Clinical Characteristics and Outcomes of Patients With Antithyroid Drug-Related Liver Injury

Adeel Ahmad Khan; Fateen Ata; Afia Aziz; Hana Elamin; Aamir Shahzad; Zohaib Yousaf; Anthony Donato

doi:10.1210/jendso/bvad133

Clinical Characteristics and Outcomes of Patients With Antithyroid Drug-Related Liver Injury

J Endocr Soc. 2023 Oct 27;8(1):bvad133. doi: 10.1210/jendso/bvad133. eCollection 2023 Dec 1.

Authors

Adeel Ahmad Khan¹, Fateen Ata¹, Afia Aziz², Hana Elamin³, Aamir Shahzad⁴, Zohaib Yousaf⁴, Anthony Donato⁴

Affiliations

¹ Department of Endocrinology, Hamad Medical Corporation, 3050, Doha, Qatar.
² Department of Internal Medicine, Hamad Medical Corporation, 3050, Doha, Qatar.
³ National University-Sudan, Khartoum 11115, Sudan.
⁴ Department of Medicine, Tower Health, West Reading, PA 19611, USA.

Abstract

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.

Keywords: antithyroid drugs; carbimazole; hepatotoxicity; liver injury; methimazole; propylthiouracil.

Publication types

Review