Prader-Willi syndrome is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity and learning difficulties. Hypogonadism occurs in both males and females, manifested by genital hypoplasia, incomplete pubertal development, and infertility. Type 2 diabetes mellitus is common in obese individuals, most likely secondary to hyperphagia. Diabetes is often difficult to control owing to learning disabilities and hyperphagia.
We report two cases of PWS in whom diabetes control significantly improved after testosterone replacement therapy (TRT).
1. SF 35-year-old male was diagnosed to have type 2 diabetes in 2005 with an HbA1c of 11.5%. Maximum oral hypoglycaemic therapy led to reduction of HbA1c to only 9.6%. He was found to have primary hypogonadism (testosterone 2.2 nmol/l, elevated LH and FSH). TRT initially with testosterone gel followed by Nebido® (Testosterone Undecanoate) resulted in a marked improvement in HbA1c to 5.3%. Oral hypoglycaemic agents were reduced in dose. His weight decreased from 92 to 81 kg.
2. SV 26-year-old male was referred with insulin-treated type 2 diabetes and hypogonadism previously managed by testosterone implant without level monitoring. His TRT was switched to Nebido®. His HbA1c fell from 7.9 to 5.2. Insulin therapy was stopped and his diabetes controlled on metformin only.
These two cases underline the importance of detection and adequate treatment of hypogonadism in PWS in relation to glycaemic control. Apart from the effect on osteoporosis and behavioural problems testosterone replacement in PWS significantly improves diabetes. Testosterone has been demonstrated to improve insulin sensitivity in men with type 2 diabetes and to reduce waist circumference and percentage body fat1.
1. Kapoor D, et al. Eur J Endocrinol 2006 154 899906.