Incidence of thyroid function test abnormalities in patients receiving immune checkpoint inhibitor therapy for cancer: A single institution retrospective review.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14569-e14569
Author(s):  
Nisha Subhash Patel ◽  
Anais Oury ◽  
Lyudmila Bazhenova ◽  
Gregory A. Daniels ◽  
Sandip Pravin Patel
Keyword(s):  
Thyroid Function ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Thyroid Function Test ◽  
Single Institution ◽  
Function Test ◽  
Checkpoint Inhibitor Therapy ◽  
Thyroid Abnormalities ◽  
New Onset

e14569 Background: With the advent of immune-checkpoint inhibitor (ICI) therapy, thyroid function test abnormalities (TFTA) are common with reported incidence range of 2-15%. Our aim was to describe the incidence of TFTAs retrospectively in patients (pts) on ICI therapy. Methods: 285 pts reviewed (178 male, 107 female; ages 16-94) of which 218 had no baseline TFTA, 61 had baseline TFTAs, and 6 had thyroidectomy (excluded). Pts received at least one dose of ipilimumab (I) and/or nivolumab (N) or pembrolizumab (P). Post-treatment TFTA was classified according to definitions of thyroid abnormalities when possible. Results: A total of 35% (76/218) pts had new onset TFTAs on ICI. Of note, 70.5% (43/61) had baseline TFTA that were exacerbated by ICI. Median time to new onset or exacerbated baseline TFTA were 46 & 33 days respectively. Of note, 65% (20/31) of pts on both I+N had new onset TFTA, compared to 31.3% (15/48) with I, 31.5% (28/89) N, 26% (13/50) P. Conclusions: Incidence of TFTAs with ICI was higher than expected in our pts. Pts with baseline TFTA and/or I+N combination therapy had higher incidence of TFTA than one agent ICI therapy. In conclusion, we recommend more frequent evaluation of TFT in the first two months, especially in those with baseline TFTA. [Table: see text]

scholarly journals Durvalumab-induced diabetic ketoacidosis followed by hypothyroidism

2019 ◽  
Vol 2019 ◽  
Author(s):  
Shivani Patel ◽  
Venessa Chin ◽  
Jerry R Greenfield
Keyword(s):  
Diabetic Ketoacidosis ◽  
Thyroid Function ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Reference Range ◽  
Checkpoint Inhibitor ◽  
Autoimmune Diabetes ◽  
Inhibitor Therapy ◽  
Thyroid Function Tests ◽  
Checkpoint Inhibitor Therapy

Summary Durvalumab is a programmed cell death ligand 1 inhibitor, which is now approved in Australia for use in non-small-cell lung and urothelial cancers. Autoimmune diabetes is a rare immune-related adverse effect associated with the use of immune checkpoint inhibitor therapy. It is now being increasingly described reflecting the wider use of immune checkpoint inhibitor therapy. We report the case of a 49-year-old female who presented with polyuria, polydipsia and weight loss, 3 months following the commencement of durvalumab. On admission, she was in severe diabetic ketoacidosis with venous glucose: 20.1 mmol/L, pH: 7.14, bicarbonate 11.2 mmol/L and serum beta hydroxybutyrate: >8.0 mmol/L. She had no personal or family history of diabetes or autoimmune disease. Her HbA1c was 7.8% and her glutamic acid decarboxylase (GAD) antibodies were mildly elevated at 2.2 mU/L (reference range: <2 mU/L) with negative zinc transporter 8 (ZnT8) and islet cell (ICA) antibodies. Her fasting C-peptide was low at 86 pmol/L (reference range: 200–1200) with a corresponding serum glucose of 21.9 mmol/L. She was promptly stabilised with an insulin infusion in intensive care and discharged on basal bolus insulin. Durvalumab was recommenced once her glycaemic control had stabilised. Thyroid function tests at the time of admission were within normal limits with negative thyroid autoantibodies. Four weeks post discharge, repeat thyroid function tests revealed hypothyroidism, with an elevated thyroid-stimulating hormone (TSH) at 6.39 mIU/L (reference range: 0.40–4.80) and low free T4: 5.9 pmol/L (reference range: 8.0–16.0). These findings persisted with repeat testing despite an absence of clinical symptoms. Treatment with levothyroxine was commenced after excluding adrenal insufficiency (early morning cortisol: 339 nmol/L) and hypophysitis (normal pituitary on MRI). Learning points: Durvalumab use is rarely associated with fulminant autoimmune diabetes, presenting with severe DKA. Multiple endocrinopathies can co-exist with the use of a single immune checkpoint inhibitors; thus, patients should be regularly monitored. Regular blood glucose levels should be performed on routine pathology on all patients on immune checkpoint inhibitor. Clinician awareness of immunotherapy-related diabetes needs to increase in an attempt to detect hyperglycaemia early and prevent DKA.

