The conundrum of differentiating Cushing's syndrome from non-neoplastic hypercortisolism: a systematic review and meta-analysis.

CONTEXT: Once hypercortisolemia is confirmed, differential diagnosis between Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome) is crucial. Due to worldwide corticotropin-releasing hormone (CRH) unavailability, accuracy of alternative tests to dexamethasone (Dex)-CRH, is clearly needed. OBJECTIVE: Assess the diagnostic accuracy of Dex-CRH test, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. METHODS: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. DATA SYNTHESIS: A total of 24 articles (1900 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 86% (81-90%; I2 28%) and 90% (84-94%; I2 15%), MSC 91% (85-94%; I2 66%) and 81% (70-89%; I2 71%), and LNSC 80% (67-89%; I2 57%) and 90% (84-93%; I2 21%), respectively. Summary receiver operating characteristics areas under the curve were Dex-CRH 0.949, desmopressin test 0.936, MSC 0.942, and LNSC 0.950 without visual or statistical significance. The overall risk of studies bias was moderate. CONCLUSION: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.

Retinal Microvascular Density and Perfusion during an Insulin-Induced Hypoglycemia Episode: A Warning Call.

Aim: To evaluate retinal vascular perfusion and density by optical coherence tomography angiography (OCTA) before, during, and after hypoglycemia in individuals with diabetes mellitus with or without diabetic retinopathy (DR). Methods: A focused clinical history was performed, followed by an ophthalmological examination to document retinopathy status. OCTA was performed at baseline, at hypoglycemia, and at glucose normalization. Eye tracking and eye alignment devices on the platform were used to obtain a macular thickness cube (512 × 128) and vascular perfusion and density protocols of 3 × 3 mm. Retinal vascular reactivity was analyzed with superficial plexus vascular perfusion and density protocols on OCTA. Results: Fifty-two participants encompassing 97 eyes fulfilled the eligibility criteria. Their mean age was 42.9 ± 15.1 years (range, 22 to 65), and 20 (38.2%) were men. We found a statistically significant difference in vascular perfusion and density when comparing all groups at baseline. The controls had higher vascular perfusion and density values than the cases. Vascular perfusion and density were significantly reduced in all groups during the hypoglycemia episode, except for vascular density in DR cases. Conclusion: Acute hypoglycemia significantly alters the retinal vascularity in DM patients with and without DR, suggesting that repeated episodes of acute hypoglycemia could exacerbate retinopathy in the long term.

Saroglitazar is noninferior to fenofibrate in reducing triglyceride levels in hypertriglyceridemic patients in a randomized clinical trial.

Saroglitazar, being a dual PPAR-α/γ agonist, has shown beneficial effect in diabetic dyslipidemia and hypertriglyceridemia. Fibrates are commonly used to treat severe hypertriglyceridemia. However, the effect of saroglitazar in patients with moderate to severe hypertriglyceridemia was not evaluated. We conducted a study to compare the efficacy and safety of saroglitazar (4 mg) with fenofibrate (160 mg) in patients with moderate to severe hypertriglyceridemia. This was a multicenter, randomized, double-blinded, double-dummy, active-control, and noninferiority trial in adult patients with fasting triglyceride (TG) levels of 500-1,500 mg/dl. The patients were randomized in a 1:1 ratio to receive daily dose of saroglitazar or fenofibrate for 12 weeks. The primary efficacy end point was the percent change in TG levels at week 12 relative to baseline. The study comprised of 41 patients in the saroglitazar group and 41 patients in the fenofibrate group. We found that the percent reduction from baseline in TG levels at week 12 was significantly higher in the saroglitazar group (least square mean = -55.3%; SE = 4.9) compared with the fenofibrate group (least square mean = -41.1%; SE = 4.9; P = 0.048). Overall, 37 treatment-emergent adverse events (AEs) were reported in 24 patients (saroglitazar: 13; fenofibrate: 11). No serious AEs were reported, and no patient discontinued the study because of AEs. We conclude that saroglitazar (4 mg) is noninferior to fenofibrate (160 mg) in reducing TG levels after 12 weeks of treatment, was safe, and well tolerated.

Scoping review of COVID-19-related systematic reviews and meta-analyses: can we really have confidence in their results?

