To investigate the clinical significance of change in QoL-AGHDA score after 1 year of growth hormone (GH) replacement. Observational data were obtained from KIMS (Pfizer International Metabolic Database). Minimal important differences (MID) for the QoL-AGHDA score and its five domains (memory and concentration, tenseness, tiredness, self-confidence, and social isolation) were calculated using an anchor-based approach with a rating of patient-perceived treatment benefit and patient-reported change in need for assistance. Perception of treatment benefit was measured using the KIMS Patient Life Situation Form (PLSF), a 5-point ordinal assessment of change (much improved, a little improved, no change, a little worse, much worse). The effect of baseline (BL) scores on MID was analysed using the QoL-AGHDA thresholds included in the New Zealand (≥16) and England (≥11) reimbursement criteria. Data from 1404 patients (52% female, 96% Caucasian, mean age [SD] of 45 [14] years) were included in the analysis. Mean GH dose [SD]was 0.20 [0.14] mg/day at BL and 0.32 [0.16] mg/day during Year 1. The Spearman correlation between change in QoL-AGHDA score and perception of treatment benefit was moderately positive (0.45; p < 0.01). The correlation was stronger for females and for patients with more impaired (higher) BL QoL-AGHDA scores. Using the anchor-based approach with patient-perceived treatment benefit, the MID for the QoL-AGHDA score was -4.61 at Year 1. Self-confidence was most sensitive and tenseness least sensitive of the domains in predicting patient-perceived treatment benefit. Patients requiring assistance at BL and not at Year 1 experienced the largest mean improvement in QoL-AGHDA score. Several national reimbursement authorities currently include the QoL-AGHDA score in eligibility criteria for access to reimbursed GH replacement. This is the first study to calculate the MID for the QoL-AGHDA score. Findings indicate that change in QoL-AGHDA score is positively correlated with patient-perceived treatment benefit.

The purpose of this study is to examine potential implications of changes in the approach to adult growth hormone (GH) replacement (GHR) over the last 15 years. Therefore, we analysed the German KIMS database as one of the largest single country pharmacoepidemiological databases on adult GH deficiency (GHD). Based on the date of their first GH application patients were assigned to three intervals (1995–1999, 2000–2004, 2005–2009). A multivariate analysis of variance with interval and sex as independent variables was conducted. Differences were analysed with respect to IGF-I standard deviation score (SDS), quality of life, latency between GHD diagnosis and first GH dose, body mass index, waist–hip ratio, lipid profile, and GH dose. All analyses were conducted at baseline, 1 year, and 3 years of GHR. We detected significant associations between time interval and patient characteristics at baseline and with treatment effects. Recently, patients with less severe GHD (mean IGF-I SDS: −2.1, −1.6, −1.0 in the 1st, 2nd and 3rd interval; p = 0.000) are treated with lower GH starting doses (mean 0.30, 0.19, 0.21 mg/day in the 1st, 2nd and 3rd interval; p = 0.000). In the first time interval, IGF-I SDS was not normalized in females after 3 years of GHR. The results of our analysis demonstrate prominent changes in patient characteristics and handling of GHR. They highlight that approach to therapy and patient inclusion criteria change over time and may represent an important confounder for any analysis in epidemiological surveillance surveys.

Background Quality of life (QoL) measures are important in growth hormone (GH) deficiency (GHD) in adults. Ideally, for use in health economics, QoL should be expressed in utilities. The aim of this study was to obtain reference values and utilities for QoL of GHD in adults in Belgium and the Netherlands. Methods The study was conducted in three stages: (1) The Quality of Life-Assessment for Growth Hormone Deficiency in Adults (QoL-AGHDA) and the EQ-5D were administered in a representative sample of 6,875 individuals from the Belgian and 1,400 individuals from the general Dutch population. The EQ-5D index can be used to estimate utilities. Using a regression, utilities were predicted from the QoL-AGHDA. (2) QoL-AGHDA scores were obtained from 299 Belgian and 234 Dutch adult patients with GHD and no GH replacement. These scores were converted to utilities and compared the burden of disease with other patient groups. (3) To test the criterion validity, the ‘standard’ EQ-5D index was used in a subsample of 64 Dutch GHD patients and compared with the predicted utilities. Results We obtained data from 1,026 Belgian (response rate = 15%) and 1,038 Dutch respondents (response rate = 74%). The Belgian mean QoL-AGHDA value was 6.95 (90% range = 14.00), and the Dutch mean was 5.48 (range = 13.00). The R 2 of the regression model to predict the EQ-5D index was 0.360 (Belgium) and 0.482 (the Netherlands). We demonstrated a considerable burden of disease in GHD patients, comparable to patients with hypertension or with type II diabetes. The criterion validity was 0.407 (intraclass correlation, ICC). Conclusions Interventions in GHD can now be evaluated more validly in Belgium and the Netherlands.

