Endocrine Dysfunction From Immune Checkpoint Inhibitors: Pearls and Pitfalls in Evaluation and Management.

Immune checkpoint inhibitors (ICPis) have proven extremely efficacious in cancer therapy but also lead to a plethora of immune-related adverse events (irAEs). The endocrine irAEs are not only quite common but also may pose a challenge to the clinician while managing a patient with cancer treated with ICPis. The clinical features of endocrine dysfunction are usually nonspecific and may overlap with concurrent illnesses, underlying the importance of accurate hormone testing and efforts toward case-finding. The management of endocrine irAEs is unique in the focus being on hormone replacement rather than curtailing the autoimmune process. Although the management of thyroid irAEs appears straightforward, adrenal insufficiency and insulin-dependent diabetes can be life-threatening if not promptly recognized and treated. This clinical review synthesizes the studies to provide pearls and pitfalls in the evaluation and management of endocrine irAEs with specific reference to guidelines from oncologic societies.

Pitfalls in Performing and Interpreting Inferior Petrosal Sinus Sampling: Personal Experience and Literature Review.

CONTEXT: Inferior petrosal sinus sampling (IPSS) helps differentiate the source of ACTH-dependent hypercortisolism in patients with inconclusive biochemical testing and imaging, and is considered the gold standard for distinguishing Cushing disease (CD) from ectopic ACTH syndrome. We present a comprehensive approach to interpreting IPSS results by examining several real cases. EVIDENCE ACQUISITION: We performed a comprehensive review of the IPSS literature using PubMed since IPSS was first described in 1977. EVIDENCE SYNTHESIS: IPSS cannot be used to confirm the diagnosis of ACTH-dependent Cushing syndrome (CS). It is essential to establish ACTH-dependent hypercortisolism before the procedure. IPSS must be performed by an experienced interventional or neuroradiologist because successful sinus cannulation relies on operator experience. In patients with suspected cyclical CS, it is important to demonstrate the presence of hypercortisolism before IPSS. Concurrent measurement of IPS prolactin levels is useful to confirm adequate IPS venous efflux. This is essential in patients who lack an IPS-to-peripheral (IPS:P) ACTH gradient, suggesting an ectopic source. The prolactin-adjusted IPS:P ACTH ratio can improve differentiation between CD and ectopic ACTH syndrome when there is a lack of proper IPS venous efflux. In patients who have unilateral successful IPS cannulation, a contralateral source cannot be excluded. The value of the intersinus ACTH ratio to predict tumor lateralization may be improved using a prolactin-adjusted ACTH ratio, but this requires further evaluation. CONCLUSION: A stepwise approach in performing and interpreting IPSS will provide clinicians with the best information from this important but delicate procedure.

HbA1c and Glucose Management Indicator Discordance: A Real-World Analysis.

Background: There can be marked discordance between laboratory and estimated (using the glucose management indicator [GMI]) glycated hemoglobin (HbA1c) from continuous glucose monitoring (CGM). This may cause errors in diabetes management. This study evaluates discordance between laboratory and CGM-estimated HbA1c (eA1C). Methods: We performed a retrospective review of patients with diabetes who use CGM. The patients were seen at the University of Washington (UW) Diabetes Care Center from 2012 to 2019. We used UW's Institute of Translational Health Sciences to extract eligible encounters from the electronic medical record. We required that patients use CGM and that HbA1c and sensor data be obtained fewer than 4 weeks apart. There were no exclusion criteria. We calculated HbA1c-GMI discordance for each subject and assessed for any impact of comorbidities. We defined HbA1c-GMI discordance as absolute difference between laboratory and eA1C. Results: This study included 641 separate office encounters. Ninety-one percent of patients had type 1 diabetes. Most patients had diabetes for greater than 20 years. The mean duration of CGM wear was 24.5 ± 8 days. Only 11% of patients had HbA1c-GMI discordance <0.1%, but 50% and 22% had differences ≥0.5% and ≥1%. There was increased discordance with advanced chronic kidney disease (estimated glomerular filtration rate <60). Discussion: We found substantial discordance between laboratory and eA1C in a real-world setting. Clinicians need be aware that HbA1c may not as accurately reflect mean glucose as previously appreciated.

More than maths and mindreading: sex differences in empathizing/systemizing covariance.

Empathizing-Systemizing theory posits a continuum of cognitive traits extending from autism into normal cognitive variation. Covariance data on empathizing and systemizing traits have alternately suggested inversely dependent, independent, and sex-dependent (one sex dependent, the other independent) structures. A total of 144 normal undergraduates (65 men, 79 women) completed the Reading the Mind in the Eyes, Embedded Figures, and Benton face recognition tests, the Autism Spectrum Quotient, and measures of digit length ratio and field of study; some also completed tests of motion coherence threshold (64) and go/no-go motor inhibition (128). Empathizing and systemizing traits were independent in women, but largely dependent in men. In men, level of systemizing skill required by field of study was directly related to social interactive and mindreading deficits; men's social impairments correlated with prolonged go/no-go response times, and men tended to apply systemizing strategies to solve problems of empathizing or global processing: rapid perceptual disembedding predicted heightened sensitivity to facial emotion. In women, level of systemizing in field was related to male-typical digit ratios and autistic superiorities in detail orientation, but not to autistic social and communicative impairments; and perceptual disembedding was related to social interactive skills but independent of facial emotion and visual motion perception.