cortodoxone and Endocrine-System-Diseases

There are limited reports on the detailed examination of steroid profiles for setting algorithms for 21-hydroxylase deficiency (21OHD) screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS).. We aimed to define an algorithm for newborn screening of 21OHD by LC-MS/MS, measuring a total of 2077 dried blood spot samples in Tokyo.. Five steroids (17α-hydroxyprogesterone [17αOHP], 21-deoxycortisol [21DOF], 11-deoxycortisol [11DOF], androstenedione [4AD], and cortisol [F]) were included in the panel of LC-MS/MS. Samples from 2 cohorts were assayed: Cohort A, 63 "screening positive" neonates who were referred to an endocrinologist (n = 26 with 21OHD; n = 37 false-positive; obtained from 2015 to 2020); and Cohort B, samples (n = 2014) with 17αOHP values in the 97th percentile or above, in the first-tier test with 17αOHP ELISA from 2020 to 2021.. Analysis of Cohort A revealed that the 3 indexes 21DOF, 11DOF/17αOHP, and (4AD + 17αOHP)/F had higher area under the curve (AUC) values (0.999, 0.997, 0.989, respectively), while the 17αOHP AUC was lower (0.970). Accordingly, in addition to 17αOHP, the 3 markers were included for defining the screening algorithm. The assay of Cohort B revealed that the new algorithm gave 92% of predicted positive predictive value without false-negative cases. We also determined the reference values for the 5 steroids at 4 to 7 days after birth, according to sex and gestational age (GA), revealing extremely low levels of 21DOF at any GA irrespective of sex differences.. Our study demonstrated the high relevance of 21DOF, (4AD + 17αOHP)/F, and 11DOF/17αOHP, rather than 17αOHP, for 21OHD screening.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Androgens; Androstenedione; Chromatography, Liquid; Cortodoxone; Endocrine System Diseases; Female; Humans; Hydrocortisone; Infant, Newborn; Male; Neonatal Screening; Steroids; Tandem Mass Spectrometry

In about 5% of cases of classical congenital adrenal hyperplasia, steroid 11 beta-hydroxylase deficiency is the underlying defect. In two publications, no biochemical abnormalities have been reported in obligate heterozygotes for 11 beta-hydroxylase deficiency. We found the typical plasma steroid pattern of 11 beta-hydroxylase deficiency and identified the R448H mutation in the CYP11B1 gene in a boy presenting with pseudoprecocious puberty at age 2 yr. Both parents and an older sister were genotyped and were heterozygous carriers for the R448H mutation in CYP11B1. In contrast to the data reported in the literature, we found increased responses of plasma 11-deoxycortisol and 11-deoxycorticosterone in the short term ACTH test in the three family members heterozygous for the R448H mutation.

Topics: Adrenal Glands; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Base Sequence; Child, Preschool; Cortodoxone; Desoxycorticosterone; Endocrine System Diseases; Exons; Female; Heterozygote; Humans; Introns; Male; Mutation; Pedigree; Puberty, Precocious; Steroid 11-beta-Hydroxylase

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

An evaluation of a new 3 h metyrapone test is presented. The test consists of one oral dose of metyrapone given at 08.00-09.00 hours, and determination of plasma deoxycortisol from a single capillary blood sample taken 3 h later. The test has been assessed in children and adolescents in conjunction with a 5 day metyrapone test, insulin test, vasopressin test, and ACTH test in forty-five reference subjects, in thirty-six hypopituitary subjects with normal or deficient ACTH secretion, in three subjects with primary adrenocortical disease and in ten subjects prior to and after pharmacological prednisone medication. During the first hour after metyrapone the plasma cortisol level decreased to almost the low level maintained for the rest of the 3 h period. The plasma deoxycortisol concentration was basally less than or equal to 35 nmol/l and increased continuously during the 3 h period to the mean level of 299 (95% confidence interval 133-669) nmol/l in the reference subjects. The new test proved to be as accurate as the insulin test in detecting ACTH deficiency. No significant rise was observed in the plasma somatotrophin (GH) level in those children who had a normal GH response to insulin hypoglycaemia.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Blood Glucose; Child; Child, Preschool; Cortodoxone; Endocrine System Diseases; Female; Growth Hormone; Humans; Hydrocortisone; Infant; Insulin; Lypressin; Male; Metyrapone

Pituitary disorders can be diagnosed more readily and precisely as a result of two recent advances: development of radioimmunoassays for direct measurement of each pituitary hormone in blood, and availability of hypothalamic hormones for use in provocative tests for secretion of thyroid-stimulating hormone, prolactin, and gonadotropic hormones.

Topics: Adrenocorticotropic Hormone; Clomiphene; Cortodoxone; Diagnosis, Differential; Endocrine System Diseases; Growth Hormone; Humans; Hypothalamo-Hypophyseal System; Insulin; Levodopa; Pituitary Function Tests; Pituitary Hormones, Anterior; Prolactin; Thyrotropin; Thyrotropin-Releasing Hormone