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Idiopathic Growth Hormone (GH) Deficiency, and GH Deficiency Secondary to Hypothalamic Germinoma: Effect of Single and Repeated Administration of Human GH-Releasing Factor (hGRF) on Plasma GH Level and Endogenous hGRF-Like Immunoreactivity Level in Cerebrospinal Fluid^*

Third Division, Department of Medicine, Kobe University School of Medicine Kobe 650, Japan

Address correspondence and requests for reprints to: Dr. Kazuo Chihara, Third Division, Department of Medicine, Kobe University School of Medicine, 7-chome, Kusunoki-choChuoh-ku, Kobe 650, Japan.

Plasma GH responses to iv administered synthetic human (GH-releasing factor-(1–44)-NH₂ (hGRF) and the concentration of endogenous hGRF-like immunoreactivity (hGRF-LI) in the cerebrospinal fluid (CSF) were examined in 16 children with GH deficiency (GHD). Ten patients had idiopathic GHD, and six had GHD secondary to germinoma. An iv bolus hGRF (1 µg/kg BW) injection test was performed the day before and the day after treatment, with a daily 1-h iv infusion of hGRF (2 µg/kg BW) for 3 days. Plasma GH increases (>5 ng/ml) after the first iv bolus injection of hGRF occurred in 2 of the 10 idiopathic GHD children and in 4 of the 6 GHD patients with germinoma, whereas the first bolus hGRF injection failed to elicit GH release in the remaining 10 patients. The mean ± SEM peak plasma GH level after the first bolus hGRF dose in the patients with germinoma (8.2 ± 2.2 ng/ml) was significantly higher than that in the idiopathic GHD patients (2.9 ± 0.9 ng/ml; P < 0.05), but significantly lower than that in normal children with short stature (18.5 ± 2.5 ng/ml; P < 0.05). In the 2 patients with germinoma and in 5 of the 8 idiopathic GHD children who did not respond to the first hGRF bolus dose, a significant plasma GH response to hGRF occurred during a daily iv infusion of hGRF for 3 consecutive days, whereas the remaining 3 idiopathic GHD children failed to respond to the daily hGRF infusions. The plasma GH response after the second hGRF bolus dose given after treatment with daily hGRF infusions for 3 days was not different from that after the first hGRF bolus in patients with germinoma or that in the idiopathic GHD children. hGRF-LI was not detected (<5.8 pg/ml) in the CSF in any of 5 patients with germinoma, whereas it was present in 5 idiopathic GHD patients (mean, 17.5 ± 0.9 pg/ml), 3 of whom were nonresponders to daily hGRF infusions.

From these results, GHD secondary to destruction of hypo-thalamic GRF neurons might be defined by the following findings: 1) lack of a GH response to the standard provocative tests acting through the hypothalamus; 2) significant increase in plasma GH after a single bolus and/or repetitive iv administration of hGRF; and 3) undetectable or extremely low levels of endogenous hGRF-LI in the CSF. Most of the idiopathic GHD patients responded to the repetitive hGRF infusion, suggesting insufficient secretion of hypothalamic hGRF as the primary defect. However, since hGRF-LI was detectable in the CSF in some of the idiopathic GHD patients, its pathogenesis must be multifactorial.

^* This work was supported in part by research grants from the Japanese Ministry of Health and Welfare; the Japanese Ministry of Education, Science, and Culture; and the Growth Science Foundation for 1981 and 1982.

Received September 14, 1983.

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