Skip to main content

Advertisement

SpringerLink
Log in

Hormonal and metabolic gender differences in a cohort of myotonic dystrophy type 1 subjects: a retrospective, case–control study

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by CTG expansion in the DMPK gene. The aim was to investigate the endocrine and metabolic aspects of DM1.

Patients and methods

Retrospective, case–control study. We compared pituitary, thyroid, adrenal, gonadal and liver function and glycolipid metabolism of 63 DM1 patients against 100 control subjects. Given age-related differences, 2 further subgroups were created to investigate the pituitary–gonadal axis: < 41 (1a) and ≥ 41 (1b) years old for male subjects and < 46 (2a) and ≥ 46 (2b) years old for female subjects. Testicular and thyroid ultrasounds were also performed in the DM1 group.

Results

FT3 and FT4 were significantly lower in DM1 men than controls, while for both males and females, thyroglobulin, ACTH and cortisol were significantly higher in the DM1 group. Gonadotropin levels were significantly higher and inhibin B and DHEA-S levels significantly lower in DM1 patients than controls for both male subgroups. Testosterone and SHBG were significantly higher in controls than in patients for subgroup 1a. Prolactin was significantly higher in patients in subgroups 1b, while testosterone was lower in subgroup 2a than in age-matched female controls. A correlation between the number of CTG repeats and the percentage of male hypogonadal subjects was found. Finally, there was a worse glucose and lipid pattern and significantly higher transaminase and gamma-GT levels in both male and female patients.

Conclusions

The high frequency of endocrine and metabolic abnormalities in DM1 highlights the importance of endocrine monitoring to enable the prompt initiation of a suitable therapy.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Harper PS (2001) Myotonic dystrophy. Monckton DG, London

    Google Scholar 

  2. Jansen G, Mahadevan M, Amemiya C, Wormskamp N, Segers B, Hendriks W, O’Hoy K, Baird S, Sabourin L, Lennon G (1992) Characterization of the myotonic dystrophy region predicts multiple protein isoform-encoding mRNAs. Nat Genet 1(4):261–266

    CAS  PubMed  Google Scholar 

  3. Udd B, Krahe R (2012) The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol 11(10):891–905

    CAS  PubMed  Google Scholar 

  4. De Antonio M, Dogan C, Hamroun D, Mati M, Zerrouki S, Eymard B, Katsahian S, Bassez G, French A (2016) Unravelling the myotonic dystrophy type 1 clinical spectrum: a sytematic registry-based study with implications for disease clasification. Rev Neurol (Paris) 172(10):572–580

    Google Scholar 

  5. Stokes M, Varughese N, Iannaccone S, Castro D (2019) Clinical and genetic characteristics of childhood-onset myotonic dystrophy. Muscle Nerve 60(6):732–738

    PubMed  Google Scholar 

  6. Miller JW, Urbinati CR, Teng-Umnuay P, Stenberg MG, Byrne BJ, Thornton C, Swanson MS (2000) Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. EMBO 19(17):4439–4448

    CAS  Google Scholar 

  7. Taneja KL, McCurrach M, Schalling M, Housman D, Singer RH (1995) Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues. J Cell Biol 128(6):995–1002

    CAS  PubMed  Google Scholar 

  8. Davis BM, McCurrach ME, Taneja KL, Singer RH, Housman DE (1997) Expansion of a CUG trinucleotide repeat in the 3′-untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts. Proc Natll Acad Sci 94:7388–7393

    CAS  Google Scholar 

  9. Czubak K, Sedehizadeh S, Kozlowski P, Wojciechowska M (2019) An overview of circular RNAs and their implications in myotonic dystrophy. Int J Mol Sci 20(18):4385. https://doi.org/10.3390/ijms20184385

    Article  CAS  PubMed Central  Google Scholar 

  10. 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(5):381–383

    CAS  PubMed  Google Scholar 

  11. Vazquez JA, Pinies JA, Martul P, De los Rios A, Gatzambide S, Busturia MA (1990) Hypothalamic-pituitary-testicular function in 70 patients with myotonic dystrophy. J Endocrinol Invest 13(5):375–379