Annual growth prediction models following growth hormone (GH) treatment have been developed to facilitate treatment guidance. However, accurately predicting height over the long term, during pre-pubertal treatment years has not been assessed and is a prerequisite for modelling of cost effective optimum height outcomes. Annual prediction models utilised data from large cohorts sourced from the KIGS database (Pfizer International Growth Database, comprising 75,000 children with growth disorders) and describe the likely annual height gain based on patients' auxological and biochemical characteristics (e.g. GH dose, age, mid parental height standard deviation [SDS] and weight SDS score) at treatment start. The most likely long-term height development was simulated prospectively up to 4 years by sequential application of existing yearly prediction algorithms for height velocity (HV) and newly developed algorithms for weight gain in pre-pubertal children with idiopathic GH Deficiency (GHD) and Turner Syndrome (TS). The long-term prediction of height was validated in new cohorts of pre-pubertal children with GHD (n= 664) or TS (n=607) from KIGS. When height was simulated from GH start in GHD, the predicted mean (SD) gain after 4 years was 30.4 (3.4) cm; the observed height gain was 30.0 (5.0) cm. In TS the corresponding predicted and observed mean gains were 27.2 (2.2) and 26.5 (3.8) cm. Sequential application of annual KIGS growth prediction models permits accurate simulation of height development during the first four years of GH treatment in GHD and TS and is applicable for patient groups from GH start. Long-term growth simulation helps managing patient's expectations and facilitates an individualised, cost effective growth hormone (GH) therapy in children.

GH replacement (GHR) is well established, and has been widely accepted to be safe in patients with a wide spectrum of pituitary pathologies. However, GHR in patients with treated germ cell tumours (GCTs) remains controversial, and its use has been cautioned (1, 2). Anecdotal experience from our centre and elsewhere (1, 2, 3) suggests that vigilant monitoring is mandatory in treated GCTs who are GH replaced. There are no published studies of long-term outcome and recurrence rates after GHR in treated GCTs. We have therefore surveyed our long-term experience with GHR in 18 adult patients with previously treated GCTs and a global experience of 142 patients from the KIMS database (Pfizer International Metabolic Database) in this diagnostic category in order to determine whether GHR plays a role in tumour relapse. This is a longitudinal observational study reporting a single centre experience and global experience using the KIMS database. The study groups comprised 18 consecutive patients with GCT treated at St Bartholomew's Hospital, London (SBH) (median duration of follow-up from diagnosis of GCT 13 years (range 0.5–44)) and 142 patients with GCT enrolled in the KIMS database (median duration of follow-up 14.8 years (0.7–36.4)). The relapse rates pre-GHR and during GHR and relapse-free survival were evaluated.

levels did not differ (patients vs. controls: 701±87 vs. 572±33mg/l, P =0.17), whereas bioactive IGF-I tended to be lower in patients (5.37±0.55 vs. 6.63±0.25mg/l, P < 0.06). Conclusion: The baseline findings of elevated free GH and low bioactive IGF-I support the concept of GH resistance in uremic hemodialysis patients. Using high dose rhGH treatment it was possible to obtain normal responses in total and bioactive IGF-I levels, showing that the GH resistance may be overcome. Nevertheless, our data imply that the response of bioactive IGF-I to GH is subnormal in hemodialysis patients.

