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Ho K.K.Y.,Centres for Health Research | Ho K.K.Y.,University of Queensland | Ho K.K.Y.,Queensland University of Technology
Journal of Clinical Endocrinology and Metabolism

This manuscript is based on an invitation lecture entitled "The Year in Pituitary" presented at the Combined 94th Annual Meeting of The Endocrine Society and of the International Congress of Endocrinology in Chicago, Illinois, on June 24, 2014. The purpose is to highlight the major advances in the pathogenesis and management of pituitary disease. The papers selected were published from major journals between January 2013 and June 2014. The material covered basic to clinical advances across pathogenesis, epidemiology, and therapy in pituitary medicine. Copyright © 2014 by the Endocrine Society. Source

Birzniece V.,Garvan Institute of Medical Research | Birzniece V.,University of New South Wales | Birzniece V.,University of Western Sydney | Magnusson N.E.,University of Aarhus | And 4 more authors.
European Journal of Endocrinology

Context : GH action is attenuated by estrogens and selective estrogen receptor modulators (SERMs) administered orally. During GH therapy in hypopituitary women, co-treatment with raloxifene, a SERM, induced a smaller gain in lean body mass (LBM) compared with estrogen, despite an equal reduction in IGF1. As a higher IGF-binding protein-3 (IGFBP3) level was observed with raloxifene co-treatment, we hypothesize that an increase in IGFBP3 reduced IGF1 bioactivity causing the attenuated anabolic effect. Objective: To assess the effects of 17β-estradiol (E2) and raloxifene on bioactive IGF1. Design: In study 1, 12 GH-deficient (GHD) women were randomized to raloxifene 120 mg/day or E2 4 mg/day for 1 month. In study 2, 16 GHD women were randomized to 1 month GH treatment alone (0.5 mg/day) and in combination with raloxifene (60 mg/day) or E2 (2 mg/day). We measured bioactive IGF1, immunoreactive IGF1 and IGF2, and IGFBP3 immunoreactivity and fragmentation. Results: Raloxifene and estrogen suppressed (P<0.05) total IGF1 equally in GHD and GH-replaced hypopituitary women. In GHD patients, neither raloxifene nor estrogen affected bioactive IGF1. GH significantly increased IGF1 bioactivity, an effect attenuated by co-treatment with raloxifene (Δ -23±7%, P<0.01) and estrogen (Δ -26±3%, P=0.06). Total IGF1 correlated (r2=0.54, P<0.001) with bioactive IGF1, which represented 3.1±0.2% of the total IGF1, irrespective of the treatments. Total IGF2 was unchanged by raloxifene and estrogen treatment. IGFBP3 was significantly higher during raloxifene administration, whereas no differences in IGFBP3 fragmentation were observed. Conclusion: Raloxifene effect on bioactive IGF1 is similar to that of estrogen despite higher IGFBP3 levels during raloxifene administration.We conclude that the observed different effects on LBM between raloxifene and estrogen treatments cannot be explained by differences in IGF1 bioactivity. © 2014 European Society of Endocrinology. Source

Yeap B.B.,University of Western Australia | Paul Chubb S.A.,University of Western Australia | Paul Chubb S.A.,PathWest Laboratory Medicine | McCaul K.A.,University of Western Australia | And 4 more authors.
European Journal of Endocrinology

Objective: Circulating IGF1 declines with age while ill-health increases. Controversy remains whether differences in the levels of IGF1 and its binding proteins 1 and 3 (IGFBP1 and IGFBP3) determine health outcomes during ageing.We examined associations of IGF1, IGFBP1 and IGFBP3 with all-cause and cardiovascular mortality in older men. Design: We conducted a prospective cohort study of community-dwelling men aged ≥70 years. Methods: Plasma collected at baseline (2001-2004) was assayed for total IGF1, IGFBP1 and IGFBP3. Incidence and causes of death from time of recruitment to 31 December 2008 were ascertained using the Western Australian Data Linkage System. Cox regression analyses were performed, adjusting for conventional cardiovascular risk factors. Results: Among 3983 men followed for 5.2 years (median), 694 deaths occurred, 243 from cardiovascular disease (CVD). There was no difference in survival according to quintiles of IGF1. Increased IGFBP1 predicted increased all-cause mortality (highest versus lowest quintile: adjusted hazard ratio (HR)=1.98, 95% confidence interval (CI)=1.52-2.57, P<0.001 for trend) and increased cardiovascular mortality (HR=3.42 (2.03-5.77), P<0.001 for trend). Decreased IGFBP3 predicted increased all-cause mortality (lowest versus highest quintile: HR=1.57, 95% CI=1.23-2.01, P=0.007 for trend). Associations of IGFBP1 and IGFBP3 with all-cause mortality were not attenuated by adjustment for IGF1 levels. Conclusions: In older men, higher IGFBP1 and lower IGFBP3 levels predict overall and CVD-related mortality, while IGF1 levels are not associated with mortality. Further studies are needed to clarify the underlying mechanisms by which IGFBP1 and IGFBP3 levels are associated with mortality risk, and whether this occurs independently of IGF1. © 2011 European Society of Endocrinology. Source

