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JCEM Case Reports Jun 2024Patients with newly diagnosed Graves disease often elect for treatment with the drug methimazole (MMI) over alternative therapies. However, MMI can commonly result in...
Patients with newly diagnosed Graves disease often elect for treatment with the drug methimazole (MMI) over alternative therapies. However, MMI can commonly result in skin allergy that in severe cases can lead to discontinuation of therapy. We present a case of Graves thyrotoxicosis with a delayed hypersensitivity reaction while on MMI. The patient was successfully treated with a novel, individualized, 27-day desensitization protocol that resulted in tolerance of MMI with subsequent improvement in thyroid indices. Previous literature has offered various rapid desensitization protocols to MMI for immediate type hypersensitivity reactions. However, in nonimmediate, delayed hypersensitivity reactions, a slower desensitization protocol can be considered. As demonstrated in this case, desensitization to MMI is a reasonable alternative in patients who wish to avoid definitive therapy who develop an initial adverse reaction to MMI, as this can occur in up to 13% of treated cases.
PubMed: 38803510
DOI: 10.1210/jcemcr/luae066 -
Cureus Apr 2024Thyrotoxicosis, also known as hyperthyroidism, is a condition characterized by the excessive production of thyroid hormones by the thyroid gland. Besides Graves'...
Thyrotoxicosis, also known as hyperthyroidism, is a condition characterized by the excessive production of thyroid hormones by the thyroid gland. Besides Graves' disease, other common causes of thyrotoxicosis include toxic multinodular goiter, toxic adenoma, and subacute thyroiditis. The treatment of thyrotoxicosis depends on the underlying cause and may include medications (e.g., antithyroid drugs, beta-blockers), radioactive iodine therapy, or surgical removal of the thyroid gland (thyroidectomy). In this report, we present two instances of thyrotoxicosis where conventional high doses of antithyroid treatment failed to control the condition effectively. This failure prompted the exploration of alternative therapeutic interventions. These cases highlight the intricacies involved in managing thyrotoxic crises that do not respond to methimazole (MMI), emphasizing the necessity for innovative approaches such as plasmapheresis and thyroidectomy. Understanding such scenarios is vital for enhancing the care provided to patients encountering resistance to standard treatments. The distinct clinical pathways and treatment strategies adopted in these cases offer valuable insights into this disease management, particularly concerning resistance to MMI.
PubMed: 38800321
DOI: 10.7759/cureus.58980 -
Medicine May 2024Thyrotoxic cardiomyopathy is a rare but severe complication of thyrotoxicosis, leading to episodes of acute heart failure. This case report highlights a rare...
RATIONALE
Thyrotoxic cardiomyopathy is a rare but severe complication of thyrotoxicosis, leading to episodes of acute heart failure. This case report highlights a rare presentation of thyrotoxic cardiomyopathy with low-output heart failure, emphasizing the importance of early diagnosis and comprehensive management. The report aims to increase awareness among clinicians about the potential reversibility of this condition and the effective strategies for managing such complex cases.
PATIENT CONCERNS
This patient presented with dyspnea and chest constriction, without any antecedent predisposing factors. Subsequently, the patient abruptly manifested symptoms indicative of acute heart failure during outpatient consultation. Electrocardiography revealed rapid atrial fibrillation with type A preexcitation syndrome, whereas cardiac ultrasonography demonstrated global cardiac enlargement with a diminished ejection fraction (EF).
DIAGNOSES
After a comprehensive evaluation, the patient was diagnosed with thyrotoxic cardiomyopathy, acute heart failure, and atrial fibrillation with preexcitation syndrome.
INTERVENTIONS
Immediate interventions comprised diuretic administration, oxygen therapy, and antiarrhythmic agents, addressing acute heart failure concomitant with preexcitation syndrome. Following a fortnight of comprehensive therapeutic measures, the patient was discharged with a prescription for oral medications, notably methimazole.
