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GH Secretion Is Impaired in Patients with Primary Hyperparathyroidism

Departments of Endocrinology (M.G., E.C., L.G., R.C., C.M., E.M.) and Surgery (P.M.), University of Pisa, 56124 Pisa, Italy; Chair of Endocrinology (L.B.), University of Insubria, 21100 Varese, Italy; and Division of Endocrinology (G.A., F.B., E.G.), University of Turin, 10126 Turin, Italy

Address all correspondence and requests for reprints to: Enio Martino, M.D., Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124 Pisa, Italy. E-mail: . emartino{at}endoc.med.unipi.it

Abstract

The activity of the GH/IGF-I axis as a function of parathyroid activity and calcium metabolism in humans has never been assessed. To address this issue, we studied 18 patients (5 men, 13 women; age range, 23–76 yr; mean, 61 yr) with primary hyperparathyroidism (PHP) due to solitary parathyroid adenoma. GH secretion was evaluated by serum IGF-I levels, spontaneous mean GH secretion over two morning hours, and GH response to arginine (ARG) alone or combined with GHRH. In five patients, serum GH concentrations were measured every 20 min for 24 h, and deconvolution analysis was performed. A group of 35 age- and sex-matched normal subjects served as controls.

Mean serum IGF-I levels in PHP were lower than in normal controls, and in six PHP patients individual serum IGF-I levels were below the age-related normal range. The mean (±SE) peak GH response to ARG alone in PHP patients was significantly lower than in normal subjects (4.0 ± 1.0 vs. 22.0 ± 1.3 µg/liter; P < 0.001). Likewise, the mean (±SE) peak GH response to ARG plus GHRH was reduced in PHP patients (9.9 ± 0.9 vs. 38.0 ± 3.5 µg/liter; P < 0.001). The mean GH concentration over two morning hours in PHP was lower (0.20 ± 0.05 vs. 1.34 ± 0.31 µg/liter; P < 0.001). The mean GH concentration over 24 h in five PHP patients was lower than in six normal controls (0.3 ± 0.1 vs. 0.7± 0.1 µg/liter; P < 0.05); the deconvolution analysis showed that 24-h GH production rate (3.0 ± 1.7 vs. 28.2 ± 4.7 µg/liter·d; P < 0.05) and mean secretory burst mass (1.2 ± 0.7 vs. 10.5 ± 2.6 µg/liter; P < 0.05), but not pulse frequency, were lower in PHP patients than in normal controls. GH half-life and approximate entropy values of 24-h GH profiles were similar in PHP patients and normal controls. No correlation was found between serum-ionized calcium or PTH levels and spontaneous or stimulated GH levels in PHP patients.

In conclusion, this study demonstrates that PHP patients have a reduction in both spontaneous and stimulated GH secretion. Accordingly, PHP should be mentioned as a further example of a metabolic condition in which GH secretion in adults is reduced.

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