Showing papers on "Propylthiouracil published in 2022"

2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease

Abstract: Hyperthyroidism caused by Graves’ disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults – antithyroid drugs (ATD), radioactive iodine (RAI) or thyroid surgery, but the risks and benefits of each modality are different. The European Thyroid Association guideline provides new recommendations for the management of pediatric GD with and without orbitopathy. Clinicians should be alert that GD may present with behavioral changes or declining academic performance in children. Measurement of serum TSH receptor antibodies is recommended for all pediatric patients with hyperthyroidism. Management recommendations include the first-line use of a prolonged course of methimazole/carbimazole ATD treatment (3 years or more), a preference for dose titration instead of block and replace ATD, and to avoid propylthiouracil use. Where definitive treatment is required either total thyroidectomy or RAI is recommended, aiming for complete thyroid ablation with a personalized RAI activity. We recommend avoiding RAI in children under 10 years of age but favor surgery in patients with large goiter. Pediatric endocrinologists should be involved in all cases.

DIO3 protects against thyrotoxicosis-derived cranio-encephalic and cardiac congenital abnormalities

Abstract: Maternal hyperthyroidism is associated with an increased incidence of congenital abnormalities at birth, but it is not clear which of these defects arise from a transient developmental excess of thyroid hormone and which depend on pregnancy stage, antithyroid drug choice, or unwanted subsequent fetal hypothyroidism. To address this issue, we studied a mouse model of comprehensive developmental thyrotoxicosis secondary to a lack of type 3 deiodinase (DIO3). Dio3–/– mice exhibited reduced neonatal viability on most genetic backgrounds and perinatal lethality on a C57BL/6 background. Dio3–/– mice exhibited severe growth retardation during the neonatal period and cartilage loss. Mice surviving after birth manifested brain and cranial dysmorphisms, severe hydrocephalus, choanal atresia, and cleft palate. These abnormalities were noticeable in C57BL/6J Dio3–/– mice at fetal stages, in addition to a thyrotoxic heart with septal defects and thin ventricular walls. Our findings stress the protecting role of DIO3 during development and support the hypothesis that human congenital abnormalities associated with hyperthyroidism during pregnancy are caused by transient thyrotoxicosis before clinical intervention. Our results also suggest thyroid hormone involvement in the etiology of idiopathic pathologies including cleft palate, choanal atresia, Chiari malformations, Kaschin-Beck disease, and Temple and other cranio-encephalic and heart syndromes.

Regulation of PTU-induced hypothyroidism in rats by Caffeic acid primarily by activating thyrotropin receptors and by inhibiting oxidative stress

Abstract: Earlier, nothing was known on the thyroid-regulatory potential of caffeic acid (CA). We investigated its role in 6-propyl-thiouracil (PTU)-induced hypothyroid rats and also worked out the possible involvement of 5’-deiodinase I (5’-DI) and thyrotropin receptor (TSHR) in its mode of action. A pre-standardized dose (100 mg/kg) of CA was orally administered to PTU-induced rats for 30 days and its effects were evaluated on the alterations in the levels of serum triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH) and hepatic 5’-D1activity; expression of thyroid TSHR, aspartate transaminase (AST), alanine transaminase (ALT), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), total cholesterol (CHOL), triglycerides (TG) and hepatic lipid peroxidation (LPO). For the first time an interaction of CA with TSHR was studied in silico. PTU significantly reduced serum levels of thyroid hormones (TH), hepatic 5’-D1 and antioxidant activities as well as TSHR expression, but increased the serum TSH, AST, ALT, TNF-α, IL-6, CHOL, TG and hepatic LPO. However, CA treatment ameliorated all these PTU-induced alterations near to normal levels. Further, the distorted histo-architecture of thyroid gland by PTU was corrected by this compound. The molecular docking study indicated that CA possesses a high binding free energy with target TSHR. These results were comparable to that of a standard pro-thyroid drug, thyroxine. CA potentially stimulated thyroid function by increasing TH levels, hepatic 5’-D1 activity and upregulation of TSHR protein expression. In addition, it attenuated the increase in oxidative stress markers, liver markers, lipids and improved the thyroid histo-architecture, thus protected from PTU-induced adverse effects. In silico studies suggested the interaction of CA with TSHR that yielded the binding energy (-6.51 kcal/mol) as compared to thyroxine (-6.10 kcal/mol) suggesting it as a highly potent thyro-stimulatory drug.

