Growth hormone (GH) enhances anaerobic capacity: impact on physical function and quality of life in adults with GH deficiency.

CONTEXT: Anaerobic capacity is impaired in adults with GH deficiency (GHD), adversely affecting physical function and quality of life (QoL). OBJECTIVE: To investigate whether GH replacement improves anaerobic capacity, physical function and QoL in adults with GHD. DESIGN: One-month double-blind placebo-controlled crossover study of GH (0·5 mg/day), followed by a 6-month open phase. PATIENTS: A total of 18 adults with GHD. MEASUREMENTS: Anaerobic power (watts) was assessed by the 30-s Wingate test, and aerobic capacity by the VO2 max (l/min) test. Physical functional was assessed by the stair climb test, chair stand test, 7-day pedometry and QoL by the AGHDA questionnaire. Lean body mass (LBM) was quantified by dual-energy X-ray absorptiometry. RESULTS: GH replacement normalized IGF-1 levels during both study phases. During the 1-month placebo-controlled study, improvement in stair climb and chair stand performance was observed during GH and placebo treatment; however, there were no significant GH effects observed in any outcome measure compared to placebo. Six months of GH treatment significantly increased anaerobic power (P < 0·05), chair stand repetitions (P < 0·0001), daily step count (P < 0·05) and QoL scores (P < 0·001) compared to baseline measurements. GH treatment did not significantly improve VO2 max. Improvement in anaerobic power independently predicted an improvement in energy and vitality domain of QoL (P = 0·03). CONCLUSIONS: GH replacement improves anaerobic capacity, physical function and QoL in a time-dependent manner in adults with GHD. Improvement in the anaerobic but not aerobic energy system is likely to underlie the improvement in QoL in patients with GHD during GH replacement.

Impairment of anaerobic capacity in adults with growth hormone deficiency.

CONTEXT: The anaerobic energy system underpins the initiation of all physical activities, including those of daily living. GH supplementation improves sprinting in recreational athletes, a performance measure dependent on the anaerobic energy system. The physiological and functional link between GH and the anaerobic energy system is unknown. OBJECTIVE: The objective was to investigate whether anaerobic capacity is impaired in adults with GH deficiency (GHD) and to assess its functional significance. DESIGN: This was a cross-sectional study. PARTICIPANTS: The participants were 13 adults with GHD and 13 age-, gender- and body mass index-matched normal subjects. MAIN OUTCOME MEASURES: Anaerobic power (watts) was assessed by the 30-second Wingate test, and aerobic capacity was assessed by the VO2max (L/min) test. The functional assessment comprised the stair-climb test, chair-stand test, and 7-day pedometry. Quality of life (QoL) was assessed by the QoL-AGHDA questionnaire. Lean body mass (LBM) was quantified by dual-energy x-ray absorptiometry. RESULTS: Mean anaerobic power (5.8 ± 0.4 vs 7.1 ± 0.3 W · kg LBM(-1); P < .05) and VO2max were significantly lower in adults with GHD. The duration of the stair-climb test was longer (19.4 ± 0.7 vs 16.5 ± 0.7 s; P < .01) in adults with GHD and correlated negatively (R(2) = 0.7; P < .0001) with mean anaerobic power. The mean number of chair-stand repetitions and daily step counts were lower, and the QoL-AGHDA score was higher in adults with GHD (P < .05). In a multiple regression analysis, age, gender, LBM, and GH status were significant predictors of mean anaerobic power. Mean anaerobic power significantly predicted stair-climb performance (P < .01) and QoL (P < .05). CONCLUSIONS: Anaerobic capacity is subnormal, and it independently predicts stair-climbing capacity and QoL in adults with GHD. We conclude that GH regulates anaerobic capacity, which determines QoL and selective aspects of physical function.

Dark adaptation in vitamin A-deficient adults awaiting liver transplantation: improvement with intramuscular vitamin A treatment.

BACKGROUND/AIMS: Although vitamin A deficiency is common in chronic liver disease, limited data exist on impairment of dark adaptation and response to therapy. The aims were (1) to assess dark adaptation in patients, (2) to assess the relationship between dark adaptation and vitamin A status, zinc and Child-Pugh score, (3) to compare perceived and measured dark adaptation and (4) to assess the dark adaptation response to intramuscular vitamin A. METHODS: This was a prospective study of 20 patients (alcoholic liver disease 10, other parenchymal diseases six, cholestatic diseases four) awaiting liver transplantation. Selection was based on low serum retinol. There were 15 age-matched controls. Dark adaptation was measured with a SST-1 dark adaptometer and perception by questionnaire. Eight patients received 50, 000 IU of retinyl palmitate, and dark adaptation was repeated at 1 month. RESULTS: Forty per cent of patients had impaired dark adaptation. Patients with alcoholic liver disease were more impaired than those with other parenchymal diseases (p=0.015). No relationship was found between dark adaptation and the biochemical indicators or Child-Pugh score. Seventy-five per cent of patients with impairment did not perceive a problem. After intervention, light of half the previous intensity could be seen (p=0.05). CONCLUSIONS: Dark-adaptation impairment was common, was worse in alcoholic liver disease, was largely not appreciated by the patients and improved with vitamin A treatment.

