Maternal leptin treatment during lactation programs the thyroid function of adult rats

Recently, we showed that both maternal malnutrition during lactation and leptin treatment during the neonatal period program thyroid function. In this study we evaluate whether maternal leptin treatment during lactation programs thyroid function of the offspring in the adulthood. The dams were divided into 2 groups: Lep-daily sc single injected with 8 microg/100 g of body weight with recombinant rat leptin during the last 3 days of lactation and control group (C) that received the same volume of saline. The 180 day-old animals received a single i.p. injection of (125)I (2.22x10(4) Bq) and they were killed 2 h after the injection. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH) and leptin concentrations were measured by radioimmunoassay. The milk of leptin-treated mothers on the last day of treatment had higher leptin (p<0.05) concentration. The pups of the leptin-treated mothers had at 21 days an unchanged T3, T4 and leptin serum concentrations with higher TSH (p<0.05). The offspring of Lep mothers had at 180 days a higher T3 (p<0.05) with normal thyroid (125)I uptake, T4 and TSH serum concentrations compared to the controls. So, the mother's hyperleptinaemia during lactation programs to a higher T3 serum concentration on the offspring, probably by a higher leptin transfer through the milk.     

Temporal evaluation of the thyroid function of rats programmed by leptin treatment on the neonatal period.

Hormones and malnutrition can imprint several changes in the beginning of life that programs homeostatic changes in the adulthood. We analyzed the thyroid function in 21, 30, 60 and 150 days old animals that were injected with leptin on the first 10 days of life, to determine whether this corresponds to a critical period for the establishment of the hormonal imprinting in the programming of the thyroid function. Pups were divided, within 24 hours of birth, into two groups: Lep group, which was injected once daily with 8 microg/100 g B.W. of recombinant mouse leptin for the first 10 days of lactation, and C-control group that received the same volume of saline. Lep group had higher leptin concentration at days 30 (+6 x , p<0.001) and 150 (+108%, p<0.05) than the controls. These animals had lower serum TT4 (-13%; p<0.05) and TT3 (-17.3%; p<0.002) at 30 days and higher serum TT4 and FT4 concentrations at 150 days (+17.5% and +10%, p<0.05 %, respectively, p<0.05) with lower serum TSH concentrations at 60 (-38.5%, p<0.05) and 150 days (-46%, p<0.05). These animals had also lower hepatic mitochondrial alpha-glycerol-3-phosphate dehydrogenase (mGPDH) activity at 21 (-22.5%; p<0.05), 30 (-50.4%; p<0.05) and 150 days (-40%; p<0.05) than the controls. These data show that the leptin injection in the beginning of lactation cause a hypothyroidism on the offspring as soon as 30 days of age and this alteration may be the imprinted factor for the programming of a higher thyroid function at the adulthood.     

Developmental plasticity in thyroid function primed by maternal hyperleptinemia in early lactation: a time-course study in rats

Pups whose mothers were leptin-treated during the last 3 days of lactation have thyroid dysfunction at adulthood. However, there was no report about leptin treatment in the first days of life or about its action on thyroid function during development. Here, we evaluated the effects of maternal leptin treatment on the first 10 days of lactation upon thyroid function of the offspring at 21, 30, and 180 days old. At birth, lactating Wistar rats were divided into: Leptin (Lep) - leptin-treated (8 μg/100 g of body weight, s.c.) for the first 10 days of lactation and Control (C, saline-treated). Mothers were killed at the end of lactation and their offspring at 21, 30, and 180 days old. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), and leptin levels in serum and milk were measured. Liver mitochondrial glycerolphosphate dehydrogenase (mGPD) activity was determined. Significant differences had p<0.05. At the end of lactation, Lep mothers had higher milk T3 (+ 30%), while their offspring had higher serum T3 (+ 20%) and TSH (+ 84%). At 30 days-old, Lep offspring showed lower TSH ( - 48%), T3 ( - 20%), and mGPDm ( - 42%). At 180 days-old, Lep group presented hyperleptinemia (1.4-fold increase), higher serum T3 (+ 22%), and lower mGPD activity ( - 57%). Maternal hyperleptinemia on lactation causes hypothyroidism in the pups at 30 days, which may program for higher serum T3 at adulthood. In conclusion, maternal hyperleptinemia during lactation, that is common in obese mothers, may have an impact in future disease development, such as thyroid dysfunction.     

