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Oncotarget Jan 2016Methimazole is commonly prescribed for patients who are thyrotoxic. Cholestatic hepatitis is a rare but serious adverse event which may be associated with interventional...
Methimazole is commonly prescribed for patients who are thyrotoxic. Cholestatic hepatitis is a rare but serious adverse event which may be associated with interventional therapy. In this case report, we present two Chinese women with cholestatic jaundice due to methimazole treatment. Both patients had a history of hyperthyroidism; initial laboratory studies of liver function were normal and cholestatic hepatitis occurred after treatment with methimazole. Concomitant liver disease, such as viral hepatitis (A, B, C, D, E), autoimmune hepatitis, primary biliary cirrhosis and calculus of bile duct, were excluded. Liver enzyme levels in both patients returned to normal after stopping methimazole therapy and taking hepatoprotective drugs. It is essential that patients are informed about the earliest symptoms of serious adverse effects of antithyroid drugs, such as hepatic toxicity, and that they are advised to stop taking the drug immediately and contact their physician if such symptoms occur.
Topics: Adult; Anti-Inflammatory Agents; Antithyroid Agents; Drug-Related Side Effects and Adverse Reactions; Female; Hepatitis; Humans; Hyperthyroidism; Jaundice, Obstructive; Methimazole; Methylprednisolone; Middle Aged; Prognosis
PubMed: 26498145
DOI: 10.18632/oncotarget.6144 -
Endocrinologia Japonica Oct 1986Serum and urinary concentrations of methimazole (MMI) were measured by high-performance liquid chromatography (HPLC) with an electrochemical detector (ECD) in 10 normal...
Serum and urinary concentrations of methimazole (MMI) were measured by high-performance liquid chromatography (HPLC) with an electrochemical detector (ECD) in 10 normal subjects and 43 hyperthyroid patients after intravenous and oral administration of the drug. The pharmacokinetic parameters of MMI were estimated in 5 normal subjects and 15 hyperthyroid patients according to a two-compartment model after intravenous injection of a 10 mg dose. The mean half-life of the distribution phase (T1/2 alpha) was 2.7 +/- 1.0 h (mean +/- SD) and 3.1 +/- 1.4 h and that of the slower-phase (T1/2 beta) was 20.7 +/- 9.6 h and 18.5 +/- 12.9 h in normal subjects and hyperthyroid patients, respectively. There were no significant differences between pharmacokinetic parameters of normal subjects and those of hyperthyroid patients. No correlations between free T4 index (FT4I) and pharmacokinetic parameters were observed. Maximum serum MMI concentrations (Cmax) (213 +/- 84 and 299 +/- 92 ng/ml) were attained 1.8 +/- 1.4 h and 2.3 +/- 0.8 h after a single dose of 10 mg in 5 normal subjects and in 15 hyperthyroid patients, respectively. In hyperthyroid patients the time taken to reach the peak concentration (Tmax) after a single dose of 10 mg was similar to that after a single 15 mg and 30 mg dose. The pharmacokinetic parameters, except Cmax and the area under the curve (AUC), were not affected by the administered dose and those, except Cmax, were not affected by the thyroid function. All urine was collected at intervals of 3 h for the first 12 h and then at 24 h and 48 h after intravenous and oral administration of MMI. In all subjects, MMI rapidly appeared in the urine and the rate of excretion was highest in the first 3 h. The cumulative urinary excretion of MMI was 5.5-8.5% of administered doses in normal subjects and hyperthyroid patients. These findings in the present study are compatible with the assumption that the extent of absorption of MMI is high, if not complete, and hyperthyroidism does not affect the kinetics of MMI, and that interindividual variation is observed in the time taken to reach the peak concentration after oral administration.
Topics: Administration, Oral; Adolescent; Adult; Aged; Chromatography, High Pressure Liquid; Female; Humans; Hyperthyroidism; Injections, Intravenous; Kinetics; Male; Metabolic Clearance Rate; Methimazole; Middle Aged
PubMed: 3830069
DOI: 10.1507/endocrj1954.33.605 -
BMJ Case Reports Jul 2020Paediatric hyperthyroidism cases are mostly caused by Grave's disease. Thyroid storm is a life-threatening condition seen rarely, in severe thyrotoxicosis, occurring in...
Paediatric hyperthyroidism cases are mostly caused by Grave's disease. Thyroid storm is a life-threatening condition seen rarely, in severe thyrotoxicosis, occurring in about 1%-2% of patients with hyperthyroidism. Antithyroid medications and beta-blockers are typically the first-line management of thyroid storm. We report a challenging case of a 15-year-old girl who presented with thyroid storm in the setting of septic shock and methimazole-induced agranulocytosis. Since the first-line agents were contraindicated, plasmapheresis was used to control the thyroid storm and as a bridging therapy to the definitive therapy of early thyroidectomy. This is the first paediatric case report that outlines the use of plasmapheresis in the management of complicated thyrotoxicosis in a setting of septic shock.
