Showing papers on "Propylthiouracil published in 2021"

Cocrystals of Propylthiouracil and Nutraceuticals toward Sustained-Release: Design, Structure Analysis, and Solid-State Characterization

Abstract: Propylthiouracil (PTU) is a clinically preferred drug to treat hyperthyroidism effectively. The sustained release of PTU is necessary because of the shortcomings of rapid release and hepatotoxicity...

Testing, Monitoring, and Treatment of Thyroid Dysfunction in Pregnancy

Abstract: Both hyperthyroidism and hypothyroidism can have adverse effects in pregnancy. The most common causes of thyrotoxicosis in pregnancy are gestational transient thyrotoxicosis and Graves' disease. It is important to distinguish between these entities as treatment options differ. Women of reproductive age who are diagnosed with Graves' disease should be counseled regarding the impact of treatment options on a potential pregnancy. Although the absolute risk is small, antithyroid medications can have teratogenic effects. Propylthiouracil appears to have less severe teratogenicity compared to methimazole and is therefore favored during the first trimester if a medication is needed. Women should be advised to delay pregnancy for at least 6 months following radioactive iodine to minimize potential adverse effects from radiation and ensure normal thyroid hormone levels prior to conception. As thyroid hormone is critical for normal fetal development, hypothyroidism is associated with adverse obstetric and child neurodevelopmental outcomes. Women with overt hypothyroidism should be treated with levothyroxine (LT4) to a thyrotropin (thyroid-stimulating hormone; TSH) goal of <2.5 mIU/L. There is mounting evidence for associations of maternal hypothyroxinemia and subclinical hypothyroidism with pregnancy loss, preterm labor, and lower scores on child cognitive assessment. Although there is minimal risk of LT4 treatment to keep TSH within the pregnancy-specific reference range, treatment of mild maternal thyroid hypofunction remains controversial, given the lack of clinical trials showing improved outcomes with LT4 treatment.

Protective effect of PPARγ agonist pioglitazone, on testicular tissue and sperm parameters in hypothyroid rats

Abstract: Both thyroid hormones and PPARγ agonists are suggested to have some effects on the reproductive system. Here, the effects of pioglitazone on testicular tissue damages in propylthiouracil (PTU)-indu...

Dose-Dependent Influence of Antithyroid Drugs on the Difference in Free Thyroxine Levels between Mothers with Graves' Hyperthyroidism and Their Neonates.

Abstract: Background Several guidelines have recommended that the use of the lowest effective dose of antithyroid drugs (ATDs) that maintains maternal serum free thyroxine (FT4) levels at or moderately above the upper limit of the reference range is appropriate for fetal euthyroid status. However, little is known about whether ATD dosage affects the difference in serum FT4 levels between the mother and neonate. We conducted a retrospective study at a tertiary hospital in Japan to investigate the dose-dependent influence of ATDs on both maternal and fetal thyroid hormone status. Materials and methods We retrospectively examined 62 pregnant women who delivered between 2007 and 2016 and were treated for Graves' hyperthyroidism with ATD at any stage during pregnancy. We selected individuals whose data on maternal FT4 level within 4 weeks of their deliveries and cord FT4 level of their infants at the time of delivery were available. Those with multiple pregnancies, iodine or glucocorticoid treatment, and fetal goiter detected by ultrasonography were excluded. Results After the exclusion criteria were applied, we recruited 40 individuals. The cord FT4 levels were significantly lower than the maternal FT4 levels in patients treated with high-dosage ATDs (methimazole >5 mg daily or propylthiouracil >100 mg daily). However, there were no significant differences between maternal and cord FT4 levels in patients treated with low-dosage ATDs (methimazole ≤5 mg daily or propylthiouracil ≤100 mg daily). We selected 35 individuals whose data on maternal thyrotropin receptor-binding inhibitory immunoglobulin (TBII) level were available. Multiple linear regression analysis adjusted for ATD dosage, maternal TBII level, and gestational period found that ATD dosage was a significant predictor of the difference in serum FT4 levels between the mother and neonate. In terms of maternal complications, multiple logistic regression analysis identified maternal free triiodothyronine (FT3) level as a significant predictor of the incidence of preterm delivery. Conclusions We found a dose-dependent influence of ATDs on the difference in serum FT4 levels between mothers with Graves' hyperthyroidism and their neonates. Further studies to evaluate the optimal target FT4 and FT3 levels for the mother and neonate during pregnancy may improve the outcome of pregnant women with Graves' hyperthyroidism.

