Evidence-Based Curricular Content Improves Student Knowledge and Changes Attitudes towards Transgender Medicine

Objective: Previous studies have demonstrated that the addition of transgender medicine content to a medical school curriculum increased students' comfort and willingness to treat transgender patients. We aimed to demonstrate that (1) evidence-based curricular content would improve knowledge of and change attitudes towards transgender medicine, and (2) students would consider cross-sex hormone therapy a legitimate treatment option for transgender patients.Methods: Curricular content with a focus on the biologic evidence for the durability of gender identity was added to the first-year medical program at Boston University School of Medicine. Immediately before and after exposure to the content, students were presented with an assessment of their knowledge of the etiology of gender identity.Results: Immediately following exposure to the content, a significant number of students changed their answer regarding the etiology of gender identity so that the number of correct responses increased from 63% (n = 56) to 93% (n = 121) (P<.001). For transgender treatment, the number of correct responses increased from 20% (n = 56) before exposure to the content to 50% (n = 121) following exposure (P<.001).Conclusion: The addition of transgender medicine content to a medical school curriculum with a focus on the biologic evidence for a durable gender identity is an effective means of educating students about the etiology of gender identity and the appropriateness of cross-sex hormone therapy as a treatment for transgender patients.     

Endocrinology Fellows' Perception of Their Confidence and Skill Level in Providing Transgender Healthcare

Objective: Both educational content and hours devoted to transgender health training of endocrinology fellows are suboptimal. The objective of this study was to assess the perspectives of endocrinology fellows on their training in transgender health.Methods: We evaluated the state of comfort and knowledge of transgender healthcare among endocrinology fellows attending Endocrine University. Surveys were administered to fellows before and after their participation in a case-based session on transgender health.Results: The majority of fellows felt that training in transgender health is important (95.9%, 189/197); however, only 58.9% reported inclusion of dedicated transgender content in their training programs. Fellows who had received transgender healthcare education, and those who had seen more transgender patients in their training, were more likely to be confident in treating patients with hormone therapy (P<.001 and P<.0001, respectively). Following the case-based session, 62.4 % of fellows reported that they would change their practice, 72.8% felt that their comfort level with transgender care had improved, and 91% felt that transgender content such as that provided in the educational session should be mandatory in endocrinology training programs. Methods most desired by fellows to improve their education included lectures from visiting professors (70.3%), participation in elective rotations (62.1%), online training modules (57.9%), and attendance at meetings with transgender topics (57.4%).Conclusion: Transgender health education of U.S. endocrinology fellows is suboptimal. Participation in a case-based session significantly increased the comfort level of endocrinology fellows in key areas of transgender health.Abbreviation: ACGME = Accreditation Council for Graduate Medical Education     

Assessment of gender-specific preventive cardiovascular knowledge among house staff: Potential impact on cardiovascular management

Background: Gender differences in cardiovascular prevention and treatment may be related to physicians' level of postgraduate training and gender.Objectives: This study was designed to assess resident physician knowledge concerning general and gender-specific preventive cardiology topics and to determine whether there were differences in that knowledge based on the physicians' level of postgraduate training or gender.Methods: A 29-item true/false questionnaire was administered to residents in a large, university-based internal medicine residency program. All questions were drawn from evidence-based practice guidelines, and a subset of questions pertained to gender-specific issues in cardiovascular disease prevention. Scores on the overall test and gender-specific subset were computed as a percentage of correct answers. Differences were compared by postgraduate year (PGY) of training and physician gender.Results: Of the 190 eligible residents, 159 (88 men, 67 women, 4 not specified) completed the questionnaire. Overall test scores differed significantly by PGY (PGY-1, 83.4% correct answers; PGY-2, 52.9%; PGY-3, 65.3%; P < 0.001 for each paired comparison), but did not differ significantly by physician gender (males, 73.5%; females, 70.0%). Performance on gender-specific items also differed by PGY (PGY-1, 72.2% vs PGY-2, 20.0%; P < 0.001; and PGY-1, 72.2% vs PGY-3, 45.1%; P < 0.001). Knowledge of gender-specific preventive cardiology did not differ significantly by physician gender (males, 56.4%; females, 49.0%).Conclusions: Residents in PGY-1 had better knowledge of preventive cardiology as assessed using this questionnaire than did residents in PGY-2 or PGY-3. Knowledge of general and gender-specific cardiology topics was not related to physician gender.     

