Scope of epidemiology and daily practice in children with type 1 diabetes in the Netherlands
Hummelink, Engelina
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Hummelink, E. (2019). Scope of epidemiology and daily practice in children with type 1 diabetes in the Netherlands. Rijksuniversiteit Groningen.
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CHAPTEr 4
Thyroid disease and type 1 diabetes mellitus
in dutch children: a nati onwide study (young
dudes-3)
Engelina Spaans, MD, Eelco Schroor, MD, PhD, Klaas Groenier, PhD, Henk Bilo, MD, PhD, Nanne Kleefstra, MD, PhD, Paul Brand, MD, PhD
objective To investigate the prevalence of overt thyroid diseases in children in the Nether-lands with and without type 1 diabetes mellitus (T1DM) study design Nationwide, retrospective cohort study in the Netherlands. Using the national registry of both healthcare reimbursement and pharmaceutical care, data of all Dutch chil-dren (aged 0-14 years) with a diagnosis of T1DM, or a diagnosis of hypo/hyperthyroidism in the period 2009-2011. results The prevalence of thyroid disease was 0.15% in children without T1DM, and 3.43% in children with T1DM (rate ratio 23.59, 95%CI: 19.92, 27.93; p < 0.001). Both hyperthyroid-ism and hypothyroidism were 24 times as likely in children with T1DM than in those without. Thyroid disease was more common in girls than in boys, both in children with T1DM (rate ratio of girls versus boys 3.07, 95% CI 2.10, 4.49) and in children without T1DM (rate ratio 1.59, 95% CI 1.49, 1.69). This sex difference was more pronounced for hypothyroidism than for hyperthyroidism. Conclusions Children with T1DM in the Netherlands are 24 times as likely to develop thyroid disease than their peers without diabetes. Girls with T1DM were more prone to thyroid disease, particularly hypothyroidism.
The incidence and prevalence of autoimmune diseases vary amongst the different diseases and between geographical regions.1 The prevalence of autoimmune thyroid disease (AITD) in a combined population of children and adults in Europe, for example, is estimated to be 3% for hypothyroidism and 0.75% for hyperthyroidism.2 The reported prevalence in the US population are slightly higher: 4.6% and 1.3% for hypothyroidism and hyperthyroidism, respectively.3 Autoimmune diseases tend to coincide, with the association between AITD and type 1 diabetes mellitus (T1DM) being the most common.4,5
Thyroid peroxidase antibodies have been found in 15-30% of adults with T1DM in comparison with 2-10% in matched controls.6 Approximately 50% of thyroid peroxidase
antibody-positive patients with T1DM will develop overt AITD.6,7 In a Dutch population of
adults with type T1DM, the average prevalence of AITD was 11.2%.8
The prevalence of AITD in children, however, is unknown, both in the general population and in children with T1DM. Studies from the previous decade reported detectable anti-thyroid antibodies in 15-19% of children with T1DM.7,9 The prevalence of such antithyroid
autoantibodies increases with age, especially in female adolescents10-12 A recent study from
Korea showed that 26% of children with newly diagnosed T1DM already had antithyroid autoantibodies, suggesting either that the prevalence of AITD in children with T1DM is increasing or that that this phenomenon is specific for Korea.13 Unfortunately, it is at present unknown what proportion of children with autothyroid autoantibodies will develop AITD, with estimates ranging from 3% to 60%.7,9,14-16 The aim of this nationwide cohort study was to investigate the prevalence of overt thyroid disease in children in the Netherlands with and without T1DM. METHods The present study is part of the Young DUDEs initiative (DUtch Diabetes Estimates), a project aimed at investigating the magnitude and impact of T1DM and its complications among children and adolescents in the Netherlands. A detailed description has been published previously.17 In the Netherlands, all children with T1DM are treated by hospital-based paediatricians. Over the time period 2009-2011, reimbursement of hospital care costs was handled na-tionwide through the registration as Diagnosis Treatment Combination (Diagnose-Behandel Combinatie [DBC] in Dutch); physicians and hospitals are required to record the appropriate codes to allow reimbursement to proceed. Each DBC code contains information about the specialty of the attending physician, the patient’s diagnosis, and the type of care provided. All DBC codes and the DBC-associated reimbursements are stored in a national database, managed by Vektis (Zeist, the Netherlands). Vektis also manages other databases such as the Basic Health Insurance Information System, containing demographic information (like
