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Prevalence of autoimmune thyroid diseases among the Turner Syndrome patients: meta-analysis of cross sectional studies



This meta-analysis was done to estimate the prevalence of autoimmune thyroid diseases (ATDs) in Turner Syndrome patients, and to determine the clinical status of thyroid autoimmune diseases that occur frequently in association with Turner Syndrome.


A total of 18 studies were included in the meta-analysis. The pooled overall prevalence of autoimmune thyroid diseases in Turner Syndrome patients was 38.6% (95% CI 29.7–47.6%), with 12.7% (95% CI 9.30–16.1%) of them had clinical hypothyroidism and 2.6% (95% CI 1.5–3.8%) had hyperthyroidism. I-squared test had a high result of heterogeneity. In subgroup analyses, the prevalence of ATDs was higher in the European region than Asian region. Autoimmune thyroid diseases are commonly associated with Turner Syndrome. Early detection of thyroid diseases by optimal screening among children with Turner Syndrome is required to ensure effective management.


Turner Syndrome (TS) is one of the most common chromosomopathies caused by numeric or structural abnormalities of the X chromosome [1,2,3]. It has a prevalence of 25–210 per 100,000 females [1]. Frequent clinical features include short stature, webbed neck, broad chest, cubitus valgus, delayed puberty and gonadal dysgenesis [4, 5].

Morbidity is considerably increased in Turner Syndrome. Several autoimmune disorders are more frequent in girls with Turner Syndrome such as: autoimmune thyroid diseases (ATDs), celiac disease, inflammatory bowel disease, psoriasis, vitiligo and juvenile rheumatoid arthritis. Likewise, there is increased risk of ischemic heart disease, hypertension and congenital malformations of the heart and urinary system [1,2,3,4,5,6].

Previous studies identified that haploinsufficiency of at least ten genes located on the X chromosome are involved in the immune regulation process, affecting self-protein exposure in the thymus and escape of auto-reactive T cells [3, 7, 8]. Bakalov et al. findings suggest that factors associated with ovarian insufficiency may be responsible for this autoimmune condition [9].

ATDs had been reported to be more frequent in girls with TS than in the general population [6, 10, 11], covering a spectrum of phenotypes. They include Hashimoto’s thyroiditis (HT)—which is considered the most common autoimmune thyroid disease, and Graves’ disease (GD)—which causes hyperthyroidism [7, 12,13,14,15,16]. Most HT forms evolve into hypothyroidism, although at presentation patients can be without clinical hypothyroidism [16].

Previous studies of the magnitude of ATDs among Turner Syndrome population remains inconsistent; wide variation of percentages for the presence of ATDs occurs in the studies [7]. Furthermore, to the best of our knowledge, there is no meta-analysis of existing contemporary evidence on the prevalence of ATDs among the TS population. Therefore, the aim of this meta-analysis is to estimate the prevalence and clinical status of ATDs in patients with TS.

Main text


In August 2018, a literature search using the electronic databases of MEDLINE/PubMed, ScienceDirect, Google Scholar and OpenGrey was done to identify all of the relevant studies clarifying the prevalence of autoimmune thyroid disease in patients with Turner Syndrome published up to date without time limitation. The search strategy was formulated by using the key words ‘Turner Syndrome’ and ‘thyroid’. Manual search for additional studies was performed using references cited in original study articles. We followed the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) [17].

Cross-sectional studies published in English, with sufficient information to estimate the prevalence of autoimmune thyroid diseases in patients with Turner Syndrome were included in this study. Study exclusion criteria included the following: Case reports, letters, editorials and studies lacking the relevant data or reported only the odd ratio in follow-up years were excluded.

Two reviewers (Sagad and Ibrahim) screened the titles and abstracts of the identified studies and assessed the full text of potentially eligible studies. Any disparity was resolved by consensus. The following information extracted from each article: authors, year, region of study, sample size and reported overall prevalence of thyroid autoimmune diseases and clinical status of thyroid diseases. We extracted the relevant data using Microsoft Office Excel.