Antithyroid Drug Treatment in Graves’ Disease

Abstract: Graves' disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through inhibition of thyroid hormone synthesis or destruction of the thyroid gland. Recurrence after antithyroid drug (ATD) treatment is common. Recent studies have shown that the longer is the duration of use of ATD, the higher is the remission rate. Considering the relationship between clinical outcomes and iodine intake, recurrence of Graves' disease is more common in iodine-deficient areas than in iodine-sufficient areas. Iodine restriction in an iodine-excessive area does not improve the effectiveness of ATD or increase remission rates. Recently, Danish and Korean nationwide studies noted significantly higher prevalence of birth defects in newborns exposed to ATD during the first trimester compared to that of those who did not have such exposure. The prevalence of birth defects was lowest when propylthiouracil (PTU) was used and decreased by only 0.15% when methimazole was changed to PTU in the first trimester. Therefore, it is best not to use ATD in the first trimester or to change to PTU before pregnancy.

Modulating Thyroid Hormone Levels in Adult Mice: Impact on Behavior and Compensatory Brain Changes.

Abstract: Thyroid hormone (TH) perturbation is a common medical problem. Because of substantial public health impact, prior researchers have studied hyper- and hypothyroidism in animal models. Although most prior research focused on in utero and/or developmental effects, changes in circulating TH levels are commonly seen in elderly individuals: approximately 20% of persons older than 80 years have clinically impactful hypothyroidism and up to 5% have clinical hyperthyroidism, with women being more often affected than men. TH disease model methodology in mice have varied but usually focus on a single sex, and the impact(s) of TH perturbation on the adult brain are not well understood. We administered thyroxine to middle-aged (13 to 14 months) male and female mice to model hyperthyroidism and TH-lowering drugs propylthiouracil (PTU) and methimazole, to induce hypothyroidism. These pharmacological agents are used commonly in adult humans. Circulating TH-level changes were observed when thyroxine was dosed at 20 µg/mL in drinking water for two weeks. By contrast, PTU and methimazole did not elicit a consistent reproducible effect until two months of treatment. No substantial changes in TH levels were detected in brain tissues of treated animals; however, pronounced changes in gene expression, specifically for TH-processing transcripts, were observed following the treatment with thyroxine. Our study indicated a robust compensatory mechanism by which the brain tissue/cells minimize the TH fluctuation in CNS by altering gene expression. Neurobehavioral changes were related to the TH perturbation and suggested potential associations between cognitive status and hyper- and hypothyroidism.

Hyperthyroidism in Pregnancy: The Delicate Balance between Too Much or Too Little Antithyroid Drug.

Abstract: Overt hyperthyroidism (HT) during pregnancy is associated with a risk of maternal–fetal complications. Antithyroid drugs (ATD) have a potential risk for teratogenic effects and fetal–neonatal hypothyroidism. This study evaluated ATD treatment and thyroid function control during pregnancy, and pregnancy outcome in women with HT. Patients and methods: A retrospective analysis of 36 single fetus pregnancies in 29 consecutive women (median age 30.3 ± 4.7 years) with HT diagnosed before or during pregnancy; a control group of 39 healthy euthyroid pregnant women was used. Results: Twenty-six women had Graves’ disease (GD, 33 pregnancies), 1 had a hyperfunctioning autonomous nodule, and 2 had gestational transient thyrotoxicosis (GTT). Methimazole (MMI) was administered in 22 pregnancies (78.5%), Propylthiouracil (PTU) in 2 (7.1%), switch from MMI to PTU in 4 (14.2%), no treatment in 8 pregnancies (3 with subclinical HT, 5 euthyroid with previous GD remission before conception). In the 8 pregnancies of GD patients diagnosed during gestation or shortly before (<6 weeks), i.e., with fetal exposure to uncontrolled HT, there was 1 spontaneous abortion at 5 weeks (3.4% of all ATD-treated pregnancies), and 1 premature delivery at 32 weeks with neonatal death in 24 h (3.4%); 1 child had neonatal hyperthyroidism (3.3% of live children in GD women) and a small atrial sept defect (4% of live children in ATD treated women). In women treated more than 6 months until conception (20 pregnancies): (a) median ATD doses were lower than those in women diagnosed shortly before or during pregnancy; (b) ATD was withdrawn in 40% of pregnancies in trimester (T)1, all on MMI < 10 mg/day (relapse in 14.2%), and in up to 55% in T3; (c) TSH level was below normal in 37%, 35% and 22% of pregnancies in T1, T2 and T3 respectively; FT4 was increased in 5.8% (T1) and subnormal in 11.75% in T2 and T3; (d) no fetal birth defects were recorded; one fetal death due to a true umbilical cord knot was registered. Mean birth weight was similar in both ATD-treated and control groups. Hyperthyroidism relapsed postpartum in 83% of GD patients (at median 3 ± 2.6 months). Conclusion: In hyperthyroid women with long-term ATD treatment before conception, drugs could be withdrawn in T1 in 40% of them, the thyroid function control was better, and pregnancy and fetal complications were rarer, compared to women diagnosed during pregnancy. Frequent serum TSH and FT4 monitoring is needed to maintain optimal thyroid function during pregnancy.