date of birth and sex) for all children registered as inhabitants in the Netherlands, and information on drug prescription. The coverage of this system is 98%.18 Claims records for pharmaceutical care with a coverage of 99% were derived from the Pharmacy Information System, containing information on the date the drug was supplied, who prescribed the drug, the specific drug that was supplied (including Anatomical Therapeutic Chemical [ATC] code), and the quantity supplied. Because all healthcare system records, including the Pharmacy Information System, use the same unique identifying number for each patient (the “Citizen Service Number”), it is possible to link all claims for any individual and thereby track each individual through all domains of healthcare and over time.19 Children 14 years of age or younger on the first of July were selected for every single year of the study period (2009-2011). In this group, individuals with at least 1 DBC claim for diabetes (pediatrics code [0316] and diabetes diagnosis code [7104], or internal medicine code [0313] and diabetes diagnosis code [221, 222 or 223]) were included. Patients were only classified as T1DM if pharmaceutical claims showed prescription and pick up of insulin (at least twice over a 4-year period 2008-2011). Patients with a diagnosis code of diabetes for whom no records of diabetes medication were found, or only records of medication except insulin, were excluded from further analysis in this study. In the same study period (2009-2011) and cohort, we examined evidence of the presence of hyperthyroidism (based on 1 or more of the pharmaceutical claim[s] for carbimazole [ATC H03BB01], propylthiouracil [ATC H03BA02], thiamazol [ATC H03BB02] or DBC claim for hyperthyroidism[7107]), or hypothyroidism (based 1 or more of the pharmaceutical claim(s) for levothyroxin [ATC H03AA01] or liothyronin [ATC H03AA02] or DBC claim for hypothyroid-ism [7108], but not for ATC H03BB01, ATC H03BA02, ATC H03BB02, or DBC-[7107]).
Furthermore, the number, sex and age of the whole population of children in the Netherlands were derived from the national Central Bureau of Statistics CBS (www.cbs. nl). Taken together, the collected data allowed us to estimate the nationwide prevalence of T1DM, thyroid disease, neither, either, or both.
Data selection, acquirement and organization were performed within the Vektis electronic environment. Before analysis, all claims and personal data were stripped from identifying characteristics to ensure anonymity: the Citizen Service Number was encrypted, date of birth converted into the person’s age, and the postal code recoded to limit its identifying properties to neighborhood level. statistical analysis To examine whether the prevalence of thyroid disease is more common in children with T1DM compared with the general population of children aged 0-14 years in different age categories (0-4, 5-9, and 10-14 years), and for boys and girls separately, we used the CBS population statistics. We used the chi square goodness-of-fit test to compare the prevalence
of thyroid disease in children with and without T1DM. In addition, the 95% CIs for the preva-lences were computed. Statistical analyses were carried out using SPSS (IBM SPSS Statistics for Windows, Version 20.0.; IBM Corp, Armonk, New York) and OpenEpi, version 3.0120
Because retrospective studies using anonymized data are exempt from ethical review under Dutch law, medical ethics approval was not required for this study. A statement to that effect was issued by the Isala Hospital Ethical Review Board. rEsulTs From 2009-2011, an average of 2 914 348 children 0-14 year of age (1 491 038 [51%] boys and 1 423 310 girls) lived in the Netherlands. There were 926 514 children 0-4 year of age (32%), 999 704 children 5-9 year olds (34%), and 988 130 children 10-14 years of age(34%). The cumulative prevalence of T1DM in children 0-14 year of age was 4186 (0.14%): 4107 known in 2009, 3947 in 2010, and 4089 in 2011.
Data on the prevalence of hyperthyroidisme and hypothyroidism in children with and without T1DM are given in tables 1 and 2, respectively. Between 2009 and 2011, the overall prevalence of thyroid disease in children 0-14 year of age in the Netherlands was 0.15% (n=4369).
Table 1. Prevalence of hyperthyroidism in children with and without type 1 diabetes mellitus.