OUTCOMES
Following the intervention, the patient showed significant improvement with the resolution of heart failure symptoms and dyspnea, restoration of sinus rhythm, improved left ventricular ejection fraction (LVEF improved from 36% to 45%), and normalization of thyroid function. These outcomes underscore the efficacy of the intervention strategy and offer a hopeful prognosis for similar cases.
LESSONS
Thyrotoxicosis may cause cardiomyopathy in patients with heart failure that manifests as dilated cardiac chambers. Clinicians should carefully screen patients for this reversible condition. Diagnosis requires a comprehensive assessment of various tests, and the therapeutic goal is to restore normal thyroid function.
Topics: Humans; Heart Failure; Thyrotoxicosis; Cardiomyopathies; Atrial Fibrillation; Electrocardiography; Female; Male; Acute Disease
PubMed: 38788008
DOI: 10.1097/MD.0000000000038305 -
American Journal of Translational... 2024To analyze the influence of propranolol (Prop) plus methimazole (MMI) on curative efficacy and thyroid function (TF) of patients with hyperthyroidism (HT).
PURPOSE
To analyze the influence of propranolol (Prop) plus methimazole (MMI) on curative efficacy and thyroid function (TF) of patients with hyperthyroidism (HT).
METHODS
In this retrospective study, 107 cases of HT presented between August 2019 and August 2021 were grouped according to different therapeutic regimens: a control group (the Con) with 53 cases treated with MMI, and a research group (the Res) with 54 cases treated with Prop + MMI. Inter-group comparisons were performed in terms of the following domains: heart rate (HR), efficacy, adverse reactions (ARs), TF parameters (free triiodothyronine, FT3; free thyroxine, FT4; thyroid stimulating hormone, TSH), hepatic function indicators (alanine aminotransferase, ALT; aspartate aminotransferase, AST), and quality of life (Short-Form 36 Item Health Survey, SF-36). Finally, multivariate analysis was performed by Logistic regression to determine the risk factors leading to the ineffectiveness of treatment.
RESULTS
The analysis showed an obviously higher total effective rate and an evidently lower AR rate in the Res compared with the Con group. Besides, the Res group had notably lower FT3, FT4, ALT and AST and statistically higher TSH after treatment compared with the baseline (before treatment) and the Con group. Higher SF-36 scores were also determined in the Res group. Finally, the results of Logistic regression analysis revealed that AST was an independent risk factor for ineffective treatment.
CONCLUSIONS
Prop plus MMI is effective in the treatment of HT, which can effectively improve the HR, thyroid hormone levels, hepatic function, and quality of life of patients, with a lower incidence of ARs.
PubMed: 38715833
DOI: 10.62347/JIYT2536 -
Endocrine Journal May 2024Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence...
Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the evidence has not been conclusive. The objective of our study was to determine whether the incidences of agranulocytosis induced by MMI and PTU exhibit dose-dependency. The subjects were 27,784 patients with untreated Graves' disease, 22,993 of whom were on an antithyroid drug treatment regimen for more than 90 days. Within this subset, 18,259 patients had been treated with MMI, and 4,734 had been treated with PTU. The incidence of agranulocytosis according to dose in the MMI group was 0.13% at 10 mg/day, 0.20% at 15 mg/day, 0.32% at 20 mg/day, and 0.47% at 30 mg/day, revealing a significant dose-dependent increase. In the PTU group, there were 0 cases of agranulocytosis at doses of 125 mg/day and below, 0.33% at 150 mg/day, 0.31% at 200 mg/day, and 0.81% at 300 mg/day, also revealing a significant dose-dependent increase. The incidence of agranulocytosis at MMI 15 mg and PTU 300 mg, i.e., at the same potency in terms of hormone synthesis inhibition, was 0.20% and 0.81%, respectively, and significantly higher in the PTU group. Our findings confirm a dose-dependent increase in the incidence of agranulocytosis with both drugs, but that at comparable thyroid hormone synthesis inhibitory doses PTU has a considerably higher propensity to induce agranulocytosis than MMI does.
