Gastrointestinal and Hepatic Issues in Women with Turner Syndrome

  • Ghassan T. WahbehEmail author
  • Amanda Bradshaw
  • Lauren White
  • Dale Lee


Patients with Turner syndrome are more prone than the general population to develop gastrointestinal inflammatory and noninflammatory conditions. Among the inflammatory condition with significant impact on growth, development, and quality of life are celiac disease and Crohn’s disease. Additionally both conditions may impact the response to hormonal therapy in TS if untreated. It is imperative to recognize the presence of celiac disease and Crohn’s disease early, despite the diagnostic challenge since the presenting signs and symptoms often overlap with TS manifestation including growth delay and amenorrhea. Among the noninflammatory manifestations are gastrointestinal bleeding and hepatic manifestations. Bleeding can be life-threatening and warrants emergent care. A multidisciplinary team approach is often needed to address such gastrointestinal manifestations to optimize patient outcomes. This chapter provides a review of the relevant gastrointestinal manifestations in individuals with TS.


Turner Celiac Crohn’s Gastrointestinal bleeding Vascular malformation 


  1. 1.
    Benchimol EI, Fortinsky KJ, Gozdyra P, Van den Heuvel M, Van Limbergen J, Griffiths AM. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis. 2011;17:423–39.CrossRefGoogle Scholar
  2. 2.
    Loddo I, Romano C. Inflammatory bowel disease: genetics, epigenetics, and pathogenesis. Front Immunol. 2015;6:551.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Goldacre MJ, Seminog OO. Turner syndrome and autoimmune diseases: record-linkage study. Arch Dis Child. 2014;99:71–3.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Bakalov VK, Gutin L, Cheng CM, Zhou J, Sheth P, Shah K, Arepalli S, Vanderhoof V, Nelson LM, Bondy CA. Autoimmune disorders in women with Turner syndrome and women with karyotypically normal primary ovarian insufficiency. J Autoimmun. 2012;38:315–21.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Pessach IM, Notarangelo LD. X-linked primary immunodeficiencies as a bridge to better understanding X-chromosome related autoimmunity. J Autoimmun. 2009;33:17–24.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Holtman GA, Lisman-van Leeuwen Y, Reitsma JB, Berger MY. Noninvasive tests for inflammatory bowel disease: a meta-analysis. Pediatrics. 2016;137:e20152126.CrossRefGoogle Scholar
  7. 7.
    Bousvaros A, Antonioli DA, Colletti RB, Dubinsky MC, Glickman JN, Gold BD, Griffiths AM, Jevon GP, Higuchi LM, Hyams JS, Kirschner BS, Kugathasan S, Baldassano RN, Russo PA. Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn’s and Colitis Foundation of America. J Pediatr Gastroenterol Nutr. 2007;44:653–74.CrossRefGoogle Scholar
  8. 8.
    Rufo PA, Denson LA, Sylvester FA, Szigethy E, Sathya P, Lu Y, Wahbeh GT, Sena LM, Faubion WA. Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations. J Pediatr Gastroenterol Nutr. 2012;55:93–108.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Long MD, Kappelman MD, Martin CF, Chen W, Anton K, Sandler RS. Role of nonsteroidal anti-inflammatory drugs in exacerbations of inflammatory bowel disease. J Clin Gastroenterol. 2016;50:152–6.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Crone J, Rami B, Huber WD, Granditsch G, Schober E. RBHWDGGSE: prevalence of celiac disease and follow-up of EMA in childrend and adolescents with type 1 diabetes mellitus. J Pediatr Gastroenterol Nutr. 2003;37:67.CrossRefGoogle Scholar
  11. 11.
    Giannotti A, Tiberio G, Castro M, Virgilii F, Colistro F, Ferretti F, Digilio MC, Gambarara M, Dallapiccola B. Coeliac disease in Williams syndrome. J Med Genet. 2001;38:767.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, Elitsur Y, Green PH, Guandalini S, Hill ID, Pietzak M, Ventura A, Thorpe M, Kryszak D, Fornaroli F, Wasserman SS, Murray JA, Horvath K. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Internal Med. 2003;163:286.CrossRefGoogle Scholar
  13. 13.
