Antithyroid Research Articles

Anti Thyroid Activity of Morinda tinctoria Roxb. Leaves against Thyroxine Induced Hyperthyroidism in Albino Wistar Rats

Anti Thyroid Activity of Morinda tinctoria Roxb. Leaves against Thyroxine Induced Hyperthyroidism in Albino Wistar Rats

Thyrotoxicosis: A rare cause of dysphagia

Excess and deficiency of thyroid hormones can have a variety of gastrointestinal manifestations ranging from heartburn, dysphagia, vomiting, diarrhea to constipation. We present a case of chronic thyrotoxic myopathy presenting as generalized weakness with bulbar involvement. He made a complete recovery with antithyroid therapy.

Thyrotoxic Periodic Paralysis after Surgery: A Case Report and Literature Review

Thyrotoxic periodic paralysis (TPP) is a rare but potentially life-threatening muscle disease in a thyrotoxic patient. Due to the lack of knowledge, the diagnosis is easily missed. Diagnosis of TPP is made by documentation of hypokalemia and hyperthyroidism in acute generalized muscle weakness. Hypokalemia is caused by an intracellular shift of potassium because of an increased Na-K-ATPase pump activity and the inhibition of the inward rectifying potassium (Kir) channels. The initial treatment aims to treat potentially life-threatening cardiac arrhythmias caused by severe hypokalemia. This can be done with potassium substitution and nonselective beta-blockers, being aware of the potential of rebound hyperkaliemia. Definitive treatment consists of avoiding triggers and correcting the hyperthyroid state with antithyroid drugs, radioactive iodine, or thyroidectomy. Once patients are, permanently euthyroid complete remission of the paralytic attacks usually occurs. We present a case of a 37-year-old male with diffuse muscle weakness after surgery. A new diagnosis of thyrotoxic periodic paralysis was made in the emergency department. This review summarizes the epidemiology, clinical manifestations, pathogenesis, diagnostics, and treatment of TPP.

Retracted: Ginsenoside Rg3 Alleviates Antithyroid Cancer Drug Vandetanib-Induced QT Interval Prolongation.

[This retracts the article DOI: 10.1155/2021/3520034.].

Transition from Hashimoto thyroiditis to Graves's Disease: an unpredictable change?

Hashimoto thyroiditis and Graves's disease are two related autoimmune disorders, representing the leading causes of hypothyroidism and hyperthyroidism. Autoimmune hypothyroidism is generally irreversible but very rarely, some patients would shift to hyperthyroidism. The aim of the study was to seek for possible clinical predictors of the transition from hypo to hyperthyroidism in patients with Hashimoto thyroiditis and to outline their clinical phenotype. Twelve patients with overt autoimmune hypothyroidism who had at least one transition from hypothyroidism to autoimmune hyperthyroidism were compared with 294 consecutive patients with autoimmune hypothyroidism and 69 consecutive patients with autoimmune hyperthyroidism that accessed the outpatient clinic over six months. Demographic, hormonal data and autoantibodies titers were compared. Prevalence of smoking habit was significantly higher in switchers compared to controls. Switchers showed a significantly higher prevalence of personal and familial history of non-thyroidal autoimmune disorders. TSH levels were significantly lower in the switcher group during the hypothyroid phase and levothyroxine dose required was lower. TSH concentrations were significantly lower while free fT4 and free fT3 values were higher in GD patients compared to switchers during the hyperthyroid phase despite comparable TRAb levels. Prevalence and type of hyperthyroid symptoms and orbitopathy were similar between switchers and GD group. Mean dose of anti-thyroid drugs was significantly higher in GD patients compared to switchers. No differences were observed in the remission rate from hyperthyroidism between the two groups, despite switchers showed a significantly lower time-to-remission. Conversion of Hashimoto Thyroiditis towards Graves' disease is a rare phenomenon which can occur almost at any time after the development of autoimmune hypothyroidism. Our findings suggest active surveillance of hypothyroid patients who require frequent reduction of levothyroxine during follow up and testing for TSHR antibodies in these patients.

