Showing papers on "Propylthiouracil published in 2020"
TL;DR: The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children.
27 citations
TL;DR: Zebrafish exposure experiments with three model compounds with distinct thyroperoxidase and deiodinase inhibition potencies provide compelling support for AOPs linking TH disruption to impaired AC inflation in fish.
Abstract: A set of adverse outcome pathways (AOPs) linking inhibition of thyroperoxidase and deiodinase to impaired swim bladder inflation in fish has recently been developed. These AOPs help to establish links between these thyroid hormone (TH) disrupting molecular events and adverse outcomes relevant to aquatic ecological risk assessment. Until now, very little data on the effects of TH disruption on inflation of the anterior chamber (AC) of the swim bladder were available. The present study used zebrafish exposure experiments with three model compounds with distinct thyroperoxidase and deiodinase inhibition potencies (methimazole, iopanoic acid, and propylthiouracil) to evaluate this linkage. Exposure to all three chemicals decreased whole body triiodothyronine (T3) concentrations, either through inhibition of thyroxine (T4) synthesis or through inhibition of Dio mediated conversion of T4 to T3. A quantitative relationship between reduced T3 and reduced AC inflation was established, a critical key event relationship linking impaired swim bladder inflation to TH disruption. Reduced inflation of the AC was directly linked to reductions in swimming distance compared to controls as well as to chemical-exposed fish whose ACs inflated. Together the data provide compelling support for AOPs linking TH disruption to impaired AC inflation in fish.
24 citations
TL;DR: In vitro:ex vivo correlations of AUR-TPO outputs indicated that less than 30% inhibition of TPO in vitro was sufficient to reduce serum T4 by 20%, a degree of regulatory significance.
17 citations
TL;DR: Metagenomics analysis of the bacterial population in fecal samples of rat models of hyperthyroidism and hypothyroidism suggested that thyroid functions may have the potential to influence the profile of gut microbiota and could be used as foundation to investigate interaction mechanism between thyroid and gut microbiome.
Abstract: Thyroid hormones are essential for the regulation of energy homeostasis and metabolic processes. However, the relationship between thyroid function and host gut microbial communities is not properly understood. To determine whether and how gut microbiota is associated with thyroid function, metagenomics analysis of the bacterial population in fecal samples of rat models of hyperthyroidism (induced by levothyroxine) and hypothyroidism (induced by propylthiouracil or thyroidectomy) was conducted through 16S rRNA gene sequencing. Our results revealed that all thyroid dysfunction models were definitely established and gut microbial composition varied according to different thyroid functional status. The relative abundance of Ruminococcus was significantly higher in the hyperthyroidism group (HE) vs both the normal and hypothyroidism groups (HO) while S24-7 was significantly higher in the HO group. The population of Prevotellaceae and Prevotella were significantly lower in the HO group vs the normal. Firmicutes and Oscillospira were significantly higher in the SHO (surgery-induced hypothyroidism) group, while Prevotellaceae and Prevotella showed lower abundance in the SHO group than the SHAM group. Present results suggest that thyroid functions may have the potential to influence the profile of gut microbiota and could be used as foundation to investigate interaction mechanism between thyroid and gut microbiome.
12 citations
TL;DR: It is verified that antithYroid drugs altered gut microbiota structure and that the gut microbiota may in turn be correlated with antithyroid drugs-induced liver injury through the intestinal endotoxemia hypothesis.
Abstract: Background: Drugs can alter the gut microbiota structure, and gut microbiota dysbiosis in turn is correlated with drug side effects through the intestinal endotoxemia hypothesis. Whether antithyroid drugs (including methimazole and propylthiouracil) cause gut microbiota dysbiosis and whether the gut microbiota is correlated with antithyroid drugs induced liver injury is unknown. Methods: Initial Graves’ disease patients were randomly divided into the methimazole group (n=20) and the propylthiouracil group (n=20) and were followed up every two weeks; 50 healthy controls were also included. The structure and function of gut microbiota were compared from the cross sectional and longitudinal levels. The correlation between the gut microbiota and clinical parameters was also determined. In addition, Sprague-Dawley rats were randomly allotted into 6 groups, including four drug groups, which received daily doses of methimazole (1.5 mg/kg/day; 2.5 mg/kg/day) or propylthiouracil (7.5 mg/kg/day; 12.5 mg/kg/day) by oral gavage, and two control groups received the vehicle. In addition to the indexes mentioned above, intestinal barrier-related indexes were also performed. Results: Results from both clinical trials and animal studies indicate that use or nonuse of drugs, different drugs, different doses and different time points all altered gut microbiota structure; and the liver function related indexes all increased which correlated with gut microbiota. In addition, lipopolysaccharide-related pathways and the lipopolysaccharide concentration in feces and serum all increased after antithyroid drugs administration. These results consistent with the destroyed intestinal barrier in animal study after antithyroid drugs administration. Conclusions: We verified that antithyroid drugs could cause gut microbiota dysbiosis and that the gut microbiota may in turn be correlated with antithyroid drugs-induced liver injury through the intestinal endotoxemia hypothesis.