    CAS  PubMed  Google Scholar 

  12. Kaminsky P, Pruna L (2012) A genetic systemic disease: clinical description of type 1 myotonic dystrophy in adults. Rev Med Interne 33(9):514–518

    CAS  PubMed  Google Scholar 

  13. Shieh K, Gilchrist JM, Promrat K (2010) Frequency and predictors of nonalcoholic fatty liver disease in myotonic dystrophy. Muscle Nerve 41(2):197–201

    CAS  PubMed  Google Scholar 

  14. Cruz Gùzman OR, Chávez García AL, Rodríguez-Cruz M (2012) Muscular dystrophies at different ages: metabolic and endocrine alterations. Int J Endocrinol 2012:485376

    PubMed Central  Google Scholar 

  15. Roussel MP, Morin M, Gagnon C, Duchesne E (2019) What is known about the effects of exercise or training to reduce skeletal muscle impairments of patients with myotonic dystrophy type 1? A scopimg review. BMC Muscoloskelet Disord 20(1):101

    Google Scholar 

  16. Win AK, Perattur PG, Pulido JS, Pulido CM, Lindor NM (2012) Increased cancer risks in myotonic dystrophy. Mayo Clin Proc 87(2):130–135

    PubMed  PubMed Central  Google Scholar 

  17. Zmuda JM, Cauley JA, Kriska A, Glynn NW, Gutai JP, Kuller LH (1997) Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men. Am J Epidemiol 146(8):609–617

    CAS  PubMed  Google Scholar 

  18. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR (2001) Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab 86(2):724–731. https://doi.org/10.1210/jcem.86.2.7219

    Article  CAS  PubMed  Google Scholar 

  19. Spaziani M, Mileno B, Rossi F, Granato S, Tahani N, Anzuini A, Lenzi A, Radicioni AF (2018) Endocrine and metabolic evaluation of classic Klinefelter syndrome and high grade aneuploidies of sexual chromosomes with male phenotype: are they different clinical conditions? Eur J Endocrinol 178:1–10

    Google Scholar 

  20. Radicioni AF, Tahani N, Spaziani M, Anzuini A, Piccheri C, Semeraro A, Tarani L, Lenzi A (2013) Reference ranges for thyroid hormones in normal Italian children and adolescents and overweight adolescents. J Endocrinol Investig 36(5):326–330

    CAS  Google Scholar 

  21. Russ G, Bigorgne C, Royer B, Rouxel A, Bienvenu-Perrard M (2011) The thyroid imaging reporting and data system (TIRADS) for ultrasound of the thyroid. J Radiol 92(7–8):701–713

    CAS  PubMed  Google Scholar 

  22. 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(11):891–892

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Van den Beld AW, Visser TJ, Feelders RA, Grobbee DE, Lamberts SW (2005) Thyroid hormone concentrations, disease, physical function, and mortality in elderly men. J Clin Endocrinol Metab 90(12):6403–6409

    PubMed  Google Scholar 

  24. De Alfieri W, Nisticò F, Borgogni T, Riello F, Cellai F, Mori C, Nante N, Di Bari M (2013) Thyroid hormones as predictors of short- and long-term mortality in very old hospitalized patients. J Gerontol A Biol Sci Med Sci 68(9):1122–1128

    PubMed  Google Scholar 

  25. Maia AL, Goemann IM, Meyer EL, Wajner SM (2011) Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease. J Endocrinol 209(3):283–297

    CAS  PubMed  Google Scholar 

  26. Pasqualetti G, Calsolaro V, Bernardini S, Linsalata G, Bigazzi R, Caraccio N, Monzani F (2018) Degree of peripheral thyroxin deiodination, frailty, and long-term survival in hospitalized older patients. J Clin Endocrinol Metab 103(5):1867–1876

