Low Urinary Estriol During Pregnancy Caused by Isolated Fetal Acth‐deficiency

Abstract

Zachmann, M., Girard, J., Duc, G., Illig, R. and Prader, A. (Departments of Pediatrics, Universities of Zurich and Basel, Switzerland). Low urinary estriol during pregnancy caused by isolated fetal ACTH-deficiency. Acta Paediatr Scand, Suppl. 277: 26, 1979.-In a 34-year-old pregnant woman, serum HPL and urinary HCG were normal, but urinary estriol was repeatedly low. A normal boy was delivered after 38 weeks gestation. During the neonatal period, he had hypoglycemia, muscular hypotonia and transient hyperbilirubinemia. The ACTH-test was normal, hut the THS-response to metyrapone was low. Serum ACTH did not respond to insulin and metyrapone. Growth hormone, TSH and gonadotropin responses to stimuli were normal. Treatment with hydrocortisone resulted in disappearance of the symptoms. It is concluded that fetal ACTH-deficiency is one of the specific endocrine causes of low maternal estriol.KEY WORDS: ACTH-deficiency, urinary estriol, metyrapone test, placental sulphatase deficiency Determinations of estriol (E,) in urine of pregnant women are widely used to monitor fetal well-being. In general, low values indicate placental insufficiency and fetal distress. In few instances, however, pregnancy progresses normally. In this situation, specific endocrine defects of the fetus or the fetoplacental unit may be the cause of reduced E,.In the following, we present evidence suggesting that low maternal E, excretion may be caused by isolated ACTH-deficiency of the fetus. MATERIALS AND METHODSThe following trivial names and abbreviations are used: ACTH = adrenocorticotrophic hormone DHA = dehydroepiandrosterone = 3p-hydroxy-androst-E, = estriol = 1.3.5(10)-estratriene-3,16a,l7/?-triol F = cortisol = hydrocortisone = 17p,17a,21-trihydro-FSH = follicle stimulating hormone GH = growth hormone 170HP = 17-hydroxy-progesterone = l7a-hydroxy-pregn-ITT = insulin tolerance test LH = luteinizing hormone LHRH = luteinizing hormone releasing hormone PRL = prolactin 5-en-17-one xypregn-4-ene-3-,20-dione 4-ene-3,20-dione T, = thyroxine T, = triiodothyronine THE = tetrahydrocortisone = 3a, 17,2l-trihydroxy-SP-THS = tetrahydrocortexolone = 3a, 17,21-trihydroxy-5P-pregnan-20-one Urinary E, in pregnancy was determined according to Brown et al. (6), urinary Porter-Silber chromogens according to Peterson & Pierce (21). Urinary THS (after single dose metyrapone, 35) and THE (before and after synthetic depot-ACTH 1 mg/m2 i.m.) were analyzed by gas chromatography on a glass capillary column (15, 32).Urinary 16-hydroxylated steroids were also assessed by gas chromatography (25).The following hormones in plasma and serum were measured radioimmunologically: ACTH (8) before and after insulin (4 IU/m2 i.v.) and 4 hours after metyrapone (500 mg/m2 p.0.). Routine radioimmunoassay procedures were used for determinations of cortisol and 170H-progesterone before and after synthetic ACTH (250 pg/m2 i.v.), testosterone and DHA-sulphate under basal conditions, GH before and after insulin (4 IU/m2 i.v.) and arginine (0.5 g/kg i.v.), TSH before and after TRH (200...

Steroid sulphatase deficiency is the major cause of extremely low oestriol production at mid-pregnancy: a urinary steroid assay for the discrimination of steroid sulphatase deficiency from other causes

“…Additional analysis of amniotic fluid steroids may well prove more profitable, since their structures and concentrations more closely reflect fetal steroid synthesis and metabolism (Homoki et al, 1983;Saenger et al, 1995). Fetal adrenal hypoplasia of varied origin must also be considered when low oestriol is found at mid-gestation (O'Donahue and Holland, 1968;Hensleigh et al, 1978;Grimberg et al, 1978;Zachmann et al, 1979;Malpuech et al, 1988;Peter et al, 1992;Muscatelli et al, 1994). Absence of neutral steroids of fetal origin from maternal urine and low fetal adrenal steroid content of amniotic fluid may be predicted.…”

Congenital Hypopituitarism as a Cause of Undetectable Estriol Levels in the Maternal Triple-Marker Screen

“…The production of these androgens is under the control of pituitary ACTH stimulation by the 7th wk of gestation (3). There are very few reports of ACTH deficiency suspected prenatally because of extremely low or undetectable maternal levels of estriol (4,5). We are reporting a child with congenital panhypopituitarism, whose diagnosis was confirmed postnatally, but in whom undetectable estriol levels in the maternal triple-marker screen led to suspected fetal adrenal insufficiency and alerted us to investigate the newborn child for this condition.…”

Maternal Anxiety and the Second-Trimester Prenatal Screening: A Prospective Cohort Study

“…Therefore, the depression of ACTH release in the fetus can lead to the decreased secretion of inhibin. In addition, the depression of ACTH release has been shown to cause a decreased production of estriol precursors, which are mainly produced in the fetal adrenal glands [20], potentially leading to reduced maternal serum estriol [21]. …”