Suppression Of Thyroid Function Research Articles

Thyroid dysfunction as a long-term post-COVID-19 complication in mild-to-moderate COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), may lead to thyroid disorders, including both thyrotoxicosis and suppression of thyroid function. The aim of the present study was to assess the post-COVID-19 effects on thyroid function in patients without history of thyroid disease after complete recovery from mild-to-moderate COVID-19. Thyroid function tests [thyroid-stimulating hormone (TSH), free thyroxine (fT4), antithyroid antibodies] were performed on 113 patients (median age of 43.0 years; 31.0% male) two months after initial SARS-CoV-2 infection. TSH and fT4 were determined again one month later in this observational, prospective study. Thyroid dysfunction was registered in 61.1% of the patients (78.3% subclinical hypothyroidism, 13% subclinical hyperthyroidism and 8.7% overt hypothyroidism) two months after COVID-19. Moderate rather than mild manifestation of COVID-19 was significantly associated with a higher risk of thyroid dysfunction (OR 5.33; 95% CI: 1.70–16.69, p = 0.002), presence of thyroglobulin antibodies and need for levothyroxine therapy. At the follow-up, the subclinical hypothyroidism persisted in 28.3% of the subjects. Moreover, the TSH level was significantly reduced in comparison to the second month after the initial COVID-19 infection in all the patients (p < 0.001), but not in those with subclinical hypothyroidism and without hormone replacement therapy. Our findings indicate that COVID-19 could have long-term, negative effects on thyroid function. Therefore, thyroid function testing should be included in the follow-up algorithm of COVID-19 survivors.

PAPILLARY CARCINOMA OF THE THYROGLOSSAL DUCT CYST: A CASE REPORT

Introduction. Thyroglossal duct cysts (TGDCs) can be diagnosed at any age. They are most common in women aged 30–40. Cysts can become malignant in 1% of patients. As a result, a very rare tumor – TGDC carcinoma ¬– develops. Some oncologists believe it is sufficient to perform surgery using the Sistrunk procedure. Other scientists insist on performing the Sistrunk procedure followed by thyroidectomy, lymph node dissection, and radioactive iodine ablation. In this report, we would like to share our successful experience in treating a patient with papillary carcinoma of PCOS. Case report. A 47-year-old woman had persistent midline neck swelling for three years. This lesion was completely asymptomatic. The patient had no cases of head and neck irradiation or a family history of thyroid gland diseases. Physical examination revealed a solid, movable, smooth mass measuring 6.0 × 5.0 × 4.0 cm on the anterior surface of the neck. The thyroid gland was of normal size, without nodules. Lymph nodes of the neck were not enlargement. During sticking out the tongue and swallowing, the tumor moved upwards. Neck ultrasound, CT scan, and fine-needle aspiration biopsy confirmed the presence of TGDC papillary carcinoma. All laboratory results, including thyroid hormones, were within normal ranges. The patient underwent the Sistrunk procedure, total thyroidectomy with central lymph node dissection, radioactive iodine ablation, and suppression of thyroid function with levothyroxine. The patient's follow-up period has been currently 110 months. There were no signs of relapse. Discussion. The etiology of the malignant transformation of the TGDC remains unknown. One of the main theories is the spontaneous development of ectopic thyroid tissue located in the cyst walls. Ultrasound, CT, and MRI are considered sufficiently informative methods. A fine-needle aspiration biopsy confirms TGDC carcinoma in 53% of patients before surgery. Virtually all patients with TGDC carcinomas undergo the Sistrunk procedure. In addition, some of them perform a total thyroidectomy. Criteria for total thyroidectomy are age older than 45 years, history of neck irradiation, tumor size greater than 4 cm, presence of regional metastases, and thyroid gland dysfunction. Postoperative radioiodine ablation and suppressive levothyroxine therapy are considered the best treatment before the start of the follow-up period. Conclusions. The treatment of patients with TGDC carcinomas should be personalized. Determining criteria should be the patient's age, gender, condition of the thyroid gland and regional lymph nodes, size of the primary tumor, resection margins, invasion of the tumor into the surrounding tissues, and family history of thyroid diseases.

