EVIDENCE AGAINST DEPLETION OF THE GROWTH-HORMONE (GH)-RELEASABLE POOLIN HUMAN PRIMARY HYPOTHYROIDISM - STUDIES WITH GH-RELEASING HORMONE, PYRIDOSTIGMINE, AND ARGININE

We investigated whether the impaired GH secretion of hypothyroid patie nts could be due to an increase in hypothalamic somatostatinergic tone . Twenty-four patients with primary hypothyroidism [20 females and 4 m ales; mean age (+/- SE), 47.5 +/- 2.7 yr] and 20 normal subjects (17 f emales and 3 males; age, 47.6 +/- 3.0 yr) were studied. In the first g roup of 12 hypothyroid patients, administration of pyridostigmine, a c holinergic agonist drug (120 mg, orally, at -60 min), notably increase d GH responses to GH-releasing hormone (GHRH; 1 mug/kg, iv, at 0 min; peak GH levels for pyridostigmine plus GHRH vs. placebo plus GHRH, 16. 6 +/- 4.9 vs. 6.0 +/- 1.8 mug/L; P < 0.01). The GH responses to pyrido stigmine plus GHRH, however, were considerably lower than those in 10 normal subjects (peak GH levels, 53.0 +/- 3.5 mug/L; P < 0.001). In th e second group of 12 hypothyroid patients, arginine infusion (30 g, iv , from 0-30 min) markedly increased the GH responses induced by GHRH a dministration (1 mug/kg, iv, at 0 min; peak GH levels for arginine plu s GHRH vs. placebo plus GHRH, 30.6 +/- 4.7 vs. 5.3 +/- -1.0 mug/L; P < 0.001). However, GH release after GHRH plus arginine was greater in 1 0 normal subjects than in the hypothyroid patients (peak GH levels, 50 .9 +/- 5.3 mug/L; P < 0.001). Pyridostigmine and arginine inhibit hypo thalamic somatostatin tone. The stimulatory effect both agents on GHRH -induced GH release indicates that reduced GH secretion in hypothyroid ism can be reversed to a considerable extent by inhibiting hypothalami c somatostatinergic tone. The relatively greater potency of arginine c ompared to pyridostigmine suggests that hypothyroid patients may have an impairment of the cholinergic pathways. Furthermore, these data sho w that hypothyroid patients have a somatotrope secretory capacity much greater than previously thought.