AIM: The aim of this study was to systematically appraise the quality of a sample of COVID-19-related systematic reviews (SRs) and discuss internal validity threats affecting the COVID-19 body of evidence. DESIGN: We conducted a scoping review of the literature. SRs with or without meta-analysis (MA) that evaluated clinical data, outcomes or treatments for patients with COVID-19 were included. MAIN OUTCOME MEASURES: We extracted quality characteristics guided by A Measurement Tool to Assess Systematic Reviews-2 to calculate a qualitative score. Complementary evaluation of the most prominent published limitations affecting the COVID-19 body of evidence was performed. RESULTS: A total of 63 SRs were included. The majority were judged as a critically low methodological quality. Most of the studies were not guided by a pre-established protocol (39, 62%). More than half (39, 62%) failed to address risk of bias when interpreting their results. A comprehensive literature search strategy was reported in most SRs (54, 86%). Appropriate use of statistical methods was evident in nearly all SRs with MAs (39, 95%). Only 16 (33%) studies recognised heterogeneity in the definition of severe COVID-19 as a limitation of the study, and 15 (24%) recognised repeated patient populations as a limitation. CONCLUSION: The methodological and reporting quality of current COVID-19 SR is far from optimal. In addition, most of the current SRs fail to address relevant threats to their internal validity, including repeated patients and heterogeneity in the definition of severe COVID-19. Adherence to proper study design and peer-review practices must remain to mitigate current limitations.

Serological follow up of positive SARS-CoV-2 cases.

OBJECTIVE: To describe the humoral response in a cohort with mild and asymptomatic SARS-CoV-2 infection previ-ously identified in a community-based serological survey. MATERIALS AND METHODS: This study was an observational follow up of 193 subjects previously identified with positive anti-SARS-CoV-2 antibodies invited for a second test 112 days after the first sampling. All completed a standardized electronic questionnaire. IgM/IgG antibodies were determined using a qualitative IgM/IgG chemiluminescent immunoassay. RESULTS: Among the 193 eligible subjects, a total of 174 (90%) attended the follow-up visit, and their serum samples were tested. Of the samples, 171 (98.3%) were still positive, and 3 (1.7%) were negative. Also, the cut-off index (COI) value of the immunoassay significantly increased from the first to the second test (P <0.001). CONCLUSIONS: Our findings support a sustained humoral response in individuals with mild and asymptomatic SARS-CoV-2 infection up to 112 days after a positive serologic baseline test, accompanied by increasing antibody titers.

Value of Patient-Centered Glycemic Control in Patients with Type 2 Diabetes.

PURPOSE OF REVIEW: Present the value of a person-centered approach in diabetes management and review current evidence supporting its practice. RECENT FINDINGS: Early evidence from glycemic control trials in diabetes resulted in most practice guidelines adopting a glucose-centric intensive approach for management of the disease, consistently relying on HbA1c as a marker of metabolic control and success. This paradigm has been recently dispelled by new evidence that shows that intensive glycemic control does not provide a significant benefit regarding patient-important microvascular and macrovascular hard outcomes when compared to moderate glycemic targets. The goals of diabetes therapy are to reduce the risks of acute and chronic complications and increase quality of life while incurring least burden of treatment and disruption to the patient's life. A person-centered approach to diabetes management is achieved through shared decision making, integration of evidence-based care and patient´s needs, values and preferences, and minimally disruptive approaches to diabetes care and at the same time offer practical guidance to clinicians and patients on achieving this type of care.

Prevalence and associated characteristics of anti-SARS-CoV-2 antibodies in Mexico 5 months after pandemic arrival.

