A case of pembrolizumab-induced severe DKA and hypothyroidism in a patient with metastatic melanoma.

A case of pembrolizumab-induced severe DKA and hypothyroidism in a patient with metastatic melanoma.

Publication date: Mar 05, 2019

Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy and improved outcomes for patients with advanced disease. Pembrolizumab, a monoclonal antibody that acts as a programmed cell death 1 (PD-1(PDCD1)) inhibitor, has been approved for the treatment of advanced melanoma and other solid tumours. Immune-related adverse events (irAEs) including endocrinopathies have been well described with this and other PD-1 inhibitors. While hypothyroidism and hyperthyroidism, and less commonly hypophysitis, are the most common endocrinopathies occurring in patients treated with pembrolizumab, the incidence of type 1 diabetes mellitus (T1DM) was low in clinical trials. We report a case of pembrolizumab-induced primary hypothyroidism and T1DM presenting with severe diabetic ketoacidosis (DKA). A 52-year-old male patient was treated with pembrolizumab for metastatic melanoma. He presented to the emergency department with a 1-day history of nausea and vomiting 2 weeks after his seventh dose of pembrolizumab, having complained of polyuria and polydipsia for 2 months before presentation. He had been diagnosed with thyroid peroxidase (TPO) antibody-negative hypothyroidism, requiring thyroxine replacement, shortly after his fifth dose. Testing revealed a severe DKA (pH: 6.99, glucose: 38.6 mmol/L, capillary ketones: 4.9 and anion gap: 34.7). He was treated in the intensive care unit as per the institutional protocol, and subsequently transitioned to subcutaneous basal-bolus insulin. After his diabetes and thyroid stabilised, pembrolizumab was recommenced to treat his advanced melanoma given his excellent response. This case highlights the importance of blood glucose monitoring as an integral part of cancer treatment protocols composed of pembrolizumab and other ICIs. Learning points: The incidence of T1DM with pembrolizumab treatment is being increasingly recognised and reported, and DKA is a common initial presentation. Physicians should counsel patients about this potential irAE and educate them about the symptoms of hyperglycaemia and DKA. The ESMO guidelines recommend regular monitoring of blood glucose in patients treated with ICIs, a recommendation needs to be incorporated into cancer treatment protocols for pembrolizumab and other ICIs in order to detect hyperglycaemia early and prevent DKA.

Hakami, O.A., Ioana, J., Ahmad, S., Tun, T.K., Sreenan, S., and McDermott, J.H. A case of pembrolizumab-induced severe DKA and hypothyroidism in a patient with metastatic melanoma. 21857. 2019 Endocrinol Diabetes Metab Case Rep (2019):

Concepts Keywords
Anion Gap Antibodies
Antibody Pembrolizumab
Basal Hyperglycemia
Blood Glucose Monitoring Diabetes mellitus
Bolus Diabetic ketoacidosis
Capillary Autoimmune diseases
Clinical Trials Metabolic disorders
Diabetes Endocrine diseases
Diabetes Mellitus RTT
Diabetic Ketoacidosis Diabetes
Endocrinopathies Clinical medicine
Glucose Organ systems
Hyperglycaemia Medicine
Hyperthyroidism Treatment protocols
Hypothyroidism Inhibitors hypothyroidism hyperthyroidism
Incidence Primary hypothyroidism T1DM
Inhibitor Vomiting
Insulin Day history nausea
Integral Pembrolizumab metastatic melanoma
Intensive Care Unit Polyuria
Ketones
Melanoma
Monoclonal Antibody
Nausea
PH
Polydipsia
Polyuria
Protocol
Subcutaneous
Thyroid
Thyroid Peroxidase
Thyroxine
Vomiting

Semantics

Type Source Name
drug DRUGBANK Thyrotropin alfa
disease DOID Thyroiditis
disease MESH Thyroiditis
drug DRUGBANK Metformin
gene UNIPROT CEP55
drug DRUGBANK Levothyroxine
disease MESH Dehydration
gene UNIPROT RASA1
gene UNIPROT RGS6
drug DRUGBANK D-glucose
drug DRUGBANK Dextrose unspecified form
gene UNIPROT THPO
gene UNIPROT TPO
disease MESH emergency
disease DOID diabetic ketoacidosis
disease MESH diabetic ketoacidosis
disease DOID type 1 diabetes mellitus
disease MESH type 1 diabetes mellitus
disease MESH hypophysitis
disease DOID hyperthyroidism
disease MESH hyperthyroidism
gene UNIPROT RPL17
gene UNIPROT PDCD1
pathway BSID Programmed Cell Death
disease DOID cancer
disease MESH cancer
gene UNIPROT MTUS1
gene UNIPROT MTUS2
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
disease DOID hypothyroidism
disease MESH hypothyroidism
drug DRUGBANK Pembrolizumab

Original Article

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