The effect on the fetal pituitary-adrenal axis of dexamethasone administration early in the second trimester of pregnancy.

OBJECTIVE: To evaluate the effect of a single dose of dexamethasone to pregnant women at early second trimester on the fetal pituitary-adrenal axis. METHODS: Thirty-eight women between 13 and 15 weeks' gestation were included in the study. Blood was taken from the mothers and their fetuses for the evaluation of plasma ACTH, cortisol, and free cortisol levels before and after treatment with a single dose of 1 mg of dexamethasone orally at 11 p.m. the night before the termination of pregnancy. RESULTS: The mean plasma ACTH was significantly lower following dexamethasone administration (8.5 ± 5.1 vs. 18.4 ± 10.9 pg/ml). Similarly, plasma cortisol was significantly lower after dexamethasone treatment (208.3: ± 168.7 vs. 772.7 ± 206.1 nmol/l), as well as plasma free cortisol levels (2.6 ± 0.0 vs. 6.1 ± 6.1 nmol/l). Mean plasma ACTH levels were not significantly different in the fetuses after dexamethasone treatment (33.6 ± 22.7 vs. 42.5 ± 21.9 pg/ml). Moreover, mean fetal plasma cortisol was not different before and after treatment (108.2 ± 27.2 vs. 94.3 ± 47.2 nmol/l), as well as the mean free cortisol levels (7.7 ± 5.2 vs. 7.0 ± 4.3 nmol/l). CONCLUSIONS: A single dose of 1 mg of dexamethasone to the mother early in the second trimester of pregnancy does not result in a significant suppression of the fetal pituitary axis.

Subnormal androgen and elevated progesterone levels in women treated for congenital virilizing 21-hydroxylase deficiency.

Clinical, anthropometric, and endocrine data were examined in 22 corticosteroid-treated, prenatally virilized women with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and in 22 matched healthy controls. In view of the androgen excess, limited growth, and subfertility associated with CAH, the investigation focused on androgenic/anabolic status and circulating progesterone levels. CAH patients were shorter and had a significantly higher body mass index than the controls. One pregnancy was reported in the CAH group compared to 15 in the controls. Five of the CAH patients were judged as undersubstituted based on greatly elevated circulating levels of 17 alpha-hydroxyprogesterone. These five patients had elevated serum levels of progesterone (P) and testosterone (T) and elevated ratios between T and sex hormone-binding globulin, but subnormal levels of dehydroepiandrosterone (DHA) and its sulfate. The remaining 17 well substituted patients had elevated follicular phase levels of P, but subnormal levels of all androgens (4-androstene-3,17-dione, T, DHA, and DHA sulfate) and subnormal T/sex hormone-binding globulin ratios. Contrary to the apprehension that normally guides the treatment of CAH, well substituted patients may be considered hypoandrogenic rather than hyperandrogenic. The elevated levels of P may have a minipill-like effect, which may be one of the causes of the differences in fertility between salt-wasting and simple virilizing CAH.

Adrenocortical carcinoma in a child with congenital hemihypertrophy.

We describe a very rare case of adrenocortical carcinoma (ACC) presenting with Cushing's virilising syndrome in a female child with congenital hemihypertrophy (CHh). CHh was of more value for early detection of ACC than Cushing's virilisation.

Diagnostic value of serum testosterone measurement in infancy: two case reports.

The diagnostic value of serum testosterone measurement and hCG stimulation during early infancy is highlighted by describing two unrelated cases in whom such investigations aided diagnosis and management. When performed on infants between 2 and 9 weeks of age, these measurements can provide valuable information on the integrity of the hypothalamic-pituitary axis in male infants and can identify the presence of testicular tissues in babies with abnormal or ambiguous genitalia.

An adrenal adenoma causing virilization of mother and infant.

A right adrenal androgen-producing adenoma was identified by CT scanning in a 33-year-old woman after delivery of an otherwise-normal, virilized female infant. Despite clinical evidence of mild chronic androgen excess, maternal reproductive function was normal. Post-partum studies showed 2-5-fold excess in maternal plasma testosterone, androstenedione and dehydroepiandrosterone-sulphate; urinary androgen metabolites were increased 3-10-fold. Androgen production from the tumour increased acutely in response to hCG administration; after removal of the tumour, androgen levels were normal and showed negligible responses to hCG. These findings lead us to speculate that endogenous chorionic gonadotrophin may have led to augmented androgen production from the adrenal tumour during pregnancy, causing fetal virilization as previously described in patients with ovarian tumours. This study demonstrates that CT scanning can be valuable in distinguishing between adrenal and ovarian androgen-producing tumours, a distinction which is often unreliable when based on physiological manipulations of hormone secretion.

Fetal and maternal virilization associated with pregnancy. A case report and review of the literature.

A masculinized female infant was born to a mother who had virilizing signs dating from the fourth month of pregnancy. Serum 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, and testosterone levels were all normal in the infant. Maternal testosterone level was markedly elevated one week post partum. Dexamethasone phosphate suppression was normal. Human chorionic gonadotropin stimulation five weeks post partum revealed further elevation of high baseline free and total testosterone levels. Free and total testosterone levels 30 weeks post partum were normal, and all maternal virilizing signs had regressed with the exception of her deepened voice. The child has had no progression of masculinization. The mother is believed to have had a luteoma of pregnancy.

[Morphology of the ovaries in congenital virilization of the external genitalia in persons with genetic and gonadal female sex]. / Morfologiia iaichnikov pri vrozhdennoi virilizatsii naruzhnykh genitalii u lits s geneticheskim i gonadnym zhenskim polom

A study was made of the resected ovarian tissue in 7 patients with congenital virilization of the external genitalia (CVEG). In patients with CVEG there occurred not very pronounced changes in the ovaries seen in diencephalic syndromes with the involvement of the ovaries into the pathological process (hypertrophy of the theca interna cells of the cystically changed follicles, hyperplasia of the intestinal tissue of the cortical layer with the transformation of individual cells into epithelioid, etc.). There were clinical signs indicating an acceleration of maturation of the diencephalic structures (some tendency to the acceleration of sexual development, and distinct signs of diencephalic pathology on the EEG). A conclusion was drawn that in the patients with CVEG the ovaries do not serve as the source of andronization of the organism. It is supposed that in these patients the source of hyperandronization existed at the period of formation of the external genitalia of the fetus and that the adrenal cortex of the fetus could serve as this source.