Endocrine Abstracts

Why should we be suspicious of simple explanations in complex problems? The past decades have seen critical advances in understanding the regulation of growth hormone (GH) secretion. I spent many fruitful yers studying the actions of synthetic GH secretagogue, the GH releasing peptide-6 (GHRP-6), on human GH secretion. GHRP-6 mimicked GH releasing hormone (GHRH) but did not bind to GHRH receptor. Powerful joint action (synergism) of GHS/ GHRH was blocked in patients with hypothalamic-pituitary disorders. Amongst our many findings was a safe and reliable test for diagnosing adult GH deficiency. Our special interest was in testing with GHRH/GHS in patients with traumatic brain injury and after cranial irradiation in whom the primary damage is in the hypothalamus causing GH deficiency. Identification of ghrelin, the natural ligand for GH secretagogue receptor, with abundant literature which accumulated over 20 years, showed the complexity of ghrelin’s actions: from GH releasing peptide to hunger hormone to glucose regulation. It was a long route to clinical utility of highly selective oral ghrelin mimetic (macimorelin) recently approved of its use in diagnosing GH deficiency in adults. Remarkable progress in collaboration with clinician investigators (investigating medical genetics) have borne fruit. We found families with genes associated with predisposition to early- onset pituitary tumors. We also hypothesized that shared genetic susceptibility may predispose a patient with a strong family history of malignancy to an early-onset pituitary tumor (in a clinical observational study). We better understood the intriguing clinical presentation of polycythaemia/ duodenal somatostatinoma with multiple paragangliomas, by discovering a mutation of the HIF-2A gene (the Pacak-Zhuang syndrome).Science is embedded in case stories.