Abstract
Objectives
Short stature and thyroid autoimmunity are common comorbidities in Turner syndrome (TS). Recombinant human growth hormone (rhGH) significantly improves height growth in TS individuals. This study aims to investigate the association of thyroid autoimmunity and the response to rhGH treatment in TS patients.
Methods
Medical records of 494 patients with TS were reviewed. Among 126 patients who regularly tested for thyroid autoantibodies, 108 patients had received rhGH treatment. Clinical characteristics, including karyotype and the presence of autoimmune thyroid diseases, as well as rhGH treatment records were analyzed. Height velocity (HV) of patients with or without thyroid autoimmunity was compared to assess the response to rhGH treatment. For patients who developed thyroid autoantibodies during rhGH treatment, HV before and after antibody presence were compared.
Results
45XO monosomy presented in 36% (176/496) of patients. 42.1% of patients (53/126) had elevated circulating anti-thyroid peroxidase antibody and anti-thyroglobulin antibody. In 108 patients who received rhGH treatment, HVs were significantly correlated to age, height, weight and BMI at the initiation of treatment. For patients who developed thyroid autoantibodies during rhGH treatment, HVs after thyroid autoantibody presence significantly decreased compared with HVs before thyroid autoantibody detection (n=44, p=0.0017).
Conclusions
Our data suggested that in TS patients who developed thyroid autoantibodies during rhGH treatment, the response to rhGH is negatively associated with the development of thyroid autoimmunity.
Funding source: The Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences
Award Identifier / Grant number: No. 2017PT32020 and No. 2018PT32001
Funding source: The CAMS Innovation Fund for Medical Science
Award Identifier / Grant number: CAMS-2016-I2M-1-002
Research funding: This work was supported by CAMS Innovation Fund for Medical Science (CAMS-2016-I2M-1-002) and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2017PT32020, No. 2018PT32001) provided funding supports in data preparation of this study.
Author contributions: Song YY and Yang HB collected data, interpreted results and prepared the manuscript. Song YY performed statistical analysis. Wang LJ and Gong FY contributed to data acquisition and provided critical feedbacks. Zhu HJ and Pan H designed, organized the study and revised the manuscript.
Competing interest: The authors have no conflicts of interest to declare.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The study protocol was approved by the Institutional Review Board of Peking Union Medical College Hospital (JS-1663).
References
1. Gravholt, C. New international clinical practice guidelines for the care of girls and women with Turner syndrome. Endocr Abstr 2017;49:GS1.1. https://doi.org/10.1530/endoabs.49.gs1.1.Search in Google Scholar
2. Ogata, T. SHOX haploinsufficiency and its modifying factors. J Pediatr Endocrinol Metab 2002;15:1289–94.Search in Google Scholar
3. Li, J, Wu, W, Liang, Y, Luo, XP. Analysis of the influencing factors of recombinant human growth hormone effect in the children with Turner syndrome. Chin J Pediatr 2018;56:866–70. https://doi.org/10.3760/cma.j.issn.0578-1310.2018.11.014.Search in Google Scholar
4. Linglart, A, Cabrol, S, Berlier, P, Stuckens, C, Wagner, K, de Kerdanet, M, et al.. Growth hormone treatment before the age of four years prevents short stature in young girls with Turner syndrome. Eur J Endocrinol 2011;164:891–7. https://doi.org/10.1530/eje-10-1048.Search in Google Scholar
