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D Maiter, R Abs, G Johannsson, M Scanlon, P J Jönsson, P Wilton and M Koltowska-Häggström

Objective: To test the hypothesis whether the effects of GH replacement therapy in adults could be affected by prior pituitary irradiation, the baseline characteristics and response to GH were evaluated in adults with severe GH deficiency (GHD), who had received or not irradiation for the treatment of pituitary adenoma or craniopharyngioma.

Design: Data from 447 patients, who had received radiotherapy (427 in addition to surgery), and 630 patients, who were operated on but not irradiated for their tumour, were retrieved from Pfizer International Metabolic Database (KIMS) and compared at baseline and 1 and 2 years following the onset of GH replacement.

Results: Irradiated and non-irradiated patients exhibited the expected phenotype of GHD at baseline. However, irradiated patients had a greater impairment in the quality of life (QoL), a higher fat mass, lower high-density lipoprotein cholesterol levels and a lower bone mineral content (BMC) than non-irradiated patients. Treatment with GH induced similar changes in both groups. After 1 year of GH replacement, there was an increase in serum IGF-I and fat-free mass, a reduction in fat mass and an improvement in QoL, all changes being equivalent in irradiated and non-irradiated patients. The lipid profile also improved with the irradiated patients showing a better response. These beneficial effects were maintained and the BMC also increased in both groups by the second year of treatment.

Conclusions: This analysis shows that prior irradiation for pituitary adenoma or craniopharyngioma does not compromise the beneficial effects of GH replacement therapy.

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U Feldt-Rasmussen, R Abs, BA Bengtsson, H Bennmarker, M Bramnert, E Hernberg-Stahl, JP Monson, B Westberg, P Wilton and C Wuster

OBJECTIVE: To compare baseline characteristics in adult patients with growth hormone (GH) deficiency (GHD) who had previously been treated for Cushing's disease or acromegaly with data from patients with GHD of other aetiologies. To study the effects of GH therapy in those patients who had completed at least 6 months of GH replacement. DESIGN: Data from a large outcomes research database (KIMS (Pharmacia International Metabolic Database)). METHODS: 135 patients were identified with previous Cushing's disease, 40 had had acromegaly, and 1392 had GHD of other aetiologies. The number of additional hormone deficiencies, and the mean age of the patients were similar in the three groups. Similar proportions of patients in each group were treated using surgery, but radiotherapy was used more often in patients with acromegaly than those with other diagnoses. RESULTS: At baseline, the prevalence of diabetes mellitus and hypertension were significantly higher in the group treated for Cushing's disease, and the prevalence of stroke was significantly higher in the group treated for acromegaly. The incidence of coronary heart disease and claudication were similar in all three groups. Patients treated for Cushing's disease had lower bone mineral density and suffered fractures more often than other GHD adults. Body mass index, waist-hip ratio, serum concentrations of lipids and standard deviation scores of serum concentrations of insulin-like-growth factor-I were similar in the three groups. The dose of GH administered was comparable in the three groups and the effects of GH replacement on waist circumference, blood pressure and quality of life were also similar across the groups. The numbers and types of adverse events reported were not different between the groups. CONCLUSIONS: These data suggest that the characteristics of patients in these diagnostic groups depend on the primary disease which resulted in GHD, and that the clinical expression of GHD does not differ between the groups. Patients with previous hypercortisolism showed more long-term effects of their disease, such as diabetes mellitus, hypertension and fractures. A benefit from GH replacement was evident in patients previously treated for acromegaly and Cushing's disease particularly in relation to quality of life.

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Roger Abs, Ulla Feldt-Rasmussen, Anders F Mattsson, John P Monson, Bengt-Åke Bengtsson, Miklós I Góth, Patrick Wilton and Maria Koltowska-Häggström

Objective: The aim of the present study was to clarify the relationship between GH deficiency (GHD) and some cardiovascular risk factors and to analyse the effect of GH replacement therapy in a large number of patients over a prolonged period of time.

Design: Data for analysis were retrieved from KIMS (Pfizer International Metabolic Database). Serum concentrations of total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides were obtained from 2589 patients at baseline and from 1206 patients after 1 and 2 years of GH replacement therapy. Body mass index (BMI), waist and hip, resting blood pressure and body composition were also measured.

Results: At baseline, the unfavourable effects of GHD were most obvious in the lipid profile demonstrating elevated mean total and LDL-cholesterol, in the increased waist circumference and the elevated BMI. The cholesterol concentration, BMI and body composition were significantly adversely affected by a number of factors, including age, sex and the use of anti-epileptic drugs. The therapeutic effect of GH was essentially uniform across the whole population. GH replacement reduced significantly the mean total and LDL-cholesterol, the waist circumference and the fat mass and was maintained during 2 years.

Conclusions: This analysis of a large number of patients confirmed that GHD adults present with an increased cardiovascular risk. The sustained improvement of the adverse lipid profile and body composition suggests that GH replacement therapy may reduce the risk of cardiovascular disease and the premature mortality seen in hypopituitary patients with untreated GHD.

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T T L L Chung, W M Drake, P N Plowman, K Metcalfe, A B Grossman, S A Akker, S L Chew, G M Besser, D M Walker, M Koltowska-Haggstrom, P Wilton, A F Mattsson and J P Monson

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Rolf C Gaillard, Anders F Mattsson, Ann-Charlotte Åkerblad, Bengt-Åke Bengtsson, José Cara, Ulla Feldt-Rasmussen, Maria Kołtowska-Häggström, John P Monson, Bernhard Saller, Patrick Wilton and Roger Abs

Objective

Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients.

Design

In KIMS (Pfizer International Metabolic Database) 13 983 GH-deficient patients with 69 056 patient-years of follow-up were available.

Methods

This study analysed standardised mortality ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of adequacy of GH replacement. Statistical significance was set to P<0.05.

Results

All-cause mortality was 13% higher compared with normal population rates (SMR, 1.13; 95% confidence interval, 1.04–1.24). Significant associations were female gender, younger age at follow-up, underlying diagnosis of Cushing's disease, craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After controlling for confounding factors, there were statistically significant negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement and SMR. For cause-specific mortality there was a negative association between 1-year IGF1 SDS and SMR for deaths from cardiovascular diseases (P=0.017) and malignancies (P=0.044).

Conclusions

GH-replaced patients with hypopituitarism demonstrated a modest increase in mortality rate; this appears lower than that previously published in GH-deficient patients. Factors associated with increased mortality included female gender, younger attained age, aetiology and lower IGF1 SDS during therapy. These data indicate that GH replacement in hypopituitary adults with GH deficiency may be considered a safe treatment.