Contribution of growth hormone deficiency to the growth failure that follows bone marrow transplantation.

Conditioning for bone marrow transplantation (BMT) by total body irradiation frequently causes growth failure. The contribution of growth hormone (GH) deficiency to this failure was assessed in 38 patients given three types of body irradiation: group 1 (n = 18) was given 12 Gy total body irradiation as six fractions, group 2 (n = 14) 10 Gy (one dose) total body irradiation, and group 3 (n = 6) 6 Gy (one dose) thoracoabdominal irradiation, which did not involve the hypothalamic-pituitary area. At the first evaluation, 2.9 +/- 0.2 (SE) years after BMT, the values for the plasma insulin-like growth factor I (IGF-I) and its GH-dependent binding protein (IGFBP-3) were similar in groups 1 and 2 but significantly greater in group 3 (p < 0.02 for IGF-I and 0.01 for IGFBP-3). These values were similar in those patients in groups 1 and 2 who had low GH peaks after stimulation (12 patients: IGF-I, 0.8 +/- 0.2 U/ml; IGFBP-3, 1.6 +/- 0.2 mg/L) and in those with normal GH peaks (20 patients: 1 +/- 0.1 U/ml and 1.8 +/- 0.1 mg/L). The decrease in height 2 years after BMT was significantly (p < 0.01) greater in group 2 than in groups 1 and 3, but 5 years after BMT it was similar in groups 1 and 2 (0.9 +/- 0.2 and 1.4 +/- 0.3 SD), significantly (p < 0.05) greater in group 2 than in group 3 (0.7 +/- 0.2 SD). The individual height changes between BMT and the last clinical evaluation before GH therapy were not correlated with the age at BMT, GH peak after stimulation, plasma IGF-I concentration, or IGFBP-3 concentration. Seven patients with GH deficiency were given GH therapy; their growth rate became normal for age (-2.1 +/- 0.9 SDS before and -0.2 +/- 0.4 SDS for the first year; not significant) without any catch-up growth. We conclude that plasma IGF-I and IGFBP-3 values are of no diagnostic value for GH deficiency after TBI. Their normal or high levels, despite low GH peaks, suggest that bone irradiation induces lesions causing resistance to IGF-I.

Preservation of ovarian function by ovarian transposition performed before pelvic irradiation during childhood.

Ovarian transposition in adults has been shown to protect ovarian function in about 60% of cases by reducing ovarian exposure to less than 4 to 7 Gy. We therefore evaluated the effect of ovarian transposition during childhood or adolescence. Eighteen girls had ovarian transposition performed at a mean (+/- SEM) age of 9.4 +/- 1.2 years (range, 1.2 to 16 years). Twelve were prepubertal and six had menstruated at the time of ovarian transposition. The initial abnormalities were Hodgkin disease (5 cases), iliac Ewing sarcoma (3), medulloblastoma (2), ovarian seminoma (1), and vaginal or uterine tumor (7). The irradiation was external in 11 cases and local by vaginal curietherapy in 7 cases. Fifteen girls received chemotherapy. The ovarian transposition was bilateral in 15 patients and unilateral in 3 cases; in the latter the other ovary had been destroyed by the tumor or by abdominal irradiation. Ovaries were placed just below the iliac crest (15 cases) or posterolateral to the uterus (3); thus, the calculated ovarian radiation dose was up to 9.5 Gy. At the time of evaluation (8.6 +/- 0.9 years after ovarian transposition), 16 girls had menstruated and 2 remained amenorrheic because of major lesions of the vagina and uterus caused by the vaginal curietherapy. Basal plasma gonadotropin values were normal. Ovulation was documented in seven cases. Two pregnancies occurred. Complications of ovarian transposition were present in four patients: intestinal occlusion, dyspareunia, functional ovarian cysts, and pelvic adhesions with tubal obstruction. We conclude that ovarian transposition, performed before abdominopelvic irradiation during childhood, can preserve ovarian function. Longer follow-up is required to assess the risk of ovarian dystrophy because of vascular lesions or chemotherapy.

Endocrine aspects and tumoral markers in intracranial germinoma: an attempt to delineate the diagnostic procedure in 14 patients.

This work outlines the endocrine abnormalities associated with intracranial germinomas (14 patients before treatment). Diabetes insipidus of various intensity was present in all cases. Adipsia is often present as well. In six patients, the first neuroradiologic examination after the onset of DI was normal. Growth hormone secretion was deficient in 11 of 13 patients. Abnormalities of TSH response to TRH were present in nine of ten (four insufficient and five exaggerated responses to TRH). Anterior pituitary dysfunction could not be predicted by the tumor site as determined by radiologic criteria. Tumoral markers have also been studied. Elevated plasma tumoral markers were found in four patients of 11 studied. Tumoral germinoma cells were present in CSF in five patients of ten, in one of them before radiologic confirmation. Pertinent endocrine evaluation and search for tumoral markers was of great value in systematic follow-up of patients with central diabetes insipidus, and could lead to early diagnosis and treatment of the tumor.