Efficacy of methimazole before the administration of radioactive iodine in the management of Graves' disease: a systematic review and meta-analysis

ABSTRACT BACKGROUND: The efficacy of anti-thyroid drugs in conjunction with radioactive iodine therapy in the management of Graves' disease is still controversial. OBJECTIVE: To compare the efficacy of pretreatment with methimazole before the administration of radioactive iodine for the treatment of Graves' disease. DESIGN AND SETTING: A systematic review and meta-analysis was conducted at a teaching/tertiary hospital in Ibadan, Nigeria. METHODS: A systematic search of the PubMed, Embase, Cochrane Library, and Web of Science databases was performed from inception to December, 2021. RESULTS: Five studies with 297 participants were included. There was no difference in the risk of persistent hyperthyroidism when radioactive iodine was used in conjunction with methimazole compared with when radioactive iodine was used alone (relative risk: 1.02, 95% confidence interval, CI: 0.62-1.66; P = 0.95, I2 = 0%). Subgroup analysis based on the duration between discontinuation of methimazole and the administration of radioactive iodine showed a lower risk of persistent hyperthyroidism when methimazole was discontinued within 7 days before radioactive iodine use, although this did not reach statistical significance (risk ratio: 0.85, CI: 0.28-2.58). CONCLUSIONS: The use of methimazole before radioactive iodine administration was not associated with an increased risk of persistent hyperthyroidism. Concerns about medication toxicity and adverse effects should be considered when clinicians make decisions on combination therapies for the treatment of Graves' disease. PROSPERO REGISTRATION: CRD42020150013, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150013.

Clinical effects of Jiakang Pingxiao prescription combined with methiimidazole on hyperthyroidism / 中国基层医药

Objective:To investigate the clinical effects of Jiakang Pingxiao prescription combined with methiimidazole on hyperthyroidism. Methods:A total of 100 patients with hyperthyroidism admitted to Shanxian Central Hospital from February 2018 to January 2021 were included in this study. They were randomly divided into a study group and a control group, with 50 patients in each group. The control group was treated with methiimidazole, and the study group was treated with Jiakang Pingxiao prescription combined with methiimidazole. Thyroid function, serum levels of osteocalcin (OCN), β-CTx, hypersensitive C-reactive protein, and interleukin-6 (IL-6) were compared between the two groups. Results:After treatment, serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) in the study group were (3.10 ± 1.36) mU/L, (5.76 ± 1.25) pmol/L, (15.22 ± 1.95) pmol/L, respectively, which were significantly lower than (4.88 ± 1.47) mU/L, (7.13 ± 1.32) pmol/L, (19.07 ± 2.02) pmol/L in the control group ( t = 5.27, 4.71, 6.29, all P < 0.05). Serum OCN, β-CTx, hS-CRP, and IL-6 in the study group were (17.36 ± 2.62) μg/L, (0.32 ± 0.04) μg/L, (4.07 ± 0.86) mg/L, and (1.38 ± 0.21) pg/L, respectively, which were significantly lower than (26.05 ± 2.88) μg/L, (0.51 ± 0.09) μg/L, (6.23 ± 0.91) mg/L, (1.89 ± 0.28) pg/L in the control group ( t = 12.37, 10.40, 7.39, 8.57, all P < 0.05). The incidence of adverse reactions in the study group was significantly lower than that in the control group [6.00% (3/50) vs. 12.00% (3/50), χ2 = 14.78, P < 0.05). Conclusion:Jikang Pingxiao prescription combined with methiimidazole can effectively reduce the inflammatory responses in patients with hyperthyroidism, inhibit the expression of OCN and β-CTX in the serum, and improve thyroid function. The combined method is scientific and reasonable, and is suitable for clinical application. It has good therapeutic effects on hyperthyroidism and is worthy of clinical promotion.

Síndrome nefrótico por enfermedad de cambios mínimos asociado a enfermedad de Graves y uso de metimazol

Introduction: Graves' disease causes kidney injury through a series of multiple mechanisms, including the treatment for this condition. Nephrotic syndrome due to minimal change disease (MCD) is an unusual form of such kidney injury; the association between methimazole use and MCD is also rare. Case presentation: A 36-year-old woman with a history of Graves' disease in use of methimazole for several months, who presents edematous syndrome due to nephrotic syndrome associated with a KDIGO stage 3 acute kidney injury. Thionamide-induced hypothyroidism and the need of thyroid hormone replacement therapy was evidenced at the time of consultation. Based on a renal biopsy, the patient was diagnosed with MCD, her condition worsened as she experienced oliguria and hypervolemia, therefore, renal replacement therapy with hemodialysis was temporarily required. Methimazole administration was suspended, and treatment consisting of prednisolone administration and levothyroxine supplementation was started, achieving hemodialysis suspension, gradual improvement of proteinuria until remission and a full-maintained recovery of renal clearance. Radioiodine therapy was implemented as definitive treatment for Graves' disease, obtaining a successful outcome. Conclusions: Graves' disease and methimazole use are possible causes of minimal change disease; systemic corticosteroid therapy is a possible management. However, further basic, clinical and epidemiological research on this subject is required.