The included studies were assessed for quality; two authors (Sagad, Ibrahim) independently using Newcastle–Ottawa Scale adapted for cross sectional studies assessment tool, with a score of ≥ 5 out of 10 considered as high quality score. We included studies of high quality score in this meta-analysis.

Relevant data were exported to OpenMeta Analyst version 10.10 software for analysis [18]. Meta-analysis of pooled prevalence with 95% CIs was carried out using a random effects model, and results were displayed in a forest plot. Heterogeneity among studies was estimated using the Cochran’s Q and I2 statistic and is considered as low, moderate or high for 25%, 50%, and 75%, respectively. Publication bias was determined using Comprehensive Meta Analysis software based on Begg’s test, Egger’s test and the symmetry of funnel plot [19, 20], and Duvall and Tweedie trim and fill method was considered for final effect size estimation when publication bias detected [21]. Subgroup analyses by continents were carried out due to high heterogeneity between studies. Significance level was set at 0.05.


After reviewing titles and abstracts of the identified studies, 704 studies were excluded. Full texts of 33 studies were screened and 15 studies of which were subsequently omitted because of low quality and insufficient data to estimate the outcomes of interest. A total of 18 studies published from (1986) to (2018) representing 2719 patients which fulfilled the eligibility criteria, were included in this meta-analysis (Table 1). The process of study selection is summarized in a flow chart shown in Additional file 1: Fig S1. Ten of the included studies were done in Europe, five studies from Asia, two from USA and one from Egypt.

Table 1 The descriptive summary of 18 studies on the prevalence of thyroid autoimmune diseases among patients with Turner Syndrome

Prevalence of autoimmune thyroid diseases ranged from 10.5 to 67.5% among reviewed studies. However, meta-analysis for the included studies showed that the pooled prevalence of ATDs among TS population was 38.6% (95% CI 29.7–47.6%) (Fig. 1), I2 test showed a high level of heterogeneity (I2 = 96.6%, P < 0.001). Based on subgroup analyses by continents, the pooled prevalence of ATDs among patients was 39.4% (95 CI 27.3–51.4%) in Europe, and 29.1% (95% CI 13.3–45.1%) in Asia (Fig. 1). Publication bias was detected based on Begg’s test (P < 0.02) and asymmetry of funnel plot (Additional file 2: Fig S2). Duvall and Tweedie trim and fill method indicated (6) potential studies missing, and the point estimate was 25.5% (95% CI 17.8–35%).

Fig. 1
figure 1

Pooled prevalence of autoimmune thyroid diseases among patients with Turner Syndrome

Pooled estimate showed that 34.2% (95% CI 26.7–41.6%) of the patients had HT (I2 = 94.9%, P < 0.001) (Additional file 3: Fig S3), 12.7% (95% CI 9.30–16.1%) of the patients had clinical hypothyroidism (I2 = 87.47%, P < 0.001) (Additional file 4: Fig S4), and 2.6% (95% CI 1.5–3.8%) had hyperthyroidism (I2 = 0%, P = 0.777) (Additional file 5: Fig S5).

We included 10 studies which assessed the association of karyotyping with the occurrence of ATDs among the Turner Syndrome patients. Frequency of ATDs was higher in patients with Iso-Xq karyotype (66.2%) (95% CI 54.4–78.0%) (Additional file 6: Fig S6) than patients with monosomy 45, X (36.9%) (95% CI 27.8–46.0%) (Additional file 7: Fig S7) and other karyotypes (33.5%) (95% CI 22.9–44.1%) (Additional file 8: Fig S8) (Table 2).