5. Soriano-Guillen, L, Coste, J, Ecosse, E, Tauber, JLM, Cabrol, S, Nicolino, M, et al.. Adult height and pubertal growth in Turner syndrome after treatment with recombinant growth hormone. J Clin Endocrinol Metab 2005;90:5197–204. https://doi.org/10.1210/jc.2005-0470.Search in Google Scholar
6. Stephure, DK, Anglin, G, Chipman, J, Daneman, D, Dean, HJ, Guyda, HJ, et al.. Impact of growth hormone supplementation on adult height in Turner syndrome: results of the Canadian randomized controlled trial. J Clin Endocrinol Metab 2005;90:3360–6. https://doi.org/10.1210/jc.2004-2187.Search in Google Scholar
7. 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;44:12. https://doi.org/10.1186/s13052-018-0447-3.Search in Google Scholar
8. Chiovato, L, Larizza, D, Bendinelli, G, Tonacchera, M, Marino, M, Mammoli, C, et al.. Autoimmune hypothyroidism and hyperthyroidism in patients with Turner’s syndrome. Eur J Endocrinol 1996;134:568–75. https://doi.org/10.1530/eje.0.1340568.Search in Google Scholar
9. Mohamed, SOO, Elkhidir, IHE, Abuzied, AIH, Noureddin, AAMH, Ibrahim, GAA, Mahmoud, AAA. Prevalence of autoimmune thyroid diseases among the Turner syndrome patients: meta-analysis of cross sectional studies. BMC Res Notes 2018;11:842. https://doi.org/10.1186/s13104-018-3950-0.Search in Google Scholar
10. Sinclair, D. Clinical and laboratory aspects of thyroid autoantibodies. Ann Clin Biochem 2006;43:173–83. https://doi.org/10.1258/000456306776865043.Search in Google Scholar
11. Mandel, S, Moreland, E, Nichols, V, Hanna, C, Lafranchi, S. Changes in insulin-like growth-factor-I (Igf-I), Igf-binding protein-3, growth-hormone (Gh)-binding protein, erythrocyte Igf-I receptors, and growth-rate during Gh treatment. J Clin Endocrinol Metab 1995;80:190–4. https://doi.org/10.1210/jcem.80.1.7530256.Search in Google Scholar
12. Michelle, M, Smith, TJ. 40 years OF IGF1: IGF1 receptor and thyroid-associated ophthalmopathy. J Mol Endocrinol 2018;61:T29–43. https://doi.org/10.1530/JME-17-0276.Search in Google Scholar
13. Xuan, SH, Kitamura, T, Nakae, J, Politi, K, Kido, Y, Fisher, PE, et al.. Defective insulin secretion in pancreatic beta cells lacking type 1 IGF receptor. J Clin Invest 2002;110:1011–9. https://doi.org/10.1172/jci0215276.Search in Google Scholar
14. Pritchard, J, Tsui, S, Horst, N, Cruikshank, WW, Smith, TJ. Synovial fibroblasts from patients with rheumatoid arthritis, like fibroblasts from Graves’ disease, express high levels of IL-16 when treated with Igs against insulin-like growth factor-1 receptor. J Immunol 2004;173:3564–9. https://doi.org/10.4049/jimmunol.173.5.3564.Search in Google Scholar
15. Wilson, JD. Peking-Union-Medical-College-Hospital, a palace of endocrine treasures. J Clin Endocrinol Metab 1993;76:815–6. https://doi.org/10.1210/jc.76.4.815.Search in Google Scholar
16. Vance, ML, Mauras, N. Growth hormone therapy in adults and children. N Engl J Med 1999;341:1206–16. https://doi.org/10.1056/nejm199910143411607.Search in Google Scholar
17. Van den Broeck, J, Hokken-Koelega, A, Wit, JM. Validity of height velocity as a diagnostic criterion for idiopathic growth hormone deficiency and Turner syndrome. Horm Res 1999;51:68–73. https://doi.org/10.1159/000023317.Search in Google Scholar
18. Elsheikh, M, Wass, JAH, Conway, GS. Autoimmune thyroid syndrome in women with Turner’s syndrome – the association with karyotype. Clin Endocrinol 2001;55:223–6. https://doi.org/10.1046/j.1365-2265.2001.01296.x.Search in Google Scholar
19. Mortensen, KH, Cleemann, L, Hjerrild, BE, Nexo, E, Locht, H, Jeppesen, EM, et al.. Increased prevalence of autoimmunity in Turner syndrome – influence of age. Clin Exp Immunol 2009;156:205–10. https://doi.org/10.1111/j.1365-2249.2009.03895.x.Search in Google Scholar
