cosyntropin and 21-deoxycortisol

Nonclassic congenital adrenal hyperplasia (NCCAH) requires exclusion before diagnosing polycystic ovary syndrome (PCOS). Increasing use of liquid chromatography and tandem mass spectrometry (LC-MS/MS) necessitates revision of immunoassay-based criteria for NCCAH. Measurement of 21-deoxycortisol (21DF) may simplify the diagnosis of heterozygosity (HTZ), the presence of 1 affected CYP21A2 allele, which currently relies on complex molecular studies.. We aimed to determine LC-MS/MS-specific criteria for NCCAH and HTZ and compare the diagnostic accuracy of 21DF and 17-hydroxyprogesterone (17OHP).. A cross-sectional study involving 99 hyperandrogenic females was performed. We identified females who had undergone both a synacthen stimulation test (SST) and CYP21A2 genotyping from 2010 to 2017, and prospectively recruited females referred for an SST to investigate hyperandrogenic symptoms from 2017 to 2021. Steroids were compared between genetically confirmed NCCAH, HTZ, and PCOS. Optimal 17OHP and 21DF thresholds for HTZ and NCCAH were determined by receiver operating characteristic analysis.. Basal 17OHP, stimulated 17OHP, and 21DF were measured in 99, 85, and 42 participants, respectively. Optimal thresholds for NCCAH were 3.0 nmol/L and 20.7 nmol/L for basal and stimulated 17OHP, respectively. Basal and stimulated 21DF thresholds of 0.31 nmol/L and 13.3 nmol/L provided 100% sensitivity with specificities of 96.8% and 100% for NCCAH, respectively. Diagnostic thresholds for HTZ of 8.0 nmol/L, 1.0 nmol/L, and 13.6 for stimulated 17OHP, 21DF, and the ratio (21DF + 17OHP)/cortisol each provided 100% sensitivity with specificities of 80.4%, 90.5%, and 85.0%, respectively.. LC-MS/MS-specific 17OHP thresholds for NCCAH are lower than those based on immunoassay. LC-MS/MS-quantified 17OHP and 21DF accurately discriminate HTZ and NCCAH from PCOS.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Androgens; Chromatography, Liquid; Cortodoxone; Cosyntropin; Cross-Sectional Studies; Female; Humans; Steroid 21-Hydroxylase; Tandem Mass Spectrometry

Long-term follow-up studies revealed that patients with subclinical hypercortisolism (SH) due to adrenocortical adenomas have an increased incidence of cardiovascular diseases and mortality. No studies have yet investigated the steroid profile and its implications in patients with SH.. The objective of the study was to analyze the steroid profile by liquid chromatography-tandem mass spectrometry in sera from patients with unilateral adrenocortical adenomas.. This was a cross-sectional study.. The study was conducted at an outpatient clinic.. Patients with adrenocortical adenomas (nonsecreting, n = 66; SH, n = 28) and 188 age- and sex-matched controls drawn from the general population participated in the study.. Cortisol, 21-deoxycortisol, 11-deoxycortisol, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, T, progesterone, 11-deoxycorticosterone, and corticosterone in the basal condition and after a 1-24 ACTH test, and clinical data were measured.. Patients with SH showed lower basal and 1-24 ACTH-stimulated levels of dehydroepiandrosterone and androstenedione than those with nonsecreting adenomas and controls. T was also lower in SH females. Receiver-operating characteristic curves showed that androgens had good accuracy in predicting SH (sensitivity and specificity were 71% and 76% for dehydroepiandrosterone and 69% and 61% for androstenedione, respectively). Increased cortisol and reduced dehydroepiandrosterone levels were independently associated with increased waist circumference. Cortisol was also independently associated with increased number of cardiovascular risk factors in SH patients. After 1-24 ACTH stimulation, the SH patients also showed increased production of 21-deoxycortisol and 11-deoxycorticosterone.. Liquid chromatography-tandem mass spectrometry steroid profile performed for the first time in sera from patients with adrenocortical adenomas showed impaired secretion of several steroids in SH patients. This fingerprint can help in better characterizing the functional status of these tumors.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Cortex Neoplasms; Adrenocortical Adenoma; Aged; Androstenedione; Cortodoxone; Cosyntropin; Cross-Sectional Studies; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Male; Middle Aged; Tandem Mass Spectrometry

