| 1. |
- Koltowska-Häggström, Maria, et al.
(författare)
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Does long-term GH replacement therapy in hypopituitary adults with GH deficiency normalise quality of life?
- 2006
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 155:1, s. 109-19
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether impaired quality of life (QoL) in adults with GH deficiency (GHD) is reversible with long-term GH therapy and whether the responses in QoL dimensions differ from each other. METHODS: QoL was measured by the Quality of Life-Assessment for Growth Hormone Deficiency in Adults (QoL-AGHDA) in general population samples in England & Wales, The Netherlands, Spain and Sweden (n = 892, 1038, 868 and 1682 respectively) and compared with corresponding patients' data from KIMS (Pfizer International Metabolic Database) (n = 758, 247, 197 and 484 respectively) for 4-6 years a follow-up. The subsets of patients from England and Wales, and Sweden with longitudinal data for 5 years' follow-up were also analysed. The change of the total QoL-AGHDA scores and responses within dimensions were evaluated. Subanalyses were performed to identify any specificity in response pattern for gender, age, disease-onset and aetiology. RESULTS: Irrespective of the degree of impairment, overall QoL improved dramatically in the first 12 months, with steady progress thereafter towards the country-specific population mean. Problems with memory and tiredness were the most serious burden for untreated patients, followed by tenseness, self-confidence and problems with socialising. With treatment, these improved in the reverse order, normalising for the latter three. CONCLUSIONS: Long-term GH replacement results in sustained improvements towards the normative country-specific values in overall QoL and in most impaired dimensions. The lasting improvement and almost identical pattern of response in each patient subgroup and independent of the level of QoL impairment support the hypothesis that GHD may cause these patients' psychological problems.
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| 2. |
- Svensson, Johan, 1964, et al.
(författare)
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Growth hormone (GH) replacement therapy in GH deficient adults: predictors of one-year metabolic and clinical response.
- 2007
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 17:1, s. 67-76
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study investigated whether baseline status could predict the responsiveness to one-year growth hormone (GH) replacement therapy in adult GH deficient (GHD) patients. DESIGN: A total of 380 European patients with adult onset GHD due to non-functioning pituitary adenoma that had been enrolled in Pfizer International Metabolic Database (KIMS), and that had completed one year of GH replacement therapy within KIMS, were studied. RESULTS: The mean initial dose of GH was 0.22 (SEM 0.01) mg/day and after one year, the mean dose was 0.36 (0.01) mg/day. The mean insulin-like growth factor-I (IGF-I) SD score increased from -1.75 (0.08) at baseline to 0.47 (0.05) after one year. Quality of life (QoL)-Assessment of GHD in Adults (QoL-AGHDA), waist circumference, waist:hip ratio, and serum lipid pattern improved. Women received a higher dose of GH than men after one year, and demonstrated similar treatment response. In multiple stepwise forward regression analyses, the one-year changes in QoL-AGHDA score, waist:hip ratio, and serum low density lipoprotein-cholesterol (LDL-C) level correlated inversely with the baseline values of the same variable. In addition, the change after one year in QoL-AGHDA score correlated inversely with duration of hypopituitarism and baseline serum high density lipoprotein-cholesterol (HDL-C) level, and the change in waist:hip ratio correlated inversely, although more weakly, with baseline serum HDL-C level and UK citizenship and positively with baseline waist circumference and the initial GH dose. The change in serum LDL-C level additionally correlated inversely with the mean GH dose and duration of hypopituitarism and positively with UK citizenship. CONCLUSIONS: Baseline status could, with moderate strength, predict the responsiveness in the same variable whereas it could not, or only weakly, predict the response in other variables. Therefore, when the decision to start GH replacement is undertaken, as many outcome variables as possible should be evaluated in order to adequately evaluate the likelihood of clinical benefit. Finally, women have a similar response to GH replacement as men when individualised GH dosing schedules are employed and should therefore be selected for GH therapy to a similar extent.
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| 3. |
- Abs, Roger, et al.
(författare)
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Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults - a KIMS database analysis.