Introducción: La enfermedad de Graves genera daño renal por múltiples mecanismos, incluyendo sus tratamientos. El síndrome nefrótico por enfermedad de cambios mínimos, es una forma inusual de dicho daño renal en la enfermedad de Graves; la asociación de esta condición renal con el metimazol también es anómalo. Presentación del caso: Una mujer de 36 años con antecedente de enfermedad de Graves en uso de metimazol hacía meses, quien debutó con síndrome edematoso por síndrome nefrótico asociado a una lesión renal aguda KDIGO etapa 3. Se evidenció hipotiroidismo inducido por la tionamida con necesidad de suplencia al momento de la consulta. Asimismo, se realizó biopsia renal que concluyó en enfermedad de cambios mínimos. La paciente progresó a oliguria con hipervolemia sin respuesta a diurético del asa por lo que requirió terapia de reemplazo renal con hemodiálisis de forma transitoria. Se retiró el metimazol, se dio manejo con prednisolona y con suplencia tiroidea, lográndose el retiro de la hemodiálisis con mejoría gradual de la proteinuria hasta la remisión y recuperación de la depuración renal de forma plena y mantenida. Se dio manejo definitivo a la enfermedad de Graves con yodo radioactivo con éxito terapéutico. Discusión y conclusiones: La enfermedad de Graves y el metimazol son causas posibles de enfermedad de cambios mínimos; el tratamiento con corticoide sistémico se postula como una posible estrategia de manejo. Se requiere más investigación básica, clínica y epidemiológica en el tema.

Neutropenia febril inducida por metimazol

Resumen: Los antitiroideos de síntesis como el metimazol, tienen como uno de sus eventos adversos la neutropenia. Si bien la misma es de baja frecuencia (0.1 - 1%), pueden conducir a infecciones graves con una mortalidad que llega al 4%. El mecanismo patogénico no está claro, se plantean una serie de alteraciones inmunológicas. El tratamiento consiste en la suspensión inmediata del medicamento y el tratamiento del proceso infeccioso. Se presentan dos casos clínicos que se manifiestan una con una infección de piel y partes blandas, y la otra con una neumopatía aguda comunitaria, constatándose una neutropenia febril severa que se vincula al uso de metimazol.

Abstract: Synthetic antithyroid drugs us methimazole have neutropenia as one of their adverse events. Although it is of low frequency (0.1 - 1%), it can lead to serious infections with a mortality rate of up to 4%. The pathogenic mechanism is not clear, a series of immunological alterations are proposed. The treatment consists of the immediate suspension of the medication and the treatment of the infectious process. Two clinical cases are presented that manifest one with a skin and soft tissue infection, and the other with an acute community lung disease, confirming a severe febrile neutropenia that is linked to the use of methimazole.

Resumo: Drogas antitireoidianas sintéticas como metimazol, têm a neutropenia como um de seus eventos adversos. Embora seja de baixa frequência (0,1 - 1%), pode levar a infecções graves com taxa de mortalidade de até 4%. O mecanismo patogênico não está claro, uma série de alterações imunológicas são propostas. O tratamento consiste na suspensão imediata da medicação e no tratamento do processo infeccioso. São apresentados dois casos clínicos que manifestam um com infecção de pele e tecidos moles e outro com doença pulmonar comunitária aguda, confirmando uma neutropenia febril grave associada ao uso de metimazol.

Antithyroid drugs-induced antineutrophil cytoplasmic antibody-associated vasculitis in children: report of three cases and literature review / 中华肾脏病杂志

