Faculty Bibliography

We describe a premature female infant exposed in utero to danazol during the first trimester of pregnancy. She was first observed in the newborn period with marked degree virilization and clinical findings suggestive of salt-losing congenital adrenal hyperplasia. This was supported by the high plasma levels of 17 alpha-hydroxyprogesterone and adrenocorticotropic hormone and low plasma cortisol level. Levels of testosterone, androstenedione, 11-deoxycortisol, and renin were also elevated. An excessive increase in the levels of 17 alpha-hydroxyprogesterone and 11-deoxycortisol to corticotropin administration associated with impaired increase in plasma cortisol level strongly suggests a partial block in the 21-hydroxylation of 17 alpha-hydroxyprogesterone. However, the high levels of 11-deoxycortisol also suggest a block of the steroid 11 beta-monooxygenase. A year later she was found to have normal basal levels of the adrenal steroids and normal response to corticotropin administration, pointing out the transitory nature of these abnormalities. It may be hypothesized that danazol produced a transitory block of the steroid 21- and 11 beta-monooxygenases in this child.

The effects of zinc deficiency and/or castration on the lipid composition of microsomal membranes of liver, small intestine and testes were studied in rats. The result showed that feeding a zinc-deficient diet to castrated rats decreased phospholipid content and consequently increased the cholesterol-to phospholipid ratio in liver microsomes. An increase in cholesterol-to phospholipid ration occurred also in small intestine and testes microsomes from rats fed the zinc-deficient diet. It is postulated, therefore, that zinc deficiency alters the lipid composition and fluidity of microsomal membranes. Zinc deficiency also affected tha activities of the enzymes involved in the formation of triglycerides and phospholipids. There was a large increase in total and specific activity of phosphatidate phosphatase and the changes in the total activity of choline phosphotransferase correlated well with the changes observed in serum or liver triglycerides and phospholipids. Stearoyl CoA desaturase, which is a control enzyme for hepatic lipogenesis, was also increased by more than 200% in zinc-deficient states, as was the diglyceride content of hepatic microsomes. These results indicate that the increased synthesis of triglycerides and phospholipids in zinc deficiency may be due to the increased availability of substrates as well as to increased activities of the enzymes involved in these processes.

Zinc levels were measured in hair and serum of boys with constitutional growth delay and familial short status and in several boys before and after oral administration of methyltestosterone. These results show the following: (1) zinc levels in boys beyond stage 3 of genital development are significantly higher than in stage 1 and 2; (2) there is a linear relationship between zinc levels and serum testosterone concentration (up to 250 ng/dL); and (3) methyltestosterone administration raised the zinc concentration in serum and hair, especially in boys with constitutional growth delay. Therefore, increased endogenous production or exogenous supply of testosterone are associated with increased zinc levels. We speculate that the relative testosterone deficiency and hypogonadotropism seen in constitutional growth delay may result in decreased zinc levels, which in turn could cause a further delay in the appearance of secondary sexual characteristics and greater growth retardation.

Premature infants have a lower selenium concentration in serum than full-term infants and children. The selenium concentration goes down quickly in infants treated for respiratory distress syndrome without supplementation. One premature infant with bronchopulmonary dysplasia had persistently low concentrations of selenium. Vitamin E supplements did not affect the serum selenium concentration in healthy premature infants. Supplementation with 3 microgram/kg of selenium in parenteral fluids prevented the fall in the concentration seen in other infants not supplemented. Premature infants and especially those treated with oxygen may warrant selenium supplementation to the parenteral nutrition solution. Vitamin E supplements alone are apparently not sufficient to prevent selenium deficiency and potential oxygen toxicity.