BACKGROUND: Seroprevalence of anti-SARS-CoV-2 antibodies is now available in several world regions to better estimate transmission dynamics. However, to date, there is no epidemiological data regarding anti-SARS-CoV-2 prevalence in Mexico. Therefore, we aimed to determine the prevalence of anti-SARS-CoV-2 antibodies and define the clinical and demographic characteristics associated with seroprevalence. METHODS: We conducted a cross-sectional serological survey in Ciudad Guadalupe, NL, Mexico. City government employees voluntarily participated during July 2020. Demographic and clinical characteristics were collected at the time of blood sampling to analyze the associated characteristics. IgM/IgG antibodies were determined using a qualitative chemiluminescent immunoassay. Descriptive statistics were used for categorical and continuous variables. Statistical significance was tested using the Chi-squared test, Student's t-test and the Mann-Whitney. Logistic regression models and the odds ratios (adjusted and unadjusted) were used to estimate the association of demographic and clinical characteristics. RESULTS: Of the 3,268 participants included, 193 (5.9%, 95% CI 5.1-6.8) tested positive for IgM/IgG against SARS-CoV-2. Sex, city of residence, and comorbidities did not show any association with having IgM/IgG antibodies. A total of 114 out of 193 (59.1%) subjects with a positive test were asymptomatic, and the odds of being positive were higher in those who reported symptoms of COVID-19 in the previous four weeks to the survey (OR 4.1, 95% CI 2.9-5.5). CONCLUSIONS: There is a low rate of SARS-CoV-2 infection among government employees that have continuously been working during the pandemic. Six in ten infections were asymptomatic, and seroprevalence is low and still far from herd immunity. Epidemiological surveillance and preventive measures should be mandatory.

Carotid Intima-Media Thickness in Patients with Subclinical Hypothyroidism: A Prospective Controlled Study.

PURPOSE: The association between subclinical hypothyroidism (SCH) and cardiovascular risk, particularly with a TSH <10 µIU/ml, remains controversial. The objective of our study was to assess the association between SCH and cardiovascular risk through carotid intima-media thickness, and alternatively, to evaluate its change after treatment with levothyroxine. METHODS: A total of 54 individuals were included in the study: 18 with SCH; 18 with overt hypothyroidism (OH); and 18 healthy controls (HC). The carotid intima-media thickness was measured in each group. In SCH, follow-up was performed at three and six months after the start of levothyroxine treatment. RESULTS: The mean age of the total population at baseline was 35.8 years. The median TSH in SCH was 6.15 µIU/ml. The carotid intima-media thickness (mean and standard deviation) was greater in SCH in comparison to the HC group: right common carotid artery (RCCA), 0.486 ± 0.106 mm and 0.413 ± 0.075 mm in SCH and HC, respectively, p=0.01 and left common carotid artery (LCCA), 0.511 ± 0.144 mm and 0.427 mm ± 0.090 in SCH and HC, respectively, p=0.03). In patients with SCH, there was a decrease in the carotid intima-media thickness after treatment with levothyroxine (RCCA and LCCA, p <0.05 at three and six months). CONCLUSIONS: There was an association between increased carotid intima-media thickness in patients with SCH in comparison with HC, even with a TSH <10 µIU/ml. The increase was reversed with levothyroxine therapy. The association of this increased thickness with important cardiovascular outcomes remains uncertain and should be evaluated in future studies.

Interventions supporting cost conversations between patients and clinicians: A systematic review.

BACKGROUND AND AIM: Discussing cost during medical encounters may decrease the financial impact of medical care on patients and align their treatment plans with their financial capacities. We aimed to examine which interventions exist and quantify their effectiveness to support cost conversations. METHODS: Several databases were queried (Embase; Ovid MEDLINE(R); Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; the Cochrane databases; and Scopus) from their inception until January 31, 2020 using terms such as "clinician*", "patient*", "cost*", and "conversation*". Eligibility assessment, data extraction and risk of bias assessment were performed independently and in duplicate. We extracted study setting, design, intervention characteristics and outcomes related to patients, clinicians and quality metrics. RESULTS: We identified four studies (1327 patients) meeting our inclusion criteria. All studies were non-randomised and conducted in the United States. Three were performed in a primary care setting and the fourth in an oncology. Two studies used decision aids that included cost information; one used a training session for health care staff about cost conversations, and the other directly delivered information regarding cost conversations to patients. All interventions increased cost-conversation frequency. There was no effect on out-of-pocket costs, satisfaction, medication adherence or understanding of costs of care. CONCLUSION: The body of evidence is small and comprised of studies at high risk of bias. However, an increase in the frequency of cost conversations is consistent. Studies with higher quality are needed to ascertain the effects of these interventions on the acceptability, frequency and quality of cost conversations.

Adrenal functional reserve in the full spectrum of chronic kidney disease.