Long-Term,Sustained, Lifestyle-Induced Weight Loss in Severe Obesity: the Get-Real Program

Objective: To study the long-term effectiveness of a patient-centered, multidisciplinary lifestyle intervention treatment in patients medically eligible for bariatric surgery.Methods: Using a case-control study design, we compared treatment results for 98 adults (mean body mass index [BMI], 44.2 kg/m²) with the outcomes of 148 controls (mean BMI, 43.0 kg/m²) receiving standard care. The approach included a phased triage for inclusion, followed by 12 lifestyle intervention group sessions alternating with individual visits for behavior, diet, and exercise instructions.Results: At 2 years, weight loss averaged 15.3 ± 1.4 kg (P<.0010) (12 ± 1% of initial body weight [IBW], P<.001; 21 ± 2% of excess body weight [EBW], P<.001) in an intention-to-treat (ITT) analysis; in completers, weight loss was 18.8 ± 1.5 kg (P<.001) (15 ± 1% IBW, P<.001; 26 ± 3% EBW, P<.001). A total of 42 patients lost ≥10% IBW. Controls remained weight stable (P =.35); 3% lost ≥10% IBW. Patients achieving weight loss that would be considered satisfactory for bariatric surgery included 20% who achieved ≥35% EBW loss, 29% who achieved a BMI <35 kg/m² (if starting BMI <50 kg/m²) or BMI <40 kg/m² (if starting BMI ≥50 kg/m²), and 37% who achieved EBW loss ≤50%. These values for completers were 31, 39, and 48%, respectively. In the 55 patients starting the program ≥4 years ago, weight loss maintenance of 12 ± 1% IBW (ITT, 16 ± 1% in completers) was observed.Conclusion: Substantial nonsurgical weight loss, maintained at 2 to 4 years, is achievable in severely obese patients using comprehensive lifestyle approaches; the efficacy/safety trade-off in obesity treatment is an important consideration in interpreting these results.Abbreviations: BMI = body mass index EBW = excess body weight HbA_1c = glycated hemoglobin IBW = initial body weight LOCFA = last observation carried forward analysis     

Virtual Orthopedic-Rehabilitation-Metabolic Collaboration for Treating Osteoporotic HIP Fractures

Objective: To evaluate the effectiveness of a virtual, closed-loop protocol that treated hip fracture patients without formal clinic visits.Methods: In this prospective cohort study, an intervention group of 85 hip fracture patients (33.6%) with vitamin D levels ≥65 nmol/L who received recommendations for osteoporosis treatment, was compared to a nonintervention group of 168 (66.4%), with vitamin D <65 nmol/L. Treatment included vitamin D loading in orthopedic and rehabilitation departments for patients from both groups, and virtual, osteoporosis treatment recommendations by Metabolic Clinic physicians to patients from the intervention group upon achieving a vitamin D level ≥65 nmol/L. Recommendations were given without requiring clinic visits. Osteoporosis drug recommendations were relayed to primary care physicians. The primary endpoint was patients receiving osteoporosis drugs within 12-months post-surgery. Secondary endpoints were patients issued drugs within 3- and 6-months post-surgery, and 1-year post-fracture mortality rates.Results: Among 253 hip fracture patients (81.3 ± 10.7 years-of-age, 68.8% women), the postintervention osteoporosis medication issue rate was higher than in the nonintervention group (48.2% versus 22.0%, respectively; P<.001). More intervention group patients received drugs 3 months (18.8% versus 2.9%; P<.001) and 6 months after surgery (40% versus 5.9%; P<.001). One-year mortality was lower among patients who received any osteoporosis medications (either through our intervention or from community physicians) than among untreated patients (5.1% versus 26.3%; P<.001).Conclusion: Virtual orthopedic-rehabilitation-metabolic collaboration increased osteoporosis treatment rates post-hip fracture. Yet, treatment rates remained <50%. Additional research is required to increase treatment rates further, such as providing drug therapy shortly after surgery, perhaps during rehabilitation, or lowering the vita-min D threshold.Abbreviations: CHS = Clalit Health Services; FLS = Fracture liaison service; HMO = Health Maintenance Organization; MMC = Meir Medical Center; PCP = primary care physician     

Observed Deficiencies in Medical Student Knowledge of Transgender and Intersex Health

