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.

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.

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.

Introduction: Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic condition in which mutations in key peptides involved in the low-density lipoprotein receptor (LDL-R) pathway result in markedly elevated levels of circulating LDL-cholesterol (LDL-C). Patients are at high risk of developing earlyonset atherosclerotic cardiovascular disease Moeber Mahzari and Hawazen Zarif are co-first authors of the manuscript.

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.

Objectives KSA has the highest prevalence of diabetes mellitus among Middle Eastern countries with a prevalence range of 21%–24%. Gestational diabetes (GDM) is a well-known risk factor for type 2 diabetes mellitus (T2DM). GDM is associated with a 7-fold increased risk of T2DM. Thus, this research assessed the prevalence and risk factors associated with the development T2DM in a cohort of patients with GDM in KSA. Methods The medical records of patients with GDM who visited the outpatient clinics of a tertiary care hospital from 2011 to 2014 were included in this study. Patients with a prior diagnosis of diabetes mellitus before pregnancy and those with GDM who did not have postpartum diabetes screening were excluded. Results A total of 123 women with GDM and underwent postpartum diabetes screening, 82 (67%) developed T2DM based on follow-up records. Approximately 45% (37/82) of patients who developed T2DM were screened ≤6 months after delivery, whereas 55%(45/82) were screened >6 months after delivery. Older patients, patients who had a higher number of pregnancies (gravidity and parity), and patients with previous GDM were more likely to develop T2DM. Conclusion In KSA, women who developed GDM, particularly those who are older, multigravid, and multiparous and who have a prior history of GDM, are at an increased risk of developing T2DM. Postpartum diabetes screening of patients with GDM within the recommended period need to be improved.

BackgroundSelf-explanation while individually diagnosing clinical cases has proved to be an effective instructional approach for teaching clinical reasoning. The present study compared the effects on diagnostic performance of self-explanation in small groups with the more commonly used hypothetico-deductive approach.MethodsSecond-year students from a six-year medical school in Saudi Arabia (39 males; 49 females) worked in small groups on seven clinical vignettes (four criterion cases representing cardiovascular diseases and three ‘fillers’, i.e. cases of other unrelated diagnoses). The students followed different approaches to work on each case depending on the experimental condition to which they had been randomly assigned. Under the self-explanation condition, students provided a diagnosis and a suitable pathophysiological explanation for the clinical findings whereas in the hypothetico-deduction condition students hypothesized about plausible diagnoses for signs and symptoms that were presented sequentially. One week later, all students diagnosed eight vignettes, four of which represented cardiovascular diseases. A mean diagnostic accuracy score (range: 0–1) was computed for the criterion cases. One-way ANOVA with experimental condition as between-subjects factor was performed on the mean diagnostic accuracy scores.ResultsStudents in the hypothetico-deduction condition outperformed those in the self-explanation condition (mean = 0.22, standard deviation = 0.14, mean = 0.17; standard deviation = 0.12; F(1, 88) = 4.90, p = 0.03, partial η2 = 0.06, respectively).ConclusionsStudents in the hypothetico-deduction condition performed slightly better on a follow-up test involving similar cases, possibly because they were allowed to formulate more than one hypothesis per case during the learning phase.

Aims Adherence therapy is a candidate intervention to improve medication adherence and clinical outcomes in patients with type 2 diabetes. The feasibility of conducting a trial of adherence therapy in this population has not been established. The objective of this study is therefore to test the feasibility of conducting a randomized controlled trial of adherence therapy in a Middle Eastern context. Design A single‐centre randomized controlled feasibility trial of adherence therapy in patients with type 2 diabetes. Methods We will undertake an initial cultural adaptation of a telephone‐delivered form of adherence therapy in four patients in a Middle Eastern context. Our subsequent feasibility trial will aim to recruit 40 non‐adherent diabetic patients that will be randomly allocated to receive eight weekly 30‐min telephone adherence therapy sessions delivered by a diabetes educator versus treatment as usual. Key outcomes of interest include the number of patients invited to take part in the trial that consent to participate and then go on to complete treatment. Result The findings of this study will determine the feasibility of undertaking a full randomized controlled trial of adherence therapy in patients with type 2 diabetes.