The Comparative Study on the Status of Bone Metabolism and Thyroid Function in Diabetic Patients with or without Ketosis or Ketoacidosis.

PurposeThis study aims to identify changes in bone turnover markers and thyroid function in diabetic ketosis (DK) and diabetic ketoacidosis (DKA).Materials and MethodsWe compared data from the Department of Endocrinology at Shanghai Pudong Hospital from 2018 to 2020 on the pancreatic status and previous glucose control, bone transformation, calcium homeostasis, and thyroid function in groups with diabetes (DM alone, n=602), DK (n=232), and DKA (n=60). Similar comparisons were made in recurrent DK (A) (n=17) and single DK (A) (n=272).ResultsThe fasting C-peptide level decreased significantly, but hemoglobin A1c (HbA1c) levels were higher in DK or DKA (p<0.05). Blood calcium and 25-hydroxyvitamin D3 (25-OH-VitD3) levels were significantly lower in DKA (p<0.05), but parathyroid hormone (PTH) levels remained constant across all three groups. The N-terminal middle molecular fragment of osteocalcin (N-MID) and β-C terminal cross-linking telopeptide of type 1 collagen (β-CTX) showed significant inverse alterations in DKA, regardless of gender or age (p<0.05). Otherwise, DKA significantly inhibited thyroid function (p<0.05). Furthermore, Spearman correlation analyses revealed a relationship between N-MID and HbA1c in DM alone (r=−0.27, p<0.01), while total triiodothyronine (TT3, r=0.62, p<0.01) or free T3 (FT3, r=0.61, p<0.01) in DK, and DKA (TT3, r=0.45, p<0.01; FT3, r=0.43, p<0.01). Multilinear regression analyses revealed that β-CTX (β=0.564), HbA1c (β=−0.196), TT3 (β=0.183), and 25-OH-VitD3 (β=−0.120) were the only independent determinants of N-MID in DM, whereas FT3 (β=0.491), β-CTX (β=0.315) in DK, and FT3 (β=0.420), β-CTX (β=0.367), TG (β=−0.278) in DKA. Only 25-OH-VitD3 was found to be significantly lower in recurrent DK (A) than in single onset DK (A) (p<0.05), and β-CTX (β=0.745) was found to be significantly independently associated with N-MID.ConclusionOur preliminary findings show a dramatic change in bone turnover markers in DM patients with DK and DKA, and this change may be related to thyroid function.

Thyroid Hormone Profile and Its Prognostic Impact on the Coronavirus Disease 2019 in Korean Patients.

BackgroundData on the association between coronavirus disease 2019 (COVID-19) and thyroid have been reported, including overt thyrotoxicosis and suppression of thyroid function. We aimed to evaluate the thyroid hormone profile and its association with the prognosis of COVID-19 in Korean patients.MethodsThe clinical data of 119 patients with COVID-19, admitted in the Myongji Hospital, Goyang, South Korea, were retrospectively evaluated. The thyroid hormone profiles were analyzed and compared based on disease severity (non-severe disease vs. severe to critical disease). Clinical outcomes were analyzed according to the tertiles of thyroid hormones.ResultsOf the 119 patients, 76 (63.9%) were euthyroid, and none presented with overt thyroid dysfunction. Non-thyroidal illness syndrome was the most common manifestation (18.5%), followed by subclinical thyrotoxicosis (14.3%) among patients with thyroid dysfunction. Thyroid stimulating hormone (TSH) and triiodothyronine (T3) levels were significantly lower in patients with severe to critical disease than in those with non-severe disease (P<0.05). Patients in the lowest T3 tertile (<0.77 ng/mL) had higher rates of mechanical ventilation, intensive care unit admission, and death than those in the middle and highest (>1.00 ng/mL) T3 tertiles (P<0.05). COVID-19 patients in the lowest T3 tertile were independently associated with mortality (hazard ratio, 5.27; 95% confidence interval, 1.09 to 25.32; P=0.038) compared with those in the highest T3 tertile.ConclusionThyroid dysfunction is common in COVID-19 patients. Changes in serum TSH and T3 levels may be important markers of disease severity in COVID-19. Decreased T3 levels may have a prognostic significance in COVID-19 related outcome.

