Because it has been found that growth hormone (GH) treatment of GH-deficient adults is able to reduce the total fat mass, the present study was undertaken to investigate the effect of GH treatment in obese subjects. The investigation was a double-blind placebo-controlled crossover study in which nine obese females were treated with GH (0.03 mg.kg ideal body wt-1.day-1) and placebo for 5 wk. Body composition was determined by dual-energy X-ray absorptiometry, and the quantity of intra-abdominal adipose tissue was determined by CT scan. Lipoprotein lipase (LPL) activity was determined in fat biopsies taken from the subcutaneous abdominal and gluteal region. GH treatment significantly reduced the total fat mass from 40.5 to 38.4 kg (i.e., 5% reduction of the total fat mass; P < 0.01), whereas the fat-free mass increased from 50.5 to 53.5 kg (P < 0.01). In addition, GH treatment significantly reduced the intra-abdominal adipose tissue determined by CT scan (reduction by 7 +/- 0.3%; P < 0.02). CT scan performed at the level of the femur showed a 7% reduction in adipose tissue and a 5% increase in muscle volume in the GH group (P < 0.05). Thus no clear regional differences in the GH-mediated reduction of the adipose tissue mass were observed. GH reduced the LPL activity by approximately 50% (P < 0.01) in the adipose tissue. Finally, GH treatment significantly increased the level of plasma free fatty acids (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective. It is well known that chronic heart failure (CHF) is associated with insulin resistance and cachexia, but little is known about the underlying substrate metabolism. The present study was undertaken to identify disturbances of basal glucose, lipid and protein metabolism. Design. We studied eight nondiabetic patients with CHF (ejection fraction 30 ± 4%) and eight healthy controls. Protein metabolism (whole body and regional muscle fluxes) and total glucose turnover were isotopically assayed. Substrate oxidation were obtained by indirect calorimetry. The metabolic response to exercise was studied by bicycle ergometry exercise. Results. Our data confirm that CHF patients have a decreased lean body mass. (controls), P < 0.01]. Patients had high circulating levels of noradrenaline, glucagon, and adiponectin, and low levels of ghrelin. We failed to observe any differences in metabolic responses between controls and patients during short-term exercise.Conclusions. In the basal fasting state patients with CHF are characterized by several metabolic abnormalities which may contribute to CHF pathophysiology and may provide a basis for targeted intervention.

Diurnal serum GH patterns were determined in 10 acromegalic patients before treatment, after 3 d continuous s.c. pump infusion and then after 3 d with three equal daily s.c. injections in both instances totalling 100 micrograms/24 h. Subcutaneous injections (33 micrograms) induced impressive suppression of serum GH lasting 3-6 h in eight patients followed by escape to pretreatment values before the next injection. In contrast, continuous infusion resulted in greater and more stable 24 h suppression to the levels reached at the nadir between injections. Suppression of mean 24 h serum GH below 5 ng/ml was achieved by pump treatment in four patients, while two patients had mean values between 5 ng/ml and 10 ng/ml. In four patients occasional or all levels were above 10 ng/ml (24 h average 12.4-102 ng/ml) implying either that adequate suppression by the SMS 201-995, was impossible during the 3 d pump infusion period, or that the dose administered was inadequate. Carbohydrate tolerance was unaffected in either regimen, indicating that reduction in insulin antagonistic hormones balanced inhibition of insulin release. Interestingly, and in contrast to somatostatin, SMS 201-995 did not inhibit TSH release. No untoward effects were observed at the moderate dosage and blood clinical chemistry was unchanged. Fairly constant diurnal serum SMS 201-995 values were obtained during pump infusion, while levels undulated inversely with serum GH during injection treatment. Average diurnal serum somatostatin-C immunoreactivity (all patients) decreased from 496 +/- 129 (mean +/- SD) to 385 +/- 100 ng/ml (P less than 0.003) during pump treatment and did not decrease further during the following 3 d injection treatment (363 +/- 76 ng/ml). The normal adult mean is 179 +/- 40 ng/ml. Computer tomographic (CT) scans of the sellar region were performed in all patients before and after the experimental week. Two patients had extracellular tumours whose size decreased from 8.2 to 4.1 cm3 and from 12.6 to 10.5 cm3. The results demonstrate that superior and stable suppression of GH secretion is obtained during continuous s.c. pump infusion of SMS 201-995.

Twelve months of GH therapy induced marked changes in soft tissue; fat mass was reduced, particularly in the trunk (61% of total fat mass reduction) whereas lean soft tissue mass increased more in the extremities. The data imply that GH-induced changes in body composition are maintained with long-term therapy.

Twice-daily GH injections, apart from producing a more physiological serum GH profile, were superior to one injection in increasing serum IGF-I and decreasing IGFBP-1 levels. Both of these changes tend to amplify the effects of the administered GH. Twice-daily injections, however, resulted in lower night-time levels of lipid intermediates.

Information on the course and outcome of pregnancies in growth hormone (GH)-deficient patients is sparse, and GH treatment during pregnancy in such women has not been described previously. We have studied fetal growth and serum levels of GH, insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) during pregnancy, as well as birth weight and hormone levels after delivery in a 25-year-old woman with idiopathic, isolated GH deficiency diagnosed at the age of 7 years. As part of a clinical trial, the patient was treated with 2 IU/M2 GH for a period of 5 years. At this time she became pregnant after donor insemination. The GH treatment was continued until variant GH production from the placenta was evident. Serum levels of GH, IGF-I and IGFBP-3 were measured monthly during pregnancy after 3 days off GH therapy. Abdominal ultrasound was performed five times. Hormonal levels were measured immediately after delivery and during the following days. Serum GH and IGF-I levels increased during the second half of pregnancy; serum IGFBP-3 remained constant throughout pregnancy at a normal level. Serum levels of GH fell within 1 h after delivery, and levels of IGF-I and IGFBP-3 decreased into the range of GH-deficient women 4 days after. The fetal biparietal diameter increased normally, and birthweight was 3.564 kg, length 52 cm. No adverse events were recorded. We conclude that the role of GH replacement during pregnancy of GH-deficient women should be investigated further.

It has been suggested that growth hormone (GH) plays a role in the regulation of Factor VIII-von Willebrand factor complex and other parameters associated with haemostasis and vascular integrity. However, limited information is available on these features in GH-deficient patients. We therefore examined, in a double-blind, placebo-controlled crossover design, the effects of 4 months' replacement therapy with biosynthetic human GH in 22 GH-deficient adults on circulating haemostatic parameters and capillary fragility. A non-significant increase in the plasma levels of von Willebrand factor antigen (p = 0.09), Factor VIII antigen (p = 0.6), fibrinogen (p = 0.4) and fibronectin (p = 0.2) was observed at the end of the GH treatment period along with a non-significant decrease in tissue-type plasminogen activator (p = 0.2). Capillary fragility tended to decrease during GH therapy (p = 0.2). All variables remained within the reference range following both the placebo and the GH treatment period. It is concluded that GH-deficient patients display normal levels of the haemostasis parameters recorded, and that 4 months of GH therapy in a conventional replacement dose does not significantly affect these values.

The aim of the present study was to look further into the question of local degradation of sc injected human GH in GH deficient patients. A comparison was made of serum GH levels after constant iv and sc infusion of the same amount of GH (33 ng\m=.\ k g \ m = -\ 1 \ m = . \ m i n \ m = -\ 1 ) in the same 9 GH deficient patients. A 3-h