Use of steroid profiles in determining the cause of adrenal insufficiency

Abstract

Hypothesis-A cortisol response to adrenocorticotropin injection is the standard test for diagnosing adrenal insufficiency. Multiple steroid hormones can now be accurately measured by tandem mass spectrometry in a single sample. The study objective was to determine whether a steroid profile, created by simultaneous measurement of ten steroid hormones by tandem mass spectrometry, would help determine the cause of adrenal insufficiency.Design-A ten-steroid profile was measured by tandem mass spectrometry during the performance of a standard high dose cortrosyn stimulation test. The steroids were measured at baseline, and 30 and 60 minutes following synthetic adrenocorticotropin injection. Adrenal insufficiency was defined as a peak cortisol level of less than 20 μg/dL. Testing was conducted in the General Clinical Research Center of a University Medical Center. Normal volunteers, patients suspected of having adrenal insufficiency, and patients with known adrenal insufficiency participated.Results-Our results showed that adrenal insufficiency of any cause was adequately diagnosed using the response of 11-deoxycortisol, dehydroepiandrosterone, or these analytes combined in a two-steroid profile. A three-steroid profile yielded a test with 100% accuracy for discriminating primary adrenal insufficiency from normal status. Primary adrenal insufficiency was well separated from secondary adrenal insufficiency using only a single aldosterone value. 11-deoxycortisol, dehydroepiandrosterone, and a two-steroid profile each provided fair discrimination between secondary adrenal insufficiency and normal status.Conclusions-We conclude that stimulated levels of aldosterone, 11-deoxycortisol, dehydroepiandrosterone, and a two-or three-steroid profile provided additional discrimination between states of adrenal sufficiency and insufficiency. It is proposed that a steroid profile measuring

Principles and Applications of LC-MS/MS for the Quantitative Bioanalysis of Analytes in Various Biological Samples

“…Due to its superior specificity, shorter runtimes and less laborious sample preparation, LC-MS/MS methods replace more and more of the conventional HPLC, GC-MS and immunoassay techniques (Taylor, 2005b;Vogeser & Seger, 2008b;Maurer, 2007). LC-MS/MS has, just as HPLC and GC-MS, the advantage that several compounds can be measures simultaneously (Holst et al, 2007). Introduction of on-line solid-phase extraction coupled to LC-MS/MS shortened chromatographic run times and allowed automation of sample preparation (de Jong et al, 2007).…”

Diagnostic Evaluation of Enzyme Activity Related to Steroid Metabolism by Mass Spectrometry-Based Steroid Profiling

“…25 In addition, it was also useful for the differential diagnosis of non-classical forms of CAH, which may not be distinguishable by clinical presentation. [25][26][27] Compared to MS profiling combined with chromatographic separation, matrix-assisted laser desorption ionization (MALDI)-MS has the advantage of high sample throughput, making it attractive for clinical applications. In addition, it has been successfully applied to measure 10 adrenal steroids, including 17-OHP, in the serum of CAH patients.…”

Steroid measurement with LC–MS/MS in pediatric endocrinology

“…In addition to the high specificity there are several other advantages. In contrast to immunoassays, which allow the measurement of only a single steroid, LC-MS/MS has the advantage that several steroid hormones can be measured simultaneously (Holst et al, 2007). This profiling allows evaluation of the status of the enzymes involved in the pathway and thus provides a better tool for diagnosis than does the measurement of one steroid alone.…”

“…The spectrum of diagnostically important metabolites in a plasma steroid profile is particularly helpful for a correct diagnosis and is also useful for the differential diagnosis of nonclassical forms of CAH, which may be indistinguishable using clinical presentation and sonography alone. (Holst et al, 2007;Sahin and Kelestimur, 1997)). Furthermore, a steroid profile contains all steroid metabolites necessary for the diagnosis and monitoring of female hyperandrogenism and is useful for monitoring treatment and compliance in CAH due to enzyme deficiencies, and after adrenal or gonadal tumor surgery.…”