BACKGROUND: Altered cortisol levels have been associated with an increase in mortality and a decrease in health-related quality of life in patients with chronic kidney disease (CKD); however, adrenal response to adrenocorticotropic hormone (ACTH) stimulation test has not been evaluated in patients with stage 3a to 5 CKD with and without renal replacement therapy (RRT). OBJECTIVE: To evaluate adrenal function in patients with CKD. MATERIALS AND METHODS: Adults with CKD underwent a low-dose cosyntropin stimulation test (1 µg synthetic ACTH), with serum cortisol levels being measured at 0, +30 and +60 minutes post-test. RESULTS: Sixty participants with stage 3, 4 and 5 CKD (with and without RRT) were included. None of the patients had adrenal insufficiency (AI). The correlation observed between cortisol concentration at baseline and 30 minutes and 1 hour after stimulation and glomerular filtration rate (GFR) was negative and statistically significant (r: -0.39 [p = 0.002], r: -0.363 [p = 0.004], r: -0.4 [p = 0.002], respectively). CONCLUSION: Since CKD early stages, cortisol levels increase as GFR decreases. Therefore, we conclude that systematic screening for AI is not necessary in CKD patients.

ANTECEDENTES: Niveles alterados de cortisol se han asociado a un incremento en la mortalidad y disminución en la calidad de vida en pacientes con enfermedad renal crónica (ERC), sin embargo, la respuesta adrenal a la prueba de estimulación con adrenocorticotropina (ACTH) no ha sido evaluada en pacientes con ERC etapas 3a a 5 con y sin terapia de reemplazo renal (TRR). OBJETIVO: Evaluar la función adrenal de pacientes con ERC. MATERIALES Y MÉTODOS: Adultos con ERC se sometieron a una prueba de estimulación con cosintropina a dosis baja (1 mg de ACTH sintética) y se midieron los niveles séricos de cortisol a los 0, +30 y +60 minutos postestimulación. RESULTADOS: 60 participantes con ERC en etapas 3, 4 y 5 (con y sin TRR) fueron incluidos. Ninguno de los pacientes presentó insuficiencia adrenal (IA). La correlación observada entre la concentración basal, a los 30 minutos y 1 hora de cortisol postestimulación y la tasa de filtrado glomerular (TFG) fue negativa y estadísticamente significativa (r: ­0.39 [p = 0.002], r: ­0.363 [p = 0.004], r: ­0.4 [p = 0.002], respectivamente). CONCLUSIÓN: Desde etapas tempranas de la ERC los niveles de cortisol se incrementan a medida que la TFG disminuye. Concluimos que no es necesario un tamizaje sistemático para detectar IA en pacientes con ERC.

SERUM MORNING CORTISOL AS A SCREENING TEST FOR ADRENAL INSUFFICIENCY.

Objective: To evaluate the performance of morning serum cortisol (MSC) compared to a 10 mg adrenocortico-tropic hormone (ACTH) stimulation test in the diagnosis of adrenal insufficiency (AI). Methods: A retrospective, cross-sectional analysis of ACTH stimulation tests were conducted. From a total of 312 potentially eligible ACTH stimulation tests, 306 met the inclusion criteria. The population was randomized into 2 groups: test (n = 159) and validation (n = 147). In the test group, the receiver operating characteristics curve test evaluated the diagnostic performance of MSC. Results: A subnormal cortisol response to ACTH was found in 25.8% of the test group. The area under the curve values of MSC to predict AI at +30 minutes, +60 minutes, or at maximal cortisol response were 0.874, 0.897, and 0.925 (95% confidence interval [CI] 0.81 to 0.92, 0.83 to 0.93, and 0.87 to 0.96). The Youden index was 234.2 mmol/L with a sensitivity of 83.3% (95% CI 65.2 to 94.3%), and a specificity of 89.1% (95% CI 82.4 to 93.9%). Positive and negative predictive values were 64.1% (95% CI 47.1 to 78.8%) and 95.8% (95% CI 90.5 to 98.6%). There was no difference in age, gender, AI prevalence, or mean serum cortisol at +30 or +60 minutes in the validation group; however, a lower mean MSC value was found. Lower sensitivity and specificity values (88.3% and 60%, respectively) were found for the 234.2 mmol/L cutoff value. Conclusion: This study supports the role of MSC as a first-step diagnostic test in patients with clinically suspected AI. The short stimulation test could be omitted in almost half of the cases. Prospective and longitudinal studies to reproduce and confirm the cutoff values proposed are warranted. Abbreviations: ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; AUC = area under the curve; CI = confidence interval; HPA = hypothalamic pituitary adrenal; ITT = insulin tolerance test; MSC = morning serum cortisol.