Objective: Lesbian, gay, bisexual, transgender, and intersex (LGBTI) patients face many well-documented disparities in care which among transgender and intersex people can often be traced to providers' lack of knowledge.Methods: We administered surveys to examine the self-assessed knowledge and attitudes of all medical students at Boston University regarding different LGBTI subpopulations. Survey questions were based on a Likert scale from 1 to 5; analysis was conducted with Wilcoxon rank sum tests.Results: Overall there was a response rate of 24%, with the number of responses varying by class. Three of the 4 surveyed classes reported lower knowledge about transgender health than LGB health. Every class reported significantly lower knowledge of intersex health in comparison to LGB. Comfort with transgender or with intersex patients was lower than with LGB patients for all surveyed classes. Students across all self-identified groups (LGBTI, ally, not an ally) reported significantly lower average responses for knowledge and comfort regarding transgender or intersex health in comparison to that of LGB. Students in their preclinical years reported lower levels of knowledge in comparison with students in their clinical years. Students who identified as LGBTI reported significantly higher knowledge and comfort with only LGB and transgender health when compared with students who didn't identify as LGBTI. Respondents more frequently requested additional learning opportunities in transgender and intersex health than in LGB health.Conclusion: Self-reported knowledge of transgender and intersex health lags behind knowledge of LGB health, though these deficits appear partially responsive to targeted educational intervention.Abbreviations: BUSM = Boston University School of Medicine LGB = lesbian, gay, and bisexual LGBT = lesbian, gay, bisexual, and transgender LGBTI = lesbian, gay, bisexual, transgender, and intersex M1 = first-year medical student class M2 = second-year medical student class M3 = third-year medical student class M4 = fourth-year medical student class     

DPP-4 Inhibitor Therapy in Patients after Pancreatic Transplant

Objective: Management of new onset hyperglycemia after pancreas transplantation (PT) is not well studied. There is a lack of information on effective and safe management options for hyperglycemia after PT. We tested the hypothesis that early intervention for hyperglycemia using a dipeptidyl peptidase-4 (DPP-4) inhibitor prolongs insulin-free graft function in patients after PT.Methods: Twenty-six patients who developed noninsulin-dependent hyperglycemia at least 1 year after PT met the inclusion criteria for this retrospective chart review. Sitagliptin, a DPP-4 inhibitor, was a commonly used therapy for hyperglycemia after PT due to its wide availability and coverage. The standard therapy group included patients who did not receive any oral or noninsulin injection therapy until insulin was clearly required to control hyperglycemia. The intervention group included patients who had received sitagliptin soon after hyperglycemia developed. The median follow-up period was 45 months. The time to hyperglycemia from 1 year after PT and time to insulin requirement after hyperglycemia development were compared between these 2 groups.Results: The time to hyperglycemia after PT was not different between the groups, but the time to insulin requirement was significantly longer in the intervention group compared with the standard therapy group (P<.001). After adjusting for body mass index (BMI), the difference remained significant (P<.001).Conclusion: Early treatment of hyperglycemia after PT with a DPP-4 inhibitor such as sitagliptin prolongs the time to insulin therapy compared with a standard observation approach. Prospective studies are needed to further investigate this observation.Abbreviations: BG = blood glucose BMI = body mass index CV = coefficient of variance DM = diabetes mellitus DPP-4 = dipeptidyl peptidase-4 HbA1c = glycated hemoglobin NODAT = new-onset diabetes after transplantation OHA = oral hypoglycemic agent PT = pancreas transplantation     

Performance of Free Versus Total Cortisol Following Cosyntropin Stimulation Testing in an Outpatient Setting

Objective: Free cortisol (FC) is potentially superior to total cortisol (TC) measurements in selected clinical settings; however, the advantages of uniform use of FC in outpatient settings are unclear. The objectives of this study were to describe the dynamic response of FC during cosyntropin stimulation testing (CST) compared to TC and to determine the rates of discordance.Methods: This is a cross-sectional study of 295 stable patients who underwent CST in an outpatient Endocrine Testing Center. The main outcome measures were TC and FC measurements during CST.Results: The mean age of the 295 subjects was 49.1 (16.9) years. Of 218 females, 43 were taking estrogen therapy (ET) at the time of testing. Adrenal insufficiency (AI) was diagnosed in 41/295 (14%) patients. The FC concentrations were associated with TC concentrations at baseline (R² = 0.77, P<.001), 30 minutes (R² = 0.87, P<.001), and 60 minutes (R² = 0.90, P<.001). The FC cutoffs for AI were 873 and 1,170 ng/dL at 30 and 60 minutes, respectively. The FC had a more pronounced fold change from baseline to peak than TC (median 3.2 vs. 1.7, P<.001). Both TC and FC at baseline were higher in females on ET compared to those who were not and to males; however, peak TC and FC values were similar. In 3/43 females on ET, FC, and TC results were discordant (P = .003).Conclusion: We report 99% concordance of TC and FC measurements in a large outpatient cohort. The discordant rates were high in females treated with ET (7%). The FC measurements during CST in females on ET may provide a more rapid and accurate diagnosis of AI.Abbreviations:ACTH = adrenocorticotropic hormoneAI = adrenal insufficiencyCBG = corticosteroid-binding proteinCST = cosyntropin stimulation testingET = estrogen therapyFC = free cortisolfΔ = fold changeROC = receiver operating characteristicTC = total cortisol     

