Purpose Sex hormones play a role in bone density, cardiovascular health and wellbeing throughout reproductive lifespan. Women with primary ovarian insufficiency (POI) have lower estrogen levels requiring hormone therapy (HT) to manage symptoms and to protect against adverse long-term health outcomes. Yet, the effectiveness of HT in preventing adverse outcomes has not been systematically assessed. We summarize the evidence regarding effects of HT on bone and cardiovascular health in women with POI. Methods A comprehensive search of the electronic databases MEDLINE, EMBASE and Scopus was conducted by a medical reference librarian from database inception to January 2016. Randomized trials and observational cohort studies with an estrogen-based HT intervention in women with POI under the age of 40 were included. Reviewers worked independently and in duplicate to assess eligibility and risk of bias, and extract data of interest from each study. Results The search identified 1670 articles; 12 met inclusion criteria. Four randomized clinical trials and 8 cohort studies at high risk of bias enrolled 806 women with POI. The most common HT formulations were transdermal estradiol and oral conjugated equine estrogen combined with medroxyprogesterone acetate. Bone mineral density was the most frequent outcome, with 3 out of 8 studies showing HT associated increase benefits. Only 1 study reported effects on fractures or vasomotor symptoms and none on cardiovascular mortality. Results regarding lipid profiles were inconsistent. Conclusions Evidence supporting bone and cardiovascular benefits of HT in women with POI is limited by high risk of bias, reliance on surrogate outcomes and heterogeneity of trials regarding the formulation, dose, route of administration and regimen of HT. Further research addressing patient important outcomes such as fractures, stroke and cardiovascular mortality are crucial to optimize benefits of this therapy. Registration PROSPERO CRD 4201603616

Purpose of reviewAdrenal insufficiency is a rare disease characterized by cortisol deficiency. The evaluation of patients suspected of having adrenal insufficiency can be challenging because of the rarity of the disease and limitations in the biochemical assessment of the cortisol status by either basal or dynamic testing [adrenocorticotropic hormone (ACTH) stimulation test]. Prompt and adequate diagnosis is of paramount importance to avoid adverse outcomes. We aimed to summarize the recent developments in the conduction and interpretation of the ACTH stimulation test for the diagnosis of adrenal insufficiency. Recent findingsThe ACTH stimulation test is commonly performed in patients suspected of having adrenal insufficiency when the basal serum cortisol levels are inconclusive. Recent literature has evaluated the impact of technical aspects such as time of the day the test is performed, type of assay and sample source used for cortisol measurement on the clinical value of this test, as well as the feasibility of reliable low dose ACTH testing. SummaryClinicians evaluating patients with suspected adrenal insufficiency should take into consideration the clinical presentation (likelihood of adrenal insufficiency before testing) when interpreting the results of the ACTH stimulation test and be aware of clinical and technical factors that can affect cortisol values and diagnostic accuracy of this test.

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Context Thyroid nodule risk stratification allows clinicians to standardize the evaluation of thyroid cancer risk according to ultrasound features. Objective To evaluate inter-rater agreement among clinicians assessing thyroid nodules ultrasound features and thyroid cancer risk categories. Design, setting, and participants We surveyed Endocrine Society and Latin American Thyroid Society members to assess their interpretation of composition, echogenicity, shape, margins, and presence of echogenic foci of ten thyroid nodule cases. The risk category for thyroid cancer was calculated following the ACR-TIRADS framework from individual responses. Main outcomes and measures We used descriptive statistics and Gwet's agreement coefficient (AC1) to assess the primary outcome of inter-rater agreement for ACR-TIRADS risk category. As secondary outomes the inter-rater agreement for individual features and subgroup analysis of inter-rater agreement for ACR-TIRADS category was performed (ultrasound reporting system, type of practice, and number of monthly appraisals). Results A total of 144 participants were included, mostly endocrinologists (82%). There was moderate level of agreement for the absence of echogenic foci (AC1 0.53, 95% confidence interval (CI) 0.24-0.81) and composition (AC1 0.54, 95%CI 0.36-0.71). The agreement for margins (AC1 0.24, 95% CI 0.15-0.33), echogenicity (AC1 0.34, 95% CI 0.22-0.46), and shape assessment (AC1 0.42, 95% CI 0.13-0.70) was lower. The overall agreement for ACR-TIRADS assessment was AC1 0.29, 95% CI 0.13-0.45. The AC1 of ACR-TIRADS among subgroups was similar. Conclusions This study found high variation of judgments about ACR-TIRADS risk category and individual features, which poses a potential challenge for the widescale implementation of thyroid nodule risk stratification.

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