Endocrine Abstracts

Introduction

Prader-Willi syndrome (PWS) is a complex genetic syndrome in which hypothalamic dysfunction leads to hyperphagia and pituitary hormone deficiencies (PHD), among others. The majority of patients have intellectual disability (ID) and use of psychotropic drugs is frequent. Due to hypotonia and the low muscle mass associated with the syndrome, adults with PWS have a low basal metabolic rate (BMR). Combined with hyperphagia, this results in high risk of obesity. Therefore, exercise 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 important to optimize thyroid function and other factors affecting BMR.

Objectives

To investigate the prevalence of hypothyroidism in adults with PWS and to provide practical screening recommendations.

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 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 difference was not statistically significant (P = 0.06). Although within the reference range, serum T3 levels (reference range: 1.3–2.3 nmol/l) were relatively high compared to free T4 levels (reference range: 13.5–24.3 pmol/l). 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% in PWS-adults (compared to 3% in the non-PWS population). 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.