Objective:To explore clinicopathological features and prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in children induced by antithyroid drugs.Methods:The clinicopathological features, treatment and prognosis of 3 children with AAV induced by antithyroid drugs in the Department of Pediatric Nephrology and Rheumatology of the First Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively, and the literatures were reviewed.Results:(1) Among the 3 cases, there were 2 females and 1 male, whose ages were 12.6, 13.9 and 13.1 years old, respectively. All patients had medication history of propylthiouracil (PTU) and/or methimazole (MMI) before onset. Initial manifestation was pallor and renal involvements with nephrotic proteinuria, hematuria and renal function abnormality, while 2 of them had hypertension. Extrarenal manifestations were also presented: case 1 presented with rash, arthralgia and cardiac insufficiency; case 2 had brain involvement with repeated convulsions; case 3 presented with arthralgia and lung involvement. They were all tested positive for p-ANCA and MPO-ANCA. Initial renal histopathology of the 3 cases were consistent with ANCA-associated glomerulonephritis, which were classified into sclerosis, crescentic and mixed class respectively. After 8 months of treatments, repeated renal biopsy of case 3 had demonstrated progression to sclerosis class. Antithyroid drugs (PTU or MMI) were discontinued in 3 cases, and the children were all treated with corticosteroid combined with intravenous pulse cyclophosphamide therapy. Plasma exchange was performed in case 2 and case 3 due to rapidly progressive glomerulonephritis and disease recurrence (suspected pulmonary hemorrhage), respectively. Case 3 was treated with rituximab combined with mycophenolate mofetil after recurrence. The extrarenal symptoms relieved quickly after treatments in all cases. P-ANCA and MPO-ANCA became negative in case 1 and case 2 after 6 months of treatments but they were persistently positive in case 3. Three cases were followed up for 24 months, 10 months and 12 months, respectively: case 1 develop chronic kidney disease (CKD) stage 2 with normal urinalysis; case 2 develop CKD stage 5 and had sudden death at home at 10-month follow-up; case 3 develop CKD stage 4 with nephrotic proteinuria and microscopic hematuria. (2) There were totally 30 pediatric cases with AAV induced by PTU and MMI, including 27 reported cases in the literature and 3 cases in this study. Symptoms of AAV appeared in children after an average administration of (37.5±4.0) months of PTU (range from one month to 96 months and 8 months of MMI alone). Kidney (28 cases, 93.3%) and lung (12 cases, 40.0%) were commonly involved, while brain (2 cases, 6.7%) was rarely involved. The pathological changes of kidney were crescent nephritis (5/23) and necrotizing pauci-immune complex nephritis (11/23). The total remission rate was 93.3% (28/30) after antithyroid drugs withdrawal and treatment with corticosteroids and immunosuppressive therapy, however, there were still severe cases with progression to CKD stage 5, and death. (3) Thirty cases were divided into complete response group ( n=19) and incomplete response group ( n=11) according to the treatment response. Compared with complete response group, the proportions of massive proteinuria (8/11 vs 5/19), fibrinoid necrosis (7/9 vs 4/14), deposition of immune complex in renal tissues (6/9 vs 2/14) and administration of immunosuppressants (10/11 vs 5/19), and degree of tubular atrophy (0/1/2/3 grade, 2/4/2/1 vs 9/5/0/0) in incomplete response group were higher (all P<0.05). Conclusions:PTU and MMI can both induce AAV in children, and AAV may occur after short-term course of administration. Kidney and lung are commonly involved while brain involvement is rarely seen. Timely withdrawal of antithyroid drugs and proper treatments with corticosteroids and immunosuppressants can result in high remission rate, though there are still some severe cases. Nephrotic-range proteinuria, renal fibrinoid necrosis, immune-complex deposition and tubular atrophy may be the risk factors of AAV for poor prognosis.

Methimazole induced agranulocytosis and hemophagocytic syndrome: One case report / 中华内分泌代谢杂志

In order to improve the level of diagnosis and treatment, we report a rare case of hyperthyroidism patient occurred agranulocytosis and hemophagocytic syndrome after taking methimazole. After methimazole treatment, agranulocytosis and infection was developed, but was improved temporarily after treatment. However because of infection, the condition was rapidly developed into hemophagocytic syndrome. Finally, the patient improved rapidly with the treatment of dexamethasone.

Efficacy of methimazole combined with 1α-hydroxyvitamin D3 in patients with Graves disease of high-titer thyrotropin receptor antibodies / 中国医师杂志

Objective:To observe the efficacy of methimazole (MMI) combined with 1α-hydroxyvitamin D3 (alfacalcidol, ALF) in patients with Graves disease of high-titer thyrotropin receptor antibodies (TRAb) and to explore new clinical strategies to reduce serum TRAb in Graves disease.Methods:120 patients with Graves disease initially diagnosed in Quanzhou First Hospital Affiliated to Fujian Medical University and the People′s Hospital Affiliated to Quanzhou Medical College from June 2017 to June 2019 were prospectively selected as the research objects. All patients received conventional dose of MMI for anti hyperthyroidism treatment. The patients were randomly divided into three groups: group A [ n=40, treated with MMI combined with high-dose ALF (0.5 μg/d)], group B [ n=37, treated with MMI combined with low-dose ALF (0.25 μg/d)] and group C ( n=43, treated with MMI only). The treatment lasted for 24 weeks. The serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid stimulating hormone (TSH) and TRAb in patients before and after above treatments were detected. The blood routine, liver function, alkaline phosphatase (ALP), 25(OH)D, serum calcium (CA) and serum phosphorus were detected regularly. Results:After drug treatment: ⑴ the thyroid function of the three groups returned to normal. The average daily dosage of MMI in group A was significantly lower than that in group B and C ( P<0.05), and that in group B was also lower than that in group C ( P<0.05), with significant difference. After 24 weeks of treatment, the daily dosage of MMI in group A and B was significantly lower than that in group C ( P<0.05). ⑵ There was no significant difference in thyroid function among the three groups. The concentration of serum TRAb in group A was significantly lower than that in group B and C ( P<0.05), and that in group B was also lower than that in group C ( P<0.05). ⑶ During the 24 week follow-up, there was no significant difference in serum 25(OH)D, ALP, Ca and P among the three groups ( P>0.05); no leukopenia in peripheral blood and no abnormal liver function were found in the three groups. Conclusions:MMI combined with ALF can effectively treat Graves′ disease, reduce the dosage of MMI drugs, decline the level of TRAb in the serum of Graves′ patients, and improve the prognosis of Graves′ disease.

