Kennedy, Randol

Immune checkpoint inhibitors (ICIs) are an important class of cancer treatment. Endocrine immune-related adverse events (E-irAEs) account for a significant proportion of irAEs in ICI-treated patients. Diagnosing E-irAEs accurately and timely can be challenging in the absence of clear categorization and standardization across oncology, endocrinology and other specialties. While existing guidelines provide some broad directions to diagnosis and management, they lack clarity on irAE-specific symptom evaluation and work-up, as well as assessment of severity. These limitations can then impact triage, time-sensitive management and care escalation to specialists such as oncoendocrinologists. The objective of this study was to develop consensus-based statements on disease definitions for E-irAEs. A core working group of endocrinologists with expertise in the oncoendocrinology field drafted a survey with statements outlining the general approach to E-irAEs, disease definition and management approach of six specific diagnoses: ir-thyroiditis thyrotoxic phase, ir-thyroiditis hypothyroidism, ir-Graves’ disease, ir-hypophysitis, ir-adrenalitis and ir-type 1 diabetes mellitus. Severity grading tables were drafted for three disease categories—“thyroid”, “pituitary and adrenal”, and “diabetes mellitus”. A two-round modified Delphi process, using the RAND/University of California Los Angeles (RAND/UCLA) Appropriateness Method, was employed. In this process, a 25-member voting panel consisting of endocrinologists, oncologists and other specialists and healthcare providers with experience in management of ICI-treated patients and irAEs was recruited. The panel rated anonymously on usability, accuracy, appropriateness or agreement of 41 items on a 9-point scale in Survey 1, after which a meeting was convened. Statements were modified based on voting results from Survey 1 and Meeting 1, and the process was repeated in Survey 2 and Meeting 2. At the end of this process, consensus was achieved for all statements. Our study findings address the gap in standardized nomenclature, clinical, laboratory and radiological evaluations, and management principles of E-irAEs. With consensus achieved from a panel of experts from a variety of disciplines, we anticipate that the statements can form the basis for standardization of the diagnostic process and improvement of patient care.

Abstract Disclosure: R. Kennedy: None. D.A. D'Alessio: None. A.V. Vella: None. Introduction: Selective arterial calcium stimulation testing (SACST) can be utilized in patients to localize solitary insulinomas when imaging is non diagnostic. While a heterogenous stimulation pattern suggests NIPHS, or multiple insulinomas this case uniquely demonstrates such a pattern with a solitary insulinoma. Clinical Case: The patient is a 48 year old female who presented to the emergency department (ED) for bizarre behavior which resolved with a sweetened drink. Serum glucose was 62 mg/dL, she was treated with IV dextrose and was discharged from the ED. She was referred to outpatient endocrinology for further evaluation where continuous glucose monitoring confirmed predominantly fasting hypoglycemia. Adrenal insufficiency was excluded. She was admitted for a 72 hour inpatient fast where the patient achieved hypoglycemia within 24 hours, with glucose 46 mg/dL (associated with neuroglycopenic symptoms), beta hydroxybutyrate < 0.18 mmol/L, insulin 3.9 mcIU/mL, proinsulin 157pmol/L, c-peptide 1.4 ng/mL and a glucose rise greater than 25mg/dL after glucagon administration. Sulfonylurea screen and insulin antibodies were negative; IGF1 within normal limits. These labs were consistent with hyperinsulinemic hypoglycemia. An MRI pancreas however did not reveal an insulinoma. The patient therefore underwent a SACST, demonstrating a 10 fold response in the territory of the gastroduodenal artery and splenic artery, as well as a 3 fold response in the superior mesenteric artery. This heterogenous pattern in addition to the marked response in each arterial territory raised the possibility of multiple insulinomas. However as there were no tumors present on imaging, medical management was initiated with close follow up. She was trialed with months of somatostatin analogs and diazoxide with minimal improvement in the frequency and severity of her hypoglycemia. About a year after her initial diagnosis, repeat abdominal imaging (CT and MRI) revealed an 8 mm arterial hyper-enhancing lesion in the body of the pancreas concerning for neuroendocrine tumor. Repeat SACST was performed, this time showing a greater than 10 fold response in all three arterial territories. Angiography showed a tumor blush that was visible when each of the three major arteries were injected sequentially. She underwent laparoscopic pancreatic enucleation. The lesion was located on the body of the pancreas, with histology confirming an insulinoma. The patient responded promptly post operatively; her symptoms resolved without further need of medical management. Conclusion: Our case shows that the interpretation of an SACST should take into account the arterial anatomy before ascribing a non-focal response to multiple territories of insulin hypersecretion. Presentation: 6/1/2024