This study investigated the prevalence and consequences of heterozygous CYP21A2 mutations in premature pubarche (PP) girls.. We investigated 36 French Mediterranean girls with isolated PP. We performed synacthen testing with 17OHP and 21-deoxycortisol evaluation, along with molecular analysis of the CYP21A2 gene in girls with abnormal elevation of one of these two adrenal steroids. Three girls (8.3%) had nonclassical adrenal hyperplasia, secondary to compound heterozygosity that associated at least one severe mutation for the three girls. A heterozygous mutation of the CYP21A2 gene was confirmed by molecular biology in eight girls (22%); a deletion of the CYP21A2 gene was found in one of them. Biological hyperandrogenism was found in the prepubertal CYP21A2 mutation carriers, whereas the four heterozygous girls who were followed long enough to have reached pubertal age presented biological and clinical hyperandrogenism.. We underline the high prevalence of heterozygous CYP21A2 mutations in girls with PP and demonstrate the usefulness of systematic screening by synacthen testing, both to improve their future clinical management and to prevent the transmission of classical adrenal hyperplasia to future offspring. Because of the severe metabolic and cardiovascular consequences of hyperandrogenism, long-term follow-up of these heterozygous patients is mandatory.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Child; Child, Preschool; Cortodoxone; Cosyntropin; Dehydroepiandrosterone Sulfate; Female; France; Heterozygote; Humans; Hyperandrogenism; Mediterranean Region; Mutation; Puberty, Precocious; Steroid 21-Hydroxylase; Testosterone

21-deoxycortisol is a steroid produced mainly by the adrenal gland. Its normal plasma baseline concentrations (0.03 to 0.30 n/ml) and its concentrations after tetracosactide injection (0.15 to 0.76 ng/ml) do not significantly vary with age, sex and phases of the menstrual cycle. 21-deoxycortisol was assayed in plasma by a specific radioimmunological method and its values were compared with those of 17-OH progesterone in heterozygous subjects with the classical and non-classical forms of 21-hydroxylase deficiency, and in the amniotic fluid of foetuses with this deficiency. Baseline concentrations of 21-deoxycortisol in the classical forms of 21-hydroxylase deficiency (n = 12; 55.36 to 186.6 ng/ml) and post-tetracosactide concentrations in non-classical late onset forms (n = 31; 4.04 to 47 ng/ml) were much higher than in normal subjects, thus making this steroid as sensitive as, or even more sensitive than 17-OH progesterone in diagnosing 21-hydroxylase deficiency. Post-tetracosactide assays of 21-deoxycortisol in 84 heterozygous subjects with 21-hydroxylase deficiency (0.70 to 5.40 ng/ml) enabled these subjects to be detected with a more than 90 percent sensitivity, which cannot be obtained with 17-OH progesterone assays. 21-deoxycortisol concentrations in the amniotic fluid of foetuses with 21-hydroxylase deficiency (n = 11; 0.391 to 0.930 ng/ml) were constantly superior to those observed in normal foetuses (n = 38; 0.034 to 0.221 ng/ml), so that the deficiency can be diagnosed with the steroid as easily as with 17-OH progesterone.

Topics: 17-alpha-Hydroxyprogesterone; 17-Hydroxycorticosteroids; Adrenal Hyperplasia, Congenital; Adult; Amniotic Fluid; Biomarkers; Child; Cortodoxone; Cosyntropin; Female; Heterozygote; Humans; Hydroxyprogesterones; Infant, Newborn; Male; Mixed Function Oxygenases; Prenatal Diagnosis; Radioimmunoassay

Sixty-three women with ultrasonically detected polycystic ovaries (PCO) were investigated for a disorder of adrenal steroid biosynthesis. Serum was obtained before, and at 30 and 60 min after, the administration of 250 micrograms tetracosactrin, and assayed for 17 alpha-OH-progesterone, 21-deoxycortisol, 17 alpha-OH-pregnenolone and dehydroepiandrosterone by radioimmunoassay following paper chromatography. Results were compared with those in 11 women with normal ovaries, seven adult females with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), and 15 women heterozygous for this defect. Although the basal-peak steroid concentration differences were significantly greater when ACTH tests were conducted between 1400 and 1700 h than between 0900 and 1000 h, absolute peak steroid concentrations were not different at either time of day. Four of 63 (6.4%) women with PCO had responses to ACTH characteristic of non-classical (late onset) 21OHD CAH, and about half the remainder had responses characteristic of 21OHD heterozygotes. There was no clear cut evidence for a deficiency in 3 beta-hydroxysteroid dehydrogenase activity in women with PCO.

Topics: 17-alpha-Hydroxypregnenolone; 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Adult; Cortodoxone; Cosyntropin; Dehydroepiandrosterone; Female; Heterozygote; Humans; Hydroxyprogesterones; Middle Aged; Polycystic Ovary Syndrome; Steroids