Hypogonadotropic Hypogonadism in Males with Glycogen Storage Disease Type 1

  • Evelyn M. Wong
  • Anna Lehman
  • Philip Acott
  • Jane Gillis
  • Daniel L. Metzger
  • Sandra SirrsEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 36)


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.

Discussion: 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.


Glycogen storage disease type I Hypoglycemia Hypogonadotropic hypogonadism Male hypogonadism Metabolic bone disease Testosterone 


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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Evelyn M. Wong
    • 1
  • Anna Lehman
    • 2
  • Philip Acott
    • 3
  • Jane Gillis
    • 4
  • Daniel L. Metzger
    • 5
  • Sandra Sirrs
    • 6
    • 7
    Email author
  1. 1.Division of Endocrinology, Department of MedicineUniversity of TorontoTorontoCanada
  2. 2.Department of Medical GeneticsUniversity of British ColumbiaVancouverCanada
  3. 3.Department of Pediatrics and Department of PharmacologyDalhousie UniversityHalifaxCanada
  4. 4.Division of Biochemical DiseaseBC Children’s Hospital, University of British ColumbiaVancouverCanada
  5. 5.Division of Pediatric Endocrinology, BC Children’s HospitalUniversity of British ColumbiaVancouverCanada
  6. 6.Division of EndocrinologyVancouver General Hospital, University of British ColumbiaVancouverCanada
  7. 7.Gordon and Leslie Diamond CentreAdult Metabolic Diseases ClinicVancouverCanada

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