Ipilimumab is a monoclonal antibody directed against CTLA4 T-lymphocyte antigen used as cancer therapy. Immune-related adverse events are common side effects and may include hypophysitis-related hypopituitarism. The clinical features of six patients with ipilimumab-induced hypophysitis (IH) are described. The clinical features of IH reported in clinical trials, including the incidence of IH by gender and the likelihood of adrenal axis recovery, are summarized. Following the development of IH, most patients remain on glucocorticoid replacement despite efforts to withdraw therapy. Analysis of gender information in published clinical trials suggests that men are more prone to developing IH than women, and few patients fully recover the pituitary–adrenal axis function. Ipilimumab and other drugs within its class are likely to be used to treat many forms of cancer. Endocrinologists should anticipate a significant increase in the incidence of autoimmune hypophysitis. Strategies for early detection of IH and long-term management should be considered.

CONTEXT Time pressure has been implicated in the suboptimal diagnostic performance of doctors and in increases in diagnostic errors. However, the reasons underlying these effects are not clear. The aim of this study was to investigate the influence of time pressure on physicians' diagnostic accuracy and to explore the mediating effects of perceived stress (emotional pathway) and number of plausible diagnostic hypotheses (cognitive pathway) on the proposed relationship.METHODS We conducted a randomised controlled experiment. A total of 75 senior internal medicine residents completed eight written clinical cases under conditions with (n = 40) or without (n = 35) time pressure. They were then asked to: (i) rate the overall stress experienced, and (ii) write down any alternative hypotheses they had thought of when diagnosing the cases. In a post hoc analysis, a mediation path analysis was performed to test the causal relationships between time pressure, perceived stress and number of alternative diagnoses. RESULTSParticipants who were under time pressure spent less time diagnosing the cases (85.54 seconds versus 181.81 seconds; p< 0.001) and had a lower mean diagnostic accuracy score (0.44 versus 0.53; p = 0.01). In addition, they reported more stress (5.80 versus 4.69; p = 0.01) and generated fewer plausible tentative hypotheses (0.37 versus 0.51; p = 0.01). Two path coefficients were found to be statistically significant; the first path coefficient referred to the relationship between time pressure and perceived stress (standardised b = 0.25, p = 0.029), and the second negative path coefficient referred to the relationship between time pressure and number of plausible alternative hypotheses (standardised b = À0.32, p< 0.01).CONCLUSIONS Time pressure adversely influences physicians' diagnostic accuracy by increasing their stress response and reducing the number of plausible hypotheses as mediators.

Alemtuzumab, an anti-CD52 monoclonal antibody, was recently approved for treatment of MS in Canada, having shown to significantly reduce relapses and disability in patients, particularly those who relapsed despite first line treatment. Offsetting its benefit however, is the development of novel secondary autoimmune disease, particularly affecting the thyroid gland in up to 36% of patients. The incidence of Alemtuzumab induced thyroid dysfunction (AITD) will likely rise as alemtuzumab becomes more widely used for treating MS. We review the clinical and investigational cues that help delineate the aetiology and management of thyrotoxicosis and hypothyroidism in ATID. AITD can be easily managed and we present a simple approach for its evaluation and management by neurologists that should be implemented prior to considering a referral to an internist or endocrinologist for further opinion or treatment.RÉSUMÉ: Maladie thyroïdienne induite par l'alemtuzumab dans la sclérose en plaques: revue et traitement. L'alemtuzumab, un anticorps monoclonal dirigé contre CD52, a récemment été approuvé pour le traitement de la sclérose en plaques (SP) au Canada. Les études ont démontré qu'il diminuait significativement les rechutes et l'invalidité chez les patients, particulièrement chez ceux qui avaient eu des rechutes malgré le traitement de première intention. Cependant, l'apparition d'une nouvelle maladie auto-immune secondaire à ce traitement, touchant la glande tyroïde chez 36% des patients, en amoindrit les bénéfices. L'incidence de la dysfonction thyroïdienne induite par l'alemtuzumab (DTIA) augmentera vraisemblablement à mesure que l'alemtuzumab sera plus fréquemment prescrit pour traiter la SP. Nous revoyons les indices cliniques et biochimiques qui aident à définir l'étiologie et le traitement de la thyrotoxicose et de l'hypothyroïdie dans la DTIA. La DTIA peut être traitée facilement et nous présentons une approche simple de son évaluation et son traitement par des neurologues. Cette approche devrait être utilisée avant d'envisager de référer le patient à un interniste ou à un endocrinologue pour connaître son opinion ou pour prescrire un traitement.

Central diabetes insipidus (CDI) is a common complication of pituitary surgery. However, it is most frequently transient. It is defined by the excretion of an abnormally large volume of dilute urine with increasing serum osmolality. The reported incidence of CDI after pituitary surgery is variable; ranging from 0-90 %. Large tumor size, gross total resection, and intraoperative cerebrospinal fluid (CSF) leak usually have an increased risk of CDI as also seen with craniopharyngioma and Rathke’s cleft cysts. It can be associated with high morbidities and mortality if not promptly recognized and treated on time. It is essential to rule out other causes of postoperative polyuria to avoid unnecessary pharmacotherapy and iatrogenic hyponatremia. Once the diagnosis of CDI is established, close monitoring is required to evaluate the response to treatment and to determine whether the CDI is transient or permanent. This review outlines the evaluation and management of patients with CDI after pituitary and suprasellar tumors surgery to help recognize the diagnosis, consider the differential diagnosis, initiate therapeutic interventions, guide monitoring, and long-term management. Keywords: Central diabetes insipidus (CDI), polydipsia, polyuria, pituitary adenoma, preoperative risk factor, and pituitary surgery, arginine vasopressin, desmopressin, and treatment.