Endocrine autoimmunity in Turner syndrome

Italian Journal of Pediatrics

Alessandra Fierabracci⁴  Marco Cappa¹  Antonietta Lombardo²  Rosa Luciano³  Antonino Crinò¹  Armando Grossi¹ 

[1] Division of Endocrinology, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy;Cytogenetics and Molecular Genetics Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy;Research Laboratories, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy;Autoimmunity Laboratory, Immunology Area, Bambino Gesù Children’s Hospital IRCCS, Piazza S. Onofrio, 4-00165 Rome, Italy

关键词: Karyotype analysis;    Thyroid disease;    Autoantibodies;    Autoimmunity;    Turner syndrome;   

Others  :  812303
DOI  :  10.1186/1824-7288-39-79

 received in 2013-09-09, accepted in 2013-12-14,  发布年份 2013

【 摘 要 】

Background

Turner syndrome is caused by numeric and structural abnormalities of the X chromosome. An increased frequency of autoimmunity as well as an elevated incidence of autoantibodies was observed in Turner patients. The aim of this study was to conduct a retrospective analysis of the incidence of autoimmunity in 66 Italian patients affected by Turner syndrome.

Methods

Sixty-six unselected and consecutive Italian Turner patients were recruited. The association between age, karyotype and the presence of clinical/pre-clinical autoimmune disorders and of autoantibodies was examined.

Results

Out of the 66 Turner patients, 26 had thyroid autoimmune disorders (39.4%), 14 patients had Hashimoto’s thyroiditis with clinical or subclinical hypothyroidism (21.2%) and 12 patients had circulating anti-thyroid antibodies, echographic pattern of diffuse hypoechogenicity and normal thyroid hormone levels (18.2%). None were affected by Graves’ disease. We analyzed the overall incidence of thyroid autoimmunity within the 3 different age groups 0–9.9, 10–19.9 and 20–29.9 years. No statistically significant difference was observed in the incidence of thyroid autoimmunity within the age-groups (χ²-test p > 0.05).

Out of the 66 patients, 31 patients had the 45,X karyotype; within this first group 14 out of 31 patients were affected by autoimmune thyroid disease. A second group of 29 patients included 19 patients with mosaicism, 5 patients with deletions and 5 patients with ring chromosome; out of these 29 patients 7 were affected by autoimmune thyroid disease. A third group included 6 patients with X isochromosome; 5 out of 6 were affected by autoimmune thyroid disease. A statistically significant difference in the frequency of thyroid autoimmunity within the different karyotype groups was observed (χ²-test p = 0.0173).

When comparing the X isochromosome group with the pooled group of other karyotypes, of note, the frequency of thyroid autoimmunity was statistically higher in the X isochromosome group (Fisher exact test p = 0.0315).

Conclusions

Our data confirm a high frequency of thyroid autoimmunity in Italian Turner patients. Patients with X isochromosome are more prone to develop thyroid autoimmunity. Further, an early assay of autoantibodies and monitoring thyroid hormones is fundamental for detecting hypothyroidism earlier and start adequate replacement therapy.