scholarly journals Checkpoint Inhibitor-Associated Autoimmune Diabetes Mellitus: A Case Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A371-A372
Author(s):  
Helen Prathiba Gnanapragasam ◽  
Rajeev Sharma
Keyword(s):  
Diabetes Mellitus ◽  
Thyroid Function ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Autoimmune Diabetes ◽  
Thyroid Function Test ◽  
Gad 65 ◽  
Checkpoint Inhibitor Therapy ◽  
Gad 65 Antibodies ◽  
New Onset

Abstract Introduction: Checkpoint Inhibitors have revolutionized the management in oncology by stimulating the immunological response to cancer. On the contrary, there is an increase in immune-related adverse effects affecting various systems including the endocrine. We report a unique case of new-onset diabetes with diabetic ketoacidosis (DKA) within 18 days of receiving checkpoint inhibitors for Merkel Cell Carcinoma. Clinical Case: An 86-year-old man diagnosed with locally advanced Merkel cell carcinoma underwent surgery and radiotherapy to his right face and neck. Four months later, the positron emission tomography (PET) scan was consistent with liver metastasis. Pembrolizumab, a programmed death receptor-1 (PD-1) inhibitor was initiated as next line treatment. Prior to starting pembrolizumab, his blood glucose was 92 mg/dL (60–120) with no previous history of diabetes mellitus. He presented 18 days later to the emergency room with altered mental status, polyuria, and polydipsia with a blood glucose of 980 mg/dL, anion gap of 26 mmol/L (5–15), and was managed for DKA with new-onset Diabetes Mellitus. HbA1C was 7.0% (4–5.6). He was discharged on subcutaneous insulin glargine once daily, pre-meals insulin aspart, and was referred to the endocrinology clinic. Further investigations obtained during the clinic visit demonstrated low C-peptide of &lt;0.7 ng/mL (0.8–6), glucose 76 mg/dL, positive glutamic acid decarboxylase (GAD-65) antibodies of &gt;25,000 nmol/mL (&lt;0.02), negative islet antigen-2 antibody, islet cell antibody and zinc transporter 8 antibodies. Other endocrine tests showed normal thyroid function, cortisol, and adrenocorticotrophic hormone (ACTH) levels. The patient was educated on checkpoint inhibitor-associated autoimmune diabetes and the need for a lifelong insulin regimen. Clinical Lesson: Our case highlights the immune-related adverse effect involving the endocrine system from checkpoint inhibitor therapy. In comparison to the other common endocrinopathies associated with checkpoint inhibitors, autoimmune diabetes is rare (~ 1–2% incidence) and only less than half demonstrate antibodies with a median time of 8 weeks since exposure. GAD-65 antibodies are the commonest antibody noted and our patient had a robust GAD-65 antibody of &gt;25,000 depleting C-peptide within 18 days of receiving the Pembrolizumab resulting in DKA with a new onset of diabetes. We conclude that diabetes mellitus is a rare but serious adverse effect of immune checkpoint inhibitor therapy. Society for Immunotherapy of Cancer Toxicity Management Working Group consensus recommendations from 2017 recommends routine screening to include baseline HbA1c, basic metabolic panel, thyroid function test, AM cortisol, and ACTH prior to treatment. It also recommends repeating the thyroid function test and basic metabolic panel to allow the monitoring of glycemic trends before each cycle.

A Systematic Review of Cases of Diabetes Mellitus following Immune Checkpoint Inhibitor Therapy for Cancer

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 204-LB ◽  
Author(s):  
KARA R. MIZOKAMI-STOUT ◽  
ROMA GIANCHANDANI ◽  
MARK MACEACHERN ◽  
RAVI M. IYENGAR ◽  
SARAH YENTZ ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy

scholarly journals Collaboration Between Rheumatology and Oncology in Immune Checkpoint Inhibitor Therapy

2018 ◽  
Vol 36 (26) ◽  
pp. 2743-2744 ◽  
Author(s):  
Donald L. Kimpel ◽  
Janet E. Lewis ◽  
Elizabeth Gaughan ◽  
William W. Grosh ◽  
Christiana Brenin
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy
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