The issue of specific effect of fluorine on the thyroid in humans remains debatable.
There is no doubt, however, that cases of experimental fluorosis are characterized by specific toxicity of fluorine to the thyroid. The hypoactivity of thyroid epithelium is observed, the destructive changes in the follicular cells increasing with the increased intoxication time (1, 9).
According to some authors (6, 12, 13), no specific fluorine toxicity to the thyroid is observed in fluorine-endemic areas. The dose and the time of exposure are considered to be the determining factor for fluorine intoxication. Under conditions of occupational exposure of industrial workers to fluorine (in the case of the workers of electrolysis workshops, it is an average exposure of 10 mg/shift), we deal with the inhalation of fluorine. The effect of fluorine through inhalation is 30 times stronger than that of fluorine ingested with the drinking water (10). Therefore the industrial effect of fluorine proved to be more powerful (by a factor of 10-20) in comparison with the endemic situation when the fluorine level in the drinking water ranges from 1.65 to 3.50 mg/L (2, 6). The reported results on the study of the iodine absorption function of the thyroid under industrial conditions are characterized by its hypofunction, whereas clinical research indicates hyperfunction of the thyroid which increases with longer employment (3). Along with this, a decrease in the level of triiodothyronine (T3) has been observed at early stages of fluorine intoxication, with the level of thyrotropic hormone (TSH) remaining normal, whereas in the case of long exposure, the decrease of thyrotropic function of the pituitary is observed (7). It can thus be concluded that the understanding of the functional state of the thyroid in the cases of industrial exposure to fluorides is not unambiguous, whereas observation results are scanty.
This paper was designed to study the specific features of thyroid function in humans under the conditions of chronic occupational exposure to fluorine.
Materials and methods
The following groups of workers of the electrolysis workshops of an aluminum plant were examined: 165 men of ages ranging from 30-55, of whom 27 men had worked at the facility for up to 10 years; 41 men who worked at the facility for 11-15 years; 40 men who worked at the facility for 16-20 years; 37 men with a service of 21-25 years; and 15 men with a service of over 25 years. Among those examined, there were men with chronic fluorine intoxication (5): 43 men with Stage 1 fluorosis (F1); 81 men with Stage 2 fluorosis (F2); and 41 men with suspected fluorosis (SF). There was also a group of 37 men with a toxic liver damage (TPP), which manifested itself in the form of a moderate cytolysis syndrome. Among them there were 24 men with F2 fluorosis, 7 men with F1 fluorosis, and 6 men with suspected fluorosis. The control group consisted of 25 men of the same ages that were not exposed to fluorine compounds. A clinical study was carried out at a hospital, in which the dimensions of the thyroid were determined by palpation. The levels of TSH, T3 and T4 were determined in the serum with the help of radioimmunoassay using the kits ELSA-2-TSH and CIS (France) on the basis of monoclonal antibodies or ???-T3-?? (Minsk, Belarus). The absorption of I-131 by the thyroid for 2, 24, and 48 hours was also studied. The results were processed using the analysis of variance with the help of the Student T test.
Results and discussion
No diffusive goiter has been found in the examined group of men. However, one third of the workers with a service of under 10 years had a 1st or 2nd degree thyroid enlargement, whereas only a few workers were characterized by the same condition in the groups of workers with longer service. The functional state of the thyroid was clinically defined as euthyroid, which coincides with the findings of some other authors (2, 3, 6). It should be pointed out, however, that most of the workers who were examined looked 3-7 years older than their passport age.
A decrease in the iodine-131 absorption function of the thyroid was detected in 40.7% of the observed workers when the interthyroid phase of iodine exchange was studied. Accumulation of I-131 by the thyroid that amounted to less than 26% for 24 hours was considered as decreased (i.e., hypofunction); accumulation that amounted to 42% was considered as increased (i.e. hyperfunction), with the normal function in the iodine-endemic area amounting to 36.6 +/- 6.0%). Note that while most of those observed had a satisfactory iodine absorption function on the first day, they were characterized by a damaged iodine organification stage on the second day, which may be indicative of a lower peroxidase activity.
