The continuum of care of anticancer treatment-induced hypothyroidism in patients with solid non-thyroid tumors: time for an intimate collaboration between oncologists and endocrinologists

ABSTRACT

Introduction

Hypothyroidism is a common adverse event of various anticancer treatment modalities, constituting a notable paradigm of the integration of the endocrine perspective into precision oncology.

Areas covered

The present narrative review provides a comprehensive and updated overview of anticancer treatment-induced hypothyroidism in patients with solid non-thyroid tumors. A study search was conducted on the following electronic databases: PubMed, Google Scholar, Scopus.com, ClinicalTrials.gov, and European Union Clinical Trials Register from 2011 until August 2021.

Expert opinion

In patients with solid non-thyroid tumors, hypothyroidism is a common adverse event of radiotherapy, high-dose interleukin 2 (HD IL-2), interferon alpha (IFN-α), bexarotene, immune checkpoint inhibitors (ICPi), and tyrosine kinase inhibitors (TKIs), while chemotherapy may induce hypothyroidism more often than initially considered. The path forward for the management of anticancer treatment-induced hypothyroidism in patients with solid non-thyroid tumors is an integrated approach grounded on five pillars: prevention, vigilance, diagnosis, treatment, and monitoring. Current challenges concerning anticancer treatment-induced hypothyroidism await counteraction, namely awareness of the growing list of related anticancer treatments, identification of predictive factors, counteraction of diagnostic pitfalls, tuning of thyroid hormone replacement, and elucidation of its prognostic significance. Close collaboration of oncologists with endocrinologists will provide optimal patient care.

KEYWORDS:

• Anticancer treatment
• bexarotene
• drug-induced hypothyroidism
• endocrine adverse events
• immune checkpoint inhibitors
• interferon-α
• interleukin 2
• L-thyroxine
• radiotherapy
• tyrosine kinase inhibitors

Article highlights

• Close collaboration between endocrinologists and oncologists is essential to resolve current preventive, diagnostic, and therapeutic conundrums regarding anticancer treatment-induced hypothyroidism in patients with solid non-thyroid tumors.

• Radiotherapy-induced hypothyroidism is a common adverse event of radiotherapy in patients with solid non-thyroid tumors when the radiation field includes the thyroid or the hypothalamus and the pituitary.

• Hypothyroidism is often related to the tyrosine kinase inhibitors and to immunotherapeutic agents—both the old ones (IFN-α and IL-2) and the revolutionary immune checkpoint inhibitors.

• Hypothyroidism related to cytotoxic agents may not be so rare as initially conceived.

• Central hypothyroidism is a well-established adverse effect of bexarotene used for treatment of refractory cutaneous T-cell lymphomas, but relevant data in the setting of solid non-thyroid tumors are still lacking.

• An individualized continuum of care of anticancer treatment-induced hypothyroidism in patients with solid non-thyroid tumors could be grounded on five pillars: prevention, vigilance, diagnosis, treatment, and monitoring.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.