Endocrine late effects of childhood cancers.

Long-term survival in children with cancer has increased markedly in the past 15 years. However, impaired linear growth and thyroid dysfunction that vary according to the age at diagnosis and treatment and to the dose and duration of radiation and chemotherapy have been described in these patients. The impact of cranial irradiation on the hypothalamic-pituitary-adrenal axis and on pubertal maturation has been less well studied. A positive correlation between the age at diagnosis and the age at onset of puberty in children who have been treated with high-dose cranial radiation therapy for central nervous system (CNS) tumors has been found recently. Frank adrenal insufficiency is uncommon after high-dose CNS irradiation, but alterations in the hypothalamic-pituitary-adrenal axis do occur. Assessments of the effects of newer modes of radiation therapy such as hyperfractionated craniospinal radiation suggest a lower incidence of primary hypothyroidism in the long term.

Impaired early growth of infants perinatally infected with human immunodeficiency virus: correlation with viral load.

OBJECTIVE: To evaluate the effect of viral load on the early growth of infants infected with human immunodeficiency virus (HIV). METHODS: Plasma concentrations of p24-antigen and HIV ribonucleic acid were measured retrospectively and correlated with growth parameters for the first 18 months of life in a cohort of 47 term infants born to HIV-infected mothers prospectively enrolled in a study of perinatal HIV transmission. Comparisons of the mean weight and length of the 18 HIV-infected and 29 uninfected infants for each interval and across intervals were made. Viral load was correlated with standard deviation scores. Infants were stratified by high and low viral load during the first 6 months of life. RESULTS: At birth, no difference in weight and length was observed between HIV-infected and uninfected infants. Between birth and 6 months of age, the infected infants grew less rapidly than the uninfected infants, a finding temporally associated with an exponential increase in HIV viremia. The linear growth of infected infants remained consistently less than that of the uninfected infants after 6 months of life, although the differences were no longer statistically significant and tended to decrease with age in parallel with declines in viral load. The median plasma concentration of HIV ribonucleic acid was significantly higher at 3, 6, 12, and 18 months in infected infants in whom growth failure developed. Infants who had a high viral load in the first 6 months of life were significantly more likely to have severe growth failure. Though the mean SD for weight of the infected infants was always less than that of the uninfected infants, the differences were small and not significant. CONCLUSIONS: Our results confirm the observation that stunting is an early frequent finding in perinatal HIV infection. The deleterious effect of HIV on linear growth appears to be correlated with the level of postnatal HIV viremia, although the exact mechanism of this association remains to be elucidated.

Relationship of growth hormone deficiency and leukemia.

The use of growth hormone (GH) has been implicated as a possible risk factor for leukemia. We present data from six patients that support a working hypothesis that an increased risk of leukemia may exist in patients with GH deficiency not related to exogenous use of GH.

Growth in congenital rubella syndrome and correlation with clinical manifestations.

Growth patterns, final stature, and clinical manifestations were studied in a review of the records of 105 patients with congenital rubella syndrome followed longitudinally. Of the patients (35 male, 51 female), 86 had achieved final heights. Three patterns of growth were observed: normal growth, growth consistently below the 5th percentile, and growth within the normal range or slightly below the 5th percentile followed by early cessation of growth and final height usually below the 5th percentile. Significant cognitive deficits were not observed in patients with normal growth patterns, except for one patient with profound mental retardation. The magnitude of the cognitive deficits was closely correlated with the degree of growth failure (p less than 0.001). We postulate that the rubella virus exerts its effect on somatic growth both in utero and postnatally, at a central and peripheral level, through multiple mechanisms.

Long-term endocrine sequelae after treatment of medulloblastoma: prospective study of growth and thyroid function.

Endocrine evaluations were performed prospectively in 22 patients with medulloblastoma (ages 2 1/2 to 23 1/2 years at diagnosis), after craniospinal radiation with or without adjuvant chemotherapy. The mean craniospinal hypothalamic-pituitary). and thyroid radiation doses were 3600 and 2400 rads, respectively. Fourteen (73%) of 19 patients who had not yet completed their growth experienced a decrease in growth velocity. However, only three of 10 of these children, who underwent growth hormone stimulation tests, had evidence of deficient growth hormone responses, suggesting that growth hormone secretory or regulatory dysfunction, rather than absolute growth hormone deficiency, is present in the majority of these children. Elevated thyroid-stimulating hormone levels were noted in 15 of 22 patients; one patient had hypothalamic hypothyroidism. Thus, the late effects of therapy for medulloblastoma include frequent endocrine morbidity involving hypothalamic-pituitary and thyroid dysfunction.