# Multigland dysfunction from immune-checkpoint inhibitors: a case of hypothyroidism, diabetes, and adrenal insufficiency

## TL;DR

A patient developed multiple endocrine issues, including hypothyroidism, diabetes, and adrenal insufficiency, after treatment with immune-checkpoint inhibitors for kidney cancer.

## Contribution

This case highlights the rare but significant occurrence of sequential multiglandular endocrine toxicities from immune-checkpoint inhibitors.

## Key findings

- A patient developed hypothyroidism, diabetes, and adrenal insufficiency during ICI therapy.
- The patient required hormone replacement and insulin therapy to manage these endocrine toxicities.
- Multigland dysfunction from ICIs is a rare but important adverse event that requires early recognition and management.

## Abstract

Immune-checkpoint inhibitors (ICIs) such as nivolumab and ipilimumab have improved outcomes in metastatic renal cell carcinoma (RCC) but can cause immune-related adverse events (irAEs), including potentially irreversible endocrine toxicities with long-term treatment implications. We present a 62-year-old man with metastatic clear-cell RCC who developed 3 distinct endocrine irAEs during ICI therapy: thyroiditis evolving into hypothyroidism, insulin-dependent diabetes mellitus with diabetic ketoacidosis, and secondary adrenal insufficiency (AI), necessitating ICI discontinuation. Additionally, he experienced immune-mediated inflammatory arthritis. His course required thyroid hormone replacement, insulin therapy, and hydrocortisone for AI. This case underscores the potential for sequential, multiglandular endocrine toxicities from ICIs, a phenomenon infrequently reported in the literature. Clinicians should remain vigilant for delayed or evolving presentations, even in the absence of autoantibodies or radiographic abnormalities. Early recognition, multidisciplinary management, and long-term follow-up are critical for ICI-associated endocrinopathies.