Medication-associated thyroid eye disease: a review

TL;DR

This review explores how certain medications can cause thyroid eye disease, highlighting drugs like alemtuzumab and immune checkpoint inhibitors as key culprits.

Contribution

The paper systematically identifies and characterizes medications associated with thyroid eye disease, emphasizing their clinical relevance.

Findings

Alemtuzumab and immune checkpoint inhibitors are frequently linked to medication-associated thyroid eye disease.

Thyroid dysfunction typically precedes orbitopathy by about 20 months in alemtuzumab cases.

ICI-associated TED can occur without underlying thyroid dysfunction, showing varied clinical presentations.

Abstract

To systematically review the literature surrounding medication-associated thyroid eye disease (TED).

A systematic search was conducted from inception to the 31st of March 2025 on PubMed, EMBASE and Web of Science. Studies describing medication-associated thyroid dysfunction and the subsequent development of TED were included. Articles without thyroid dysfunction and/or the absence of orbitopathy were excluded.

A total of 23 studies met the inclusion criteria. Implicated medications included alemtuzumab, immune checkpoint inhibitors (ICI), amiodarone and lenalidomide. The mean onset of thyroid dysfunction from commencement of alemtuzumab was 26.3 ± 12.2 months (Range: 7 to 53.3 months); and the mean onset of developing orbitopathy from thyroid dysfunction was 19.9 ± 21.4 months (Range: 0 to 96 months). Graves’ disease was the most common condition resulting in the development of alemtuzumab-associated TED. ICIs reported to cause TED included ipilimumab (anti-CTLA-4 drug), tremelimumab (anti-CTLA-4 drug), durvalumab (PD-1 inhibitor) and nivolumab (PD-1 inhibitor). Anti-CTLA4 drugs, such as ipilimumab and tremelimumab, were the most common agents implicated in the development of ICI-associated TED. ICIs may also incite orbital inflammation in the absence of thyroid dysfunction. A single case-report of amiodarone- and lenalidomide-associated TED was noted.

Medication-associated TED is an important differential consideration in the work-up of orbital inflammatory disease. The clinico-radiological manifestations and the principles of management of medication-associated TED were similar to that of de novo TED. Certain medications, such as various ICIs, may demonstrate different clinical phenotypes of orbital inflammation, inciting either TED or a “TED-like” orbitopathy without evidence of underlying thyroid dysfunction.

What is known?
Orbital inflammatory disease (OID) has a wide range of aetiologies and may be secondary to various medication adverse effects.

Orbital inflammatory disease (OID) has a wide range of aetiologies and may be secondary to various medication adverse effects.

What is new?

Medication-associated thyroid eye disease (TED) represents an important pattern of involvement within the spectrum of OID.

Medications which may cause TED include: Alemtuzumab (anti-CD52 monoclonal antibody), various immune checkpoint inhibitors (ICI), amiodarone and lenalidomide. Medication-associated TED is an important differential consideration in the work-up of OID and is relevant to clinicians across a range of disciplines.

Medications which may cause TED include: Alemtuzumab (anti-CD52 monoclonal antibody), various immune checkpoint inhibitors (ICI), amiodarone and lenalidomide.

Medication-associated TED is an important differential consideration in the work-up of OID and is relevant to clinicians across a range of disciplines.

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