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GH Replacement (gh + replacement)
Selected AbstractsTherapeutic aspects of growth hormone and insulin-like growth factor-I treatment on visceral fat and insulin sensitivity in adultsDIABETES OBESITY & METABOLISM, Issue 1 2007K. C. J. Yuen Growth hormone (GH) is generally considered to exert anti-insulin actions, whereas insulin-like growth factor I (IGF-I) has insulin-like properties. Paradoxically, GH deficient adults and those with acromegaly are both predisposed to insulin resistance, but one cannot extrapolate from these pathological conditions to determine the normal metabolic roles of GH and IGF-I on glucose homeostasis. High doses of GH treatment have major effects on lipolysis, which plays a crucial role in promoting its anti-insulin effects, whereas IGF-I acts as an insulin sensitizer that does not exert any direct effect on lipolysis or lipogenesis. Under physiological conditions, the insulin-sensitizing effect of IGF-I is only evident after feeding when the bioavailability of circulating IGF-I is increased. In contrast, many studies in GH deficient adults have consistently shown that GH replacement improves the body composition profile although these studies differ considerably in terms of age, the presence or absence of multiple pituitary hormone deficiency, and whether GH deficiency was childhood or adult-onset. However, the improvement in body composition does not necessarily translate into improvements in insulin sensitivity presumably due to the anti-insulin effects of high doses of GH therapy. More recently, we have found that a very low dose GH therapy (0.1 mg/day) improved insulin sensitivity without affecting body composition in GH-deficient adults and in subjects with metabolic syndrome, and we postulate that these effects are mediated by its ability to increase free ,bioavailable' IGF-I without the induction of lipolysis. These results raise the possibility that this low GH dose may play a role in preventing the decline of ,-cell function and the development of type 2 diabetes in these "high risk" subjects. [source] Partial growth hormone deficiency in adults; should we be looking for it?CLINICAL ENDOCRINOLOGY, Issue 4 2010Stephen M. Shalet Summary Quantitatively, GH secretion exists as a continuum in states ranging from good health through to hypopituitarism. Currently, GH replacement is considered only for adults designated as being severely GH deficient (GHD). In clinical practice the gold standard, on which the biochemical diagnosis of severe GHD is based, centres on the presence of two or more additional anterior pituitary hormone deficits. Cohorts of adults with partial GHD (Growth Hormone Insufficiency [GHI]) have been reported with adverse body composition changes, dyslipidaemia, insulin resistance, altered cardiac performance and increased carotid intima-media thickness. The diagnosis of GHI in an individual patient, however, is extremely difficult because such patients rarely exhibit additional anterior pituitary hormone deficits, and the levels of GH-dependent proteins, including IGF-I, are normal in the majority. Currently, GH replacement therapy should only be considered in a patient characterized as GHI by dynamic GH testing in whom there is a plausible cause for hypopituitarism and in whom the IGF-I level is pathologically low. [source] Growth hormone (GH) replacement in hypopituitary adults with GH deficiency evaluated by a utility-weighted quality of life index: a precursor to cost,utility analysisCLINICAL ENDOCRINOLOGY, Issue 1 2008Maria Ko, towska-Häggström Summary Objectives To examine quality of life (QoL) measured by a utility-weighted index in GH-deficient adults on GH replacement and analyse the impact of demographic and clinical characteristics on changes in utilities during treatment. Design Utilities for items in the QoL-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDAutility) were estimated based on data obtained from the general population in England and Wales (E&W). These estimates were used to calculate QoL changes in GH-treated patients and compare these with normative population values. Patients A total of 894 KIMS patients (53% women) from E&W were followed for 1 to 6 years. Measurements QoL-AGHDAutility at baseline and at the last reported visit, total QoL-AGHDAutility gain and QoL-AGHDAutility gain per year of follow-up. Results QoL-AGHDAutility in patients before GH treatment differed from the expected population values [0·67 (SD 0·174) vs. 0·85 (SD 0·038), P < 0·0001], constituting a mean deficit of ,0·19 (SD 0·168). There was a difference in the mean QoL-AGHDAutility deficit for men [,0·16 (SD 0·170)] and women [,0·21 (SD 0·162)] (P < 0·001). The main improvement occurred during the first year of treatment [reduction of a deficit to ,0·07 (SD 0·163) (P < 0·001) in the