12 citations
TL;DR: A large number of patients with newly diagnosed acute pancreatitis from 2000 to 2013 were identified as the case group from the Taiwan Longitudinal Health Insurance Database 2000, which contains data from 1996 to 2013, and an association between acute pancreatritis and usage of thionamides was unable to demonstrate.
Abstract: Background: Thionamides have been extensively used to treat patients with hyperthyroidism worldwide. Recent pharmacovigilance studies have revealed a safety signal between carbimazole or methimazole and pancreatitis. The associated risk remains unclear. Methods: We identified patients with newly diagnosed acute pancreatitis from 2000 to 2013 as the case group from the Taiwan Longitudinal Health Insurance Database 2000, which contains data from 1996 to 2013. Each patient with acute pancreatitis was matched for age, sex, comorbidities, and cancer with four controls through propensity score matching. A total of 52 patients without matched controls were excluded. Sensitivity analyses including the 52 excluded patients were performed using a matching ratio of 1:2. Odds ratios (ORs) along with 95% confidence intervals (CIs) for the association were estimated using multivariate logistic regression. Results: We included 9204 and 36,816 patients in the case and control groups, respectively. The proportions of patients who had used thionamides, carbimazole, methimazole, and propylthiouracil were similar in these two groups. In addition, the adjusted OR (CI) for the association of acute pancreatitis with thionamides was 1.03 (0.86-1.24), with carbimazole it was 0.90 (0.63-1.30), with methimazole it was 1.05 (0.84-1.31), and with propylthiouracil it was 1.00 (0.74-1.34). The sensitivity analysis results were unchanged. Conclusions: We were unable to demonstrate an association between acute pancreatitis and usage of thionamides.
9 citations
TL;DR: Thymoquinone may have a potential protective effect against hypothyroidism-induced renal injury acting through the attenuation of the oxidative stress and upregulation of renal catalase gene expression.
Abstract: Background. The association between hypothyroidism and renal diseases has been described in many studies. Nigella Sativa was among the recently reported natural product that has the potential to prevent renal tissue damage and fibrosis. The aim of this study was to evaluate the possible protective effect of thymoquinone on the structure of the renal cortex of hypothyroid rats and explore the mechanism behind it. Methods. An experimental model of hypothyroidism was induced in adult male Wistar rats by administration of propylthiouracil (6 mg/kg/body weight). One hypothyroid group was treated with thymoquinone at the dose of 50 mg/kg/body weight and compared to the untreated group. Thyroid function and oxidant/antioxidant status were assessed in the serum. Catalase gene expression was assessed using the real-time polymerase chain reaction. The kidney was assessed both histologically and immunohistochemically. Results. Administration of propylthiouracil resulted in a significant decrease in the serum levels of nitric oxide, reduced glutathione, and superoxide dismutase activity while the level of malondialdehyde significantly ( ) increased. Administration of thymoquinone alleviated this effect on the thyroid hormones and significantly increased the serum levels of antioxidants. Thymoquinone significantly ( ) upregulated catalase transcription by about 24-fold and could block the hypothyroidism-induced glomerular and tubular injury. Conclusion. Thymoquinone may have a potential protective effect against hypothyroidism-induced renal injury acting through the attenuation of the oxidative stress and upregulation of renal catalase gene expression.
8 citations
TL;DR: In this article, a polyherbal teabag containing 1076 μg of gallic acid and 1131 μg of rutin was found to contain potent antioxidants that may be responsible for the pro-thyroid activity.
Abstract: Hypothyroidism is the most frequent consequence of the interaction of a large variety of drugs, environmental pollutants and industrial chemicals with the thyroid gland. It is associated with diminished endocrine function which may lead to hyperlipidemia, diabetes, Alzheimer’s disease, weight gain, and other metabolic disorders. The present study evaluates the pro-thyroid activity of a bioactive fraction from a polyherbal teabag in rats with hypothyroidism induced by propylthiouracil. The teabag was formulated to stimulate synthesis and/or release of T4 and affectthe conversion of T4 to T3. Phytoconstituents of the polyherbal teabag are potent antioxidants that may be responsible for the pro-thyroid activity. The tea-extract (1000 mg) was found to contain 1076 μg of gallic acid and 1131 μg of rutin from HPTLC analysis. Rats received propylthiouracil (8 mg/kg) for the first 15days followed by the polyherbal tea-extract (500, 1000 and 1500 mg/kg), the standard drug levothyroxine (0.1 mg/kg), aerobic exercise, and a combination of tea-extract (1000 mg/kg) and aerobic exercise daily along with propylthiouracil for the next 30 days. Finally, rats received their respective treatments alone without propylthiouracil for 15 more days. Lipid profile and levels of glucose, insulin, T3, T4, TSH, cortisol, homocysteine, creatinine, uric acid, malondialdehyde, glucose-6 phosphatase, and endogenous antioxidants were determined. All treatments attenuated significantly the propylthiouracil-elevated TSH, homocysteine, creatinine, uric acid, glucose-6-phosphatase, insulin, and malondialdehyde levels, and restored favorably the propylthiouracil-altered lipid profile, T3, T4, and endogenous antioxidant levels. The polyherbal tea-extract (1000 and 1500 mg/kg) treatment and thecombination treatment of tea-extract (1000 mg/kg) with aerobic exercise displayed significant restoration of the suboptimalthyroid function. This may be due to a favorablemodulation ofthe hypothalamic-pituitary–thyroid and the hypothalamic–pituitary–adrenal axes.