Prescription medication use during pregnancy in the United States from 2011 to 2020: trends and safety evidence

Medication use during pregnancy has increased in the United States despite the lack of safety data for many medications. This study aimed to inform research priorities by examining trends in medication use during pregnancy and identifying gaps in safety information on the most commonly prescribed medications. We identified population-based cohorts of commercially (MarketScan 2011-2020) and publicly (Medicaid Analytic eXtract/Transformed Medicaid Statistical Information System Analytic Files 2011-2018) insured pregnancies ending in live birth from 2 health care utilization databases. Medication use was based on filled prescriptions between the date of last menstrual period through delivery, as well as the period before the last menstrual period and during specific trimesters. We also included a cross-sectional representative sample of pregnancies ascertained by the National Health and Nutrition Examination Survey (2011-2020), with information on prescription medication use during the preceding month obtained through maternal interviews. Teratogen Information System was used to classify the available evidence on teratogenic risk. Among over 3 million pregnancies, the medications most commonly dispensed at any time during pregnancy were analgesics, antibiotics, and antiemetics. The top medications were ondansetron (16.8%), amoxicillin (13.5%), and azithromycin (12.4%) in MarketScan, nitrofurantoin (22.2%), acetaminophen (21.3%; mostly as part of acetaminophen-hydrocodone products), and ondansetron (19.5%) in Medicaid Analytic eXtract/Transformed Medicaid Statistical Information System Analytic Files, and levothyroxine (5.0%), sertraline (2.9%), and insulin (2.9%) in the National Health and Nutrition Examination Survey group. The most commonly dispensed suspected teratogens during the first trimester were antithyroid medications. The use of antidiabetic and psychotropic medications has continued to increase in the United States during the last decade, opioid dispensation has decreased by half, and antibiotics and antiemetics continue to be common. For one-quarter of medications, there is insufficient evidence available to characterize their safety profile in pregnancy. There is a need for more drug research in pregnant patients. Future research should focus on anti-infectives with high utilization and limited level of evidence on safety for use during pregnancy. Although lack of evidence is not evidence of safety concerns, it does not indicate risk either. In many instances, the benefits outweigh the risks when these medications are used clinically, and some of the medications with no proven safety may be necessary to treat patients.

The Presence of Anti-TPO Antibodies Increase the Likelihood of Post-I131 Hypothyroidism.

The use of radioactive iodine in the treatment of hyperthyroidism is common practice. However, a standardized treatment protocol with regard to radioactive iodine treatment (RAI) remains subject to discussion. We retrospectively analyzed 100 patient records. Patient diagnosis, age, gender, body mass index (BMI), dose of radioactive iodine, thyroid size, the 24 h radioiodine uptake (24 h RAIU) and protein bound iodine (PBI) were deducted, as well as the use of antithyroid drugs prior to RAI. Biochemical parameters were obtained, such as TSH, fT4, fT3, Anti-TPO, Anti-TG antibodies and thyroid stimulating antibodies. After 5 years of follow-up, 46% of the patients proved to be hypothyroid, whereas 8% of the patients were not cured after one dose of RAI. One year after RAI, a larger proportion of patients with a toxic nodule developed hypothyroidism compared to patients with a multinodular goiter (MNG) (44.2% vs. 21.2%). Radioactive iodine dose, PBI, RAIU, BMI, size of the thyroid gland, diagnosis, age and TPO-antibodies showed statistically significant differences in the development of hypothyroidism. Furthermore, thiamazole pretherapy was shown to be a predictor of hypothyroidism, as well as a high PBI value, exhibiting a positive predictive value of 85.2% when the PBI exceeded 0.16. We suggest a standardized measurement of TPO-Ab's to further determine their role in the development of hypothyroidism after RAI. The empirical dosing regimen was very effective, illustrating a 92% cure rate after 1 dose.

The genetics of Graves' disease.

Graves' disease (GD) is the commonest cause of hyperthyroidism and has a strong female preponderance. Everyday clinical practice suggests strong aggregation within families and twin studies demonstrate that genetic factors account for 60-80% of risk of developing GD. In this review, we collate numerous genetic studies and outline the discoveries over the years, starting with historic candidate gene studies and then exploring more recent genome-wide linkage and association studies, which have involved substantial cohorts of East Asian patients as well as those of European descent. Variants in genes including HLA, CTLA4, and PTPN22 have been shown to have substantial individual effects on disease susceptibility. In addition, we examine emerging evidence concerning the possibility that genetic variants may correlate with relevant clinical phenotypes including age of onset of GD, severity of thyrotoxicosis, goitre size and relapse of hyperthyroidism following antithyroid drug therapy, as well as thyroid eye disease. This review supports the inheritance of GD as a complex genetic trait, with a growing number of more than 80 susceptibility loci identified so far. Future implementation of more targeted clinical therapies requires larger studies investigating the influence of these genetic variants on the various phenotypes and different outcomes of conventional treatments.

