The association of post-radiation thyroid nodular disease with compensated hypothyroidism

In a comprehensive survey of the literature on the effects of ionising radiation on the human thyroid gland, Maxon et al (1977) found that the majority of thyroid neoplasms reported following external irradiation had occurred after doses not exceeding 20 Gy. This fits the concept that a dosage of 30 Gy or more would be likely to sterilise the thyroid follicular cells and render the gland atrophic rather than neoplastic. However, during the past decade, the development of thyroid neoplasia, particularly papillary carcinoma, has been described after 40–50 Gy external irradiation to the neck in the treatment of malignant disease (McDougall et al, 1980; Petronius et al, 1982; Rosen et al, 1984). The development of subclinical or overt hypothyroidism is also documented, as indicated by a compensatory rise in the level of circulating thyroid stimulating hormone (TSH) (Constine et al, 1984). Thus the development of thyroid neoplasia in these circumstances can be regarded to result from irradiation initiated carcinogenesis promoted by the TSH-induced hyperplasia of surviving non-sterilised follicular cells. Judging from the findings in a similar situation in experimental rats one would expect the development of multiple tumours in the thyroid gland (Doniach, 1956; Lindsay et al, 1961). In fact, multiple tumours and multinodularity of the human thyroid gland have been reported after therapeutic external irradiation of the neck, by Doniach et al (1966), McKenzie and Hope-Stone (1975), McDougall et al (1980) and Petronius et al (1982). Petronius and colleagues noted an elevated level of TSH in their patients.