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GH Deficiency Caused by Cranial Irradiation during Childhood: Factors and Markers in Young Adults

Pediatric Endocrinology (L.A., R.B.) and Neurosurgery (C.S.-R.) Departments, Physiology Laboratory (C.T.), Université René Descartes and Hôpital Necker-Enfants Malades, Assistance Publique-Hopitaux de Paris; Pediatric Oncology Department (J.M.Z.), Institut Curie, Paris; and Pediatric Oncology Department (O.H.), Institut Gustave Roussy, Villejuif, France

Address all correspondence and requests for reprints to: R. Brauner, M.D., 211 avenue Daumesnil, 75012 Paris, France.

Abstract

Cranial irradiation alters hypothalamic-pituitary function. We reevaluated 90 patients with GH deficiency caused by fractionated cranial irradiation performed at age 4.9 ± 0.4 (SE) yr when they were 15.7 ± 0.2 yr old. Group 1 received 18 Grays (Gy) (7 cases) or 24 Gy (21 cases) for acute lymphoblastic leukemia; group 2, 30–40 Gy for medulloblastoma (22 cases); group 3, 45–60 Gy for optic glioma and various tumors (30 cases); and group 4, 40–50 Gy for retinoblastoma (10 cases).

The mean GH peaks after an arginine insulin test in group 3 (1.9 ± 0.4 µg/liter) was lower than in groups 1 (4.8 ± 0.5 µg/liter, P < 0.001) and 2 (3.4 ± 0.5 µg/liter, P < 0.03). The mean plasma IGF-I concentrations in group 3 [-3.8 ± 0.2 z score (zs)] was lower than in groups 1 (-2.4 ± 0.3 zs, P < 0.001) and 2 (-3.1 ± 0.2 zs, P < 0.02), as was the mean in group 4 (-3.9 ± 0.3 zs, P < 0.01 compared with group 1 and P < 0.05 compared with group 2). GH peaks and IGF-I were correlated positively (P = 0.0001) and negatively with dose (P < 0.001 for GH and P = 0.0001 for IGF-I), but not with age at irradiation. Among the 43 patients with GH peaks below 3 µg/liter, 41 (95%) had plasma IGF-I less than -2 zs. The body mass index (BMI), plasma insulin, and leptin were similar in the four groups. They were positively correlated with each other (P < 0.001 for BMI compared with insulin and with leptin, respectively, and P < 0.01 for insulin compared with leptin), but not with age or dose of irradiation, or with markers of GH secretion.

In conclusion, in patients with GH deficiency caused by cranial irradiation, the residual GH secretion and plasma IGF-I depend on the dose. Almost all the patients with severe GH deficiency had low plasma IGF-I. BMI, leptin, and insulin seem to be independent of GH status.

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