- 2006
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 155:1, s. 79-90
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the present study was to clarify the relationship between GH deficiency (GHD) andsome cardiovascular risk factors and to analyse the effect of GH replacement therapy in a large numberof patients over a prolonged period of time.Design: Data for analysis were retrieved from KIMS (Pfizer International Metabolic Database). Serumconcentrations of total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein(LDL)-cholesterol and triglycerides were obtained from 2589 patients at baseline and from 1206patients after 1 and 2 years of GH replacement therapy. Body mass index (BMI), waist and hip, restingblood pressure and body composition were also measured.Results: At baseline, the unfavourable effects of GHD were most obvious in the lipid profiledemonstrating elevated mean total and LDL-cholesterol, in the increased waist circumference and theelevated BMI. The cholesterol concentration, BMI and body composition were significantly adverselyaffected by a number of factors, including age, sex and the use of anti-epileptic drugs. The therapeuticeffect of GH was essentially uniform across the whole population. GH replacement reduced significantlythe mean total and LDL-cholesterol, the waist circumference and the fat mass and was maintainedduring 2 years.Conclusions: This analysis of a large number of patients confirmed that GHD adults present with anincreased cardiovascular risk. The sustained improvement of the adverse lipid profile and bodycomposition suggests that GH replacement therapy may reduce the risk of cardiovascular disease andthe premature mortality seen in hypopituitary patients with untreated GHD.
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| 4. |
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| 5. |
- Filipsson, Helena, 1966, et al.
(författare)
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The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients.
- 2006
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:10, s. 3954-61
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hypopituitary patients with untreated GH deficiency and patients on inappropriately high doses of glucocorticoid (GC) share certain clinical features. OBJECTIVE: The aim of the study was to examine the influence of GC substitution on clinical characteristics in hypopituitary patients before and after GH replacement therapy. METHOD: A total of 2424 hypopituitary patients within the KIMS (Pfizer International Metabolic Database) were grouped according to ACTH status. Comparisons were performed between subjects on hydrocortisone (HC) (n = 1186), cortisone acetate (CA) (n = 487), and prednisolone/dexamethasone (n = 52), and ACTH-sufficient patients (AS) (n = 717) before and after 1 yr of GH treatment in terms of body mass index, waist and hip circumference, blood pressure, glucose, glycosylated hemoglobin (HbA1c), serum lipids, IGF-I, and comorbidity. Hydrocortisone equivalent (HCeq) doses were calculated, and measurements were adjusted for sex and age. RESULTS: At baseline, the HC group had increased total cholesterol, triglycerides, waist circumference, and HbA1c, and the prednisolone/dexamethasone group had increased waist/hip ratio as compared with AS. After HCeq dose adjustment, the HC group retained higher HbA1c than the CA group. GC-treated patients showed a dose-related increase in serum IGF-I, body mass index, triglycerides, low-density lipoprotein cholesterol and total cholesterol levels. Subjects with HCeq doses less than 20 mg/d (n = 328) at baseline did not differ from AS in metabolic endpoints. The 1-yr metabolic response to GH was similar in all GC groups and dose categories. All new cases of diabetes (n = 12), stroke (n = 8), and myocardial infarction (n = 3) during GH treatment occurred in GC-treated subjects. CONCLUSION: HCeq doses of at least 20 mg/d in adults with hypopituitarism are associated with an unfavorable metabolic profile. CA replacement may have metabolic advantages compared with other GCs.
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| 6. |
- Hoybye, Charlotte, et al.
(författare)
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Impact of the primary aetiology upon the clinical outcome of adults with childhood-onset GH deficiency
- 2007
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 157:5, s. 589-596
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The impact of the aetiology of childhood-onset GH deficiency (CO-GHD) on the clinical presentation during adulthood and the response to GH replacement has been poorly defined. Our study aims to characterize CO-GHD in adults due to different aetiologies and evaluate the effect of 2 years of GH replacement therapy. Design and methods: Data from 353 adults with CO-GHD from Pfizer International Metabolic Database KIMS were retrospectively grouped according to GHD aetiology: non-organic disorder (n=147), organic pituitary disease (n=159), and brain tumour (n=47). Extent of pituitary dysfunction, IGF-I concentration, lipid concentrations and quality-of-life (QoL) were assessed at baseline and after 2 years of GH replacement. Results: GHD was diagnosed at a later age in the organic pituitary group than in the other groups, resulting in a shorter duration of GH treatment during childhood. However, the final height was greater in the organic pituitary group. Panhypopituitarism was most common in the non-organic disorder and in the organic pituitary groups, while isolated GHD was more prominent in the brain tumour group. Serum IGF-I levels were the lowest in the non-organic group. QoL was the poorest in the brain tumour group. Lipid profile and QoL improved significantly during GH replacement. Conclusion: The adverse consequences of CO-GHD in adulthood vary between aetiologies, but improve similarly with GH treatment. It is, therefore, important to consider retesting all patients with CO-GHD in early adulthood and, if persistent severe GHD is confirmed, recommence GH replacement.