Cardiovascular protective effect of nano selenium in hypothyroid rats: protection against oxidative stress and cardiac fibrosis

Abstract: ABSTRACT Background Nano selenium (Nano Sel) has many therapeutic properties including antioxidant, anticancer, and anti-inflammatory actions. Objective Impacts of Nano Sel administration against cardiac fibrosis and heart and aorta tissue oxidative damage observed in hypothyroid rats were explored. Methods The animals were randomly grouped and treated as: 1) Control; 2) Propylthiouracil (PTU) in which PTU was added to the drinking water (0.05%) to induce hypothyroidism; 3–5) PTU-Nano Sel 50, PTU-Nano Sel 100, and PTU-Nano Sel 150 groups, which received daily PTU plus 50,100 or 150 µg/kg of Nano Sel for 6 weeks intraperitoneally. The heart and aorta tissues were removed under deep anesthesia and then biochemical parameters including malondialdehyde (MDA), total thiol groups, catalase (CAT), and superoxide dismutase (SOD), as well as cardiac fibrosis were assessed. Results Hypothyroidism induced by PTU was remarkably associated with myocardial hypertrophy and perivascular fibrosis in Masson’s trichrome staining. Moreover, hypothyroidism increased MDA level, while it subtracted total thiol group content and activity of SOD and CAT. Treatment with Nano Sel recovered hypothyroidism-induced cardiac fibrosis in the histological assessment. Nano Sel also promoted CAT and SOD activity and thiol content, whereas alleviated MDA levels in the heart and aorta tissues. Conclusion Results propose that administration of Nano Sel exerts a protective role in the cardio vascular system via preventing cardiac fibrosis and inhibiting oxidative stress.

Propylthiouracil drug adsorption on pristine, Cu, Ag, and Au decorated AlP nanosheets

Abstract: B3LYP, M06-2X, and B97D density functionals are utilized for probing the effect of decorating Cu, Ag, and Au on the sensing performance of an aluminum phosphide nanosheet (AlPNS) in detecting the propylthiouracil (PTU) drug. We predict that the interaction of pure AlPNS with PTU is physisorption, and the sensing response (SR) of AlPNS is approximately 3.1. The adsorption energy of PTU changes from −5.1 to −18.7, −18.9, and −19.3 kcal/mol by decorating the Cu, Ag, and Au metals into the AlPNS, respectively. Also, the corresponding sensing response (SR) meaningfully rises to 53.4, 65.1, and 84.2. It indicates that by increasing the atomic number of metals, the sensitivity of metal decorated AlPNS (metal@AlPNS) is increased. Therefore, we found that Au-decorating much more increases the sensitivity of AlPNS toward PTU drug. The SR of metal@AlPNS slightly decreases in the water solvent. • Sensing response of AlP nanosheet to the propylthiouracil (PTU) drug is 3.1 at 298 K. • By Au decoration on AlP nanosheet, the sensing response increased to 84.2. • A short recovery time of 11.6 s was predicted for PTU desorption from the Au-decorated AlP surface.

Investigation of the effect of boron on thyroid functions and biochemical parameters in hypothyroid induced‐rats

Abstract: In the study investigating the effects of boron on thyroid hormones and some biochemical parameters in hypothyroid rats, 49 Wistar Albino male rats were divided into seven groups; (Control (C), Hypothyroidism (H), boron groups (B10, and B20), hypothyroid + boron groups (HB10 and HB20), and Treatment (T). Four groups (H, HB10, HB20, and T) were administered 10 mg/kg (B10 and HB10), 20 mg/kg (B20 and HB20) boron for 3 weeks, respectively after hypothyroidism was induced using Propycil® containing propylthiouracil (PTU). Thyroid hormone analyses and biochemical measurements were made from the serum and thyroid gland tissue was examined histopathologically. According to the findings, the fT3 level increased in the B10 group compared to the control group (p < 0.05). While AST, ALT, and ALP activities were found to be higher in the hypothyroid group than in the control group, AST and ALP activities in the HB10 and HB20 groups decreased to values close to the control group. Total cholesterol levels were found to be lower in boron‐given groups compared to control and hypothyroid groups (p < 0.05). Sodium iodide symporter (NIS) immunoreactivity was found to be high in hypothyroid rat groups. As a result, it was observed that the increased AST and ALP activities in rats decreased with boron administration. The serum hormone levels measured in the study are not sufficient to understand the effect of boron on the thyroid gland, and it was concluded that further studies at the molecular level are needed to understand the effects of boron on the thyroid gland.

