Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports

Abstract Background Since 2011 six immune checkpoint inhibitors (ICI) have been approved to treat patients with many advanced solid tumor and hematological malignancies to improve their prognosis. Case reports of their endocrine immune-related adverse events [irAEs]) are increasingly published as more real-world patients with these malignancies are treated with these drugs. They alert physicians of a drug’s AEs (which may change during a drug’s life cycle) and contribute to post-marketing safety surveillance. Using a modified framework of Arksey and O’Malley, we conducted a scoping review of the spectrum and characteristics of ICI-induced endocrinopathies case reports before and after ICIs are marketed. Methods In July 2017, we searched, without date and language restrictions, 4 citation databases for ICI-induced endocrinopathies. We also hand-searched articles’ references, contents of relevant journals, and ran supplemental searches to capture recent reports through January 2018. For this study, a case should have information on type of cancer, type of ICI, clinical presentation, biochemical tests, treatment plus temporal association of ICI initiation with endocrinopathies. Two endocrinologists independently extracted the data which were then summarized and categorized. Results One hundred seventy nine articles reported 451 cases of ICI-induced endocrinopathies - 222 hypopituitarism, 152 thyroid disorders, 66 diabetes mellitus, 6 primary adrenal insufficiencies, 1 ACTH-dependent Cushing’s syndrome, 1 hypoparathyroidism and 3 diabetes insipidus cases. Their clinical presentations reflect hormone excess or deficiency. Some were asymptomatic and others life-threatening. One or more endocrine glands could be affected. Polyglandular endocrinopathies could present simultaneously or in sequence. Many occur within 5 months of therapy initiation; a few occurred after ICI was stopped. Mostly irreversible, they required long-term hormone replacement. High dose steroids were used when non-endocrine AEs coexisted or as therapy in adrenal insufficiency. There was variability of information in the case reports but all met the study criteria to make a diagnosis. Conclusions The spectrum of ICI-induced endocrinopathies is wide (5 glands affected) and their presentation varied (12 endocrinopathies). Clinical reasoning integrating clinical, biochemical and treatment information is needed to properly diagnose and manage them. Physicians should be vigilant for their occurrence and be able to diagnose, investigate and manage them appropriately at onset and follow-up.https://deepblue.lib.umich.edu/bitstream/2027.42/147443/1/40842_2018_Article_73.pd

Evaluation of Hemoglobin A1c Criteria to Assess Preoperative Diabetes Risk in Cardiac Surgery Patients

Objective: Hemoglobin A1c (A1C) has recently been recommended for diagnosing diabetes mellitus and diabetes risk (prediabetes). Its performance compared with fasting plasma glucose (FPG) and 2-h post-glucose load (2HPG) is not well delineated. We compared the performance of A1C with that of FPG and 2HPG in preoperative cardiac surgery patients. Methods: Data from 92 patients without a history of diabetes were analyzed. Patients were classified with diabetes or prediabetes using established cutoffs for FPG, 2HPG, and A1C. Sensitivity and specificity of the new A1C criteria were evaluated. Results: All patients diagnosed with diabetes by A1C also had impaired fasting glucose, impaired glucose tolerance, or diabetes by other criteria. Using FPG as the reference, sensitivity and specificity of A1C for diagnosing diabetes were 50% and 96%, and using 2HPG as the reference they were 25% and 95%. Sensitivity and specificity for identifying prediabetes with FPG as the reference were 51% and 51%, respectively, and with 2HPG were 53% and 51%, respectively. One-third each of patients with prediabetes was identified using FPG, A1C, or both. When testing A1C and FPG concurrently, the sensitivity of diagnosing dysglycemia increased to 93% stipulating one or both tests are abnormal; specificity increased to 100% if both tests were required to be abnormal. Conclusions: In patients before cardiac surgery, A1C criteria identified the largest number of patients with diabetes and prediabetes. For diagnosing prediabetes, A1C and FPG were discordant and characterized different groups of patients, therefore altering the distribution of diabetes risk. Simultaneous measurement of FGP and A1C may be a more sensitive and specific tool for identifying high-risk individuals with diabetes and prediabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90436/1/dia-2E2011-2E0074.pd

Severe hyperglycemia and insulin resistance in patients with SARS-CoV-2 infection: a report of two cases

Abstract Background Severe insulin resistance is an uncommon finding in patients with type 2 diabetes but is often associated with difficult to managing blood glucose. While severe insulin resistance is most frequently seen in the setting of medication side effects or rare genetic conditions, this report of two cases highlights the presence of severe insulin resistance in the setting of severe COVID-19 and explores how this may contribute to the poor prognosis of patients with diabetes who become infected with SARS-CoV-2. Case presentation Here we present the cases of two African-American women with pre-existing type 2 diabetes who developed severe COVID-19 requiring mechanical ventilation and concurrent severe insulin resistance with total daily insulin dose requirements of greater than 5 unit/kg. Both patients received aggressive insulin infusion and subcutaneous insulin therapy to obtain adequate glucose management. As their COVID-19 clinical course improved, their severe insulin resistance improved as well. Conclusions The association between critical illness and hyperglycemia is well documented in the literature, however severe insulin resistance is not commonly identified and may represent a unique clinical feature of the interaction between SARS-CoV-2 infection and type 2 diabetes.http://deepblue.lib.umich.edu/bitstream/2027.42/174033/1/40842_2021_Article_121.pd

Can a single interactive seminar durably improve knowledge and confidence of hospital diabetes management?

Abstract Background Safe and effective diabetes management in the hospital is challenging. Inadequate knowledge has been identified by trainees as a key barrier. In this study we assess both the short-term and long-term impact of an interactive seminar on medical student knowledge and comfort with hospital diabetes management. Methods An interactive seminar covering hospital diabetes management and utilizing an audience response system was added to the third-year medical student curriculum. Students were given a multiple choice assessment immediately before and after the seminar to assess their comprehension of the material. Students were also asked to rate their confidence on this topic. Approximately 6 months later, students were given the same assessment to determine if the improvements in hospital diabetes knowledge and confidence were durable over time. Students from the preceding medical school class, who did not have a hospital diabetes seminar as a part of their curriculum, were used as a control. Results Fifty–three students participated in the short-term assessment immediately before and after the seminar. The mean score (maximum 15) was 7.7 +/- 2.7 (51%) on the pre-test and 11.4 +/- 1.8 (76%) on the post-test (p < 0.01). 75 students who attended the seminar completed the same set of questions 6 months later with mean score of 9.2 ± 2.3 (61%). The control group of 100 students who did not attend seminar had a mean score of 8.8 ± 2.5 (58%). The difference in scores between the students 6-months after the seminar and the control group was not significantly different (p = 0.30). Conclusions Despite initial short-term gains, a single seminar on hospital diabetes management did not durably improve trainee knowledge or confidence. Addition of repeated and focused interactions during clinical rotations or other sustained methods of exposure need to be evaluated.http://deepblue.lib.umich.edu/bitstream/2027.42/134749/1/40842_2016_Article_38.pd