Increased Bone Turnover in Type 2 Diabetes Patients Randomized to Bariatric Surgery Versus Medical Therapy at 5 Years

Objective: The aim of our study was to determine the 5-year outcomes of bariatric surgery versus intensive medical therapy on bone turnover in patients with type 2 diabetes mellitus (T2DM) from the STAMPEDE trial.Methods: This was an ancillary investigation of a 5-year randomized control trial at a single tertiary care center involving 95 patients aged 48.5 ± 8 years with obesity (body mass index &lsqb;BMI], 36.5 ± 3.6 kg/m²) and uncontrolled T2DM (glycated hemoglobin 9.3 ± 1.6% &lsqb;78 mmol/mol]). Patients were randomized to intensive medical therapy (IMT; n = 25), Roux-en-Y gastric bypass (RYGB; n = 37), or sleeve gastrectomy (SG; n = 33) for diabetes treatment. Bone formation marker osteocalcin (OC), bone resorption marker serum C-telopeptide of type 1 collagen (CTX), and intact parathyroid hormone (PTH) were assessed at baseline and 5 years postintervention. Analysis with key clinical parameters and outcomes (i.e., age, menopausal status, gender, weight loss) was performed.Results: Percent change in CTX at 5 years increased in both surgical groups, by 137 ± 108% in RYGB (P<.001) and 61.1 ± 90% in SG (P<.001) compared to 29.8 ± 93% in IMT (P = .12). OC also increased from baseline in the surgical cohorts, by 138 ± 19% in RYGB (P<.001) and 71 ± 69% in SG (P<.001) compared to 43.8 ± 121.1% in IMT (P = .83). Increases in both CTX and OC correlated linearly with increases in PTH levels in RYGB patients (P<.001). Increase in CTX correlated with decreased BMI in SG patients (P = .039).Conclusion: In patients with T2DM, bone turnover remains chronically elevated at 5 years following RYGB, and to a lesser extent in SG patients.Abbreviations: BMI = body mass index; BTM = bone turnover marker; CTX = C-telopeptide of type 1 collagen; HbA1c = glycated hemoglobin; IMT = intensive medical therapy; OC = osteocalcin; PPI = proton-pump inhibitor; PTH = parathyroid hormone; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; T2DM = type 2 diabetes mellitus; TZD = thiazolidinedione     

The Association Between Tumor Tissue Calcification,Obesity, and Thyroid Cancer Invasiveness In A Cohort Study

Objective: We examined the relationships between tumor tissue calcifications of papillary thyroid cancer (PTC), body mass index (BMI), and tumor invasiveness.Methods: This was a retrospective analysis of 13,995 patients with PTC. Comparisons were made between the clinical and pathologic features of the tumor tissue calcifications group and non–tumor tissue calcifications group. Odds ratios (ORs) of tumor tissue calcifications, BMI, and tumor invasiveness features were calculated using a binary logistic regression model. We analyzed the relationship between tumor tissue calcifications and certain characteristics of thyroid cancer based on the pathologic findings.Results: BMI was positively correlated with tumor tissue calcifications in patients with PTC (OR, 1.015; P = .011), and obesity increased the risk of tumor tissue calcifications (OR, 1.374; P = .038). Calcifications were positively correlated with T-size (OR, 1.899; P<.001), multifocality (OR, 1.217; P<.001), extrathyroidal extension (ETE) (OR, 1.287; P<.001), high T-stage (OR, 1.765; P<.001), N+ (OR, 1.763; P<.001), and a higher number of lymph node metastases (OR, 1.985; P<.001). Compared with normal-weight patients with tumor tissue calcifications, obese patients with tumor tissue calcifications had an increased risk of ETE (OR_obesity, 1.765 vs. OR_normal, 1.300) and N+ (OR_obesity, 1.992 vs. OR_normal, 1.784).Conclusion: Tumor tissue calcifications are positively correlated with the invasiveness of PTC. Obesity further promotes the risk of tumor invasiveness in PTC combined with tumor tissue calcifications. These findings suggest that more comprehensive evaluations by trained pathologists may help physicians identify the optimal therapeutic regimens in the postoperative period.Abbreviations: BMI = body mass index; CI = confidence interval; ETE = extrathyroidal extension; FT3 = free triiodothyronine; OR = odds ratio; PTC = papillary thyroid carcinoma; RET = rearranged during transfection; TTC = tumor tissue calcification; US = ultrasonography; USC = ultrasonography calcification; WHO = World Health Organization     