7 citations
6 citations
TL;DR: The therapeutic difficulties and successful preoperative treatment with plasmapheresis in a 63-year-old patient admitted to the Endocrinology Clinic with severe hyperthyroidism, during the course of giant toxic nodular goiter and agranulocytosis are described.
Abstract: Agranulocytosis is a rare but very serious complication of thyrostatic therapy. In severe hyperthyroidism, the removal of circulating thyroid hormones by plasmapheresis may be an effective therapeutic option. This report describes the therapeutic difficulties and successful preoperative treatment with plasmapheresis in a 63-year-old patient admitted to the Endocrinology Clinic with severe hyperthyroidism, during the course of giant toxic nodular goiter and agranulocytosis, which occurred after 2 weeks of taking methimazole. During hospitalization, methimazole treatment was discontinued and therapy with steroids, a beta blocker, propylthiouracil, Lugol's solution, lithium carbonate, and antibiotics were initiated. Granulocyte colony growth stimulating factor was also used to resolve agranulocytosis. Due to the failure to achieve euthyreosis using this approach, we decided to conduct thyroid surgery, as a life-saving action, after preparation of the patient by plasmapheresis. Two plasmapheresis procedures were performed, resulting in a decrease in the concentration of free thyroid hormones. Total thyroidectomy was performed and there were no complications during surgery. We conclude that plasmapheresis may be considered as an effective alternative treatment option for the preparation of patients with hyperthyroidism for surgery, when the clinical situations prevent the use of conventional treatments for hyperthyroidism and when immediate life-saving surgery is necessary.
6 citations
TL;DR: Propylthiouracil could be used in the treatment of hyperthyroidism, thus protecting endothelial cells from damage, and was shown to cause a certain degree of endothelial injury to the abdominal aorta in rats.
Abstract: The aim of the research is to explore the relationship between hyperthyroidism, iodine, antithyroid drugs (propylthiouracil) and vascular endothelial injury. In total, 136 SD rats were randomly allocated into the control group, the hyperthyroidism group, the hyperthyroidism propylthiouracil group, the hyperthyroidism low iodine group, the high iodine group, and the endothelial injury group. Rats were raised for 60 days. Afterward, indicators concerning endothelial damage were determined, including the von Willebrand Factor (vWF), thrombomodulin (TM), nitric oxide (NO), endothelin 1 (ET-1), and P-selectin, as well as the plant hemagglutinin sample type oxidized low-density lipoprotein receptor 1 (LOX-1) from the aorta and the number of endothelial progenitor cells (EPCs) in whole blood. The hyperthyroidism group had significantly higher values for vWF, TM, NO, ET-1, and P-selectin in serum and a higher number of EPCs in whole blood compared with the control group, similar to the LOX-1 expression in abdominal aorta. The hyperthyroidism low iodine group had significantly higher values for vWF, ET-1, and P-selectin in serum and a higher number of EPCs in whole blood compared with those of the control group, as was the case for LOX-1 expression in the abdominal aorta. The hyperthyroidism propylthiouracil group had significantly higher values for FT4 in the serum compared with those in the control group. The electron microscope showed that hyperthyroidism caused a certain degree of endothelial injury to the abdominal aorta in rats. Hyperthyroidism can damage the vascular endothelium and is a high-risk factor for cardio-cerebrovascular disease. Propylthiouracil could be used in the treatment of hyperthyroidism, thus protecting endothelial cells from damage.
TL;DR: It is suggested that arecoline inhibits pineal–testis function in experimentally induced hypothyroid rats.