Topics: Adolescent; Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Sepsis; Thyroid Crisis
PubMed: 32636230
DOI: 10.1136/bcr-2020-235536 -
Ugeskrift For Laeger Sep 2014The treatment of choice for hyperthyroidism in pregnancy is antithyroid drugs, but the potential risk of birth defects is of major concern. For the use of thiamazole and... (Review)
Review
The treatment of choice for hyperthyroidism in pregnancy is antithyroid drugs, but the potential risk of birth defects is of major concern. For the use of thiamazole and carbimazole, there is consistent evidence of an increased risk of birth defects, which are often severe. For the use of propylthiouracil, the evidence is less clear. These birth defects may be less severe, and a Danish study which included all birth defects diagnosed before the age of two years showed an increased risk of birth defects in the face and neck region and in the urinary system after the use of propylthouracil.
Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Female; Humans; Hyperthyroidism; Infant, Newborn; Methimazole; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Propylthiouracil; Risk Factors
PubMed: 25294327
DOI: No ID Found -
BMC Endocrine Disorders Jan 2019Zinc-α2-glycoprotein (ZAG) is a recently novel lipolytic adipokine implicated in regulation of glucose and lipid metabolism in many metabolic disorders. In vitro and...
BACKGROUND
Zinc-α2-glycoprotein (ZAG) is a recently novel lipolytic adipokine implicated in regulation of glucose and lipid metabolism in many metabolic disorders. In vitro and animal studies suggest that thyroid hormones (TH) up-regulates ZAG production in hepatocytes. However, there is no data evaluating the possible relationship between ZAG and TH in a human model of hyperthyroidism. The objective of the present study is to assess the association of serum ZAG levels with TH and lipid profile in patients with hyperthyroidism before and after methimazole treatment.
METHODS
A total of 120 newly diagnosed overt hyperthyroidism and 122 healthy control subjects were recruited. Of them, 39 hyperthyroidism patients were assigned to receive methimazole treatment as follow-up study for 2 months.
RESULTS
The clinical consequence showed that serum ZAG levels were elevated in patients with hyperthyroidism (P < 0.01). Adjust for age, gender and BMI, serum ZAG levels were positively related with serum free T3 (FT3), free T4 (FT4) levels and negatively correlated with serum total cholesterol (TC), low density lipoprotein cholesterol (LDLC) levels in hyperthyroidism subjects (all P < 0.01). After methimazole treatment, serum ZAG levels were decreased and the decline was associated with decreased FT3, FT4 and increased TC levels (all P < 0.001).
CONCLUSION
We conclude that ZAG may be involved in the pathogenesis of lipid metabolism disorder in patients with hyperthyroidism.
TRIAL REGISTRATION
ChiCTR-ROC-17012943 . Registered 11 October 2017, retrospectively registered.
Topics: Adult; Antithyroid Agents; Biomarkers; Female; Follow-Up Studies; Humans; Hyperthyroidism; Male; Methimazole; Prognosis; Prospective Studies; Seminal Plasma Proteins; Thyroid Hormones; Zn-Alpha-2-Glycoprotein
PubMed: 30670019
DOI: 10.1186/s12902-019-0336-9 -
Medicine Dec 2018Insulin autoimmune syndrome (IAS) is a rare endocrine disease characterized by repeated fasting hypoglycemia or episodes of hypoglycemia late after meals, elevated serum...
RATIONALE
Insulin autoimmune syndrome (IAS) is a rare endocrine disease characterized by repeated fasting hypoglycemia or episodes of hypoglycemia late after meals, elevated serum insulin, and positivity for insulin autoantibody (IAA) or insulin receptor antibody (IRA). We summarize the clinical manifestations and treatment experiences of 3 patients with IAS.
PATIENT CONCERNS
One patient with >20-year history of type 2 diabetes mellitus had irregular episodes of hypoglycemia 2 years of after treatment with insulin. Another patient with a 6-year history of type 2 diabetes mellitus presented irregular episodes of hypoglycemia after 6 months of treatment with insulin. One patient with a history of Graves' disease showed hypoglycemia after administration of thiamazole.
