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Thyroid : Official Journal of the... Dec 2023When the antithyroid drugs were discovered in the early 1940s, they were immediately recognized as a revolutionary new treatment for hyperthyroidism. Although much has...
When the antithyroid drugs were discovered in the early 1940s, they were immediately recognized as a revolutionary new treatment for hyperthyroidism. Although much has been learned about their mechanism of action and clinical utility, they continue to be used today in much the same way as they have been since their introduction. In 1995, Dr. Clark Sawin gave an address on the history of antithyroid drug development at the 11th International Thyroid Congress in Toronto, Ontario, Canada. In his review, Dr. Sawin recounted the original observations by Drs. Julia and Cosmo Mackenzie and Curt Richter at the Johns Hopkins University School of Medicine, and how their work ultimately led to Dr. Edwin (Ted) B. Astwood's seminal 1943 report on the use of thiourea and thiouracil in the Journal of the American Medical Association. He also described the development of propylthiouracil and methimazole as less toxic alternatives. He concluded his remarks by noting the often-serendipitous pathway of drug development and the role of pharmaceutical companies in the process. Antithyroid drugs remain a cornerstone of thyroid therapeutics. It is informative to review the process by which they came into use, as this is a seminal part of the history of thyroid disease in the 20th century. This knowledge may also spark additional research leading to new pharmacotherapies for patients with hyperthyroidism.
Topics: Male; Humans; Antithyroid Agents; Graves Disease; Methimazole; Propylthiouracil; Hyperthyroidism; Ontario
PubMed: 37594736
DOI: 10.1089/thy.2022.0410 -
Cureus Jul 2023Hyperthyroidism is more common in women and the sensitivity of thyroid function changes during pregnancy. Excess levels of thyroid hormones and thioamides have a major... (Review)
Review
Hyperthyroidism is more common in women and the sensitivity of thyroid function changes during pregnancy. Excess levels of thyroid hormones and thioamides have a major impact on maternal and fetal outcomes. Our aim was to perform an extensive literature review and provide relevant details concerning the analytical and clinical aspects of the potential effects of the two main drugs used (methimazole and propylthiouracil) in newborns. A thorough literature review was conducted using PubMed and Google Scholar databases. In total, 10 relevant studies were identified and data from these studies were extracted and then extrapolated into results after analysis. Three out of four studies that used methimazole and carbimazole, one and two, respectively, showed adverse fetal outcomes requiring surgical management for congenital anomalies like aplasia cutis, patent vitellointestinal duct, and gastroschisis. Out of the three studies that used propylthiouracil, one baby underwent surgery for bilateral pyelectasis, vesicovaginal fistula, anal stenosis, and polydactyly. The findings of the aforementioned studies provide enough evidence to imply that the use of methimazole and carbimazole to treat antenatal hyperthyroidism has worse fetal outcomes than the use of propylthiouracil. Also, given the paucity of data in the existing literature regarding propylthiouracil's effects on newborns, further studies in this demographic are needed.
PubMed: 37551246
DOI: 10.7759/cureus.41505 -
JCEM Case Reports Jan 2024
PubMed: 38178959
DOI: 10.1210/jcemcr/luad166 -
Scientific Reports Nov 2023Although antithyroid drug (ATD)-induced agranulocytosis is a significant concern, its risks associated with long-term use and re-administration are not fully elucidated....
Although antithyroid drug (ATD)-induced agranulocytosis is a significant concern, its risks associated with long-term use and re-administration are not fully elucidated. Therefore, we performed this study to determine the incidence of ATD-induced leukopenia and G-CSF administration using administrative claims database. Retrospective cohort study. This study was performed using the DeSC Japanese administrative claims database. A total of 12,491 patients with newly diagnosed Graves' disease (GD) who received methimazole or propylthiouracil between April 2014, and February 2021 among 3.44 million patients in the database were included in the study. We measured the six-year incidence of leukopenia and granulocyte colony-stimulating factor (G-CSF) administration. The incidence of leukopenia and G-CSF administration was 1.34% (168 patients) and 0.30% (38 patients), respectively. Leukopenia had a dose-dependent and biphasic incidence. The incidence of leukopenia and G-CSF administration was 37.2 (0.7%) and 8.0 (0.2%) per 1000 person-years during the first 72 days of ATD initiation, whereas it was 3.1 and 0.7 per 1000 person-years during the subsequent 6 years, respectively. The incidence of both outcomes was comparable between first administration and re-administration of ATD. The incidence of ATD-induced leukopenia and G-CSF administration was high in the first 72 days, with a reduced risk for at least 6 years thereafter. The incidence was similar between first administration and re-administration. ATD, a standard therapy, is often administered for a long period; therefore, our findings can guide the treatment of GD.