Interactions among thyroid hormones and serum lipid levels in association with PCB exposure in the Mohawk Akwesasne population

Alterations in thyroid function and serum lipid levels were assessed in relation to exposure to polychlorinated biphenyls (PCBs) and three chlorinated pesticides (DDE, hexachorobenzene and mirex) in a sample of Akwesasne Mohawk adults. This population is highly exposed to PCBs because of living in close proximity to three aluminum foundries that used PCBs as hydraulic fluids, which then contaminated local fish, wildlife, water, air and soils. The goal was to assess interactions between thyroid function (TSH, T3, T4 and fT4) and serum lipids (cholesterol, triglycerides and total serum lipids) in relation to concentrations of 101 PCB congeners and three chlorinated pesticides. Previous studies in this population have shown that elevated concentrations of PCBs resulted in suppression of thyroid function in adolescents, and increased risk of clinical hypothyroidism in adults, as well as an elevation in serum lipids. However in adjusted analyses of PCB concentrations of 703 adults we find only small and inconsistent associations between serum PCB levels and thyroid function. The most striking observations were strong significant positive associations between TSH and T3 with serum lipids and a negative association with fT4 in women. Because elevated serum lipids increase risks of other diseases the respective roles of thyroid hormones and PCBs in regulation of serum lipids requires additional study.

Outcomes in pregnant women associating autoimmune thyroiditis and COVID-19

Coronavirus spectrum infections (especially with SARS-CoV-2) particularly influence the thyroid axis, with both thy­ro­to­xi­co­sis as well as suppression of thyroid function, thus deter­mi­ning severe pregnancy and perinatal outcomes. How­ever, the role of the thyroid autoimmunity and SARS-CoV-2 viral load in COVID-19-related thyroid dysfunction is unclear.

Thyroid Function Before, During, and After COVID-19.

ContextThe effects of COVID-19 on the thyroid axis remain uncertain. Recent evidence has been conflicting, with both thyrotoxicosis and suppression of thyroid function reported.ObjectiveWe aimed to detail the acute effects of COVID-19 on thyroid function and determine if these effects persisted on recovery from COVID-19.DesignA cohort observational study was conducted.Participants and SettingAdult patients admitted to Imperial College Healthcare National Health Service Trust, London, UK, with suspected COVID-19 between March 9 to April 22, 2020, were included, excluding those with preexisting thyroid disease and those missing either free thyroxine (FT4) or thyrotropin (TSH) measurements. Of 456 patients, 334 had COVID-19 and 122 did not.Main Outcome MeasuresTSH and FT4 measurements were recorded at admission, and where available, in 2019 and at COVID-19 follow-up.ResultsMost patients (86.6%) presenting with COVID-19 were euthyroid, with none presenting with overt thyrotoxicosis. Patients with COVID-19 had a lower admission TSH and FT4 compared to those without COVID-19. In the COVID-19 patients with matching baseline thyroid function tests from 2019 (n = 185 for TSH and 104 for FT4), TSH and FT4 both were reduced at admission compared to baseline. In a complete case analysis of COVID-19 patients with TSH measurements at follow-up, admission, and baseline (n = 55), TSH was seen to recover to baseline at follow-up.ConclusionsMost patients with COVID-19 present with euthyroidism. We observed mild reductions in TSH and FT4 in keeping with a nonthyroidal illness syndrome. Furthermore, in survivors of COVID-19, thyroid function tests at follow-up returned to baseline.

The Flavonoid Quercetin Induces AP-1 Activation in FRTL-5 Thyroid Cells.

