Skip to main content

Advertisement

SpringerLink
Log in

Endocrine function in 97 patients with myotonic dystrophy type 1

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

The aim of this study was to investigate the endocrine function and its association to number of CTG repeats in patients with myotonic dystrophy type 1 (DM1). Concentration of various hormones and metabolites in venous blood was used to assess the endocrine function in 97 patients with DM1. Correlation with CTGn expansion size was investigated with the Pearson correlation test. Eighteen percent of the DM1 patients had hyperparathyroidism with increased PTH compared with 0.5% in the background population. Of these, 16% had normocalcemia and 2% had hypercalcemia. An additional 3% had hypercalcemia without elevation of PTH; 7% had abnormal TSH values (2% subnormal and 5% elevated TSH levels); 5% of the patients had type 2 diabetes mellitus; 17% of the male DM1 patients had increased LH and low levels of plasma testosterone indicating absolute androgen insufficiency. Another 21% had increased LH, but normal testosterone levels, indicating relative insufficiency. Numbers of CTG repeats correlated directly with plasma PTH, phosphate, LH, and tended to correlate with plasma testosterone for males. This is the largest study of endocrine dysfunction in a cohort of Caucasian patients with DM1. We found that patients with DM1 have an increased risk of abnormal endocrine function, particularly calcium metabolism disorders. However, the endocrine dysfunction appears not to be of clinical significance in all of the cases. Finally, we found correlations between CTGn expansion size and plasma PTH, phosphate, and testosterone, and neck flexion strength.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Harper PS (2009) Endocrine and other systemic abnormalities in myotonic dystrophy. In: Bromage M (ed) Myotonic dystrophy. Harcourt Publishers, New York

    Google Scholar 

  2. Klein AF, Gasnier E, Furling D (2011) Gain of RNA function in pathological cases: focus on myotonic dystrophy. Biochimie 93(11):2006–2012

    Article  PubMed  CAS  Google Scholar 

  3. Thornton C (1999) The myotonic dystrophies. Semin Neurol 19:25–33

    Article  PubMed  CAS  Google Scholar 

  4. Morrone A, Pegoraro E, Angelini C, Zammarchi E, Marconi G, Hoffman EP (1997) RNA metabolism in myotonic dystrophy: patient muscle shows decreased insulin receptor RNA and protein consistent with abnormal insulin resistance. J Clin Invest 99:1691–1698

    Article  PubMed  CAS  Google Scholar 

  5. Salehi LB, Bonifazi E, Stasio ED, Gennarelli M, Botta A, Vallo L, Iraci R, Massa R, Antonini G, Angelini C, Novelli G (2007) Risk prediction for clinical phenotype in myotonic dystrophy type 1: data from 2, 650 patients. Genet Test 11:84–90

    Article  PubMed  CAS  Google Scholar 

  6. Perini GI, Menegazzo E, Ermani M, Zara M, Gemma A, Ferruzza E, Gennarelli M, Angelini C (1999) Cognitive impairment and (CTG)n expansion in myotonic dystrophy patients. Biol Psychiatry 46:425–431

    Article  PubMed  CAS  Google Scholar 

  7. Clarke NR, Kelion AD, Nixon J, Hilton-Jones D, Forfar JC (2001) Does cytosine-thymine-guanine (CTG) expansion size predict cardiac events and electrocardiographic progression in myotonic dystrophy? Heart 86:411–416

    Article  PubMed  CAS  Google Scholar 

  8. Melacini P, Villanova C, Menegazzo E, Novelli G, Danieli G, Rizzoli G, Fasoli G, Angelini C, Buja G, Miorelli M (1995) Correlation between cardiac involvement and CTG trinucleotide repeat length in myotonic dystrophy. J Am Coll Cardiol 25:239–245

    Article  PubMed  CAS  Google Scholar 

  9. Annane D, Duboc D, Mazoyer B, Merlet P, Fiorelli M, Eymard B, Radvanyi H, Junien C, Fardeau M, Gajdos P (1994) Correlation between decreased myocardial glucose phosphorylation and the DNA mutation size in myotonic dystrophy. Circulation 90:2629–2634

    PubMed  CAS  Google Scholar 

  10. Marcon M, Briani C, Ermani M, Menegazzo E, Iurilli V, Feltrin GP, Novelli G, Gennarelli M, Angelini C (1998) Positive correlation of CTG expansion and pharyngoesophageal alterations in myotonic dystrophy patients. Ital J Neurol Sci 19:75–80