20. El-Mansoury, M, Bryman, I, Berntorp, K, Hanson, C, Wilhelmsen, L, Landin-Wilhelmsen, K. Hypothyroidism is common in Turner syndrome: results of a five-year follow-up. J Clin Endocrinol Metab 2005;90:2131–5. https://doi.org/10.1210/jc.2004-1262.Search in Google Scholar
21. Devernay, M, Bolca, D, Kerdjana, L, Aboura, A, Gerard, B, Tabet, A-C, et al.. Parental origin of the X-chromosome does not influence growth hormone treatment effect in Turner syndrome. J Clin Endocrinol Metab 2012;97:E1241–8. https://doi.org/10.1210/jc.2011-3488.Search in Google Scholar
22. Kochi, C, Longui, CA, Lemos-Marini, SHV, Guerra, GJ, Melo, MB, Calliari, LEP, et al.. The influence of parental origin of X chromosome genes on the stature of patients with 45 X Turner syndrome. Genet Mol Res 2007;6:1–7.Search in Google Scholar
23. Smith, TJ. Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases? Pharmacol Rev 2010;62:199–236. https://doi.org/10.1124/pr.109.002469.Search in Google Scholar
24. Alzaid, A, Castro, R, Wang, T, Secombes, CJ, Boudinot, P, Macqueen, DJ, et al.. Cross talk between growth and immunity: coupling of the IGF axis to conserved cytokine pathways in rainbow trout. Endocrinology 2016;157:1942–55. https://doi.org/10.1210/en.2015-2024.Search in Google Scholar
25. Bilbao, D, Luciani, L, Johannesson, B, Piszczek, A, Rosenthal, N. Insulin-like growth factor-1 stimulates regulatory T cells and suppresses autoimmune disease. EMBO Mol Med 2014;6:1423–35. https://doi.org/10.15252/emmm.201303376.Search in Google Scholar
26. Smith, TJ, Hegedüs, L, Douglas, RS. Role of insulin-like growth factor-1 (IGF-1) pathway in the pathogenesis of Graves’ orbitopathy. Best Pract Res Clin Endocrinol Metabol 2012;26:291–302. https://doi.org/10.1016/j.beem.2011.10.002.Search in Google Scholar
27. Kuzawa, CW, Chugani, HT, Grossman, LI, Lipovich, L, Muzik, O, Hof, PR, et al.. Metabolic costs and evolutionary implications of human brain development. Proc Natl Acad Sci USA 2014;111:13010–5. https://doi.org/10.1073/pnas.1323099111.Search in Google Scholar
28. McDade, TW. Life history theory and the immune system: steps toward a human ecological immunology. Yearbk Phys Anthropol 2003;122:100–25. https://doi.org/10.1002/ajpa.10398.Search in Google Scholar
29. Larsson, HE, Vehik, K, Haller, MJ, Liu, X, Akolkar, B, Hagopian, W, et al.. Growth and risk for islet autoimmunity and progression to type 1 diabetes in early childhood: the environmental determinants of diabetes in the young study. Diabetes 2016;65:1988–95.10.2337/db15-1180Search in Google Scholar PubMed PubMed Central
30. Urlacher, SS, Ellison, PT, Sugiyama, LS, Pontzer, H, Eick, G, Liebert, MA, et al.. Tradeoffs between immune function and childhood growth among Amazonian forager-horticulturalists. Proc Natl Acad Sci USA 2018;115:E3914–21. https://doi.org/10.1073/pnas.1717522115.Search in Google Scholar
31. Lamb, MM, Yin, X, Zerbe, GO, Klingensmith, GJ, Dabelea, D, Fingerlin, TE, et al.. Height growth velocity, islet autoimmunity and type 1 diabetes development: the diabetes autoimmunity study in the young. Diabetologia 2009;52:2064–71. https://doi.org/10.1007/s00125-009-1428-2.Search in Google Scholar
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Original Articles
- The utility of next-generation sequencing technologies in diagnosis of Mendelian mitochondrial diseases and reflections on clinical spectrum
- PATRO children, a multi-center, non-interventional study of the safety and effectiveness of Omnitrope® (somatropin) treatment in children: update on the United States cohort
- Effect of vitamin K2 and vitamin D3 on bone mineral density in children with acute lymphoblastic leukemia: a prospective cohort study
