Faculty Bibliography

In adults patients, administration of human growth hormone and growth hormone synthesized by recombinant DNA technology (rGH) results in sodium and fluid retention and weight gain. This study was performed to determine whether rGH administration in children with idiopathic short stature (ISS) caused any clinical evidence of sodium retention. The parameters assessed included blood pressure, height, weight, plasma renin activity (PRA), aldosterone, and atrial natriuretic peptide (ANP). These were measured in nine treated children after 0, 3, 6, 9, and 12 months of growth hormone therapy; seven untreated children served as controls. After 12 months, the treated children had no significant increases in measurements of blood pressure, PRA, aldosterone, and ANP. Although treated children gained more weight than control patients, they also grew faster. Therefore, there was no significant difference in weight for height percentile for treated children when compared with normal controls. After 1 year of therapy, the administration of rGH to children with ISS does not result in any clinically significant evidence of sodium retention.

The production of 14CO2 in the breath from an intravenous dose of [14C-N-methyl]-erythromycin (the erythromycin breath test [ERMBT]) and the measurement of the ratio of 6-beta-cortisol to free cortisol (6-beta-F/FF) in the urine have each been proposed as means of measuring hepatic P450IIIA catalytic activity in patients. We found that there was a significant correlation between the results of each test (r = 0.59, p less than 0.001) in 47 patients who were without liver disease and who were not taking medications believed to influence P450IIIA catalytic activity. In the 24 of these patients who were subsequently treated with the P450IIIA substrate cyclosporine, the ERMBT result was highly correlated with the mean trough cyclosporine blood level observed; however, there was no correlation between urinary 6-beta-F/FF and the cyclosporine blood levels. In a separate study of a patient during the anhepatic phase of liver transplantation surgery, the ERMBT result decreased by greater than 85%, whereas urinary 6-beta-F/FF decreased by just 50%. We conclude that the ERMBT and urinary 6-beta-F/FF do not always provide similar information about P450IIIA catalytic activity in patients, possibly because of extrahepatic production of 6-beta-F. Of the two tests, the ERMBT appears to provide the most relevant information for cyclosporine administration.

We investigated possible abnormalities of central-nervous-system regulation of luteinizing hormone secretion in the polycystic-ovary syndrome by determining the plasma concentrations of luteinizing hormone over a 24-hour period in five teenage girls with the syndrome; profiles of prolactin and cortisol were also obtained. Four of the five patients had strikingly abnormal plasma luteinizing hormone profiles: whereas normal pubertal girls have a daily surge in secretion of luteinizing hormone that is coterminous with their nocturnal sleep period, our patients had surges that were grossly desynchronized from their sleep period, occurring seven to eight hours later in the daytime than normal. The chronobiologic disturbance involved only luteinizing hormone; the profiles of cortisol and prolactin were normal. This finding points to the central nervous system as the probable locus of the initiating pathophysiology of polycystic-ovary syndrome.