    Article  PubMed  CAS  Google Scholar 

  11. Moxley RT III, Logigian EL, Martens WB, Annis CL, Pandya S, Moxley RT, Barbieri CA, Dilek N, Wiegner AW, Thornton CA (2007) Computerized hand grip myometry reliably measures myotonia and muscle strength in myotonic dystrophy (DM1). Muscle Nerve 36:320–328

    Article  PubMed  Google Scholar 

  12. Kinoshita M, Komori T, Ohtake T, Takahashi R, Nagasawa R, Hirose K (1997) Abnormal calcium metabolism in myotonic dystrophy as shown by the Ellsworth-Howard test and its relation to CTG triplet repeat length. J Neurol 244:613–622

    Article  PubMed  CAS  Google Scholar 

  13. Lee FI, Hughes DT (1964) Systemic effects in dystrophia myotonica. Brain 87:521–536

    Article  PubMed  CAS  Google Scholar 

  14. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  PubMed  CAS  Google Scholar 

  15. Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion JP, Hudson T (1992) Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3’ end of a transcript encoding a protein kinase family member. Cell 68:799–808

    Article  PubMed  CAS  Google Scholar 

  16. Reardon W, MacMillan JC, Myring J, Harley HG, Rundle SA, Beck L, Harper PS, Shaw DJ (1993) Cataract and myotonic dystrophy: the role of molecular diagnosis. Br J Ophthalmol 77:579–583

    Article  PubMed  CAS  Google Scholar 

  17. Carstensen B, Kristensen JK, Ottosen P, Borch-Johnson K (2008) On behalf of the steering group of the National Diabetes Register: the Danish National Diabetes Register: trends in incidence, prevalence and mortality. Diabetologia 51(12):2187–2196

    Article  PubMed  CAS  Google Scholar 

  18. Mosekilde L, Kassem M (1999) Medicinsk Kompendium. Nyt Nordisk Forlag Arnold Busck, Copenhagen

    Google Scholar 

  19. Harada S, Matsumoto T, Ikeda K, Fukumoto S, Ihara Y, Ogata E (1987) Association of primary hyperparathyroidism with myotonic dystrophy in two patients. Arch Intern Med 147:777–778

    Article  PubMed  CAS  Google Scholar 

  20. Molina MJ, Lara JI, Riobo P, Guijarro S, Moreno A, Del PC, Gonzalo A, Rovira A, Herrera-Pombo JL (1996) Primary hyperthyroidism and associated hyperparathyroidism in a patient with myotonic dystrophy: steinert with hyperthyroidism and hyperparathyroidism. Am J Med Sci 311:296–298

    Article  PubMed  CAS  Google Scholar 

  21. Konagaya Y, Konagaya M, Mano Y, Takayanagi T, Tomita A (1985) Evaluation of renal parathyroid hormone receptor function in myotonic dystrophy. J Neurol Sci 70:339–346

    Article  PubMed  CAS  Google Scholar 

  22. Yoshida H, Oshima H, Saito E, Kinoshita M (1988) Hyperparathyroidism in patients with myotonic dystrophy. J Clin Endocrinol Metab 67:488–492

    Article  PubMed  CAS  Google Scholar 

  23. Laurberg P, Pedersen KM, Hreidarsson A, Sigfusson N, Iversen E, Knudsen PR (1998) Iodine intake and the pattern of thyroid disorders: a comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland, Denmark. J Clin Endocrinol Metab 83:765–769

    Article  PubMed  CAS  Google Scholar 

  24. Fukazawa H, Sakurada T, Yoshida K, Kaise N, Kaise K, Nomura T, Yamamoto M, Saito S, Takase S, Yoshinaga K (1990) Thyroid function in patients with myotonic dystrophy. Clin Endocrinol (Oxf) 32:485–490

    Article  CAS  Google Scholar 

  25. Steinbeck KS, Carter JN (1982) Thyroid abnormalities in patients with myotonic dystrophy. Clin Endocrinol (Oxf) 17:449–456

    Article  CAS  Google Scholar 

  26. Daumerie C, Lannoy N, Squifflet JP, Verellen G, Verellen-Dumoulin C (1994) High CTG repeat number in nodular thyroid tissue from a myotonic dystrophy patient. J Med Genet 31:891–892