Thyrotoxicosis after a massive levothyroxine ingestion: A case report

Abstract: BACKGROUND The literature on thyrotoxicosis caused by excessive ingestion of exogenous thyroid hormone is limited, and most cases reported have involved pediatric clinical studies. CASE SUMMARY A 21-year-old woman initially presented with palpitation and chest tightness after an overdose of levothyroxine (10 mg). The patient transiently lost consciousness and developed atrial fibrillation during hospitalization. We used propylthiouracil to decrease the peripheral conversion of T4 to T3 and inhibit the synthesis of endogenous thyroxine, propranolol to control heart rate, hydrocortisone to correct severe thyrotoxicosis, and hemoperfusion to increase levothyroxine clearance. The patient recovered and was discharged. CONCLUSION For patients with thyrotoxicosis after taking excess levothyroxine, it is critical to monitor vital signs and initiate effective treatment.

Cardiovascular protective effects of PPARγ agonists in hypothyroid rats: protection against oxidative stress

Abstract: ABSTRACT Hypothyroidism disturbs redox homeostasis and takes part in cardiovascular system dysfunction. Considering antioxidant and cardio-protective effects of PPAR-γ agonists including pioglitazone (POG) and rosiglitazone (RSG), the present study was aimed to determine the effect of POG or RSG on oxidants and antioxidants indexes in the heart and aorta tissues of Propylthiouracil (PTU)-induced hypothyroid rats. Materials and methods The animals were divided into six groups: (1) Control; (2) propylthiouracil (PTU), (3) PTU-POG 10, (4) PTU-POG 20, (5) PTU-RSG 2, and (6) PTU-RSG 4. Hypothyroidism was induced in rats by giving 0.05% propylthiouracil (PTU) in drinking water for 42 days. The rats of PTU-POG 10 and PTU-POG 20 groups received 10 and 20 mg/kg POG, respectively, besides PTU, and the rats of PTU-RSG 2 and PTU-RSG 4 groups received 2 and 4 mg/kg RSG, respectively, besides PTU. The animals were sacrificed, and the serum of the rats was collected to measure thyroxine level. The heart and aorta tissues were also removed for the measurement of biochemical oxidative stress markers. Results Hypothyroidism was induced by PTU administration, which was indicated by lower serum thyroxine levels. Hypothyroidism also was accompanied by a decrease of catalase (CAT), superoxide dismutase (SOD) activities, and thiol concentration in the heart and aorta tissues while increased level of malondialdehyde (MDA). Interestingly, administration of POG or RSG dramatically reduced oxidative damage in the heart and aorta, as reflected by a decrease in MDA and increased activities of SOD, CAT, and thiol content. Conclusion The results of this study showed that administration of POG or RSG decreased oxidative damage in the heart and aorta tissues induced by hypothyroidism in rats.

Efficacy of propylthiouracil in the treatment of pregnancy with hyperthyroidism and its effect on pregnancy outcomes: A meta-analysis

