Abstract: PUB203
Concurrent Immune Checkpoint Inhibitor-Induced Autoimmune Diabetes, Thyroiditis, and AKI After Pembrolizumab Administration
Session Information
Category: Onconephrology
- 1600 Onconephrology
Authors
- Elmahi, Mahmoud, Stony Brook Medicine, Stony Brook, New York, United States
- Ali, Selma, Stony Brook Medicine, Stony Brook, New York, United States
- Sheikh, Fatima Danish, Stony Brook Medicine, Stony Brook, New York, United States
Introduction
Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), including endocrine and renal toxicity. ICI-induced diabetes mellitus is rare but life-threatening and often presents abruptly as diabetic ketoacidosis (DKA).
Case Description
A 43-year-old male with stage III clear cell renal cell carcinoma status post left radical nephrectomy was started on pembrolizumab. He presented a few weeks later with projectile non-bilious, non-bloody emesis, fatigue, severe back pain, dry mouth and increased fluid intake. On arrival, he was tachycardic and hypotensive (HR 133 bpm, BP 95/47 mmHg, RR 26). He received emergent management for hyperkalemia in the setting of DKA. He was treated with an insulin infusion and aggressive fluid resuscitation. Laboratory evaluation demonstrated profound insulin deficiency with C-peptide 0.2 ng/mL and markedly elevated GAD antibodies >250 IU/mL, confirming autoimmune beta-cell destruction. His course was complicated by acute kidney injury (AKI) in the setting of severe DKA. Subsequently, he was diagnosed with immune-mediated thyroiditis progressing to hypothyroidism and was treated with levothyroxine.
Discussion
This case highlights pembrolizumab-induced autoimmune diabetes presenting as fulminant DKA with concurrent thyroiditis and AKI. The relatively modest HbA1c reflects the abrupt onset typical of this condition. Concurrent thyroiditis further supports systemic immune activation. From a nephrology perspective, AKI in patients receiving ICIs has a broad differential. In this patient, the AKI was a prerenal injury which progressed to acute tubular injury due to severe volume depletion from osmotic diuresis, hemodynamic instability and hyperosmolar state. Distinguishing DKA-associated AKI from ICI-induced intrinsic renal injury is critical, as management differs significantly. While DKA-related AKI is treated with supportive care, ICI-associated acute interstitial nephritis often requires immunosuppression and discontinuation of therapy. Unlike other irAEs, ICI-induced diabetes is typically irreversible, necessitating lifelong insulin therapy.
Acknowledgment
ICIs can cause rapid-onset, life-threatening endocrinopathies. Nephrologists should be aware of this entity given its association with severe metabolic derangements and AKI.