Coronary risk in growth hormone deficient hypopituitary adults: increased predicted risk is due largely to lipid profile abnormalities

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. European Journal of Endocrinology 161 S75-S83

Section: Discussionmentioning

confidence: 99%

From isolated GH deficiency to multiple pituitary hormone deficiency: an evolving continuum – a KIMS analysis

Klose

Jonsson²,

Abs³

et al. 2009

“…Increased mortality ratio is observed in both CD (1) and hypopituitary patients without GH replacement (21)(22)(23)(24)(25), most often related to cardio-and cerebrovascular risk factors. GH replacement has been shown to improve the adverse body composition, cardiovascular risk factors (25,26), and poor QoL associated with GHD (27,28).…”

Section: Analysis Bmentioning

confidence: 99%

“…GH replacement has been shown to improve the adverse body composition, cardiovascular risk factors (25,26), and poor QoL associated with GHD (27,28). In CD, markers of cardiovascular risk remain abnormal for up to 5 years after surgery (29).…”

Section: Analysis Bmentioning

confidence: 99%

Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease

Höybye¹,

Ragnarsson²,

Jönsson³

et al. 2010

Objective: Patients in remission from Cushing's disease (CD) have many clinical features that are difficult to distinguish from those of concomitant GH deficiency (GHD). In this study, we evaluated the features of GHD in a large cohort of controlled CD patients, and assessed the effect of GH treatment. Design and methods: Data were obtained from KIMS, the Pfizer International Metabolic Database. A retrospective cross-sectional comparison of background characteristics in unmatched cohorts of patients with CD (nZ684, 74% women) and nonfunctioning pituitary adenoma (NFPA; nZ2990, 39% women) was conducted. In addition, a longitudinal evaluation of 3 years of GH replacement in a subset of patients with controlled CD (nZ322) and NFPA (nZ748) matched for age and gender was performed. Results: The cross-sectional study showed a significant delay in GHD diagnosis in the CD group, who had a higher prevalence of hypertension, fractures, and diabetes mellitus. In the longitudinal, matched study, the CD group had a better metabolic profile but a poorer quality of life (QoL) at baseline, which was assessed with the disease-specific questionnaire QoL-assessment of GHD in adults. After 3 years of GH treatment (mean dose at 3 years 0.39 mg/day in CD and 0.37 mg/day in NFPA), total and low-density lipoprotein cholesterol decreased, while glucose and HbAlc increased. Improvement in QoL was observed, which was greater in the CD group (K6 CD group versus K5 NFPA group, P!0.01). Conclusion: In untreated GHD, co-morbidities, including impairment of QoL, were more prevalent in controlled CD. Overall, both the groups responded similarly to GH replacement, suggesting that patients with GHD due to CD benefit from GH to the same extent as those with GHD due to NFPA.

“…During the past two decades, evidence has emerged linking hypopituitarism with cardiovascular risk factors, including hyperlipidaemia (11,12,13,14), visceral adiposity (15,16), insulin resistance (17) and vascular endothelial dysfunction (18,19,20).…”

Section: Introductionmentioning

confidence: 99%

Overall and cause-specific mortality in GH-deficient adults on GH replacement

Gaillard

Mattsson²,

Åkerblad³

et al. 2012

118

108

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 followup, 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 (PZ0.017) and malignancies (PZ0.044). 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.