Abstract: Background Hyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is generally treated with propylthiouracil (PTU). However, previous studies about the effects of propylthiouracil on maternal or foetal are contentious. Objective This meta-analysis was carried out to investigate the safety and efficacy of propylthiouracil during pregnancy. Materials and methods PubMed, EBSCO, Embase, Scopus, Web of Science, Cochrane, CNKI, Wanfang and VIP database were searched from inception until August 31, 2021 for all available randomized controlled trials (RCTs) or cohort studies that evaluated the efficacy of propylthiouracil and its effects on pregnancy outcomes. Odds ratio (OR) and 95% confidence interval (CI) were used for binary variables, weighted mean difference (WMD) and 95% confidence interval (CI) were used for continuous variables. RevMan5.4 and Stata 16.0 were used for performing the meta-analysis. Results The researchers examined data from 13 randomized controlled trials and cohort studies involving 18948 infants. Congenital anomalies were not significantly associated with PTU in the pooled results (OR = 1.03, 95%CI: 0.84–1.25, P = 0.80, I2 = 40.3%). There were no statistically significant differences in neonatal hypothyroidism (OR = 0.55, 95%CI: 0.06–4.92, P = 0.593, I2 = 57.0%) or hepatotoxicity (OR = 0.34, 95%CI: 0.08–1.48, P = 0.151, I2 = 0.0%) exposed to PTU compared to the control group. The serum levels of FT3, FT4, TT3, and TT4 were significantly lower in the propylthiouracil group compared to the control group. Conclusion This meta-analysis confirmed the beneficial effects of propylthiouracil treatment, namely the risks of adverse pregnancy outcomes were not increased, and it also proved PTU’s efficacy in the treatment of pregnant women with hyperthyroidism. The findings supported the use of propylthiouracil during pregnancy with hyperthyroidism in order to improve clinical pregnancy outcomes in patients with thyroid dysfunction.

Predictive performance and verification of physiologically based pharmacokinetic model of propylthiouracil

Abstract: Background: Propylthiouracil (PTU) treats hyperthyroidism and thyroid crisis in all age groups. A variety of serious adverse effects can occur during clinical use and require attention to its pharmacokinetic and pharmacodynamic characteristics in various populations. Objective: To provide information for individualized dosing and clinical evaluation of PTU in the clinical setting by developing a physiologically based pharmacokinetic (PBPK) model, predicting ADME characteristics, and extrapolating to elderly and pediatric populations. Methods: Relevant databases and literature were retrieved to collect PTU’s pharmacochemical properties and ADME parameters, etc. A PBPK model for adults was developed using PK-Sim® software to predict tissue distribution and extrapolated to elderly and pediatric populations. The mean fold error (MFE) method was used to compare the differences between predicted and observed values to assess the accuracy of the PBPK model. The model was validated using PTU pharmacokinetic data in healthy adult populations. Result: The MFE ratios of predicted to observed values of AUC0-t, Cmax, and Tmax were mainly within 0.5 and 2. PTU concentrations in various tissues are lower than venous plasma concentrations. Compared to healthy adults, the pediatric population requires quantitative adjustment to the appropriate dose to achieve the same plasma exposure levels, while the elderly do not require dose adjustments. Conclusion: The PBPK model of PTU was successfully developed, externally validated, and applied to tissue distribution prediction and special population extrapolation, which provides a reference for clinical individualized drug administration and evaluation.

Metformin and alpha lipoic acid ameliorate hypothyroidism and its complications in adult male rats

Abstract: The current study evaluates the effect of metformin (MET) and /or alpha lipoic acid (ALA) on hypothyroidism and its adverse effects on the cardiac, renal, and, hepatic functions in rats.Rats were divided into five groups: control, rat model of hypothyroidism induced by propylthiouracil (PTU), rat model of hypothyroidism treated with MET, rat model of hypothyroidism treated with ALA, and rat model of hypothyroidism treated with MET and ALA. At the end of the experiment, body weight gain was determined and the blood samples were collected from orbital plexus to measure the serum levels of thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) by ELISA, glucose level, the activities of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), and the levels of urea and creatinine spectrophotometrically.Rat model of hypothyroidism revealed a significant decrease in T4 (p < 0.001) and T3 (p < 0.001) and a significant increase in TSH (p < 0.005). This was accompanied by a significant decrease in the body weight gain (p < 0.025) and a significant increase in LDH (p < 0.001), CK-MB (p < 0.001) AST (p < 0.01), ALT (p < 0.016), ALP (p < 0.001), glucose (p < 0.001), urea (p < 0.001) and creatinine (p < 0.001). MET restored T4, T3 and TSH to control values. Treatment with ALA restored T3 and TSH levels. Treatment with Met and /or ALA reduced the levels of glucose, urea and creatinine and the activities of LDH, CK-MB, AST, ALT, and ALP to control-like values. Only ALA improved the reduced body weight gain induced by hypothyroidism.The present findings indicate the ameliorative effects of MET and /or ALA on hypothyroidism and its adverse effects on cardiac, renal and hepatic functions.The online version contains supplementary material available at 10.1007/s40200-022-01063-7.

