INTRODUCTION: Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of expression of paternally transcribed genes in a highly imprinted region of chromosome 15q11-13. The clinical phenotype has been well characterized, mostly related to hypothalamic dysfunction. Even though central hypothyroidism has been documented in 20-30% of patients with PWS, thyroid function during the first 2 years of life has not been clearly defined. OBJECTIVE: To evaluate hypothalamic-pituitary-thyroid function in infant PWS patients. STUDY DESIGN: Eighteen patients with PWS, aged 0.16-2 years, were included in a prospective study. PWS diagnosis was based on clinical features and molecular analysis. Serum total (T) T4, free (F) T4, T3 and thyroid-stimulating hormone (TSH) were evaluated in the patients with PWS included in the study. Serum hormone values were compared to those of a large reference population of the same age. RESULTS: In 13 of 18 patients with PWS (72.2%), serum TT4 and/or FT4 levels were below the 2.5th percentile of the reference population, while in only one PWS patient serum T3 was below this cut-off. CONCLUSION: The results of this study suggest that transient or definitive thyrotropin-releasing hormone (TRH)-TSH thyroid axis dysfunction may frequently be present in infant PWS patients. Paediatricians should be aware of this dysfunction in this critical period of thyroid hormone action on neurological development.
INTRODUCTION:Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of expression of paternally transcribed genes in a highly imprinted region of chromosome 15q11-13. The clinical phenotype has been well characterized, mostly related to hypothalamic dysfunction. Even though central hypothyroidism has been documented in 20-30% of patients with PWS, thyroid function during the first 2 years of life has not been clearly defined. OBJECTIVE: To evaluate hypothalamic-pituitary-thyroid function in infantPWSpatients. STUDY DESIGN: Eighteen patients with PWS, aged 0.16-2 years, were included in a prospective study. PWS diagnosis was based on clinical features and molecular analysis. Serum total (T) T4, free (F) T4, T3 and thyroid-stimulating hormone (TSH) were evaluated in the patients with PWS included in the study. Serum hormone values were compared to those of a large reference population of the same age. RESULTS: In 13 of 18 patients with PWS (72.2%), serum TT4 and/or FT4 levels were below the 2.5th percentile of the reference population, while in only one PWSpatient serum T3 was below this cut-off. CONCLUSION: The results of this study suggest that transient or definitive thyrotropin-releasing hormone (TRH)-TSH thyroid axis dysfunction may frequently be present in infantPWSpatients. Paediatricians should be aware of this dysfunction in this critical period of thyroid hormone action on neurological development.
Authors: J C Hodge; E Mitchell; V Pillalamarri; T L Toler; F Bartel; H M Kearney; Y S Zou; W H Tan; C Hanscom; S Kirmani; R R Hanson; S A Skinner; R C Rogers; D B Everman; E Boyd; C Tapp; S V Mullegama; D Keelean-Fuller; C M Powell; S H Elsea; C C Morton; J F Gusella; B DuPont; A Chaubey; A E Lin; M E Talkowski Journal: Mol Psychiatry Date: 2013-04-16 Impact factor: 15.992