Screening for thyroid disease of 15±17-year-old schoolchildren in an area with normal iodine intake

Transcription

1 Journal of Internal Medicine 2001; 250: 208±212 Screening for thyroid disease of 15±17-year-old schoolchildren in an area with normal iodine intake M. MILAKOVIC 1,G.BERG 2, R. EGGERTSEN 1, G. LINDSTEDT 3 &E.NYSTROÈ M 4 From the 1 MoÈlnlycke Primary Health Care and Research Centre, Department of Primary Health Care, and Departments of 2 Oncology, 3 Clinical Chemistry and 4 Endocrinology, Sahlgrenska University Hospital, GoÈteborg University, GoÈteborg, Sweden Abstract. Milakovic M, Berg G, Eggersten R, Lindstedt G, NystroÈm E (Sahlgrenska University Hospital, GoÈteborg, Sweden). Screening for thyroid disease of 15±17-year-old schoolchildren in an area with normal iodine intake. J Intern Med 2001; 250: 208±212. Objective. The prevalence of thyroid disease in Swedish schoolchildren is today insuf ciently known. The aim of the study was therefore to determine the prevalence of abnormal thyroid function and thyroid autoimmunity in teen-age schoolchildren and to compare the ndings with a healthy control group of 60±65-year-old inhabitants from the same community. Setting. A semirural community of approximately inhabitants. Design. Cross-sectional study. Main outcome measures. Thyroid volume and serum concentrations of serum thyrotropin (TSH), total and free thyroxine (T4), total and free 3,5,3 triiodothyronine (T3), and antithyroperoxidase antibodies (TPOAb). Results. Four schoolchildren (7%, 59 screened) had elevated TPOAb concentration, three of the subjects being girls (8%). One girl with a goitre was overtly hypothyroid and one girl showed borderline-high serum TSH concentration suggesting subclinical autoimmune thyroid disease. One euthyroid boy had a goitre and high concentration of TPOAb. The serum free T3 concentration was signi cantly higher in 15±17-year-old than 60±65- year-old (7.4 vs. 6.4 pmol L ±1, P < 0.001). The concentrations of other thyroid hormones and of TSH in 15±17-year-old did not differ from those of the 60±65-year-old. Conclusions. We found three cases of thyroid disease in need of immediate attention or later follow-up. The prevalence of autoimmune thyroid disease was high as indicated from TPOAb measurements. Thyroid tests including TPOAb measurement should be performed on wide indications when teenagers seek medical advice. The reference intervals for teen-age children for commonly used rst line tests (TSH and free T4) do not differ from those for adults. Keywords: schoolchildren, screening, thyroid disease, thyroid volume, TPOAb, TSH. Introduction Sweden has had iodine supplementation through table salt since 1936, and the country since then has been considered to be iodine-repleted. Whereas the nutritional status of the general population in Sweden, like that in western Europe, has improved considerably during the latter half of the last century, this may not be true for the younger generation. In fact, during the last two to three decades, pronounced changes in the life-style of young people have taken place in Sweden probably including changes in eating habits and in opinions regarding food additives such as the use of including table salt. Also, ideals as regards body shape are known to adversely affect a safe and sound food intake. Schools serve lunches, which sometimes are poorly attended by several children. The effects as regards nutritional status of schoolchildren have been studied only poorly, but the occurrence of a widespread iron de ciency both in girls and boys seems to be a well established fact [1]. 208 ã 2001 Blackwell Science Ltd

