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

  • M. SpazianiEmail author
  • A. Semeraro
  • E. Bucci
  • F. Rossi
  • M. Garibaldi
  • M. A. Papassifachis
  • C. Pozza
  • A. Anzuini
  • A. Lenzi
  • G. Antonini
  • A. F. Radicioni
Original Article



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.


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.


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.


Steinert’s disease Myotonic dystrophy type 1 Multi-systemic involvement Endocrine function Metabolic impairment Liver function 



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


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

Compliance with ethical standards

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.


  1. 1.
    Harper PS (2001) Myotonic dystrophy. Monckton DG, LondonGoogle Scholar
  2. 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):261–266PubMedCrossRefGoogle Scholar
  3. 3.
    Udd B, Krahe R (2012) The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol 11(10):891–905PubMedCrossRefGoogle Scholar
  4. 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):572–580CrossRefGoogle Scholar
  5. 5.
    Stokes M, Varughese N, Iannaccone S, Castro D (2019) Clinical and genetic characteristics of childhood-onset myotonic dystrophy. Muscle Nerve 60(6):732–738PubMedCrossRefGoogle Scholar
  6. 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):4439–4448CrossRefGoogle Scholar
  7. 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):995–1002PubMedCrossRefGoogle Scholar
  8. 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 94:7388–7393CrossRefGoogle Scholar
  9. 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. CrossRefPubMedCentralGoogle Scholar
  10. 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):381–383PubMedCrossRefGoogle Scholar
  11. 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):375–379PubMedCrossRefGoogle Scholar
  12. 12.
    Kaminsky P, Pruna L (2012) A genetic systemic disease: clinical description of type 1 myotonic dystrophy in adults. Rev Med Interne 33(9):514–518PubMedCrossRefGoogle Scholar
  13. 13.
    Shieh K, Gilchrist JM, Promrat K (2010) Frequency and predictors of nonalcoholic fatty liver disease in myotonic dystrophy. Muscle Nerve 41(2):197–201PubMedGoogle Scholar
  14. 14.
    Cruz Gùzman OR, Chávez García AL, Rodríguez-Cruz M (2012) Muscular dystrophies at different ages: metabolic and endocrine alterations. Int J Endocrinol 2012:485376PubMedCentralCrossRefGoogle Scholar
  15. 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):101CrossRefGoogle Scholar
  16. 16.
    Win AK, Perattur PG, Pulido JS, Pulido CM, Lindor NM (2012) Increased cancer risks in myotonic dystrophy. Mayo Clin Proc 87(2):130–135PubMedPubMedCentralCrossRefGoogle Scholar
  17. 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):609–617PubMedCrossRefGoogle Scholar
  18. 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. CrossRefPubMedGoogle Scholar
  19. 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 178:1–10CrossRefGoogle Scholar
  20. 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):326–330Google Scholar
  21. 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):701–713PubMedCrossRefGoogle Scholar
  22. 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):891–892PubMedPubMedCentralCrossRefGoogle Scholar
  23. 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):6403–6409PubMedCrossRefGoogle Scholar
  24. 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):1122–1128PubMedCrossRefGoogle Scholar
  25. 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):283–297PubMedCrossRefGoogle Scholar
  26. 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):1867–1876PubMedCrossRefGoogle Scholar
  27. 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):699–707PubMedCrossRefGoogle Scholar
  28. 28.
    Carter JN, Steinbeck KS (1985) Reduced adrenal androgens in patients with myotonic dystrophy. J Clin Endocrinol Metab 60(3):611–614PubMedCrossRefGoogle Scholar
  29. 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):3169–3176PubMedGoogle Scholar
  30. 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):4276–4283PubMedCrossRefGoogle Scholar
  31. 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):912–920PubMedCrossRefGoogle Scholar
  32. 32.
    Henriksen OA, Sundsfjord JA, Nyberg-Hansen R (1978) Evaluation of the endocrine functions in dystrophia myotonica. Acta Neurol Scand 58:178–189PubMedCrossRefGoogle Scholar
  33. 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):415–418PubMedCrossRefGoogle Scholar
  34. 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 82:178–184PubMedGoogle Scholar
  35. 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):702–710PubMedCrossRefGoogle Scholar
  36. 36.
    Pizzi A, Fusi S, Forti G, Marconi G (1985) Study of endocrine function in myotonic dystrophy. Ital J Neurol Sci 6(4):457–467PubMedCrossRefGoogle Scholar
  37. 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):59–65PubMedCrossRefGoogle Scholar
  38. 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 13:375–379CrossRefGoogle Scholar
  39. 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):168–174PubMedGoogle Scholar
  40. 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):2373–2381PubMedCrossRefGoogle Scholar
  41. 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):2084–2087PubMedCrossRefGoogle Scholar
  42. 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):265–271PubMedCrossRefGoogle Scholar
  43. 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):1247–1253PubMedCrossRefGoogle Scholar
  44. 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 276:60–65PubMedCrossRefGoogle Scholar
  45. 45.
    Dahlqvist JR, Ørngreen MC, Witting N, Vissing J (2015) Endocrine function over time in patients with myotonic dystrophy type 1. Eur J Neurol 22:116–122PubMedCrossRefGoogle Scholar
  46. 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):273–277CrossRefGoogle Scholar
  47. 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 11:130–133PubMedCrossRefGoogle Scholar
  48. 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 26:292–295PubMedCrossRefGoogle Scholar
  49. 49.
    Heatwole C, Miller J, Martens B, Moxley R (2006) Laboratoty abnormalities in ambulatory patients with myotonic dystrophy type 1. Arch Neurol 63:1149–1153PubMedCrossRefGoogle Scholar
  50. 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):e0148264PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  1. 1.Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Policlinico Umberto ISapienza University of RomeRomeItaly
  2. 2.Centre for Rare DiseasesPoliclinico Umberto IRomeItaly
  3. 3.Department of Neurosciences, Mental Health and Sensory Organs (NESMOS)Sapienza University of RomeRomeItaly

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