Short Stature in Childhood - Challenges and Choices
ABSTRACT A family seeks evaluation and treatment of short stature in their 11.5-year-old son. He previously was in the 3rd percentile for height, but his growth rate has slowed during the past 2 years, and his height is now just below the 1st percentile (Fig. 1). His mother is 5 ft 0 in. (152 cm), and his father is 5 ft 6 in. (167 cm). The child's size at birth was normal. His medical history and a review of systems are unremarkable. His physical examination is normal and shows prepubertal development. The complete blood count, erythrocyte sedimentation rate, thyrotropin, tissue transglutaminase antibody, and insulin-like growth factor I (IGF-I) levels and growth hormone levels after provocative testing are normal. His skeletal maturation (bone age) is approximately 9 years, and his predicted adult height is 5 ft 5 in. (165 cm) plus or minus 1.3 in. (3.3 cm).(1) How should his condition be managed?
- SourceAvailable from: sciencedirect.com09/2013; 24(5):847-856. DOI:10.1016/S0716-8640(13)70232-3
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ABSTRACT: Growth hormone (GH) exerts a diverse array of physiological actions that includes prominent roles in growth and metabolism, with a major contribution via stimulating insulin-like growth factor-1 (IGF-1) synthesis. GH achieves its effects by influencing gene expression profiles, and Igf1 is a key transcriptional target of GH signaling in liver and other tissues. This review examines the mechanisms of GH-mediated gene regulation that begin with signal transduction pathways activated downstream of the GH receptor and continue with chromatin events at target genes, and additionally encompasses the topics of negative regulation and crosstalk with other cellular inputs. The transcription factor Stat5b is regarded as the major signaling pathway by which GH achieves its physiological effects, including in stimulating Igf1 gene transcription in liver. Recent studies exploring the mechanisms of how activated Stat5b accomplishes this are highlighted, which begin to characterize epigenetic features at regulatory domains of the Igf1 locus. Further research in this field offers promise to better understand the GH-IGF-1 axis in normal physiology and disease and identify strategies to manipulate the axis to improve human health.Molecular Endocrinology 05/2014; 28(7):me20141099. DOI:10.1210/me.2014-1099 · 4.02 Impact Factor
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ABSTRACT: The prevalence of pediatric obesity in the United States is nearly 17%. Most cases are "exogenous", resulting from excess energy intake relative to energy expenditure over a prolonged period of time. However, some cases of obesity are "endogenous", associated with hormonal, genetic, or syndromic disorders such as hypothyroidism, Cushing's syndrome, growth hormone deficiency, defective leptin signaling, mutations in the melanocortin 4 receptor, and Prader-Willi and Bardet-Biedl syndromes. This article reviews the hormonal, monogenic, and syndromic causes of childhood obesity and identifies critical features that distinguish "endogenous" obesity disorders from the more common exogenous obesity. Findings that raise suspicion for endogenous obesity include onset in infancy, lack of satiety, poor linear growth, dysmorphic features, and cognitive dysfunction. Selection and interpretation of appropriate laboratory tests and indications for subspecialist referral are also discussed. [Pediatr Ann. 2014;43(9):e218-e224.].Pediatric Annals 08/2014; 43(9):e218-e224. DOI:10.3928/00904481-20140825-08 · 0.61 Impact Factor