Background Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This document describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition. Methods The American Thyroid Association (ATA) previously cosponsored guidelines for the management of thyrotoxicosis that were published in 2011. Considerable new literature has been published since then, and the ATA felt updated evidence-based guidelines were needed. The association assembled a task force of expert clinicians who authored this report. They examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to update the 2011 text and recommendations. The strength of the recommendations and the quality of evidence supporting them were rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. Results Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' orbitopathy; and management of other miscellaneous causes of thyrotoxicosis. New paradigms since publication of the 2011 guidelines are presented for the evaluation of the etiology of thyrotoxicosis, the management of Graves' hyperthyroidism with antithyroid drugs, the management of pregnant hyperthyroid patients, and the preparation of patients for thyroid surgery. The sections on less common causes of thyrotoxicosis have been expanded. Conclusions One hundred twenty-four evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.

/pdf/2016-american-thyroid-association-guidelines-for-diagnosis-1a9h72rzxu.pdf

2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis

http://medclerk.weebly.com/uploads/6/8/9/5/6895084/aace_hyper_thyroidism.pdf

Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists

Graves disease is an autoimmune disorder characterized by goitre, hyperthyroidism and, in 25% of patients, Graves ophthalmopathy. The hyperthyroidism is caused by thyroid hypertrophy and stimulation of function, resulting from interaction of anti-TSH-receptor antibodies (TRAb) with the TSH receptor on thyroid follicular cells. Measurements of serum levels of TRAb and thyroid ultrasonography represent the most important diagnostic tests for Graves disease. Management of the condition currently relies on antithyroid drugs, which mainly inhibit thyroid hormone synthesis, or ablative treatments ((131)I-radiotherapy or thyroidectomy) that remove or decrease thyroid tissue. None of these treatments targets the disease process, and patients with treated Graves disease consequently experience either a high rate of recurrence, if receiving antithyroid drugs, or lifelong hypothyroidism, after ablative therapy. Geographical differences in the use of these therapies exist, partially owing to the availability of skilled thyroid surgeons and suitable nuclear medicine units. Novel agents that might act on the disease process are currently under evaluation in preclinical or clinical studies, but evidence of their efficacy and safety is lacking.

Diagnosis and management of Graves disease: a global overview

Propylthiouracil (PTU) was introduced for clinical use in July 1947 for Graves' disease (GD) treatment. Over the 60 years that this medication has been used, reports of PTU-related liver failure and death have accumulated. On October 28, 2008, an expert panel evaluated PTU drug safety in children at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) It is estimated that about 4000 pediatric patients per year with GD are being treated with antithyroid drugs (ATDs) in the United States, and up to 30% of pediatric patients with GD are being treated with PTU. The risk of severe PTU-induced liver failure is estimated as 1 in 2000–4000 children. The number of children developing reversible PTU-induced liver injury is estimated to be at least 1 in 200. Routine biochemical surveillance of liver function and hepatocellular integrity is not useful in identifying children who will develop liver failure. Children appear to be at higher risk for PTU-induced liver injury than adults. PTU should not be used as first line therapy for the treatment of GD in children. Current PTU use in children taking this medication should be stopped in favor of alternate therapies.

/pdf/propylthiouracil-ptu-hepatoxicity-in-children-and-21y112zoty.pdf

Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use

Aims

The evidence of hepatotoxicity of antithyroid drugs (ATDs) is limited to case reports or spontaneous reporting. This study aimed to quantify the incidence and comparative risks of hepatotoxicity for methimazole (MMI)/carbimazole (CBM) vs. propylthiouracil (PTU) in a population-based manner.



Methods

We conducted a cohort study of hyperthyroidism patients initially receiving MMI/CBM or PTU between 1 January 2004 and 31 December 2008 using the Taiwan National Health Insurance Research Database. The examined hepatotoxicity consisted of cholestasis, non-infectious hepatitis, acute liver failure and liver transplant, with the incidences and relative risks being quantified by Poisson exact methods and Cox proportional hazard models, respectively.



Results

The study cohort comprised 71 379 ATD initiators, with a median follow-up of 196 days. MMI/CBM vs. PTU users had a higher hepatitis incidence rate (3.17/1000 vs. 1.19/1000 person-years) but a lower incidence of acute liver failure (0.32/1000 vs. 0.68/1000 person-years). The relative risk analysis indicated that any use of MMI/CBM was associated with a 2.89-fold (95% CI 1.81, 4.60) increased hepatitis risk compared with PTU, with the risk increasing to 5.08-fold for high dose MMI/CBM (95% CI 3.15, 8.18). However, any MMI/CBM use vs. PTU was not related to an increased risk of cholestasis (adjusted hazard ratio [HR] 1.14, 95% CI 0.40, 3.72) or acute liver failure (adjusted HR 0.54, 95% CI 0.24, 1.22).



Conclusions

MMI/CBM and PTU exert dissimilar incidence rates of hepatotoxicity. Compared to PTU, MMI/CBM are associated in a dose-dependent manner with an increased risk for hepatitis while the risks are similar for acute liver failure and cholestasis.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bcp.12336

Antithyroid drug-related hepatotoxicity in hyperthyroidism patients: a population-based cohort study.

OBJECTIVE:To report 2 fatal cases of fulminant hepatic failure associated with propylthiouracil treatment against hyperthyroidism.CASE SUMMARY:Two women, 30 and 32 years old with no previous liver disease, were treated with propylthiouracil against Graves' disease. Both patients developed jaundice after a 4- and 5-month treatment period, respectively. The disease was similar to viral hepatitis, with a progressive course to severe liver dysfunction and death, along with multisystem organ failure despite extensive therapeutic measures. One of the patients was pregnant and subsequently miscarried. Neither patient had a history of alcoholism, drug abuse, blood transfusion, or exposure to hepatitis A, B, or C. Extrahepatic obstruction was ruled out with an abdominal ultrasonogram. Serologic studies and immunologic tests were negative. A submassive necrosis was shown in a postmortem histologic study.DISCUSSION:Naranjo probability scale criteria applied to both cases confirm the adverse reactions as probable. Th...

Isabel B Lopez

Papers

Fulminant Hepatic Failure Associated with Propylthiouracil