Evaluation of the Dexamethasone Suppression Test for the Diagnosis of Glucocorticoid-Remediable Aldosteronism1

Abstract

Glucocorticoid-remediable aldosteronism (GRA) is a rare form of inherited hypertension caused by a characteristic gene duplication. With the advent of definitive genetic testing for GRA, the performance of the traditional screening test for GRA, the dexamethasone suppression test (DST), can be evaluated. We compared the DST to direct genetic testing in 24 patients referred for genetic screening for GRA (12 GRA positive and 12 GRA negative) based on clinical and biochemical findings, DST, and family history. Plasma aldosterone was measured before and after oral dexamethasone administration to determine the extent to which aldosterone was suppressed by glucocorticoids in each patient group. The results of the DST in these subjects were also compared to those in 19 historical patients with primary aldosteronism [4 bilateral hyperplasia and 15 aldosteroneproducing adenoma (APA)] reported previously. The DST differentiated GRA-positive from GRA-negative patients with 92% sensitivity and 100% specificity. Cutoffs based on the post-DST plasma aldosterone level (Ͻ4 ng/dL) or percent suppression compared to baseline (Ͼ80%) were equally effective in correctly diagnosing GRA (only one GRA-positive patient would have been incorrectly diagnosed). However, DST in 15 APA patients revealed that 33% had greater than 80% suppression of aldosterone, and 1 had aldosterone levels below 4 ng/dL.We conclued that a post-DST aldosterone level below 4 ng/dL will correctly diagnose GRA patients with high sensitivity and specificity. Suppression compared to baseline can be misleading, as evidenced by the results in APA patients and referred subjects who genetically screened negative. (J Clin Endocrinol Metab 82: 3570 -3573, 1997)

Acute Severe Hypovolemic Hyponatremia in a Patient on Intravenous Dexamethasone

“…Prolonged administration of dexamethasone induces adrenal cortical atrophy, and abrupt discontinuation following protracted use may precipitate acute adrenal insufficiency [8]. Additionally, dexamethasone suppresses the release of aldosterone from the adrenal cortex [9,10].…”

“…Abrupt withdrawal of dexamethasone after prolonged therapy may precipitate acute adrenal insufficiency [8]. Besides, dexamethasone also suppresses aldosterone release from the adrenal cortex [9,10]. In a setting of acute volume depletion, it is not inconceivable that dexamethasone may precipitate hypovolemic hyponatremia attributable to its limited mineralocorticoid activity.…”

Laboratory Diagnostics of Primary Hyperaldosteronism and its Peculiarities (Literature Review)

“…However, given that this subtype of primary hyperaldosteronism is rare (<1% of all patients with primary hyperaldosteronism), the feasibility of such testing is questionable. Therefore, it is not recommended to test for the confirmation of primary hyperaldosteronism in patients younger than 20 years of age; also, only those patients with a family history of primary hyperaldosteronism or stroke at a young age (under 40 years) should be tested [26, 27].…”

Primary Hyperaldosteronism: When to Suspect It and How to Confirm Its Diagnosis

“…The FST is based on the suppression of renin, angiotensin-II, and aldosterone production secondary to extrinsic mineralocorticoid excess. One additional test, the dexamethasone suppression test (DST) [77], is used when glucocorticoid-remediable aldosteronism is suspected: young onset HT induced by PA. Other tests, in addition to suppression of renin-angiotensin-II, seek the blockade of physiological ACTH stimulus of aldosterone production to diminish the rate of false positives [78,79]. A recently described test combining a double blockade of angiotensin-II stimulus (using captopril and valsartan) with the blockade of ACTH stimulus of aldosterone production (using dexamethasone) could be of use in some clinical situations [78].…”