2 THYROID DISEASE IN SCHOOLCHILDREN 209 Thyroid disease is common in adults, but is also present in childhood, even if the incidence has been considered to be low [2, 3]. To which extent recent changes in dietary intake in schoolchildren has affected the prevalence of goitre and of thyroid dysfunction is, however, unknown. With that background, we therefore decided to investigate the prevalence of undiagnosed goitre, thyroid dysfunction and thyroid autoimmunity in teenagers of today in a Swedish community. Three school-classes (children aged 15±17 years) were screened for thyroid disease with a brief physical investigation including ultrasound determination of thyroid volume and biochemical testing of thyroid function and autoimmunity. We also investigated an adult control group to establish whether adult reference values for biochemical tests could be applied to the teen-age group. Subjects and methods Study community The investigation was performed in MoÈlnlycke, a semirural community on the Swedish west coast comprising approximately inhabitants. The area is iodine-repleted, the medium urinary iodine concentration being approximately 200 lg L -1 (to be published). Schoolchildren The investigation was carried out in a senior level high school comprising of approximately 1100 pupils at the time of investigation. The school has two school nurses and one (part-time) school physician. We invited the pupils in three school classes, 15±17 years of age, for an investigation of the size and function of the thyroid gland, subjects participating being offered a cinema ticket as compensation. All invited subjects (40 girls and 23 boys) accepted to participate in the study the invitation. Blood was sampled in 59 subjects, who were included in the present investigation. Adult control subjects In 1994, using of cial population records, we selected every second man and woman in MoÈlnlycke (488 individuals) for a population study. As part of a follow-up of this group of individuals, we invited 73 persons for a second health survey including thyroid investigation. A total of 62 individuals (85%), 38 women and 24 men, accepted the invitation. The subjects received a questionnaire regarding medical treatment and previous and present thyroid disease. Investigation procedure The individuals were evaluated 08:00±10:00 a.m. with physical examination, ultrasound examination of the thyroid gland, blood sampling and recording of weight and height. Thyroid volume Ultrasound examination was performed with an Acuson 128 ultrasound unit with a 7.5-MHz transducer. The volume of each lobe was calculated by the formula: V (ml) ˆ length width thickness (mm). The thyroid volume was the sum of the volume of both lobes. The volume of the isthmus was not included. Biochemical methods Serum thyrotropin (TSH), total thyroxine (T4), free thyroxine (free T4), total 3,5,3 -triiodothyronine (T3) and free 3,5,3 -triiodothyronine (free T3) were analysed by luminometric methods in a Vitros ECi instrument using reagents from Ortho-Clinical Diagnostics, Amersham, UK. Serum antibodies against the TSH receptor (TRAb) were analysed by a competitive radioreceptor assay (RSR Limited, Cardiff, UK), and serum antibodies against thyroperoxidase (TPOAb) by a competitive luminiscence immunoassay (BRAHMS Diagnostica GmbH, Berlin, Germany). The study was approved by the Ethics Committee of GoÈteborg University, and informed consent was obtained from each subject (parents for teenagers) before inclusion. Results The mean serum concentrations of thyroid-related hormones of the 15±17-year-old schoolchildren are shown in Table 1. No schoolchildren were on any medical therapy, and had no history of thyroid disease. The ndings are compared with those in the

3 210 M. MILAKOVIC et al. Table 1 Serum concentration [mean (median)] of TSH, reference interval 0.2±3.0 mu L )1 and serum concentrations [mean (SD)] of free T4 (FT4), reference interval 11±27 pmol L )1 ; T4, reference interval 70±140 pmol L )1 ; free T3 (FT3), reference interval 3.3±7.6 pmol L )1 ; and T3, reference interval 1.5±3.0 nmol L )1 in 15±17-year-old schoolchildren and 60±65-year-old controls Age group TSH (mu L) FT4 (pmol L )1 ) T4 (nmol L )1 ) FT3 (pmol L )1 ) T3 (nmol L )1 ) 15± (0.86) 13.5 (1.7) 100 (22) 7.4 (0.77) 2.4 (0.85) 60± (1.40) 13.3 (2.1) 95 (17) 6.6 (0.68) 1.9 (0.25) Difference ns ns ns P < ns 60±65 year-old subjects, where nine individuals with levothyroxine and oestrogen substitution therapy have been excluded (53 individuals remaining). The concentrations of TSH