Previous studies have shown that quercetin inhibits thyroid function both in vitro and in vivo. An attempt to evaluate the effect of quercetin at the promoter level of the thyroid-specific genes led to the observation that this compound induces the basal activity of the reporter vector. Therefore, the action of quercetin has been evaluated on the basal activity of several reporter vectors: The PGL3 basic, promoter and control vectors from Promega, and a pSV-based chloramphenicol acetyltransferase (CAT) reporter vector. In the Fisher Rat Thyroid cell Line FRTL-5 thyroid cells transiently transfected, quercetin 10 μM increased the basal activity of all the reporter vectors evaluated, although the degree of the effect was significantly different among them. The analysis of the difference among the regulatory regions of these vectors identified the activator protein 1 (AP-1) binding site as one of the potential sites involved in the quercetin effect. Electromobility shift assay experiments showed that the treatment with quercetin induced the binding of a protein complex to an oligonucleotide containing the AP-1 consensus binding site. This is the first study showing an effect of quercetin on AP-1 activity in thyroid cells. Further studies are in progress to understand the role of AP-1 activation in the effects of quercetin on thyroid function.

Developmental timing of perchlorate exposure alters threespine stickleback dermal bone

Adequate levels of thyroid hormone are critical during development and metamorphosis, and for maintaining metabolic homeostasis. Perchlorate, a common contaminant of water sources, inhibits thyroid function in vertebrates. We utilized threespine stickleback (Gasterosteus aculeatus) to determine if timing of perchlorate exposure during development impacts adult dermal skeletal phenotypes. Fish were exposed to water contaminated with perchlorate (30mg/L or 100mg/L) beginning at 0, 3, 7, 14, 21, 42, 154 or 305days post fertilization until sexual maturity at 1year of age. A reciprocal treatment moved stickleback from contaminated to clean water on the same schedule providing for different stages of initial exposure and different treatment durations. Perchlorate exposure caused concentration-dependent significant differences in growth for some bony traits. Continuous exposure initiated within the first 21days post fertilization had the greatest effects on skeletal traits. Exposure to perchlorate at this early stage can result in small traits or abnormal skeletal morphology of adult fish which could affect predator avoidance and survival.

Content of circulating extracellular DNA, plasma activities of matrix metalloproteinases, and ultrastructure of the myocardium in hypothyroid rats with hypercholesterolemia.

Free circulating extracellular DNA, plasma activities of matrix metalloproteinases in hypothyroid rats, and ultrastructural changes in the myocardium were studied under conditions of experimental hypercholesterolemia. For suppression of thyroid function, the animals received antithyroid drug mercazolyl under conditions of cholesterol diet. Hypercholesterolemia in hypothyroid rats (thyroxine concentration 2-fold below the normal) was paralleled by a pronounced increase of the concentration of free circulating extracellular DNA and total matrix metalloproteinases 2 and 7 activity. These changes were associated with lytic and destructive changes in cardiomyocytes and blood capillary endotheliocytes. Changes in the cardiomyocyte and endotheliocyte ultrastructure were more pronounced in hypothyroid rats.

Low Dose Bexarotene Treatment Rescues Dopamine Neurons and Restores Behavioral Function in Models of Parkinson’s Disease

Nurr1 is a nuclear hormone receptor (NucHR) strongly implicated in the growth, maintenance, and survival of dopaminergic neurons. Nurr1 may be unable to bind ligands directly, but it forms heterodimers with other NucHRs that do. Using bioluminescence resonance energy transfer (BRET) assays to directly monitor interactions of Nurr1 with other NucHRs, we found the cancer drug bexarotene (Targretin, also LGD1069) displayed biased interactions with Nurr1-RXR heterodimers compared with RXR-RXR homodimers. Remarkably, at doses up to 100-fold lower than those effective in rodent cancer models, bexarotene rescued dopamine neurons and reversed behavioral deficits in 6-hydroxydopamine (6-OHDA) lesioned rats. Compared to the high doses used in cancer therapy, low doses of bexarotene have significantly milder side effects including a reduced increase in plasma triglycerides and less suppression of thyroid function. On the basis of extrapolations from rat to human doses, we hypothesize that low oral doses of bexarotene may provide an effective and tolerated therapy for Parkinson's disease (PD).