Hyperthyroidism management during pregnancy and lactation (Review).

Abstract: Thyroid dysfunction is a significant public health issue, affecting 5-10 more women compared to men. The estimated incidence is up to 12% and only for women the treatment rises up to 4.3 billion dollars annually. Thyroid pathology can have a major impact on female fertility and it can only be detected when preconception tests are performed. Untreated or poorly treated hyperthyroidism in a mother can affect the fetal development and pregnancy outcome. Between 0.1 and 0.4% of the pregnancies are affected by clinical hyperthyroidism. Thyroid dysfunction is associated with higher rates of pregnancy loss. Hyperthyroidism can complicate fetal health problems intrauterinely and in the neonatal period. The TSH receptor is stimulated by TSH and HCG which has a similar structure. This can lead to gestational thyrotoxicosis. Hyperthyroidism can be treated with propylthiouracil or methimazole and in selected cases, surgical treatment or radioactive iodine can be chosen. In pregnancy, the most used treatment is represented by propylthiouracil which can be used from the first trimester. The aim of this review is to assess the current data regarding the impact of thyroid dysfunction on pregnancy and to synthesize the treatment options during pregnancy and lactation.

Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism.

Abstract: The clinical effectiveness of supportive therapy with thyroid hormones in drug-resistant depression is well-known; however, the mechanisms of action of these hormones in the adult brain have not been fully elucidated to date. We determined the effects of venlafaxine and/or L-thyroxine on metabolic parameters and markers involved in the regulation of synaptic plasticity and cell damage in an animal model of coexisting depression and hypothyroidism, namely, Wistar Kyoto rats treated with propylthiouracil. In this model, in relation to the depression model itself, the glycolysis process in the brain was weakened, and a reduction in pyruvate dehydrogenase in the frontal cortex was normalized only by the combined treatment with L-thyroxine and venlafaxine, whereas changes in pyruvate and lactate levels were affected by all applied therapies. None of the drugs improved the decrease in the expression of mitochondrial respiratory chain enzymes. No intensification of glucocorticoid action was shown, while an unfavorable change caused by the lack of thyroid hormones was an increase in the caspase-1 level, which was not reversed by venlafaxine alone. The results indicated that the combined administration of drugs was more effective in normalizing glycolysis and the transition to the Krebs cycle than the use of venlafaxine or L-thyroxine alone.

Syringic acid, a novel thyroid hormone receptor-β agonist, ameliorates propylthiouracil-induced thyroid toxicity in rats.

Abstract: The aim of this study was to evaluate the potential of syringic acid (SA) against propylthiouracil (PTU)-induced hypothyroidism in rats. SA at a prestandardized dose, 50 mg/kg/day, was orally administered to PTU-induced hypothyroid rats for 30 days, and alterations in the levels of serum triiodothyronine (T3 ), thyroxine (T4 ), thyrotropin (TSH), alanine transaminase (ALT), and aspartate transaminase (AST); tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6); total cholesterol (CHOL) and triglycerides (TG); hepatic lipid peroxidation (LPO) and antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione content), as well as histological changes in liver and thyroid were examined. The molecular interactions of the ligand, SA, with thyroid-related protein targets, such as human thyroid hormone receptor β (hTRβ), and thyroid peroxidase (TPO) protein, were studied using molecular docking. Whereas in hypothyroid animals, T4 , T3 , and antioxidants were decreased, there was an increase in TSH, TNF-α, IL-6, ALT, AST, and hepatic LPO; administration of SA in PTU-induced animals reversed all these indices to near normal levels. SA also improved the histological features of liver and thyroid gland. Our study clearly demonstrates SA as a novel thyroid agonist for augmenting the thyroid functions in rats. Molecular docking analysis reveals that SA possesses good binding affinity toward both the targets, hTRβ and TPO. Through this approach, for the first time we provide the evidence for SA as a novel thyroid agonist and suggest a receptor-mediated mechanism for its thyroid stimulatory potential.

