Sintilimab-induced diabetes mellitus and thyroid dysfunction in patient with gastric adenocarcinoma: A case report and literature review.

RATIONALE

Immune checkpoint inhibitors bring hope to cancer patients but may also lead to severe immune-related adverse events (irAEs). Although irAEs during treatment are well-characterized, delayed immune-related events (DIRE) remain underreported. Here, we report a case of sintilimab-induced delayed immune-related diabetes mellitus, accompanied by ICI-related thyroid disease (ICI-TD). Cases involving both ICI-TD and ICI-related diabetes mellitus (ICI-DM) are also relatively rare. This study systematically aggregates dual endocrine irAEs to provide valuable insights for clinical practice.

PATIENT CONCERNS

A 60-year-old Chinese male diagnosed with gastric adenocarcinoma received a multimodal treatment regimen consisting of sintilimab, chemotherapy, and apatinib. He completed 3 cycles of chemotherapy and 4 cycles of sintilimab. Due to disease progression, sintilimab was discontinued, but apatinib was continued for an additional 1 month. No further antitumor therapy was administered afterward. Four months later, he was admitted to the emergency department due to persistent nausea, vomiting, and abdominal pain.

DIAGNOSES

Thyroid dysfunction induced by sintilimab was identified during treatment. His laboratory tests contributed to the diagnosis of diabetes ketoacidosis. Fulminant type 1 diabetes mellitus attributed to sintilimab met diagnostic criteria: plasma glucose 42.01 mmol/L, glycated hemoglobin 7.5%, C-peptide <0.02 µg/L, and negative islet autoantibodies.

INTERVENTIONS

Levothyroxine replacement therapy was initiated for hypothyroidism, whereas diabetes ketoacidosis during hospitalization required intensive insulin therapy combined with fluid resuscitation.

OUTCOMES

The patient exhibited persistent blood glucose fluctuations during hospitalization, including 2 hypoglycemic episodes. Post-treatment stabilization required basal-bolus insulin at discharge, with continued levothyroxine for hypothyroidism.

LESSONS

We report a rare case of concurrent ICI-TD and ICI-DM following sintilimab therapy. This case underscores the potential for DIRE, with onset occurring months posttreatment. Combined with a systematic review of existing cases, this study provides critical insights into surveillance strategies and pathogenesis of irAEs.