Stress-Induced Graves Disease: Spontaneous Recovery After Stress Relief.

Emotional stress is a precipitating factor for Graves disease (GD). However, the influence of stress relief on the course of GD is unknown. Here, we present a series of patients diagnosed with stress-induced GD in whom stress relief alone led to remission of GD. We report on 11 patients in whom hyperthyroid symptoms started just after severe emotional stress. All patients had suppressed thyroid-stimulating hormone (TSH) levels and elevated free thyroxine (FT4; 22.2-49.5 pmol/L) and TSH-receptor antibody (TRAb; 0.57-40 U/L) levels and were subsequently diagnosed with stress-induced GD. However, all patients declined antithyroid drug treatment. Surprisingly, clinical and biochemical remission was observed in 9 out of 11 patients after 1 to 3 and 2 to 7 months of self-reported stress relief, respectively. Five patients showed long-lasting remission (median follow-up 2.3 years). In 4 patients, remission was initially achieved, but GD relapsed 1 to 4 years afterwards. In 2 patients, treatment with antithyroid drugs was initiated because of rapidly increasing FT4 levels. Baseline FT4 and TRAb levels tended to be higher in patients who did not achieve remission. Furthermore, patients without long-lasting remission were more frequently known to have prior thyroid disease. We report on a series of patients with stress-induced GD in whom stress relief alone led to remission of GD (thus without antithyroid drugs). This may indicate that clinicians could consider stopping antithyroid drug treatment or at least shortening the treatment period after stress relief in patients with stress-induced GD.

Living donor liver transplantation for a patient with acute liver failure following thyroid storm: a case report

BackgroundThyroid storm can be complicated by liver dysfunction, which may occasionally progress to acute liver failure. We herein report a case of acute liver failure following thyroid storm that was treated with living donor liver transplantation after resuscitation from cardiopulmonary arrest.Case reportThe patient was a woman in her 40 s who had been diagnosed with an abnormal thyroid function. She suffered from fatigue and vomiting, and was found to have consciousness disorder, a fever, and tachycardia with a neck mass. She was diagnosed with thyroid storm and was referred to our hospital. After arrival, she went into cardiopulmonary arrest and veno-arterial extracorporeal membrane oxygenation was initiated. In addition to treatment for thyroid storm with antithyroid drugs, steroids, and plasma exchange, extracorporeal life support was required for 5 days. However, despite improvements in her thyroid function, her liver function deteriorated. We planned living donor liver transplantation for acute liver failure after ensuring the recovery and control of the thyroid function following total thyroidectomy. The donor was her husband who donated the right lobe of his liver. Although she experienced acute cellular rejection after surgery, and other complications—including intra-abdominal hemorrhaging and ischemic changes in the intestine—her liver function and general condition gradually improved. One year after living donor liver transplantation, the patient was in a good condition with a normal liver function.ConclusionsTo our knowledge, this is the first report of living donor liver transplantation in a patient with acute liver failure following thyroid storm. Liver transplantation should be recognized as an effective treatment for acute liver failure following thyroid storm.

The Origin of Antithyroid Drugs

The Origin of Antithyroid Drugs

Effect of previous administration of potassium iodine and different durations of low iodine diets for radioiodine therapy on the treatment of Graves' disease in iodine-rich areas.