Leptin treatment during lactation increases transfer of iodine through the milk

We have previously shown that protein restriction during lactation is associated with changes in iodine secretion into the milk and that a pup's serum leptin concentration was increased at the end of lactation. So, here we evaluate whether leptin treatment during lactation affects iodine transfer through the milk to the pups. Lactating rats were divided into two groups: the leptin (Lep) group, single injected with recombinant rat leptin (8 microg/100g of body weight, daily for 3 consecutive days), and the control (C) group that received the same volume of saline. We studied iodine transfer to the pups through the milk on Days 4, 12 and 21 of lactation. In those days, the dams were separated from their pups for 4 h. Then, the mothers received an injection of 131I (2.22x10(4) Bq ip) and the pups were allowed to nurse for 2 h. The animals were sacrificed 2 h later. Leptin, total serum T3 and total serum T4 concentrations were higher (P<.05) in pups of Lep mothers only on Day 4, suggesting a higher transfer of leptin through the milk at this period, probably with a direct stimulatory effect on thyroid hormone secretion. In other periods, however, even without a detectable increase in a pup's serum leptin concentration, maternal leptin administration increased the pup's thyroid iodine uptake (Day 12, 39%; Day 21, 34%), probably caused by a higher transfer of iodine through the milk, since they had a higher gastric content of 131I on Days 12 (31%) and 21 (128%).     

Leptin-programmed rats respond to cold exposure changing hypothalamic leptin receptor and thyroid function differently from cold-exposed controls

We showed that neonatal leptin treatment programmes for hyperleptinemia and central leptin resistance both at 30days-old and adulthood, while programmes for lower serum T3 at 30days-old, but higher thyroid hormones (TH) at adulthood. As in these animals, acute cold at 30days-old normalized leptinemia and restored the expression of hypothalamic leptin receptor (OBR), here we evaluate the effect of cold exposure on the thyroid function and OBR in adult rats programmed by neonatal hyperleptinemia. Pups were divided into 2 groups: Lep-injected with leptin (8μg/100g/BW, sc) for the first 10days of lactation, and C-injected with saline. At 150days, both groups were subdivided into: LepC and CC, which were exposed to 8°C for 12h. Serum leptin, TH, TSH, liver type I and brown adipose tissue (BAT) type II deiodinases (D1 and D2) activities, liver mitochondrial alpha-glycerol-3-phosphate dehydrogenase (mGPD) activity and adrenal catecholamine content were measured. Hypothalamic and thyroid OBR protein contents were evaluated. Differences were significant when p<0.05. Lep group had hyperleptinemia (+19%), higher T4 (+20%) and T3 (+30%) with lower TSH (-55%), higher liver D1 (1.4 fold-increase), lower BAT D2 (-44%) and liver mGPD activities (-55%), higher adrenal catecholamines (+44%), lower hypothalamic OBR (-51%) and normal thyroid OBR. Cold exposure normalized leptinemia, D1, mGPD, catecholamine and hypothalamic OBR. However, cold exposure further increased TH and decreased D2. Thus, cold exposure normalizes most of the changes programmed by neonatal hyperleptinemia, at the expense of worsening the hyperthyroidism and BAT thermogenesis.     

Leptin treatment during the neonatal period is associated with higher food intake and adult body weight in rats.

For this study, we have determined the effects of neonatal leptin treatment on the evolution of body weight. Experiment 1: pups were divided into two groups: LepF - injected with leptin (8 micro g/100 g of body weight) for the first 10 days of lactation and control (C) - receiving saline. Experiment 2: pups were divided into two groups: LepL - injected with the same leptin concentration of experiment one for the last 10 days of lactation, and C, which received saline. Body weight and food intake were monitored until age 150 days, after which leptin concentrations were measured by ELISA. The LepF group had a significant increase in body weight (p < 0.05) from day 98 onward, in food intake (p < 0.05) from day 74 onward, and higher serum leptin concentration compared to the control (108 %, p < 0.05). The LepL group had a significant increase in body weight (p < 0.05) from day 113 onward, in food intake from day 121 onward (p < 0.001), and higher serum leptin concentration compared to controls (6.9 %, p < 0.05). These results suggest that both periods of lactation constituted a critical window for body weight and food intake programming, but the effects are more marked when the leptin is injected within the first ten days.     

