# Thyroid inflammation and underactive thyroid from checkpoint inhibitors

Source: https://onco.cc/protocols/irae-thyroid/  
OnCo record `irae-thyroid` (Protocol). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Immunotherapy often inflames the thyroid gland. It can briefly make the thyroid overactive (racing heart, sweating, shakiness) and then underactive (tiredness, feeling cold), and the underactive phase is often permanent. It is found on routine blood tests, treated with tablets rather than steroids, and immunotherapy usually carries on.

## Summary

The commonest endocrine irAE. Hypothyroidism occurs in about 8% on PD-(L)1 inhibitors, 3% on CTLA-4 inhibitors and 15% on combinations (SITC 2021); ESE 2022 gives 3.9 to 8.5%, 2.5 to 3.8% and 10.2 to 16.4%, with onset at a median 8 to 12 weeks. A thyrotoxic phase, typically 4 to 6 weeks after starting and lasting about 6 weeks, often precedes it, and hypothyroidism is often permanent.

Monitoring: TSH and free T4 every 4 to 6 weeks on treatment and every 6 to 12 months after (SITC; ESE suggests before every cycle for the first 6 months). Thyrotoxicosis is treated with beta-blockers for symptoms; persistent thyrotoxicosis needs assessment for Graves' disease with TSH receptor antibodies. Morning cortisol is checked before levothyroxine, because replacing thyroid hormone in untreated adrenal insufficiency can precipitate a crisis. High-dose glucocorticoids are not used for thyroiditis (ESE, +000). Immunotherapy is usually continued.

The two guidelines differ on when and how much levothyroxine to start: SITC considers it for a persistently raised TSH with normal free T4 and starts at 1.5 to 1.6 µg/kg/day in young healthy patients; ESE suggests it when free T4 is low and TSH above 10 mIU/L (++00), advises against routine treatment for TSH 4 to 10 with normal free T4 (+000), and starts at 1.0 µg/kg/day. ESMO 2022 could not be read.

## Fields

- Kind: Protocol
- Last checked: 2026-11-11
- Also known as: checkpoint inhibitor thyroiditis; ICI thyroiditis; immune-related hypothyroidism; immunotherapy thyroid problems; ir-thyroiditis; immune-related thyrotoxicosis
- Tags: protocol; irae; endocrine

## Connected records

- protocols: [Baseline tests and monitoring before and during checkpoint inhibitor treatment](https://onco.cc/protocols/checkpoint-inhibitor-baseline-and-monitoring/), [Checkpoint inhibitor hypophysitis and adrenal insufficiency: emergency treatment, replacement and steroid emergency card](https://onco.cc/protocols/irae-hypophysitis-adrenal/), [Eye side effects of checkpoint inhibitors: dry eye, uveitis and optic neuritis](https://onco.cc/protocols/irae-ocular/), [Immune-related type 1 diabetes and diabetic ketoacidosis from checkpoint inhibitors](https://onco.cc/protocols/irae-diabetes/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Avelumab](https://onco.cc/drugs/avelumab/), [Cemiplimab](https://onco.cc/drugs/cemiplimab/), [Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Tremelimumab](https://onco.cc/drugs/tremelimumab/)
- institutions: [American Society of Clinical Oncology (ASCO)](https://onco.cc/institutions/asco/), [European Society for Medical Oncology (ESMO)](https://onco.cc/institutions/esmo/), [Society for Immunotherapy of Cancer](https://onco.cc/institutions/sitc/)
- terms: [Immune-related adverse events (irAEs)](https://onco.cc/terms/irae/), [Immune-related endocrinopathies (thyroiditis, hypophysitis)](https://onco.cc/terms/immune-endocrinopathy/)
- key papers: [ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors](https://onco.cc/key-papers/paper-asco-irae-guideline-jco-2021/)

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