total cohort]; however, patients' utilities remained lower than those recorded for the general population during subsequent follow-up (P < 0·001). Despite an observed impact of age, primary aetiology, disease onset and comorbidities on QoL-AGHDAutility, all patients showed a similar beneficial response to treatment. Conclusions QoL-AGHDAutility efficiently monitors treatment effects in patients with GHD. The study confirmed the QoL-AGHDAutility deficit before treatment and a similar QoL-AGHDAutility gain observed after commencement of GH replacement in all patients. [source] Unmasking of central hypothyroidism following growth hormone replacement in adult hypopituitary patientsCLINICAL ENDOCRINOLOGY, Issue 1 2007Amar Agha Summary Background, The effect of GH replacement on thyroid function in hypopituitary patients has hitherto been studied in small groups of children and adults with conflicting results. Objective, We aimed to define the effect and clinical significance of adult GH replacement on thyroid status in a large cohort of GH-deficient patients. Patients and method, We studied 243 patients with severe GH deficiency due to various hypothalamo-pituitary disorders. Before GH treatment, 159 patients had treated central hypothyroidism (treated group) while 84 patients were considered euthyroid (untreated group). GH dose was titrated over 3 months to achieve serum IGF-1 concentration in the upper half of the age-adjusted normal range. Serial measurements of serum T4, T3, TSH and quality of life were made at baseline and at 3 and 6 months after commencing GH replacement. Results, In the untreated group, we observed a significant reduction in serum T4 concentration without a significant increase in serum T3 or TSH concentration; 30/84 patients (36%) became hypothyroid and needed initiation of T4 therapy. Similar but lesser changes were seen in the treated group, 25 of whom (16%) required an increase in T4 dose. Patients who became hypothyroid after GH replacement had lower baseline serum T4 concentration, were more likely to have multiple pituitary hormone deficiencies and showed less improvement in quality of life compared with patients who remained euthyroid. Conclusion, GH deficiency masks central hypothyroidism in a significant proportion of hypopituitary patients and this is exposed after GH replacement. We recommend that hypopituitary patients with GH deficiency and low normal serum T4 concentration should be considered for T4 replacement prior to commencement of GH in order to provide a robust baseline from which to judge the clinical effects of GH replacement. [source] Does growth hormone cause cancer?CLINICAL ENDOCRINOLOGY, Issue 2 2006P. J. Jenkins Summary The ability of GH, via its mediator peptide IGF-1, to influence regulation of cellular growth has been the focus of much interest in recent years. In this review, we will explore the association between GH and cancer. Available experimental data support the suggestion that GH/IGF-1 status may influence neoplastic tissue growth. Extensive epidemiological data exist that also support a link between GH/IGF-1 status and cancer risk. Epidemiological studies of patients with acromegaly indicate an increased risk of colorectal cancer, although risk of other cancers is unproven, and a long-term follow-up study of children deficient in GH treated with pituitary-derived GH has indicated an increased risk of colorectal cancer. Conversely, extensive studies of the outcome of GH replacement in childhood cancer survivors show no evidence of an excess of de novo cancers, and more recent surveillance of children and adults treated with GH has revealed no increase in observed cancer risk. However, given the experimental evidence that indicates GH/IGF-1 provides an antiapoptotic environment that may favour survival of genetically damaged cells, longer-term surveillance is necessary; over many years, even a subtle alteration in the environmental milieu in this direction, although not inducing cancer, could result in acceleration of carcinogenesis. Finally, even if GH/IGF-1 therapy does result in a small increase in cancer risk compared to untreated patients with GH deficiency, it is likely that the eventual risk will be the same as the general population. Such a restoration to normality will need to be balanced against the known morbidity of untreated GH deficiency. [source] Serum homocysteine concentrations in children with growth hormone (GH) deficiency before and after 12 months GH replacementCLINICAL ENDOCRINOLOGY, Issue 5 2004Valentina Esposito Summary objective, This open, prospective study was designed to evaluate the effect of growth hormone deficiency (GHD) and GH replacement therapy on serum homocysteine (Hcy) concentration in children with GHD. subjects, Seventeen prepubertal children with GHD (11 boys and six girls) aged 8·6 ± 1·9 