Table 2 Descriptive summary of 10 studies on the prevalence of ATDs among patients with different karyotypes of Turner Syndrome


We have updated estimate of the global prevalence of autoimmune thyroid diseases in Turner Syndrome population. Existing evidence from 18 included studies showed that more than one-third of patients with Turner Syndrome had autoimmune thyroid diseases. This finding is higher as compared to previous reviews done by Gravholt and Davenport [38, 39] reporting 10–25% as prevalence of autoimmune thyroid disease among Turner Syndrome population. Likewise, De Marqui et al. and Chen et al. [5, 34] revealed that ATDs are the most common autoimmune disorders occur in TS.

Discrepancy between prevalence rates from included studies might be attributable to the differences of karyotyping, diagnostic methods and age of presentation among patients [7], as well as demographic characteristics [34]. In this meta-analysis, the prevalence rate of ATDs in iso-Xq karyotype patient was higher than other karyotypes. Effect of karyotyping was supported by several studies. Bakalov et al. and Elsheikh et al. [9, 29] reported that the risk for HT was higher in the Iso-chromosome Xq population. Mortensen et al. and Chen et al. [28, 34] showed that the frequency of ATDs increase with age, although ATDs can occur before the age of 8 years [7]. Previous systematic review suggests screening for thyroid diseases to continue throughout adult life [11].

Findings of this meta-analysis confirm higher prevalence rate of hypothyroidism status than grave’s disease in TS patients diagnosed with thyroid autoimmunity. Similar findings were reported by several studies [29, 30, 40, 41], and Hashimoto’s thyroiditis was found to be the most common autoimmune disorder in TS girls [40]. Euthyroidism with absence of signs and symptoms a common clinical phenotype in TS patients diagnosed with thyroid autoimmunity. Transition from one clinical phenotype to another over time can occur [14].

Geographic gaps exist in the data on ATDs in Turner Syndrome population, especially in the American and African countries. The studies included in this meta-analysis were mostly from Europe and only one study from Africa.

Autoimmune thyroid diseases occur with increased frequency in patients with Turner Syndrome. Health care providers need to be aware of the clinically important association between thyroid diseases and Turner Syndrome. Optimal screening and early detection of thyroid diseases among children with Turner Syndrome are required to ensure effective management.


The findings of this study need to be considered in the context of some limitations. Articles in non-indexed journals and non-published papers were not searched, which might make publication bias. Inclusion of studies published only in English may cause language bias. Also, this study did not determine the possible risk factors that may contribute for the occurrence of ATDs in Turner Syndrome patients.



autoimmune thyroid disease


Turner Syndrome


Hashimoto’s thyroiditis


Graves’ disease


  1. Gravholt C. Epidemiological, endocrine and metabolic features in Turner Syndrome. Eur J Endocrinol. 2004;151(6):657–87.

    Article  CAS  Google Scholar 

  2. Aversa T, Gallizzi R, Salzano G, Zirilli G, De Luca F, Valenzise M. Atypical phenotypic aspects of autoimmune thyroid disorders in young patients with Turner Syndrome. Ital J Pediatr. 2018;44(1):12.

    Article  Google Scholar 

  3. Aversa T, Lombardo F, Valenzise M, Messina M, Sferlazzas C, Salzano G, et al. Peculiarities of autoimmune thyroid diseases in children with Turner or Down syndrome: an overview. Ital J Pediatr. 2015;41(1):39.

    Article  Google Scholar 

  4. Morgan T. Turner Syndrome: diagnosis and management. Am Fam Physician. 2007;76(3):405–10.

    PubMed  Google Scholar 

  5. De Marqui A. Turner Syndrome and genetic polymorphism: a systematic review. Revista Paulista de Pediatria. 2015;33(3):363–70 (English Edition).

    Article  Google Scholar 

  6. Wasniewska M, Aversa T, De Luca F, Valenzise M, Messina M, Lombardo F. Epidemiological, pathophysiological and clinical peculiarities of Graves’ disease in children with Down and Turner Syndrome: a literature review. Health. 2014;06(12):1447–52.

