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Hypogonadotropic Hypogonadism in Males with Glycogen Storage Disease Type 1

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

Abstract

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.

Keywords

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

References

  1. Baillargeon J et al (2015) Risk of venous thromboembolism in men receiving testosterone therapy. Mayo Clin Proc 90:1038–1045CrossRefPubMedGoogle Scholar
  2. Bali DS et al (2013) Glycogen storage disease type I. In: Pagon RA et al (eds) GeneReviews® [Internet]. University of Washington, Seattle; 1993–2016. http://www.ncbi.nlm.nih.gov/books/NBK1312/. Retrived 1 May 2016
  3. Bhasin S et al (2010) Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 95:2536–2559CrossRefPubMedGoogle Scholar
  4. Borst SE et al (2014) Cardiovascular risks and elevation of serum DHT vary by route of testosterone administration: a systematic review and meta-analysis. BMC Med 12:211CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bousson V et al (2001) Distribution of intracortical porosity in human midfemoral cortex by age and gender. J Bone Miner Res 16:1308–1317CrossRefPubMedGoogle Scholar
  6. Breen KM, Karsch FJ (2006) New insights regarding glucocorticoids, stress and gonadotropin suppression. Front Neuroendocrinol 27:233–245CrossRefPubMedGoogle Scholar
  7. Clarke BL, Khosla S (2010) Physiology of bone loss. Radiol Clin North Am 48:483–495CrossRefPubMedPubMedCentralGoogle Scholar
  8. Corona G et al (2014) Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert Opin Drug Saf 13:1327–1351CrossRefPubMedGoogle Scholar
  9. Duan Y et al (1999) Parathyroid hormone deficiency and excess: similar effects on trabecular bone but differing effects on cortical bone. J Clin Endocrinol Metab 84(2):718–722CrossRefPubMedGoogle Scholar
  10. Dunger DB et al (1982) Growth and endocrine changes in the hepatic glycogenoses. Eur J Pediatr 138:226–320CrossRefPubMedGoogle Scholar
  11. Fernandez-Balsells MM et al (2010) Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab 95:2560–2575CrossRefPubMedGoogle Scholar
  12. Gaillard RC, Wehrenberg WB (1996) Glucocorticoids and growth. Curr Opin Endocrinol Diabetes 3:227–232CrossRefGoogle Scholar
  13. Giannini S et al (1997) Bone density and skeletal metabolism in patients with orthotopic ileal neobladder. J Am Soc Nephrol 8(10):1553–1559PubMedGoogle Scholar
  14. Giannitrapani L et al (2006) Sex hormones and risk of liver tumor. Ann N Y Acad Sci 1089:228–236CrossRefPubMedGoogle Scholar
  15. Gore AC et al (2006) Glucocorticoid repression of the reproductive axis: effects on GnRH and gonadotropin subunit mRNA levels. Mol Cell Endocrinol 256:40–48CrossRefPubMedGoogle Scholar
  16. Greenspan SL et al (2005) Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer. J Clin Endocrinol Metab 90:6410–6417CrossRefPubMedGoogle Scholar
  17. Khosla S et al (2008) Comparison of sex steroid measurements in men by immunoassay versus mass spectroscopy and relationships with cortical and trabecular volumetric bone mineral density. Osteoporos Int 19:1465–1471CrossRefPubMedPubMedCentralGoogle Scholar
  18. Luton JP et al (1977) Reversible gonadotropin deficiency in male Cushing’s disease. J Clin Endocrinol Metab 45:488–495CrossRefPubMedGoogle Scholar
  19. Noto RA et al (2003) Improved growth with growth hormone therapy in a child with glycogen storage disease Ib. Acta Paediatr 92:977–985CrossRefPubMedGoogle Scholar
  20. Saketos M et al (1993) Suppression of the hypothalamic-pituitary-ovarian axis in normal women by glucocorticoids. Biol Reprod 49:1270–1276CrossRefPubMedGoogle Scholar
  21. Santiago JV et al (1980) Epinephrine, norepinephrine, glucagon, and growth hormone release in association with physiological decrements in the plasma glucose concentration in normal and diabetic man. J Clin Endocrinol Metab 51:877–883CrossRefPubMedGoogle Scholar
  22. Silverberg SJ et al (1989) Skeletal disease in primary hyperparathyroidism. J Bone Miner Res 4:283–291CrossRefPubMedGoogle Scholar
  23. Weaver CM, Heaney RP (2013) Nutrition and osteoporosis. In: Rosen CJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism. Wiley, Ames, pp 361–364CrossRefGoogle Scholar
  24. Wolfsdorf JI, Holm IA, Weinstein DA (1999) Glycogen storage diseases: phenotypic, genetic, and biochemical characteristics and therapy. Endocrinol Metab Clin North Am 28(4):801–823CrossRefPubMedGoogle Scholar

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
  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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