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Nature of Altered Growth Hormone Secretion in Hyperthyroidism^*

Endocrine Section, Department of Internal Medicine, Salem Veterans Administration Hospital (A.I., G.L.) Salem, Virginia 24153
the Interdisciplinary Graduate Biophysics Program and Departments of Pharmacology and Internal Medicine, University of Virginia Health Sciences Center (M.L.J., J.D.V) Charlottesuille, Virginia 22908

Address all correspondence and requests for reprints to: Dr. Johannes D. Veldhuis, Division of Endocrinology and Metabolism, Box 202, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908.

Hyperthyroidism is accompanied by various neuroendocrine regulatory disturbances that affect not only the thyrotropic, but also the gonadotropic, corticotropic, and somatotropic axes. To examine the nature of alterations in neuroendocrine control mechanisms that direct the somatotropic axis in hyperthyroidism, we have applied a novel deconvolution technique designed to estimate the number, amplitude, and mass of significant underlying GH secretory events after the influence of GH metabolic clearance has been removed mathematically. To this end, blood was sampled at 10-min intervals for 24 h in seven hyperthyroid and seven age-matched euthyroid men. The subsequent GH time series were assayed by immunoradiometric assay (sensitivity, 0.08 ng/mL) and submitted to quantitative deconvolution analysis. We found that hyperthyroid compared to euthyroid men 1) had significantly more GH secretory bursts per 24 h (viz. 15 ± 1.0 vs. 10 ± 1.1; P = 0.017); 2) secreted 3 times as much GH per burst (3.7 ± 0.80 vs. 1.3 ± 0.42 ng/mL distribution vol; P = 0.013); 3) achieved a maximal rate of GH secretion in each burst 2.3-fold higher than that in control men (0.14 ± 0.028 vs. 0.060 ± 0.015 ng/mL·min; P = 0.017); and 4) had 3.7-fold higher 24-h endogenous GH production rates (P < 0.01). Neither hyperthyroid nor euthyroid men had significant interburst (tonic) GH secretion.

We conclude that the somatotropic axis in hyperthyroid men is marked by a higher frequency of spontaneous GH secretory bursts, a higher rate of maximal GH secretion attained per burst, and a larger mass of GH released per burst. These neuroregulatory disturbances result in a nearly 4-fold increase in the 24-h production rate of GH in thyrotoxicosis.

^* This work was supported in part by NIH Grant RR-00847 (to the Clinical Research Center of the University of Virginia), Research Career Development Award 1-KO4-HD-00634 (to J.D.V.), Grant GM-28928 (to M.L.J.), Diabetes and Endocrinology Research Center Grant NIH DK-38942, NIH-supported Clinfo Data Reduction Systems, V.A. Medical Research Funds (to A.I.), and support by the Biodynamics Institute and the Pratt Foundation.

Received April 6, 1990.

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