Disturbance of thyroidal iodine metabolism in BB/W rat.

To investigate the thyroid function in Bio-Breeding Worcester (BB/W) rats, we have examined the iodine metabolism, serum TSH and thyroid hormone levels in 8- and 16-week-old BB/W and normal Wistar (W) rats. At 8 weeks of age, serum TSH levels were significantly higher in BB/W rats than in W rats, although there was no difference in the serum levels of free T3 and free T4. Furthermore, the thyroidal radioactive iodine incorporation at 48 h was significantly lower in BB/W rats, suggesting that they might have some defects in iodine organification. At 16 weeks of age, serum TSH levels were also significantly higher in BB/W rats than in W rats. Furthermore, serum TSH levels in 16-week-old BB/W rats were significantly higher than in 8-week-old BB/W rats. The thyroid weight was significantly greater in BB/W rats, probably due to the increased serum TSH. The thyroidal radioactive iodine uptake at 48 h and the iodine content in the thyroid homogenates were significantly lower in BB/W rats. These results suggest that BB/W rats have some defect in iodine metabolism resulting in impaired thyroid hormone synthesis.     

Long-term effects of malnutrition during lactation on the thyroid function of offspring.

Some studies have shown that the mother's nutritional condition may influence offspring's endocrine function through metabolic imprinting. Recently, we showed that the kind of maternal malnutrition during lactation affects adult body weight of the offspring and it is related to milk composition. We studied lactating rats fed an 8 % protein-restricted diet (PR), a control 23 % protein diet (C), and an energy-restricted diet group (ER). After weaning, all animals received a normal diet until they were 180 days of age. At this time, the animals received a single i. p. injection of (131)I and were sacrificed 2 h after the injection. Total triiodothyronine (TT3) and total thyroxin (TT4) serum concentrations were measured by enzyme immunoassay. The PR group had significantly a higher thyroid (131)I uptake, TT3 serum concentration and in TT4 serum concentration, compared to the controls. The ER group had only significantly higher TT3 serum concentration. These results showed that thyroid function regulation in adulthood may depend on maternal nutritional condition during lactation. Probably, PR group had a high thyroid function, whereas the ER group only had an increase in the deiodination of T4. The hyperthyroidism in the PR group could explain the low body weight observed in those animals.     

Transfer of iodine through the milk in protein-restricted lactating rats

Iodine supply is important to avoid neonatal hypothyroidism. This study evaluated whether protein restriction during lactation affects iodine transfer to the pups through the milk. We studied lactating rats fed an 8% protein-restricted diet (PR), a control 23% protein diet (C), and an energy-restricted diet group (ER). On days 4, 12 and 21, mothers were separated from their pups for 4 h, injected with (131)I IP, and put together with their pups. The animals were killed 2 h later. PR pups had a significant decrease in iodine uptake in the gastric content and duodenal mucosa on the 4th day. On the contrary, at 12 and 21 days radioiodine was increased in the gastric content and in the duodenal mucosa. ER pups had an increase in iodine uptake in the gastric content and in the duodenal mucosa only at the end of lactation. The thyroid iodine uptake in PR pups was significantly decreased on the 4th day and significantly increased on the 21st day compared to control. When injected IP with an equivalent amount of (131)I, the PR pups had a decrease in thyroid iodine uptake on the 4th and 12th day, while ER pups had no significant changes. So, these data suggest that protein restriction during lactation was associated with lower iodine secretion into the milk in the beginning of lactation. However, at the end of lactation, an adaptation process seems to occur leading to a higher transfer of iodine through the milk that compensates the impairment of thyroid iodine uptake in these pups.     

Leptin and prolactin, but not corticosterone, modulate body weight and thyroid function in protein-malnourished lactating rats.

