Category: Diabetes/Prediabetes/Hypoglycemia

Monitor: 7


Saturday, Apr 27
10:00 AM – 10:30 AM

Objective :

A 64-year-old Caucasian male with a history of thymic squamous cell carcinoma underwent resection and adjuvant radiation. The patient’s disease progressed with metastases to the bilateral lungs and liver, despite three lines of adjuvant chemotherapy. He was subsequently started on palliative therapy with pembrolizumab. Following the fourth cycle of pembrolizumab, the patient presented to the hospital with a two-day history of nausea, vomiting, and fatigue. He was diagnosed with diabetic ketoacidosis (DKA) with serum glucose of 891 mg/dL, beta-hydroxybutyric acid of 8.8 mmol/L, pH of 7.14, bicarbonate of 14 mEq/L, and anion gap of 26 mEq/L. The hemoglobin A1c was 8.9%. CT imaging of the abdomen did not show any abnormalities of the pancreas. The patient did not have a prior history of diabetes, nor was he on steroids. He was initially treated with intravenous insulin, and transitioned to long-acting insulin upon discharge. One month later, his hemoglobin A1c was noted to have improved to 6.6%, though he remained insulin-dependent.

Methods : n/a

Results : n/a

Discussion :

Pembrolizumab is a monoclonal antibody against the programmed death receptor-1 (PD-1) pathway. By blocking this immune checkpoint that typically inhibits T-cell activation, it activates the immune system to attack cancer cells. This also affects normal, healthy cells leading to adverse effects including immune-mediated colitis, pneumonitis, hepatitis, hypothyroidism, and nephritis. Autoimmune diabetes is rare, as it was reported in only 0.2% of patients receiving pembrolizumab in three randomized, active-controlled clinical trials. Review of literature shows twelve reported cases of pembrolizumab-induced autoimmune diabetes, eight of which involved patients presenting with DKA. The mechanism by which PD-1 inhibitors induce autoimmune diabetes is not fully understood. However, in non-obese diabetic mice models, PD-1 blockade has been shown to result in type 1 diabetes mellitus. In addition, studies in humans have suggested that patients with type 1 diabetes mellitus have reduced PD-1 expression on T-cells. Thus, it is hypothesized that PD-1 inhibitors may lead to T-cell activation, causing an autoimmune reaction against beta cells of the pancreas. Immunotherapy is expanding as a potential treatment option for various cancer types. It is important for healthcare providers to be aware of the potentially life-threatening immune-related adverse effects of immunotherapy.

Conclusion :

Our case described a patient with metastatic thymic cancer who developed new-onset autoimmune diabetes induced by pembrolizumab. Though rare, awareness should be raised particularly with the increasingly widespread use of immunotherapy.


Stephanie Sam

Internal Medicine Resident Physician
MercyOne Des Moines Medical Center - Department of Internal Medicine
Des Moines, Iowa

Dr. Sam is a current 2nd-year resident physician in Internal Medicine at Mercy Medical Center in Des Moines, Iowa.

Mohamed Elfeki

Internal Medicine Resident Physician
University of Iowa Des Moines, Department of Internal Medicine
Des Moines, Iowa

Dr. Elfeki is a current 2nd-year resident physician in Internal Medicine at the University of Iowa in Des Moines, Iowa

Teck K. Khoo

Iowa Diabetes and Endocrinology Center, Mercy Clinics
Des Moines, Iowa

Dr. Khoo is an endocrinologist at the Iowa Diabetes and Endocrinology Center in Des Moines, Iowa