    Article  Google Scholar 

  7. Grossi A, Crinò A, Luciano R, Lombardo A, Cappa M, Fierabracci A. Endocrine autoimmunity in Turner Syndrome. Ital J Pediatr. 2013;39(1):79.

    Article  Google Scholar 

  8. Jørgensen K, Rostgaard K, Bache I, Biggar R, Nielsen N, Tommerup N, et al. Autoimmune diseases in women with Turner’s syndrome. Arthritis Rheum. 2010;62(3):658–66.

    Article  Google Scholar 

  9. Bakalov V, Gutin L, Cheng C, Zhou J, Sheth P, Shah K, et al. Autoimmune disorders in women with Turner Syndrome and women with karyotypically normal primary ovarian insufficiency. J Autoimmun. 2012;38(4):315–21.

    Article  Google Scholar 

  10. Wasniewska M, Salerno M, Corrias A, Mazzanti L, Matarazzo P, Corica D, et al. The evolution of thyroid function after presenting with Hashimoto Thyroiditis is different between initially Euthyroid girls with and those without Turner Syndrome. Horm Res Paediatr. 2016;86(6):403–9.

    Article  CAS  Google Scholar 

  11. Bondy C. Care of girls and women with Turner Syndrome: a guideline of the Turner Syndrome study group. J Clin Endocrinol Metab. 2007;92(1):10–25.

    Article  CAS  Google Scholar 

  12. El-Mansoury M, Bryman I, Berntorp K, Hanson C, Wilhelmsen L, Landin-Wilhelmsen K. Hypthyroidism is common in Turner Syndrome: results of a five-year follow-up. J Clin Endorinol Metab. 2005;90:2131–5.

    Article  CAS  Google Scholar 

  13. Ivarsson S, Ericsson U, Nilsson K, Gustafsson J, Hagenäs L, Häger A, et al. Thyroid autoantibodies, Turner’s syndrome and growth hormone therapy. Acta Paediatr. 1995;84(1):63–5.

    Article  CAS  Google Scholar 

  14. Brix T, Hegedüs L. Twin studies as a model for exploring the aetiology of autoimmune thyroid disease. Clin Endocrinol. 2012;76(4):457–64.

    Article  CAS  Google Scholar 

  15. Medeiros CC, Marini SH, Baptista MT, Guerra G Jr, Maciel-Guerra AT. Turner’s syndrome and thyroid disease: a transverse study of pediatric patients in Brazil. J Pediatr Endocrinol Metab. 2000;13:357–62.

    Article  CAS  Google Scholar 

  16. Caturegli P, De Remigis A, Rose N. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 2014;13(4–5):391–7.

    Article  CAS  Google Scholar 

  17. Liberati A, Altman DG, Tetzlaf J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1–34.

    Article  Google Scholar 

  18. OpenMetaAnalyst, Wallace BC, Dahabreh IJ, Trikalinos TA, Lau J, Trow P, Schmid CH. Closing the gap between methodologists and end-users: R as a computational back-end. J Stat Softw. 2012;49:5.

    Google Scholar 

  19. Borenstein M, Hedges LV, Higgins J, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1(2):97–111.

    Article  Google Scholar 

  20. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;1:1088–101.

    Article  Google Scholar 

  21. Duval S, Tweedie R. Trim and fll: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56(2):455–63.

    Article  CAS  Google Scholar 

  22. Hamza RT, Raof NA, Abdallah KO. Prevalence of multiple forms of autoimmunity in Egyptian patients with Turner Syndrome: relation to karyotype. J Pediatr Endocrinol Metab. 2013;26:545–50.

    Article  CAS  Google Scholar 

  23. Germain EL, Plotnick LP. Age-related anti-thyroid antibodies and thyroid abnormalities in Turner Syndrome. Acta Paediatr Scand. 1986;75:750–5.