years were studied before and after 12 months of GH replacement therapy at a dose of GH of 30 µg/kg/day. Seventeen healthy children acted as controls and were matched for age, sex and body mass index (BMI). methods, At study entry, height, weight, blood pressure, serum Hcy, serum IGF-I, total-low density lipoprotein (LDL)- and high density lipoprotein (HDL) cholesterol, triglycerides, free T4, free T3, vitamin B12, folate, glucose and creatinine were measured in all subjects. The atherogenic index (AI) was also calculated as the ratio of total cholesterol/HDL cholesterol (T/HDL). In GHD children these parameters were also revaluated after 12 months of GH therapy. results, At study entry height and serum IGF-I were significantly lower, as expected, in GHD patients than in controls (P < 0·0001 and P < 0·007, respectively). Serum Hcy levels were significantly higher in GHD patients than in healthy children (8·4 ± 2·9 vs. 6·0 ± 2·9 µmol/l; P < 0·03), although the absolute values were within the normal values for age and sex. There were no significant differences at baseline with respect to blood pressure, serum vitamin B12, folate, fT3, fT4, lipid profile, creatinine and glucose levels. After 12 months of GH replacement therapy height and serum IGF-I increased significantly compared to pretreatment values (P < 0·0001); serum Hcy levels decreased significantly (6·0 ± 3·3 µmol/l; P < 0·002) compared to baseline values, becoming similar to control values. Total cholesterol (3·5 ± 0·6 mmol/l) and the AI (2·5 ± 0·8) decreased significantly with respect to both pretreatment (4·2 ± 1·0 mmol/l; P < 0·0002 and 3·4 ± 0·8; < 0·002, respectively) and control values (4·2 ± 0·4 mmol/l; P < 0·0005 and 3·3 ± 1·1; P = 0·02, respectively). conclusions GHD in children is associated with higher serum levels of Hcy compared to controls, without significantly affecting the lipid profile. GH replacement for 12 months significantly decreased the Hcy levels and improved the lipid profile with a decrease of total cholesterol and the total/HDL cholesterol ratio, compared to pretreatment values. Given the small number of patients, further larger studies are needed to clarify whether these results may have significant effects in the prevention of cardiovascular disease in adulthood. [source] Assessment of quality of life in adults receiving long-term growth hormone replacement compared to control subjectsCLINICAL ENDOCRINOLOGY, Issue 1 2003I. A. Malik Summary objective There are few studies of quality of life (QOL) in adults with growth hormone deficiency (GHD) compared to matched control populations without GHD. These have shown impairments in a variety of QOL measures, which improve but do not normalize after short-term replacement with GH. There is little information on QOL in long-term treated GHD patients compared with controls without GHD. patients and methods A total of 120 adults with GHD who had received GH replacement for at least 1 year were identified from the neuroendocrine clinic. Patients were asked to complete eight QOL questionnaires and an Energy Visual Analogue Scale (VAS). Results were compared with 83 control subjects without GHD from the local population who agreed to complete seven of the QOL questionnaires (excluding Disease Impact scale) and the energy VAS. The eight questionnaires were a combination of generic and disease-specific questionnaires used to assess health related QOL, namely: Short Form-36 (SF-36), Nottingham Health Profile (NHP), Disease Impact, Life Fulfilment and Satisfaction scales, Mental Fatigue Questionnaire (MFQ) and Self Esteem scale, Hospital Anxiety Depression (HAD) scale and QOL-AGHDA (assessment of GHD in adults). results Eighty-nine patients returned questionnaires and 85 (71%) had complete data for analysis. The mean (SD) duration of GH replacement was 36·0 ± 26·4 (range 13,159) months. Mean age was 43·9 ± 15·8 years (37 males) in treated GHD patients compared to a mean age 41·7 ± 10·5 years (32 males) in the controls. Mean IGF-1 levels were 22·5 ± 13·6 nmol/l in the GHD patients and the mean dose of GH replacement was 1·2 ± 0·4 IU daily. Analysis of the QOL questionnaires from the GH treated patients revealed highly significant impairments in all measures (most P , 0·0001, except life fulfilment-material, P = 0·33) compared to the control population. conclusions This large population with treated GH deficiency have significant impairments in multiple aspects of QOL despite replacement with GH and other pituitary hormones for at least 1 year (mean 3 years). It is likely therefore that other factors in addition to GH deficiency must influence QOL in these patients. Further strategies to improve QOL in these individuals should therefore be considered, e.g. psychological support and treatments and physical treatments (such as exercise programmes). [source] | ||||||||||