【 授权许可】

   
2013 Grossi et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Grossi A, Palma A, Zanni G, Novelli A, Loddo S, Cappa M, Fierabracci A: Multiorgan autoimmunity in a Turner syndrome patient with partial monosomy 2q and trisomy 10p. Gene 2013, 515:439-443.
• [2]Larizza D, Calcaterra V, Martinetti M: Autoimmune stigmata in Turner syndrome: when lacks an X chromosome. J Autoimmun 2009, 33:25-30.
• [3]McCarthy K, Bondy CA: Turner syndrome in childhood and adolescence. Expert Rev Endocrinol Metab 2008, 3:771-775.
• [4]Dias Mdo C, Castro LC, Gandolfi L, Almeida RC, Córdoba MS, Pratesi R: Screening for celiac disease among patients with Turner syndrome in Brasília, DF, midwest region of Brazil. Arq Gastroenterol 2010, 47:246-249.
• [5]Menasha J, Levy B, Hirschhorn K, Kardon NB: Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12-year study. Genet Med 2005, 7:251-263.
• [6]Bianchi I, IIeo A, Gershwin ME, Invernizzi P: The X chromosome and immune associated genes. J Autoimmun 2012, 38:J187-J192.
• [7]Jөrgensen KT, Rostgaard K, Bache I, Biggar RJ, Nielsen NM, Tommerup N, Frisch M: Autoimmune diseases in women with Turner’s syndrome. Arthritis Rheum 2010, 62:658-666.
• [8]Fierabracci A: Unravelling the role of infectious agents in the pathogenesis of human autoimmunity: the hypothesis of the retroviral involvement revisited. Curr Mol Med 2009, 9:1024-1033.
• [9]Germain EL, Plotnick LP: Age-related anti-thyroid antibodies and thyroid abnormalities in Turner syndrome. Acta Paediatr Scand 1986, 75:750-755.
• [10]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, 38:315-321.
• [11]Cogni G, Chiovato L: An overview of the pathogenesis of thyroid autoimmunity. Hormones (Athens) 2013, 12:19-29.
• [12]Chiovato L, Larizza D, Bendinelli G, Tonacchera M, Marinó M, Mammoli C, Lorini R, Severi F, Pinchera A: Autoimmune hypothyroidism and hyperthyroidism in patients with Turner's syndrome. Eur J Endocrinol 1996, 134:568-575.
• [13]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, 13:357-362.
• [14]Medeiros CC, De Lemos-Marini SH, Filho MB, Camargo EE, Santos AO, Magna LA, Guerra-Júnior G, Baptista MT, Maciel-Guerra AT: Turner’s syndrome and subclinical autoimmune thyroid disease: a two-year follow-up study. J Pediatr Endocrinol Metab 2009, 22:109-118.
• [15]Bettendorf M, Doerr HG, Hauffa BP, Lindberg A, Mehls O, Partsch CJ, Schwarz HP, Stahnke N, Ranke MB: 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, 19:149-154.
• [16]Marcocci C, Bartalena L, Martino E, Fenzi GF: Graves’ disease and Turner’s syndrome. J Endocrinol Invest 1980, 3:429-431.
• [17]Livadas S, Xekouki P, Fouka F, Kanaka-Gantenbein C, Kaloumenou I, Mavrou A, Constantinidou N, Dacou-Voutetakis C: Prevalence of thyroid dysfunction in Turner’s syndrome: a long-term follow-up study and brief literature review. Thyroid 2005, 15:1061-1066.
• [18]Elsheikh M, Wass JA, Conway GS: Autoimmune thyroid syndrome in women with Turner’s syndrome-the association with karyotype. Clin Endocrinol (Oxf) 2001, 55:223-226.
• [19]Sparkes RS, Motulsky AG: The Turner syndrome with isochromosome X and Hashimoto’s thyroiditis. Ann Intern Med 1967, 67:132-144.
• [20]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, 26:545-550.
• [21]De Kerdanet M, Lucas J, Lemee F, Lecornu M: Turner’s syndrome with X-isochromosome and Hashimoto’s thyroiditis. Clin Endocrinol (Oxf) 1994, 41:673-676.
• [22]Reato G, Morlin L, Chen S, Furmaniak J, Smith BR, Masiero S, Albergoni MP, Cervato S, Zanchetta R, Betterle C: Premature ovarian failure in patients with autoimmune Addison’s disease: clinical, genetic, and immunological evaluation. J Clin Endocrinol Metab 2011, 96:E1255-E1261.
• [23]Cooper DS, Biondi B: Subclinical thyroid disease. Lancet 2012, 379:1142-1154.
• [24]Marcocci C, Vitti P, Cetani F, Catalano F, Concetti R, Pinchera A: Thyroid ultrasonography helps to identify patients with diffuse lymphocytic thyroiditis who are prone to develop hypothyroidism. J Clin Endocrinol Metab 1991, 72:209-213.
• [25]Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R, Troncone R, Giersepen K, Branski D, Catassi C, Lelgeman M, Mäki M, Ribes-Koninckx C, Ventura A, Zimmer KP: SPGHAN Working Group on Coeliac Disease Diagnosis; ESPGHAN Gastroenterology Comittee; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition: European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012, 54:136-160.
• [26]Bright GM, Blizzard RM, Kaiser DL, Clarke WL: Organ-specific autoantibodies in children with common endocrine disease. J Pediatr 1982, 100:8-14.
• [27]Gluck M, Attanasio A, Speer U, Butenandt O, Tietze HU, Scherbaum WA: Prevalence of autontibodies in endocrine organs in girls with Ulrich-Turner syndrome aged 5–14 years. Hor Res 1992, 38:114-119.
• [28]Mortensen KH, Cleemann L, Hjerrild BE, Nexo E, Locht H, Jeppesen EM, Gravholt CH: Incrased prevalence of autoimmunity in Turner syndrome-influence of age. Clin Exp Immunol 2009, 156:205-210.
• [29]Kucharska AM, Czarnocka B, Demkow U: Anti-natrium/iodide symporter antibodies and other anti-thyroid antibodies in children with Turner’s syndrome. Adv Exp Med Biol 2013, 756:131-138.
• [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, 84:909-912.
• [31]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, 90:2131-2135.
• [32]Aghini-Lombardi F, Antonangeli L, Martino E, Vitti P, Maccherini D, Leoli F, Rago T, Grasso L, Valeriano R, Balestrieri A, Pinchera A: The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey. J Clin Endocrinol Metab 1999, 84:561-566.
• [33]McLeod DS, Cooper DS: The incidence and prevalence of thyroid autoimmunity. Endocrine 2012, 42:252-265.
• [34]Bonamico M, Pasquino AM, Mariani P, Danesi HM, Culasso F, Mazzanti L, Petri A, Bona G: Italian Society Of Pediatric Gastroenterology Hepatology (SIGEP); Italian Study Group for Turner Syndrome (ISGTS). Prevalence and clinical picture of celiac disease in Turner syndrome. J Clin Endocrinol Metab 2002, 87:5495-5498.
• [35]Gawlik A, Kaczor B, Kaminska H, Zachurzok-Buczynska A, Gawlik T, Malecka-Tendera E: Quality of medical follow-up of young women with Turner syndrome treated in one clinical center. Horm Res Paediatr 2012, 77:222-228.
• [36]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, 56:983-986.