Clinical efficacy of methimazole in the treatment of hyperthyroidism / 中国基层医药

Objective:To investigate the clinical efficacy of methimazole in the treatment of hyperthyroidism.Methods:A total of 110 patients with hyperthyroidism who received treatment in Zhuji Central Hospital between January 2016 and June 2019 were included in this study. They were randomly assigned to receive treatment either with propylthiouracil (control group, n = 55) or methimazole (observation group, n = 55) for 6 successive months. Thyroid function indicators, bone metabolism indicators, clinical efficacy, and adverse events were compared between the control and observation groups. Results:After treatment, free triiodothyronine (FT 3), free thyroxine (FT 4) and thyroid stimulating hormone (TSH) levels in the observation group were (4.46 ± 1.02) pmol/L, (14.45 ± 2.16) pmol/L and (1.89 ± 0.64) mU/L respectively, which were significantly lower than those in the control group [(6.37 ± 1.38) pmol/L, (18.54 ± 4.46) pmol/L and (3.47 ± 0.99) mU/L, t = 8.254, 6.121, 9.940, all P < 0.05). Calcitonin level in the observation group was significantly higher than that in the control group [(68.62 ± 6.75) ng/L vs. (61.45 ± 6.47) ng/L, t = 5.687, P < 0.05]. Bone Gla-protein level in the observation group was significantly lower than that in the control group [(6.38 ± 1.64) ng/L vs. (8.21 ± 2.19) ng/L, t = 4.960, P < 0.05]. Total effective rate in the observation group was significantly higher than that in the control group [92.73% (51/55) vs. 78.18% (43/55), χ2= 4.681, P < 0.05]. Adverse reaction rate in the observation group was significantly lower than that in the control group [9.09% (5/55) vs. 25.45% (14/55), χ2= 5.153, P < 0.05]. Conclusion:Methimazole is safe and effective in the treatment of hyperthyroidism, which can effectively improve thyroid function and bone metabolism. This study is of certain clinical significance and innovation.

Pharmaceutical care for a patient with pancytopenia and liver injury induced by methimazole / 药学实践杂志

Objective To explore the treatment of pancytopenia and liver injury induced by methimazole and provide medication therapy reference for clinical pharmacists in clinical practice. Methods The clinical pharmacists provided clinical interventions by the evaluation of adverse drug reactions, assessment of the therapeutic effects, adjustment of therapeutic regime based on the patient′s disease condition. Results The physician adopted the recommendations from the clinical pharmacists. The patient with pancytopenia and liver injury induced by methimazole gradually recovered with biochemical indices back to normal levels. Conclusion The therapeutic outcome was improved with clinical pharmacist’s knowledge on medication, optimization of therapeutic regime and implement of pharmaceutical care.

Utilidad del carbonato de litio, yoduro inorgánico y plasmaféresis en una paciente con hipertiroidismo severo y agranulocitosis por tiamazol en tiempos de COVID-19 / Usefulness of lithium carbonate, inorganic iodide and plasmapheresis in a patient with severe hyperthyroidism and agranulocytosis due to thiamazole in times of COVID-19

RESUMEN Mujer de 43 años con diagnóstico reciente de enfermedad de Graves-Basedow ingresa a urgencias por infección de tejidos blandos, agranulocitosis por tiamazol e hipertiroidismo descompensado. La paciente requería tratamiento definitivo para hipertiroidismo, pero dado el contexto de la pandemia por SARS-CoV-2 no se contaba con yodo radioactivo (131I) por lo que se planteó la tiroidectomía total. Se necesitaba una preparación preoperatoria rápida y eficaz por lo que se decidió compensar su hipertiroidismo con lugol, carbonato de litio, dexametasona y finalmente plasmaféresis antes de cirugía. Con ello se logró disminuir los niveles de hormonas tiroideas en el tiempo deseado y se procedió al tratamiento quirúrgico definitivo. Se presenta el caso por lo anecdótico y por ser necesario el conocimiento del manejo en escenarios, como esta pandemia, donde no haya acceso a 131I.

ABSTRACT A 43-year-old woman with a recent diagnosis of Graves-Basedow disease was admitted to the emergency room due to soft tissue infection, thiamazole agranulocytosis, and severe hyperthyroidism. The patient required definitive treatment for hyperthyroidism, but given the context of the SARS-COV-2 pandemic, radioactive iodine was not available, so she prepared for total thyroidectomy. A rapid and effective preoperative preparation was required, so it was decided to compensate her hyperthyroidism with lugol, lithium carbonate, dexamethasone and finally plasmapheresis before surgery. Thyroid hormone levels normalized in a short time, and the thyroidectomy was performed. The case is presented because of the anecdotal and because knowledge of management in scenarios, such as this pandemic, where there is no access to 131I.