Size of the Largest Metastatic Focus to the Lymph Node is Associated with Incomplete Response of Pn1 Papillary Thyroid Carcinoma

Objective: To evaluate the influence of the size of the metastatic focus in lymph nodes (LNs) on therapeutic response among papillary thyroid cancer (PTC) and cervical pathologically proven LN metastases (pN1).Methods: Patients with pN1 PTC who underwent total or near-total thyroidectomy, LN dissection, and postoperative radioactive iodine therapy in a university hospital between 2014 and 2016 were retrospectively reviewed. Furthermore, 554 patients were assigned to three groups according to the size of the metastatic focus in the LNs (≤0.2 cm, 0.2 to 1.0 cm, ≥1.0 cm). Structural incomplete response (SIR) was defined as structural or functional evidence of disease with any thyroglobulin level and/or anti-thyroglobulin antibodies.Results: Among the 554 patients, the proportion of patients with SIR was 2.5% (4/161) in group 1, 13.9% (37/267) in group 2, and 46.8% (59/126) in group 3 (χ² = 100.073; P<.001). The optimal cutoff value of the size of the largest metastatic focus to the LNs was 0.536 cm to predict SIR with a corresponding sensitivity of 0.82, a specificity of 0.716, and an area under the curve of 0.821 (95% confidence interval &lsqb;CI], 0.777 to 0.864; P<.001). Size of the largest metastatic focus to the LNs was confirmed to be an independent predictive factor for SIR (odds ratio, 9.650; 95% CI, 4.925 to 18.909; P<.001).Conclusion: In patients with pN1 PTC, there is an association between the size of the largest metastatic focus to the LNs and incomplete response.Abbreviations: AJCC = American Joint Committee on Cancer; ATA = American Thyroid Association; BIR = biochemical incomplete response; CI = confidence interval; ER = excellent response; ETE = extranodal extension; 18F-FDG = 18F-fluorodeoxyglucose; IDR = indeterminate response; LN = lymph node; OR = odds ratio; PET/CT = positron emission tomography/computed tomography; pN1 = pathologically proven LN metastases; PTC = papillary thyroid carcinoma; RAI = radioactive iodine; ROC = receiver operating characteristic; SIR = structural incomplete response; sTg = stimulated thyroglobulin; TgAb = anti-thyroglobulin antibody; TSH = thyroid-stimulating hormone     

A Simple Curriculum Content Change Increased Medical Student Comfort with Transgender Medicine

ObjectiveA barrier to safe therapy for transgender patients is lack of access to care. Because transgender medicine is rarely taught in medical curricula, few physicians are comfortable with the treatment of transgender conditions. Our objective was to demonstrate that a simple content change in a medical school curriculum would increase students' willingness to care for transgender patients.MethodsCurriculum content was added to the endocrinology unit of the Boston University second-year pathophysiology course regarding rigidity of gender identity, treatment regimens, and monitoring requirements. All medical students received an online, anonymous questionnaire 1 month prior to and 1 month after receiving the transgender teaching. The questionnaire asked about predicted comfort using hormones to treat transgender individuals. Shifts in the views of the second-year students were compared with views of students not exposed to the curriculum change.ResultsPrior to the unit, 38% of students self-reported anticipated discomfort with caring for transgender patients. In addition, 5% of students reported that the treatment was not a part of conventional medicine. Students in the second-year class were no different than other students. Subsequent to the teaching unit, the second-year students reported a 67% drop in discomfort with providing transgender care (P<.001), and no second-year students reported the opinion that treatment was not a part of conventional medicine.ConclusionA simple change in the content of the second-year medical school curriculum significantly increased students' self-reported willingness to care for transgender patients.(Endocr Pract. 2013;19:633-637)     

The Synergy to Enable Glycemic Control Following Emergency Department Discharge Program for Adults with Type 2 Diabetes: Step-Diabetes

