What is the role of a dexamethasone suppression test in the workup of primary hyperaldosteronism?

Updated: Oct 19, 2018
  • Author: George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London); Chief Editor: Robert P Hoffman, MD  more...
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Answer

In cases of bilateral aldosterone secretion or when the diagnosis is suspected on the basis of the family history, GRA can be excluded by means of a 4-day dexamethasone suppression test (using a dosage of 0.5 mg every 6 h).

The aldosterone, renin and cortisol levels can be measured before suppression testing, after 2 days of testing, and after 4 days of testing. In patients without GRA, aldosterone levels typically fall by approximately 50% and return to the reference range by the end of testing; however, persistent suppression of aldosterone levels to less than 4 ng/dL are reported in patients with GRA. Plasma cortisol suppression (ie, < 5 mcg/dL) is used as an index of the dexamethasone effect. Compared with direct genetic testing, this test achieves a sensitivity of 92% and a specificity of 100% for the diagnosis of GRA.

Biochemically unique, markedly elevated levels of 18-oxocortisol and 18-hydroxycortisol (>100 nmol/day) are also observed in GRA and have been shown to be better than the dexamethasone suppression test for the diagnosis of GRA.

Mutation analysis for the hybrid gene that gives rise to GRA can now be accomplished by means of Southern blotting or a long polymerase chain reaction (PCR) technique. This study is likely to supersede the time-intensive dexamethasone suppression test.

In patients with FH-II, suppression of plasma aldosterone concentration may vary in response to glucocorticoid suppression test (partial, transient, blunted reduction or unresponsive). [42]

FH-III is a distinct disorder characterized by a paradoxical increase of aldosterone after ACTH suppression in some patients, while others demonstrate no response.

Of interest, data have shown that the titer of circulating autoantibodies directed against the second loop of the angiotensin 1 receptor (AT1AA), as well as the serum levels of parathyroid hormone, were both higher in patients with APA than those with IHA or essential hypertension, with only a small overlap between values for patients with APA and IHA. [43, 44] Hence, the determination of those parameters may provide helpful additional information for the diagnostic discrimination between these conditions.


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