    PubMed  Google Scholar 

  27. Emerenziani GP, Izzo G, Vaccaro MG, Quattrone A, Lenzi A, Aversa A (2019) Gender difference and correlation between sexuality, thyroid hormones, cognitive, and physical functions in elderly fit. J Endocrinol Invest 42(6):699–707

    CAS  PubMed  Google Scholar 

  28. Carter JN, Steinbeck KS (1985) Reduced adrenal androgens in patients with myotonic dystrophy. J Clin Endocrinol Metab 60(3):611–614

    CAS  PubMed  Google Scholar 

  29. Johansson Ǻ, Carlström K, Ahrén B, Cederquist K, Krylborg E, Forsberg H, Olsson T (2000) Abnormal cytokine and adrenocortical hormone regulation in myotonic dystrophy. J Clin Endocrinol Metab 85(9):3169–3176

    CAS  PubMed  Google Scholar 

  30. Johansson Ǻ, Andrew R, Forsberg H, Cederquist K, Walker BR, Olsson T (2001) Glucocorticoid metabolism and adrenocortical reactivity to ACTH in myotonic dystrophy. J Clin Endocrinol Metab 86(9):4276–4283

    CAS  PubMed  Google Scholar 

  31. Ørngreen MC, Arlien-Søborg P, Duno M, Hertz JM, Vissing J (2012) Endocrine function in 97 patients with myotonic dystrophy type 1. J Neurol 259(5):912–920

    PubMed  Google Scholar 

  32. Henriksen OA, Sundsfjord JA, Nyberg-Hansen R (1978) Evaluation of the endocrine functions in dystrophia myotonica. Acta Neurol Scand 58:178–189

    CAS  PubMed  Google Scholar 

  33. May PB, Renny A, Bastek J, Giglio W, Schneider G, Ertel N (1980) Diminished prolactin reserve with myotonic dystrophy. J Endocrinol Invest 3(4):415–418

    CAS  PubMed  Google Scholar 

  34. Canal N, Smirne S, Comi G, Guidobono F, Pecile A, Caviezel F (1982) Study on growth hormone and prolactin secretions in myotonic dystrophy. Acta Neurol Belg 82:178–184

    CAS  PubMed  Google Scholar 

  35. Passeri E, Bugiardini E, Sansone VA, Pizzoccaro A, Fulceri C, Valaperta R, Borgato S, Costa E, Bandera F, Ambrosi B et al (2015) Gonadal failure is associated with visceral adiposity in myotonic dystrophies. Eur J Clin Invest 45(7):702–710

    CAS  PubMed  Google Scholar 

  36. Pizzi A, Fusi S, Forti G, Marconi G (1985) Study of endocrine function in myotonic dystrophy. Ital J Neurol Sci 6(4):457–467

    CAS  PubMed  Google Scholar 

  37. 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(1):59–65

    CAS  PubMed  Google Scholar 

  38. Vasquez JA, Pinies JA, Martul P, De los Rios A, Gatzambide S, Busturia MA (1990) Hypotalamic-pituitary-testicular function in 70 patients with Myotonic Dystrophy. J Endocrinol Invest 13:375–379

    Google Scholar 

  39. Lou XY, Nishi Y, Haji M, Antoku Y, Tanaka S, Ikuyama S, Yanase T, Takayanagi R, Nawata H (1994) Reserved Sertoli cell function in the hypogonadic male patients with myotonic dystrophy. Fukuoka Igaku Zasshi 85(5):168–174

    CAS  PubMed  Google Scholar 

  40. Francomano D, Greco EA, Lenzi A, Aversa A (2013) CAG repeat testing of androgen receptor polymorphism: is this necessary for the best clinical management of hypogonadism? J Sex Med 10(10):2373–2381

    CAS  PubMed  Google Scholar 

  41. Kunej T, Teran N, Zorn B, Peterlin B (2004) CTG amplification in the DM1PK gene is not associated with idiopathic male subfertility. Hum Reprod 19(9):2084–2087