Abstract: Arecoline is known to cause endocrine dysfunction. In the current article role of arecoline on pineal-testis activity was investigated in hypothyroid rats induced by propylthiouracil (PTU). PTU treatment caused thyroid dysfunction ultrastructurally with a fall in T3 and T4 levels followed by a rise of thyroid stimulating hormone (TSH) level. Pineal activity was impaired by PTU treatment, as evident from degenerated synaptic ribbons and mitochondria of the pinealocytes with depletion of pineal and serum N-acetyl serotonin and melatonin levels. Leydig cell function was suppressed, evident from reduced smooth endoplasmic reticulum and depletion of testosterone level. Sex accessories function was impaired by showing scanty rough endoplasmic reticulum with depletion of fructose and sialic acid levels. Arecoline treatment that caused pineal dysfunction and testicular stimulation in control rats, suppressed both pineal and testis functions after PTU treatment. The findings suggest that arecoline inhibits pineal-testis function in experimentally induced hypothyroid rats.
TL;DR: It is demonstrated that administration of NS hydroalcoholic extract in the neonatal and juvenile growth period has an improving effect on the liver function of PTU- induced hypothyroid rats.
Abstract: Aim: Propylthiouracil (PTU) is frequently used as an antithyroid medication. It is also commonly used to induce hypothyroidism in rodents. PTU administration and hypothyroidism have been sh...
TL;DR: Evidence that TH dysregulation alters NOSs profiles is provided, which suggests that N OSs/nitric oxide (NO) is possibly involved in the regulation of female reproduction.
Abstract: Thyroid hormones (THs) are vital for normal reproductive function and dysregulation of TH impairs follicular development. Although the functions of THs on female reproduction are of great interest, the mechanisms still remain unclear. Many studies have shown that NO plays important roles in female reproduction. In the present study, we investigate the effects of TH dysregulation on nitric oxide synthase types (NOS) expression in rats. Propylthiouracil (PTU) and L-thyroxine were administered to rats to induce hypo- and hyperthyroidism, respectively. Ovarian histology was detected by immunohistochemistry (IHC) and protein or mRNA content was analyzed by Western blotting or RT-PCR, respectively. The results showed that NOS1, NOS2 and NOS3 expressions were detected in the oocyte, granulosa cell and theca cell in all follicular stages, which were up-regulated by eCG treatment. NOS1 protein content was increased in both PTU and L-thyroxine treatments. There were no significant differences in NOS2 levels between the treatment and the control group. However, NOS3 was only increased in the hyperthyroid group. These results were consistent with the IHC staining. The present study provides evidence that TH dysregulation alters NOSs profiles, which suggests that NOSs/nitric oxide (NO) is possibly involved in the regulation of female reproduction.
TL;DR: This case is the first to describe a patient who experienced concomitant agranulocytosis and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis as an adverse effect of propylthiouracil treatment for Graves’ disease.
Abstract: Summary This case is the first to describe a patient who experienced concomitant agranulocytosis and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis as an adverse effect of propylthiouracil treatment for Graves' disease. A 42-year-old female with Graves' disease presented to the emergency department (ED) with a 2-week history of fevers, night sweats, transient lower limb rash, arthralgia, myalgia and fatigue. She had been taking propylthiouracil for 18 months prior to presentation. On admission, agranulocytosis was evident with a neutrophil count of 0.36 × 109/L and immediately propylthiouracil was stopped. There was no evidence of active infection and the patient was treated with broad-spectrum antibodies and one dose of granulocyte colony-stimulation factor, resulting in a satisfactory response. On further investigation, ANCAs were positive with dual positivity for proteinase 3 and myeloperoxidase. There was no evidence of end-organ damage secondary to vasculitis, and the patient's constitutional symptoms resolved completely on discontinuation of the drug precluding the need for immunosuppressive therapy. Learning points Continued vigilance and patient education regarding the risk of antithyroid drug-induced agranulocytosis is vital throughout the course of treatment. ANCA-associated vasculitis is a rare adverse effect of antithyroid drug use. Timely discontinuation of the offending drug is vital in reducing end-organ damage and the need for immunosuppressive therapy in drug-induced ANCA-associated vasculitis. Similarities in the pathogenesis of agranulocytosis and drug-induced ANCA-associated vasculitis may offer insight into an improved understanding of vasculitis and agranulocytosis.
TL;DR: It appears, about 15 compounds, as evidenced by LC–MS/MS study, mostly phenolics are involved in this anti-thyroid effects of the test compound.
