Endocrine Abstracts (2001) 2 SP4

Recent studies in normal and abnormal growth hormone secretion

GM Besser

St Bartholomew's Hospital, London

The nature of the hypothalamic factors which control GH secretion in animals and man have emerged since the description of somatostatin (SS) in the early 1970s. Confusion originally arose when the ubiquitous distribution and apparent non-specificity of the actions of SS were established. Understanding of the paracrine nature of SS's action and the dependence of the specificity of its effects upon the locus of secretion and its short half-life in the circulation provided for an unusual mechanism of specificity. The effects of GHRH to promote GH release and the inverse relationship between its secretion and that of SS explained much of the phenomena relating to GH secretion. The more recent description of Ghrelin and the synthetic non-GHRH GH-releasing peptides relating structurally to opioid peptides have added a new dimension. Binding sites in both the hypothalamus and pituitary suggest physiological actions at both sites but the dominant effect appears to be at the hypothalamus and requiring the presence of GHRH. The perplexing origin of Ghrelin from the stomach needs further study.

The pathological features of acromegaly have been better defined in recent times and the effects of different forms of therapy more closely analysed. It is becoming clear that most patients with acromegaly require multiple modalities of treatment for successful outcome including surgery, radiotherapy and medical treatment. The major revolution has been to establish that much lower levels of GH are required than previously thought, to restore the poor prognosis of patients with acromegaly back towards normal. Intensive efforts are required to produce low mean serum GH levels and these must fall to <5.0 mU/l or 2.0 ng/ml. While it is easier to follow the biochemical progress by measuring circulating IGF-1, few data relating to lifetime prognosis and normalisation of IGF-1 exist. Thus it seems wise to follow both GH and IGF-1 levels. Therapy with dopamine agonists, the first medical treatment to be effective, only rarely restores GH levels to safe values. The use of SS analogues, either in the subcutaneous or the depot form, restores GH to safe levels more frequently but by no means always and there are often significant side-effects; this is not surprising in view of the profile of hormone inhibition of SS and its analogues. Nevertheless treatment using these peptides constitutes a major advance. Even more exciting are the effects of the new GH receptor-blocking drug Pegvisamont. This agent has dramatic effects on resolution of the clinical features of acromegaly and restoration of IGF-1 levels to normal in over 90% of patients. Clearly GH levels do not fall on this treatment and clinically it is vital to follow IGF-1 levels. The remarkable increased incidence of colonic neoplasia recently demonstrated that it is of great clinical importance and stresses the vital need to restore GH and IGF-1 levels to normal as soon as possible.

Over recent years the newly recognised syndrome of GH deficiency in the adult has emerged. Initially controversial it is now accepted as a reality, although the precise indications are still not clear. Practical issues relating to initiation, maintenance and monitoring of GH replacement in growth hormone-deficient patients are still being developed

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