    Hill ID, Dirks MH, Liptak GS, Colletti RB, Fasano A, Guandalini S, Hoffenberg EJ, Horvath K, Murray JA, Pivor M, Seidman EG. Guidelines for diagnosis and treatment of celiac disease in children: recommendations of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2005;40:1–19.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Moayeri HB. Prevalence of celiac disease in patients with Turner’s syndrome. Acta Med Iran. 2005;43:287–90.Google Scholar
  15. 15.
    Mårild K, Størdal K, Hagman A, Ludvigsson JF. Turner syndrome and celiac disease: a case-control study. Pediatrics. 2016;137:e20152232.CrossRefGoogle Scholar
  16. 16.
    Frost AR, Band MM, Conway GS. Serologically screening for coeliac disease in adults with Turner’s syndrome: prevalence andc linical significance of endomysium antibody positivity. Eur J Endocrinol. 2009;160:877–81.CrossRefGoogle Scholar
  17. 17.
    Bonamico M, Pasquino AM, Mariani P, Danesi HM, Culasso F, Mazzanti L, et al. Prevalence and clinical picture of celiac disease in Turner syndrome. J Clin Endocrinol Metab. 2002;87:5495–8.CrossRefGoogle Scholar
  18. 18.
    Gillett PM, Gillett HR, Israel DM, Metzger DL, Stewart L, Chanoine JP, et al. Increased prevalence of celiac disease in girls with Turner syndrome detected using antibodies to endomysium and tissue transglutaminase. Can J Gastroenterol. 2000;14:915.CrossRefGoogle Scholar
  19. 19.
    Dias M, Castro L, Gandolfi L, Almeida R, Corboda M, Pratesi R. Screening for celiac disease among patients with Turner syndrome in Brasilia, DF, Midwest region of Brazil. Arg Gastroenterol. 2010;47:246–9.CrossRefGoogle Scholar
  20. 20.
    Bettendorf M, Doerr HG, Hauffa BP, Lindberg A, Mehls O, Partsch CJ, et al. Prevalence of autoantibodies associated with thyroid and celiac disease in Ullrich-Turner syndrome in relation to adult height after growth hormone treatment. J Pediatric Endocrinol. 2006;19:149–54.CrossRefGoogle Scholar
  21. 21.
    Mortensen KH, Cleemann L, Hjerrild BE, Nexo E, Locht H, Jeppesen EM, Gravholt CH. Increased prevalence of autoimmunity in Turner syndrome-influence of age. Clin Exp Immunol. 2009;156:205–10.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Arslan D, Kuyucu T, Kendirci M, Kurtoglu S. Celiac disease and Turner’s syndrome: patient report. J Pediatr Endocrinol. 2000;13:1629–31.Google Scholar
  23. 23.
    Gravholt CH, Andersen NH, Conway GS, et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol. 2017;177(3):G1–G70.Google Scholar
  24. 24.
    Sollid LM, Lie BA. Celiac disease genetics: current concepts and practical applications. Clin Gastroenterol Hepatol. 2005;3:843–51.CrossRefGoogle Scholar
  25. 25.
    Mills JR, Murray JA. Contemporary celiac disease diagnosis: is a biopsy avoidable? Curr Opin Gastroenterol. 2016;32:80–5.CrossRefGoogle Scholar
  26. 26.
    Lisser H, Curtis LE, et al. The syndrome of congenitally aplastic ovaries with sexual infantilism, high urinary gonadotropins, short stature and other congenital abnormalities; tabular presentation of 25 previously unpublished cases. J Clin Endocrinol Metab. 1947;7:665–87.CrossRefGoogle Scholar
  27. 27.
    Haddad HM, Wilkins L. Congenital anomalies associated with gonadal aplasia; review of 55 cases. Pediatrics. 1959;23:885–902.PubMedGoogle Scholar
  28. 28.
    Eroglu Y, Emerick KM, Chou PM, Reynolds M. Gastrointestinal bleeding in Turner’s syndrome: a case report and literature review. J Pediatr Gastroenterol Nutr. 2002;35:84–7.CrossRefGoogle Scholar
  29. 29.
    Boyle JT. Gastrointestinal bleeding in infants and children. Pediatr Rev. 2008;29:39–52.CrossRefGoogle Scholar
  30. 30.
    Schultz LS, Assimacopoulos CA, Lillehei RC. Turner’s syndrome with associated gastrointestinal hemorrhage: a case report. Surgery. 1970;68:485–8.PubMedGoogle Scholar
  31. 31.
    Scott T. Turner’s syndrome and vermiform phlebectasia of the bowel. Trans Am Clin Climatol Assoc. 1968;79:45–50.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Frame B, Rao DS, Ohorodnik JM, Kwa DM. Gastrointestinal hemorrhage in Turner syndrome. Long-term follow-up with postmortem examination. Arch Intern Med. 1977;137:691–2.CrossRefGoogle Scholar
  33. 33.
    Qureshi MA, Mouzaki M, Le T. Diagnosis of small bowel telangiectasia in Turner’s syndrome using capsule endoscopy. J Pediatr Endocrinol Metab. 2009;22:759–62.CrossRefGoogle Scholar