The effects of hypothyroidism and hyperthyroidism on placental Hofbauer cells of pregnant rats.

Abstract: We investigated the effects of maternal thyroid disorders on Hofbauer cells of both the placenta and the fetus in pregnant rats. We divided 21 rats into three groups: control group, induced hypothyroidism (hypo) group and induced hyperthyroidism (hyper) group. Hypothyroidism was induced using propylthiouracil and hyperthyroidism was induced using L-thyroxine. We measured maternal weight, maternal free thyroxine, fetal weight, fetal viability and placental morphology. At the end of the experiment, fetuses of the hypo and hyper groups were less developed than those of the control group. In the hypo and hyper groups, the thickness of the labyrinth zone was decreased, but thickness of the basal zone and decidua basalis was increased. The number of Hofbauer cells was increased in both the hypo and hyper groups. Vascular endothelial growth factor expression was increased in both the hypo and hyper groups compared to controls. Our findings indicate that maternal thyroid disorders exert a negative effect on fetal growth and placental development.

The positive effect of black seed (Nigella sativa L.) essential oil on thyroid hormones in rats with hypothyroidism and hyperthyroidism.

Abstract: In our study, the effect of essential oil obtained from Nigella sativa L. (NSE) on thyroid hormones and antioxidant balance in hypothyroidism (HT) and hyperthyroidism (HP) models induced by propylthiouracil(PTU) and L-thyroxine(LT4 ), respectively, in rats were investigated for 4 weeks. NSE was administered by gastric gavage at a dose of 200 mg/kg body weight. In this study, 48 male Wistar albino rats with an average weight of 180-290 g and age 5-6 months were divided into eight groups, as follows: groups with HT, (1) control, (2) HT, (3) NSE, and (4) HT + NSE; groups with HP, (1) control, (2) HP, (3), and NSE (4) HP + NSE. As a result, we found that NSE administration increased total triiodothyronine (TT3 ) and decreased nitric oxide in HT + NSE. Besides, it decreased TT3 in HP + NSE and increased total antioxidant capacity. Our findings suggest that NSE may have beneficial effects on thyroid gland abnormalities owing to its antioxidant properties. PRACTICAL APPLICATIONS: Essential oils derived from Nigella sativa L. seed contain many bioactive substances such as thymoquinone and cymene. This paper emphasizes the effect of NSE on thyroid hormone abnormalities and negative oxidative state that occurs in HT and HP models. The present study provides evidence of a positive effect of NSE particularly on TT3 levels in the HT and HP models. It can therefore be assumed that NSE could be used as a supportive natural alternative source to improve thyroid hormone levels and relieve increased oxidative stress.

Pregnancy-induced increased heart rate is independent of thyroid hormones.

Abstract: Background The heart rate increases by 10–20 beats per minute (bpm) throughout pregnancy in women, reaching maximum heart rate in the third trimester. During pregnancy, important changes in thyroid hormones also occur, with increases of up to 50% in the levels of triiodothyronine (T3), the biological active thyroid hormone. In addition, T3 has been shown to regulate cardiac electrophysiology. Objective Thus, in the present study the potential contribution of T3 in pregnancy-induced increased heart rate was explored. Methods We compared the heart rate between nonpregnant and pregnant mice under control conditions and after altering thyroid hormone levels with T3 and propylthiouracil (PTU, an antithyroid drug) treatments. Results Consistent with the clinical data, we found a 58% rise in T3 levels during pregnancy in mice. Although pregnant mice had a higher baseline heart rate (607 ± 8 bpm, P = .004) and higher T3 levels (1.9 ± 0.4 nM, P = .0005) than nonpregnant mice (heart rate: 546 ± 16 bpm; T3 levels: 1.2 ± 0.1 nM), their heart rate responded similarly to T3 treatment as nonpregnant mice (nonpregnant: Δ130 ± 22 bpm; pregnant: Δ126 ± 17 bpm, P = .858). Additionally, the heart rate remained significantly elevated (607 ± 11 bpm, P = .038) and comparable to untreated pregnant mice, after the use of the antithyroid drug PTU, although T3 levels (1.3 ± 0.2 nM, P = .559) returned to nonpregnant values. Conclusion Based on these results, it is unlikely that T3 contributes significantly to the pregnancy-induced increased heart rate.

