Diagnosis of adrenal cortical dysfunction by liquid chromatography-tandem mass spectrometry

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to measu re G metabolic compounds of the adrenocorticosteroid pathway simultaneously on residual specimens from patients who had previously been previously dia gnosed, on the basis of immunoassays, as having congenital adrenal hyperpla sia (CAH), 11 beta -hydroxylase deficiency, 21-hydroxylase deficiency, or A ddison disease (adrenal insufficiency). Two subjects with normal adrenal fu nction had serum cortisol values of 13.6 and 8.3 mug/dL and serum cortisone values of 2.1 and 0.6 mug/dL, but the rest of the compounds were undetecta ble. Two patients with 11 beta -hydroxylase deficiency had serum 11 beta -d eoxycortisol values of 14.3 and 10.0 mug/dL and serum 11-deoxycorticosteron e values of 3.9 and 1.0 mug/dL, but their serum levels of cortisol and cort isone were diminished. A patient with 21-hydroxylase deficiency had a highl y increased serum 17-hydroxyprogesterone concentration of 28.5 mug/dL (or 2 8,500 ng/dL, the traditional unit to report this assay) and a serum 21-deox ycortisol concentration of 6.9 mug/dL (this is a pathologic marker of 21-hy droxylase deficiency that is nondetectable in sera of healthy subjects). Th is patient also had diminished concentrations of serum cortisol and cortiso ne (0.9 and 0.3 mug/dL, respectively). At 30 and 60 min after corticotropin (ACTH) stimulation, serum cortisol was the only compound that showed a dra matic increase in the normal subjects; the patient with 21-hydroxylase defi ciency showed an increase of serum 17-hydroxprogesterone level, but no incr ease of serum cortisol level; the patient with Addison disease showed no in crease in the levels of serum cortisol or other compounds. Metyrapone, whic h blocks 11 beta -hydroxylase activity, increased the serum 11-deoxycortico steroid levels and decreased the serum cortisol level. This pilot study dem onstrates that it is feasible to use LC-MS/MS for the laboratory diagnosis of adrenal cortical dysfunction. The authors envision that LC-MS/MS may soo n become an ideal analytical technique for the diagnosis of such endocrine diseases. (received I November 2000, accepted 6 February 2001).