Pembrolizumab-Induced Hypothyroidism and Diabetes Mellitus: A Rare Case Presentation Post-Treatment

TL;DR

A patient developed type 1 diabetes and hypothyroidism after pembrolizumab treatment, highlighting rare but important side effects of this cancer therapy.

Contribution

Presents a rare case of pembrolizumab-induced diabetes and hypothyroidism, emphasizing the need for clinical awareness of these endocrine immune-related adverse events.

Findings

Pembrolizumab treatment was associated with severe hyperglycemia and suppressed C-peptide levels, indicating type 1 diabetes.

Abnormal thyroid function tests confirmed pembrolizumab-induced hypothyroidism.

Symptoms occurred two months post-treatment, underscoring delayed onset of immune-related adverse events.

Abstract

Pembrolizumab is a humanized monoclonal antibody that targets programmed death-1 (PD-1), a cell surface receptor expressed on activated T lymphocytes. By blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, pembrolizumab enhances T-cell-mediated immune responses against tumor cells. This immunotherapeutic strategy has shown significant clinical benefit in a range of malignancies, including metastatic melanoma, non-small cell lung cancer, and renal cell carcinoma.

However, its mechanism of action can also disrupt immune self-tolerance, leading to immune-related adverse events (irAEs), particularly involving endocrine organs. These irAEs may manifest as autoimmune thyroiditis, hypophysitis, or, more rarely, insulin-dependent diabetes mellitus.

In this case, the patient presented to a rural district general hospital with a several-week history of fatigue, polydipsia, and polyuria approximately two months after completing a one-year course of pembrolizumab for metastatic melanoma. Given the delayed and nonspecific symptom onset, diagnosis required a high degree of clinical suspicion. Laboratory investigations revealed severe hyperglycemia, suppressed C-peptide levels, and abnormal thyroid function tests. These findings were consistent with pembrolizumab-induced type 1 diabetes mellitus and hypothyroidism, both of which are recognized, though uncommon, endocrine irAEs.

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