Hypogonadotropic Hypogonadism in Males with Glycogen Storage Disease Type 1.
BACKGROUND
Glycogen storage disease type 1 is an autosomal recessive disorder with an incidence of 1 in 100,000. Long-term complications include chronic blood glucose lability, lactic academia, short stature, osteoporosis, delayed puberty, gout, progressive renal insufficiency, systemic or pulmonary hypertension, hepatic adenomas at risk for malignant transformation, anemia, vitamin D deficiency, hyperuricemic nephrocalcinosis, inflammatory bowel syndrome (type 1b), hypertriglyceridemia, and irregular menstrual cycles. We describe hypogonadotropic hypogonadism as a novel complication in glycogen storage disease (GSD) type 1. Case Studies and Methods: Four unrelated patients with GSD 1a (N = 1) and 1b (N = 3) were found to have hypogonadotropic hypogonadism diagnosed at different ages. Institutional Research Ethics Board approval was obtained as appropriate. Participant consent was obtained. A retrospective chart review was performed and clinical symptoms and results of investigations summarized as a case series.


RESULTS
All patients were confirmed biochemically to have low luteinizing hormone (LH) and follicular stimulating hormone (FSH), and correspondingly low total testosterone. Clinical symptoms of hypogonadism varied widely. Investigations for other causes of hypogonadotropic hypogonadism were unremarkable. In addition, all patients were found to have disproportionately low bone mineral density at the lumbar spine compared to the hip. Common to all patients was erratic metabolic control, including recurrent hypoglycemia and elevated lactate levels.


CONCLUSIONS
Recurrent elevations in cortisol in response to hypoglycemia may be the underlying pathology leading to suppression of gonadotropin-releasing hormone (GnRH) release. Incorporating clinical and/or biochemical screening of the hypothalamic-pituitary-gonadal axis may be important in the management of this disease. Testosterone therapy however needs to be carefully considered because of the risk of hepatic adenomas.
Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
Evelyn M
EM
Wong
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Anna
A
Lehman
Department of Pediatrics and Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
Philip
P
Acott
Division of Biochemical Disease, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
Jane
J
Gillis
Division of Pediatric Endocrinology, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
Daniel L
DL
Metzger
Division of Endocrinology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada. Sandra.Sirrs@vch.ca.|Gordon and Leslie Diamond Centre, Adult Metabolic Diseases Clinic, 2775 Laurel St., Level 4, Vancouver, BC, Canada, V5Z 1M9. Sandra.Sirrs@vch.ca.
Sandra
S
Sirrs
Glycogen storage disease type I; Hypoglycemia; Hypogonadotropic hypogonadism; Male hypogonadism; Metabolic bone disease; Testosterone