A Case of Methimazole-Induced Acute Pancreatitis With an HLA Allele Causing Antithyroid Drug-Induced Agranulocytosis

Abstract: Abstract Among the side effects of methimazole (MMI) for the treatment of Graves’ disease, MMI-induced acute pancreatitis (MIP) is a rare adverse reaction, with only 7 cases being reported to date. However, 2 large-scale population-based studies recently revealed that the risk of MIP was significantly higher, ranging from 0.02% to 0.56%. Although MIP is common in middle-aged and elderly Asian women, its pathogenesis remains largely unknown. We herein present a case of a 72-year-old Japanese woman with Graves’ disease who developed MIP 12 days after the initiation of MMI. The MMI was discontinued, the patient was switched to propylthiouracil (PTU) therapy, and pancreatitis gradually resolved. Serological human leukocyte antigen (HLA) typing identified HLA-DRB1*08:03:02. This HLA allele was previously detected in a patient with MIP and is one of the major risk factors for agranulocytosis induced by antithyroid drugs, including PTU as well as MMI. In cases of MIP, PTU is being considered as an alternative to MMI; however, its safety needs further investigation and patients require close monitoring after the switch to PTU. Further studies are warranted, particularly on the relationship between MIP and the presence of HLA alleles causing antithyroid drug-induced agranulocytosis.

Drug-induced hypersensitivity syndrome induced by propylthiouracil: case report and literature review

Abstract: Drug-induced hypersensitivity syndrome (DIHS) is a rare, potentially life-threatening systemic drug reaction. Antithyroid drugs (ATDs) causing DIHS have seldom been reported before.We present a case of propylthiouracil (PTU)-induced DIHS, which included fever, skin rash, lymphadenopathy, hepatosplenomegaly, serious liver and kidney dysfunction, peripheral blood eosinophilia, and atypical lymphocytosis. Following supportive therapy, intravenous immunoglobulin (IVIG), and systemic corticosteroid, the patient experienced a resolution of fever and rash combined with progressive normalization of hematological index and organ function. These clinical features, and the skin lesion biopsy confirmed DIHS diagnosis.To our knowledge, this is the second reported case of PTU-induced DIHS worldwide and the first human leukocyte antigen (HLA) typing of PTU-induced DIHS. Clinicians should cautiously distinguish hyperthyroidism etiology and identify the indication of ATDs. Timely recognition and formal DIHS treatment are required in patients with ATDs.

Elevation of serum creatine kinase induced by anti-thyroid drugs: Two case reports and a literature review

Abstract: Anti-thyroid drugs (ATDs), such as methimazole (MMI) and propylthiouracil (PTU), are the most common treatment options for hyperthyroidism. Although effective, well-known adverse effects include agranulocytosis, toxic hepatitis, vasculitis, and arthralgias. Myalgia and elevation of serum creatine kinase (CK) are relatively rare, with an unclear mechanism. Rapid decrease in the thyroid hormone level may be associated with ATD-related myopathy; however, direct effects of the drug on muscle tissue cannot be excluded. Here we report on two Chinese patients with myalgia and an elevated CK due to ATDs. Early recognition of this rare medication-induced adverse effect and close monitoring of the CK level are particularly important. Physicians and pharmacists should inform the patients about the earliest symptoms of adverse effects for patients to know when to discontinue the drug. If adverse events occur, different treatment strategies such as ATD dose reduction and switching to alternative ATDs can be applied depending on the case.

Thymoquinone protects the testes of hypothyroid rats by suppressing pro-inflammatory cytokines and oxidative stress and promoting SIRT1 testicular expression

