Transient Thyroiditis Followed by Exacerbation of Hypothyroidism After Immune Checkpoint Inhibitor Therapy (Nivolumab and Ipilimumab) in a Patient With Pre-existing Autoimmune Hypothyroidism: A Case Report

Our plain-English summary of Transient Thyroiditis Followed by Exacerbation of Hypothyroidism After Immune Checkpoint Inhibitor Therapy (Nivolumab and Ipilimumab) in a Patient With Pre-existing Autoimmune Hypothyroidism: A Case Report, by G. Hayakawa, M.M. Leibowitz, S. Datta, et al (Curēus, 2023).

The study

• Authors: G. Hayakawa, M.M. Leibowitz, S. Datta, S.O. Oyibo
• Journal: Curēus
• Published: 2023;15(5):e39439
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Treatment with immune checkpoint inhibitors has improved the prognosis of solid tumors. However, immune-related adverse events (IRAEs), including exacerbation of pre-existing autoimmune disease, are common and have become more frequent with combination therapy. The literature is scanty regarding reports of the use of combination immune checkpoint therapy in patients with pre-existing autoimmune hypothyroidism. We report a case of a man with a history of hypothyroidism, who developed transient thyroiditis, characterized by a thyrotoxic phase followed by a severe hypothyroid phase soon after receiving combination therapy (nivolumab and ipilimumab) for the treatment of a malignant pleural mesothelioma. He had been on a stable low dose of levothyroxine for 12 years prior to this episode. His levothyroxine requirement markedly increased soon after the episode of immune checkpoint inhibitor-induced thyroiditis. Immune checkpoint inhibitors can cause destructive thyroiditis followed by exacerbation of hypothyroidism in patients with pre-existing autoimmune hypothyroidism, such that patients end up on a higher dose of levothyroxine. This case will add to the growing literature regarding thyroid IRAEs associated with the use of immune checkpoint inhibitors in patients with pre-existing autoimmune thyroid disease.

Copyright © 2023, Hayakawa et al.

In plain English

This case report described one 65-year-old man with a malignant pleural mesothelioma and a history of autoimmune hypothyroidism (Hashimoto's disease). For 12 years he had taken a stable 50 mcg daily dose of levothyroxine (0.6 mcg/kg body weight). The article does not mention asbestos exposure. He received two intravenous doses of nivolumab three weeks apart and one dose of ipilimumab, both immune checkpoint inhibitor drugs. Two weeks after the second nivolumab dose, a routine blood test showed thyrotoxicosis (excess thyroid hormone), although he had no new symptoms. His thyroid-stimulating hormone (TSH) was 0.02 mU/L and his free thyroxine was 42.3 pmol/L. His levothyroxine was cut to 25 mcg daily, and four weeks later his TSH was normal (1.8 mU/L). A test four weeks after that showed severe hypothyroidism, with TSH at 82.2 mU/L. His dose was raised to 75 mcg and then to 125 mcg daily (1.5 mcg/kg) over two months. He continued the drug therapy and remained well. The authors scored the event as grade 2. They concluded that immune checkpoint inhibitors can cause destructive thyroiditis followed by worsening of pre-existing autoimmune hypothyroidism. As a case report, it describes one patient, not how often this occurs.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (single patient)
• Who was studied: One 65-year-old man with pre-existing autoimmune hypothyroidism (Hashimoto's disease) who was being treated for a right-sided malignant pleural mesothelioma. He also had type 2 diabetes, ischemic heart disease and a right internal carotid artery occlusion. He was referred to the endocrinology department. The authors were based at Peterborough City Hospital, UK.
• Exposure: Immune checkpoint inhibitor drugs: two intravenous doses of nivolumab given three weeks apart and a single intravenous dose of ipilimumab. The article does not discuss asbestos or any fiber exposure.
• Main results:
  • Before treatment, the patient had been stable for 12 years on 50 mcg daily of levothyroxine (0.6 mcg/kg body weight).
  • Two weeks after the second nivolumab dose, blood tests in this patient showed thyrotoxicosis. TSH was 0.02 mU/L (reference 0.3-4.2), free thyroxine was 42.3 pmol/L (reference 12.0-22.0) and free triiodothyronine was 10.3 pmol/L (reference 3.1-6.8). He had no new symptoms.
  • The patient's anti-thyroid peroxidase antibodies were elevated at 311 IU/mL (reference under 34), but lower than at his original Hashimoto's diagnosis. His thyroid receptor antibodies were normal.
  • Ultrasound showed an atrophic thyroid gland with heterogeneous echogenicity and no increased vascularity.
  • After levothyroxine was reduced to 25 mcg daily, TSH normalized to 1.8 mU/L four weeks later. A repeat test four weeks after that showed severe hypothyroidism: TSH 82.2 mU/L and free T4 5.2 pmol/L.
  • The levothyroxine dose was increased to 75 mcg daily, then to 125 mcg daily (1.5 mcg/kg body weight) over the next two months.
  • The adverse event was scored grade 2 under the common terminology criteria for adverse events, because the patient had no symptoms but required medical intervention.
  • The patient remained adequately replaced on 125 mcg daily of levothyroxine and continued nivolumab and ipilimumab therapy.
• The authors' conclusion: The authors concluded that immune checkpoint inhibitors can cause destructive thyroiditis followed by exacerbation of hypothyroidism in patients with pre-existing autoimmune hypothyroidism.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Nivolumab (Opdivo), Ipilimumab (Yervoy), Prognosis, Immune-Related Adverse Events, Pleural Mesothelioma.

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