Abstract: Untreated hyperthyroidism may develop serious complications. This attempt was made to investigate the potential of Aloe vera gel in regulating experimentally induced hyperthyroidism in rats. Female Wistar rats were made hyperthyroid with L-thyroxine (L-T4) at 0.5 mg/kg/day, i.p. for 14 days and the effects of Aloe vera methanolic fraction (AVMF) (50 or 500 mg/kg/day, p.o.,) and a conventional antithyroid drug propylthiouracil (PTU) (10 mg/kg, i.p.) for 30 days were studied in those hyperthyroid rats. At the end, alterations in serum thyroid hormones and thyroid stimulating hormone (TSH); hepatic 5′mono-deiodinase-1(5′D1) activity, oxidative stress markers and antioxidants; serum inflammatory cytokines and the expression of thyrotropin receptor in thyroid gland were evaluated in all experimental animals. Hyperthyroid condition was confirmed by an increase in thyroid hormone levels and hepatic 5′D-1 activity with a decrease in TSH. However, either AVMF or PTU treatment in hyperthyroid rats decreased the levels of thyroid hormones and 5′D1 activity. AVMF administration in T4-induced rats also decreased the oxidative stress markers such as thiobarbituric acid reactive substances and lipid hydroperoxides and increased the antioxidant levels in liver tissues. Levels of liver marker enzymes, cytokines and different lipids were decreased in T4-induced AVMF treated rats. Further, a down regulation in the TSHR expression in thyroid was observed in AVMF or PTU treated groups. All these thyroid inhibiting effects were supported by an improvement in thyroid histology in hyperthyroid rats. It appears, about 15 compounds, as evidenced by LC–MS/MS study, mostly phenolics are involved in this anti-thyroid effects of the test compound.
25 Apr 2020
TL;DR: Continuous treatment with an antithyroid drug PTU induced a hypothyroid state that was associated with impaired renal and hepatic functions in rabbits, and Thyroid glands of PTU-treated rabbits showed variable sized-follicles lined by multiple layers of follicular cells, which displayed signs of hyperactivity as the average follicular cell height.
Abstract: This study was designed to investigate the effect of continuous treatment with the anti-thyroid drug, propylthiouracil (PTU), on renal and hepatic functions in rabbits as an experimental animal model. Animals were randomly divided into four different isolated groups (n = 10); Group I received normal saline. Group II, III, and IV were daily administrated with PTU in oral dosing of 50, 75, and 150 mg/kg, BWT, respectively, for three successive weeks. Serum T3 and T4 levels were measured in all groups. Increased serum creatinine and blood urea nitrogen levels (P<0.05) were also associated. Moreover, liver enzymes levels, aspartate aminotransferase, alanine aminotransferase, and total serum cholesterol levels showed a significant increase in a dose and time decedent manner. Thyroid glands of PTU-treated rabbits showed variable sized-follicles lined by multiple layers of follicular cells, which displayed signs of hyperactivity as the average follicular cell height. The diameter of its width was significantly increased compared with that in the control group. Besides, follicles were filled with a variable quantity of low-dense vacuolated colloids. Kidneys of such animals showed tubulointerstitial nephritis, glomerular atrophy, and multiple focal areas of mononuclear cell reaction. While the observed hepatic lesions were in the form of severe congestion in central vein and hepatic artery, hepatocellular necrosis, and granulocytic lymphoid cellular responses around portal areas associated with peri-portal fibrosis. Such lesions were dependent on doses of PTU. This study referred to that continuous treatment with an antithyroid drug PTU induced a hypothyroid state that was associated with impaired renal and hepatic functions in rabbits.
TL;DR: Patients with longstanding untreated hyperthyroidism and consequentially developed thyrotoxicosis-induced cardiomyopathy may be dependent on the induced hyperadrenergic state to compensate for low-output cardiac failure, therefore it is important to exercise caution when initiating beta-adrenaline blockade.
TL;DR: In a real life situation there is delay in the diagnosis of hyperthyroidism during pregnancy but even without propylthiuracil, an “Adequate” control can be reached in up to 20.53% of cases based on a methimazole monotherapy.
Abstract: Hyperthyroidism is one of the main endocrinopathies during pregnancy. The aim of this project was to identify the degree of control of hyperthyroid pregnant women based on the recommendations of the American Thyroid Association (ATA) in a real situation without the availability of propylthiouracil. This was a descriptive, retrospective and longitudinal study, including medical files of pregnant women with hyperthyroidism between 18 and 35 years. They were classified as having "Adequate" control if their thyroid profiles were within the recommendations of the ATA and had no adrenergic symptoms; and were categorized as having "Inadequate" control if they were not stabilized with monotherapy, or if they required high doses of antithyroid drugs or beta-blockers or showed serious complications including the need of an Intensive Care Unit (ICU) for mothers or neonates. The Chi square test was performed between treatment groups during the third trimester and the complications of pregnant women or neonates. A total of 173 hyperthyroid pregnant women were studied with an average age of 21 ± 4.7 years. Of the 33 patients with hyperthyroidism who received monotherapy with methimazole until the end of pregnancy, 23 (69.69%) were classified as having "Adequate" control. In a real life situation there is delay in the diagnosis of hyperthyroidism during pregnancy but even without propylthiuracil, an “Adequate” control can be reached in up to 20.53% of cases based on a methimazole monotherapy.
TL;DR: It is indicated that ALA alone and together with T4 may be useful in reducing oxidative stress in thyroid dysfunctions and was found to ameliorate the changes as a result of oxidative stress arising from T4 replacement therapy.
TL;DR: The case of a 38-year-old female who presented to the emergency department for an impending thyroid storm and was subsequently admitted to the intensive care unit with elevated liver enzymes is delineated.