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| 7. |
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| 8. |
- Kołtowska-Häggström, Maria, et al.
(författare)
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Growth hormone replacement in hypopituitary adults with growth hormone deficiency evaluated by a utility-weighted quality of life index: a precursor to cost-utility analysis
- 2007
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 68:1, s. 122-129
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
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| 10. |
- Monson, John P., et al.
(författare)
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Growth hormone (GH) replacement decreases serum total and LDL-cholesterol in hypopituitary patients on maintenance HMG CoA reductase inhibitor (statin) therapy
- 2007
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 67:4, s. 623-628
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Tidskriftsartikel (refereegranskat)abstract
- Objective Adult onset GH deficiency (GHD) is characterized by abnormalities of serum lipoprotein profiles and GH replacement results in favourable alterations in serum total and low density lipoprotein (LDL)-cholesterol. Preliminary evidence has indicated that the effect of GH replacement in this respect may be additive to that of HMG CoA reductase inhibitor (statin) therapy. We have examined this possibility during prospective follow-up of adult onset hypopituitary patients enrolled in KIMS (Pfizer International Metabolic Database), a pharmacoepidemiological study of GH replacement in adult hypopituitary patients. Design Lipoprotein profiles were measured centrally at baseline and after 12 months GH replacement therapy. Patients Sixty-one hypopituitary patients (30 male, 31 female) on maintenance statin therapy (mean 2·5 ± 2·7 SD years before GH) (statin group - SG) and 1247 (608 male, 639 female) patients not on hypolipidaemic therapy (nonstatin group - NSG) were studied. All patients were naive or had not received GH replacement during the 6 months prior to study. Patients who developed diabetes mellitus during the first year of GH therapy or in the subsequent year and those with childhood onset GHD were excluded from this analysis. An established diagnosis of diabetes mellitus was present in 18% SG and 4·4% NSG at baseline. Measurements Serum concentrations of total, high density lipoprotein (HDL)-cholesterol, triglycerides and IGF-I were measured centrally in all patients and LDL-cholesterol was estimated using Friedewald's formula. Results The relative frequency of various statin use was simvastatin 52% (15·8 ± 8-1 mg, mean ± SD), atorvastatin 30% (14·4 ± 7·8 mg), pravastatin 9·8% (31·6 mg ± 13-9 mg), lovastatin 6·6% (17·5 ± 5 mg) and fluvastatin 1·6% (40 mg). Baseline serum total and LDL-cholesterol (mean ± SD) were 5·2 ±1-4 and 3·1 ± 1·3 mmol/l in SG and 5·8 ± 1·2 and 3-7 ± 1·0 mmol/l in NSG, respectively (P < 0·0001, SG vs. NSG).After 12 months GH replacement (SG: 0·32 ±0·17 mg/day; NSG: 0-38 ± 0·1 mg/day) serum total and LDL-cholesterol decreased by a mean (±SD) of 0·48 (± 1·25) mmol/l (P< 0-0004) and 0-53 (±1·08) mmol/l (P< 0·0001) in SG and by 0·30 (± 0·89) mmol/l (P<0·0001) and 0-28 (± 0·80) mmol/l (P<0·0001) in NSG, respectively. There were no significant changes in HDL-cholesterol or triglycerides in either group (SG vs. NSG: NS). A relationship between LDL-cholesterol at baseline and the decrease in LDL-cholesterol after 12 months GH was evident in both groups (SG: R=-0·54, P< 0·001; NSG: R=-0·4, P< 0·001) and a similar relationship for cholesterol was observed. Conclusions These data indicate that GH replacement exerts additional beneficial effects on lipoprotein profiles in patients on maintenance statin therapy, confirming that the effects of these interventions are complementary rather than exclusive.
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