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Acta Endocrinologica (Bucharest,... 2023Maternal antibodies in cases of chronic autoimmune thyroiditis may be transferred to the baby via the transplacental route, leading to transient hyperthyroidism or...
OBJECTIVES
Maternal antibodies in cases of chronic autoimmune thyroiditis may be transferred to the baby via the transplacental route, leading to transient hyperthyroidism or hypothyroidism. The development of hyperthyroidism in one sibling and hypothyroidism in the other, however, is an extremely rare condition. We present two siblings, one with transient neonatal hyperthyroidism and the other with transient neonatal hypothyroidism, born to a euthyroid mother who was being treated for Hashimoto's thyroiditis.
CASE PRESENTATION
A term male baby was evaluated due to tachycardia, high fT4 and low TSH. Following a diagnosis of Neonatal thyrotoxicosis, the patient was started on methimazole and propranolol treatments. The doses were gradually reduced and methimazole was stopped in the 5 month of treatment. A male baby was referred with elevated TSH identified in the neonatal screening program, with TSH >100 mIU/L and fT4 7.5 pmol/l (N: 12-22) found in a venous blood sample. The patient was started on 50 µg/day LT4, which was gradually decreased and stopped when the baby was 5.5 months old.
CONCLUSION
It should be kept in mind that antibodies may change character in mothers with autoimmune thyroiditis, and may cause different clinical pictures in babies in different pregnancies.
PubMed: 38356967
DOI: 10.4183/aeb.2023.386 -
Fundamental & Clinical Pharmacology Feb 2024Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody...
Comparison of agranulocytosis and anti-neutrophil cytoplasmic antibody-associated vasculitis caused by two antithyroid drugs: A pharmacovigilance study using the WHO international database.
BACKGROUND
Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real-world large pharmacovigilance database.
METHODS
We searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non-case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non-cases). We further analyzed information for the cases of agranulocytosis and AAV.
RESULTS
Among 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake.
CONCLUSIONS
This is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real-world setting.
PubMed: 38342499
DOI: 10.1111/fcp.12991 -
The Journal of Physical Chemistry. B Feb 2024Oxidative reactions of the hydroxyl radical (·OH) with methimazole (MMI), an antithyroid drug, are crucial for understanding its fate in oxidizing environments. By...
Oxidative reactions of the hydroxyl radical (·OH) with methimazole (MMI), an antithyroid drug, are crucial for understanding its fate in oxidizing environments. By synergistically integrating density functional theory and ultraperformance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF MS/MS) techniques, we elucidated the transients and transformation products (TPs) arising from the ·OH-MMI reactions. We probed two hydrogen-atom abstraction (HA) reactions, three radical adduct formation reactions, and single electron transfer (SET) at the M06-2/6-311++G(d,p)/SMD(water) level. All proposed reaction channels, except for HA from the methyl group and SET, were found to be barrier-free. SET is the dominant oxidation pathway, accounting for 44% of oxidations, as determined by branching ratio analysis. The selenium analogue, MSeI, exhibited minor reactivity differences compared to MMI, yet its overall patterns resembled those of ·OH-MMI reactions. TPs were generated experimentally by reacting MMI with ·OH produced by UV-photolysis of HO. Eight TPs were identified from an approximately 24% degradation of MMI using UPLC-Q-TOF MS/MS analysis, and an additional two TPs were identified from the approximately 52% degraded MMI sample. The exact identities of all of the TPs were established through their corresponding fragmentation patterns. This study elucidates the drug's susceptibility to free radical species under physiologically relevant conditions.
PubMed: 38320124
DOI: 10.1021/acs.jpcb.3c07913 -
Endocrine Practice : Official Journal... Apr 2024To assess response predictors to radioactive iodine (RAI) therapy without using thyroid uptake for dose estimate in patients pretreated with methimazole.
OBJECTIVE
To assess response predictors to radioactive iodine (RAI) therapy without using thyroid uptake for dose estimate in patients pretreated with methimazole.
METHODS
Retrospective analysis was performed of patients with Graves' disease treated with RAI doses determined without using uptake studies.
RESULTS
In 242 patients (median age, 41.9 years; 66.1% female), initial mean free thyroxine (FT4) level was 4.7 ng/dL with an estimated thyroid size of 49.15 g. Prior to RAI therapy, average methimazole dose was 22.7 mg/day. Mean RAI dose was 737.0 ±199.4 MBq (19.9 ± 5.4 mCi). Two hundred eight patients (85.9%) responded to RAI therapy; 185 (88.9%) became hypothyroid and 23 (11.1%) became euthyroid. The majority (90.4%) responded within 6 months of therapy with a quicker response (13.9 ± 8.3 vs 17.5 ± 13.5 weeks) for those treated with doses per gram of ≥14.8 MBq (0.4 mCi). Thirty-four nonresponders had a higher initial FT4 level and larger thyroid size with a lower RAI dose per gram of thyroid tissue. In multivariate analysis, the independent response predictor to therapy was dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) (hazard ratio, 3.18; 95% CI, 1.1-9.7). Doses per gram of 14.8 to 18.1 MBq (0.4-0.5 mCi) achieved maximal response rate without added advantage of higher doses. Thyroid size prior to RAI therapy, FT4 levels at diagnosis, and age were inversely related to response.