Thyroid Suppression in Patients With Primary Hyperparathyroidism: Does It Improve the Pre-Surgical Scintigraphy Localisation?

IntroductionScintigraphy with technetium-sestamibi (MIBI) is the test of choice for localising adenomas in patients with primary hyperparathyroidism (PHPT). In some studies it has emerged that the increase in sensitivity of this test could be associated with a decrease in the uptake of the radiotracer by the thyroid gland. The aim of this study is to analyse our experience in patients with a negative scintigraphy with MIBI, and in whom the study was repeated after suppression of thyroid function with thyroxine. Material and methodsA prospective evaluation was performed on 17 patients who, between January 2006 and April 2011, had PHPT and negative imaging using scintigraphy with MIBI and who had the test repeated after the administration of thyroxine. The scintigraphy data and the correlation with the findings in the surgical intervention are reviewed. ResultsThe mean TSH at the time of repeating the MIBI was 0.12±0.1mIU/L. Of the 17 patients included, the scintigraphy under thyroid suppression was positive in 13 of them (76.5%), and in the other 4 (23.5%) patients no image suggestive of adenoma was found. In the cases where the MIBI was positive after suppression, the positive predictive value (PPV) was 100%. ConclusionSuppression of thyroid function by giving thyroxine can help to improve the sensitivity of MIBI in patients with previously negative scintigraphy studies and help in the minimally invasive treatment of patients with PHPT.

Fragments of Genomic DNA Released by Injured Cells Activate Innate Immunity and Suppress Endocrine Function in the Thyroid

Activation of innate and acquired immune responses, which can be induced by infection, inflammation, or tissue injury, may impact the development of autoimmunity. Although stimulation of cells by double-stranded DNA (dsDNA) has been shown to activate immune responses, the role of self-genomic DNA fragments released in the context of sterile cellular injury is not well understood. Using cultured thyroid cells, we show that cell injury prompts the release of genomic DNA into the cytosol, which is associated with the production of type I interferons, inflammatory cytokines, and chemokines. Molecules necessary for antigen processing and presentation to lymphocytes are also induced in thyroid cells by injury. dsDNA strongly suppressed the expression of sodium/iodide symporter and radioiodine uptake. To identify molecules responsible for sensing cytosolic dsDNA, we directly identified the cellular proteins that bound a dsDNA Sepharose column by mass spectrometry. Our analysis identified histone H2B, which was previously demonstrated to be an essential factor that mediates the activation of innate immunity induced by dsDNA. Knockdown of histone H2B using specific small interfering RNA abolished cell injury-induced innate immune activation and increased sodium/iodide symporter expression. These results indicate that genomic DNA fragments released by cell injury are recognized by extrachromosomal histone H2B, which results in the activation of genes involved in both innate and acquired immune responses in thyroid cells and suppression of thyroid function. These results suggest that sterile thyroid injury, in the absence of infection, may be sufficient to trigger autoimmune reaction and to induce thyroid dysfunction.

Suppression of Thyroid Function by Seaweed “Kombu” (Laminaria japonica) Supplement Seen in a Patient with Alopecia Areata: A Case Report

A 36-year old woman with severe alopecia areata was treated by intravenous corticosteroid pulse therapy, resulting in complete remission a year later. At her visit to us for follow-up, we found her thyroid swelling while she did not feel any symptom indicative of thyroid abnormality. Careful history taking revealed that she had kept taking supplement of seaweed “Kombu” (Laminaria japonica) (1g rhizoid/day) by herself for a year. Results of blood tests were: free T3, 2.7 pg/ml (normal: 2.3-4.3 pg/ml); free T4, 0.7 ng/ml (normal: 0.9-1.7 ng/ml) and TSH, 27.5 μU/ml (normal: 0.5- 5.0 μU/ml) in the serum. Thyroid echo imaging revealed weight of thyroid as 28.68 g, which is larger than normal (8-20 g). Collectively, we diagnosed her as having thyroid suppression by iodine of the seaweed supplement and therefore advised her to prohibit its intake. Two months later, her blood tests showed normalization of thyroid hormone synthesis.

