline in GFR.

Primary aldosteronism: current knowledge and controversies in Conn's syndrome.

Primary aldosteronism has been recognized as a common cause of secondary hypertension, accounting for approximately 10% of the hypertensive population. Screening should be applied in hypertensive patients presenting with one of the following: hypokalemia, refractory hypertension, suggestive family history, or an incidentally detected adrenal mass. The most advocated screening test at present is the aldosterone-to-renin ratio, which has a high sensitivity but low specificity. The specificity increases if patients with low aldosterone concentrations are excluded. Published cut-off values vary depending on the hormone assay and the investigated population. Before screening, antihypertensive treatment, especially aldosterone antagonists and beta-blockers, should be discontinued. A pathologic result requires additional work up to prove mineralocorticoid excess. Subtype differentiation is performed by adrenal venous sampling combined with imaging (CT or MRI). One-third of cases are due to aldosterone-producing adenomas, for which the preferred treatment is laparoscopic adrenalectomy. Bilateral adrenal hyperplasia (idiopathic aldosteronism) underlies two-thirds of cases and requires treatment with aldosterone antagonists. Treatment is started with low doses of spironolactone (25-50 mg once daily), which often results in substantial improvements in hypertension.

Screening for primary aldosteronism.

Normokalaemic manifestation of primary aldosteronism is a frequent cause of secondary hypertension. It occurs in approximately 5-12% of all patients with hypertension, primarily patients with severe and uncontrolled blood pressure. Main causes are bilateral adrenal hyperplasia (2/3 of cases) and aldosterone-producing adenoma (1/3 of cases). Screening is performed by measurement of the aldosterone/renin ratio, which is raised in affected patients. Suspicion of primary aldosteronism due to a pathological ratio requires confirmatory testing e.g. by saline infusion test or fludrocortisone suppression test. If the diagnosis is confirmed, the underlying cause of aldosterone excess needs to be identified because therapy differs. First, adrenal imaging (CT/MRI) is performed, which is followed by postural testing in cases with a unilateral lesion. Concordant results confirm the diagnosis of an aldosterone-producing adenoma and allow treatment to proceed to adrenalectomy. In cases of equivocal results or normal/bilaterally enlarged adrenal glands on imaging, adrenal venous sampling must be performed for subtype differentiation.

Automated chemiluminescence-immunoassay for aldosterone during dynamic testing: comparison to radioimmunoassays with and without extraction steps.

BACKGROUND: Measurements of aldosterone have become more common since the recognition that primary aldosteronism is a more frequent cause of hypertension than previously believed. Our aim was to compare concentrations reported by 4 assays for samples obtained after saline infusion during dynamic testing. METHODS: We tested 104 participants (27 with primary aldosteronism, 30 with essential hypertension, and 47 healthy controls) with the intravenous saline infusion test (2.0 L isotonic saline over 4 h), with repetitive sampling. In all blood samples, aldosterone concentration was measured by an in-house RIA after extraction and chromatography, by 2 commercially available RIAs without extraction (Aldosterone Maia, Adaltis; Active Aldosterone, Diagnostics Systems Laboratories) and by an automated CLIA (Advantage, Nichols Institute Diagnostics). RESULTS: Correlation coefficients for results of pairs of assays ranged from 0.74 to 0.98. Agreement between commercial assays and in-house RIA was best at the low to intermediate concentrations after saline infusion. Mean (SD) Adaltis and DSL RIA results were 2- to 3-times higher [healthy participants: 78 (25) ng/L and 56 (18) ng/L, respectively] than those obtained by Nichols CLIA [17 (8) ng/L] and in-house RIA [23 (18) ng/L]. Aldosterone concentrations measured by the Nichols CLIA were below the limit of detection (limit of the blank) in 27 of 47 healthy participants. CONCLUSIONS: Aldosterone concentrations reported by the Adaltis and DSL nonextraction RIAs were consistently higher than those produced by the Nichols CLIA and the in-house RIA. The convenient Nichols CLIA showed better agreement with the in-house RIA, but the concentrations in healthy participants were frequently undetectable by this method. Uncritical application of cutoff values from the literature must be avoided.

Confirmatory testing in normokalaemic primary aldosteronism: the value of the saline infusion test and urinary aldosterone metabolites.

OBJECTIVE: Primary aldosteronism has recently been recognized as the most frequent cause of secondary hypertension. Since most patients are normokalaemic, differentiation to essential hypertension is challenging. As differentiation by baseline aldosterone/renin ratio may be insufficient, diagnosis should be confirmed by additional tests. However, as most confirmatory tests have been evaluated in hypokalaemic primary aldosteronism only, we reassessed the value of the saline infusion test and 24 h urinary aldosterone metabolites as confirmatory tests for both normo- and hypokalaemic primary aldosteronism under current antihypertensive medication. PATIENTS AND METHODS: 25 patients with primary aldosteronism (11 hypokalaemic, 14 normokalaemic), 29 patients with essential hypertension and 47 normotensive subjects were studied. The hypertensives received their usual medication with the exception of spironolactone. All subjects underwent a standard saline infusion test (determination of plasma aldosterone before and after 2.0 liters of isotonic saline for 4 hours i.v.) and collected a 24 h urine sample for examination of urinary tetrahydroaldosterone and aldosterone-18-glucuronide. RESULTS: In hypokalaemic primary aldosteronism the saline infusion test showed a reasonable sensitivity (91%) and specificity (90%). However, the test failed to differentiate sufficiently between essential hypertension and normokalaemic primary aldosteronism (sensitivity 57%, specificity 90%). Similarly, urinary tetrahydroaldosterone had higher sensitivity in hypokalaemic than in normokalaemic primary aldosteronism (sensitivity 64% vs 36%, specificity 100%), whereas for aldosterone-18-glucuronide, no differences in hypo- and normokalaemic primary aldosteronism were found (sensitivity 45% and 43%, specificity 100%). CONCLUSIONS: These data show that the saline infusion test as an established test in classical hypokalaemic primary aldosteronism is not a reliable test in the normokalaemic variant of the disease. Due to its low accuracy, determination of urinary aldosterone metabolites did not prove useful in confirming either normo- or hypokalaemic patients. We conclude from our data that these tests should not be used as confirmatory testing in the normokalaemic variant of primary aldosteronism.