T1dM+/
hyperthyroidism - Hyperthyroidism+T1dM+/ Hyperthyroidism+T1dM-/ Hyperthyroidism-T1dM-/
Total
Boys Girls Boys Girls Boys Girls Boys Girls
2009 2,138 1,969 4 (0.19%) 6 (0.30%) 105 (0.01%) 239 (0.02%) 1,491,858 1,422,810 2,923,058 0-4 yr 166 123 0 (0.00%) 0 (0.00%) 37 (0.01%) 36 (0.01%) 475,990 454,248 931,556 5-9 yr 680 621 1 (0.15%) 0 (0.00%) 22 (0.00%) 39 (0.01%) 515,857 492,373 1,010,634 10-14 yr 1,292 1,225 3 (0.23%) 6 (0.49%) 46 (0.01%) 164 (0.03%) 500,011 476,189 980,868 2010 2,076 1,871 4 (0.19%) 8 (0.43%) 98 (0.01%) 222 (0.02%) 1,486,510 1,418,087 2,912,911 0-4 yr 155 128 0 (0.00%) 0 (0.00%) 27 (0.01%) 30 (0.01%) 472,683 450,874 924,881 5-9 yr 656 590 0 (0.00%) 0 (0.00%) 28 (0.01%) 32 (0.01%) 511,691 489,226 1,003,249 10-14 yr 1,265 1,153 4 (0.32%) 8 (0.69%) 43 (0.01%) 160 (0.03%) 502,136 477,987 984,781 2011 2,102 1,987 3 (0.14%) 7 (0.35%) 103 (0.01%) 232 (0.02%) 1,483,271 1,415,259 2,907,075 0-4 yr 149 122 0 (0.00%) 0 (0.00%) 29 (0.01%) 32 (0.01%) 471,622 450,192 923,106 5-9 yr 650 617 0 (0.00%) 1 (0.16%) 23 (0.00%) 39 (0.01%) 502,757 480,120 985,229 10-14 yr 1,303 1,248 3 (0.23%) 6 (0.48%) 51 (0.01%) 161 (0.03%) 508,892 484,947 998,740 The prevalence of thyroid disease was 0.15% (4230/2 905 932; 95% CI 0.14- 0.15) in children without T1DM, compared with 3.43% (139/4048; 95% CI 2.90- 4.04) in children with T1DM (rate ratio 23.59; 95%CI: 19.92- 27.93; p < .001). The prevalence of hyperthyroidism was
0.015% (95% CI: 0.010- 0.013) in children without T1DM vs 0.27% (95% CI 0.14- 0.47) in chil-dren with T1DM (rate ratio 23.71; 95% CI 13.01- 43.23; p < .001) (Table 1). The prevalence of hypothyroidism was 0.134% (95% CI 0.1299- 0.138) in children without diabetes vs 3.16% (95% CI 2.65- 3.75) in children with T1DM (rate ratio 23.58; 95%CI 19.77- 28.12; p < .0005) (Table 2). The rate ratio of thyroid disease in girls vs boys in children without T1DM was 1.59 (95% CI 1.49- 1.69) vs 3.07 (95%CI 2.10- 4.49) in children with T1DM. The rate ratio of girls vs boys for hyperthyroidism in children without T1DM was 2.37 (95%CI 1.88- 3.00) vs 1.90 (95%CI 0.56- 6.48) in children with T1DM. The rate ratio of girls vs boys for hypothyroidism was 1.54 (95%CI 1.44- 1.64) in children without T1DM compared to 3.12 (95%CI 2.10- 4.63) in children with T1DM. Overall, children with T1DM were 24 times as likely to have hyperthyroidism and 24 times as likely to have hypothyroidism as children without T1DM. The female preponderance for thyroid disease was more pronounced for hypothyroidism than for hyperthyroidism. Table 2. Prevalence of hypothyroidism in children with and without diabetes mellitus type 1. T1dM+/
hypothyroidism- hypothyroidism+T1dM+/ hypothyroidism+T1dM-/ hypothyroidism-T1dM-/
Total
Boys Girls Boys Girls Boys Girls Boys Girls
2009 2,138 1,969 24 (1.12%) 91 (4.62%) 1,512 (0.10%) 2,302 (0.16%) 1,491,858 1,422,810 2,923,058 0-4 yr 166 123 0 (0.00%) 1 (0.81%) 479 (0.10%) 476 (0.10%) 475,990 454,248 931,556 5-9 yr 680 621 8 (1.18%) 13 (2.09%) 428 (0.08%) 592 (0.12%) 515,857 492,373 1,010,634 10-14 yr 1,292 1,225 16 (1.24%) 77 (6.29%) 605 (0.12%) 1234 (0.26%) 500,011 476,189 980,868 2010 2,076 1,871 36 (1.73%) 106 (5.67%) 1,584 (0.11%) 2,309 (0.16%) 1,486,510 1,418,087 2,912,911 0-4 yr 155 128 1 (0.65%) 3 (2.34%) 508 (0.11%) 472 (0.10%) 472,683 450,874 924,881 5-9 yr 656 590 6 (0.91%) 13 (2.20%) 427 (0.08%) 580 (0.12%) 511,691 489,226 1,003,249 10-14 yr 1,265 1,153 29 (2.29%) 90 (7.81%) 649 (0.13%) 1257 (0.26%) 502,136 477,987 984,781 2011 2,102 1,987 38 (1.81%) 89 (4.48%) 1,647 (0.11%) 2,337 (0.17%) 1,483,271 1,415,259 2,907,075 0-4 yr 149 122 0 (0.00%) 1 (0.82%) 508 (0.11%) 451 (0.10%) 471,622 450,192 923,106 5-9 yr 650 617 11 (1.69%) 11 (1.78%) 441 (0.09%) 559 (0.12%) 502,757 480,120 985,229 10-14 yr 1,303 1,248 27 (2.07%) 77 (6.17%) 698 (0.14%) 1327 (0.27%) 508,892 484,947 998,740 disCussioN In this Dutch nationwide study, we found that children with T1DM are much more likely to have thyroid disease compared to their peers without T1DM. The relative risk of thyroid disease in children 0-14 year to age with T1DM was 24 (3.43% vs 0.15%). This held true both for hyperthyroidism and hypothyroidism. Girls with T1DM were more likely to have thyroid disease than boys, in particular hypothyroidism.