as well as of total and free T4 do not differ from those of the adult population. The free T3 concentrations are signi cantly higher (P < 0.001) in the 15±17-year-old. The prevalence of increased TPOAb concentration (>100 U L ±1 ) in 15±17 years group is shown in Table 2 and compared with 60±65 years group. The serum concentrations of TSH and thyroid hormones of teenagers with increased TPOAb concentration and/or goitre (>16.0 ml) are shown in Table 3. One girl with goitre was clinically hypothyroid with a goitre having high TSH and low free T4 concentration (case 1, Table 3). One girl (case 2) without goitre showed a borderline TSH value and lownormal free T4. Taking these tests and the presence Table 2 Number of individuals with increased TPOAb concentration (>100 U L )1 ) in 15±17-year-old schoolchildren and 60±65-year-old Age group With TPOAb elevation Normal TPOAb 15±17 (Girls) ±17 (Boys) ±17 (All) ±65 (Women) ±65 (Men) ±65 (All) 9 53 of TPOAb in consideration, this individual was classi ed as running a high risk of later developing clinical hypothyroidism. One boy (case 3, Table 1) with a goitre had normal concentrations of TSH and normal thyroid hormones (euthyroid Hashimoto's disease). The ultrasound examinations revealed four children (7%) with a goitre (>16 ml, WHO recommended normative volume, 97th percentile, 15-year-old children [4]). Two of these had elevated TPOAb concentrations (see Table 3) of whom one was hypothyroid and the other was considered to be at risk for the development of hypothyroidism. Two individuals with a goitre but TPOAb concentration below the cut-off limit had normal hormone concentrations. Discussion In the present investigation of 59 teenagers, we detected one girl (case 1, Table 3) with previously not diagnosed hypothyroidism, and one girl (case 2, Table 3) with a high risk of developing hypothyroidism within a few years. Other two children (case 3 and 4, Table 3) had moderately elevated TPOAb concentrations but normal hormone concentrations. To our opinion, these three euthyroid TPOAb positive children must be followed up at regular intervals as should the two TPOAb negative cases with a pronounced goitre. Table 3 Thyroid related hormones in 15±17-year-old schoolchildren with TPOAb and/or goitre (thyroid volume >16 ml, see text). Reference intervals are given in Table 1 No Sex Thyroid volume (ml) TSH (mu L )1 ) FT4 (pmol L )1 ) T4 (nmol L )1 ) FT3 (pmol L )1 ) T3 (nmol L )1 ) TPOAb (U L )1 ) 1 Female Female Male Female Female Female

4 THYROID DISEASE IN SCHOOLCHILDREN 211 It is our experience that doctor's delay in diagnosing of hyper- or hypothyroidism may be considerable in schoolchildren. The reason for this seems to be that symptoms of thyroid disease are often misinterpreted as problems associated with adolescence and teenager life style. The results indicate, that reference intervals of TSH, free T4 and total T4 for adults can be used in the investigation also of this age group. Free T3 values are signi cantly higher in the 15±17 years age group. In a large population study of women [5], we observed an inverse relationship between age and total T3 concentrations in the age range 26±72 years with the exception for an increase in T3 concentration during the menopausal transition. Our nding of two schoolchildren with a clinically signi cant thyroid disease in a group of teenage schoolchildren regarded as healthy, emphasize the importance of improved somatic health-care monitoring within the school, and the importance of also including thyroid tests, TSH in the rst place [6], in the investigation of schoolchildren who seek health care. Sweden is an iodine suf cient area, with iodine added to table salt since Today, it is, however, possible, that some households will try to decrease the use of table salt, and even use noniodine salt. On the other hand, eating habits in our area may have changed, food containing more iodine ( sh, milk and cheese) becoming more popular. Noncongenital hypothyroidism in Sweden, with few exceptions, is an autoimmune disease. We found elevated TPOAb concentrations