    Article  CAS  Google Scholar 

  24. Yeşilkaya E, Bereket A, Darendeliler F, Baş F, Poyrazoğlu Ş, Küçükemre Aydın B, Darcan Ş, Dündar B, Büyükinan M, Kara C, Sarı E, Adal E, Akıncı A, Atabek ME, Demirel F, Çelik N, Özkan B, Özhan B, Orbak Z, Ersoy B, Doğan M, Ataş A, Turan S, Gökşen D, Tarım Ö, Yüksel B, Ercan O, Hatun Ş, Şimşek E, Ökten A, Abacı A, Döneray H, Özbek MN, Keskin M, Önal H, Akyürek N, Bulan K, Tepe D, Emeksiz HC, Demir K, Kızılay D, Topaloğlu AK, Eren E, Özen S, Abalı S, Akın L, Selver Eklioğlu B, Kaba S, Anık A, Baş S, Ünüvar T, Sağlam H, Bolu S, Özgen T, Doğan D, Deniz Çakır E, Şen Y, Andıran N, Çizmecioğlu F, Evliyaoğlu O, Karagüzel G, Pirgon Ö, Çatlı G, Can HD, Gürbüz F, Binay Ç, Baş VN, Fidancı K, Polat A, Gül D, Açıkel C, Demirbilek H, Cinaz P, Bondy C. Turner Syndrome and associated problems in Turkish children: a multicenter study. J Clin Res Pediatr Endocrinol. 2015;7:27–36.

    Article  Google Scholar 

  25. Hoxha P, Babameto-Laku A, Vyshka G, Gjoka K, Minxuri D, Myrtaj E, et al. Turner Syndrome in Albania and the efficacy of its treatment with growth hormone. J Pediatr Endocrinol Metab. 2015;28(11–12):1227–34.

    CAS  PubMed  Google Scholar 

  26. Bettendorf M, Doerr H, Hauffa B, Lindberg A, Mehls Ο, Partsch C, 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 Pediatr Endocrinol Metab. 2006;19(2):149–54.

    Article  CAS  Google Scholar 

  27. Calcaterra V, Klersy C, Muratori T, Caramagna C, Brizzi V, Albertini R, et al. Thyroid ultrasound in patients with Turner Syndrome: influence of clinical and auxological parameters. J Endocrinol Invest. 2010;34(4):260–4.

    Article  Google Scholar 

  28. Mortensen KH, Cleemann L, Hjerrild BE, Nexo E, Locht H, Jeppesen EM, Gravholt H. Incrased prevalence of autoimmunity in Turner Syndrome-influence of age. Clin Exp Immunol. 2009;156:205–10.

    Article  CAS  Google Scholar 

  29. Elsheikh M, Wass JA, Conway GS. Autoimmune thyroid syndrome in women with Turner’s syndrome-the association with karyotype. Clin Endocrinol (Oxf). 2001;55:223–6.

    Article  CAS  Google Scholar 

  30. Radetti G, Mazzanti L, Paganini C, Bernasconi S, Russo G, Rigon F, Cacciari E. Frequency, clinical and laboratory features of thyroiditis in girls with Turner’s syndrome. The Italian Study Group for Turner’s syndrome. Acta Paediatr. 1995;84:909–12.

    Article  CAS  Google Scholar 

  31. De Kerdanet M, Lucas J, Lemee F, Lecornu M. Turner’s syndrome with X-isochromosome and Hashimoto’s thyroiditis. Clin Endocrinol (Oxf). 1994;41:673–6.

    Article  Google Scholar 

  32. Livadas S, Xekouki P, Fouka F, Kanaka-Gantenbein C, Kaloumenou I, Mavrou A, et al. Prevalence of thyroid dysfunction in Turner’s syndrome: a long-term follow-up study and brief literature review. Thyroid. 2005;15(9):1061–6.

    Article  CAS  Google Scholar 

  33. Chang P, Tsai WY, Hou JW, Hsiao PH, Lee JS. Autoimmune thyroiditis in children with Turner Syndrome. J Formos Med Assoc. 2000;Vol 99 No:11.