The Epidemiology of Environmental Perchlorate Exposure and Thyroid Function: A Comprehensive Review

To review the epidemiological literature relevant to evaluating the risk of adverse effects on thyroid function associated with environmental perchlorate exposure. All studies investigating possible adverse effects of environmental perchlorate exposure on thyroid function in adults or in pregnant women and their newborns were critically evaluated. There is no credible or consistent evidence from any of the numerous studies using a variety of designs that environmental exposure to perchlorate has any adverse effect on thyroid function, whether measured as changes in thyroid hormone levels or, among newborns, as the diagnosis of primary congenital hypothyroidism. The absence of adverse effects of environmental perchlorate on the thyroid likely reflects the very low perchlorate exposure levels worldwide, compared with much higher levels of exposure to nitrate and thiocyanate, goitrogens that inhibit thyroid function by the identical mechanism of action proposed for perchlorate. Adjusted for potency, perchlorate accounts for <1% of the inhibition of iodide uptake in the thyroid resulting from environmental exposure to nitrate and thiocyanate. Occupational studies of workers with substantially higher perchlorate exposure than the general population indicate that even extended exposure to high perchlorate levels does not adversely affect thyroid function. There is no epidemiologic evidence that environmental or occupational exposure to perchlorate adversely affects thyroid function in the United States. Even if all perchlorate could be removed from the environment, >99% of the inhibition of iodide uptake in the thyroid resulting from exposure to environmental goitrogens would remain.

Interleukin-6 Is Not a Second Mediator of Interleukin-1 Induced Suppression of Thyroid Function in Cultured Human Thyrocytes

Interleukin-6 Is Not a Second Mediator of Interleukin-1 Induced Suppression of Thyroid Function in Cultured Human Thyrocytes

Pubertal exposure to thiodiazole copper inhibits thyroid function in juvenile female rats

Thiodiazole copper, as a thiadiazole fungicide, is widely used in China. The structure of thiodiazole copper shows a close relationship with N,N-methylene-bis (2-amino-1,3,4-thiadiazole) (Bis-A-TDA), which is a teratogen. A few studies have shown that some of the thiadiazole fungicides act as endocrine disruptors via disturbance in thyroid hormone homeostasis. Little is known about the effect of pubertal exposure to thiodiazole copper on the thyroid in pubertal female rats. Based on the protocol of the 20-day Pubertal Female Assay, we attempt to estimate the possible effects of exposure to thiodiazole copper on thyroid hormone and hepatic enzyme activity in female rats. Postnatal days (PND) 22-old Sprague–Dawley rats were administered with thiodiazole copper daily by oral gavage at doses 0, 4, 10, 20 or 30 mg/kg/day for 20 days. After treatments, the rats were sacrificed for blood collection; the reproductive organs, liver, pituitary, adrenal and thyroid gland were harvested. The results indicated that changes in thyroid endpoints following thiodiazole copper administration decreased serum triiodothyronine (T 3) and thyroxine (T 4) concentrations, increased thyroid stimulating hormone (TSH) concentrations and the weight of thyroid gland, induced hepatic uridine diphosphate glucuronyl transferase (UDPGT) activities in the highest dose group and produced thyroid gland hyperplasia. No histological changes were observed in uterus and ovaries moreover, age and weight at vaginal opening (VO) were unaffected by thiodiazole copper in all treatment groups. The absolute weights of liver and kidney were found to have decreased significantly in female rats. These data and changes demonstrate that thiodiazole copper is likely a thyroid disrupter in female rat following exposure during development, but doesnot have effect on the development of pubertal female rats. Further studies using environmentally relevant doses are needed for hazard identification.

