Effects of smoking on thyroid function.

Cigarette smoking has multiple effects on thyroid function. These include both pro(e.g. thyroidstimulating) and anti-thyroid actions and also actions that increase susceptibility to or exacerbation of the manifestations of Graves’ disease. In this issue of the Journal, Gasparoni et al. describe the effects of parental smoking on fetal thyroid secretion and also on thyroid function of some of the same infants at one year of age (1). Before considering the results of this new study, it seems appropriate to review briefly earlier work on the effects of smoking on the thyroid in adults. In normal adults, smoking has either no effect on thyroid function and size or a weak pro-thyroid effect. The abnormalities described include small goiters and small, thyrotropin-independent increases in thyroid function, most often small increases in serum triiodothyronine and thyroglobulin concentrations (see references 2 and 3 for reviews). These findings suggest that smoking in some way directly stimulates thyroid growth and function, but how it might do so is not known. Nicotine causes sympathetic activation, which can increase thyroid secretion. Alternatively, nicotine or some other component of tobacco smoke might have direct thyroid-stimulating actions. Despite the association with goiter and small increases in thyroid secretion, in several case-control studies smoking was not a risk factor for either non-toxic or toxic multinodular goiter, indicating that its overall contribution to these disorders must be small (4, 5). Most, if not all, of the subjects in these studies and in those to be described were women. Nevertheless, the conclusions are probably applicable to men. Among patients with subclinical hypothyroidism, those who smoke have higher serum thyrotropin concentrations, a higher serum ratio of tri-iodothyronine to free thyroxine, and higher serum cholesterol and lowdensity lipoprotein cholesterol concentrations than those who do not smoke (6). In contrast, among patients with overt hypothyroidism, smokers and nonsmokers have similar serum thyrotropin and thyroid hormone concentrations, but more symptoms, signs and biochemical and physiological changes of hypothyroidism (6). Thus smoking reduces thyroid secretion in patients with subclinical hypothyroidism and exacerbates the peripheral effects of thyroid deficiency in those patients and in patients with overt hypothyroidism. Notwithstanding these results, in the same case-control studies cited above smoking was not a risk factor for chronic autoimmune thyroiditis (4, 5), although it was associated with postpartum thyroiditis, a precursor of chronic autoimmune thyroiditis, in one study (7). At the other end of the spectrum, there is substantial evidence that smoking is a risk factor for Graves’ hyperthyroidism, and especially Graves’ ophthalmopathy (4, 5, 8, 9). In a case-control study done in The Netherlands, for example, the odds ratio for smoking among patients with Graves’ hyperthyroidism was 1.9. It was 7.7 among those with Graves’ hyperthyroidism and ophthalmopathy, and the ophthalmopathy was more severe in those who smoked (5). How might smoking contribute to the pathogenesis of Graves’ disease? It might alter the structure of the thyrotropin receptor, making it more immunogenic in a way that leads to the production of thyrotropin-receptor stimulating antibodies that react strongly with retro-orbital tissue. It might augment immunologic responsiveness to whatever factor initiates Graves’ disease or, on the other hand, it might impair restoration of tolerance to thyroid auto-antigens. Lastly, it might in some way sensitize retro-orbital tissue to the antibodies or other substances that cause ophthalmopathy. The results of the effects of parental smoking on thyroid function of fetuses or infants aged one year, as described by Gasparoni et al. (1), provide additional insight into the interrelationships between smoking and thyroid dysfunction. They found that infants whose mothers and fathers smoked had higher cord serum thyroglobulin and thiocyanate concentrations than infants whose parents did not smoke. The infants had no other evidence of thyrotropin-independent thyroid stimulation, such as increased serum thyroxine or triiodothyronine or decreased serum thyrotropin concentrations, as has been reported by others (10). Thyroid size was not determined, but in another study it was increased in infants born of mothers who smoked (11). Of note is their finding that cord serum thyroglobulin concentrations were increased in the infants whose fathers, but not mothers, smoked, indicating that the component(s) of tobacco smoke that stimulates thyroglobulin secretion can be transferred passively. Also of note is the finding that at age one year the infants whose fathers and mothers both smoked had higher serum thyroglobulin and thiocyanate concentrations than the infants whose parents did not smoke (the infants whose European Journal of Endocrinology (1998) 138 368–369 ISSN 0804-4643