    Google Scholar 

  34. Chen R, Zhang Y, Yang X, Lin X, Yuan X. Thyroid disease in Chinese girls with Turner Syndrome. J Pediatr Endocrinol Metab. 2015;28(1–2):201–5.

    PubMed  Google Scholar 

  35. Fukuda I, Hizuka N, Kurimoto M, Morita J, Tanaka S, Yamakado Y, Takano K. Autoimmune thyroid diseases in 65 Japanese women with Turner Syndrome. Endocr J. 2009;56:983–6.

    Article  Google Scholar 

  36. Huang Y, Lee C, Wu M, Liu S, Tung Y, Ho H, et al. The spectrum of 45, X/46, XY mosaicism in Taiwanese children: the experience of a single center. J Formos Med Assoc. 2018.

    Article  PubMed  Google Scholar 

  37. Wu H, Li H. Karyotype classification, clinical manifestations and outcome in 124 Turner Syndrome patients in China. Annales d’Endocrinologie. 2018.

    Article  PubMed  Google Scholar 

  38. Claus Højbjerg Gravholt. Aspects of the treatment of Turner Syndrome. Expert Opin Pharmacother. 2001;2(10):1633–47.

    Article  Google Scholar 

  39. Davenport ML. Aspects of the treatment of Turner Syndrome. J Clin Endocrinol Metab. 2010;95(4):1487–95.

    Article  CAS  Google Scholar 

  40. Aversa T, Messina M, Mazzanti L, Salerno M, Mussa A, Faienza M, et al. The association with Turner Syndrome significantly affects the course of Hashimoto’s thyroiditis in children, irrespective of karyotype. Endocrine. 2014;50(3):777–82.

    Article  Google Scholar 

  41. Gawlik A, Gawlik T, Januszek-Trzciakowska A, Patel H, Malecka-Tendera E. Incidence and dynamics of thyroid dysfunction and thyroid autoimmunity in girls with Turner’s syndrome: a long-term follow-up study. Horm Res Paediatr. 2011;76(5):314–20.

    Article  CAS  Google Scholar 

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Authors’ contributions

SM: involved in the conception of the research idea; SM and IE: undertook data extraction and analysis; SM, IE, AA, AN, GI and AM: interpreted the results and drafted the manuscript. All authors revised the final manuscript. All authors read and approved the final manuscript.


The authors would like to acknowledge Abdalla Omer for helping us in data extraction.

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The authors declare that they have no competing interests.

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The dataset generated during this study are available from the corresponding author on reasonable request.

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Correspondence to Sagad Omer Obeid Mohamed.

Additional files

Additional file 1: Fig S1.

The flow diagram for the process of study selection and systematic review of literature.

Additional file 2: Fig S2.

Funnel plot showing evidence of publication bias among 18 studies in a meta-analysis of ATDs prevalence in TS population. Six missing studies added in the left side.

Additional file 3: Fig S3.

Pooled prevalence of HT among patients with Turner Syndrome diagnosed with ATDs.

Additional file 4: Fig S4.

Pooled prevalence of clinical hypothyroidism among patients with Turner Syndrome diagnosed with ATDs.

Additional file 5: Fig S5.

Pooled prevalence of hyperthyroidism among patients with Turner Syndrome diagnosed with ATDs.

Additional file 6: Fig S6.

Pooled prevalence of ATDs among patients with Iso-Xq karyotype of Turner Syndrome.

Additional file 7: Fig S7

Pooled prevalence of ATDs among patients with monosomy 45, X karyotype of Turner Syndrome.

Additional file 8: Fig S8.

Pooled prevalence of ATDs among patients with other forms of karyotypes of Turner Syndrome.

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Mohamed, S.O.O., Elkhidir, I.H.E., Abuzied, A.I.H. et al. Prevalence of autoimmune thyroid diseases among the Turner Syndrome patients: meta-analysis of cross sectional studies. BMC Res Notes 11, 842 (2018).

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