Pubertal exposure to bismerthlazol inhibits thyroid function in juvenile female rats

Bismerthiazol, as a thiadiazole fungicide, is widely used in China. The structure of bismerthiazol shows a close relationship to N, N-methylene-bis (2-amino-1,3,4-thiadiazole) (Bis-A-TDA), which is a teratogen. A few studies have shown that this fungicide acts as an endocrine disruptor in mature rats via disturbance in thyroid hormone homeostasis at a certain dose. Little is known about the effect of pubertal exposure to bismerthiazol on the development in pubertal female rats. Based on the protocol of the 20-Day Pubertal Female Assay, postnatal days (PND) 22 old SD rats were administered with bismerthiazol daily by oral gavage at doses of 0, 10, 20 or 40 mg/kg/day for 20 days. After treatment, the rats were sacrificed for blood collection; the reproductive organs, liver, pituitary, adrenal and thyroid gland were harvested. The results indicated that changes in thyroid endpoints following bismerthiazol administration were decreased serum triiodothyronine (T 3) and thyroxine (T 4) concentrations, increased thyroid stimulating hormone (TSH) concentrations and the ratios of thyroid gland weights, and produced thyroid gland hyperplasia. No histological changes were observed in the uterus and ovaries; moreover, the age and weight at vaginal opening (VO) were unaffected by bismerthiazol in all treatment groups. These data and changes demonstrate that bismerthiazol is likely a thyroid disrupter in female rat following exposure during development, but does not affect the development of pubertal female rats. Further studies using environmentally relevant doses are needed for hazard identification.

Promoting effect of o-aminoazotoluene on hepatocarcinogenesis is accompanied by the increase in inflammatory and proliferative processes in liver tissue and decrease in the concentration of free thyroxin in the blood

o-Aminoazotoluene in noncarcinogenic doses promoted the development of liver tumors in female ICR mice induced by administration of diethylnitrosamine during early ontogeny. Severe inflammatory infiltration and proliferation of oval cells were found in liver tissue of these animals. The concentration of free thyroxin decreased in the blood. Our results supplement published data that promoters of hepatocarcinogenesis inhibit thyroid function.

AMELIORATION OF l‐THYROXINE‐INDUCED HYPERTHYROIDISM BY COUMARIN (1,2‐BENZOPYRONE) IN FEMALE RATS

1. The efficacy of coumarin (1,2-benzopyrone) was examined for the regulation of hyperthyroidism in female rats. 2. Coumarin was administered (10 mg/kg per day for 15 days) to l-thyroxine (L-T(4))-induced hyperthyroid as well as to euthyroid rats and changes in serum concentrations of thyroid hormones and in associated parameters, such as serum cholesterol, activity of hepatic 5'-monodeiodinase (5'DI) and glucose-6-phosphatase (G-6-Pase), glycogen content, bodyweight and daily food consumption, were analysed. Simultaneously, changes in hepatic lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were also investigated. 3. Although L-T(4) administration increased serum levels of thyroid hormones, the activity of hepatic 5'DI, G-6-Pase and LPO and daily food consumption, it decreased the level of serum cholesterol, hepatic glycogen content and the activities of anti-oxidant enzymes, such as SOD, CAT and GSH. 4. However, simultaneous administration of coumarin for 15 days to a group of hyperthyroid animals reversed most of the aforementioned changes, indicating its potential to ameliorate hyperthyroidism. Moreover, the drug did not increase, but rather decreased, hepatic LPO, suggesting its safe nature. 5. The present findings reveal a positive role for coumarin in the regulation of hyperthyroidism without any hepatotoxicity. It also appears that the test compound inhibits thyroid function at both a glandular level and at the level of peripheral conversion of T(4) to tri-iodothyronine.