Growth hormone-releasing hormone: clinical studies and therapeutic aspects

Growth hormone-releasing hormone (GHRH) stimulates GH secretion in man and the hormonal response is specific. The attenuation of GH response to bolus GHRH after prior exposure of GHRH of up to 24 h was not demonstrated in normal or GH-deficient subjects after more prolonged exposure. This suggests that the partial loss of responsiveness to GHRH may reflect short-term negative feedback by GH. The stimulatory effect of clonidine and L-dopa on GH release is mediated via GHRH. Other stimuli like hypoglycaemia, arginine and propranolol augment GH release in man by modulating hypothalamic somatostatin secretion. Although GHRH test can differentiate between hypothalamic or pituitary cause of GH deficiency, it is of little diagnostic value in children with short stature. Favourable results have been observed in 60-70% of GH-deficient children treated with GHRH, but the dose and mode of administration are still being explored. We found that low dose (1-2 micrograms/kg) GHRH given subcutaneously every 3 h by a pump was effective in promoting growth in 5 of 7 patients after 1 year. Treatment was continued for 2-4 years in 4 patients and growth velocities ranging from 4.5 to 8.2 cm/year were maintained using a dose of 3 micrograms/kg/pulse.