Objective: To evaluate a diabetes (DM) care delivery model among hyperglycemic adults with type 2 DM being discharged from the emergency department (ED) to home. The primary hypothesis was that a focused education and medication management intervention would lead to a greater short-term improvement in glycemic control compared to controls.Methods: A 4-week, randomized controlled trial provided antihyperglycemic medications management using an evidence-based algorithm plus survival skills diabetes self-management education (DSME) for ED patients with blood glucose (BG) levels ≥200 mg/dL. The intervention was delivered by endocrinologist-supervised certified diabetes educators. Controls received usual ED care.Results: Among 101 participants (96% Black, 54% female, 62.3% Medicaid and/or Medicare insurance), 77% completed the week 4 visit. Glycated hemoglobin A1C (A1C) went from 11.8 ± 2.4 to 10.5 ± 1.9% (P<.001) and 11.5 ± 2.0 to 11.1 ± 2.1% in the intervention and control groups, respectively (P = .012). At 4 weeks, the difference in A1C reduction between groups was 0.9% (P = .01). Mean BG decreased for both groups (P<.001), with a higher percentage of intervention patients (65%) reaching a BG <180 mg/dL compared to 29% of controls (P = .002). Hypoglycemia rates did not differ by group, and no severe hypoglycemia was reported. Medication adherence (Modified Morisky Score©) improved from low to medium (P<.001) among intervention patients and did not improve among controls.Conclusions: This study provides evidence that a focused diabetes care delivery intervention can be initiated in the ED among adults with type 2 diabetes and hyperglycemia and safely and effectively completed in the ambulatory setting. Improvement in short-term glycemic outcomes and medication adherence were observed.Abbreviations: A1C = glycated hemoglobin A1C BG = blood glucose BMI = body mass index CDE = certified diabetes educator CI = confidence interval DM = diabetes mellitus DSME = diabetes self-management education ED = emergency departmentMMAS-8 = Modified Morisky Medication Scale PCP = primary care provider POC = point of care SQ = subcutaneous     

Predictors of Nonattendance at an Endocrinology Outpatient Clinic

Objective: To identify predictors potentially contributing to patients' nonattendance or to same-day cancellation of scheduled appointments at an adult endocrinology office practice.Methods: A retrospective, records-based, cross-sectional study was conducted using data from 9,305 electronic medical records of patients presenting at a U.S. metropolitan adult endocrinology clinic in 2013. Statistical analyses included multivariate regression, calculated odds ratios, and posttest probabilities.Results: Of 29,178 total patient visits analyzed, 68% were attended by patients. Of total scheduled appointments, 7% resulted in nonattendance and 5% in same-day cancellation. The most significant predictors of nonatten-dance were a previous history of nonattendance (P<.001), uncontrolled diabetes (P<.001), and new patients to the practice (P<.001). Long lead-time to appointment (P = .001), younger age (P<.001), and certain insurance carriers (P<.001) also were significant predictors.Conclusion: Specific predictors of nonattendance at scheduled appointments were identified using statistical analysis of electronic medical record data. Previous history of nonattendance and having uncontrolled diabetes (especially in patients newly referred to the practice) are among these significant predictors. Identifying specific predictors for nonattendance enables targeted strategies to be developed.Abbreviations:APRN = Advanced Practice Registered NurseCI = confidence intervalDM = diabetes mellitusEMR = electronic medical recordHbA1c = glycated hemoglobinNS = no-showOR = odds ratioSDC = same-day cancellation     

A Review of Breast Development in Cisgender Women and Implications for Transgender Women

Objective: The objective of this article is to describe the hormonal pathways required for breast development in cisgender women and to review the current available literature describing breast growth and breast cancer risk in transgender women.Methods: Literature review and discussion.Results: Early mammary tissue development occurs prenatally. This process is hormone-independent and occurs similarly in males and females. Breast tissue is quiescent until puberty, at which time surging estrogen levels in cisgender girls mediate breast development and growth. Adult breast tissue composition further evolves in cisgender women during pregnancy, lactation, and menopause, revealing the ever-changing interplay between breast structure and hormonal environment.Conclusion: Breast growth is a significant physical endpoint in the hormonal treatment of transgender women. Transgender hormone regimens, which typically pair an estrogen with an anti-androgen, can help achieve this goal.     