To examine whether adherence to a low-iodine diet (LID) enhances the therapeutic efficacy of radioiodine therapy (RAI) in Graves' hyperthyroidism (GH) in iodine-rich areas. We retrospectively evaluated 185 patients with GH from Aichi (n = 114) and Hokkaido (n = 71) Prefectures. Patients aged ≥ 18years with GH who underwent RAI between December 2012 and March 2022 were divided into subgroups based on pretreatment with anti-thyroid drug (ATD) or potassium iodide (KI). Patients were followed up with LID from 18days (group A) or 7days (group H) before RAI to 3days after RAI. The dose of radioactive iodine 131 (131I) was adjusted to deliver > 100Gy to the thyroid. The associations between urinary iodine concentration on UIC2 vs. 24hRU and UIC2 vs. the 1-year RAI success rate (SR) were investigated. Compared with UIC1, UIC2 was significantly decreased in all subgroups (P < 0.01). An inverse correlation between UIC2 and 24hRU was observed in the four groups; however, the difference was insignificant. The SR in groups A and H was 85% and 89%, respectively. Univariate analysis revealed no association between UIC2 and SR in each group. Additionally, stratification of the 185 patients into quartiles using UIC2 yielded no significant differences in SR (p = 0.79). LID sufficiently reduced UIC in patients undergoing RAI. Although a lower UIC2 may increase 24hRU, it did not increase the success of RAI. The benefit of LID in enhancing the efficacy of RAI in GH treatment remains uncertain.

Graves’ disease – management of Graves’ orbitopathy and thyrotoxicosis, including new therapies

Graves' disease (GD) is the most common cause of hyperthyroidism in countries with adequate iodine supply, and its main extrathyroid manifestation is thyroid orbitopathy. For many years, thyrotoxicosis has been treated with antithyroid drugs, radioactive iodine therapy and thyroidectomy, and glucocorticoids have remained the standard treatment of thyroid eye disease (TED). Currently, there is a growing trend of using targeted therapies in the treatment of thyroid orbitopathy (TO). The significant development of immunobiology, a better understanding of the pathophysiology of the disease and a multitude of studies on new therapies give hope for better treatment results and an improvement in the quality of life of patients. The aim of the paper is to discuss the current principles of management of Graves' disease, including thyroid orbitopathy, with particular emphasis on new therapeutic methods. The potent role of K1-70TM and small molecule thyroid stimulating hormone (TSH) receptor antagonists in the treatment of hyperthyroidism is indicated. Not only do we point out the promising outcomes of combining glucocorticoids with mycophenolates, but also highlight the use of teprotumumab, rituximab, cyclosporin A, azathioprine, methotrexate, tocilizumab and sirolimus in the therapy of active moderate to severe form of orbitopathy. The protective and supportive effect of statins in the treatment of TED is noted. The limitations of the research results mentioned in the paper are remarked and the need for further randomized studies of long-term safety and efficacy in a larger group of patients is underlined.

Current and promising therapies based on the pathogenesis of Graves' ophthalmopathy.

Graves' ophthalmopathy (GO) is a hyperthyroidism-related and immune-mediated disease that poses a significant threat to human health. The pathogenesis of GO primarily involves T cells, B cells, and fibroblasts, suggesting a pivotal role for the thyrotropin-antibody-immunocyte-fibroblast axis. Traditional treatment approaches for Graves' disease (GD) or GO encompass antithyroid drugs (ATDs), radioactive iodine, and beta-blockers. However, despite decades of treatment, there has been limited improvement in the global incidence of GO. In recent years, promising therapies, including immunotherapy, have emerged as leading contenders, demonstrating substantial benefits in clinical trials by inhibiting the activation of immune cells like Th1 and B cells. Furthermore, the impact of diet, gut microbiota, and metabolites on GO regulation has been recognized, suggesting the potential of non-pharmaceutical interventions. Moreover, as traditional Chinese medicine (TCM) components have been extensively explored and have shown effective results in treating autoimmune diseases, remarkable progress has been achieved in managing GO with TCM. In this review, we elucidate the pathogenesis of GO, summarize current and prospective therapies for GO, and delve into the mechanisms and prospects of TCM in its treatment.

Thyroid medications and patient adherence: understanding prescription patterns and factors influencing treatment compliance