A population-based study found orders for thyroxin prescription region in Scotland on 0.14% of subject 0-22 years of age from a distinct region in Scotland, suggesting a similar prevalence of hypothyroidism as we found.21
Most previous studies describing the prevalence of thyroid disease in children with T1DM used the presence of antithyroid autoantibodies as a proxy. These antibodies are found more often in children with T1DM than in those without T1DM4,11,22-29 In a US population aged 0-21 years, 4.2% of the T1DM population was clinically diagnosed with AITD,3 which is slightly higher than the 3.43% found in our study. The difference is likely owing to the difference in age selection. A recent Taiwanese population-based case-control study showed a 6.65-fold increased incidence rate ratio of thyroid disease in T1DM compared with children without T1DM, with incidence rate ratios of 2.74 for simple and unspecified goiter, 6.95 for thyrotoxicosis, and 6.54 for unspecified hypothyroidism.30
The prevalence of hyperthyroidism in children with T1DM found in this study (0.27%) is within the range of those reported in previous studies (0.20% -0.46%).31 Similarly, the 1:2.8 male:female ratio of thyroid disease in our study is comparable to that found in a previous study.21 The higher prevalence of thyroid disease in girls with T1DM has also been found in other autoimmune diseases. Unfortunately, there is no good explanation for this phenomenon.10 A major strength of this study is the nationwide coverage of population prevalence data on both T1DM and thyroid disease, allowing us to compare the prevalence of thyroid disease in children 0-14 year of age with and without T1DM. The 2 separate databases (healthcare insurance and pharmacy) used provide a 98% -99% coverage.18 As a limitation, some misclas-sification of T1DM through incorrect registration of diagnosis codes is always possible and ,theoretically, we miss out on all information with regards to treatment and diagnoses not represented though reimbursement information.
Another limitation of this study is that we could not differentiate between congenital and acquired hypothyroidism because the DBC codes do not distinguish between these 2 types of hypothyroidism. Based on an annual incidence of 75 to 80 neonates with congenital hypothyroidism diagnosed through newborn screening in the Netherlands 32, the total group
of children 0-14 year of age in our study will contain approximately 1200 children with con-genital hypothyroidism. Reanalysis of our data, assuming that these patients with congenital hypothyroidism were divided equally between the groups of children with and without diabetes, showed that the male:female ratio in diabetes related thyroid disease remained comparable (see Appendix). The International Society for Pediatric and Adolescent Diabetes suggests that thyroid function should be measured in every newly diagnosed child with T1DM, and this measurement should be repeated annually33. This consensus is followed by
Dutch pediatricians strengthening the accuracy of the prevalence figure of thyroid disease in children with T1DM in our study. Underreporting of thyroid disease in children without diabetes cannot be excluded, however.