DIAGNOSIS
Serum islet cell antibody (ICA) and glutamic acid decarboxylase antibody (GADA) were negative, while antibody insulin autoantibodies were positive in all the 3 patients. Two patients demonstrated diabetes mellitus after an oral glucose tolerance test, while one had normal glucose tolerance. Furthermore, serum insulin levels significantly elevated and did not matched C peptide levels. No abnormalities were found on enhanced MRI of the pancreas, and all 3 patients were clinically diagnosed with IAS.
INTERVENTIONS
In case one, insulin aspart 30 injection was withdrawn after admission. In addition, the patient was prescribed sublingual acarbose 3 times daily. Two weeks after admission, prednisone acetate was administered orally once daily at night. In case 2, insulin aspart 30 injection was withdrawn after admission, the patient was prescribed sublingual acarbose 3 times daily with a meal. Five days after admission, oral prednisone acetate was administered once daily at night. In case 3, oral propylthiouracil was prescribed and thiamazole withdrawn after admission, and the patient consumed an extra meal before sleeping.
OUTCOMES
At the 3-month follow-up visit, the hypoglycemic episodes had disappeared, serum insulin levels were significantly decreased, and insulin antibody (IA) levels were no longer detectable in all 3 patients.
LESSONS
For those patients with high-insulin hypoglycemia, IAA should be evaluated if serum insulin concentrations are inconsistent with C peptide levels. Therapeutically, a lower dose of glucocorticoids with more appropriate medication timing can be used to achieve good results.
Topics: Adult; Aged; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Diabetes Mellitus, Type 2; Female; Graves Disease; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Methimazole; Middle Aged; Syndrome
PubMed: 30572448
DOI: 10.1097/MD.0000000000013486 -
Neurotoxicology Mar 2017Perinatal hypothyroidism causes serious damage to auditory functions that are essential for vocalization development. In rat pups, perinatal hypothyroidism potentially...
Perinatal hypothyroidism causes serious damage to auditory functions that are essential for vocalization development. In rat pups, perinatal hypothyroidism potentially affects the development of ultrasonic vocalization (USV) as a result of hearing deficits. This study examined the effect of perinatal hypothyroidism on the development of USVs in rat pups. Twelve pregnant rats were divided into three groups and treated with the anti-thyroid drug methimazole (MMI) via drinking water, from gestational day 15 to postnatal day (PND) 21. The MMI concentration (w/v) was 0% (control group), 0.01% (low-dose group), or 0.015% (high-dose group). After birth, the pups were individually separated from the dam and littermates on PNDs 5, 10, 15, and 20, and their USVs were recorded for 5min. On PNDs 5 and 10, compared with the control group, the low- and high-dose groups exhibited reductions of both frequency-modulated and downward USVs. On PND 15, however, the low- and high-dose groups displayed increases in number, duration, and amplitude of USVs compared with those in the control group. Lower body weights were observed for the low- and high-dose groups than for the control group. Total thyroxine concentrations in plasma were dose-dependently reduced. The onset of auditory functions appeared on PNDs 11-14. Thus, the rat pups were unable to hear externally produced USVs before PND 11. USVs emitted on PNDs 5 and 10 might have been spontaneous and independent of the pups' own or littermate-emitted USVs. The developmental retardation of vocalization-related organs or muscles might underlie the acoustic alterations of USVs on PNDs 5 and 10. The greater number, duration, and amplitude of USVs on PND 15, after which the hearing onset occurred, suggested that the elevation of auditory thresholds occurred as a result of hearing deficits in the low- and high-dose groups. Perinatal hypothyroidism appears to have caused acoustic alterations in the USV development.
Topics: Acoustic Stimulation; Acoustics; Age Factors; Analysis of Variance; Animals; Animals, Newborn; Antithyroid Agents; Body Weight; Disease Models, Animal; Dose-Response Relationship, Drug; Hearing Loss; Hypothyroidism; Methimazole; Rats; Rats, Wistar; Reflex, Startle; Thyroid Hormones; Vocalization, Animal
PubMed: 27241349
DOI: 10.1016/j.neuro.2016.05.017 -
Clinical Medicine & Research Sep 2009We describe a 37-year-old man with a 4-month history of episodic muscular weakness, involving mainly lower-limbs. Hypokalemia was documented in one episode and managed... (Review)
Review
We describe a 37-year-old man with a 4-month history of episodic muscular weakness, involving mainly lower-limbs. Hypokalemia was documented in one episode and managed with intravenous potassium chloride. Hyperthyroidism was diagnosed 4 months after onset of attacks because of mild symptoms. The patient was subsequently diagnosed as having thyrotoxic periodic paralysis associated with Graves' disease. Treatment with propranolol and methimazol was initiated and one year later he remains euthyroid and symptom free. Thyrotoxic periodic paralysis is a rare disorder, especially among Caucasians, but it should always be considered in patients with acute paralysis and hypokalemia, and thyroid function should be evaluated.