PubMed: 38710619
DOI: 10.1507/endocrj.EJ24-0135 -
Cureus Apr 2024We report a case of a 17-year-old girl who developed toxic epidermal necrolysis (TEN) secondary to preoperative iodine administration before thyroidectomy for Graves'...
We report a case of a 17-year-old girl who developed toxic epidermal necrolysis (TEN) secondary to preoperative iodine administration before thyroidectomy for Graves' disease. Past medical history was significant for COVID-19 and multisystem inflammatory syndrome in Children (MISC-C), with subsequent diagnoses of type 1 diabetes mellitus (T1DM), Addison disease, and Graves' disease. Her Graves disease was initially managed with methimazole. While there are reported cases of Stevens-Johnson syndrome (SJS) and TEN due to methimazole, the patient had discontinued methimazole over one month prior. Therefore, she likely represents the first case of TEN reported secondary to potassium iodide solution in a pediatric patient. Given the rarity of TEN in pediatric patients, our case highlights the challenges in managing complex autoimmune conditions and underscores the importance of careful medication choices in such cases.
PubMed: 38707124
DOI: 10.7759/cureus.57618 -
Cureus Mar 2024This case report explores a rare presentation of restless legs syndrome (RLS) in a 59-year-old female with a history of Graves' disease (GD), highlighting the diagnostic...
This case report explores a rare presentation of restless legs syndrome (RLS) in a 59-year-old female with a history of Graves' disease (GD), highlighting the diagnostic challenges and the importance of considering thyroid dysfunctions in RLS. The patient, previously diagnosed and treated for GD, presented with acute nocturnal discomfort in her lower limbs, along with symptoms of fatigue, weight loss, and palpitations. Physical examinations and thyroid function tests indicated a recurrence of GD. Her RLS symptoms notably resolved following the treatment of GD with methimazole, pointing towards secondary RLS induced by GD. This case emphasizes the necessity of a comprehensive diagnostic approach in RLS, particularly in differentiating it from mimicking conditions including leg cramps, arthritis, peripheral neuropathy, and drug-induced akathisia, and identifying underlying etiologies like thyroid dysfunctions. The resolution of RLS symptoms after GD treatment underlines the potential link between thyroid dysfunctions, iron metabolism, and the dopaminergic system in RLS pathophysiology.
PubMed: 38694425
DOI: 10.7759/cureus.57354 -
Toxicology Apr 2024Thyroid hormone (TH) system disrupting compounds can impair brain development by perturbing TH action during critical life stages. Human exposure to TH system disrupting...
Thyroid hormone (TH) system disrupting compounds can impair brain development by perturbing TH action during critical life stages. Human exposure to TH system disrupting chemicals is therefore of great concern. To better protect humans against such chemicals, sensitive test methods that can detect effects on the developing brain are critical. Worryingly, however, current test methods are not sensitive and specific towards TH-mediated effects. To address this shortcoming, we performed RNA-sequencing of rat brains developmentally exposed to two different thyroperoxidase (TPO) inhibiting compounds, the medical drug methimazole (MMI) or the pesticide amitrole. Pregnant and lactating rats were exposed to 8 and 16 mg/kg/day(d) MMI or 25 and 50 mg/kg/d amitrole from gestational day 7 until postnatal day 16. Bulk-RNA-seq was performed on hippocampus from the 16-day old male pups. MMI and amitrole caused pronounced changes to the transcriptomes; 816 genes were differentially expressed, and 425 gene transcripts were similarly affected by both chemicals. Functional terms indicate effects from key cellular functions to changes in cell development, migration and differentiation of several cell populations. Of the total number of DEGs, 106 appeared to form a consistent transcriptional fingerprint of developmental hypothyroidism as they were similarly and dose-dependently expressed across all treatment groups. Using a filtering system, we identified 20 genes that appeared to represent the most sensitive, robust and dose-dependent markers of altered TH-mediated brain development. These markers provide inputs to the adverse outcome pathway (AOP) framework where they, in the context of linking TPO inhibiting compounds to adverse cognitive function, can be used to assess altered gene expression in the hippocampus in rat toxicity studies.