Thyroid problems are common in India affecting around 42 million people. Early diagnosis and therapy play an important role in managing this endocrine disorder. Hypothyroidism and hyperthyroidism are the most common thyroid disorders and are treated with thyroid hormone replacement therapy and antithyroid drugs. However, medication adherence, side effects, and misunderstanding of the importance of medication lead to inconsistent intake. This study aimed to evaluate the pattern of prescribing and adherence to thyroid medication. This cross-sectional study was conducted over 6 months in a tertiary care hospital, involving 188 patients with thyroid disorders. Data was collected using a validated form and medication adherence rationing scale. The collected data, including MARS scores, were entered into Microsoft Excel and analyzed using IBM SPSS Version 25. Quantitative data were analyzed using the mean and standard deviation, while categorical data were summarized using frequencies and percentages. The Chi-square test was used to evaluate associations, with a significance level of p &lt; 0.05. In our study, 163 participants diagnosed with hypothyroidism exhibited a notable adherence rate of 89.57%. The 25 hyperthyroid patients showed strong adherence to the recommended drugs, with those provided methimazole having the highest adherence rate (52.0%). No statistically significant connections were found when examining the variables affecting drug adherence. Levothyroxine and methimazole were the preferred medications for managing hypothyroidism and hyperthyroidism, respectively. A high adherence rate among patients indicates heightened awareness and understanding of their condition, as well as consistent adherence to the medication schedule. These findings emphasize the importance of early diagnosis, appropriate prescription patterns, and patient adherence in effectively managing thyroid disorders.

Antithyroid drug-induced leukopenia and G-CSF administration: a long-term cohort study

Although antithyroid drug (ATD)-induced agranulocytosis is a significant concern, its risks associated with long-term use and re-administration are not fully elucidated. Therefore, we performed this study to determine the incidence of ATD-induced leukopenia and G-CSF administration using administrative claims database. Retrospective cohort study. This study was performed using the DeSC Japanese administrative claims database. A total of 12,491 patients with newly diagnosed Graves’ disease (GD) who received methimazole or propylthiouracil between April 2014, and February 2021 among 3.44 million patients in the database were included in the study. We measured the six-year incidence of leukopenia and granulocyte colony-stimulating factor (G-CSF) administration. The incidence of leukopenia and G-CSF administration was 1.34% (168 patients) and 0.30% (38 patients), respectively. Leukopenia had a dose-dependent and biphasic incidence. The incidence of leukopenia and G-CSF administration was 37.2 (0.7%) and 8.0 (0.2%) per 1000 person-years during the first 72 days of ATD initiation, whereas it was 3.1 and 0.7 per 1000 person-years during the subsequent 6 years, respectively. The incidence of both outcomes was comparable between first administration and re-administration of ATD. The incidence of ATD-induced leukopenia and G-CSF administration was high in the first 72 days, with a reduced risk for at least 6 years thereafter. The incidence was similar between first administration and re-administration. ATD, a standard therapy, is often administered for a long period; therefore, our findings can guide the treatment of GD.

Significance of thyroperoxidase and thyroglobulin antibodies in medically treated Graves' disease.

Thyroperoxidase (TPOAb) and thyroglobulin (TgAb) antibodies are highly prevalent in Graves' disease (GD), but their significance is controversial. We retrospectively analyzed TPOAb and TgAb levels and evolution in 136 patients with newly diagnosed GD between 2000 and 2022, treated with anti-thyroid drugs (ATD) in a block-and-replace (B+R) regimen for at least 12 months and followed up for at least 1 year after ATD discontinuation or until disease relapse. At diagnosis, 98 out of 136 (72%) patients were TPOAb positive and 73 out of 136 (54%) patients were TgAb positive. The presence of TPOAb or TgAb antibodies at diagnosis was generally not related to GD presentation and did not influence the risk of relapse (P = 0.304 and P = 0.348, respectively). There was less TED (thyroid eye disease) in TgAb-positive patients than TgAb-negative patients at diagnosis (11 out of 73 (15.1%) versus 21 out of 63 (33.3%) P = 0.012). In contrast, the presence of TPOAb at diagnosis was not associated with TED (P = 0.354). The absence of TgAb at diagnosis (P = 0.05) and time to euthyroidism (P = 0.009), but not smoking or TRAb levels, were associated with TED in multivariate logistic regression. TPOAb and TgAb levels during treatment and after its discontinuation were not predictive of relapse, except for lower titers of TgAb at 18 months in patients who relapsed (P = 0.034). In GD patients treated with a first course of ATD in a B+R regimen we observed lower titers of TgAb at the end of treatment in patients who relapsed and a significant protection against TED in patients with positive TgAb at diagnosis, irrespectively of TPOAb.