CONCLUSION
RAI therapy for Graves' disease without uptake studies for dose estimates is an effective treatment method. In patients pretreated with methimazole, an RAI dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) showed high response rate. Prospective studies are needed to confirm the viability of this simplified and cost-effective approach.
Topics: Humans; Female; Adult; Male; Methimazole; Iodine Radioisotopes; Retrospective Studies; Thyroid Neoplasms; Graves Disease
PubMed: 38307459
DOI: 10.1016/j.eprac.2024.01.010 -
AACE Clinical Case Reports 2024To report a case of adenomyosis in a woman with hyperprolactinemia which resolved after initiation of dopamine agonist therapy.
BACKGROUND/OBJECTIVE
To report a case of adenomyosis in a woman with hyperprolactinemia which resolved after initiation of dopamine agonist therapy.
CASE REPORT
A 35-year-old woman with a history of Graves' disease was referred for evaluation of hyperthyroidism in March 2020. She was started on methimazole and thyroid function normalized. The patient also had a history of a pituitary microadenoma and was previously treated with cabergoline which was stopped after 12 months as she became pregnant.In July 2020, the patient began to have polymenorrhea. Hyperprolactinemia was thought to be an unlikely cause as it most often causes hypogonadotropic hypogonadism with amenorrhea. A pelvic ultrasound demonstrated a bulky uterus with adenomyosis. Gynecology recommended treating adenomyosis by lowering her prolactin levels. She was started on cabergoline 0.25 mg weekly in October 2021. Within 2 months of initiation of cabergoline, she had resolution of symptoms and radiological resolution of adenomyosis.
DISCUSSION
Prolactin has been implicated in the pathogenesis of adenomyosis, endometriosis and leiomyomas suggesting that a decrease in prolactin levels may suppress these lesions. The pathogenesis of adenomyosis has been related to direct prolactin effects in the promotion of gland/cell proliferation and function.
CONCLUSION
We conclude that prolonged elevation in prolactin may result in the development of adenomyosis and subsequent prolonged abnormal uterine bleeding. Dopamine agonists, like cabergoline, inhibit the synthesis and secretion of prolactin from the pituitary gland and may have a role in the management of adenomyosis in patients with hyperprolactinemia.
PubMed: 38303768
DOI: 10.1016/j.aace.2023.11.002 -
Hormone Research in Paediatrics Jan 2024Agranulocytosis is a rare, but serious complication of methimazole (MMI) use for Graves' disease (GD). Treatment requires discontinuation of MMI, and the use of...
INTRODUCTION
Agranulocytosis is a rare, but serious complication of methimazole (MMI) use for Graves' disease (GD). Treatment requires discontinuation of MMI, and the use of propylthiouracil (PTU) is also contraindicated. Few reports exist about the optimal alternative treatment regimens for the management of thyrotoxicosis in these medically complex patients in the pediatric population.
CASE REPORT
We report prolonged saturated solution of potassium Iodide (SSKI) use (29 days) in a 17-year-old female with GD and MMI-induced agranulocytosis, who presented with septic shock. Her treatment course also included beta-blockade, cholestyramine, and granulocyte colony stimulating factor. We performed a review of the literature on the use of SSKI in the management of thyrotoxicosis, as well as best practices from the view of endocrinology, infectious disease, hematology, surgery, and intensivists, for the evaluation and management of MMI-induced agranulocytosis.
DISCUSSION
The management of MMI-induced agranulocytosis and associated sequelae require subspecialty input and intensive evaluation and monitoring. Alternative treatments to manage hyperthyroidism and control symptoms of thyrotoxicosis during agranulocytosis are a bridge to definitive therapy, and include beta-blockade, SSKI, cholestyramine, steroids, lithium, and plasmapheresis.
PubMed: 38295777
DOI: 10.1159/000536508 -
Cureus Dec 2023A systematic assessment is crucial to confirm the diagnosis of pulmonary hypertension (PH) and classify it based on its etiological mechanism. This case report describes...