Novel Selective Spectrophotometric Methods For The Determination Of Methimazole In Pure Form And In Pharmaceutical Formulation

Objective: To develop and validate new, selective spectrophotometric colorimetric analytical methods for the quantification of methimazole in its pure form and in its pharmaceutical preparations. Methods: Method A is based on the oxidation of methimazole with potassium permanganate in alkaline medium, the manganate ion produced was measured at λmax= 610 nm. Method B is a kinetic determination of methimazole using fixed-time method based on the oxidation of methimazole using known excess of cerium (IV) nitrate in acidic medium and assessing the unreacted Ce (IV) by adding a fixed amount of methyl orange and measuring the absorbance of the resultant solution at λmax=507 nm which is equivalent to the unreacted methyl orange. The reaction conditions and analytical parameters are investigated and optimized. Method validation was carried out according to ICH guidelines in terms of linearity, LOD, LOQ, precision, and accuracy. Results: Beer’s law is obeyed in the range of 1.50–15.00 μg/ml for method A and 0.25–3.00 μg/ml for method B. The developed methods were subjected to the detailed validation procedure. The proposed spectrophotometric methods were applied for the determination of the methimazole in its pure form and in its pharmaceutical formulation. The percentage recoveries were found to be 100.82 % and 99.85 % in the pharmaceutical formulation for the two proposed methods, respectively. Conclusion: Both developed spectrophotometric methods, considered as green analytical chemistry, were found to be novel, highly selective and can be applied for the quality control of methimazole in its pure form and in its pharmaceutical formulation based on the simplicity, applicability of the parameters, accessibility of the reagents employed and reasonably low time of analysis.

Embarazo y lesión hepática inducida por medicamentos. Reporte de un caso y revisión de la literatura / Pregnancy and drug-induced liver injury. Case report and literature review

La lesión hepática inducida por medicamentos o DILI (del inglés, Drug-Induced Liver Injury) es una condición relativamente rara, y más aún durante el embarazo. Usualmente es subdiagnosticada, y cuando se presenta en nuestro medio, pocas veces es notificada a los sistemas de registros nacionales, con un importante subregistro a nivel nacional y de Latinoamérica. Su forma de presentación clínica, tiempo de latencia, patrón de lesión hepática y reacciones idiosincráticas dificultan el diagnóstico oportuno, así como la ausencia tanto de pruebas diagnósticas objetivas, como de cambios histológicos patognomónicos que confirmen esta entidad. Se presenta el primer caso reportado en la literatura de una mujer en primer trimestre de gestación, quien cursó con DILI secundario al uso de tionamidas por sospecha clínica de hipertiroidismo.

Drug-induced liver injury (DILI) is a relative rare condition among general population and among pregnant women. It is usually underdiagnosed, and when identified, it is rarely notified to the national registry systems, especially locally, and in general in Latin America. Clinical presentation, time before symptom onset, patterns of liver injury and idiosyncratic reactions make an early diagnosis difficult, as well as the absence of diagnostic tests or histological changes that are unique to this pathology to confirm the diagnosis. We present the first case reported in the literature of a woman, who during the first trimester of pregnancy presented with DILI, secondary to the use of thionamides due to suspected hyperthyroidism.

Clinical characteristics of insulin autoimmune syndrome caused by methimazole in Chinese population / 中国临床药理学与治疗学

AIM: To explore the clinical features of insulin autoimmune syndrome (IAS) induced by methimazole in Chinese population. METHODS: The literature on IAS cases caused by methimazole in the Chinese population published before and after June 30, 2019 was collected for retrospective analysis.RESULTS:The age of onset of men was earlier than that of women, and the sex ratio was 1:2.31 in 95 patients.After taking methimazole 30 mg/d, IAS occurred most from one month to three months,characterized by neuropathic hypoglycemia as the first symptoms at night and early in the morning,blood sugar below 2 mmol/L,insulin concentration≥100 mU/L, IAA positive and no obvious abnormalities in pancreas imaging.The symptoms gradually relieved after symptomatic treatment and stopped taking methimazole. There was no significant difference in the time of hypoglycemia disappearance between the 54 patients who received hormone therapy and non-hormone therapy.CONCLUSION:Methimazole-induced IAS is a clinically rare autoimmune disease. It should be treated promptly occuring hypoglycemia or hyperglycemia during medication.The prognosis of IAS is generally good after proper treatment.

Antineutrophil cytoplasmic antibodies in patients treated with methimazole: a prospective Brazilian study / Anticorpos anticitoplasma de neutrófilos em pacientes tratados com metimazol: um estudo prospectivo brasileiro