Molar Pregnancy–Induced Hyperthyroidism: The Importance of Early Recognition and Timely Preoperative Management

Abstract Hyperthyroidism due to gestational trophoblastic disease (GTD) is a rare but potentially life-threatening condition. Optimal perioperative management is crucial for favorable outcomes and prevention of thyroid storm. However, scarce data exist defining the ideal approach to this complex clinical presentation. This case report describes a first-time pregnant 32-year-old woman who was found to be biochemically hyperthyroid in the context of a 10-week gestation molar pregnancy. Despite her biochemical values, the patient remained clinically asymptomatic of her thyroid disease. The Gynecology and Anesthesiology services urgently consulted Endocrinology, and empiric treatment for prevention of potential impending thyroid storm was initiated prior to operative uterine evacuation. After 2 uneventful dilation and curettages with chemotherapy and a transient prescription of antithyroid medication, the patient normalized her human chorionic gonadotropin (hCG) level and recovered to biochemical euthyroidism. Other than a pruritic rash that may have been due to propylthiouracil, the patient's hyperthyroidism improved without further complications. This case highlights the importance of recognizing the link between GTD and thyrotoxicosis to allow for timely initiation of appropriate preoperative treatment. Fortunately, the multidisciplinary approach facilitated management to prevent evolution to thyroid storm.

Advancing Preoperative Strategies for Thyroidectomy in Graves' Disease: A Narrative Review.

Graves' disease is an autoimmune disorder characterized by thyroid-stimulating antibodies that can potentially lead to thyrotoxicosis, goiter, skin disease, and eye disease. Available treatment options for Graves' disease include management with antithyroid drugs (ATDs), thyroid ablation with radioactive iodine (RAI), and surgical thyroid gland removal. For individuals unable to reach a normal thyroid hormone level, promptly considering a thyroidectomy is essential. Preoperative strategies to achieve a euthyroid state prevent thyroid storms and minimize postoperative complications and are therefore crucial. While variations in professional guidance exist, this review focuses on standard medical interventions as well as compares respective guidelines set forth by the American Thyroid Association, the European Thyroid Association, the American Association of Clinical Endocrinology, and the American Association of Endocrine Surgeons. There is consensus among these organizations underscoring the importance of rendering patients euthyroid prior to surgery and the use of ATDs. Most guidelines recommend screening for vitamin D deficiency as well as endorse thyroidectomy as the preferred treatment option for hyperthyroidism with skilled surgeons. Nevertheless, discrepancies do become apparent in aspects such as potassium iodide (SSKI) course duration and preoperative dexamethasone administration. By understanding these differing approaches, healthcare professionals can more effectively manage Graves' disease prior to surgery, resulting in improved patient outcomes and enhanced surgical success.

Tetrabromobisphenol A exerts thyroid disrupting effects but has little overt impact on postnatal brain development and neurobehaviors in mice

Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant. There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals, but different results were also reported, along with inconsistent reports regarding its neurotoxicity. Here, we investigated thyroid disrupting effects and neurotoxicity of TBBPA (5, 50, 500 µg/(kg·day)) to male mice following maternal and direct exposure through drinking water, with the anti-thyroid drug propylthiouracil (PTU) as the positive control. On postnatal day (PND) 15, we expectedly observed severe thyroid compensatory hyperplasia and cerebellar developmental retardation in PTU-treated pups. The highest dose of TBBPA also caused thyroid histological alteration but had no effects on cerebellar development in terms of Purkinje cell morphology and the thickness of the internal granular layer and the molecular layer of the cerebellum. During puberty and adulthood, the thyroid morphological alterations became more pronounced in the TBBPA-treated animals, accompanied by decreased serum thyroid hormone levels. Furthermore, the 50 and 500 µg/(kg·day) TBBPA groups showed a significant decrease in the serum level of serotonin, a neurotransmitter associated with anxiety behaviors. Correspondingly, the highest dose group displayed anxiety-like behaviors in the elevated plus-maze test on PND 35, but this neurobehavioral alteration disappeared on PND 56. Moreover, no changes in neurobehavioral parameters tested were found in TBBPA-treated animals at puberty and adulthood. Altogether, all observations show that TBBPA can exert thyroid disrupting effects but has little overt impact on brain development and neurobehaviors in mice, suggesting that thyroid disruption does not necessarily cause overtly adverse neurodevelopmental outcomes.