Diagnostic accuracy of the triglyceride-glucose index for gestational diabetes screening: a practical approach.

The oral glucose tolerance test (OGTT) remains as the gold standard to diagnose gestational diabetes mellitus (GDM); however, this test may be inconvenient and costly. Hence, other easy to perform and accurate diagnostic alternatives would be valuable for maternal care. The objective of the study was to assess the diagnostic performance of the TyG index to screen for GDM at 24-28 of pregnancy. A total of 140 pregnant women who received the one-step 2 h 75 g OGTT were included. Overall GDM prevalence was 27.1% according to IADSPG criteria. The mean TyG index value in the GDM group was significantly higher than the TyG index for the no GDM group (4.88 ± 0.70 versus 4.68 ± 0.19, p<.001). A sensitivity of 89% [95% CI 0.75-0.97] and a specificity of 50% [95% CI 0.39-0.60)], accompanied by a high negative predictive value of 93% was observed. No differences were found in maternal and neonatal outcomes irrespective of the TyG cutoff value for GDM. According to our results, the TyG index may be a highly sensitive and easy to perform screening test for GDM.

Acanthosis nigricans in middle-age adults: A highly prevalent and specific clinical sign of insulin resistance.

BACKGROUND: Insulin resistance (IR) precedes the diagnosis of many metabolic and non-metabolic illnesses, including type 2 diabetes mellitus (T2DM). Acanthosis nigricans (AN) is a clinical sign associated with IR. However, AN prevalence and diagnostic accuracy in middle-age adults before or at the time of prediabetes/diabetes diagnosis remain uncertain. METHODS: With the aim to define AN prevalence and diagnostic accuracy, adults between 40 and 60 years of age were consecutively invited to participate in the study. Participants were categorised into one of two main groups: individuals with normoglycaemia (group 1) and hyperglycaemia (group 2 [ie, prediabetes/diabetes]). Demographic, clinical, anthropometric characteristics, homeostasis model assessment of IR, homeostatic model assessment of ß-cell function, as well as the presence of AN on the neck, axillae, elbows and knuckles were assessed. RESULTS: A total of 320 consecutive participants with a mean age of 49.3 years (59.4% women) were included. Overall, AN prevalence was 46.3%, while AN in group 1 and group 2 was 36.3% and 49.6%, respectively (P = .04). The most common affected sites in group 1 (n = 80) were the knuckles (21.2%) and the neck (17.5%), while in group 2 (n = 240), the neck (29.6%) followed by the knuckles (26.7%). The specificity and positive predictive value of AN for IR were 0.85 and 0.86 in group 1 and 0.90 and 0.96 in group 2, respectively. CONCLUSIONS: In middle-age adults, within the entire spectrum of carbohydrate tolerance, AN is highly prevalent and specific. This finding supports its assessment as a reliable and convenient clinical sign of IR. The understanding of AN behaviour through different carbohydrate tolerance strata, and its different locations, could lead to early detection of individuals at high metabolic risk or help direct a more pathophysiological treatment approach in patients with T2DM.

Eliciting the Patient's Agenda- Secondary Analysis of Recorded Clinical Encounters.

