Endocrine Abstracts

Introduction: The glycogen storage disease (GSD) is a rare disorder of carbohydrate metabolism resulting from the defective synthesis and utilization of glycogen. GSD-1a is a subtype of GSD caused by a deficiency in glucose-6-phosphatase activity, which leads to decreased conversion of glucose-6-phosphate to glucose. The dominant features at presentation are hypoglycemia and lactic acidemia. Long-term complications include blood glucose lability, lactic acidemia, short stature, decreased bone mineral density, delayed puberty, hypertension, dyslipidemia and hepatic adenomas. Hypogonadotropic hypogonadism has been hypothesized as a possible complication. It may be explained by recurrent hypoglycemia in GSD patients, as the subsequent elevation in cortisol may lead to suppression of GnRH, LH and FSH. Treatment with testosterone is directed at restoring levels to normal but must always be carefully considered.

Case report: A 20-year-old male was referred to our Endocrinology outpatient clinic due to suspected hypogonadotropic hypogonadism. The patient was diagnosed with GSD-1a at the age of 9 months and referred periods of poor therapeutic compliance during late childhood and adolescence. Since the age of 14, he was followed in a Pediatric Endocrinology outpatient clinic due to the absence of secondary sexual characteristics and at the age of 20 was medicated with testosterone enantate (50 mg every 4 weeks) during 4 months. The left-hand wrist X-ray before testosterone therapy showed bone age equal to chronological age. Family target height was 173±8 cm and both parents reported normal pubertal development. In the Endocrinology first appointment (1 month after testosterone suspension), the physical exam revealed height 166 cm, Tanner stage 5 pubic hair, Tanner stage 3 axillary hair, testicular volume < 4mL and absence of facial hair. Blood analysis (3 months after testosterone suspension) showed low serum testosterone concentration with low serum LH and FSH and low GH and IGF-1. The other pituitary axis hormones, ferritin and iron saturation were normal. Pituitary and head MRI was normal. He initiated testosterone undecanoate therapy (1000 mg every 12 weeks) and has current normal testosterone values.

Discussion: Distinguishing between constitutional delayed growth and puberty and hypogonadotropic hypogonadism may be difficult. In this case, the absence of spontaneous pubertal development until the age of 18, the underlying disease, having no family history of delayed puberty and the fact that the bone age is equal to chronological age may be in favor of hypogonadism. Poor therapeutic compliance during childhood and adolescence may have contributed to recurrent hypoglycemia and hyperlactatemia and consequently hypogonadotropic hypogonadism.