Abstract: Antithyroid drug-induced severe liver injury is an uncommon but serious complication. We hereby delineate the case of a 38-year-old female who presented to the emergency department for an impending thyroid storm. After initiation of a single dose of propylthiouracil, her liver enzymes went into the thousands. She was subsequently admitted to the intensive care unit. Propylthiouracil was discontinued and corticosteroids were initiated with the resolution of her elevated liver enzymes. On follow-up, her liver function was at its baseline and thyroid hormone levels were under control. We hope this report will encourage clinicians to cast a broad differential diagnosis in patients presenting with liver injury in the acute setting. Furthermore, it is imperative to raise awareness regarding the ever-increasing list of pharmacologic agents that can perpetuate drug-induced hepatotoxicity.
12 Mar 2020
TL;DR: The objective of this paper is to review the research in detection and management of Graves’ disease (thyrotoxicosis) during and after pregnancy, and discuss thyroid receptor antibodies, etiology of Grave’s disease, pregnancy related complications, infants’ thy rotoxicosis management, as well as post-partum management, guidelines and counseling offered to pregnant women.
Abstract: Thyroid dysfunction alters the physiological events of pregnancy that may have serious outcomes if left untreated. Hyperthyroidism (a thyroid disease) is related to complications during pregnancy. A challenging task for the physician is to correctly diagnose and properly manage hyperthyroidism in pregnant women. Hyperthyroidism is an autoimmune disease caused by excessive production of thyroxin hormone. The objective of this paper is to review the research in detection and management of Graves’ disease (thyrotoxicosis) during and after pregnancy. This paper discusses thyroid receptor antibodies, etiology of Grave’s disease (thyrotoxicosis), pregnancy related complications, infants’ thyrotoxicosis management, as well as post-partum management, guidelines and counseling offered to pregnant women. Literature search was conducted using the keyword ‘hyperthyroidism’ in conjunction with pregnancy, anti-thyroid drugs and birth defects in Pubmed, Google Scholar and Medline. Maintaining thyroid gland may reduce the complications of pregnancy. At the beginning of pregnancy, low doses of anti-thyroid drugs are usually recommended to women by endocrinologists. However, the use of these drugs is completely stopped after 4 – 8 weeks of gestation. Propylthiouracil is the preferred anti-thyroid drug used in the first trimester in case of preconception to decrease the risk of teratogenicity. Carbimazole may be used in the first three months. Early diagnosis and maintaining normal hormone concentration by reducing the level of thyroid receptor antibodies as well as anti-thyroid drugs is essential in order to prevent maternal and fetal complications. Counseling and guidelines provided by endocrinologists constitute the key to a healthy and successful pregnancy.
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TL;DR: The results of this study confirmed the protective role of Spirulina versus PTU associated hypothyroidism, hyperlipidemia, hepatic, and nephrotoxicity and elucidate its defensive effect against various PTU toxicities.
Abstract: Background: Propylthiouracil (PTU) is a drug widely used in the management of hyperthyroidism. The drug was observed to cause hepatitis and fulminant liver failure.Spirulinais documented to exhibit several therapeutic effectsincluding hepatoprotective, nephroprotective, and antioxidant activities.
Objective: This study aimed to assess the nutritional value of Spirulina,and to examine its ameliorative effects against PTU-induced hypothyroidism associated with hyperlipidemia, liver, and kidney toxicity in rats.
Materials and Methods: This experiment was carried out on 50 rats (5 groups, n = 10). Hypothyroidism was induced in 40 ratsvia injecting 10 mg/kg/day PTUfor 6 weeks.
Results: The results of this study showed that Spirulina contains 57.30 % of its dry weight proteins while it contains only 8.2% of its dry weight fats. It contains several minerals and vitamins (E and β-carotene).Spirulina increases the final body weight, food intake, and body weight gain % values compared to PTU rats. The Alga increased FT3 and FT4 levels, while decrease TSH level compared to PTU rats. Spirulina significantly decreased serum liver enzymes (ALT, AST, and ALP) and serum kidney function markers (creatinine and urea) compared to PTU rats. Besides, it reduced serum lipid profile markers (TC, TG, and LDL-C) and increased HDL-C. The Alga reduced the lipid peroxidation product and increased glutathione peroxidase concentrations.
Conclusion: The results of this study confirmed the protective role of Spirulina versus PTU associated hypothyroidism, hyperlipidemia, hepatic, and nephrotoxicity. The antioxidant impact of Spirulina may elucidate its defensive effect against various PTU toxicities.
06 Jul 2020
TL;DR: History taking, physical examination, thyroid function test, and maintaining euthyroidism during pregnancy is a key to reduce the risk of maternal and fetal complication.