BACKGROUND: Eliciting patient concerns and listening carefully to them contributes to patient-centered care. Yet, clinicians often fail to elicit the patient's agenda and, when they do, they interrupt the patient's discourse. OBJECTIVE: We aimed to describe the extent to which patients' concerns are elicited across different clinical settings and how shared decision-making tools impact agenda elicitation. DESIGN AND PARTICIPANTS: We performed a secondary analysis of a random sample of 112 clinical encounters recorded during trials testing the efficacy of shared decision-making tools. MAIN MEASURES: Two reviewers, working independently, characterized the elicitation of the patient agenda and the time to interruption or to complete statement; we analyzed the distribution of agenda elicitation according to setting and use of shared decision-making tools. KEY RESULTS: Clinicians elicited the patient's agenda in 40 of 112 (36%) encounters. Agendas were elicited more often in primary care (30/61 encounters, 49%) than in specialty care (10/51 encounters, 20%); p = .058. Shared decision-making tools did not affect the likelihood of eliciting the patient's agenda (34 vs. 37% in encounters with and without these tools; p = .09). In 27 of the 40 (67%) encounters in which clinicians elicited patient concerns, the clinician interrupted the patient after a median of 11 seconds (interquartile range 7-22; range 3 to 234 s). Uninterrupted patients took a median of 6 s (interquartile range 3-19; range 2 to 108 s) to state their concern. CONCLUSIONS: Clinicians seldom elicit the patient's agenda; when they do, they interrupt patients sooner than previously reported. Physicians in specialty care elicited the patient's agenda less often compared to physicians in primary care. Failure to elicit the patient's agenda reduces the chance that clinicians will orient the priorities of a clinical encounter toward specific aspects that matter to each patient.

Participants' awareness of ethical compliance, safety and protection during participation in pharmaceutical industry clinical trials: a controlled survey.

BACKGROUND: The rapid increase of industry-sponsored clinical research towards developing countries has led to potentially complex ethical issues to assess. There is scarce evidence about the perception of these participants about the ethical compliance, security, and protection. We sought to evaluate and contrast the awareness and perception of participants and non-participants of industry-sponsored research trials (ISRT) on ethical, safety, and protection topics. METHODS: A Cases-control survey conducted at twelve research sites in México. Previous and current participants of ISRT (cases) as well as non-participants (controls) with one of four chronic diseases, were asked to complete the survey which focused on ethical compliance and protection issues of ISRT, and the perception of participating in a trial. RESULTS: A total of 604 cases and 604 controls were surveyed. Cases significantly answered that ethics committees are aware of what is happening in studies (50.5% vs. 33.8%, P = ≤ 0.001), and that medical care of industry-sponsored research trials is better than their usual medical care (77.2% vs. 38.2%, P = < 0.001). The same proportion of cases and controls thought patients must receive economical reimbursement for participating in a research study (49.5% vs. 53.1%, P = 0.205). The informed consent of the pharmaceutical clinical trial was fully read by 90.4% of the cases. Most cases were satisfied or very satisfied with their overall study participation (35.6 and 62.3%, respectively). CONCLUSION: Previous and current participants of industry-sponsored research trials have a more positive attitude towards ethics committees, the quality of medical care of the research trials, and the main purpose of economical reimbursements, when compared to non-participants.

Hypoglycemia Among Patients with Type 2 Diabetes: Epidemiology, Risk Factors, and Prevention Strategies.

PURPOSE OF REVIEW: Hypoglycemia is the most common and often treatment-limiting serious adverse effect of diabetes therapy. Despite being potentially preventable, hypoglycemia in type 2 diabetes incurs substantial personal and societal burden. We review the epidemiology of hypoglycemia in type 2 diabetes, discuss key risk factors, and introduce potential prevention strategies. RECENT FINDINGS: Reported rates of hypoglycemia in type 2 diabetes vary widely as there is marked heterogeneity in how hypoglycemia is defined, measured, and reported. In randomized controlled trials, rates of severe hypoglycemia ranged from 0.7 to 12 per 100 person-years. In observational studies, hospitalizations or emergency department visits for hypoglycemia were experienced by 0.2 (patients treated without insulin or sulfonylurea) to 2.0 (insulin or sulfonylurea users) per 100 person-years. Patient-reported hypoglycemia is much more common. Over the course of 6 months, 1-4% non-insulin users reported need for medical attention for hypoglycemia; 1-17%, need for any assistance; and 46-58%, any hypoglycemia symptoms. Similarly, over a 12-month period, 4-17% of insulin-treated patients reported needing assistance and 37-64% experienced any hypoglycemic symptoms. Hypoglycemia is most common among older patients with multiple or advanced comorbidities, patients with long diabetes duration, or patients with a prior history of hypoglycemia. Insulin and sulfonylurea use, food insecurity, and fasting also increase hypoglycemia risk. Clinical decision support tools may help identify at-risk patients. Prospective trials of efforts to reduce hypoglycemia risk are needed, and there is emerging evidence supporting multidisciplinary interventions including treatment de-intensification, use of diabetes technologies, diabetes self-management, and social support. Hypoglycemia among patients with type 2 diabetes is common. Patient-centered multidisciplinary care may help proactively identify at-risk patients and address the multiplicity of factors contributing to hypoglycemia occurrence.

