BIOCHEMICAL DIAGNOSIS OF ADRENAL INSUFFICIENCY: THE ADDED VALUE OF DEHYDROEPIANDROSTERONE SULFATE MEASUREMENTS

Objective: To review biochemical tests used in establishing the challenging diagnosis of adrenal insufficiency. Methods: We reviewed the relevant literature, including our own data, on various biochemical tests used to determine adrenal function. The advantages and limitations of each approach are discussed. Results: Baseline measurements of serum cortisol are helpful only when they are very low (<= 5 mu g/dL) or clearly elevated, whereas baseline plasma adrenocorticotropic hormone levels are helpful only when primary adrenal insufficiency is suspected. Measurements of baseline serum dehydroepiandrosterone sulfate (DHEA-S) levels are valuable in patients suspected of having adrenal insufficiency. Although serum DHEA-S levels are low in patients with primary or central adrenal insufficiency, a low level of this steroid is not sufficient by itself for establishing the diagnosis. A normal age-and sex-adjusted serum DHEA-S level, however, practically rules out the diagnosis of adrenal insufficiency. Many patients require dynamic biochemical studies, such as the 1-mu g cosyntropin test, to assess adrenal function. Conclusion: In establishing the diagnosis of central adrenal insufficiency, we recommend measurements of baseline serum cortisol and DHEA-S levels. In addition to these, determination of plasma levels of aldosterone, adrenocorticotropic hormone, and renin activity is necessary when primary adrenal insufficiency is suspected. With a random serum cortisol level of >= 12 mu g/dL in the ambulatory setting or a normal age-and sex-adjusted DHEA-S level (or both), the diagnosis of adrenal insufficiency is extremely unlikely. When serum DHEA-S levels are low or equivocal, however, dynamic testing will be necessary to determine hypothalamic-pituitary-adrenal axis function.