Topics: Adult; Graves Disease; Humans; Hyperthyroidism; Hypokalemia; Male; Methimazole; Paralyses, Familial Periodic; Potassium Chloride; Propranolol; Treatment Outcome
PubMed: 19625499
DOI: 10.3121/cmr.2009.816 -
Medicine Jan 2020Myalgia and elevated creatine kinase (CK) have been reported during the treatment of hyperthyroid patients. The causes of these symptoms are usually considered to be... (Review)
Review
RATIONALE
Myalgia and elevated creatine kinase (CK) have been reported during the treatment of hyperthyroid patients. The causes of these symptoms are usually considered to be treatments of antithyroid drugs (ATDs), thyroidectomy or radio-iodine (131-I). However, the underlying cause may be the rapid correction of thyrotoxicosis (or relative hypothyroidism), which was usually neglected in clinical practice.
PATIENT CONCERNS
This report describes a case of a 25-year-old female with typical symptoms and laboratory test results of Grave hyperthyroidism. The patient complained about fatigue and myalgia 7 weeks after receiving methimazole (MMI) treatment. Blood tests showed dramatically elevated serum CK level, although free triiodothyronine (FT3) and free thyroxine (FT4) level had returned to the normal reference range. MMI was; therefore, discontinued and the patient's muscular symptoms disappeared quickly with the normalization of CK level and the relapse of hyperthyroidism. Later she received 131-I treatment and suffered similar muscular symptoms when FT3 and FT4 decreased to the normal range. This time, her symptoms were quickly relieved by levothyroxine (L-T4) replacement treatment.
DIAGNOSES
Myopathy induced by rapid correction of hyperthyroidism (or relative hypothyroidism).
INTERVENTIONS
MMI was discontinued after the patient's first episode of muscular symptoms. And for her second episode of muscular injury after 131-I treatment, we initiated L-T4 supplementation.
OUTCOMES
For the 2 episodes of muscular injury after ATDs or 131-I treatment, both of the interventions mentioned above brought a rapid relief of symptoms accompanied with normalization of CK level and restoration of thyroid hormone level.
LESSONS
Myopathy can be caused by a rapid reduction of thyroid hormone during the treatment of hyperthyroidism. This relative hypothyroidism syndrome should be considered if patients make complaints about fatigue and myalgia, even when thyroid hormone level is within the normal range during the antithyroid treatments. Serum CK level and thyroid function should be closely monitored post antithyroid treatments. Reduction of ATD dosage or replacement of thyroid hormone is suggested to relieve muscular symptoms.
Topics: Adult; Antithyroid Agents; Creatine Kinase; Female; Graves Disease; Humans; Methimazole; Myalgia; Recurrence; Thyroxine
PubMed: 32011514
DOI: 10.1097/MD.0000000000018878 -
Biological Trace Element Research Jun 2013The aim of this research was to assess plasma magnesium (Mg) concentration, the frequencies of activated T CD4+ and T CD8+ lymphocytes and B lymphocytes in adolescents...
The aim of this research was to assess plasma magnesium (Mg) concentration, the frequencies of activated T CD4+ and T CD8+ lymphocytes and B lymphocytes in adolescents with hyperthyroidism due to Graves' disease (GD), and to assess changes in the above-mentioned parameters during methimazole (MMI) treatment. The frequencies of activated T and B cells were measured by flow cytometry method and plasma Mg concentration was determined by spectrophotometry method in 60 adolescents at the time of GD diagnosis and after receiving the normalisation of the thyroid hormones levels. The control group consisted of 20 healthy volunteers. We observed lower plasma Mg concentration, and higher frequencies of activated T and B lymphocytes in the study group before the treatment in comparison with healthy controls, and with study group in MMI-induced euthyreosis (p < 0.01).Statistically significant negative correlations between the percentages of activated T CD3+, T CD4+, T CD8+ and B CD19+ lymphocytes, and plasma Mg concentration before the treatment were found (r < -0.335, p < 0.002). After the treatment no vital differences in plasma Mg concentration, and in percentages of activated cells between GD patients and controls were found, except CD8+CD25+ cells (p = 0.03). The present study demonstrates that both activated T and B cells might play an important role in the pathogenesis of GD, and activation is related to Mg plasma level. The use of MMI in treatment of hyperthyroidism due to GD leads to decrease the frequencies of activated lymphocytes and normalisation of Mg levels.
Topics: Adolescent; Antithyroid Agents; Graves Disease; Humans; Lymphocyte Activation; Magnesium; Methimazole
PubMed: 23661330
DOI: 10.1007/s12011-013-9690-z