Effects of increasing levothyroxine on pregnancy outcomes in women with uncontrolled hypothyroidism.

OBJECTIVE: Uncontrolled hypothyroidism has been associated with an increased risk of adverse pregnancy outcomes. We aimed to assess the effectiveness of increasing levothyroxine (LT4) dose on reducing the risk of adverse outcomes for pregnant women with TSH level greater than the recommended 1st trimester limit. DESIGN, PATIENTS, MEASUREMENTS: We reviewed the electronic medical records of pregnant women evaluated from January 2011 to December 2013, who had history of LT4-treated hypothyroidism and were found to have TSH > 2·5 mIU/l in 1st trimester. Women were divided into two groups: group A - LT4 dose was increased within two weeks from the TSH test, group B - LT4 dose remained stable. We compared the frequency of pregnancy loss (primary outcome) and other prespecified pregnancy-related adverse outcomes between groups. RESULTS: There were 85 women in group A (median TSH: 5·0, interquartile range 3·8-6·8 mIU/l) and 11 women in group B (median TSH: 4·5, interquartile range 3·2-4·9 mIU/l). The groups were not different in baseline clinical and socioeconomic characteristics. The mean interval between TSH test and LT4 dose increase was 4·5 (SD 4·6) days. Pregnancy loss was significantly lower in group A (2/85, 2·4%) vs group B (4/11, 36·4%) (P = 0·001). Other pregnancy-related adverse outcomes were similar between groups. CONCLUSIONS: Increasing LT4 dose for women with uncontrolled hypothyroidism in the 1st trimester of pregnancy was associated with a decreased risk of pregnancy loss. Given the limitations of our study, this association awaits further confirmation from larger studies.

IMAGE-GUIDED THERMAL ABLATION OF ADRENAL METASTASES: HEMODYNAMIC AND ENDOCRINE OUTCOMES.

OBJECTIVE: Image-guided thermal ablation of adrenal metastases has been increasingly used for local tumor control. This procedure has been associated with hypertensive urgency; however, endocrine complications have not been clearly described. Our objective was to assess the hemodynamic behavior and risk for adrenal insufficiency related to adrenal ablation. Additionally, we sought to understand the utility of preprocedural α-blockade to prevent periprocedural hemodynamic complications. METHODS: This was a retrospective study of patients undergoing image-guided ablation of adrenal metastases between 2003 and 2015 at our institution. We reviewed electronic medical records to obtain clinical information, including α-blockade preparation, periprocedural hemodynamic parameters, interventions, and postablation adrenal function. RESULTS: Thermal ablation was performed in 58 patients (46 men [79%]; median age, 66 years) with 60 adrenal metastases ablated in 62 sessions. Alpha-blockade was used pre-ablation in 49 (79%) sessions; it was associated with less hypertensive urgency (23 [47%] for α-blockade vs. 10 [77%] for no α-blockade; P = .048) but higher need for vasopressors (22 [45%] for α-blockade vs. 1 [8%] for no α-blockade; P = .02) during ablation. Adrenal insufficiency occurred in 13 (22%) patients, of whom 10 had history of contralateral adrenalectomy or metastases, and only 3 of 13 had a normal-appearing contralateral adrenal gland. CONCLUSION: Hemodynamic changes during ablation of adrenal metastases are common. Pre-ablation α-blockade decreases the severity of the hypertensive episode, at the expense of higher need for vasopressors periprocedurally. Adrenal function should be assessed after adrenal metastasis ablation, as adrenal insufficiency may occur after such treatment. ABBREVIATIONS: ACTH = adrenocorticotropic hormone BP = blood pressure CT = computed tomography DBP = diastolic blood pressure HR = heart rate IQR = interquartile range IV = intravenous MAP = mean arterial pressure MWA = microwave ablation RFA = radiofrequency ablation SBP = systolic blood pressure.