Improvements in Metabolic Control in Adults with Type 2 Diabetes Following Referral to a Diabetes Center, 2005–2010

Objective: We aimed to compare metabolic control in adults with diabetes in the general population to those newly referred to a diabetes center and after 1 year of specialty care.Methods: We performed a retrospective comparison of adults with diabetes aged ≥20 years data from the National Health and Nutrition Examination Survey (NHANES, n = 1,674) and a diabetes center (n = 3,128) from 2005–2010. NHANES participants represented the civilian, non-institutionalized U.S. population. Diabetes center referrals lived primarily around eastern Massachusetts. The proportion attaining targets for glycated hemoglobin A1c (A1c), blood pressure (BP), low-density lipoprotein (LDL) cholesterol, or all 3 (ABC control) and the proportion prescribed medications to lower A1c, BP, or cholesterol were evaluated.Results: Compared to the general sample, a smaller proportion of new diabetes center referrals had A1c <7% (<53 mmol/mol, 24% vs. 53%, P<.001), BP <130/80 mm Hg (38% vs. 50%, P<.001), and ABC control (5.6% vs. 17%, P<.001) but not LDL<100 mg/dL (<2.6 mmol/L, 54% vs. 53%, P = .65). After 1 year, more diabetes center referrals attained targets for A1c (40%), BP (38%), LDL (67%), and ABC control (15%) (P<.001 for all versus baseline). ABC control was not different between the general sample and diabetes center referrals at 1 year (P = .16). After 1 year, a greater percentage of diabetes center referrals compared to the general sample were prescribed medications to lower glucose (95% vs. 72%), BP (79% vs. 64%), and cholesterol (77% vs. 54%)(all P<.001).Conclusion: Compared to the general population, glycemic control was significantly worse for adults newly referred to the diabetes center. Within 1 year of specialty care, ABC control increased 270% in the setting of significant therapy escalation.Abbreviations:A1c = glycated hemoglobin A1cABC = composite of A1c, blood pressure, and cholesterolACEi = angiotensin-converting enzyme inhibitorARB = angiotensin receptor blockerBMI = body mass indexBP = blood pressureEHR = electronic health recordLDL = low-density lipoproteinNCHS = National Center for Health StatisticsNHANES = National Health and Nutrition Examination SurveyPCP = primary care provider     

Serum Hormone Concentrations in Transgender Individuals Receiving Gender-Affirming Hormone Therapy: A Longitudinal Retrospective Cohort Study

ObjectiveTo examine the association of various gender-affirming hormone therapy regimens with blood sex hormone concentrations in transgender individuals.MethodsThis retrospective study included transgender people receiving gender-affirming hormone therapy between January 2000 and September 2018. Data on patient demographics, laboratory values, and hormone dose and frequency were collected. Nonparametric tests and linear regression analyses were used to identify factors associated with serum hormone concentrations.ResultsOverall, 196 subjects (134 transgender women and 62 transgender men), with a total of 941 clinical visits, were included in this study. Transgender men receiving transdermal testosterone had a significantly lower median concentration of serum total testosterone when compared with those receiving injectable preparations (326.0 ng/dL vs 524.5 ng/dL, respectively, P = .018). Serum total estradiol concentrations in the transgender women were higher in those receiving intramuscular estrogen compared with those receiving oral and transdermal estrogen (366.0 pg/mL vs 102.0 pg/mL vs 70.8 pg/mL, respectively, P < .001). A dose-dependent increase in the hormone levels was observed for oral estradiol (P < .001) and injectable testosterone (P = .018) but not for intramuscular and transdermal estradiol. Older age and a history of gonadectomy in both the transgender men and women were associated with significantly higher concentrations of serum gender-affirming sex hormones.ConclusionIn the transgender men, all routes and formulations of testosterone appeared to be equally effective in achieving concentrations in the male range. The intramuscular injections of estradiol resulted in the highest serum concentrations of estradiol, whereas transdermal estradiol resulted in the lowest concentration. There was positive relationship between both oral estradiol and injectable testosterone dose and serum sex hormone concentrations in transgender people receiving GAHT.     

Unfavorable Responses to Radioiodine Therapy in N1b Papillary Thyroid Cancer: A Propensity Score Matching Study