To understand the role of hormonal changes in the lower food ingestion and body weight in protein-restricted lactating rats as well as the higher serum T (3), higher deiodination, iodide and T (3) milk transfer, we measured maternal serum prolactin, leptin, TSH and corticosterone, which are hormones that could influence those parameters. After birth, dams were separated into: control-fed with a 23 % protein diet (n = 12) and PR (protein-restricted)-fed with an 8 % protein diet (n = 12). At the 4 (th) and 21 (st) day of lactation, half of the animals in each group were sacrificed. PR dams presented hyperleptinemia (day 4: + 20 %; day 21: + 19 %; p < 0.05) and hypoprolactinemia (day 4: - 85 %; day 21: - 92 %; p < 0.05), which could help explain the lower food consumption and body weight in lactating PR rats since leptin is anorexigenic and prolactin is orexigenic. Also, this hyperleptinemia could contribute for the increase in serum T (3) of PR dams, since leptin stimulates T (3) production, especially acting on deiodinases. Serum corticosterone was not different between PR and C groups, and TSH was lower only at the end of lactation. Thus, we suggest that both leptin and prolactin could play an important role in the body weight and thyroid hormone changes observed in protein-malnourished lactating rats.     

Association of Iodine and Iron with Thyroid Function

Iodine and iron are essential elements for healthy thyroid function. However, little is known about the association of iron and iodine with thyroid function in the general US population. We investigated iron and iodine status in relation to concentrations of thyroid hormones. We included 7672 participants aged 20 and older from three surveys (2007–2008, 2009–2010, and 2011–2012) of the National Health and Nutrition Examination Survey. Serum thyroid measures (including free and total T3 and T4, and TSH), serum iron concentration, and urinary iodine concentrations were measured. Multivariate linear regression models were conducted with serum thyroid measures as dependent variables and combinations of serum iron concentration and urinary iodine concentration as predictors with covariate adjustment. Logistic regression models were performed with TSH levels (low, normal, and high) and combinations of serum iron concentration and urinary iodine concentration. Overall, 10.9% of the study population had low iron; 32.2 and 18.8% had low or high iodine levels, respectively. Compared with normal levels of iron and iodine, normal iron and high iodine were associated with reduced free T3 and increased risk of abnormal high TSH. Combined low iron and low iodine was associated with reduced free T3 and increased TSH. In addition, high iodine was associated with increased risk of abnormal high TSH in females but not in males. Thyroid function may be disrupted by low levels of iron or abnormal iodine, and relationships are complex and sex-specific. Large prospective studies are needed to understand the mechanisms by which iron interacts with iodine on thyroid function.     

Excess Iodine and High-Fat Diet Combination Modulates Lipid Profile, Thyroid Hormone, and Hepatic LDLr Expression Values in Mice

The aim of this study was to illustrate the combined effect of excess iodine and high-fat diet on lipid metabolism and its potential molecular mechanism. Sixty Balb/c mice were randomly allocated to three control groups or three excess iodine groups and fed with a high-fat diet in the absence or presence of 1,200 μg/L iodine for 1, 3, or 6 months, respectively. Serum lipid parameters and serum thyroid hormones were measured. Expressions of scavenger receptor class B type-I (SR-BI) and low density lipoproteins receptor (LDLr) mRNA and protein in liver were detected. Thyroid histology and liver type 1 iodothyronine deiodinase activity were analyzed. At the end of 3 and 6 months, compared with control, serum TC, TG, and LDL-C in excess iodine group were significantly lower (p < 0.05). LDLr expression in liver was increased significantly (p < 0.05) and parallel to the change of serum TC and TG. TT3 and TT4 levels in serum were elevated and TSH decreased significantly (p < 0.05). Liver type I iodothyronine deiodinase activity was significantly higher (p < 0.05) than control at the end of 6 months. Moreover, a time course damage effect of excess iodine combined with high-fat diet on thyroid glands was observed. The present findings demonstrated that excess iodine combined with high-fat diet could cause damage to thyroid glands and lead to thyroid hormone disorder. Those in turn caused the upregulation of hepatic LDLr gene, which resulted in the disorder in serum lipids.     