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. METHODS: Totally 104 male and female patients were enrolled in a 50-week, exploratory, open-label and randomized study. Eligible patients were randomized to receive either octreotide LAR 20 mg every 28 days or to undergo surgery. Efficacy was assessed by changes in mean GH and IGF-I serum concentrations, at weeks 12, 24 and 48. Tumour volume was assessed by contrast-enhanced MRI. In both groups, treatment adjustment was performed for patients uncontrolled at week 12 or 24. Octreotide LAR patients received a dose increased to 30 mg or, if already receiving this dose, investigator and patients could decide to cross-over to surgery. Patients uncontrolled after surgery received octreotide LAR 20 mg, increased to 30 mg if acromegaly was still uncontrolled. RESULTS: Overall success rates at weeks 24 and 48 were 25% and 28% for the octreotide LAR group and 49% and 39% for the surgery group. Only the difference observed at week 24 was statistically significant (P = 0.047). Both groups had a significant (> 20%) tumour shrinkage: 73% of patients in the octreotide LAR group and 95% in the surgery group. Major differences between octreotide LAR and surgery group in the occurrence of adverse events were gastrointestinal (71%vs. 27%), hepatobiliary (41%vs. 8%) and respiratory (5%vs. 28%). CONCLUSION: This first randomized study in unselected patients indicates that the 48-week treatment outcome of octreotide LAR as first-line treatment of acromegaly does not significantly differ from surgery. As a complete response to surgery in GH-secreting macro-adenomas can be difficult, first-line therapy with octreotide LAR can be considered as a viable alternative for most patients with acromegaly, due to its low complication rate.

The role of growth hormone replacement in a growth hormone deficient patient with underlying cardiomyopathy and severe congestive heart failure.

It has been reported that growth hormone (GH) deficiency induced cardiomyopathy responds to growth hormone replacement therapy. We describe the case of a middle-aged male with cardiomyopathic heart failure and growth hormone deficiency of the adult secondary to surgical panhypopituitarism. We demonstrate clinical and hemodynamic improvement of cardiac function with growth hormone replacement therapy despite underlying structural heart disease.

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.

GH treatment in adults with chronic liver disease: a randomized, double-blind, placebo-controlled, cross-over study.

Patients with chronic liver disease (CLD) are catabolic and GH-resistant. The effects of supraphysiological recombinant human GH (rhGH; 0.2 IU.kg(-1).d(-1)) treatment in adults with CLD were assessed in a randomized, double-blind, placebo-controlled cross-over trial (4-wk dietary run-in, 4-wk treatment, and 2-wk wash-out phases). Nine adults with mild- to moderate-severity CLD participated (median age, 49 yr; three males and six females; Child's classification A in six and B in three). Biopsy-proven etiologies were: alcohol (four patients), primary biliary cirrhosis (three patients), non-A, non-B, non-C hepatitis (one patient), and cryptogenic (one patient). Treatment with rhGH increased serum IGF-I (median increase over placebo, +93 microg.liter(-1); P = 0.004), IGF-binding protein-3 (+0.9 mg.liter(-1): P = 0.004), and acid labile subunit (+10.7 nM; P = 0.004). Total body potassium (+8.0 g; P = 0.023), body weight (+1.6 kg; P = 0.008), and total body water (by bioelectrical impedance; +4.9 kg; P = 0.004) increased. Resting metabolic rate (+313 ml.kg(-1).min(-1); P = 0.004) and lipid oxidation (+1072.0 kcal.d(-1); P = 0.032) increased. Metabolic changes included increased fasting plasma glucose (+1.2 mM; P = 0.008), insulin (+33.8 mU.liter(-1); P = 0.004), C-peptide (+0.7 nM; P = 0.004), and free-fatty acids (+0.1 mEq.liter(-1); P = 0.04). Clinical side effects included worsening edema and ascites. Hepatocellular function did not change. Therefore, rhGH treatment in CLD: 1) overcame hepatic GH resistance; 2) may have improved whole-body protein catabolism; 3) increased lipolysis and lipid oxidation; 4) increased insulin resistance; and 5) had potent antinatriuretic effects. Long-term safety and efficacy require further assessment.