Hypofunction was observed in half of the examined workers with a service of over 20 years as well as those who had F2 fluorosis. On the contrary, the frequency of hyperfunction occurrence (which amounts to 30% in the workers with a short period of service in the facility) distinctly decreases and is reduced to individual cases both with more years of service and in the cases of stage 2 fluorosis (F2) (see the Figure).
Figure: Frequency (n %) of hypofunction (clear columns) and hyperfunction (shaded columns) depending on the time of service (a) and the disease stage (b).
Thus, the interthyroid phase of iodine exchange in the case of chronic exposure to fluorides is defined as decreased (hypofunction), and can be used as one of the signs for diagnosing chronic fluorine intoxication.
The workers who worked in the facility for over 10 years had a significant decrease in T3 level in comparison with the control group, with its level further decreasing with longer service, reaching low values which correspond to hypothyroidism (see the Table) in the men with a service of over 20 years as well as in those who had F2 fluorosis.
The frequency of detecting low levels of T3 in workers with longer exposure amounted to 47%, with the values clearly increasing with longer exposure time and higher disease stage, amounting to as high a level as 65% with a service of 20 and more years and to 54.4% with fluorosis F2 (see Table). The T4 level did not change considerably, which suggests that the hormone biosynthesis in the thyroid has not been damaged. A decrease in the T3 level against the normal background level of T4 was also observed by other authors in fluorine-endemic areas and under conditions of occupational exposure to fluorides (2, 7).
The men in the main examined group had a significantly elevated TSH level in comparison with the control group. The number of people with a TSH level slightly higher than the upper range among the workers of the facilities was 1.5 times higher than that of the control group, 21.7 and 14%, respectively. With an increased exposure and a higher fluorosis stage, a tendency toward an increased TSH level was observed. The differences in the TSH blood level of the workers with a service of over 10 years are significant in comparison with those of the workers who were exposed for under 10 years. No significant differences in the TSH blood levels were observed in the fluorosis stage 1 and 2 patients and people with suspected fluorosis.
Thus, studying the thyroid state in the workers of the electrolytic workshops as a function of exposure time to fluorides and the disease stage showed certain specific features of the functional state of thyroid which is not accompanied by the clinical picture of either hypo- or hyperthyroidism. The reduction in thyroid iodine absorption function increasing with the increase of exposure time and the more advanced disease stage is moderate and does not result in the disruption of the biosynthesis and secretion of thyroid hormones, to which the unchanged T4 level testifies. A decrease in T3 concentration which increases with the increase of the service and a more advanced fluorosis stage is quite pronounced and corresponds to hypothyroidism. Most probably, the low T3 level syndrome is due to the effect of fluorine on the peripheral conversion of T4 to T3 at the cell-target level, although this effect may be indirect and may result from the disruption of the functional activity of the other endocrine glands. In particular, the decrease in the androgenic status under the conditions of chronic fluorine intoxication that was rather well studied in recent years (8) can result in the associated changes in the thyroid function (4, 14).
The low level T3 syndrome may be associated with liver damage, which is frequently observed in cases of fluorosis. The highest frequency of occurrence (75.6%) of the low T3 concentration syndrome is observed in the group of workers with TPP (toxic liver damage) (see Table). This supports the importance of the role of liver in the peripheral deiodination of T4 occurring in the liver parenchyme (11). Liver must be playing a crucial role in causing a low level T3 syndrome. The low-level T3 syndrome which is observed in many acute and chronic pathological states and metabolic conditions similar to starvation or undernourishment may result in lower metabolism which is aimed at energy conservation.
1. Abnormalities in the thyroid function characterized by a decreased iodine absorption function of the thyroid, a low level T3 syndrome, and a slight increase of the TSH level are observed in cases of chronic fluorine intoxication in the industrial workers.
2. The observed changes progressed with the increase of the time of exposure to fluorides and a more advanced disease stage.
3. The highest frequency of occurrence of the low level T3 syndrome was observed in workers with chronic fluoride intoxication including TPP (toxic liver damage).
4. The lowered iodine absorption function of the thyroid and/or the low level T3 syndrome can serve as diagnostic signs of chronic fluorine intoxication.
5. The decrease in the T3 level most probably occurs due to the disrupted conversion of T4 to T3 at the cell- target level. The disruption of conversion may be caused by fluorine affecting the enzyme system of deiodination as well as the toxic liver damage it causes.