In conclusion, this study shows an overall prevalence of 3.43% for thyroid disease, and of 0.27% and 3.16% for hyperthyroidism and hypothyroidism, respectively, in children 0-14 years of age with T1DM. This shows that children with T1DM are approximately 24 times more likely to have thyroid disease (24 times both for hyperthyroidism and for hypothyroid- ism) compared to children without T1DM. The results of our study support recommenda-tions for regular screening of thyroid function in children with T1DM.
rEfErENCEs 1. Wang L, Wang F-S, Gershwin ME. Human autoimmune diseases: a comprehensive update. J Intern Med 2015; 278: 369–95. 2. Garmendia Madariaga A, Santos Palacios S, Guillén-Grima F, Galofré JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab 2014; 99: 923–31. 3. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002; 87: 489–99. 4. Warncke K, Fröhlich-Reiterer EE, Thon A, Hofer SE, Wiemann D, Holl RW, et al. Polyendocrinopathy in children, adolescents, and young adults with type 1 diabetes: a multicenter analysis of 28,671 patients from the German/Austrian DPV-Wiss database. Diabetes Care 2010; 33: 2010–2. 5. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2011; 34 Suppl 1: S62–9. 6. Van den Driessche A, Eenkhoorn V, Van Gaal L, De Block C. Type 1 diabetes and autoimmune polyglan-dular syndrome: a clinical review. Neth J Med 2009; 67: 376–87. 7. Karavanaki K, Kakleas K, Paschali E, Kefalas N, Konstantopoulos I, Petrou V, et al. Screening for associ-ated autoimmunity in children and adolescents with type 1 diabetes mellitus (T1DM). Horm Res 2009; 71: 201–6. 8. Nederstigt C, Corssmit EPM, de Koning EJP, Dekkers OM. Incidence and prevalence of thyroid dysfunc-tion in type 1 diabetes. J Diabetes Complications 2016; 30: 420–5. 9. Fröhlich-Reiterer EE, Hofer S, Kaspers S, Herbst A, Kordonouri O, Schwarz H-P, et al. Screening fre-quency for celiac disease and autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus—data from a German/Austrian multicentre survey. Pediatr Diabetes 2008; 9: 546–53. 10. Kordonouri O, Hartmann R, Deiss D, Wilms M, Grüters-Kieslich A. Natural course of autoimmune
thyroiditis in type 1 diabetes: association with gender, age, diabetes duration, and puberty. Arch Dis Child 2005; 90: 411–4. 11. Riquetto ADC, de Noronha RM, Matsuo EM, Ishida EJ, Vaidergorn RE, Soares Filho MD, et al. Thyroid function and autoimmunity in children and adolescents with Type 1 Diabetes Mellitus. Diabetes Res Clin Pract 2015; 110(1): e9–11. 12. Holl RW, Bohm B, Loos U, Grabert M, Heinze E, Homoki J. Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Effect of age, gender and HLA type. Horm Res 1999; 52: 113–8. 13. Jung ES, Han DK, Yang EM, Kim MS, Lee D-Y, Kim CJ. Thyroid autoimmunity in children and adolescents with newly diagnosed type 1 diabetes mellitus. Ann Pediatr Endocrinol Metab 2014; 19: 76–9. 14. Kakleas K, Soldatou A, Karachaliou F, Karavanaki K. Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM). Autoimmun Rev 2015; 14: 781–97. 15. Dagdelen S, Hascelik G, Bayraktar M. Simultaneous triple organ specific autoantibody profiling in adult patients with type 1 diabetes mellitus and their first-degree relatives. Int J Clin Pract 2009; 63: 449–56. 16. Glastras SJ, Craig ME, Verge CF, Chan AK, Cusumano JM, Donaghue KC. The role of autoimmunity at diagnosis of type 1 diabetes in the development of thyroid and celiac disease and microvascular complications. Diabetes Care 2005; 28: 2170–5. 17. Spaans EAJM, Gusdorf LMA, Groenier KH, Brand PLP, Veeze HJ, Reeser HM, et al. The incidence of type 1 diabetes is still increasing in the Netherlands, but has stabilised in children under five (Young DUDEs-1). Acta Paediatr 2015; 104: 626–9.
