Importance Determining the diagnostic accuracy of “exclusion” tests for primary aldosteronism (PA) compared to the aldosterone-to-renin ratio (ARR) is fundamental to avoid invasive subtyping in false-positive patients at screening. Objective To assess the accuracy of exclusion tests for PA using the diagnosis of unilateral PA as reference. Data Sources PubMed, EMBASE, Web of Science and Cochrane Library databases. Study Selection Studies that met tight quality criteria published from January 1st, 1970 to December 31st, 2021. Data Extraction and Synthesis Data were extracted following the PRISMA methodology. We performed a two-stage meta-analysis that entailed an exploratory and a validation phase based on a “golden” or “gold” diagnostic standard, respectively. Pooled specificity, negative likelihood ratio, diagnostic odds ratio, and summary area under the ROC curve (sAUROC) were calculated. Main Outcome and Measure The accuracy of exclusion tests. Findings 31 datasets comprising a total of 4,242 patients fulfilling the predefined inclusion criteria were meta-analyzed. Pooled accuracy estimates (sAUROC) did not differ between the ARR (0.95, 95% CI: 0.92-0.98), the captopril challenge test (CCT) (0.92, 95% CI: 0.88-0.97), and the saline infusion test (SIT) (0.96, 95% CI: 0.94-0.99). Solid information could not be obtained for the fludrocortisone suppression test and the furosemide upright test, which were assessed in only one study each. Conclusions and Relevance The apparently high diagnostic accuracy of the CCT and the SIT was due to the selection of patients with an elevated ARR and thus a high pre-test probability of unilateral PA; however, neither test furnished a diagnostic gain over the ARR. Therefore, the systematic use of these exclusion tests in clinical practice is not justified by available evidence.
Primary adrenal insufficiency (AI) due to bilateral adrenalectomy is not uncommon and causes skin hyperpigmentation, which worsens quality of life. Case description: A 50-year-old lady presented with skin hyperpigmentation after spare adrenalectomy for recurrent primary aldosteronism. In 2002 she has her first unilateral adrenalectomy and was cured at follow-up. After 16 years she developed primary aldosteronism, which was treated by spare adrenalectomy. She thereafter developed AI and started glucocorticoid replacing therapy, which did not prevent the development of full-blown skin hyperpigmentation. The addition of a low dose of dexamethasone (0.5 mg/day) to the ongoing adrenal replacement therapy normalized her plasma adrenocorticotropic hormone (ACTH) levels and regressed skin hyperpigmentation without causing Cushing-like symptoms or signs. Conclusions: This clinical case provides compelling evidence for a place for low-dose dexamethasone for regressing skin pigmentation in patients with primary AI.
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