超声弹性成像联合血清TSH、TT3、TT4在甲状腺结节良恶性诊断的临床价值研究

目的:探讨超声弹性成像联合血清促甲状腺激素(TSH)、总三碘甲状腺原氨酸(TT3)、总甲状腺素(TT4)在甲状腺结节良恶性诊断的临床价值。方法:选择2018年1月至2019年12月我院收治的甲状腺结节患者80例,根据病理检查结果分为良性结节组(48例),恶性结节组(32例),所有患者术前进行血清TSH、TT3、TT4及超声弹性成像检查,比较各组血清TSH、TT3、TT4水平及超声弹性成像评分,分析甲状腺结节患者血清TSH、TT3、TT4水平与超声弹性成像评分的相关性,超声弹性成像联合血清TSH、TT3、TT4在甲状腺恶性结节诊断的临床价值。结果:恶性结节组血清TSH、TT3、TT4水平显著高于良性结节组,超声弹性成像评分高分比例显著高于良性结节组(P<0.05),经Pearson相关分析显示,甲状腺结节患者血清TSH、TT3、TT4水平与超声弹性成像评分呈正相关(P<0.05)。以病理诊断为金标准,超声弹性成像联合血清TSH、TT3、TT4诊断甲状腺恶性结节的灵敏度为96.88%,特异度为93.75%,准确度为95.00%,灵敏度、特异度和准确度优于单独血清TSH、TT3、TT4检测和单独超声弹性成像检测。结论:超声弹性成像联合血清TSH、TT3、TT4对甲状腺结节良恶性的鉴别诊断具有较好的临床价值。     

Chronic leptin treatment inhibits liver mitochondrial alpha-glycerol-beta-phosphate dehydrogenase in euthyroid rats.

Leptin modulates the hypothalamus-pituitary-thyroid axis and peripheral metabolism of thyroid hormones (THs). We have studied the effect of acute and chronic leptin treatment upon liver mitochondrial glycerol phosphate dehydrogenase activity (mGPD), whose expression and activity are TH dependent. We performed 2 experiments: 1) acute leptin treatment - LepA: adult rats received a single leptin injection (8 microg/100 g BW); 2) chronic leptin treatment - LepC: adult rats received leptin (8 microg/100 g BW) daily, for 6 days. In both experiments, control groups were saline-treated. All rats were sacrificed 2 hours after the last dose. Liver mGPD activity was determined by colorimetric method. Liver D1 activity was measured by the release of (125)I from (125)I-rT3. Serum hormones were measured by RIA. LepA rats showed higher serum thyroid stimulating hormone (TSH) (+ 64%, p<0.05), free T4 (+ 34%, p<0.05), free T3 (+ 64%, p<0.05), and liver D1 activity (+ 85%, p<0.05), but no change in mGPD activity. Since THs increase mGPD activity, the unchanged level in the acute experiment is suggestive of an inhibitory role of leptin. LepC rats presented lower mGPD activity (-1.7-fold, p<0.05) and higher liver D1 activity (+ 32%, p<0.05), but no alteration in serum TSH and free THs. Our results show that leptin downregulates mGPD activity, mainly when hyperleptinemia is chronic.     

The nature of thyrotropin stimulation of thyroid function in Japanese quail: prolonged thyrotropin exposure is necessary to increase thyroidal 125I uptake

Single injections of thyrotropin (TSH) increase serum T4 and thyroidal 32P uptake but not thyroidal 125I uptake regardless of dosage, exposure time or age. Chronic TSH exposure, with 3 or more days of injection, does increase thyroidal 125I uptake. Studies using iodine (I) supplementation indicated that the increased thyroidal radioiodine uptakes seen with chronic TSH administration were not due to an I deficiency in the thyroid resulting from high hormone release. Labeled and unlabeled experiments comparing the effects of single vs. multiple injections of TSH were used to describe the effects of TSH on hormone release, hormone production and thyroidal I uptake.     

Leptin serum concentration,food intake and body weight in rats whose mothers were exposed to malnutrition during lactation

We had shown that adult animals, whose mothers were submitted to protein or energy restriction during lactation, differ from controls in their body weight and thyroid function. The aim of this study was to evaluate, from birth through six months of age, leptin serum concentration, body weight and food intake in animals whose mothers received protein or energy restricted-diet during lactation as follows: control (C)-23% protein; protein-restricted (PR)-8% protein; energy-restricted (ER)-23% protein, in restricted quantity, according to the mean ingestion of the PR group. After weaning (day 21) all pups had free access the control diet. Body weight of pups from PR mothers were always lower than those from controls (p < 0.05), while body weight of pups from ER mothers surpassed that of the C group significantly at 140 days of age. The food intake was lower in both offspring from PR and ER mothers, normalizing on the 32th day in pups from ER mothers and on the 52th day in pups from PR mothers. Leptin serum concentration in both offspring from PR and ER mothers were significantly decreased on the 12th day (p < 0.05) and increased on the 21st day (p < 0.05) compared to control. After weaning there was no differences among the groups. It is possible that changes in leptin concentration during lactation in the offspring of malnourished groups could permanently modify the setpoint for body weight control.     