Topics: Humans; Antithyroid Agents; Cohort Studies; Retrospective Studies; Graves Disease; Neutropenia; Granulocyte Colony-Stimulating Factor; Thrombocytopenia
PubMed: 37935745
DOI: 10.1038/s41598-023-46307-5 -
Journal of the Endocrine Society Dec 2023Antithyroid drugs (ATDs) are the cornerstone of hyperthyroidism management. Hepatotoxicity due to ATDs can range from mild transaminase elevation to liver... (Review)
Review
CONTEXT
Antithyroid drugs (ATDs) are the cornerstone of hyperthyroidism management. Hepatotoxicity due to ATDs can range from mild transaminase elevation to liver transplantation requirement and mortality.
OBJECTIVE
The primary objective of the systematic review was to assess the clinical characteristics and outcomes of patients with drug induced liver injury (DILI) due to ATDs.
METHODS
We conducted a systematic review of PUBMED, SCOPUS, and EMBASE on characteristics and outcomes of adults (>18 years) with DILI due to ATDs. We defined DILI as bilirubin ≥2.5 mg/dL or international normalized ratio >1.5 with any rise in alanine aminotransferase (ALT), aminotransferase (AST), or alkaline phosphatase (ALP), or an elevation of ALT or AST >5 times or ALP >2 times the upper limit of normal without jaundice/coagulopathy.
RESULTS
The review included 100 articles describing 271 patients; 148 (70.8%) were female (N = 209). Mean age was 42.9 ± 17.2 years. Graves' disease was the most common indication for ATDs. Carbimazole/methimazole (CBM/MMI) was the most common offending agent (55.7%). DILI pattern was hepatocellular in 41.8%, cholestatic in 41.3%, and mixed in 16.9%. Outcomes included death in 11.8%, liver transplantation in 6.4%, partial improvement in 2.2%, and complete resolution in 79.6% with a median time (IQR) to resolution of 45 (20-90) days. Patients in the propylthiouracil (PTU) group had higher initial bilirubin, initial AST, initial ALT, peak ALT, peak AST, severe and fatal DILI, liver transplantation, and mortality than CBM/MMI. Rechallenge of antithyroid medication was infrequently reported (n = 16) but was successful in 75%.
CONCLUSION
DILI due to ATDs can present with different patterns and should prompt immediate drug discontinuation. Referral to a hepatologist should be considered if severe as transplantation is sometimes required. PTU-induced DILI may have worse outcomes than CBM/MMI.
PubMed: 38178906
DOI: 10.1210/jendso/bvad133 -
Cureus Nov 2023Agranulocytosis is a rare but life-threatening complication of methimazole and propylthiouracil, antithyroid drugs (ATDs) prescribed for the treatment of...
Agranulocytosis is a rare but life-threatening complication of methimazole and propylthiouracil, antithyroid drugs (ATDs) prescribed for the treatment of hyperthyroidism. We report the case of a 41-year-old female who presented to our institution with complaints of fevers, chills, sore throat, myalgias, and generalized weakness one month after treatment initiation with methimazole. A complete blood count at admission revealed agranulocytosis with an absolute neutrophil count of 0/μl. After discontinuation of the medication, she was treated with granulocyte-colony stimulating factor and intravenous broad-spectrum antibiotics, which improved her condition on day seven of hospitalization. Although agranulocytosis is a rare complication of antithyroid drugs, providers must maintain a high index of clinical suspicion as prompt diagnosis and treatment are essential. After the diagnosis is confirmed with an absolute neutrophil count <500/μl, management involves discontinuation of the offending agent and initiation of intravenous broad-spectrum antibiotics. Granulocyte-colony stimulating factor, commonly employed in addition to antibiotics, is a controversial treatment option and more research demonstrating its efficacy is necessitated. Preventing mortality associated with antithyroid drug-induced agranulocytosis is achieved through patient education at the time of ATD initiation.
