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Title: Clinical and metabolic studies on hypopituitarism and growth hormone treatment in adults
Author: Beshyah, Salem Arifi
Awarding Body: University of London
Current Institution: Imperial College London
Date of Award: 1995
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The aim this work was to investigate clinical and metabolic consequences of hypopituitarism and the effects of growth hormone (GH) replacement therapy in adults. At baseline, early changes of atherosclerosis were detected using ultrasonography of the peripheral arteries, echocardiography, Doppler scanning and exercise electrocardiography. Abnormalities of glucose tolerance and plasma lipids were detected. Obesity, increased total-body and central fat mass and reduced bone mass were found. Forty patients (aged 19-67 years) entered a double blind placebo controlled trial of GH treatment (daily dose; 0.02-0.05 lU/kg body weight) for 6 months followed by open trial for 12 months. In the controlled study, lean body mass increased, body fat decreased and exercise tolerance increased on GH treatment. No changes in muscle strength nor plasma lipids were observed. Post-prandial plasma glucose increased, as did fasting and postprandial insulin levels on GH therapy. GH increased bone turn-over but bone mineral mass did not change. To study the long-term effects of GH therapy, data were pooled from the two phases of the trial. Thirty four, 27 and 11 patients were treated with GH for 6, 12 and 18 months respectively. The earlier effects on body composition and exercise tolerance were maintained. Minor but significant increases were observed in muscle strength in certain groups. Plasma total and low density lipoprotein cholesterol decreased on long-term GH treatment. Fasting and post-prandial plasma glucose and insulin levels increased. The increase in markers of bone turnover was sustained with no change in bone mineral mass over 6-18 months of GH treatment. Side effects were mainly due to fluid retention. In conclusion, hypopituitary patients on conventional therapy have premature cardiovascular disease, increased frequency of cardiovascular risk factors, abnormal body composition and reduced bone mass. GH therapy produced desirable effects on body composition, exercise tolerance, muscle strength and circulating lipids but produced minor hyperglycemia and hyperinsulinaemia.
Supervisor: Johnston, Desmond G. Sponsor: Novo Nordisk Pharmaceuticals
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral