Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline
01 May 2006-The Journal of Clinical Endocrinology and Metabolism (The Endocrine Society)-Vol. 96, Iss: 6, pp 1587-1609
TL;DR: GH therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD, and the risks associated with GH treatment are low.
Abstract: Growth hormone treatment can provide benefits in body composition, bone, and quality of life in adults with confirmed growth hormone deficiency.
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TL;DR: Treatment of Cushing's syndrome is essential to reduce mortality and associated comorbidities and the choice of second-line treatments, including medication, bilateral adrenalectomy, and radiation therapy, must be individualized to each patient.
Abstract: Objective: The objective is to formulate clinical practice guidelines for treating Cushing's syndrome. Participants: Participants include an Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. The European Society for Endocrinology co-sponsored the guideline. Evidence: The Task Force used the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned three systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process: The Task Force achieved consensus through one group meeting, several conference calls, and numerous e-mail communications. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Conclusions: Treatment of Cushing's syndrome is essential to reduce mortality and associ...
838 citations
TL;DR: GH and IGF-I secretion are decreased in aging individuals, and abnormalities in the GH/IGF-I axis play a role in the pathogenesis of the osteoporosis of anorexia nervosa and after glucocorticoid exposure.
Abstract: GH and IGF-I are important regulators of bone homeostasis and are central to the achievement of normal longitudinal bone growth and bone mass. Although GH may act directly on skeletal cells, most of its effects are mediated by IGF-I, which is present in the systemic circulation and is synthesized by peripheral tissues. The availability of IGF-I is regulated by IGF binding proteins. IGF-I enhances the differentiated function of the osteoblast and bone formation. Adult GH deficiency causes low bone turnover osteoporosis with high risk of vertebral and nonvertebral fractures, and the low bone mass can be partially reversed by GH replacement. Acromegaly is characterized by high bone turnover, which can lead to bone loss and vertebral fractures, particularly in patients with coexistent hypogonadism. GH and IGF-I secretion are decreased in aging individuals, and abnormalities in the GH/IGF-I axis play a role in the pathogenesis of the osteoporosis of anorexia nervosa and after glucocorticoid exposure.
772 citations
TL;DR: Using an evidence-based approach, this guideline addresses important clinical issues regarding the evaluation and management of hypopituitarism in adults, including appropriate biochemical assessments, specific therapeutic decisions to decrease the risk of co-morbidities due to hormonal over-replacements or under-replacement, and managing hypopitsuits during pregnancy, pituitary surgery, and other types of surgeries.
Abstract: Objective: To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults. Participants: The participants include an Endocrine Society-appointed Task Force of six experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology co-sponsored this guideline. Evidence: The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the Pituitary Society, and the European Society of ...
496 citations
TL;DR: The number of childhood cancer survivors is expected to increase as a result of the rising pediatric cancer incidence and improved long-term survival rates and the Childhood Cancer Survivor Study has improved the understanding of the long- term mortality and morbidity in this high-risk population.
Abstract: Cancer is diagnosed in >12 000 children and adolescents in the United States each year.1 Progress in cancer therapeutics over the past 40 years has remarkably improved survival rates for most childhood malignancies. For all pediatric cancers, 5-year survival increased from 58% for children diagnosed between 1975 and 1977 to 82% for those diagnosed between 1999 and 2006.2 In the United States, this success translates into >325 000 survivors of childhood cancer, of whom 24% are now >30 years from diagnosis.3 During this same period, the incidence of many histological subtypes of childhood cancer has increased, including acute lymphoblastic leukemia (ALL), acute myeloid leukemia, non-Hodgkin lymphoma, neuroblastoma, and soft-tissue and germ-cell tumors.3 Consequently, the number of childhood cancer survivors is expected to increase as a result of the rising pediatric cancer incidence and improved long-term survival rates.3
The increasing number of survivors soon revealed acute and delayed modality-specific toxicities and their impact on quality of life and early mortality. In their seminal 1974 publication, Meadows and D’Angio4 described the wide array of potential late effects of successful therapy for childhood cancer. In the past 2 decades, the Childhood Cancer Survivor Study has also improved our understanding of the long-term mortality and morbidity in this high-risk population. Among young adult survivors of childhood cancer diagnosed between 1970 and 1986, at least 1 of 6 domains of health status (general health, mental health, functional status, activity limitations, cancer-related pain, and cancer-related anxiety) declined moderately to severely in 44%.5 The cumulative incidence of a chronic health condition 30 years after cancer diagnosis is now 73%, with a cumulative incidence of 42% for severe, disabling, or life-threatening conditions or death attributable to a chronic condition.6 Also by 30 years after cancer diagnosis, the cumulative mortality rate from causes …
417 citations
TL;DR: Updated information regarding the early diagnosis and management of individuals with Prader-Willi syndrome is important for all physicians and will be helpful in anticipating and managing or modifying complications associated with this rare obesity-related disorder.