  34. 34.
    Nudell J, Brady P. A case of GI hemorrhage in a patient with Turner’s syndrome: diagnosis by capsule endoscopy. Gastrointest Endosc. 2006;63:514–6.CrossRefGoogle Scholar
  35. 35.
    Jolley C, Langham MR Jr, Dillard R, Novak D. Intraoperative endoscopy in a child with Turner’s syndrome and gastrointestinal hemorrhage: a case report. J Pediatr Surg. 2001;36:951–2.CrossRefGoogle Scholar
  36. 36.
    O’Hare JP, Hamilton M, Davies JD, Corrall RJ, Mountford R. Oestrogen deficiency and bleeding from large bowel telangiectasia in Turner’s syndrome. J R Soc Med. 1986;79:746–7.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Van Cutsem E. Georges Brohee Prize. Oestrogen-progesterone, a new therapy of bleeding gastrointestinal vascular malformations. Acta Gastroenterol Belg. 1993;56:2–10.PubMedGoogle Scholar
  38. 38.
    Vase P. Estrogen treatment of hereditary hemorrhagic telangiectasia. A double-blind controlled clinical trial. Acta Med Scand. 1981;209:393–6.CrossRefGoogle Scholar
  39. 39.
    Holleran G, Hall B, Breslin N, McNamara D. Long-acting somatostatin analogues provide significant beneficial effect in patients with refractory small bowel angiodysplasia: results from a proof of concept open label mono-centre trial. United European Gastroenterol J. 2016;4:70–6.CrossRefGoogle Scholar
  40. 40.
    Bridwell T. Gonadal dysgenesis (Turner’s syndrome) with associated liver disease and bleeding esophageal varices. Henry Ford Hosp Med Bull. 1959;7:156–60.PubMedGoogle Scholar
  41. 41.
    Roulot D. Liver involvement in Turner syndrome. Liver Int. 2013;33:24–30.CrossRefGoogle Scholar
  42. 42.
    Lee MC, Conway GS. Liver dysfunction in Turner syndrome and its relationship to = exogenous oestrogen. Eur J Gastroenterol Hepatol. 2013;25:1141–5.PubMedGoogle Scholar
  43. 43.
    Larizza D, Locatelli M, Vitali L, Vigano C, Calcaterra V, Tinelli C, Sommaruga MG, Bozzini A, Campani R, Severi F. Serum liver enzymes in Turner syndrome. Eur J Pediatr. 2000;159:143–8.CrossRefGoogle Scholar
  44. 44.
    Koulouri O, Ostberg J, Conway GS. Liver dysfunction in Turner’s syndrome: prevalence, natural history = and effect of exogenous oestrogen. Clin Endocrinol. 2008;69:306–10.CrossRefGoogle Scholar
  45. 45.
    Calcaterra V, Brambilla P, Maffe GC, Klersy C, Albertini R, Introzzi F, Bozzola E, Bozzola M, Larizza D. Metabolic syndrome in Turner syndrome and relation between body = composition and clinical, genetic, and ultrasonographic characteristics. Metab Syndr Relat Disord. 2014;12:159–64.CrossRefGoogle Scholar
  46. 46.
    Chiche L, Adam JP. Diagnosis and management of benign liver tumors. Semin Liver Dis. 2013;33:236–47.CrossRefGoogle Scholar
  47. 47.
    Roulot D, Degott C, Chazouilleres O, Oberti F, Cales P, Carbonell N, Benferhat S, Bresson-Hadni S, Valla D. Vascular involvement of the liver in Turner’s syndrome. Hepatology. 2004;39:239–47.CrossRefGoogle Scholar
  48. 48.
    Gravholt CH, Naeraa RW, Nyholm B, Gerdes LU, Christiansen E, Schmitz O, Christiansen JS. Glucose metabolism, lipid metabolism, and cardiovascular risk factors in adult Turner’s syndrome. The impact of sex hormone replacement. Diabetes Care. 1998;21:1062–70.CrossRefGoogle Scholar
  49. 49.
    Cheah E, La Hei E, O’Loughlin E. Melena and hyperammonemic seizures in a Turner syndrome patient. Gastroenterology. 2015;148:302–3.CrossRefGoogle Scholar
  50. 50.
    Elsheikh M, Hodgson HJ, Wass JA, Conway GS. Hormone replacement therapy may improve hepatic function in women with Turner’s syndrome. Clin Endocrinol. 2001;55:227–31.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Ghassan T. Wahbeh
    • 1
    Email author
  • Amanda Bradshaw
    • 2
  • Lauren White
    • 2
  • Dale Lee
    • 3
  1. 1.Pediatrics-Gastroenterology, Inflammatory Bowel Disease CenterSeattle Children’s Hospital, University of WashingtonSeattleUSA
  2. 2.GastroenterologySeattle Children’s HospitalSeattleUSA
  3. 3.Pediatrics-Gastroenterology, Clinical Nutrition & Celiac ProgramSeattle Children’s Hospital, University of WashingtonSeattleUSA

Personalised recommendations