    CAS  PubMed  Google Scholar 

  42. Francomano D, Fattorini G, Gianfrilli D, Paoli D, Sgrò P, Radicioni A, Romanelli F, Di Luigi L, Gandini L, Lenzi A, Aversa A (2016) Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study. J Endocrinol Invest 39(3):265–271

    CAS  PubMed  Google Scholar 

  43. Antonini G, Clemenzi A, Bucci E, De Marco E, Morino S, Di Pasquale A, Latino P, Ruga G, Lenzi A, Vanacore N et al (2011) Hypogonadism in DM1 and its relationship to erectile dysfunction. J Neurol 258(7):1247–1253

    CAS  PubMed  Google Scholar 

  44. Matsumura T, Iwahashi H, Funahasci T, Takahashi MP, Saito T, Yasui K, Saito T, Iyama A, Toyooka K, Fujimura H et al (2009) A cross sectional study for glucose intolerance of myotonic distrophy. J Neurol Sci 276:60–65

    CAS  PubMed  Google Scholar 

  45. Dahlqvist JR, Ørngreen MC, Witting N, Vissing J (2015) Endocrine function over time in patients with myotonic dystrophy type 1. Eur J Neurol 22:116–122

    CAS  PubMed  Google Scholar 

  46. Vujnic M, Peric S, Popovic S, Raseta N, Ralic V, Dobricic V, Novakovic I, Rakocevic-Stojanovic V (2015) Metabolic syndrome in patients with Myotonic dystrophy type 1. Muscle Nerve 2(2):273–277

    Google Scholar 

  47. Kalafateli M, Triantos C, Tsamandas A, Kounadis G, Labropoulou-Karatza C (2012) Abnormal liver function tests in a patient with myotonic dystrophy type 1. Ann Hepatol 11:130–133

    CAS  PubMed  Google Scholar 

  48. Achiron A, Barak Y, Magal N, Shohat M, Cohen M, Barar R, Gadoth N (1998) Abnormal liver tests results in myotonic dystrophy. J Clin Gastroenterol 26:292–295

    CAS  PubMed  Google Scholar 

  49. Heatwole C, Miller J, Martens B, Moxley R (2006) Laboratoty abnormalities in ambulatory patients with myotonic dystrophy type 1. Arch Neurol 63:1149–1153

    PubMed  Google Scholar 

  50. Dogan C, De Antonio M, Hamroun D, Varet H, Fabbro M, Rougier F, Amarof K et al (2016) Gender as a modifying factor influencing myotonic dystrophy type 1 phenotype severity and mortality: a nationwide multiple databases cross-sectional observational study. PLoS One 11(2):e0148264

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Marie-Hélène Hayles MITI for the language revision.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Author information

Authors and Affiliations

  1. Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Policlinico Umberto I, Sapienza University of Rome, Level - 1, Room 33, Rome, Italy

    M. Spaziani, A. Semeraro, F. Rossi, M. A. Papassifachis, A. Anzuini, A. Lenzi & A. F. Radicioni

  2. Centre for Rare Diseases, Policlinico Umberto I, Rome, Italy

    M. Spaziani, A. Semeraro, F. Rossi, M. A. Papassifachis, C. Pozza & A. F. Radicioni

  3. Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, Rome, Italy

    E. Bucci, M. Garibaldi & G. Antonini

Authors
  1. M. Spaziani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Semeraro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Bucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Garibaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. A. Papassifachis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. Pozza
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. Anzuini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. Lenzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G. Antonini
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. A. F. Radicioni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Spaziani.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.The study was approved by the Policlinico Umberto I Ethics Committee (Sapienza University of Rome).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Spaziani, M., Semeraro, A., Bucci, E. et al. Hormonal and metabolic gender differences in a cohort of myotonic dystrophy type 1 subjects: a retrospective, case–control study. J Endocrinol Invest 43, 663–675 (2020). https://doi.org/10.1007/s40618-019-01156-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-019-01156-w

Keywords

Search

Navigation