Abstract: Background: Hypothyroidism has been linked to many testicular structural and dysfunctional changes in males. Thymoquinone (TQ) has shown a potent testicular protective effect through its antioxidant, anti-inflammatory, antiapoptotic, fertility-enhancing, and endocrine modulatory activities. Objectives: This study aimed to investigate the efficacy of TQ in preserving the testicular structure of a model of experimentally induced hypothyroidism in rats and identify the mechanism behind this effect. Materials and methods: Propylthiouracil (PTU) was used to induce hypothyroidism in adult male Wistar rats, who were then treated with TQ (50 mg/kg/body weight) for 4 weeks and compared to the untreated rats. Thyroid hormonal profile, oxidants/antioxidants profile, and serum testosterone levels were assessed. Gene expression and immune expression of SIRT1 and pro-inflammatory cytokines TNF-α and NF-κB were also assessed in the testicular tissue. Results: TQ administration successfully improved PTU-induced disturbance in the thyroid hormonal profile (T3, T4, and TSH), serum testosterone level, and pancreatic antioxidants compared to the untreated hypothyroid group. TQ significantly downregulated (p = 0.001, p ˂ 0.001) TNF-α and NF-κB transcription, while it significantly upregulated (p = 0.01) SIRT1 transcription in the testes of hypothyroid rats. TQ markedly relieved the histopathological testicular changes induced by PTU and significantly increased (p = 0.002, p = 0.01) the sectional area of seminiferous tubules and germinal epithelial height, respectively. TUNEL-positive apoptotic germinal cells were significantly decreased (p ˂ 0.001), while PCNA-positive proliferating germinal cells and androgen receptor expression were significantly increased (p ˂ 0.001) in the testes of TQ-treated hypothyroid rats. Conclusion: Thymoquinone could limit the hypothyroidism-induced structural changes in the testis, mostly through the upregulation of SIRT1 expression, which seems to mediate its promising antioxidant, anti-inflammatory and antiapoptotic effects that were evident in this study. Therefore, TQ is recommended as an adjuvant safe supplement in managing hypothyroidism, especially in males.

Thymoquinone Ameliorate Hepatorenal Toxicity Associated With Propylthiouracil-Induced Hypothyroidism in Juvenile Rats.

Abstract: An increasing number of studies suggest that hypothyroidism may lead to hepatorenal toxicity. This study examined whether thymoquinone (TQ), the main active Nigella sativa constituent, could prevent the detrimental influences of hepatorenal toxicity of hypothyroidism during the juvenile period in rats.The male rats were randomly divided into four groups (n = 7), including control, propylthiouracil (PTU), PTU-TQ 5 mg/kg, and PTU-TQ 10 mg/kg. PTU was dissolved in drinking water at a concentration of 0.05% and administered for six weeks. In the PTU-TQ5 and PTU-TQ10 groups, animals received PTU plus 5 mg/kg and 10 mg/kg of the TQ (i.p.) for six weeks, respectively. The rats were evaluated after TQ treatment by measuring serum markers of liver and kidney function tests as well as oxidative stress biomarkers in liver and kidney tissues.Administration of TQ (5 and 10 mg/kg) decreased oxidative stress damage in liver and kidney tissue in hypothyroidism rats with improvement in activities of antioxidant enzymes and a decrease in MDA in both liver and kidney homogenates. Furthermore, TQ treatment significantly inhibited the elevation of serum biochemical markers of liver and kidney function associated with this hepatorenal toxicity.These results suggest that the protective effect of TQ in hypothyroidism-induced hepatorenal toxicity in rats is attributed to its ability to reduce oxidative stress in hepatic and renal tissues. However, more studies are recommended to investigate the exact mechanism (s) for the effect of TQ on hepatorenal outcomes of hypothyroidism in human subjects.

Melatonin Modulates Hypophyseal-Thyroid Function through Differential Activation of MT1 and MT2 Receptors in Hypothyroid Mice

Abstract: Hypothyroidism is characterized by the low level of thyroid hormones in circulation, which affects the normal metabolic activities of organisms. Propylthiouracil (PTU) induced hypothyroid condition impairs the antioxidant defense system and therefore normal physiology alters. Melatonin influences most physiological activities and is also known for its antioxidative properties. Melatonin modulates physiological activities through receptor-mediated as well as non-receptor-mediated pathways. In this study, we evaluated the involvement of melatonin MT1 and MT2 receptors in the modulation of hypophyseal-thyroid function in PTU-induced hypothyroid mice. We have noted the decreased level of T3 and T4 and increased level of TSH hormone in PTU-treated mice. Melatonin treatment counteracted the PTU-caused changes in circulatory T3, T4, and TSH hormones. PTU treatment caused increased MT1 receptor protein expression in the thyroid as well as the pituitary gland while increased MT2 receptor protein in the pituitary gland. Melatonin treatment caused increased TSH receptor protein in the thyroid gland. Melatonin induced MT2 receptor protein expression in both the thyroid and pituitary glands whereas MT1 receptor proteins in the pituitary gland. This study may suggest that melatonin regulates hypophyseal-thyroid function through differential sensitization of MT1 and MT2 receptors on the pituitary and thyroid glands in hypothyroid mice.

