No abstract

The increasing use of fluoride for prevention of dental caries poses the problem as to whether this halogen has antagonistic properties towards iodine, whereby it could hamper the success of iodine prophylaxis of endemic goitre. Review of the literature shows that some authors have found an inhibition by fluoride of various steps of thyroid hormone biosynthesis in animal experiments. By and large, the inhibition was only slight and it was elicited only with fluoride doses greatly in excess of those recommended for caries prevention. The inhibition was not consistently present and other authors could not confirm it in comparable experiments. There is no convincing evidence that fluoride produces true goitres with epithelial hyperplasia in experimental animals. There are some reports based on casual observations that fluoride is goitrogenic in man. On the other hand, several good studies with adequate exposed and control populations failed to detect any goitrogenic effect of fluoride in man. It is noteworthy in particular that fluoride does not potentiate the consequences of iodine deficiency in populations with a borderline or low iodine intake. Published data failed to support the view that fluoride, in doses recommended for caries prevention, adversely affects the thyroid.

Naturally occurring euthyroid goitres in man and goitres produced in experimental animals by iodine deficiency or goitrogen feeding both have in common a thyroglobulin of low iodine content. The latter experimental goitres are always depleted of colloid and thyroglobulin. In contrast, natural goitres often contain excessive amounts of colloid which may accumulate because of endocytosis becoming refractory to TSH. We tested the hypothesis that minute doses of goitrogens could lower the iodine content of thyroglobulin without colloid depletion. We then examined whether such a low-dose 'classical' goitrogen could induce excessive colloid storage rather than depletion if acting in concert with lithium, a cation which blocks endocytosis. Rats on an adequate iodine intake were fed minimal doses of methimazole either alone or combined with lithium chloride. Chronic minimal-dose methimazole treatment lowered the iodine content of thyroglobulin without changing thyroglobulin content and thyroid weight. In contrast, addition of lithium to methimazole, produced goitres containing supranormal amounts of poorly iodinated thyroglobulin. We conclude that borderline doses of goitrogens can lower iodination of thyroglobulin without causing hyperplasia and colloid depletion. Thyroglobulin-rich goitres can be obtained by adding a second goitrogen which inhibits endocytosis. As an alternative to Marine's hypothesis of colloid goitre formation we suggest that inhibition of endocytosis, e g by goitrogens of the lithium type, could cause colloid and thyroglobulin accumulation in human iodine deficiency goitre.Endemie goitres in man are usually of the colloid variety, i.e. they contain large follicles filled with poorly iodinated thyroglobulin. By contrast, goitres produced experimentally by an iodine-deficient diet or by goitrogens show the histologie picture of hyperplasia, i.e. their follicles are lined by a highly columnar epithelium, the follicular lumina are de¬ pleted of colloid and contain only small amounts of poorly iodinated thyroglobulin. The pathogenesis of colloid goitre has been controversial for many years. Marine & Lenhart (1909) hypothesized that in response to iodine deficiency the thyroid goes first through a period of hyperplasia, then even¬ tually, because of iodine repletion or a decreased requirement for thyroid hormone, enters a resting phase with colloid storage, a sequence of events referred to as the 'Marine Cycle'. Experimentally, a histologie picture resembling colloid goitre was produced in several species by removal of the TSH stimulus on thyroid glands previously rendered hyperplastic (Astwood & Bissell 1944; Follis 1959a,b; Greer et al. 1967; Ölen 1969) or on entirely normal glands (Rosenberg & Cavalieri 1971;Smeds et al. 1977). In the latter case thyro¬ globulin of a low iodine content accumulated, but, due to the lack of TSH, the glands were presum¬ ably below normal size rather than goitrous. Unless one accepts Marine's explanation, one is therefore left with the dilemma how to explain goitre form...

In view of the recommendation that fluoride supplements via drinking water or table salt prevent dental caries, we analyzed whether fluoride had antithyroid properties in a sensitive experimental model. Rats were given either 60 or 200 micrograms/ml fluoride in the drinking water. This raised the serum fluoride concentration from 0.165 to 0.246 in the first and to 0.576 micrograms/ml in the second instance. Although the higher fluoride dose was near the toxic range, no antithyroid effect was observed. Neither organification of iodine, nor any subsequent step of thyroid hormone biosynthesis (transformation of monoiodotyrosine to diiodotyrosine and then to thyroxine) were affected. Fluoride had no effect on thyroglobulin content of the thyroid gland or on the degree of iodination of thyroglobulin.

Histological preparations from human nodular goitres reveal the presence of variable and sometimes considerable amounts of acellular material separating the individual follicles. Part of this interstitial tissue consists histologically of fibrous strands. However, quantitative data on the fibrous tissue content of goitres are scarce. In the present study the proportion of fibrous tissue in normal human thyroids and human goitres was determined biochemically by measuring their content of collagen, the predominant component of fibrous tissue. Total collagen content increased in parallel to thyroid weight. The relative collagen content, however, decreased slightly but significantly with increasing thyroid weight. The collagen/DNA ratio (= fibrous tissue/cell number ratio) was not higher in goitres than in normal human thyroids. These results indicate that in goitre growth, there is no disproportionate accumulation of fibrous tissue accompanying the multiplication of thyroid follicular cells. They are in line with the earlier findings that despite histological heterogeneity, the main component of nodular goitres is newly generated follicles.