Abstract Introduction: The side effects of antithyroid drugs are well known. Antineutrophil cytoplasmic antibody-associated vasculitis is a severe adverse reaction. Most studies evaluating antineutrophil cytoplasmic antibodies related to antithyroid drugs have been carried out with patients treated with propylthiouracil, but less information is available for methimazole. Furthermore, most studies that investigated antineutrophil cytoplasmic antibodies related to antithyroid drugs were conducted on Asian populations. Objective: To evaluate the frequency of antineutrophil cytoplasmic antibodies and antineutrophil cytoplasmic antibodies-positive vasculitis in an adult population of Brazilian patients treated with methimazole. Methods: This was a prospective study. We evaluated patients ≥18 years with Graves' disease who have been using methimazole for at least 6 months (Group A, n = 36); with Grave's disease who had been previously treated with methimazole but no longer used this medication for at least 6 months (Group B, n = 33), and with nodular disease who have been using methimazole for at least 6 months (Group C, n = 13). Results: ANCA were detected in 17 patients (20.7%). Four patients (4.9%) had a strong antineutrophil cytoplasmic antibodies-positive test. The frequency of antineutrophil cytoplasmic antibodies was similar in the groups. When Groups A and B were pooled and compared to Group C to evaluate the influence of Grave's disease, and when Groups A and C were pooled and compared to Group B to evaluate the influence of methimazole discontinuation, no difference was found in the frequency of antineutrophil cytoplasmic antibodies. No difference was observed in sex, age, etiology of hyperthyroidism, anti-TSH receptor antibodies, dose or time of methimazole use between patients with versus without antineutrophil cytoplasmic antibodies. The titers of these antibodies were not correlated with the dose or time of methimazole use. None of the antineutrophil cytoplasmic antibodies-positive patient had clinical event that could potentially result from vasculitis. Conclusion: This clinical study of a Brazilian population shows a considerable frequency of antineutrophil cytoplasmic antibodies in patients treated with methimazole but the clinical repercussion of these findings remains undefined.

Resumo Introdução: Os efeitos adversos de drogas antitireoidianas são conhecidos. Vasculite associada a anticorpos anticitoplasma de neutrófilos é uma reação adversa grave. A maioria dos estudos que avaliam anticorpos anticitoplasma de neutrófilos relacionado a drogas antitireoidianas envolveu pacientes tratados com propiltiouracil, entretanto menos informação se encontra disponível para o metimazol. Além disso, a maioria dos estudos que investigaram anticorpos anticitoplasma de neutrófilos relacionado a drogas antitireoidianas foi conduzida em populações asiáticas. Objetivo: Avaliar a frequência de anticorpos anticitoplasma de neutrófilos e vasculite anticorpos anticitoplasma de neutrófilos-positivo em uma população adulta de pacientes brasileiros tratados com metimazol. Método: Este foi um estudo prospectivo. Avaliamos pacientes ≥ 18 anos com doença de Graves com o uso de metimazol há pelo menos seis meses (Grupo A, n = 36); com doença de Graves previamente tratados com metimazol, mas que não usaram esse medicamento por pelo menos seis meses (Grupo B, n = 33) e com doença nodular em uso de metimazol há pelo menos seis meses (Grupo C, n = 13). Resultado: Anticorpos anticitoplasma de neutrófilos foram detectados em 17 pacientes (20,7%). Quatro pacientes (4,9%) tinham anticorpos anticitoplasma de neutrófilos fortemente positivos. A frequência de anticorpos anticitoplasma de neutrófilos foi semelhante nos grupos. Quando os Grupos A e B foram somados e comparados ao Grupo C para avaliar a influência da doença de Graves, e quando os Grupos A e C foram somados e comparados ao Grupo B para avaliar a influência da interrupção do metimazol, não foi encontrada diferença na frequência de anticorpos anticitoplasma de neutrófilos. Não houve diferença em relação a sexo, idade, etiologia do hipertireoidismo, anticorpos antirreceptor de TSH, dose ou tempo de uso de metimazol entre pacientes com e sem anticorpos anticitoplasma de neutrófilos. Os títulos desses anticorpos não se correlacionaram com dose ou tempo de uso de metimazol. Nenhum paciente anticorpos anticitoplasma de neutrófilos-positivo apresentou evento clínico resultante de vasculite. Conclusão: Este estudo clínico de uma população brasileira apresenta frequência considerável de anticorpos anticitoplasma de neutrófilos em pacientes tratados com metimazol, mas a repercussão clínica desse achado permanece indefinida.

Neutropenia febril asociada a la ingesta de metimazol: reporte de caso / Febrile neutropenia associated with methimazole ingestion: case report

La neutropenia se define como un recuento absoluto de neutrófilos menor a 1500 células /µL. Se debe a la disminución en la producción de granulocitos o al aumento en su destrucción, ya sea a nivel medular o periférico. Según la clasificación de la Organización Mundial de la Salud (OMS) los grados de neutropenia van de 0 a IV, de acuerdo a la magnitud de la disminución del recuento de neutrófilos. El grado IV es el de mayor riesgo y corresponde a recuentos por debajo de 500 células/µL. El impacto en la morbimortalidad asociada a la neutropenia no está vinculado con la disminución directa del recuento celular, sino con los procesos infecciosos asociados a los que son propensos los pacientes que la presentan. Existen diversas condiciones por las que se puede desarrollar neutropenia, entre las que se encuentran las infecciones, las malignidades y los fármacos. Estos últimos pueden generar eventos adversos por mecanismos dosis dependiente, como en el caso de la quimioterapia citotóxica o por una reacción idiosincrática. Se presenta el caso de una paciente femenina de 37 años de edad, con antecedentes de tirotoxicosis, tratada con propanolol y metimazol durante cuatro semanas, quien además de manifestaciones tóxicas, presentó neutropenia febril muy grave, que mejoró luego de suspensión del antitiroideo. Se pretende resaltar la asociación de neutropenia febril como complicación de uso de tionamidas y la importancia del seguimiento con exámenes de laboratorios para un diagnóstico oportuno(AU)

