Obesity is reaching an epidemic state and has a major impact on health and economy. In most cases, obesity is caused by lifestyle factors. However, the risk of becoming obese differs highly between... Show moreObesity is reaching an epidemic state and has a major impact on health and economy. In most cases, obesity is caused by lifestyle factors. However, the risk of becoming obese differs highly between people. Individual's differences in lifestyle, genetic, and neuroendocrine factors play a role in satiety, hunger and regulation of body weight. In a small percentage of children and adults with obesity, an underlying hormonal or genetic cause can be found. The aim of this review is to present and compare data on the extreme ends of the obesity and undernutrition spectrum in patients with Prader-Willi syndrome (PWS), Bardet-Biedl syndrome (BBS), acquired hypothalamic obesity in craniopharyngioma patients, and anorexia nervosa. This may give more insight into the role of neuroendocrine factors and might give direction for future research in conditions of severe obesity and underweight. Show less
Context: The phenotype and response to GH treatment of children with an IGF1R defect is insufficiently known.Objective: To develop a clinical score for selecting children with short stature for... Show moreContext: The phenotype and response to GH treatment of children with an IGF1R defect is insufficiently known.Objective: To develop a clinical score for selecting children with short stature for genetic testing and evaluate the efficacy of treatment.Design and Setting: Case series with an IGF1R defect identified in a university genetic laboratory.Patients and Interventions: Of all patients with sufficient clinical data, 18 had (likely) pathogenic mutations (group 1) and 7 had 15q deletions including IGF1R (group 2); 19 patients were treated with GH.Main Outcome Measures: Phenotype and response to GH treatment.Results: In groups 1 and 2, mean (range) birth weight, length, and head circumference (HC) SD scores (SDSs) were -2.1 (-3.7 to -0.4), -2.7 (-5.0 to -1.0), and -1.6 (-3.0 to 0.0), respectively. At presentation, height, HC, and serum IGF-1 SDSs were -3.0 (-5.5 to -1.7), -2.5 (-4.2 to -0.5), and +1.2 (-1.3 to 3.2), respectively. Feeding problems were reported in 15 of 19 patients. A clinical score with 76% sensitivity is proposed. After 3 years of GH treatment [1.1 (0.2) mg/m 2 /d] height gain in groups 1 (n = 12) and 2 (n = 7) was 0.9 SDS and 1.3 SDS (at a mean IGF-1 of 3.5 SDS), less than reported for small for gestational age (1.8 SDS).Conclusion: A clinical score encompassing birth weight and/or length, short stature, microcephaly, and IGF-1 is useful for selecting patients for IGF1R analysis. Feeding problems are common and the growth response to GH treatment is moderate. Show less
Finken, M.J.J.; Steen, M. van der; Smeets, C.C.J.; Walenkamp, M.J.E.; Bruin, C. de; Hokken-Koelega, A.C.S.; Wit, J.M. 2018
Context and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. Design and... Show moreContext and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. Design and Participants: A randomized, placebo-controlled, double-blind, dose-response study was performed in 10 centers in The Netherlands. One hundred thirty-three patients with TS were included in age group 1 (2-7.99 yr), 2 (8-11.99 yr), or 3 (12-15.99 yr). Patients were treated with GH (1.33 mg/m(2) . d) from baseline, combined with placebo(Pl) or Oxin low (0.03 mg/kg . d) or conventional (0.06 mg/kg . d) dose from the age of 8 yr and estrogens from the age of 12 yr. Adult height gain (adult height minus predicted adult height) and safety parameters were systematically assessed. Results: Compared with GH + Pl, GH + Ox 0.03 increased adult height gain in the intention-to-treat analysis (mean +/- SD, 9.5 +/- 4.7 vs. 7.2 +/- 4.0 cm, P < 0.02) and per-protocol analysis (9.8 +/- 4.9 vs. 6.8 +/- 4.4 cm, P = 0.02). Partly due to accelerated bone maturation (P < 0.001), adult height gain on GH + Ox 0.06 was not significantly different from that on GH + Pl (8.3 +/- 4.7 vs. 7.2 +/- 4.0 cm, P = 0.3). Breast development was slower on GH + Ox (GH + Ox 0.03, P = 0.02; GH + Ox 0.06, P = 0.05), and more girls reported virilization on GH + Ox 0.06 than on GH + Pl (P < 0.001). Conclusions: In GH-treated girls with TS, we discourage the use of the conventional Ox dosage (0.06 mg/kg . d) because of its low benefit to risk ratio. The addition of Ox 0.03 mg/kg . d modestly increases adult height gain and has a fairly good safety profile, except for some deceleration of breast development. (J Clin Endocrinol Metab 95: 1151-1160, 2010) Show less
