Background/Aims: On behalf of the Drug and Therapeutics, and Ethics Committees of the Pediatric Endocrine Society, we sought to update the guidelines published in

/pdf/guidelines-for-growth-hormone-and-insulin-like-growth-factor-2g2tno4fut.pdf

Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency.

Acromegaly usually occurs owing to a growth-hormone-secreting adenoma in the pituitary gland, which leads to metabolic and anatomical changes in the patient. This Expert Consensus Document outlines the current recommendations for the treatment of acromegaly as determined by the Acromegaly Consensus Group in March 2013.

/pdf/expert-consensus-document-a-consensus-on-the-medical-2uokjvt0rk.pdf

Expert consensus document: A consensus on the medical treatment of acromegaly

BACKGROUND

To our knowledge, no publication providing overarching guidance on the conduct of systematic reviews of observational studies of etiology exists.

METHODS AND FINDINGS

Conducting Systematic Reviews and Meta-Analyses of Observational Studies of Etiology (COSMOS-E) provides guidance on all steps in systematic reviews of observational studies of etiology, from shaping the research question, defining exposure and outcomes, to assessing the risk of bias and statistical analysis. The writing group included researchers experienced in meta-analyses and observational studies of etiology. Standard peer-review was performed. While the structure of systematic reviews of observational studies on etiology may be similar to that for systematic reviews of randomised controlled trials, there are specific tasks within each component that differ. Examples include assessment for confounding, selection bias, and information bias. In systematic reviews of observational studies of etiology, combining studies in meta-analysis may lead to more precise estimates, but such greater precision does not automatically remedy potential bias. Thorough exploration of sources of heterogeneity is key when assessing the validity of estimates and causality.

CONCLUSION

As many reviews of observational studies on etiology are being performed, this document may provide researchers with guidance on how to conduct and analyse such reviews.

/pdf/cosmos-e-guidance-on-conducting-systematic-reviews-and-meta-1j1ds2pql6.pdf

COSMOS-E: Guidance on conducting systematic reviews and meta-analyses of observational studies of etiology.

Acromegaly is a chronic systemic disease with many complications and is associated with increased mortality when not adequately treated. Substantial advances in acromegaly treatment, as well as in the treatment of many of its complications, mainly diabetes mellitus, heart failure, and arterial hypertension, were achieved in the last decades. These developments allowed change in both prevalence and severity of some acromegaly complications and furthermore resulted in a reduction of mortality. Currently, mortality seems to be similar to the general population in adequately treated patients with acromegaly. In this review, we update the knowledge in complications of acromegaly and detail the effects of different acromegaly treatment options on these complications. Incidence of mortality, its correlation with GH (cumulative exposure vs last value), and IGF-I levels and the shift in the main cause of mortality in patients with acromegaly are also addressed.

Systemic Complications of Acromegaly and the Impact of the Current Treatment Landscape: An Update.

Recent advances indicate that biological aging is a potentially modifiable driver of late-life function and chronic disease and have led to the development of geroscience-guided therapeutic trials such as TAME (Targeting Aging with MEtformin). TAME is a proposed randomized clinical trial using metformin to affect molecular aging pathways to slow the incidence of age-related multi-morbidity and functional decline. In trials focusing on clinical end-points (e.g., disease diagnosis or death), biomarkers help show that the intervention is affecting the underlying aging biology before sufficient clinical events have accumulated to test the study hypothesis. Since there is no standard set of biomarkers of aging for clinical trials, an expert panel was convened and comprehensive literature reviews conducted to identify 258 initial candidate biomarkers of aging and age-related disease. Next selection criteria were derived and applied to refine this set emphasizing: (1) measurement reliability and feasibility; (2) relevance to aging; (3) robust and consistent ability to predict all-cause mortality, clinical and functional outcomes; and (4) responsiveness to intervention. Application of these selection criteria to the current literature resulted in a short list of blood-based biomarkers proposed for TAME: IL-6, TNFα-receptor I or II, CRP, GDF15, insulin, IGF1, cystatin C, NT-proBNP, and hemoglobin A1c. The present report provides a conceptual framework for the selection of blood-based biomarkers for use in geroscience-guided clinical trials. This work also revealed the scarcity of well-vetted biomarkers for human studies that reflect underlying biologic aging hallmarks, and the need to leverage proposed trials for future biomarker discovery and validation.

/pdf/a-framework-for-selection-of-blood-based-biomarkers-for-479n3fwbe4.pdf

A framework for selection of blood-based biomarkers for geroscience-guided clinical trials: report from the TAME Biomarkers Workgroup.

Context: IGF-I plays a central role in metabolism and growth regulation. High IGF-I levels are associated with increased cancer risk and low IGF-I levels with increased risk for cardiovascular disease. Objective: Our objective was to determine the relationship between circulating IGF-I levels and mortality in the general population using random-effects meta-analysis and dose-response metaregression. Data Sources: We searched PubMed, EMBASE, Web of Science, and Cochrane Library from 1985 to September 2010 to identify relevant studies. Study Selection: Population-based cohort studies and (nested) case-control studies reporting on the relation between circulating IGF-I and mortality were assessed for eligibility. Data Extraction: Data extraction was performed by two investigators independently, using a standardized data extraction sheet. Data Synthesis: Twelve studies, with 14,906 participants, were included. Overall, risk of bias was limited. Mortality in subjects with low or high IGF-I levels was compared ...

Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality.

Context: The long-term prevalence of adrenal insufficiency after transsphenoidal surgery for GH-secreting pituitary adenomas is unknown. However, recently a single study reported a high prevalence of adrenal insufficiency in acromegalic patients after surgical and/or medical treatment without postoperative radiotherapy. Objective: The objective of the study was to assess the prevalence and incidence rates of adrenal insufficiency in consecutive patients during long-term follow-up after successful transsphenoidal surgery for acromegaly. Design: In 91 consecutive patients in remission after transsphenoidal surgery only, we retrospectively reviewed insulin tolerance tests, CRH stimulation tests, metyrapone tests, and ACTH stimulation tests used to assess corticotrope function. Results: Early postoperatively, insufficient adrenal function was observed in 16 patients (18%), which was transient in eight and irreversible in eight other patients in the first year of postoperative follow-up. Therefore, after the f...

/pdf/low-incidence-of-adrenal-insufficiency-after-transsphenoidal-4rvy4zymj4.pdf

Low Incidence of Adrenal Insufficiency after Transsphenoidal Surgery in Patients with Acromegaly: A Long-Term Follow-Up Study

Results: Early postoperatively, insufficient adrenal function was observed in 16 patients (18%), which was transient in eight and irreversible in eight other patients in the first year of postoperative follow-up. Therefore, after the first year, the prevalence of adrenal insufficiency was 9%. Late, new-onset adrenal insufficiency developed in only three patients 13, 18, and 24 yr after surgery. The incidence rate of late adrenal insufficiency after successful surgery was 2/1000 person-years. After long-term follow-up, a median of 8.1 (1–31 yr), the prevalence of secondary adrenal insufficiency was 12% in patients in remission after surgery for acromegaly.

Anne Marij G. Burgers

Papers

Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality.

Low Incidence of Adrenal Insufficiency after Transsphenoidal Surgery in Patients with Acromegaly: A Long-Term Follow-Up Study

Low incidence of adrenal insufficiency after transsphenoidal surgery in patients with acromegaly: a long-term follow-up study

Circulating insulin-like growth factor 1 (IGF1) and mortality: meta-analysis and dose-response meta-regression