What investigations would you conduct to determine a role for viral infections in the pathogenesis of acute thyroiditis?

The best method available to proof that a virus is linked with a particular disease is administer the virus to human volunteers and see whether the persons develop the disease or not. This has been done in studies of rhinovirus and gastroenteritis virus infections. However, this is not ethically defensible for more serious infections such as acute thyroiditis. Therefore other evidence would have to be sought, such as;

• The isolation or detection of the virus from patients suffering from the disease, preferably from the affected organ
• Seroepidemiological evidence
• The reproduction of the disease in experimental animals
• The reproduction of the pathology in organ/tissue culture

To begin the investigation, patients diagnosed having acute thyroiditis should be recruited. A detailed history should be obtained from such patients especially in relation to whether they may have suffered a presumed virus illness such as influenza-like symptoms before the thyroiditis, whether they had been in contact with other people with thyroiditis or flu-like symptoms, and whether they are in any risk groups for particular virus infections eg. are they homosexuals or intravenous drug abusers. Paired acute and convalescent serum specimens should be collected from patients and tested against a large number of viral antigens to see whether rising levels or a high titre of antibody is consistently present against a particular virus(es). If an IgM assay is available for that particular virus, it will be useful to demonstrate the presence of IgM. However, if the disease is caused by reactivating virus, then IgM may be absent.

Thyroid biopsy and other specimens such as throat swabs, saliva, urine and faeces should be collected from the patients and virus isolation be carried out. Consistent isolation of a virus from the thyroid would constitute as important evidence for a role of the virus in the disease. However, one cannot exclude the possibility that the virus may only be a passenger virus. One must also bear in mind that it may not be possible to find the virus in the thyroid if immunopathological mechanisms are involved since the virus does not have to be present. In that case, one may get the virus being isolated from other sites. Many viruses cannot be routinely cultured. If serological evidence indicates that a particular non-cultivable virus is implicated, then other means would have to be used to demonstrate the presence of the virus in the thyroid or other sites, such as the detection of virus antigen by immunofluorescence, virus particles by electron microscopy, or viral nucleic acids by hybridization or by the polymerase chain reaction. Increasingly, novel molecular techniques are used in the discovery of novel viruses such as the use of RDA (representative differential amplification) for HCV and HGV.

By far the most important evidence for a role of virus in the pathogenesis of acute thyroiditis would come from the detection of the virus in the thyroid of a patient with thyroiditis together with serological evidence. The known epidemiology of the suspected virus should correspond to the epidemiology of acute thyroiditis eg. if the virus is an arbovirus, there should be a history of contact with the insect vector with the patient, if the virus is sexually transmitted, it should be more common in particularly sexually active individuals such as homosexuals.

Supplementary evidence for a role of the virus may be obtained by attempting to culture the virus in organ or tissue culture of the thyroid. Histological lesions identical to those seen in the patients may be induced. Replication of the virus in the tissue may be demonstrated by the detection of virus antigens or nucleic acid. In addition, one may inoculate experimental animals, especially those which are closely related to humans such as chimpanzees to see whether acute thyroiditis is induced. Although, supplementary evidence is useful, they are by no means vital in associating a virus with the disease.

Once good evidence is available that a particular virus in involved in acute thyroiditis. Further evidence may be available in the future in the following manner (1) specific chemotherapy for the virus may augment the disease, and (2) vaccination against this virus should lead to a decrease in the incidence of acute thyroiditis.