in about 8% of teenage girls, i.e. in the same range as previously reported for this age group [7, 8]. The presence of TPOAb in about 25% of adult females is also in good accordance with previously reported data [9]. Three children of four with presence of TPOAb had a thyroid condition, suggesting that analysis of TPOAb should be performed in addition to TSH in thyroid screening of teenagers. In screening for thyroid disease, some seemingly euthyroid individuals with increased or borderline increased TSH concentration will be identi ed. These individuals may have symptoms of hypothyroidism not recognized. This may represent a special problem with the age group studied in this investigation. If the child has relatives with thyroid disease and/or has elevated concentrations of TPOAb, the risk for developing hypothyroidism is increased [10]. Although expectance has been advocated in euthyroid children with persistent increase of TSH [11, 12], it is our belief, that it is very dif cult to exclude borderline thyroid insuf ciency, a condition which may be of de nite importance both for teenagers and earlier age groups [13]. Thus, in the child with this hormonal pattern, even if there is only a faint suspicion of the presence of symptoms, which may be related to hypothyroidism ± also unspeci c like tiredness ± levothyroxine may be tried for 6 months [14]. Euthyroid children with elevated TSH concentration must be followed-up, and special attention given to individuals with elevated TPOAb concentrations. References 1 Hallberg L, Hulten L, Lindstedt G et al. Prevalence of iron de ciency in Swedish adolescents. Pediatr Res 1993; 34: 680±7. 2 Hunter I, Greene SA, MacDonald TM, Morris A. Prevalence and aetiology of hypothyroidism in the young. Arch Dis Child 2000; 83: 207±10. 3 Perrild H, Lavard L, Brock-Jacobsen B. Clinical aspects and treatment of juvenile Graves'disease. Exp Clin Endocrinol Diabetes 1997; 105 (Suppl. 4): 55±7. 4 WHO/ICDDIDD. Recommended normative values for thyroid volume in children aged 6±15 years. Bull World Health Organ 1997; 75: 95±7. 5 NystroÈm E, Bengtsson C, Lindquist O, Lindberg S, Lindstedt G, Lundberg P-A. Serum triiodothyronine and hyperthyroidism in a population sample of women. Clin Endocrinol 1984; 20: 31±42. 6 Surks MI, Chopra IJ, Mariash CN, Nicoloff JT, Solomon DH. American Thyroid Association guidelines for use of laboratory tests in thyroid disorders. JAMA 1990; 263: 1529±32. 7 Lindberg B, Ericsson UB, Fredriksson B et al. The coexistence of thyroid autoimmunity in children and adolescents with various allergic diseases. Acta Paediatr 1998; 87: 371±4. 8 Lindberg B, Ericsson UB, Ljung R, Ivarsson SA. High prevalence of thyroid autoantibodies at diagnosis of insulin-dependent diabetes mellitus in Swedish children. J Lab Clin Med 1997; 130: 585±9. 9 Massoudi MS, Meilahn EN, Orchard TJ et al. Prevalence of thyroid antibodies among healthy middle-aged women. Findings from the thyroid study in healthy women. Ann Epidemiol 1995; 5: 229± Vanderpump MPJ, Tunbridge WMG, French JM, Appleton D, Bates D, Clark F. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham survey. Clin Endocrinol 1995; 43: 55± Moore DC. Natural course of `subclinical' hypothyroidism in childhood and adolescence. Arch Pediatr Adolesc Med 1996; 150: 293±7. 12 Ty eld LA, Abusrewil SS, Jones SR, Savage DC. Persistent hyperthyrotropinaemia since the neonatal period in clinically euthyroid children. Eur J Pediatr 1991; 150: 308±9.

5 212 M. MILAKOVIC et al. 13 Rivkees SA, Bode HH, Crawford JD. Long-term growth in juvenile acquired hypothyroidism: the failure to achieve normal adult stature. N Engl J Med 1988; 318: 599± NystroÈm E, Caidahl K, Fager G, WikkelsoÈ C, Lundberg P-A, Lindstedt G. A double-blind cross-over study of L-thyroxine treatment of women with `subclinical' hypothyroidism. Clin Endocrinol 1988; 29: 63±76. Received 23 January 2001; revision received 6 June 2001; accepted 7 June Correspondence: Ernst NystroÈm, Department of Endocrinology, Sahlgrenska University Hospital, SE-41345, Gothenburg, Sweden (fax: ; ernst.nystrom@medic.gu.se).