Deficient 3β-Hydroxy-5-Ene Steroid Secretion by Newborn Infants

Abstract

Congenital adrenal hypoplasia is reported in two siblings. The first died at 16 months of purulent bronchopneumonia after a history of adrenal insufficiency. No gross adrenal tissue was found at autopsy and urinary steroids were not excreted in detectable amounts before death. In a subsequent uncomplicated pregnancy, extremely low estrogens were recorded in the last trimester. Analysis of steroids in the urine of the neontate by gas chromatography revealed virtual absence of 3 beta-hydroxy-5-ene steroids. These suggest hypoplasia of the fetal adrenal cortex. Metabolites of cortisol were excreted in normal amounts and responded adequately to ACTH stimulation. Neonatal hyponatremia was associated with subnormal excretion of corticosterone and aldosterone metabolites. It is proposed that in the perinatal period, the fetal zone is required for mineralocorticoid synthesis, possibly by providing essential precursor steroids, e.g. 21-hydroxypregnenolone.

Definitive Diagnosis of Enzymatic Deficiencies of Steroidogenesis in At-Risk Newborns and Infants by Urinary Marker Analysis Using GC/MS-SIM

“…A lack of fetal adrenal zone steroids in the 11-day-old male newborn studied by us led to the diagnosis of congenital adrenal hypoplasia. A similar case was reported Shackleton et al [30].…”

“…The defect in 3P-HSD activity was incomplete. Low excretion of the cortisol metabolite THE was confirmed ( [30]. In I patient, X-linkcd congenital hypoplasia was diagnosed by molecular genetic study [unpubl.…”

The influence of prenatal dexamethasone treatment on urinary excretion of adrenocortical steroids in newborns

“…The physiological role of the fetal zone is not quite understood. Lack of the fetal zone in fetuses with congenital adrenal hypoplasia does not cause any problems with the pregnancy or birth and is not life-threatening [15].…”

“…Selected steroid metabolites, derived from the fetal adrenal zone and de®nitive adrenal zone were determined quantitatively by GC mass spectrometry-selected ion monitoring [9]. The following were determined: metabolites derived from the fetal adrenal zone; 16a-hydroxydehydroepiandrosterone (16a-OHDHA), 16a-hydroxypregnenolone (16OHPN¢), from de®nitive adrenal zone, such as the cortisol metabolite tetrahydrocortisone (THE), metabolites of 17a-hydroxyprogesterone, 17a-hydroxypregnanolone (17-OHPN), 3a,15b,17a-trihydroxy-5b-pregnan-20-one (15,, pregnanetriol (PT) and metabolite of 21-deoxycortisol, 11-oxo-pregnanetriol (11-OPT). The metabolites of 17a-hydroxyprogesterone and 21-deoxycortisol were considered to be CAH(21-OH) markers.…”

Development of Laboratory Investigations in Disorders of Sex Development

“…In Zürich, under Andrea Prader's leadership, Milos Zachmann developed GC for steroid urinary metabolites to diagnose adrenal and gonadal enzyme deficiencies [Sandberg et al, 1965;Zachmann et al, 1970Zachmann et al, , 1971Zachmann et al, , 1972Blau et al, 1987]. During the same period, Shackleton began to refine GC in the USA to measure steroid metabolites and to couple it to mass spectrometry [Shackleton et al, 1968[Shackleton et al, , 1979[Shackleton et al, , 1990Shackleton and Honour, 1976;Peterson et al, 1985;Wudy et al, 1992;Krone et al, 2010;Shackleton, 2010].…”