Hematological disorders of propylthiouracil in thyroid patients at tertiary care hospital of hyderabad

Abstract: Objective: To find out the frequency of anemia, agranulocytosis and thrombocytopenia in hyperthyroid patients after the use of propylthiouracil. Study Design: Cross sectional study. Place and Duration of Study: Out Door Patients Department and Pathology Laboratory in Liaquat University Medical & Health Sciences, Hospital Hyderabad/Jamshoro, from May 2016 to Apr 2017. Methodology: Two hundred cases, comprising of adult patients were categorized into five groups, age group 15-30 years 79 (39.5%) patients presenting the highest out of total, age group 31-45 years 68 (34%) patients, age group 46-60 years 36 (18%), age group 61-75 years 14 (7%) patients, age group >75 years 3 (1.5) patients. Complete blood count was analyzed on Sysmex Kx21 and thyroid profiles were analyzed on Elecysis 2010 from the Pathology Department. SPSS version 22 was used for data analysis. Result: Out of total patients, 32 (16%) were males and 168 (84%) were females with mean age of 37.44 ± 14.82 years. Majority of patients 68 (34%) were anemic, while 4 (2%) had agranulocytosis and 11 (5.5%) had thrombocytopenia. Headache was reported in 111 (55.5%), exophthalmos in 106 (53%), sore throat in 172 (86%), fever in 136 (68%) and weight loss in 95 (47.5%) patients. Conclusion: Propylthiouracil causes defective hematopoiesis in hyperthyroid patients because propylthiouracil has adverse suppressive effects on bone marrow.

Thymoquinone Preserves Pancreatic Islets Structure Through Upregulation of Pancreatic β-Catenin in Hypothyroid Rats.

Abstract: Background Altered status of thyroid hormones, which have a key role in regulating metabolism, was reported to affect glucose homeostasis and insulin secretion. Objective This study was designed to assess the impact of propylthiouracil (PTU)-induced hypothyroidism on the pancreatic islet cells and the efficacy of thymoquinone (TQ) in alleviating this impact and explore the mechanism behind it alleviating oxidative stress and affecting β-catenin expression. Materials and Methods PTU (6 mg/kg/body weight) was used to induce hypothyroidism in Wistar rats. Four groups of rats (n=6 each) were utilized in this study. Untreated hypothyroid and TQ-treated hypothyroid groups (50 mg/kg/body weight for 4 weeks) were included. Thyroid functions, antioxidant profile and pancreatic β-catenin and IL-10 mRNA were measured. Histopathological and immunohistochemical assessment of the pancreas was performed. Results PTU administration induced a hypothyroid status that was associated with a marked disturbed oxidant/antioxidant status and a significant hyperglycemia (p<0:001), hypoinsulinemia (p=0.01) and decreased HOMA-β-cell (p<0.001). Islet cells of hypothyroid pancreas showed many degenerative changes with increased apoptosis, reduced insulin β-catenin immunoexpression. Administration of TQ alleviated these effects on the thyroid function, antioxidants, structure of pancreatic islet cells. Up-regulation of β-catenin, IL-10 and CAT gene expression in pancreatic islets after treatment with TQ supported its antioxidant and preserving β-cell function and viability mechanistic action. Conclusion TQ alleviated PTU-induced hypothyroidism changes in insulin homeostasis and pancreatic β cells mostly through its antioxidant effect as well as up-regulation of pancreatic β-catenin expression.

Rash and cholestatic liver injury caused by methimazole in a woman with Turner syndrome and Graves's disease: a case report and literature review.

