Increased frequency of subclinical hypothyroidism and thyroid-associated antibodies in siblings of children and adolescents with type 1 diabetes mellitus

doi:10.1530/eje.1.02008

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Increased frequency of subclinical hypothyroidism and thyroid-associated antibodies in siblings of children and adolescents with type 1 diabetes mellitus

A Mohn, S Di Michele, R Faricelli¹, S Martinotti¹ and F Chiarelli

Department of Paediatrics and ¹ Department of Clinical Pathology, University of Chieti, Chieti, Italy

(Correspondence should be addressed to A Mohn; Email: amohn{at}unich.it)

In recent years, it has been well established that early detectionof thyroid autoimmunity or disease in children is important,leading to the idea of treating patients with subclinical hypothyroidismin the presence of high serum thyroid antibody, as progressionto overt hypothyroidism is common (1). Furthermore, thyroxinereplacement therapy started early in patients with subclinicalhypothyroidism reduces the risk of hyperlipidemia and atheroscleroticheart disease (2). Disease-associated autoantibodies can beeasily used as a tool to identify patients at increased riskof progression to clinical thyroid dysfunction. Because siblingsof patients with type 1 diabetes mellitus (T1DM) share the HLA-riskalleles, we asked whether they might be at increased risk ofthyroid autoimmunity and disease.

Therefore, screening for thyroid-correlated antibodies, togetherwith thyroid function testing, was offered to siblings of childrenand adolescents with T1DM. We excluded siblings of diabeticpatients with thyroid autoimmunity or disease. As a controlgroup, we also analyzed sera from healthy children and adolescentsmatched for age and sex without a family history of autoimmunedisease. All children were Caucasian from the Abruzzo regionof Italy. Written, informed consent was obtained from the parentsof all children and adolescents before entry to the study.

A single blood sample was taken for thyroid function testing(thyroid-stimulating hormone (TSH) and free thyroxine (FT4))and antibodies to thyroglobulin (TG) and to thyroid peroxidase(TPO).

Thyroid hormone levels were determined by double-antibody radioimmunoassay.Normal basal values for our laboratory were 6–18 pg/mlfor FT4 and 0.3–4.1 µU/ml for TSH. Antibodies toTG and TPO were quantitated by ELISA. A titer exceeding 100IU/ml was considered positive. Patients with positive thyroidantibodies were considered to be affected by autoimmune thyroiditiswith subclinical hypothyroidism when increased serum TSH (>5µUI/ml) concentration with normal FT4 values was found.

The screening was performed in 123 siblings (67 M, 56 F) outof 151 (70 M, 81 F) aged 9.2 ± 4.5 years. These childrenwere matched with 140 control subjects (81 M, 59 F) aged 9.2± 3.8 years (Table 1). The data were evaluated statisticallyby Fisher’s exact probability test with SPSS, Version10.0 (SPSS, Chicago, IL, USA).

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Table 1 Frequency of autoimmune phenomena in siblings of T1DM patients compared to controls without family history of T1DM.

Among the group of siblings, nine children (4 M, 5 F) testedpositive for antibodies to TG (mean 358 IU/ml, range 108–761)and to TPO (mean 758 IU/ml, range 100–1982). Three ofthese children presented subclinical hypothyroidism: two adolescentgirls (TSH, 9.5 and 7.64 µU/ml; FT, 4.7 and 12 pg/ml respectively)and a 6-year-old boy (TSH, 8.45 µU/ml; FT, 4.8 pg/ml).These three children were started on treatment with L-thyroxine.In the control group, two girls aged 8.8 and 9.8 years respectivelypresented antibodies to TG (mean 107 IU/ml, range 88–126)and to TPO (mean 181 IU/ml, range 150–202) (P = 0.01)with normal thyroid function.

Despite the relatively small number of subjects, this cross-sectionalstudy highlights that siblings of patients with T1DM presenta frequency of 7% of thyroid-associated antibodies, which issignificantly higher than in normal controls and is in linewith previous studies (3–5). Furthermore, in our population,we detected an increased frequency of thyroid dysfunction, whichis less common, as routine screening for siblings of diabeticpatients is usually not performed (6). Although the adolescentgirls might have been diagnosed by a thorough clinician, whichreflects the occurrence within the general population, the boywas at high risk of remaining undetected for a long time. Thissmall study demonstrates that clinicians should be highly awareof the possibility of thyroid dysfunction in this population,and early diagnostic procedures should be performed, especiallyin consideration of the well-documented long-term complicationsof undiagnosed hypothyroidism.