Pituitary enlargement due to primary hypothyroidism: growth hormone response to GHRH, GHRP-6 and GHRH plus GHRP-6.

GH secretion after growth hormone-releasing hormone (GHRH), growth hormone releasing peptide-6 (GHRP-6) and after combined administration of both peptides was studied in a patient with lactotrope and thyrotrope hyperplasia due to primary hypothyroidism. Pituitary pseudotumor disappeared after thyroid hormone replacement; this was evidenced by magnetic resonance imaging (NMR). There was no difference between areas under the curve (AUCzero-120 min) during GHRH test before and after thyroid hormone replacement (136.5 vs 129.0 micrograms/l min). Maximal GH increases over basal values (delta GH) did not change (1.5 and 1.9 micrograms/l). GH secretion induced by GHRP-6 increased after treatment (AUCzero-120 min 197.2 vs 650.4 micrograms/l min). delta GH increments were 4.0 and 18.3 micrograms/l before and after therapy respectively. When the peptides were administered together a synergistic effect on GH secretion was observed but GH release was much more powerful after pituitary pseudotumor disappearance (AUCzero-120 min 1043.2 vs 2046.7 micrograms/l min). This was accompanied by increased delta GH (22.7 vs 35.5 micrograms/l). The synergic action of peptides normalized in euthyroid condition and after the resolution of pituitary pseudotumor mainly due to improved GH response to GHRP-6. Blunted response of GH to GHRP-6 and GHRP-6 plus GHRH were in part due to known effects of hypothyroidism on GH secretion. Hypothalamopituitary disconnection and/or decrease in the synthesis of an unknown factor in the hypothalamus which mediates the effects of GHRP-6 may have participated in the GH responsiveness of this patient. This case adds to in vivo evidence that GHRP-6 operates through a non-GHRH dependent mechanism.