Abstract: BACKGROUND Rash and cholestatic liver injury caused by methimazole (MMI) in patients with Turner syndrome (TS) and Graves's disease (GD) are rarely reported, and there is a paucity of reports on the management of this condition. It is not clear whether propylthiouracil (PTU) can be used as a safe alternative in this case. CASE PRESENTATION A 37-year-old woman was admitted to our hospital with rash, severe pruritus and a change in urine colour after 2 months of GD treatment with MMI. Physical examination showed rash scattered over the limbs and torso, mild jaundice of the sclera and skin, short stature, facial moles, immature external genitals and diffuse thyroid gland enlargement. Liver function tests indicated an increase in total bilirubin, direct bilirubin, total bile acid, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase and alkaline phosphatase. The level of sex hormones suggested female hypergonadotropic hypogonadism. The karyotype of peripheral blood was 46, X, i(X)(q10)/45, X. After excluding biliary obstruction and other common causes of liver injury, combined with rash and abnormal liver function following oral administration of MMI, the patient was diagnosed as having TS with GD and rash and cholestatic liver injury caused by MMI. MMI was immediately discontinued, and eleven days after treatment with antihistamine and hepatoprotective agents was initiated, the rash subsided, and liver function returned to nearly normal. Because the patient did not consent to administration of 131I or thyroid surgery, hyperthyroidism was successfully controlled with PTU. No adverse drug reactions were observed after switching to PTU. CONCLUSIONS While patients with TS and GD are undergoing treatment with MMI, their clinical manifestations, liver functions, and other routine blood test results should be closely monitored. When patients with TS and GD manifest adverse reactions to MMI such as rash and cholestatic liver injury, it is necessary to discontinue MMI and treat with antihistamine and hepatoprotective agents. After the rash subsides and liver function returns to nearly normal, PTU can effectively control hyperthyroidism without adverse drug reactions.

Thyroid Storm in a Patient With COVID-19.

Abstract: Objective: A thyroid storm is a severe exacerbation of thyrotoxicosis that can cause significant morbidity and mortality. The emergence of the novel coronavirus (SARS-CoV-2) that originated in Wuhan, China, has become a worldwide pandemic. We present the first documented case of thyroid storm (as defined by the Burch-Wartofsky criteria) in a patient with COVID-19. Methods: Laboratory and diagnostic studies, including thyroid function tests, thyroid antibody testing, SARS-CoV-2 nasopharyngeal polymerase chain reaction testing, and thyroid ultrasound were performed. Results: A 25-year-old woman presented to the hospital with dry cough, dyspnea, palpitations, weight loss, diarrhea, and anxiety. Physical examination revealed exophthalmos with proptosis and chemosis, tachycardia, diffusely enlarged goiter with bruit, and fine tremor. Laboratory results demonstrated a thyroid-stimulating hormone level of <0.01 mIU/L (normal range [NR], 0.44-5.3 mIU/L), free thyroxine level of 5.34 ng/dL (NR, 0.64-1.42 ng/dL), total triiodothyronine level of 654 ng/dL (NR, 87-178 ng/dL), and thyroid-stimulating immunoglobulin level of 7.18 IU/L (NR, 0.00-0.55 IU/L). Thyroid ultrasound revealed heterogeneous echotexture with increased vascularity. Nasopharyngeal COVID-19 testing was positive. She was treated promptly with propranolol, propylthiouracil, and hydrocortisone with improvement in symptoms, and later switched to methimazole. Her COVID-19 course was uncomplicated, and she left the hospital with minimal respiratory symptoms. Conclusion: Thyroid storms are one of the more prevalent endocrine emergencies and are often precipitated by acute events including infections. Patients with thyroid storms may have concomitant SARS-CoV-2 infection that could influence the clinical course and severity of the disease. In patients with symptoms of thyrotoxicosis and respiratory symptoms, clinicians should consider performing a COVID-19 test.

Henoch-Schönlein Purpura (IgA Vasculitis) in Association with Thyrotoxicosis.

