Fluoride (F) is mainly ingested through drinking water and food. In addition to producing dental and skeletal fluorosis, excess fluoride may also affect the functioning of many organs including the thyroid gland. The present study investigated the thyroid function of subjects with dental fluorosis from F-endemic areas of Gaya region, Bihar, India and compared it with control individuals from Bodh Gaya. The mean F concentration in groundwater of F-endemic area was 2.82 ±0.18 mg/L (range 0.62-7.2 mg/L), while that of control area was 0.49 ±0.04 mg/L (range 0.21-0.76 mg/L). Abnormal levels of T3, T4 and TSH were found in the study subjects from both control as well as F-endemic areas.
RESULTS AND DISCUSSION
The mean F concentration in groundwater, F exposure dose, mean F level in the serum and urine of study subjects are shown in Table 1. For a given concentration of F in groundwater, the exposure dose for children was more than that of adults. Although the study subjects of control area consumed water with F < 1 mg/L, the mean F concentration in serum and urine of controls exceeded the normal upper limit of 0.02 mg/L and 0.1 mg/L respectively (Susheela et al 2005). Data suggest that these subjects were exposed to F from sources other than drinking water. The levels of thyroid hormones in control and fluorotic subjects are shown in Table 2. Further, abnormality in the concentration of thyroid hormone levels was noted in subjects of control area (Table 3). The level of TT3 was found to be low in only one child and high only in one adult woman. The TSH level was found to be low in 4 children and one female. Three out of 4 children with low TSH had normal TT4 and TT3 indicative of possible hyperthyroidism, the fourth one had normal TT3 but high TT4. The single female with low TSH had normal TT4 and TT3 levels. Three females and 4males had high TSH levels. Of these, two females and three males had normal TT4 and TT3 levels suggestive of subclinical hypothyroidism.
Abnormal ranges of T3, T4 and TSH were also found in the study subjects from F endemic areas (Table 4). None of the study subjects showed normal TT3 with high TSH and low TT4 levels indicating the absence of primary hypothyroidism. Ten out of 30 children, 5/30 females and 3/33 adult males had elevated TSH. Of these 3/10 children, 3/5 females and 2/3 males displayed increased TSH levels together with normal TT4 and TT3 indicating the possible occurrence of subclinical hypothyroidism. Unfortunately, the sample size is small and estimation of TT4 and TT3 appears to be insufficient. Estimation of FT3 and FT4 would give a clear picture.
The mean TT4, TT3 and TSH levels were significantly higher in the children of F endemic area compared to control (Table 5). However, the adult males and females showed significantly higher TSH levels as compared to control, the difference in TT3 and TT4 being insignificant. Higher serum TT3 and TT4 in the children of F endemic areas was reported by Xiaowei and Xiaohong (1994). Higher serum TSH values in children of F endemic areas were detected by Xiaoli et al (1999) and Xiang et al (2009). Liu et al (2008) and Xiuan et al (2006) found higher serum TSH in young pigs and rats exposed to high concentration of F in diet. As stated earlier,
all the study subjects of F endemic area suffered with dental fluorosis. The 30 children considered in this study also showed skeletal deformities, 6/30 were mentally also challenged and deaf. Thyroid hormone derangements arising due to F toxicity have been postulated to result in low IQ, deaf mutism and cretinism in children (He et al 1989, Du et al 1991).
Earlier studies in rats, mice, pigs, cows and humans also showed that the thyroid gland is sensitive to F (Yu 1985, Yu et al 1988; Susheela et al 2005; Ge et al 2005 a; 2005b; Bouaziz et al 2005, Cinar and Selcuk 2005; Zhan et al 2006). Possibly F mimics TSH, considered to be TSH analogue and may be active in both the presence and absence of TSH (Susheela et al 2005). This suggests that F might induce thyroid dysfunction as noted by Liu et al (2002). Further, Zeng et al (2012) found that F under experimental concentrations decreased cell viability and induced cell apoptosis in human thyroid cells. Surprisingly Hosur et al (2012) did not find any marked alterations in thyroid hormone concentrations in subjects with dental fluorosis. The results of the present study indicate that F toxicity may result in thyroid dysfunction especially in children with or without dental fluorosis. F toxicity may produce abnormalities in metabolic functions and oxidative stress. Oxidative stress in the brain may lead to reduction in learning-memory ability (Allen and Rana 2003; Wu et al 2006; Gao et al 2009). It was noted that even the residents of F non-endemic areas may be prone to fluorosis especially non-skeletal fluorosis due to consumption of F from sources other than drinking water. Therefore, estimation of blood and urine F level of human subjects is required together with groundwater F estimation. Further study is required with larger sample size and estimation of FT3 and FT4 is preferable over TT3 and TT4.