# Clinical Course and Risk Factors of Lenvatinib‐Related Hypothyroidism in Hepatocellular Carcinoma: A Retrospective Cohort Study

## TL;DR

This study examines how lenvatinib affects thyroid function in liver cancer patients and identifies risk factors for hypothyroidism.

## Contribution

The study identifies age and lenvatinib dose as significant predictors of hypothyroidism in hepatocellular carcinoma patients.

## Key findings

- 21% of patients developed hypothyroidism during lenvatinib therapy.
- Age ≤ 63 years and higher lenvatinib doses were significant predictors of hypothyroidism.
- Levothyroxine therapy at lower doses was effective in managing TSH levels in most patients.

## Abstract

Lenvatinib‐related hypothyroidism occurs in 16%–22% of patients with hepatocellular carcinoma and may affect treatment management. Previous studies have reported elevated serum thyroid stimulating hormone (TSH) levels despite levothyroxine therapy, indicating the need for research on the optimal levothyroxine dose during lenvatinib therapy.

We aimed to explore the effect of lenvatinib on thyroid function, focusing on lenvatinib pharmacokinetics and factors influencing hypothyroidism development.

A retrospective cohort study involving 56 patients with hepatocellular carcinoma treated with lenvatinib was conducted at the Mie University Hospital. The primary outcome was grade ≥ 2 hypothyroidism. Demographic data, treatment details, and clinical outcomes were analyzed to identify factors associated with lenvatinib‐related hypothyroidism. In addition, we assessed the levothyroxine dose administered during treatment and the dose required to achieve TSH levels < 10 mIU/L. Twelve patients (21%) developed hypothyroidism during lenvatinib therapy. The median levothyroxine dose and time to onset of hypothyroidism were 25.0 [25.0–50.0] μg/day and 81.0 [15.0–208.0] days, respectively. Levothyroxine therapy was initiated at either a low or recommended dose, with 10 patients achieving TSH levels < 10 mIU/L. Significant predictors of hypothyroidism included age ≤ 63 years and a higher daily lenvatinib dose (≥ 0.152 mg/kg/day).

Initiation of levothyroxine therapy, even at lower doses, may be effective in managing lenvatinib‐related hypothyroidism. Underweight patients (e.g., body weight < 50 kg) require particular attention due to their increased susceptibility to hypothyroidism. Even though this study has limitations such as a small sample size and the lack of multivariate analysis, it provides valuable information for managing lenvatinib‐related hypothyroidism.