Abstract: Graves' disease is the most common cause of hyperthyroidism, which is characterized by thyroid antibodies and the following clinical manifestations: goiter, ophthalmopathy, and pretibial myxedema. On the other hand, Henoch-Schonlein purpura is an IgA-mediated small-vessel vasculitis. Review of the literature showed a relationship between propylthiouracil overdose and the following Henoch-Schonlein purpura (IgA vasculitis) as a side effect. The patient was a 31-year-old woman with a chief complaint of tremor and significant weight loss who contracted pruritic palpable purpura during her disease course. Then, she underwent the treatment of hyperthyroidism by methimazole which intensified her cutaneous lesions. The diagnosis of Henoch-Schonlein purpura (IgA vasculitis) was confirmed after skin biopsy. Finally, she was treated with colchicine, prednisolone, and radioiodine ablation, which caused her lesions to disappear. The temporal priority of pruritic palpable skin lesions to hyperthyroidism treatment with methimazole suggested that Henoch-Schonlein purpura (IgA vasculitis) was related to hyperthyroidism and was intensified by antithyroid agents in this patient.

Propylthiouracil: A Thyro-Suppressive as well as Haemato-Suppressive to Induce Agranulocytosis in Hyperthyroid Patients

Abstract: Background: Propylthiouracil (PTU) is a thyro-suppressive medication commonly used for the treatment of hyperthyroidism, but may cause agranulocytosis, which rises the mortality of patients. Objective: To evaluate the prevalence of agranulocytosis in hyperthyroid patients after the use of Propylthiouracil. The aim of the current research is to access the drug utilization and investigation of PTU which aids in accessing rational therapy and other aspects related to the patient’s safety. Methodology: A cross- sectional study conducted from May 2016 to April 2017 at Liaquat University of Medical and Health Sciences, Hospital Hyderabad/ Jamshoro. 150 prescriptions were collected by non-probability consecutive sampling technique from the adults with Hyperthyroidism patients using Propylthiouracil. Thyroid function tests were conducted using Immunoassay Elecysis 2010. The blood profile tests were evaluated on Sysmex kx21. The collected data was evaluated using the Statistical Package for Social Sciences (SPSS). Results: The data revealed that the propylthiouracil-induced agranulocytosis in 4 hyperthyroid patients (n=2 males, n=2 females) and the prevalence of Propylthiouracil-induced agranulocytosis was 2.7%. Conclusion: It was observed that Propylthiouracil damages the hematopoietic stem cells and precursors of granulocytes in bone marrow can cause agranulocytosis.

Prescription of Sageretia hamosa Brongn Relieved Goiter through Promoted Apoptosis of Thyroid Cells via miR-511-3p and PTEN/PI3K/Akt Pathway.

Abstract: Goiter is thyroid enlargement, in China, Sageretia hamosa Brongn (SHB) can be used to treat goiter, but it has not been reported. Therefore, data analytics of SHB prescription on thyroid were explored in this study to provide a theoretical support for SHB in the treatment of goiter. In this study, rat in goiter model was constructed by using propylthiouracil (PTU) and treated with SHB prescription. Thyroid function about the triiodothyronine (T3), free thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured by ELISA; thyroid coefficient was calculated after weighed thyroid; and HE staining was applied to assess the morphology of thyroid tissue. miRNA microarrays were employed to detect miRNA expression in thyroid tissue of rats. Expression of miR-511-3p was measured by RT-qPCR; expression of proteins (PTEN and apoptosis-related proteins) was tested by western blotting; relationship between miR-511-3p and PTEN was investigated by dual luciferase reporter gene assay; cell viability rate was determined by CCK-8; and cell cycle distribution and apoptosis rate were detected by flow cytometry. The results showed that SHB prescription ameliorated goiter and downregulated miR-511-3p. miR-511-3p targeted PTEN in thyroid cells and PTEN negatively regulated the activation of PI3K/Akt pathway. Furthermore, the inhibition of apoptosis in thyroid cells caused by the overexpression of miR-511-3p or the activation of PI3K/Akt pathway was reversed by treatment of SHB prescription, inhibition of miR-511-3p, or overexpression of PTEN. In conclusion, SHB prescription promoted apoptosis of thyroid through decreased miR-511-3p and regulated PTEN/PI3K/Akt pathway, it might suggest possible medical applications.

Fetal Hypothyroidism Impairs Aortic Vasorelaxation Responses in Adulthood: Involvement of Hydrogen Sulfide and Nitric Oxide Cross talk.