- Diagnostic utility of fine needle aspiration cytology in pediatric thyroid nodules based on Bethesda Classification
- Ultrasonographic determination of thyroid volume in infants and children from Aegean region of Turkey and comparison with national and international references
- Association of thyroid autoimmunity and the response to recombinant human growth hormone in Turner syndrome
- Evaluating transition in Turner syndrome in the West of Scotland
- Short-term effects of gonadotropin-releasing hormone analogue treatment on leptin, ghrelin and peptide YY in girls with central precocious puberty
- Metabolic syndrome and risk factors after hematopoietic stem cell transplantation in children and adolescents
- Urinary bisphenol A levels in prepubertal children with exogenous obesity according to presence of metabolic syndrome
- Associations of insulin-induced lipodystrophy in children, adolescents, and young adults with type 1 diabetes mellitus using recombinant human insulin: a cross-sectional study
- Incidence of diabetes in children and adolescents in Dhaka, Bangladesh
- Case Reports
- False-positive very long-chain fatty acids in a case of autoimmune adrenal insufficiency
- Prepubescent unilateral gynecomastia secondary to excessive soy consumption
- Detection of hepatocyte nuclear factor 4A(HNF4A) gene variant as the cause for congenital hyperinsulinism leads to revision of the diagnosis of the mother
- Coexistence of dyschondrosteosis associated to SHOX deficiency, pseudohypoparathyroidism 1B, and chronic autoimmune thyroiditis: a case report
Articles in the same Issue
- Frontmatter
- Original Articles
- The utility of next-generation sequencing technologies in diagnosis of Mendelian mitochondrial diseases and reflections on clinical spectrum
- PATRO children, a multi-center, non-interventional study of the safety and effectiveness of Omnitrope® (somatropin) treatment in children: update on the United States cohort
- Effect of vitamin K2 and vitamin D3 on bone mineral density in children with acute lymphoblastic leukemia: a prospective cohort study
- Diagnostic utility of fine needle aspiration cytology in pediatric thyroid nodules based on Bethesda Classification
- Ultrasonographic determination of thyroid volume in infants and children from Aegean region of Turkey and comparison with national and international references
- Association of thyroid autoimmunity and the response to recombinant human growth hormone in Turner syndrome
- Evaluating transition in Turner syndrome in the West of Scotland
- Short-term effects of gonadotropin-releasing hormone analogue treatment on leptin, ghrelin and peptide YY in girls with central precocious puberty
- Metabolic syndrome and risk factors after hematopoietic stem cell transplantation in children and adolescents
- Urinary bisphenol A levels in prepubertal children with exogenous obesity according to presence of metabolic syndrome
- Associations of insulin-induced lipodystrophy in children, adolescents, and young adults with type 1 diabetes mellitus using recombinant human insulin: a cross-sectional study
- Incidence of diabetes in children and adolescents in Dhaka, Bangladesh
- Case Reports
- False-positive very long-chain fatty acids in a case of autoimmune adrenal insufficiency
- Prepubescent unilateral gynecomastia secondary to excessive soy consumption
- Detection of hepatocyte nuclear factor 4A(HNF4A) gene variant as the cause for congenital hyperinsulinism leads to revision of the diagnosis of the mother
- Coexistence of dyschondrosteosis associated to SHOX deficiency, pseudohypoparathyroidism 1B, and chronic autoimmune thyroiditis: a case report