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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Baillargeon J et al (2015) Risk of venous thromboembolism in men receiving testosterone therapy. Mayo Clin Proc 90:1038–1045
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
Bhasin S et al (2010) Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 95:2536–2559
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 12:211
Bousson V et al (2001) Distribution of intracortical porosity in human midfemoral cortex by age and gender. J Bone Miner Res 16:1308–1317
Breen KM, Karsch FJ (2006) New insights regarding glucocorticoids, stress and gonadotropin suppression. Front Neuroendocrinol 27:233–245
Clarke BL, Khosla S (2010) Physiology of bone loss. Radiol Clin North Am 48:483–495
Corona G et al (2014) Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert Opin Drug Saf 13:1327–1351
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):718–722
Dunger DB et al (1982) Growth and endocrine changes in the hepatic glycogenoses. Eur J Pediatr 138:226–320
Fernandez-Balsells MM et al (2010) Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab 95:2560–2575
Gaillard RC, Wehrenberg WB (1996) Glucocorticoids and growth. Curr Opin Endocrinol Diabetes 3:227–232
Giannini S et al (1997) Bone density and skeletal metabolism in patients with orthotopic ileal neobladder. J Am Soc Nephrol 8(10):1553–1559
Giannitrapani L et al (2006) Sex hormones and risk of liver tumor. Ann N Y Acad Sci 1089:228–236
Gore AC et al (2006) Glucocorticoid repression of the reproductive axis: effects on GnRH and gonadotropin subunit mRNA levels. Mol Cell Endocrinol 256:40–48
Greenspan SL et al (2005) Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer. J Clin Endocrinol Metab 90:6410–6417
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 19:1465–1471
Luton JP et al (1977) Reversible gonadotropin deficiency in male Cushing’s disease. J Clin Endocrinol Metab 45:488–495
Noto RA et al (2003) Improved growth with growth hormone therapy in a child with glycogen storage disease Ib. Acta Paediatr 92:977–985
Saketos M et al (1993) Suppression of the hypothalamic-pituitary-ovarian axis in normal women by glucocorticoids. Biol Reprod 49:1270–1276
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 51:877–883
Silverberg SJ et al (1989) Skeletal disease in primary hyperparathyroidism. J Bone Miner Res 4:283–291
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 361–364
Wolfsdorf JI, Holm IA, Weinstein DA (1999) Glycogen storage diseases: phenotypic, genetic, and biochemical characteristics and therapy. Endocrinol Metab Clin North Am 28(4):801–823
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Additional information
Communicated by: Olaf Bodamer, MD PhD
Appendices
Take-Home Message
Hypogonadotropic hypogonadism is an important complication in glycogen storage disease (GSD) type 1 and incorporating clinical and/or biochemical screening of the hypothalamic–pituitary–gonadal axis may be important in the management of this disease.
Details of the Contributions of Individual Authors
All authors have been involved in the conception and design, analysis and interpretation of data, and drafting and revision of the article for important intellectual content.
Name of One Author Who Serves as Guarantor for the Article
SS accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.
Competing Interests
None of the authors have competing interests to declare.
Funding
None.
Patient Consent Statement
The patients have consented to the publication of their medical information.
Rights and permissions
Copyright information
© 2017 SSIEM and Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Wong, E.M., Lehman, A., Acott, P., Gillis, J., Metzger, D.L., Sirrs, S. (2017). Hypogonadotropic Hypogonadism in Males with Glycogen Storage Disease Type 1. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 36. JIMD Reports, vol 36. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_38
Download citation
DOI: https://doi.org/10.1007/8904_2016_38
Received:
Revised:
Accepted:
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-56137-9
Online ISBN: 978-3-662-56138-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)