Neutropenia is defined as an absolute neutrophil count less than 1500 cells / μL. It is due to the decrease in the production of granulocytes or increase in their destruction, either at the medullary or peripheral level. According to the classification of the World Health Organization (WHO) the degrees of neutropenia range from 0 to IV, taking into account the magnitude of the decrease in the neutrophil count. Grade IV is the highest risk and corresponds to counts below 500 cells /μL. The impact on morbidity and mortality associated with neutropenia is not linked to the direct reduction of the cell count, but to the associated infectious processes to which patients who present it are prone. There are several conditions under which neutropenia can develop, including infections, malignancies and drugs. The latter can generate adverse effects by dose-dependent mechanisms, as in the case of cytotoxic chemotherapy or an idiosyncratic reaction. Next, the case of a female patient of thirty-seven years of age, with a history of thyrotoxicosis, treated with propanolol and methimazole for four weeks, who in addition to toxic manifestations, presents very severe febrile neutropenia that improves after suspension of the antithyroid. We aim to highlight the association of febrile neutropenia as a complication of thionamide use and the importance of follow-up with laboratory tests for an opportune diagnosis(AU)

Debilidad muscular con hipokalemia e hipertiroidismo en un adolescente con síndrome de Down / Muscle weakness with hypokalemia and hyperthyroidism in an adolescent with Down syndrome

La hipokalemia aguda es una causa poco frecuente de debilidad muscular. La parálisis periódica tirotóxica es una complicación infrecuente de la tirotoxicosis, en sus diferentes etiologías, en la cual se produce hipokalemia por un flujo masivo de potasio al compartimiento intracelular, que provoca parálisis muscular, que afecta, principalmente, la musculatura proximal de los miembros inferiores. Es importante reconocer esta entidad para instaurar un tratamiento adecuado que incluya el rápido suplemento de potasio y el uso de beta-bloqueantes no selectivos. El tratamiento del hipertiroidismo subyacente y el retorno al estado eutiroideo es imprescindible para la resolución de los episodios de parálisis periódica tirotóxica. Aquí se presenta a un paciente de 13 años de edad con síndrome de Down que consultó por debilidad muscular de los miembros inferiores y trastorno de la marcha, asociada a hipokalemia aguda, en el que se realizó el diagnóstico de hipertiroidismo por enfermedad de Graves.

Acute hypokalemic paralysis is a rare cause of acute weakness. Thyrotoxic periodic paralysis (TPP) is an unusual complication of hyperthyroidism. It is characterized by sudden onset of hypokalemia condition resulting from a shift of potassium into cells and paralysis that primarily affects the lower extremities. Failure to recognize TPP may lead to improper management. Treatment of TPP includes replacing potassium rapidly, using nonselective beta-blockers and correcting the underlying hyperthyroidism as soon as possible. TPP is curable once euthyroid state is achieved. We describe a 13-year-old male with Down syndrome who presented with acute onset of lower extremity weakness secondary to acute hypokalemia and was found to have new onset Graves' disease.

Treatment of patients with hyperthyroidism complicated with liver failure with methimazole cream: a report of 2 cases and literature review / 吉林大学学报(医学版)

Objective: To investigate the efficacy of local application of methimazole cream in the patients with hyperthyroidism complicated with liver failure∗ and to provide reference for its clinical treatment. Methods: Two patients were admitted to hospital with jaundice as the main performance. Liver function and coagulation function supported the diagnosis of liver failure. The thyroid function indicators suggested hyperthyroidism. Combined with other related examination results∗ liver failure, hyperthyroidism and hepatitis B virus were diagnosed, and the local treatment of methimazole cream and other related treatments were given. Results: After treatment, the liver function of two patients returned to normal and the thyroid function was improved. After follow-up, one patient changed the external use of methimazole cream to oral treatment, and another patient was still treated in a local manner. Conclusion: There is a conflict in the treatment of hyperthyroidism complicated with liver failure. The local application of methimazole cream in the topic of reducing the risk of liver damage caused by drugs has good results in the treatment of hyperthyroidism. This method also provides the new ideas for its clinical treatment.

Comparison of effects of propylthiouracil and methimazole on pregnancy outcomes and glucose and lipid metabolism in patients with hyperthyroidism in pregnancy / 国际检验医学杂志