Propylthiouracil-Induced Skin Vasculitis

Abstract: The use of propylthiouracil (PTU) is associated with the development of autoantibodies, namely, antineutrophil cytoplasmic antibodies (ANCAs), which are associated with the pathogenesis of ANCA-associated systemic vasculitis, most often related to the myeloperoxidase subtype (ANCA-MPO). The authors report the case of a 61-year-old woman on PTU for one year who was referred to Internal Medicine for a three-month evolution of painless non-blanching purple patches, non-pruriginous, involving the chest and legs. The autoimmunity revealed ANCA antibody positivity, with a cutaneous biopsy compatible with leukocytoclastic vasculitis/necrotizing vasculitis with involvement of small and medium-sized vessels. Clinical improvement was noted after the drug was discontinued, with the resolution of the analytical changes.

Propylthiouracil-Induced Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis with Renal and Lung Involvement

Abstract: Propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a rare and heterogeneous disease. Moreover, optimal treatment is still lacking. We described the case of a 44-year-old lady with underlying Graves’ disease who had cough, blood-streaked sputum, and impaired renal function. A strongly positive anti-myeloperoxidase antibody (>200 U/mL) along with pauci-immune glomerulonephritis and pulmonary hemorrhage resulted in the diagnosis of PTU-induced AAV, given that the patient had been on PTU for 3 years. PTU withdrawal, therapeutic plasma exchanges, and oral cyclophosphamide provided favorable clinical and biochemical outcomes. She remained well on azathioprine 50 mg daily as maintenance therapy and clinically euthyroid with carbimazole 2.5 mg daily. The effective treatment for drug-induced ANCA vasculitis remains controversial, but rapid withdrawal of the offending medication should be the mainstay of treatment. In severe drug-induced ANCA vasculitis with pulmonary hemorrhage and/or life-threatening organ involvement such as kidney failure requiring dialysis, therapeutic plasma exchange with immunosuppressants is often required. In this case, we have shown that patient achieved remission after therapeutic plasma exchange with cyclophosphamide in the acute stage of treatment and remained symptom-free with azathioprine in the maintenance phase of treatment for 24 months.

Cost-Effectiveness Analysis of Antithyroid Drug (Propylthiouracil) Compared to Radioactive Iodine for the Treatment of Graves’ Disease in Ethiopia

Abstract: Graves' disease is an autoimmune disorder caused by stimulating antibodies. The peak incidence of Graves' disease occurs among patients aged 30 to 60 years. Radioactive iodine (RAI) and antithyroid drug (ATD) have been well-established therapies for the treatment of Graves' disease for several decades. However, there remain large variations in practice among physicians in the preferred modality and the method of administration.To assess the cost-effectiveness of ATD (propylthiouracil) compared to RAI from a health care payer perspective in Ethiopia.Markov model was constructed by using TreeAge software 2021 with different parameters, such as ATD, RAI, treatment failure, treatment success, hypothyroidism, and supplemental thyroxine to conduct a cost-effectiveness analysis. A hypothetical 40-year-old female patient with symptomatic Graves' hyperthyroidism was simulated to estimate expected lifetime health outcomes, quality-adjusted life years (QALYs) and costs, discounted at 3%.RAI has lesser QALYs (14.19) and is less expensive (US$ 3583.22), while ATD has higher QALYs (16.54) and is more expensive (US$ 12531.68). The result showed that there was no dominant treatment option. The incremental cost-effectiveness ratio was US$ 3811.6 per QALY which was greater than one to three times the cost-effectiveness threshold of Ethiopia (US$ 783).In this cost-effectiveness analysis, RAI was the preferred treatment strategy for Graves' disease, since the cost needed to get one extra QALY through ATD was greater than one to three times the cost-effectiveness threshold of Ethiopia.