The Incidence of Autoimmune Thyroid Disease: A Systematic Review of the Literature

Anita McGrogan; Helen E. Seaman; John W. Wright; Corinne S. de Vries

Disclosures

Clin Endocrinol. 2008;69(5):687-696. 

In This Article

Discussion

Incidence rates of autoimmune hypothyroidism varied between 2·2/100 000/year and 498·4/100 000/year whereas incidence rates of autoimmune hyperthyroidism varied between 0·7/100 000/year and 99/100 000/year. Thyroid disease had a higher incidence in women.

In their review of the epidemiology of thyroid diseases, Tunbridge and Caldwell[6] point out that complications arise due to problems of definition, selection criteria and different techniques used for the measurement of thyroid function. In addition, symptoms of thyroid disease may be nonspecific or attributed to other diseases, which makes diagnosis more difficult.[33]

When thyroid disease is caused by environmental factors, such as levels of iodine, incidence rates have been found to vary between locations and over time.[34,35,36,37] For instance, in their study of the prevalence of thyroid disease in the elderly, Laurberg et al.[38] found a high prevalence of hypothyroidism in Iceland, where the intake of iodine was high, but in Jutland, where iodine intake was low, a high prevalence of hyperthyroidism was found. In this review of autoimmune thyroid disease, the papers we identified came from a limited range of geographical areas. Consequently we could not comment on the absence or presence of differences in incidence rates between different geographical locations.

There were over 100-fold differences in the incidence rates of various studies. Higher incidence rates tended to be due to the type of study conducted (e.g. where screening was used and therefore subclinical cases were included in the rates). The two prospective studies[9,12] produced the highest incidence rates of thyroid disease. One of these only included women aged 70–81 years;[14] the other used a multitude of data sources to evaluate and screen incident cases in the entire population and is the most comprehensive study we identified. The incidence rates of hypothyroidism in this study, which was carried out in the UK, were between 250 and 350/100 000/year (depending on the subgroup of the population). This was among the higher rates identified, partly as a result of the inclusion of subclinical cases. By contrast, a study carried out in Spain using a selected outpatients list reported an incidence rate in women of 45·4/100 000/year for hypothyroid disease; they will have missed any cases of thyroid disease who did not present at the participating outpatient clinic. In general, the incidence rates identified in the prospective studies will be more accurate. The difficulty with using these rates for post hoc evaluation of changes in incidence rates is that the prospective studies will have included subclinical cases.

Looking at the results for hyperthyroidism from retrospective studies, it is useful to note that the studies conducted in a similar way, through case finding from questionnaires, medical records or test results,[3,14,18,19,21,27] produced similar incidence rates even though these studies covered different time periods between 1972 and 1999. This is an important finding as it indicates that, for autoimmune thyroid disease, the rates appear to be constant over time. However, a recent study from Scotland[15] found that the incidence of hyperthyroidism in females and hypothyroidism in males increased between 1997 and 2001. The authors note that this may be partly explained by an increase in the number of thyroid tests being carried out in the region, leading to an increased number of subclinical cases being identified. If this were a correct assumption then increases in the incidence rates for both types of thyroid disease and in both males and females would be expected unless there was differential testing between males and females. A true increase in incidence of thyroid disease caused by autoimmunity or some other cause cannot be ruled out but it is also possible that the increase seen was caused by an artefact. The studies included in this review mostly covered Caucasian populations, therefore we are unable to comment on potential differences in incidence rates between different ethnic groups.

In reviews covering the epidemiology of thyroid disorders, the distinction has been made between subclinical and overt hypothyroidism and hyperthyroidism.[1,2,6,11] In this review we have found only two studies that were conducted in a way that would include both subclinical and overt cases of hypothyroidism or hyperthyroidism: Vanderpump et al.[9] and Sundbeck et al.[12] examined all patients in their study cohorts for thyroid disease, which allowed them to detect subclinical cases of hypothyroidism and hyperthyroidism. All other studies used methods of case finding that did not involve the screening of patients. As Vanderpump et al. pointed out, cases will be missed unless patients are screened for thyroid disease;[9] except for incidental findings subclinical disease will not, by definition, be readily detected clinically. In addition, the point where a patient is diagnosed and treated for thyroid disease, and when their disease becomes overt, differs widely in clinical practice and this will have resulted in differences in incidence rates between different geographical locations. However, given the combination of differences in rates and study design in different geographical locations, we cannot exclude the possibility that there is a geographical component to variations in incidence of thyroid disease.

Only two prospective and truly population-based studies[9,13] were identified. It could be argued that studies that were not population based or collected data retrospectively are more prone to producing under- or overestimated rates. For example, retrospective studies rely more heavily on physician or patient recall and will not necessarily identify all patients if records were destroyed, sent on to different hospitals, or otherwise lost for research purposes. These instances will have led to underestimated incidence rates. Inclusion of nonautoimmune disease (which may be more difficult to establish retrospectively) will have led to overestimated rates. Finally, retrospective assessment of population size or person-time contributed is often more difficult and therefore more prone to error than prospective collection of this information.

In an assessment of the incidence of autoimmune thyroid disease another important consideration is the likely cause of thyroid disease. Hypothyroidism may be caused by other factors including the exogenous causes of medication with lithium, radioiodine or anti-thyroid drugs and thyroidectomy as well as the endogenous cause of autoimmune thyroiditis.[1,2] Similarly, in addition to autoimmune Graves' disease, hyperthyroidism may be caused by overzealous thyroid hormone replacement therapy, or by other endogenous thyroid disease including acute viral thyroiditis, toxic multinodular goitre or an autonomous adenoma. Rare causes include struma ovarii and pituitary hypersection of TSH.[2] In this report, where possible, only incidence rates for autoimmune causes of thyroid disease have been included, although most papers did not specify in detail the causes of the thyroid disease reported. Associated with this issue is the possibility that euthyroid subjects with thyroid antibodies in the serum were included in incidence rates in those retrospective study designs that solely used results of biochemical tests for the diagnosis of thyroid disease. Therefore, it is possible that the rates presented overestimate the incidence of autoimmune thyroid disease.

The majority of studies included were conducted in the USA, Scandinavia and the UK. The absence of reports on incidence rates of autoimmune thyroid disease from the rest of the world is striking and possibly reflects the more substantial problem of iodine-related thyroid disease in these other regions. Endemic goitre affects 200 million people throughout the world, particularly in the Himalayas, Andes, parts of Africa and eastern and southern Europe.[4] Areas where iodine prophylaxis has been introduced more recently include Poland,[35] Austria[39] and Switzerland;[40] studies of thyroid disorders in these countries tend to focus on iodine-related rather than autoimmune thyroid disease.

This review of incidence of thyroid disease has highlighted difficulties in ensuring that all cases and only those cases of thyroid disease caused by autoimmunity, whether subclinical or overt, are included in the incidence rates. The most accurate incidence rates available come from prospective studies that screen patients. However, it is thought that retrospective case-finding procedures produce useful estimations of incidence rates providing the above limitations are taken into account.

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