Yeap B.B.,University of Western Australia | Chubb S.A.P.,University of Western Australia | Chubb S.A.P.,PathWest Laboratory Medicine | McCaul K.A.,University of Western Australia | And 5 more authors.
European Journal of Endocrinology

Objective: Abdominal aortic aneurysm (AAA) is most prevalent in older men. GH secretion declines with age resulting in reduced IGF1 levels. IGF1 and its binding proteins (IGFBPs) are expressed in vasculature, and lower IGF1 levels have been associated with cardiovascular risk factors and disease. However, the relationship of the IGF1 system with aortic dilation and AAA is unclear. We tested the hypothesis that circulating IGF1 and IGFBPs are associated with AAA and aortic diameter in older men. Design: A cross-sectional analysis involving 3981 community-dwelling men aged 70-89 years was performed. Methods: Abdominal aortic diameter was measured by ultrasound. Plasma total IGF1, IGFBP1 and IGFBP3 were measured by immunoassays. Results: After adjustment for age, body mass index, waist:hip ratio, smoking, hypertension, dyslipidemia, diabetes, coronary heart disease and serumcreatinine, a higher IGF1 levelwas associated withAAA (odds ratio (OR)/1 S.D. increase 1.18, 95% confidence interval (CI) 1.05-1.33, P=0.006), as was the ratio of IGF1/IGFBP3 (OR=1.22, 95% CI 1.10-1.35, P<0.001). Highest IGF1 concentrations compared with lowest quintile were significantly associated with AAA (quintile (Q) 5 vs Q1: OR=1.80, 95% CI 1.20-2.70, P=0.004) aswere IGF1/IGFBP3 ratios (Q5 vs Q1: OR=2.52, 95% CI 1.59-4.02, P<0.001). IGF1 and IGFBP1 were independently associated with aortic diameter (bZ0.200, 95% CI 0.043-0.357, P=0.012 and β=0.274, 95% CI 0.098-0.449, P=0.002 respectively). Conclusions: In older men, higher IGF1 and an increased ratio of IGF1/IGFBP3 are associated with AAA, while IGFBP1 is independently associated with increased aortic diameter. Components of the IGF1 system may contribute to, or be a marker for, aortic dilation in ageing men. © 2012 European Society of Endocrinology. Source

Yeap B.B.,University of Western Australia | Paul Chubb S.A.,University of Western Australia | Paul Chubb S.A.,PathWest Laboratory Medicine | Lopez D.,University of Western Australia | And 4 more authors.
Clinical Endocrinology

Summary Objective Ageing is associated with frailty and decreased anabolic hormones, insulin-like growth factor-I (IGF-I) and testo;?>sterone. We hypothesized that components of the IGF-I system, in conjunction with testosterone, modulate frailty risk in the elderly. We examined associations between IGF-I, its binding proteins IGFBP1 and IGFBP3 and testosterone with frailty in men. Design Observational study of 3 447 community-dwelling men aged 70-89 years assessed in 2001-04, with 1 654 reassessed in 2008-09. Methods Baseline total IGF-I, IGFBP1, IGFBP3 and testosterone were assayed. Frailty was assessed using the FRAIL scale, comprising 5 domains: fatigue; difficulty climbing stairs; difficulty walking >100 m; >5 illnesses; weight loss >5%. Men with ≥ 3 domains were considered frail. Results At baseline, 527 men (15·3%) were frail. Frail men had lower IGFBP3 (3 630 ng/ml vs not frail: 3 800 ng/ml, P < 0·001) and comparable IGFBP1 (23·5 vs 21·5 ng/ml, P = 0·09). In multivariate analyses, higher IGFBP1 was associated with increased prevalence of frailty (highest vs lowest quartile Q4:Q1, adjusted odds ratio [OR] = 1·39, 95% CI = 1·03-1·88) . New-onset frailty arose in 260 (17·5%) of 1 484 men. Lower baseline IGF-I predicted new-onset frailty (Q1:Q4 OR = 1·48, 95% CI = 1·00-2·20) as did higher IGFBP1 (Q4:Q1 OR = 1·59, 95% CI = 1·01-2·50). Men with both IGF-I and free testosterone in Q1 had greater odds of prevalent frailty (OR = 2·13, 95% CI = 1·54-2·95). Conclusions Older men with higher IGFBP1 level, or both lower IGF-I and testosterone, are more likely to be frail, while those with lower IGF-I and higher IGFBP1 are more likely to become frail. Components of the IGF-I system may be biomarkers or independent predictors of frailty. © 2012 Blackwell Publishing Ltd. Source

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