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Effects of Growth Hormone Replacement Therapy on 1,25-Dihydroxyvitamin D and Calcium Metabolism^*

Division of Endocrinology, Children's Hospital Research Foundation, Department of Pediatrics (S.B.), Departments of Radiology and Biochemistry (I-W.C), and Division of Neonatology, Department of Pediatrics and Department of Obstetrics and Gynecology (R.C.TJ, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229

Address requests for reprints to: Dr. Stephen Burstein, Section of Pediatric Endocrinology, University of Chicago Medical Center, 5825 South Maryland Avenue, Box 118, Chicago, Illinois 60637.

To elucidate the changes in mineral metabolism and blood concentrations of calciotropic hormones which accompany GH therapy, we studied 12 GH-deficient children for 5 days before and for 1 week after high dose (5 IU/day) GH therapy, and again at 1 month, 3 months, and 1 yr of replacement therapy (0.1 IU/kg to a maximum dose of 2 IU three times weekly). All responded with acceleration of height velocity, and bone ages advanced appropriately.

Fasting serum ionized calcium levels did not change: 4.11 ± 0.06 (SEM) mg/dl before, 4.19 ± 0.05 for the week of high dose therapy, and 4.20 ± 0.14 during replacement therapy. Likewise, fasting serum parthormone did not vary: 38.9 ± 2.6 µleq/ml before to 44.1 ± 9.2 at 1 yr. Twenty four-hour nephrogenous cyclic AMP (NcAMP) did not vary over the first week (1.2 ± 0.7 nmol/dl glomerular filtrate before, 1.3 ± 0.4 after 1 week), but increased to 5.3 ± 1.9 after 1 yr ( < 0.001). The response of ionized calcium and parathormone to a standardized disodium EDTA infusion of 50 mg/kg also did not change. The mean fasting serum calcitonin level was not different before therapy (29.4 ± 2.8 pg/ml), after 1 week (21.5 ± 1.8), or after 1 yr (42.4 ± 11.0). However, the mean serum 1,25-dihydroxyvitamin D concentration rose from 33.1 ± 3.3 pg/ml before therapy to 68.3 ± 12.3 on the seventh day of high dose therapy ( < 0.01), returning to pretherapy values by 1 month. We conclude that high dose GH therapy in GH-deficient children raises 1,25-dihydroxyvitamin D concentration acutely, but that long term, physiological replacement therapy does not cause such an effect. Because NcAMP excretion rose in the absence of an increase in serum parathormone concentration, we conclude that GH sensitizes the kidney to a cAMP-mediated effect of parathormone. (J Clin Endocrinol Metab 56: 1246, 1983)

^* Supported by Grant RR-00123 from the General Clinical Research Center Branch of the United States Public Health Service, by a Trustee Grant from the Children's Hospital Research Foundation, University of Cincinnati College of Medicine (to S.B.), and by NICHD HD-11725 (to R.C.T.).

Received March 11, 1982.

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