GROWTH-HORMONE SECRETION IN HIV-POSITIVE VERSUS HIV-NEGATIVE HEMOPHILIC MALES WITH ABNORMAL GROWTH AND PUBERTAL DEVELOPMENT

Growth and pubertal development in hemophilic males, age 6-19 years at baseline, were evaluated over a 3.5-year period in 207 HIV-positive a nd 126 HIV-negative subjects as part of the Hemophilia Growth and Deve lopment Study. Methods: Thyroid function, insulin-like growth factor I (IGF-1) levels, bone age, cranial magnetic resonance image normality, CD4(+) counts, and serum testosterone levels of study participants wer e measured at baseline. An extensive endocrine evaluation was performe d in subjects who demonstrated declines in height for age (measurement <5th percentile with two pervious heights >10th percentile), who had not achieved Tanner stage 4 level of pubertal development by age 15 ye ars or who had abnormal growth velocity, which included assessment of peak stimulated growth hormone response after clonidine stimulation, 1 2-hour growth hormone profiles, and serum beta carotene levels (trigge red protocol). Results: For almost the entire group (similar to 99%), thyroid function tests were normal for age. IGF-1 levels were normal f or 93% of the cohort. A total of 120 subjects, 89 HIV-positive and 31 HIV-negative, had an abnormality of growth, pubertal development, or b oth; 34 (11.1%) HIV-positive and 4 (3.6%) HIV-negative subjects had de clines in height (p =.001), 20 (23.3%) HIV-positive and 5 (15.8%) HIV- negative subjects had not achieved Tanner stage 4 by 15 years of age ( p =.372) and 59 (43.4%) HIV-positive and 23 (25.6) HIV-negative subjec ts had abnormal growth velocity (p < 0.001). Among subjects with abnor mal height or growth velocity, the HIV-positive group had significantl y lower mean age-adjusted testosterone levels than did the HIV-negativ e group (p =.030). Within the HIV-positive group, older subjects with abnormal height or growth velocity had significantly lower mean bone a ge than subjects of similar age without growth abnormalities (p =.0092 ). Extensive testing was done in 39 patients (32 HIV-positive, 7 HIV-n egative). Half of the HIV-positive subjects had mean 12-hour growth ho rmone levels <3 ng/ml, 47% had peak stimulated levels <10 ng/ml, 28% h ad peak spontaneous values <10 ng/ml, and 38% had low levels of IGF-1. In the HIV-positive cohort, there was no difference in the rate of ab normalities of growth hormone secretion between those with CD4(+) coun ts greater than or equal to or <200 cells/mm(3) and between those subj ects that met the 1987 Centers for Disease Control (CDC) surveillance definition of AIDS. In the subset of HIV-positive patients with abnorm al peak growth hormone levels after clonidine stimulation, growth horm one response correlated positively with CD4(+) count (r =.657, p =.005 6) and beta carotene concentration (R =.596, p =.0192). Conclusions: T he results of this longitudinal study suggest that abnormalities of gr owth and pubertal development, particularly an abnormal growth velocit y, are common in HIV-infected hemophilic boys and adolescents. These a bnormalities might serve as indicators of the presence of HIV infectio n in this at-risk population. Since thyroid function tests and IGF-1 l evels were normal, the etiology of growth impairment in HIV infection does not appear to be secondary to inadequate caloric intake or acquis ition, or severe illness such as that caused by recurrent or persisten t infection. Rather, HIV infection appears to lead to diminished growt h hormone production or release and decreased androgen secretion, even before the development of AIDS and immunocompromise. These results pr ovide a rationale for trials of treatment with growth hormone or andro gens in patients with abnormalities of endocrine function.