A systematic assessment is crucial to confirm the diagnosis of pulmonary hypertension (PH) and classify it based on its etiological mechanism. This case report describes a young woman with a recent diagnosis of Graves' disease who presented with exertional dyspnea and fatigue. The initial ultrasound heart examination indicated moderate tricuspid regurgitation, an increased estimated systolic pulmonary artery pressure (sPAP), and suggestive alterations of atrial septal communication. For a more detailed characterization of this aspect, a transesophageal echocardiogram (TEE) was performed, which confirmed, through the agitated saline injection method, the presence of a patent foramen ovale (PFO). Further investigation for common causes of pulmonary hypertension yielded negative results. Treatment with methimazole and radioiodine ablation with glucocorticoid coverage was made. One year later, the patient reached a euthyroid state and reported an improvement in the symptoms. Follow-up transthoracic echocardiogram revealed resolution of pulmonary hypertension, with a normal sPAP and normal-sized right chambers. Right heart catheterization confirmed the normal findings. Hyperthyroidism is considered a potential cause of pulmonary hypertension through the effects of high cardiac output and autoimmune-induced pulmonary vascular endothelium injury. As such, it should be included in the etiological investigation of suspected pulmonary hypertension, as its cardiovascular manifestations may be completely reversible without the need for targeted therapy.
PubMed: 38292963
DOI: 10.7759/cureus.51377 -
Thyroid hormone resistance and large goiter mimicking infiltrative carcinoma in a pediatric patient.Journal of Pediatric Endocrinology &... Feb 2024Resistance to thyroid hormone (RTH) is a genetic condition, caused by mutations in the thyroid hormone receptor gene and characterized by impaired end organ...
OBJECTIVES
Resistance to thyroid hormone (RTH) is a genetic condition, caused by mutations in the thyroid hormone receptor gene and characterized by impaired end organ responsiveness to thyroid hormone. Here we describe a novel case of THR associated with large goiter mimicking infiltrative c.
CASE PRESENTATION
A 13-year-old male with a hyperthyroid phenotype of RTH diagnosed as a toddler, on methimazole and nadolol therapies presented with an increase in goiter size and possible nodule. Thyroid ultrasound was concerning for a diffuse infiltrative process or malignancy. Methimazole was discontinued and he underwent further imaging, fine needle aspiration and core biopsies. Biopsy results were reassuring and imaging findings were subsequently attributed to RTH rather than malignancy. He started every other day liothyronine therapy, which led to a decrease in goiter size, thyroglobulin level, and improvement of hyperthyroid symptoms.
CONCLUSIONS
This is the first case to our knowledge describing the above thyroid imaging findings in association with RTH. It also adds important information to the pediatric literature regarding management of the hyperthyroid phenotype of RTH, including the role of liothyronine therapy.
Topics: Male; Humans; Child; Adolescent; Thyroid Hormone Resistance Syndrome; Triiodothyronine; Methimazole; Thyroid Hormones; Goiter; Hyperthyroidism; Carcinoma
PubMed: 38272022
DOI: 10.1515/jpem-2023-0466 -
Spectrochimica Acta. Part A, Molecular... Apr 2024Excessive use of antithyroid drug methimazole (MMI) in pharmaceutical samples can cause hypothyroidism and symptoms of metabolic decline. Hence, it is urgent to develop...
Excessive use of antithyroid drug methimazole (MMI) in pharmaceutical samples can cause hypothyroidism and symptoms of metabolic decline. Hence, it is urgent to develop rapid, low cost and accurate colorimetric method with peroxidase-like nanozymes for determination of MMI in medical, nutrition and pharmaceutical studies. Herein, Fe single atoms were facilely encapsulated into N, P-codoped carbon nanosheets (Fe SAs/NP-CSs) by a simple pyrolysis strategy, as certified by a series of characterizations. UV-vis absorption spectroscopy was employed to illustrate the high peroxidase-mimicking activity of the resultant Fe SAs/NP-CSs nanozyme through the typical catalysis of 3,3',5,5'-tetramethylbenzidine (TMB) oxidation. The catalytic mechanism was scrutionously investigated by the fluorescence spectroscopy and electron paramagnetic resonance (EPR) tests. Additionally, the introduced MMI had the ability to reduce the oxidation of TMB (termed oxTMB) as a peroxidase inhibitor, coupled by fading the blue color. By virtue of the above findings, a visual colorimetric sensor was established for dual detection of methimazole (MMI) with a linear scope of 5-50 mM and a LOD of 1.57 mM, coupled by assay of HO at a linear range of 3-50 mM. According to the irreversible oxidation of the drug, its screening with acceptable results was achieved on the sensing platform even in commercial tablets The Fe SAs/NP-CSs nanozyme holds great potential for clinical diagnosis and drug analysis.
Topics: Carbon; Colorimetry; Methimazole; Hydrogen Peroxide; Peroxidase; Oxidoreductases; Peroxidases; Coloring Agents; Pharmaceutical Preparations
PubMed: 38266603
DOI: 10.1016/j.saa.2024.123934