Relationship of thyroid function with genetic subtypes and treatment with growth hormone in Prader–Willi syndrome
Authors: Schmok Tiffany , Surampalli Abhilasha , Khare Manaswitha , Zandihaghighi Setarah , Baghbaninogourani Rounak , Patolia Brinda , Gold June‐Anne , Naidu Ajanta , Cassidy Suzanne B. , Kimonis Virginia E. 
Published: June 2024

AbstractPrader–Willi syndrome (PWS) is the most common genetic syndrome with obesity and results from loss of expression of paternally inherited genes on chromosome 15q11‐q13 by a variety of mechanisms which include large deletions (70%–75%), maternal uniparental disomy (UPD) (20%–30%), and imprinting defects (2%–5%) or balanced translocations. Individuals often have a characteristic behavior disorder with mild intellectual disability, infantile hypotonia associated with poor sucking, short stature, and obesity. PWS is characterized by hypothalamic–pituitary axis dysfunction with growth hormone (GH) deficiency, hypogonadism, and several other hormonal deficiencies resulting in short stature, centrally driven excessive appetite (hyperphagia), central obesity, cryptorchidism, and decreased lean body mass. In this study, we determined and sought differences in the incidence of thyroid abnormalities among the common genetic subtypes in a cohort of 52 subjects with PWS because there was limited literature available. We also sought the effects of growth hormone (GH) treatment on the thyroid profile. Fifty‐two subjects with a genetically confirmed diagnosis of PWS were included in this study at the University of California, Irvine. Blood samples for baseline thyroxine stimulating hormone (TSH) and free thyroxine (fT4) levels were obtained in the morning after an overnight fast for 8–12 h. Statistical analyses were performed with SPSS (SPSS Inc., 21.0). Mean values were analyzed by one‐way ANOVA, and student's t‐test and statistical significance were set at p < 0.05. The subjects included 26 males and 26 females with an age range of 3–38 years. There were 29 subjects with chromosome 15q11‐q13 deletions and 23 with UPD; 28 were GH treated currently or in the past, and 24 never received GH. There was no significant difference in age or body mass index (BMI) (kg/m2) between GH‐treated versus non‐GH‐treated groups. BMI was higher in the deletion group compared to the UPD group (p = 0.05). We identified two individuals who were clinically diagnosed and treated for hypothyroidism, one of whom was on GH supplements. We identified two additional individuals with subclinical hypothyroidism who were not on GH treatment, giving a frequency of 7.6% (4/52) in this cohort of patients. We did not find significant differences in thyroid function (TSH) in the deletion versus UPD groups. We found significant differences in thyroid function, however, between GH‐treated and non‐GH‐treated groups. The mean TSH was lower (2.25 ± 1.17 uIU/M, range 0.03–4.92 uIU/M versus 2.80 ± 1.44 uIU/M, range 0.55–5.33 uIU/M respectively, p = 0.046), and the free T4 levels were significantly higher (1.13 ± 0.70 and 1.03 ± 0.11 ng/dL, respectively, p = 0.05) in the GH‐treated individuals compared to non‐GH‐treated individuals. In this cohort of subjects with PWS, we identified two previously diagnosed individuals with hypothyroidism and two individuals with subclinical hypothyroidism (4/52, 7.6%), three of whom were not receiving GH treatment. We did not find any significant differences in thyroid function between molecular subtypes; however, we found that euthyroid status (lower TSH levels and higher free T4 levels) was significantly higher in individuals who were treated with GH compared to the untreated group. We recommend that individuals with PWS should be screened regularly for thyroid deficiency and start treatment early with GH in view of the potentially lower incidence of thyroid deficiency.