PubMed: 38054132
DOI: 10.7759/cureus.48264 -
Medicine Nov 2023Hypoglycemia is common in patients with glucose regulation disorders and related diabetic treatments but is rare in nondiabetic patients. Severe hypoglycemia can cause... (Review)
Review
RATIONALE
Hypoglycemia is common in patients with glucose regulation disorders and related diabetic treatments but is rare in nondiabetic patients. Severe hypoglycemia can cause harm to patients' cognition, consciousness, central nervous system, cardiovascular and cerebrovascular system, and even death. However, the most fundamental way to control hypoglycemia is to identify the cause and deal with the primary disease. This article introduces 3 cases of nondiabetic hypoglycemia with different causes, aiming to improve our understanding of nondiabetic hypoglycemia and improve the ability of early diagnosis and differential diagnosis.
PATIENT CONCERNS
Case 1 is a 19-year-old female with a history of recurrent coma, and magnetic resonance imaging and endoscopic ultrasound of the pancreas suggest insulinoma. Case 2 is a 74-year-old male with a history of viral hepatitis, and computerized tomography shows multiple nodules in the liver, which is diagnosed as liver cancer. Case 3 is a 39-year-old female with a history of taking methimazole, who tested positive for insulin antibodies, and was diagnosed with insulin autoimmune syndrome.
DIAGNOSIS
All 3 patients were diagnosed with nondiabetic hypoglycemia, but the causes varied, and included insulinoma, non-islet cell tumor-induced hypoglycemia, and insulin autoimmune syndrome.
INTERVENTIONS
Case 1 underwent pancreatic tail resection; case 2 refused anti-tumor treatment and received glucose injections for palliative treatment only; and case 3 stopped taking methimazole.
OUTCOMES
After surgery, the blood sugar in case 1 returned to normal, and the blood sugar in case 2 was maintained at about 6.0 mmol/L. The symptoms of hypoglycemia gradually improved in case 3 after stopping the medication.
LESSONS
Non-diabetic hypoglycemia requires further examination to clarify the cause, and the correct differential diagnosis can provide timely and effective treatment, improving the patient's prognosis.
Topics: Male; Female; Humans; Young Adult; Adult; Aged; Insulinoma; Blood Glucose; Methimazole; Insulin; Pancreatic Neoplasms; Early Detection of Cancer; Hypoglycemia
PubMed: 38013348
DOI: 10.1097/MD.0000000000036273 -
Acta Veterinaria Hungarica Oct 2023A 16-year-old castrated male Persian cat was presented with weight loss, anorexia and dyspnoea. Tachycardia and tachypnoea were observed upon presentation. The cat was...
A 16-year-old castrated male Persian cat was presented with weight loss, anorexia and dyspnoea. Tachycardia and tachypnoea were observed upon presentation. The cat was previously diagnosed with hyperthyroidism and left ventricular hypertrophy and received methimazole, but was subsequently not followed up and treated appropriately. Thoracic radiography revealed mild pleural effusion, interstitial lung pattern, moderate cardiomegaly and moderate-to-severe dilation of the pulmonary artery and pulmonary vein. On echocardiography, the left ventricular hypertrophy, identified earlier, shoed partial regression. Therefore, the previous myocardial hypertrophy was diagnosed as a hypertrophic cardiomyopathy phenotype related to hyperthyroidism. ST-segment elevation was identified on electrocardiography, and the thyroid profile examination revealed increased total thyroxine and free thyroxine and decreased thyroid-stimulating hormone levels, suggesting myocardial injury and uncontrolled hyperthyroidism, respectively. In addition, normal N-terminal pro-B-type natriuretic peptide and high cardiac troponin I levels were found. Based on these findings, the observed congestive heart failure was considered as a sequel of myocardial injury caused by uncontrolled hyperthyroidism. Clinical signs resolved after intravenous administration of furosemide and butorphanol, oxygen supply and thoracocentesis. Furosemide and pimobendan were additionally administered, and the cat was discharged. This case demonstrates that myocardial damage due to chronic uncontrolled hyperthyroidism may cause heart failure in cats.
Topics: Cats; Male; Animals; Hypertrophy, Left Ventricular; Thyroxine; Furosemide; Cardiomyopathy, Hypertrophic; Heart Failure; Cardiomegaly; Hyperthyroidism; Phenotype; Cat Diseases
PubMed: 37527008
DOI: 10.1556/004.2023.00815