    Article  PubMed  CAS  Google Scholar 

  27. Okuno T, Mori K, Furomi K, Takeoka T, Kondo K (1981) Myotonic dystrophy and hyperthyroidism. Neurology 31:91–93

    Article  PubMed  CAS  Google Scholar 

  28. Pagliara S, Spagnuolo E, Ambrosone L, Barbato A, Tesauro P, Rambaldi M (1985) Hyperthyroidism and Addison’s disease in a patient with myotonic dystrophy. Arch Intern Med 145:919–920

    Article  PubMed  CAS  Google Scholar 

  29. Peterson DM, Bounds JV Jr, Karnes WE (1976) Clinical observations on thyrotoxicosis coexisting with myotonic dystrophy. Mayo Clin Proc 51:176–179

    PubMed  CAS  Google Scholar 

  30. Savkur RS, Philips AV, Cooper TA (2001) Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet 29:40–47

    Article  PubMed  CAS  Google Scholar 

  31. Mastrogiacomo I, Bonanni G, Menegazzo E, Santarossa C, Pagani E, Gennarelli M, Angelini C (1996) Clinical and hormonal aspects of male hypogonadism in myotonic dystrophy. Ital J Neurol Sci 17:59–65

    Article  PubMed  CAS  Google Scholar 

  32. Machuca-Tzili L, Brook D, Hilton-Jones D (2005) Clinical and molecular aspects of the myotonic dystrophies: a review. Muscle Nerve 32:1–18

    Article  PubMed  CAS  Google Scholar 

  33. Kinoshita M, Takahashi R, Hasegawa T, Komori T, Nagasawa R, Hirose K, Tanabe H (1996) (CTG)n expansions in various tissues from a myotonic dystrophy patient. Muscle Nerve 19:240–242

    Article  PubMed  CAS  Google Scholar 

  34. Mastrogiacomo I, Pagani E, Novelli G, Angelini C, Gennarelli M, Menegazzo E, Bonanni G, Dallapiccola B (1994) Male hypogonadism in myotonic dystrophy is related to (CTG)n triplet mutation. J Endocrinol Invest 17:381–383

    PubMed  CAS  Google Scholar 

  35. Marchini C, Lonigro R, Verriello L, Pellizzari L, Bergonzi P, Damante G (2000) Correlations between individual clinical manifestations and CTG repeat amplification in myotonic dystrophy. Clin Genet 57:74–82

    Article  PubMed  CAS  Google Scholar 

  36. Martorell L, Martinez JM, Carey N, Johnson K, Baiget M (1995) Comparison of CTG repeat length expansion and clinical progression of myotonic dystrophy over a five year period. J Med Genet 32:593–596

    Article  PubMed  CAS  Google Scholar 

  37. Tome S, Holt I, Edelmann W, Morris GE, Munnich A, Pearson CE, Gourdon G (2009) MSH2 ATPase domain mutation affects CTG*CAG repeat instability in transgenic mice. PLoS Genet 5:e1000482

    Article  PubMed  Google Scholar 

  38. Nakamura A, Kojo T, Arahata K, Takeda S (1996) Reduction of serum IgG level and peripheral T-cell counts are correlated with CTG repeat lengths in myotonic dystrophy patients. Neuromuscul Disord 6:203–210

    Article  PubMed  CAS  Google Scholar 

  39. Griggs RC, Kingston W, Jozefowicz RF, Herr BE, Forbes G, Halliday D (1989) Effect of testosterone on muscle mass and muscle protein synthesis. J Appl Physiol 66:498–503

    PubMed  CAS  Google Scholar 

Download references

Conflicts of interest

The authors report no conflicts of interest.

Author information

Authors and Affiliations

  1. Neuromuscular Research Unit 3342, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark

    M. C. Ørngreen & J. Vissing

  2. Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    M. C. Ørngreen, P. Arlien-Søborg & J. Vissing

  3. Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    M. Duno

  4. Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark

    J. M. Hertz

Authors
  1. M. C. Ørngreen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Arlien-Søborg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Duno
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. M. Hertz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Vissing
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. C. Ørngreen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ørngreen, M.C., Arlien-Søborg, P., Duno, M. et al. Endocrine function in 97 patients with myotonic dystrophy type 1. J Neurol 259, 912–920 (2012). https://doi.org/10.1007/s00415-011-6277-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-011-6277-5

Keywords

Search

Navigation