Abstract: Thyroid hormones have a wide range of effects on growth, differentiation, evolution, metabolism, and physiological function of all tissues, including the vascular bed. In this study, the effect of fetal hypothyroidism on impairment of aortic vasorelaxation responses in adulthood was investigated with emphasis on possible involvement of hydrogen sulfide (H2S)/nitric oxide interaction. Two groups of female rats were selected. After mating and observation of vaginal plaque, one group received propylthiouracil (200 ppm in drinking water) until the end of pregnancy and another group had no propylthiouracil treatment during the fetal period. In adult rats, aortic relaxation responses to l-arginine and GYY4137 were assessed in the presence or absence of Nω-nitro-L-arginine methyl ester hydrochloride and dl-propargylglycine in addition to the biochemical measurement of thyroid hormones and some related factors. Obtained findings showed a lower vasorelaxation response for GYY4137 and l-arginine in the fetal hypothyroidism group, and preincubation with Nω-nitro-L-arginine methyl ester hydrochloride or dl-propargylglycine did not significantly aggravate this weakened relaxation response. In addition, aortic levels of sirtuin 3, endothelial nitric oxide synthase, cystathionine gamma-lyase, and H2S were significantly lower in the fetal hypothyroidism group. Meanwhile, no significant changes were obtained regarding serum levels of thyroid hormones including free triiodothyronine;, total triiodothyronine, free thyroxine, total thyroxine, and thyroid-stimulating hormone in adult rats. It can be concluded that hypothyroidism in the fetal period has inappropriate effects on the differentiation and development of vascular bed with subsequent functional abnormality that persists into adulthood, and part of this vascular abnormality is mediated through weakened interaction and/or cross talk between H2S and nitric oxide.

Myopathy Associated with Treatment of Graves' Disease.

Abstract: Here, we report a case of an increase in serum creatine kinase (CK) concentration in an 11-year-old girl being treated for Graves’ disease with antithyroid drugs (ATDs). The patient complained of myalgia two weeks after methimazole treatment. Triiodothyronine (T3) and free thyroxine (FT4) levels were normal, but the serum CK level was significantly elevated. After switching to propylthiouracil, the serum CK level decreased to normal, and the myalgia was resolved. The development of myopathy during the treatment of hyperthyroidism may be considered as an adverse reaction of MMI. In this report, we present a rare pediatric case, along with a discussion on the possible causes of myopathy that occurred during the treatment of Graves’ disease. A careful follow-up (serum CK levels and thyroid function) and treatment reassessment should always be considered after antithyroid treatment.

When a storm showers the blood clots: a case of thyroid storm with systemic thromboembolism

Abstract: Summary Thyroid storm is a rare but potentially life-threatening complication of excessive thyroid hormone action. It is associated with a hypercoagulable state and reported to increase the risk of thromboembolism. However, the role of anticoagulation in thyroid storm still remains controversial and inconclusive. A 22-year-old male with no significant past medical history presented with acute severe generalised abdominal pain. He was found to be profoundly thyrotoxic on arrival at our institution and subsequently diagnosed with thyroid storm secondary to newly diagnosed Graves’ disease. Extensive thromboses of the splanchnic, iliac, femoral veins and pulmonary arteries were subsequently demonstrated on CT scan. He had prolonged bowel ileus as a sequela of mesenteric ischaemia requiring total parenteral nutrition and non-oral forms of anti-thyroid drugs for management of hyperthyroidism. He was in sinus rhythm throughout his inpatient stay, and there was no personal history of prothrombotic conditions. His thrombophilia screen was normal. He eventually required jejunectomy due to jejunal ischaemia from extensive involvement of portal and mesenteric veins. He underwent radioiodine ablation for definitive treatment. He is currently hypothyroid and receiving thyroxine replacement. Thyroid storms are hypercoagulable states and can be associated with extensive thromboembolism even in the absence of atrial fibrillation. To our knowledge, this is the first report of severe extensive thromboembolism complicated by severe mesenteric ischaemia and bowel ileus in the setting of a thyroid storm. Routine prophylactic anticoagulation should be considered in those presenting with thyroid storms. Learning points Prolonged use of rectal propylthiouracil (PTU) for managing hyperthyroidism was effective in a patient who cannot take oral anti-thyroid drugs. Hyperthyroidism is a hypercoagulable state due to an imbalance between coagulation and fibrinolytic factors. Thyroid storm can be associated with extensive thromboembolism even in the absence of atrial fibrillation; routine prophylactic anticoagulation should be considered in the setting of thyroid storms.