Abstract: Background : Hyperthyroid is a hypermetabolic condition caused by abnormal thyroid gland function resulting in overproduction and overexpression of thyroid hormone. The prevalence of hyperthyroid during pregnancy is 0.1-0.4%, where 85% of case are presented as grave’s disease. Objective : To report the treatment of uncontrolled hyperthyroid during pregnancy. Method : Case Report Case : Ms. S, Female, 33 years old, presenting with brethlessness since 5 days before admission. Breathlessness persist and aggravated by lying down position. The patient has history of hyperthyroid since 1 years before admission. The blood pressure was 120/80 mmHg, respiration rate 28 times/min, and body temperature 36,7oC. Uterus fundal height 26 cm, cephalic presentation, fetal heart rate 130 times/min, single fetus intrauterine and alive. Laboratoric test for leukocyte: 21,300/ul, T4 level 22.8 mg/dl dan T3 level 2.9 mg/dl. The patient diagnosed with G3P2A0 31-week gestational age single alive fetus intrauterine with uncontrolled hyperthyroid and bilateral pleural effusion. Treatment consist of propylthiouracil as the drug of choice for anti-thyroidal drug, nifedipine for gestational hypertension and furosemide to treat the pleural effusion. Conclusion : History taking, physical examination, thyroid function test, and maintaining euthyroidism during pregnancy is a key to reduce the risk of maternal and fetal complication. Keywords: hyperthyroid, pregnancy , IUGR
TL;DR: According to the results of this study, hypothyroidism and hyperthyroidism are associated with a disturbance in the oxidation state of the body, and the use of antioxidants can help improve these diseases, especially in hyperthyoidism, due to enhanced metabolism and production of more free radicals.
Abstract: Background: Thyroid functional disorders are relatively common in the general population. Different factors play a role in the development of thyroid disorders. These factors can be associated with the deterioration of the oxidation state of the body and the induction of oxidative stress. Thyroid hormones play an important role in the oxidation state. Objectives: Regarding the role of oxidative stress in different pathologies and the development of various complications, including thyroid disorders, we aimed to compare the biochemical and oxidative stress parameters in hypo and hyperthyroid rat models. Methods: Twenty-one male Wistar rats were assigned into three groups of control, hypothyroid, and hyperthyroid. Hypothyroidism and hyperthyroidism were inducted with PTU (propylthiouracil) and LTX (levothyroxine), respectively. After five weeks of induction, serum biochemical factors and oxidative stress parameters, such as TAC (total antioxidant capacity), MDA (Malondialdehyde), and the thiol group, were measured in these groups. Results: The means of TAC, MDA and UA (uric acid) in the hyperthyroid group were significantly higher than those in the hypothyroid group (P < 0.01, P < 0.01, P < 0.05) but the mean of thiol in the hypothyroid group was significantly higher than that of the hyperthyroid group (P < 0.01). Also, the mean of TAC level in the hypothyroid group was significantly lower than the control group (P < 0.05) and the mean of thiol group in the hypothyroid group was significantly higher than the control group (P < 0.05), but there was no other significant difference between the groups compared to the control group. Among the biochemical parameters, the mean LDH (lactate dehydrogenase) in the hyperthyroid group also showed a significant difference in comparison to the hypothyroid group (P < 0.05), but there was no significant difference between the groups in the mean of the other biochemical parameters. Conclusions: According to the results of this study, hypothyroidism and hyperthyroidism are associated with a disturbance in the oxidation state of the body, and the use of antioxidants can help improve these diseases, especially in hyperthyroidism, due to enhanced metabolism and production of more free radicals.
TL;DR: This dataset describes serum T4 level, body weight gain and day of eye opening in offspring mice exposed to the TH synthesis inhibitor propylthiouracil (PTU) from gestational day (GD) 15 to postnatal day (PND) 25.
TL;DR: A distinct subcellular distribution of SST and SSTR subtypes in the thyroid is revealed and provides a new insight for the role of S ST and S STR sub types in hypothyroidism in addition to its well-established role in negative regulation of hormonal secretion.
Abstract: Propylthiouracil (PTU)-induced hypothyroidism is a well-established model for assessing hormonal and morphological changes in thyroid as well as other central and peripheral tissues. Somatostatin (SST) is known to regulate hormonal secretion and synthesis in endocrine tissues; however, nothing is currently known about the distribution of SST and its receptor in hypothyroidism. In the present study, the comparative immunohistochemical distribution of SST and somatostatin receptors (SSTRs) were analyzed in PTU-induced hypothyroid rats. Rats were treated with PTU for 15 days followed by a co-administration of levothyroxine (LVT) for 15 days. After PTU and LVT treatments (day 30), rats were further administered LVT alone for 15 more days (day 45). The subcellular distribution of SST and SSTR subtypes was determined by peroxidase immunohistochemistry in the thyroid gland collected from control and treated rats. SST and SSTR subtypes were found to be moderately expressed in control thyroid tissues. SST and SSTR subtypes like immunoreactivity increased significantly in follicular and parafollicular epithelial cells in the thyroid of PTU-treated rats. The PTU-induced changes in the expression of SST and SSTR subtypes were suppressed by the administration of the LVT. In addition to thyroid tissues, SST and SSTRs expression was also changed in non-follicular tissues including blood vessels, smooth muscle cells, and connective tissue following treatments. The present study revealed a distinct subcellular distribution of SST and SSTR subtypes in the thyroid and provides a new insight for the role of SST and SSTR subtypes in hypothyroidism in addition to its well-established role in negative regulation of hormonal secretion.