OBJECTIVEThe impact of growth hormone (GH) replacement on plasma brain natriuretic peptide (BNP) in association with cardiac morphology and function in adults with growth hormone deficiency (GHD) was evaluated.SUBJECTS AND METHODSFifty nine adult patients with GHD (29 men, age 19-59 years) received a starting dose of 0.1-0.2 mg/day recombinant GH, which was subsequently adjusted to the 50th percentile of normal serum insulin-like growth factor (IGF-1) over a 6 month period. Plasma BNP and IGF-I levels before, 3 and 6 months after treatment were determined, as were the echocardiographic data, such as ejection fraction (EF), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVST), posterior wall thickness (PWT), left ventricular mass (LVM), E/A wave and deceleration time (DT).RESULTSMean plasma BNP levels (53.1+/-8 pg/ml) and echocardiographic parameters were within the normal range at baseline, although men had higher LVM, IVST, PWT, LVEDV and LVEDD, respectively. A significant decrease in plasma BNP was observed after 6 months (27+/-5.6 pg/ml, P<0.05). No significant changes in echocardiographic parameters were observed except for a mild tendency to increase in LVM, and a borderline decrease in DT (181+/-8.1 vs. 155+/-9 ms, P<0.01).CONCLUSIONSSix months GH replacement therapy induced a significant decrease in plasma BNP levels despite the majority of patients having plasma BNP within the normal range at baseline. A borderline decrease in diastolic deceleration time was observed, the clinical significance of which is unclear.

Objective To describe baseline clinical presentation, treatment effects and evolution of isolated GH deficiency (IGHD) to multiple pituitary hormone deficiency (MPHD) in adult-onset (AO) GHD. Design Observational prospective study. Methods Baseline characteristics were recorded in 4110 patients with organic AO-GHD, who were GH naïve prior to entry into the Pfizer International Metabolic Database (KIMS; 283 (7%) IGHD, 3827 MPHD). The effect of GH replacement after 2 years was assessed in those with available follow-up data (133 IGHD, 2207 MPHD), and development of new deficiencies in those with available data on concomitant medication (165 IGHD, 3006 MPHD). Results IGHD and MPHD patients had similar baseline clinical presentation, and both groups responded similarly to 2 years of GH therapy, with favourable changes in lipid profile and improved quality of life. New deficiencies were observed in 35% of IGHD patients, which was similar to MPHD patients with one additional deficit other than GH. New deficiencies most often presented within the first year but were observed up to 6 years after GH commencement. Conversion of IGHD into MPHD was not predicted by aetiology, baseline characteristics, surgery or radiotherapy, whereas in MPHD additional deficits were predicted by age ( P <0.001) and pituitary disease duration ( P <0.01). Conclusion Both AO-IGHD and -MPHD patients have similar baseline clinical presentation and respond equally well to 2 years of GH replacement. Hypopituitarism in adults seems to be a dynamic condition where new deficiencies can appear years after the initial diagnosis, and careful endocrine follow-up of all hypopituitary patients, including those with IGHD, is warranted.

The last decade has seen a proliferation in options for testosterone replacement. However, little is known as to the benefits of different treatment modalities. Our objective was to determine the testosterone prescription pattern and to examine the impact on various outcome measures.A total of 816 adult-onset hypopituitary males on stable pituitary replacement for at least 1 year were identified from the KIMS database. Patients were classified as either eugonadal (n = 106), or hypogonadal (n = 710) on intramuscular (IM, n = 558), oral (n = 74), transdermal (n = 61), and depot (n = 17) testosterone.After 1 year of stable pituitary replacement therapy, body composition, cardiovascular parameters, GH replacement and quality of life were not significantly different in androgen-replaced hypogonadal patients compared to eugonadal patients. There were no differences in outcome variables within the hypogonadal group according to the testosterone replacement regimen used and no difference in response to GH therapy.The majority of hypopituitary patients in the last decade have received IM testosterone. Body composition, cardiovascular parameters, GH replacement and quality of life were not different between eugonadal and hypogonadal patients and were not differentially affected by the mode of testosterone replacement. These findings are reassuring that there is no major difference in response to different testosterone replacement regimens.