Thyroid Function in Adults With Prader-Willi Syndrome

Abstract

Abstract Introduction: Prader-Willi syndrome (PWS) is a complex genetic syndrome in which hypothalamic dysfunction leads to extreme appetite (hyperphagia) and pituitary hormone deficiencies (PHD), among others. Compared with the ‘general endocrine population’, the population of adults with PWS is characterized by a high prevalence of intellectual disability (ID) and frequent use of psychotropic drugs. Due to hypotonia and the low muscle mass associated with the syndrome, adults with PWS have a low basal metabolic rate (BMR) and a high risk of developing obesity. Therefore, exercising is extremely important. However, PHD like hypothyroidism can cause fatigue and exercise intolerance. If left untreated, hypothyroidism can lead to a further decrease in BMR, an increase in Body Mass Index (BMI) and increased cardiovascular risk. As mortality in PWS is high (3% yearly) and often related to cardiovascular problems and obesity, it is of utmost importance to optimize thyroid function and other factors affecting BMR. Methods: In 122 adults with PWS (median age 29 y [IQR 21-39], median BMI 29 kg/m2 [IQR 26-36]), we measured TSH, free T4 and T3 (the active form of thyroid hormone) and searched the medical history for use of medication and any pre-existing diagnosis of hypothyroidism. Moreover, we performed an extensive literature search and summarized the current literature on hypothyroidism, T3 and T4 levels in adults with PWS. Results: Hypothyroidism was present in 17% and more prevalent in females (23%) than in males (10%), even though this was not statistically significant (P=0.06). Although within the reference range, serum T3 levels were relatively high compared to free T4 levels. T3 levels were significantly lower in patients that used psychotropic medication (n=45) than in patients that did not (median 1.7 [IQR 1.5-2.0] vs 2.1 [IQR 1.7-2.3], P=0.013). Conclusion: We found a prevalence of hypothyroidism of 17% (compared to 3% in the non-PWS population). T3 levels were relatively high, which might be explained by increased peripheral conversion of T4 to T3 by deiodinase type 2. Levels of the active thyroid hormone T3 were significantly lower in patients using psychotropic medication. Based on our findings, we recommend 1) yearly screening of thyroid hormone levels in adults with PWS to avoid negative effects of untreated hypothyroidism on BMR, BMI and cardiovascular risk and 2) extra monitoring of the active thyroid hormone T3 in patients using psychotropic drugs.