cortodoxone and Addison-Disease

Topics: Addison Disease; Adrenal Gland Diseases; Adrenocorticotropic Hormone; Biomarkers; Chromatography, Paper; Colorimetry; Cortodoxone; Cushing Syndrome; Dexamethasone; Gas Chromatography-Mass Spectrometry; Humans; Metyrapone; Radioimmunoassay; Reference Values; Specimen Handling; Thyroid Diseases

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to measure 6 metabolic compounds of the adrenocorticosteroid pathway simultaneously on residual specimens from patients who had previously been previously diagnosed, on the basis of immunoassays, as having congenital adrenal hyperplasia (CAH), 11 beta-hydroxylase deficiency, 21-hydroxylase deficiency, or Addison disease (adrenal insufficiency). Two subjects with normal adrenal function had serum cortisol values of 13.6 and 8.9 micrograms/dL and serum cortisone values of 2.1 and 0.6 microgram/dL, but the rest of the compounds were undetectable. Two patients with 11 beta-hydroxylase deficiency had serum 11 beta-deoxycortisol values of 14.9 and 10.0 micrograms/dL and serum 11-deoxycorticosterone values of 3.9 and 1.0 microgram/dL, but their serum levels of cortisol and cortisone were diminished. A patient with 21-hydroxylase deficiency had a highly increased serum 17-hydroxyprogesterone concentration of 28.5 micrograms/dL (or 28,500 ng/dL, the traditional unit to report this assay) and a serum 21-deoxycortisol concentration of 6.9 ug/dL (this is a pathologic marker of 21-hydroxylase deficiency that is nondetectable in sera of healthy subjects). This patient also had diminished concentrations of serum cortisol and cortisone (0.9 and 0.3 microgram/dL, respectively). At 30 and 60 min after corticotropin (ACTH) stimulation, serum cortisol was the only compound that showed a dramatic increase in the normal subjects; the patient with 21-hydroxylase deficiency showed an increase of serum 17-hydroxyprogesterone level, but no increase of serum cortisol level; the patient with Addison disease showed no increase in the levels of serum cortisol or other compounds. Metyprapone, which blocks 11 beta-hydroxylase activity, increased the serum 11-deoxycorticosteroid levels and decreased the serum cortisol level. This pilot study demonstrates 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 soon become an ideal analytical technique for the diagnosis of such endocrine diseases.

Topics: 17-alpha-Hydroxyprogesterone; Addison Disease; Adrenal Cortex Diseases; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Aged; Chromatography, Liquid; Cortisone; Cortodoxone; Desoxycorticosterone; Female; Humans; Hydrocortisone; Male; Mass Spectrometry; Metyrapone; Middle Aged

Topics: 17-alpha-Hydroxyprogesterone; Addison Disease; Adrenal Cortex Hormones; Adrenal Hyperplasia, Congenital; Child; Chromatography, High Pressure Liquid; Cortodoxone; Cushing Syndrome; Endocrine System Diseases; Humans; Hydrocortisone; Hydroxyprogesterones; Radioimmunoassay; Spectrophotometry, Ultraviolet

Hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis in depression has received considerable attention, particularly in the now numerous studies utilizing the dexamethasone suppression test. The possibility of HPA axis hypoactivity in this population however has not been similarly explored. To examine this latter possibility, the metyrapone test, a well-established neuro-endocrine assay for determining pituitary reserve, was administered to ten endogenously depressed males and ten matched controls. Consistent with the findings of an earlier study on ten female depressives, one of the depressed males but none of the controls showed clear evidence of HPA axis hypoactivity. This suggests that HPA axis dysfunction in depressives may be more complex than originally anticipated. This finding also has implications for the psychiatric symptomatology classically associated with such illnesses as Addison's disease.

Topics: Addison Disease; Adult; Cortodoxone; Depressive Disorder; Dexamethasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Metyrapone; Middle Aged; Pituitary-Adrenal System