18. Struijs JN, Mohnen SM, Molema CCM, de Jong-van Til JT, Baan CA. Effects of bundled payment on curative health care costs in the Netherlands. RIVM 2012, http: //www.rivm.nl/bibliotheek/rap-porten/260013001.pdf. 19. The Government of the Netherlands. The citizen service number (BSN). http: //www.government.nl/ issues/identification-documents/the-citizen-service-number. 20. Dean AG, Sullivan KM, Soe MM. OpenEpi: Open Source Epidemiologic Statistics for Public Health, Version 3.01. www.OpenEpi.com. 21. Hunter I, Greene SA, MacDonald TM, Morris AD. Prevalence and aetiology of hypothyroidism in the young. Arch Dis Child 2000; 83: 207–10. 22. Radetti G, Paganini C, Gentili L, Bernasconi S, Betterle C, Borkenstein M, et al. Frequency of Hashi-moto’s thyroiditis in children with type 1 diabetes mellitus. Acta Diabetol 1995; 32: 121–4. 23. Lorini R, d’Annunzio G, Vitali L, Scaramuzza A. IDDM and autoimmune thyroid disease in the pediatric age group. J Pediatr Endocrinol Metab JPEM 1996; 9 Suppl 1: 89–94. 24. Ghawil M, Tonutti E, Abusrewil S, Visentini D, Hadeed I, Miotti V, et al. Autoimmune thyroid disease in Libyan children and young adults with type 1 diabetes mellitus. Eur J Pediatr 2011; 170: 983–7. 25. Kordonouri O, Klinghammer A, Lang EB, Grüters-Kieslich A, Grabert M, Holl RW. Thyroid autoimmu-nity in children and adolescents with type 1 diabetes: a multicenter survey. Diabetes Care 2002; 25: 1346–50. 26. Al-Khawari M, Shaltout A, Qabazard M, Al-Sane H, Elkum N. Prevalence of thyroid autoantibodies in children, adolescents and young adults with type 1 diabetes in Kuwait. Med Princ Pract Int J Kuwait Univ Health Sci Cent 2015; 24: 280–4. 27. Ergür AT, Oçal G, Berberoğlu M, Adıyaman P, Sıklar Z, Aycan Z, et al. Celiac disease and autoimmune thyroid disease in children with type 1 diabetes mellitus: clinical and HLA-genotyping results. J Clin Res Pediatr Endocrinol 2010; 2: 151–4. 28. Araujo J, Brandão LAC, Guimarães RL, Santos S, Falcão EA, Milanese M, et al. Prevalence of autoim-mune thyroid disease and thyroid dysfunction in young Brazilian patients with type 1 diabetes. Pediatr Diabetes 2008; 9: 272–6. 29. Kordonouri O, Deiss D, Danne T, Dorow A, Bassir C, Grüters-Kieslich A. Predictivity of thyroid autoan-tibodies for the development of thyroid disorders in children and adolescents with Type 1 diabetes. Diabet Med J Br Diabet Assoc 2002; 19: 518–21. 30. Lu M-C, Chang S-C, Huang K-Y, Koo M, Lai N-S. Higher Risk of Thyroid Disorders in Young Patients with Type 1 Diabetes: A 12-Year Nationwide, Population-Based, Retrospective Cohort Study. PloS One 2016; 11: e0152168. 31. Dost A, Rohrer TR, Fröhlich-Reiterer E, Bollow E, Karges B, Böckmann A, et al. Hyperthyroidism in 276 Children and Adolescents with Type 1 Diabetes from Germany and Austria. Horm Res Pædiatrics 2015; 84: 190–8. 32. Kempers MJ, Lanting CI, van Heijst AF, van Trotsenburg AS, Wiedijk BM, de Vijlder JJ et al. Neonatal screening for congenital hypothyroidism based on thyroxine, thyrotropin, and thyroxine- binding globulin measurement: potentials and pitfalls.J Clin Endocrinol Metab 2006; 91: 3370-6
33. Kordonouri O, Klingensmith G, Knip M, Holl RW, Aanstoot H-J, Menon PSN, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Other complications and diabetes-associated conditions in children and adolescents. Pediatr Diabetes 2014; 15 Suppl 20: 270–8
Number of children with diabetes and hypothyroidism and children without diabetes and hypothyroidism
year
T1dM+/hypothyroidism+ T1dM-/hypothyroidism+
Boys Girls Boys Girls
2009 24 91 1512 2302 2010 36 106 1584 2309 2011 38 89 1647 2337 Number of children with diabetes and hypothyroidism and children without diabetes and hypothyroidism after leaving out the estimated number of children with congenital hypothyroidism year T1dM+/hypothyroidism+ T1dM-/hypothyroidism+
Boys Girls Boys Girls
2009 24 91 1006 1644
2010 36 106 1081 1655