Abstract: Introduction
Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. There are three main genetic subtypes in PWS: paternal 15q11-q13 deletion (65–75 % of cases), maternal uniparental disomy 15 (20–30 % of cases), and imprinting defect (1–3 %). DNA methylation analysis is the only technique that will diagnose PWS in all three molecular genetic classes and differentiate PWS from Angelman syndrome. Clinical manifestations change with age with hypotonia and a poor suck resulting in failure to thrive during infancy. As the individual ages, other features such as short stature, food seeking with excessive weight gain, developmental delay, cognitive disability and behavioral problems become evident. The phenotype is likely due to hypothalamic dysfunction, which is responsible for hyperphagia, temperature instability, high pain threshold, hypersomnia and multiple endocrine abnormalities including growth hormone and thyroid-stimulating hormone deficiencies, hypogonadism and central adrenal insufficiency. Obesity and its complications are the major causes of morbidity and mortality in PWS.
414 citations
References
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TL;DR: A system for grading the quality of evidence and the strength of recommendations that can be applied across a wide range of interventions and contexts is developed, and a summary of the approach from the perspective of a guideline user is presented.
Abstract: Users of clinical practice guidelines and other recommendations need to know how much confidence they can place in the recommendations Systematic and explicit methods of making judgments can reduce errors and improve communication We have developed a system for grading the quality of evidence and the strength of recommendations that can be applied across a wide range of interventions and contexts In this article we present a summary of our approach from the perspective of a guideline user Judgments about the strength of a recommendation require consideration of the balance between benefits and harms, the quality of the evidence, translation of the evidence into specific circumstances, and the certainty of the baseline risk It is also important to consider costs (resource utilisation) before making a recommendation Inconsistencies among systems for grading the quality of evidence and the strength of recommendations reduce their potential to facilitate critical appraisal and improve communication of these judgments Our system for guiding these complex judgments balances the need for simplicity with the need for full and transparent consideration of all important issues
7,608 citations
TL;DR: It is concluded that growth hormone has a role in the regulation of body composition in adults, probably through its anabolic and lipolytic actions.
Abstract: In a double-blind, placebo-controlled trial, we studied the effects of six months of growth hormone replacement in 24 adults with growth hormone deficiency. Most of the patients had acquired growth hormone deficiency during adulthood as a consequence of treatment for pituitary tumors, and all were receiving appropriate thyroid, adrenal, and gonadal hormone replacement. The daily dose of recombinant human growth hormone (rhGH) was 0.07 U per kilogram of body weight, given subcutaneously at bedtime. The mean (+/- SE) plasma concentration of insulin-like growth factor I increased from 0.41 +/- 0.05 to 1.53 +/- 0.16 U per liter during rhGH treatment. Treatment with rhGH had no effect on body weight. The mean lean body mass, however, increased by 5.5 +/- 1.1 kg (P less than 0.0001), and the fat mass decreased by 5.7 +/- 0.9 kg (P less than 0.0001) in the group treated with growth hormone; neither changed significantly in the placebo group. The basal metabolic rate, measured at base line and after one and six months of rhGH administration, increased significantly; the respective values were 32.4 +/- 1.4, 37.2 +/- 2.2, and 34.4 +/- 1.6 kcal per kilogram of lean body mass per day (P less than 0.001 for both comparisons). Fasting plasma cholesterol levels were lower (P less than 0.05) in the rhGH-treated group than in the placebo group, whereas plasma triglyceride values were similar in the two groups throughout the study. We conclude that growth hormone has a role in the regulation of body composition in adults, probably through its anabolic and lipolytic actions.
1,411 citations
TL;DR: The observations indicate that life expectancy is shortened in patients with hypopituitarism, and growth-hormone deficiency could be a factor in this increased mortality from cardiovascular disease.
1,394 citations
TL;DR: This long-term follow-up of the Cholesterol Lowering Atherosclerosis Study cohort indicated that progression of coronary artery disease was predictive of coronary events, and the objective was to determine whether carotid arterial intima-media thickness predicts coronary events.
Abstract: Background: Carotid arterial intima-media thickness is used as a noninvasive surrogate end point to measure progression of atherosclerosis, but its relation to coronary events has not been fully ex...
1,226 citations
TL;DR: Age at diagnosis, female sex, and above all, craniopharyngioma were significant independent risk factors and specific endocrine-axis deficiency, with the exception of untreated gonadotropin deficiency, does not seem to have a role.
912 citations