SMS 201-995 and thyroid function in acromegaly: acute, intermediate and long-term effects.

The acute (TRH-stimulation test), intermediate (0-6 days administration), and long-term (0-30 months administration) effects of SMS 201-995 (octreotide) treatment on thyroid function were studied. Subcutaneous injection of 100 micrograms SMS 201-995 one hour before 200 micrograms TRH intravenously reduced serum TSH response area by more than 50% in 8 healthy volunteers. After 3 days of continuous subcutaneous infusion (CSI) of SMS 201-995 in 9 acromegalic patients (100 micrograms/24 h) a slight but significant decrease in serum total triiodothyronine (TT3) and a concomitant increase in serum TSH were demonstrated, indicating an initial inhibitory effect on peripheral deiodination of thyroxine. After a further 3 days treatment serum T3 and TSH had returned to prevalues. Six of the nine acromegalics were treated with SMS 201-995 (100-1500 micrograms/24 h) and admitted for diurnal hormone profiles on 13 occasions over 30 months. Apart from a barely significant increase in serum TSH, no changes in thyroid function were noted. The study was especially designed to detect minute changes over time in thyroid hormones. The only long-term effect of SMS 201-995 was the barely significant clinically irrelevant increase in serum TSH, possibly caused by a slight inhibition of peripheral deiodination of thyroxine.     

Effects of maternal leptin treatment during lactation on the body weight and leptin resistance of adult offspring

We investigate whether leptin treatment to lactating rats affects food intake, body weight and leptin serum concentration and its anorectic effect on their adult offspring. Lactating rats were divided into 2 groups: Lep-single injected with recombinant rat leptin (8 microg/100 g of body weight, daily for the last 3 consecutive days of lactation) and control group (C) that received the same volume of saline. After weaning all pups had free access to the control diet, their body weight and food intake were monitored at each 4 days until 180 days of age, when they were tested for its food intake and response to either leptin (0.5 mg/kg body wt, ip) or saline vehicle. The offspring of the leptin-treated dams gained more weight and had higher food intake from day 37 onward (p<0.05), higher amount of retroperitoneal white adipose tissue (RPWAT) (37%, p<0.05) and higher leptin serum concentration (40%, p<0.05) at 180 days of age compared to control group. The food intake at 2, 4, 6 and 24 h was unaffected after acute injection of leptin in these animals, suggesting resistance to the anorectic effect of leptin. The maternal leptin treatment during lactation makes their adult offspring more susceptible to overweight with resistance to the anorectic effect of leptin.     

Thyroid status of female rhesus monkeys and preliminary information on impact of perchlorate administration

Thyroid status was assessed in adult female rhesus monkey breeders at the California National Primate Research Center at the beginning of the breeding season. The 95% confidence intervals for thyrotropin (TSH), thyroxine (T(4)) and triiodothyronine (T(3)) (n = 66-80) were similar to those previously reported in smaller samples of macaque monkeys. Based on human criteria, 10 of 80 monkeys (12%) were hypothyroid (TSH > 2.0 μIU/mL). Because hypothyroxinaemia can be a risk factor in pregnancy, T(4) status was compared with past breeding history, breeding outcome for that season and general health records in a subset of 42 breeders. Age, weight and parity did not differ between monkeys in the lowest T(4) quartile as compared with those in the upper three quartiles. However, T(4) concentrations were significantly associated with the number of missed menstrual cycles during the previous breeding season. In additional work, three healthy lactating rhesus monkeys were given three different doses of environmental contaminant and thyroid iodine uptake inhibitor, ammonium perchlorate (0.006, 0.34, 12.8 mg/kg/day, respectively) in food for two weeks. Thyroid status variables (TSH, T(4), T(3), thyroid radioactive iodine uptake) were then measured. In the monkey receiving the highest perchlorate dose, iodine uptake was suppressed relative to baseline. The study shows the availability of tools to study thyroid status in rhesus monkeys, the variability of thyroid status in the breeder colony and the potential ability of environmental factors to influence thyroid status.