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    ABSTRACT: Context: Acromegaly is associated with reduced life expectancy, which has been reported to be normalized if treatment is successful in controlling GH/IGF-I levels. Objective: Most previous studies have invariably used the last available GH/IGF-I, which may be biased as it only assesses exposure at a single point in time. We compared the last available GH/IGF-I analysis to a "time-dependent" and cumulative method, during follow-up to assess risk of mortality in the West Midlands Acromegaly study (n = 501). Results: Using the last available GH, there was a statistically significant increase in mortality comparing groups as low as GH ≤ 1 μg/L vs >1 μg/L (relative risks [RR] 1.8, P = .03). This was not the case when using the "time-dependent method," where only comparisons of GH values of GH ≤5 μg/L vs >5 μg/L were suggestive of being associated with an increased risk of mortality (RR = 1.5, P = .08). When the time-dependent GH method of analysis was used, the RR of mortality at each level was lower and the associated P value was less significant. Irrespective of using the last available or time-dependent method, when IGF-I was divided into levels according to quartile or arbitrary cutoffs, there was no significant increase in mortality with higher levels. Conclusions: This study emphasizes the potential bias of using the latest available GH/IGF-I levels to predict mortality. Our study again highlights the limitations of IGF-I in predicting mortality.
    No preview · Article · Nov 2013 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease spanning from simple benign steatosis through to steatohepatitis with fibrosis and scarring that can eventually lead to cirrhosis. Its prevalence is rising rapidly and is developing into the leading indication for liver transplantation world-wide. Abnormalities in endocrine axes have been associated with NALFD, including hypogonadism, hypothyroidism, growth hormone deficiency and hypercortisolaemia. In some instances, correction of the endocrine defects has been shown to have a beneficial impact. Whilst in patients with type 2 diabetes the association with NAFLD is well established and recognised, there is a more limited appreciation of the condition amongst common endocrine diseases presenting with hormonal excess or deficiency. In this review, we examine the published data that have suggested a mechanistic link between endocrine abnormalities and NAFLD and summarize the clinical data endorsing these observations.
    No preview · Article · May 2013 · European Journal of Endocrinology
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    ABSTRACT: CONTEXT: Inactivating mutations in the enzyme hexose-6-phosphate dehydrogenase (H6PDH- encoded by H6PD) causes Apparent Cortisone Reductase Deficiency (ACRD). H6PDH generates cofactor NADPH for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 encoded by HSD11B1) oxo-reductase activity, converting cortisone to cortisol. Inactivating mutations in HSD11B1 cause true cortisone reductase deficiency (CRD). Both ACRD and CRD present with HPA axis activation and adrenal hyperandrogenism. OBJECTIVE: To describe the clinical, biochemical and molecular characteristics of two additional female children with ACRD, and to illustrate the diagnostic value of urinary steroid profiling in identifying and differentiating a total of six ACRD and four CRD cases. DESIGN: Clinical, biochemical, and genetic assessment of two female patients presenting during childhood. In addition, results of urinary steroid profiling in a total of ten ACRD/ CRD patients were compared to identify distinguishing characteristics. RESULTS: Case 1 was compound heterozygous for R109AfsX3, and a novel P146L missense mutation in H6PD. Case 2 was compound heterozygous for novel nonsense mutations Q325X and Y446X in H6PD. Mutant expression studies confirmed loss of H6PDH activity in both cases. Urinary steroid metabolite profiling by gas chromatography/ mass spectrometry (GC/MS) suggested ACRD in both cases. In addition, we were able to establish a steroid metabolite signature differentiating ACRD and CRD, providing a basis for genetic diagnosis and future individualized management. CONCLUSIONS: Steroid profile analysis of a 24h-urine collection provides a diagnostic method for discriminating between ACRD and CRD. This will provide a useful tool in stratifying unresolved adrenal hyperandrogenism in children with premature adrenarche, and adult females with PCOS.
    Full-text · Article · Nov 2012 · European Journal of Endocrinology
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