NOVEMBER 2001
[KIGS/KIMS Outcomes Research, Pharmacia AB, Stockholm, Sweden]
Data concerning visits to the doctor, number of days in hospital, and amount of sick leave were obtained from patients included in KIMS (Pharmacia International Metabolic Database), a large pharmacoepidemiological survey of hypopituitary adults with GHD, for 6 months before GH treatment and for 6-12 months after the start of treatment. Assistance required with normal daily activities was recorded at baseline and after 12 months of GH therapy. Quality of life (QoL) (assessed using a disease-specific questionnaire, QoL-Assessment of GHD in Adults) and satisfaction with physical activity during leisure time were also assessed. For the total group (n = 304), visits to the doctor, number of days in hospital, and amount of sick leave decreased significantly (P < 0.05) after 12 months of GH therapy. Patients also needed less assistance with daily activities, although this was significant (P < 0.01) only for the men. QoL improved after 12 months of GH treatment (P < 0.001), and both the amount of physical activity and the patients' satisfaction with their level of physical activity improved after 12 months (P < 0.001). In conclusion, GH replacement therapy, in previously untreated adults with GHD, produces significant decreases in the use of healthcare resources, which are correlated with improvements in QoL. [Hernberg-Stahl E, Luger A, Abs R, Bengtsson BA, Feldt-Rasmussen U, Wilton P, Westberg B, Monson JP; KIMS International Board., KIMS Study Group. Pharmacia International Metabolic Database, "Healthcare consumption decreases in parallel with improvements in quality of life during GH replacement in hypopituitary adults with GH deficiency," J Clin Endocrinol Metab. 2001 Nov;86(11):5277-81]
OCTOBER 2001
Research Centre for Endocrinology and Metabolism, University Hospital, Goteborg, Sweden: In this 1-center study, including 118 consecutive adults (70 men and 48 women; mean age, 49.3 yr; range, 22-74 yr) with adult-onset GH deficiency, the effects of 5 yr of GH replacement on body composition, bone mass, and metabolic indices were determined. The mean initial GH dose was 0.98 mg/d. The dose was gradually lowered, and after 5 yr the mean dose was 0.48 mg/d. The mean IGF-I SD score increased from -1.73 at baseline to 1.66 at study end. A sustained increase in lean body mass and a decrease in body fat were observed. The GH treatment increased total body bone mineral content as well as lumbar (L2-L4) and femur neck bone mineral contents. BMD in lumbar spine (L2-L4) and femur neck were increased and normalized at study end. Total cholesterol and low density lipoprotein cholesterol decreased, and high density lipoprotein cholesterol increased. At 5 yr, serum concentrations of triglycerides and hemoglobin A(1c) were reduced compared with baseline values. In conclusion, 5 yr of GH substitution in GH-deficient adults is safe and well tolerated. The effects on body composition, bone mass, and metabolic indices were sustained. The effects on body composition and low density lipoprotein cholesterol were seen after 1 yr, whereas the effects on bone mass, triglycerides, and hemoglobin A(1c) were first observed after years of treatment. [Gotherstrom G, vensson J, Koranyi J, Alpsten M, Bosaeus I, Bengtsson B, Johannsson G, “A prospective study of 5 years of GH replacement therapy in GH-deficient adults: sustained effects on body composition, bone mass, and metabolic indices,” J Clin Endocrinol Metab. 2001 Oct;86(10):4657-65]
OCTOBER 2001
Department of Medical Sciences, University Hospital, Uppsala, Sweden: The safety and effects of a fixed low dose of growth hormone (GH), 0.17 mg/day was evaluated for 3 months, on glucose metabolism, serum lipids, body composition and cardiac function in 53 GH deficient adults aged 18-78 years. At 3 months, serum levels of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and lipoprotein (a) and lean body mass were increased (P<0.05). Total and low density lipoprotein cholesterol levels and fat mass were reduced (P<0.05). There was an increase in the serum glucose value at 120 min after an oral glucose tolerance test performed at 3 months (P<0.05), no other changes in glucose metabolism or in cardiac function were noted. Side-effects were few and mild. This fixed low-dose regime resulted in improvements in body composition and lipid profile, without causing serious side effects. This is therefore a valid method to institute GH replacement in adults. [Gillberg P, Bramnert M, Thoren M, Werner S, Johannsson G, "Commencing growth hormone replacement in adults with a fixed low dose. Effects on serum lipoproteins, glucose metabolism, body composition, and cardiovascular function," Growth Horm IGF Res. 2001 Oct;11(5):273-81]
AUGUST 2001
Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Liverpool, United Kingdom: Leptin contributes to the regulation of body weight in healthy individuals and is secreted by adipocytes in a diurnal pattern, with superimposed pulsatility. The circulating leptin concentration is increased in both normally obese and untreated adult GH deficiency, a syndrome characterized by increased adiposity. In this study, leptin circadian and ultradian rhythm, leptin pulsatility and its relationship with body fat mass were examined in 12 adult GH deficiency patients (6 men) before and 1 month after GH replacement. All subjects with adult GH deficiency had hypopituitarism subsequent to pituitary surgery and were stabilized on conventional pituitary hormone replacement. Plasma leptin was measured over 24 h at 30-min intervals, and changes in body composition were recorded using bioelectrical impedance. The 24-h mean leptin concentration decreased from 2.04 /- 0.04 nmol/liter in untreated adult GH deficiency patients to 1.64 /- 0.03 nmol/liter after 1 month of GH replacement (P < 0.0001). Before GH replacement, patients demonstrated a significant mean leptin circadian rhythm (P < 0.001), with a mesor of 2.05 /- 0.03 nmol/liter and a superimposed ultradian frequency of 2.0 /- 0.1 cycles/d. After GH replacement, the circadian rhythm was preserved (P < 0.001), but mesor decreased to 1.65 /- 0.01 nmol/liter (P < 0.0001), and leptin ultradian frequency increased to 16.0 /-0.2 cycles/d (P < 0.0001). Pulse analysis (ULTRA) revealed 3.1 /- 0.9 pulses/24 h in untreated adult GH deficiency patients, which significantly increased to 9.9 /- 2.2 pulses/24 h after 1 month of GH replacement (P < 0.001). There was no significant change in body mass index or body fat mass after 1 month of GH replacement. The body fat percentage significantly reduced from 36.5 /- 2.8% to 35.5 /- 2.7% after 1 month of GH replacement (P < 0.05). This change in body fat percentage was explained by a significant increase in lean body mass, from 56.2 /- 2.8 kg at baseline to 57.4 /- 2.7 kg after 1 month (P < 0.05). A significant correlation was observed between plasma leptin and body fat percentage at baseline and 1 month after GH replacement (both, r = 0.7; P < 0.01) in the absence of a significant correlation between leptin and body fat mass before and after GH replacement (P = 0.13 and P = 0.11, respectively). Thus, untreated adult GH deficiency is associated with elevated 24-h leptin concentration, preserved circadian rhythm, and decreased pulsatility. The secretory pattern is restored after GH replacement, with a significant reduction in the 24-h mean leptin concentration, maintenance of circadian rhythm, and increased pulsatility. This GH-induced change in the leptin secretory pattern precedes significant changes in body fat mass and may therefore be independent of changes in adipose tissue. Restoration of leptin pulsatility may be of clinical benefit, and this data could lead to novel approaches for leptin manipulation in the future. [Ahmad AM, Guzder R, Wallace AM, Thomas J, Fraser WD, Vora JP, "Circadian and ultradian rhythm and leptin pulsatility in adult GH deficiency: effects of GH replacement," J Clin Endocrinol Metab. 2001 Aug;86(8):3499-506]
JULY 2001
Department of Medicine, University of Bochum, Bochum, Germany: We examined long-term changes in BMD with GH treatment in GH-deficient adults over a period of 6 years. Twelve GH-deficient patients (four women, eight men) with a mean age of 42.5 years (range 24-61 years) at the beginning of GH replacement. Eleven patients suffered in addition from LH/FSH insufficiency, eight from TSH insufficiency and eight from ACTH insufficiency. Before the start of GH substitution, the insufficient anterior pituitary axes were fully substituted for an average of 9.8 years (range 2-22 years). Average daily GH dose was 2.4 IU (SD 0.86). BMD and bone area were measured at annual intervals at the lumbar spine and at the proximal femur using dual-X-ray absorptiometry. Under GH substitution, serum insulin-like growth factor I concentrations increased by 140 microg/l compared to pretherapeutic values (P = 0.0003). BMD at the lumbar spine increased by 0.16 g/cm2 (P = 0.0005), corresponding to a mean increase of 15.9% or an increase of the BMD Z-score by 1.53 SD. Increases in BMD were independently observed from years 3 to 6 by a mean of 5.8% (P = 0.0087). This increase was paralleled by an increase in the area of the lumbar vertebrae. Bone area also increased at selected sites of the proximal femur, but there was no consistent increase in BMD at the proximal femur. GH therapy in GH-deficient adults is able to progressively increase BMD and bone area at the lumbar spine over a period of at least 6 years. [Clanget C, Seck T, Hinke V, Wuster C, Ziegler R, Pfeilschifter J, “Effects of 6 years of growth hormone (GH) treatment on bone mineral density in GH-deficient adults,” Clin Endocrinol (Oxf). 2001 Jul;55(1):93-9]