PubMed: 38685447
DOI: 10.1016/j.tox.2024.153822 -
Medicines (Basel, Switzerland) Apr 2024The human leucocyte antigen (HLA) allele variability was studied in cohorts of patients with idiosyncratic drug-induced liver injury (iDILI). Some reports showed an... (Review)
Review
The human leucocyte antigen (HLA) allele variability was studied in cohorts of patients with idiosyncratic drug-induced liver injury (iDILI). Some reports showed an association between HLA genetics and iDILI, proposing HLA alleles as a potential risk factor for the liver injury. However, the strength of such assumptions heavily depends on the quality of the iDILI diagnosis, calling for a thorough analysis. Using the PubMed database and Google Science, a total of 25 reports of case series or single cases were retrieved using the terms HLA genes and iDILI. It turned out that in 10/25 reports (40%), HLA genetics were determined in iDILI cases, for which no causality assessment method (CAM) was used or a non-validated tool was applied, meaning the findings were based on subjective opinion, providing disputable results and hence not scoring individual key elements. By contrast, in most iDILI reports (60%), the Roussel Uclaf Causality Assessment Method (RUCAM) was applied, which is the diagnostic algorithm preferred worldwide to assess causality in iDILI cases and represents a quantitative, objective tool that has been well validated by both internal and external DILI experts. The RUCAM provided evidence-based results concerning liver injury by 1 drug class (antituberculotics + antiretrovirals) and 19 different drugs, comprising 900 iDILI cases. Among the top-ranking drugs were amoxicillin-clavulanate (290 cases, HLA A*02:01 or HLA A*30:02), followed by flucloxacillin (255 cases, HLA B*57:01), trimethoprim-sulfamethoxazole (86 cases, HLA B*14:01 or HLA B*14:02), methimazole (40 cases, HLA C*03:02), carbamazepine (29 cases, HLA A*31:01), and nitrofurantoin (26 cases, HLA A*33:01). In conclusion, the HLA genetics in 900 idiosyncratic drug-induced liver injury cases with evidence based on the RUCAM are available for studying the mechanistic steps leading to the injury, including metabolic factors through cytochrome P450 isoforms and processes that activate the innate immune system to the adaptive immune system.
PubMed: 38667507
DOI: 10.3390/medicines11040009 -
Physiological Reports Apr 2024Thyroid hormones regulate metabolic rate, nutrient utilization, growth, and development. Swine are susceptible to thyroid suppression in response to disease or...
Thyroid hormones regulate metabolic rate, nutrient utilization, growth, and development. Swine are susceptible to thyroid suppression in response to disease or environmental conditions, but the physiological impact of such disruption has not been established. The objective of this study was to evaluate the impact of hypothyroidism induced with the antithyroid medication methimazole (MMI). 10 mg/kg MMI significantly decreased circulating triiodothyronine (T3) for the duration of treatment but had only a transient effect on circulating thyroxine (T4). Thyroid tissue weight was significantly increased by more than 3.5-fold in response to MMI treatment. Histologically, the eosinophilic colloid was largely absent from the thyroid follicle which displayed a disorganized columnar epithelium consistent with goiter. MMI induced hypothyroidism has no effect on growth rate over 28 days. Hepatic expression of genes associated with thyroid metabolism (DIO1, DIO2, and DIO3), lipid utilization (CD36, FASN, and ACACA), apoptosis (TP53, PERP, SIVA1, and SFN) and proliferation (CDK1, CDK2, CDK4, and CDKN1A) were unaffected by treatment. Collectively these results demonstrate that MMI induces mild systemic hypothyroidism and pronounced goiter, indicating a strong homeostatic central regulation within the hypothalamic pituitary thyroid axis. This combined with limited peripheral effects, indicates resilience to hypothyroidism in modern swine.
Topics: Animals; Methimazole; Hypothyroidism; Swine; Antithyroid Agents; Thyroid Gland; Female; Triiodothyronine; Liver; Thyroxine; Male
PubMed: 38658325
DOI: 10.14814/phy2.16007