Objective To compare the effects of propylthiouracil and methimazole on pregnancy outcomes and glucose and lipid metabolism in patients with hyperthyroidism in pregnancy, and to analyze the security.Methods Totally 92patients with hyperthyroidism in pregnancy were divided into the observation group (46cases) and control group (46cases).Patients in both groups were given routine adjuvant therapy, such asβ-blocker, liver protection, increasing white blood cells.The patients in observation group were treated with propylthiouracil while the patients in control group were treated with methimazole.The thyroxine levels (TSH, T3, T4, FT3, FT4), pregnancy outcomes, glucose and lipid metabolism (FPG, FINS, TC, TG), liver function indicators (ALT, ALP, AST) and maternal complications of two groups were compared after treatment for 3months.Results The TSH level of the observation group was significantly higher than that of the control group, and the T3, T4, FT3, FT4levels of the observation group were significantly lower than those of the control group (P＜0.05).The incidence of premature birth, miscarriage, intrauterine fetal death, fetal distress and gestational hypertension of observation group were significantly lower than those of the control group, but the incidence of full-term production of observation group was significantly higher than that of the control group (P＜0.05).The FPG, FINS, TC and TG levels of the observation group were significantly lower than those of the control group (P＜0.05).The increased amplitude of ALT, ALP, AST of the observation group were significantly lower than those of the control group (P＜0.05).There were puerperal infection, hyperthyroid heart disease, diabetes, oligohydramnios, placental abruption, pregnancy-induced hypertension and other complications occurred in both two groups, but the incidence of the observation group were significantly lower than those of the control group (P＜0.05).Conclusion Compared with methimazole, propylthiouracil is more beneficial to improve thyroid function, pregnancy outcome and glucose and lipid metabolism in patients with hyperthyroidism in pregnancy, and has higher security.

Treatment of patients with hyperthyroidism complicated with liver failure with methimazole cream:A report of 2 cases and literature review / 吉林大学学报(医学版)

Objective:To investigate the efficacy of local application of methimazole cream in the patients with hyperthyroidism complicated with liver failure, and to provide reference for its clinical treatment.Methods:Two patients were admitted to hospital with jaundice as the main performance.Liver function and coagulation function supported the diagnosis of liver failure.The thyroid function indicators suggested hyperthyroidism.Combined with other related examination results, liver failure, hyperthyroidism and hepatitis B virus were diagnosed, and the local treatment of methimazole cream and other related treatments were given.Results:After treatment, the liver function of two patients returned to normal and the thyroid function was improved.After follow-up, one patient changed the external use of methimazole cream to oral treatment, and another patient was still treated in a local manner.Conclusion:There is a conflict in the treatment of hyperthyroidism complicated with liver failure.The local application of methimazole cream in the topic of reducing the risk of liver damage caused by drugs has good results in the treatment of hyperthyroidism.This method also provides the new ideas for its clinical treatment.

Patrones de prescripción de medicamentos antitiroideos en una población de Colombia / Patterns of prescription of antithyroid drugs in a Colombian population

Resumen Introducción: en Colombia no se conoce la prevalência de los trastornos asociados a tirotoxicosis ni se dispone de estudios fármacoepidemiológicos acerca de la prescripción de los medicamentos antitiroideos. Objetivo: determinar los patrones de prescripción de los antitiroideos y variables asociadas a su uso en una población de pacientes en Colombia. Métodos: estudio de corte transversal, realizado entre enero 1 y marzo 30 de 2015 sobre los hábitos de prescripción de medicamentos antitiroideos en una población afiliada al sistema de salud colombiano. Se midieron variables sociodemográficas, farmacológicas y de comedicación. Se diseñó una base de datos sobre el consumo de medicamentos y se utilizaron pruebas t de student, X 2 y modelos de regresión logística. Resultados: un total de 327 pacientes en tratamiento con medicamentos antitiroideos fueron incluidos. La edad media fue de 53.7±18.1 años y 78.3% de pacientes correspondió a mujeres. El metimazol se prescribió en 95.4% de los pacientes, el propiltiouracilo en 4.6%. En 76.8% de pacientes se presentó comedicación; en particular con antihipertensivos (38.2%) y adicionalmente con propranolol (34.3%). Conclusiones: la tendencia de prescripción de medicamentos antitiroideos en Colombia es similar a lo reportado en diferentes estudios a nivel mundial. El principal medicamento antitiroideo es metimazol, con una tasa de uso mayor a la reportada en Norteamérica y en estudios europeos. Las dosis del metimazol y de propiltiouracilo reportadas en este estudio se ajustan a las recomendaciones de la Asociación Americana de Endocrinología Clínica.

Abstract Introduction: the prevalence of disorders associated with thyrotoxicosis is not known in Colombia, nor pharmacoepidemiological studies are available on the prescription of antithyroid drugs. Objective: to determine the prescription patterns of antithyroid drugs and variables associated with their use in a population of Colombian patients. Methods: cross-sectional study, conducted between January 1 and March 30, 2015 on the prescription habits of antithyroid drugs in a population affiliated with the Colombian Health System. Sociodemographic, pharmacological and comedication variables were measured. A database on drug consumption was designed and student t-tests, X 2 and logistic regression models were used. Results: a total of 327 patients in treatment with antithyroid drugs were included. The mean age was 53.7 ± 18.1 years and 78.3% of patients corresponded to women. Methimazole was prescribed in 95.4% of patients, propylthiouracil in 4.6%. In 76.8% of patients, comedication was present in particular with antihypertensive agents (38.2%) and additionally with propranolol (34.3%). Conclusions: the prescription tendency of antithyroid drugs in Colombia is similar to that reported in different studies worldwide. The main antithyroid drug is methimazole, with a rate of use higher than that reported in North America and in European studies. The doses of methimazole and propylthiouracil reported in this study are in accordance with the recommendations of the American Association of Clinical Endocrinology.