Growth hormone secretion in HIV-positive versus HIV-negative hemophilic males with abnormal growth and pubertal development. The Hemophilia Growth and Development Study.
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 and 126 HIV-negative subjects as part of the Hemophilia Growth and Development 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 were measured at baseline. An extensive endocrine evaluation was performed 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 years or who had abnormal growth velocity, which included assessment of peak stimulated growth hormone response after clonidine stimulation, 12-hour growth hormone profiles, and serum beta carotene levels (triggered protocol).


RESULTS
For almost the entire group (-99%), thyroid function tests were normal for age. IGF-1 levels were normal for 93% of the cohort. A total of 120 subjects, 89 HIV-positive and 31 HIV-negative, had an abnormality of growth, pubertal development, or both; 34 (11.1%) HIV-positive and 4 (3.6%) HIV-negative subjects had declines 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 subjects had abnormal growth velocity (p < 0.001). Among subjects with abnormal height or growth velocity, the HIV-positive group had significantly lower mean age-adjusted testosterone levels than did the HIV-negative group (p = .030). Within the HIV-positive group, older subjects with abnormal height or growth velocity had significantly lower mean bone age than subjects of similar age without growth abnormalities (p = .0092). Extensive testing was done in 39 patients (32 HIV-positive, 7 HIV-negative). Half of the HIV-positive subjects had mean 12-hour growth hormone levels <3 ng/ml, 47% had peak stimulated levels <10 ng/ml, 28% had 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 abnormalities of growth hormone secretion between those with CD4+ counts > or = or <200 cells/mm3 and between those subjects that met the 1987 Centers for Disease Control (CDC) surveillance definition of AIDS. In the subset of HIV-positive patients with abnormal peak growth hormone levels after clonidine stimulation, growth hormone response correlated positively with CD4+ count (r = .657, p = .0056) and beta carotene concentration (R = .596, p = .0192).


CONCLUSIONS
The results of this longitudinal study suggest that abnormalities of growth and pubertal development, particularly an abnormal growth velocity, are common in HIV-infected hemophilic boys and adolescents. These abnormalities might serve as indicators of the presence of HIV infection in this at-risk population. Since thyroid function tests and IGF-1 levels were normal, the etiology of growth impairment in HIV infection does not appear to be secondary to inadequate caloric intake or acquisition, or severe illness such as that caused by recurrent or persistent infection. Rather, HIV infection appears to lead to diminished growth hormone production or release and decreased androgen secretion, even before the development of AIDS and immunocompromise. These results provide a rationale for trials of treatment with growth hormone or androgens in patients with abnormalities of endocrine function.
Ratner Kaufman
F
F
Department of Pediatrics, USC School of Medicine, Childrens Hospital Los Angeles, California 90027, USA.
Gertner
J M
JM
Sleeper
L A
LA
Donfield
S M
SM
D000293:Adolescent; D000328:Adult; D000365:Age Determination by Skeleton; D001827:Body Height; D018791:CD4 Lymphocyte Count; D002648:Child; D006130:Growth Disorders / Q000150:complications / Q000209:etiology* / Q000821:virology; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000097:blood / Q000150:complications*; D006467:Hemophilia A / Q000150:complications* / Q000378:metabolism*; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D011628:Puberty, Delayed / Q000150:complications / Q000209:etiology* / Q000821:virology; D012886:Skull / Q000000981:diagnostic imaging; D013739:Testosterone / Q000032:analysis / Q000097:blood; D013961:Thyroid Gland / Q000502:physiology; D019207:beta Carotene / Q000032:analysis / Q000097:blood
D019207:beta Carotene; D019382:Human Growth Hormone; D013739:Testosterone; D007334:Insulin-Like Growth Factor I