Ross C. Cuneo

The Effects of Treatment with Recombinant Human Growth Hormone on Body Composition and Metabolism in Adults with Growth Hormone Deficiency

In a double-blind, placebo-controlled trial, we studied the effects of six months of growth hormone replacement in 24 adults with growth hormone deficiency. Most of the patients had acquired growth hormone deficiency during adulthood as a consequence of treatment for pituitary tumors, and all were receiving appropriate thyroid, adrenal, and gonadal hormone replacement. The daily dose of recombinant human growth hormone (rhGH) was 0.07 U per kilogram of body weight, given subcutaneously at bedtime. The mean (+/- SE) plasma concentration of insulin-like growth factor I increased from 0.41 +/- 0.05 to 1.53 +/- 0.16 U per liter during rhGH treatment. Treatment with rhGH had no effect on body weight. The mean lean body mass, however, increased by 5.5 +/- 1.1 kg (P less than 0.0001), and the fat mass decreased by 5.7 +/- 0.9 kg (P less than 0.0001) in the group treated with growth hormone; neither changed significantly in the placebo group. The basal metabolic rate, measured at base line and after one and six months of rhGH administration, increased significantly; the respective values were 32.4 +/- 1.4, 37.2 +/- 2.2, and 34.4 +/- 1.6 kcal per kilogram of lean body mass per day (P less than 0.001 for both comparisons). Fasting plasma cholesterol levels were lower (P less than 0.05) in the rhGH-treated group than in the placebo group, whereas plasma triglyceride values were similar in the two groups throughout the study. We conclude that growth hormone has a role in the regulation of body composition in adults, probably through its anabolic and lipolytic actions.

Skeletal Muscle Performance in Adults with Growth Hormone Deficiency

Skeletal muscle mass and function were assessed in 24 adults (16 males, 8 females) with severe, long-standing GH deficiency. Compared to 41 untrained controls (26 males, 15 females), adults with GH deficiency had reduced cross-sectional area of thigh muscle/body weight (p = 0.01), reduced quadriceps force/weight (males: p = 0.002; females: p less than 0.0001), and reduced quadriceps force/muscle area (males: p = 0.005). This suggests (a) that adults with GH deficiency have reduced skeletal muscle mass due, in part, to the absence of the anabolic effects of GH, and (b) that skeletal muscle force may be reduced due to altered muscle mass, contractile elements/muscle fibre, anaerobic energy supply, neural recruitment of fibres, or a combination of these.

Octreotide LAR vs. surgery in newly diagnosed patients with acromegaly: a randomized, open-label, multicentre study.

Objective  This prospective randomized study evaluated the efficacy and safety of octreotide LAR vs. surgery in newly diagnosed acromegalic patients.

Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liver disease

OBJECTIVE Increased serum GH concentrations and GH responses to a variety of stimuli have been reported in patients with chronic liver disease (CLD). We Investigated the pulsatile pattern of endogenous GH release and GH‐binding protein (GHBP) and insulin‐like growth factor‐I (IGF‐I) diurnal profiles in adults with cirrhosis, in comparison with healthy, matched control subjects.

Growth Hormone Deficiency and Quality of Life

Quality of life research in adults with growth hormone deficiency (GHD) is a developing field. It has been recognised that adults with childhood onset GHD suffer social and psychological disadvantages. The effects of GHD of adult onset have only been shown relatively recently. Assessment of these patients, using measures of physical and psychological well-being, has demonstrated that adults with GHD perceive themselves as much less healthy compared with matched controls. The majority of studies investigating the effects of growth hormone replacement therapy indicate that quality of life improves with treatment, although this is not a consistent finding.

Pathogenesis and assessment of malnutrition in liver disease.

Malnutrition is a common development in end-stage liver disease. Its progression is insidious and its presentation is much less dramatic than other complications of cirrhosis. In the past, many hepatologists have regarded it as part and parcel of the disease and this may explain why there have been limited attempts to define its exact contribution to patient outcome or to evaluate methods of reversing its progress. Despite more intensive research of late, many fundamental questions still remain unanswered. These questions include: (i) what are the dominant pathophysiological factors which cause wasting and malnutrition to develop; (ii) what are the most reliable methods of assessing the nutritional status of cirrhotic patients; and (iii) what is the prognostic influence of malnutrition once it does develop? The aim of this article is to review these three basic issues.

Growth hormone and protein metabolism.

Adults with growth hormone (GH) deficiency have decreased lean body mass which can be normalized by GH treatment. The anabolic action of GH involves redistribution of nitrogen from ureogenesis to the extrahepatic anabolic process together with stimulation of amino acid uptake and protein synthesis.

Controversies Regarding the Effects of Growth Hormone on the Heart

Growth hormone (GH) profoundly affects the developing and adult myocardium. Adult patients with GH deficiency (GHD) and GH excess (acromegaly) provide important models in which to understand the effects of GH in adult cardiac physiology. An increasing body of clinical and experimental evidence illustrates the specific physiological abnormalities that are likely associated with the excess cardiovascular mortality observed in both acromegaly and GHD. Because human GH replacement is now available to treat adults with GHD, new questions emerge about the long-term cardiovascular effects of replacement therapy. In multiple trials, GH therapy for congestive heart failure has been proved ineffective in the absence of preexisting GHD. Case reports suggest that, in the setting of GHD, GH therapy can exert a potent beneficial effect on congestive heart failure. Long-term studies addressing cardiovascular morbidity and mortality are needed to assess the role of GH therapy for GHD.

Metabolic Effects of Hypopituitarism and Acromegaly1

Hypopituitarism is associated with reduced lean body mass and increased body fat, while in acromegaly the converse is true. Fasting plasma glucose is increased in acromegaly but fasting plasma insulin

Strength training improves submaximum cardiovascular performance in older men

ABSTRACT Purpose: To determine if 16 weeks of strength training can improve the cardiovascular function of older men during sub‐maximum aerobic exercise. Methods: Twenty four men aged 70‐80 yr were randomly assigned to a strength training (ST; n = 12) and control group (C; n = 12). Training consisted of 3 sets of 6 ‐ 10 repetitions at 70% to 90% of 1RM, 3 times per week, on an incline squat machine for 16 weeks, followed by 4 weeks detraining. Leg strength and maximum oxygen consumption (VO2 max) were assessed every 4 weeks of the 20‐week study. Cardiovascular function was assessed during submaximum cycle exercise at 40 Watts, 50% and 70% of VO2 max before training, after 16 weeks training, and after 4 weeks detraining. Results: At 40 Watts, heart rate (HR), systolic blood pressure, and rate pressure product (RPP) were lower and stroke volume (SV) significantly higher after 16 weeks training and 4 weeks detraining: at 50% VO2 max, HR and RPP were lower after 16 weeks training and 4 weeks detraining: at 70% VO2 max, cycle ergometry power, VO2 and arterio‐venous oxygen difference (a ‐ &OV0456;O2) were higher after 16 weeks training. Leg strength and VO2 max increased after 16 weeks training, with leg strength remaining above pre‐training levels after 4‐weeks detraining. Conclusions: Sixteen weeks of strength training significantly improves the cardiovascular function of older men. Therefore strength training not only increases muscular strength and hypertrophy but also provides significant cardiovascular benefits for older individuals.