TL;DR: In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy, and in patients with newly diagnosed Graves’ hyperthyroidism, continued long-term low-dose MMI can be considered.
Abstract: Graves’ disease (GD) is a systemic autoimmune disorder characterized by the infiltration of thyroid antigen-specific T-cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues. Stimulatory autoantibodies (Ab) in GD activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy. Graves’ hyperthyroidism is treated by decreasing thyroid hormone synthesis with the use of ATD, or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly diagnosed Graves’ hyperthyroidism are usually medically treated for 12–18 months with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36-month course of MMI is recommended. Patients with persistently high TSH-R-Ab at 12–18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered. Thyroidectomy should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in Graves’ patients with active/severe orbitopathy, and steroid prophylaxis is warranted in Graves’ patients with mild/active orbitopathy receiving RAI.
01 Jan 2020
TL;DR: A 49-year-old female with Graves’ disease admitted in the authors' emergency room for a 6-week history of fever, weight loss, jaundice, exertional dyspnea, palpitations, and diarrhea is reported, and therapeutic plasma exchange (TPE) is effective in decreasing circulating thyroid hormone levels.
Abstract: Thyroid storm is a life-threatening condition with mortality rates reaching up to 20 to 30%. First-line treatment includes inhibition of thyroid hormone synthesis, prevention of release of preformed hormones, blocking of peripheral FT4 to FT3 conversion, enhancing hormone clearance, and definitive radioactive iodine ablation. However, in the presence of life-threatening adverse effects (e.g., agranulocytosis) and contraindications (e.g., fulminant hepatic failure), therapeutic plasma exchange (TPE) can be used to rapidly remove circulating thyroid hormones, antibodies, and cytokines in plasma; this is recommended by the American Society of Apheresis (ASFA) and the American Thyroid Association (ATA) as second-line treatment for thyroid storm. Here, we report a 49-year-old female with Graves’ disease admitted in our emergency room for a 6-week history of fever, weight loss, jaundice, exertional dyspnea, palpitations, and diarrhea. Her initial thyroid hormone levels were: FT4 64.35 (NV 9.01–19.05 pmol/L), FT3 23.91 (NV: 2.89–4.88 pmol/L), and TSH 0.00000 (NV: 0.35-4.94 mIU/L) and we managed her as a case of thyroid storm (Burch-Wartofsky score 70) by initiating high dose propylthiouracil. However, her sensorium deteriorated and serum bilirubin continued to rise from 307.2 on admission to 561.6 umol/L on the 5th hospital day (NV: 3 - 22 umol/L). TPE was performed after consultation with the Division of Hematology. Over the treatment course, her thyroid hormones normalized: FT4 13.18 pmol/L, FT3 2.30 pmol/L. However, despite TPE, her symptoms worsened and she became comatose, had hypotension despite vasopressors and developed new-onset atrial fibrillation. She expired on her 7th hospital day from multiorgan failure. TPE is effective in decreasing circulating thyroid hormone levels. However, it had no effect on clinically important outcomes as our patient still deteriorated and eventually succumbed. We still wrote and submitted this case report since if only successful cases were reported, the true effectiveness rate of TPE could not be determined.
TL;DR: Two cases of thyroid hormone alterations revealing clinical emergencies that require early diagnosis and prompt treatment are presented and an increased antithyroperoxidase antibody is revealed.
Abstract: We present two cases of thyroid hormone alterations revealing clinical emergencies that require early diagnosis and prompt treatment. The first patient, a 56-year-old woman, presented in the emergency room with psychomotor agitation, disorientation and headache. She was very agitated, incapable of standing still, looked very thin, feverish, tachycardic and presented no alteration at neurological examination with negative meningeal signs. Analyses revealed a severe hyperthyroidism. She initiated propylthiouracil 100 mg 8/8 h. After six months, thyroid function was normal. The second patient, a 54-year-old woman, was transferred from the Psychiatry Department due to memory and behavior changes for the past two weeks. She presented visual and auditive hallucinations and inadequate daily behavior. Analyses revealed a severe hypothyroidism. She was medicated with levothyroxine 100 ug/day. At the third month, she presented normalized thyroid function, normal thyroid ultrasound and an increased antithyroperoxidase antibody.