Objective: Regional nodal metastases carry prognostic significance in papillary thyroid cancer (PTC). However, whether different locational nodal metastases correlate with different therapeutic responses remains controversial. We innovatively applied the response to therapy restratification system to evaluate the dynamic disease status after surgery and radioactive iodine (RAI) therapy in PTC patients with different locational nodal metastases.Methods: A total of 585 nondistant-metastatic PTC patients who underwent total thyroidectomy and RAI therapy were retrospectively enrolled. Patients with nodal metastases were categorized into N1a and N1b groups. Propensity score matching was used to balance the bias between the 2 groups. Therapeutic responses were dynamically evaluated, and responses to RAI therapy were classified into excellent (ER), indeterminate (IDR), biochemical incomplete (BIR) and structural incomplete response (SIR).Results: N1b group patients showed a significantly higher pre-ablation stimulated thyroglobulin (Ps-Tg) level than N1a group patients (7.4 ng/mL versus 3.2ng/mL, P<.001). After RAI therapy, N1b group patients took a longer time to achieve ER (9.86 months versus 3.29 months, P<.001) and exhibited a higher proportion of non-ER (IDR, BIR, and SIR) (39.15% versus 17.46%, P<.001) compared to N1a group patients. In logistic regression, N1b and Ps-Tg ≥10 ng/mL were confirmed to be independent factors predicting non-ER (odds ratio: 2.591, and 9.196, respectively). In Cox regression, patients with N1b disease and Ps-Tg ≥10 ng/mL showed significantly lower hazards for achieving ER (hazard ratio: 0.564, and 0.223, respectively).Conclusion: N1b PTC patients showed inferior responses to surgery and RAI therapy compared to N1a patients. N1b was confirmed to be an independent factor predicting unfavorable responses to RAI therapy.Abbreviations: AJCC = American Joint Committee on Cancer; ATA = American Thyroid Association; BIR = biochemical incomplete response; BRAF^V600E = proto-oncogene B-Raf V600E mutation; CI = confidence interval; CT = computed tomography; DNA = deoxyribonucleic acid; DTC = differentiated thyroid cancer; ER = excellent response; ETE = extrathyroidal extension; HR = hazard ratio; IDR = indeterminate response; LNM = lymph node metastasis; N1a = central cervical LNM; N1b = lateral cervical LNM; OR = odds ratio; PSM = propensity score matching; Ps-Tg = pre-ablation stimulated thyroglobulin; PTC = papillary thyroid cancer; RAI = radioactive iodine; SIR = structural incomplete response; Tg = thyroglobulin; TgAb = thyroglobulin antibody; TSH = thyroid-stimulating hormone     

Orthopedic-Metabolic Collaborative Management for Osteoporotic Hip Fracture

Objective: Osteoporotic hip fractures are associated with increased morbidity, mortality, and secondary fractures. Although osteoporosis treatment can reduce future fracture risk, patients often do not receive it. We report results of a coordinator-less fracture liaison service in Israel addressing hip fracture patients. The primary endpoint was attending the Metabolic Clinic. Secondary endpoints included vitamin D measurement, calcium and vitamin D recommendations, initiation of osteoporosis treatment, and mortality 1-year post-fracture.Methods: This prospective study included 219 hip fracture patients who were compared with historical controls. Data on hospitalized patients were collected before and after implementation of a structured protocol for hip fracture patients, led by a multidisciplinary team, without a coordinator.Results: The study included 219 and 218 patients ≥60 years old who were operated on in 2013 and 2012, respectively. Metabolic Clinic visits increased from 6.4 to 40.2% after the intervention (P<.001). Among 14 patients who attended the Clinic in 2012, 85.7% began osteoporosis therapy; among 88 who attended in 2013, 45.5% were treated at the first visit. Vitamin D measurements and calcium and vitamin D supplementation increased postintervention (0.5–80.1%, P<.001; 30.8–84.7%, P<.001, respectively). Patients receiving osteoporosis medications had lower mortality rates than untreated patients (4.3% vs. 21.8%).Conclusion: An Orthopedic-Metabolic team implemented by existing staff without a coordinator can improve osteoporosis care for hip fracture patients. Yet, gaps remain as only 40% had Metabolic Clinic follow-up postintervention, and of these, only half received specific treatment recommendations. Hospitals are encouraged to adopt secondary fracture prevention protocols and continuously improve them to close the gaps between current management and appropriate metabolic assessment and treatment.Abbreviations: CHS = Clalit Health Services; CI = confidence interval; FLS = fracture liaison service; HMO = health maintenance organization; OR = odds ratio     

Dysregulation Of The Hypothalamic-Pituitary-Adrenal Axis Increases Central Body Fat Accumulation In Males Affected By Diabetes Mellitus And Late-Onset Hypogonadism

Objective: Functional hypercortisolism (FH) is a condition which occurs in some clinical states, such as major depression, eating disorders, numerous psychiatric conditions, and diabetes mellitus (DM) and which exerts several negative systemic effects. No data exist on the potentially harmful role of FH on body composition. In this retrospective study, we evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis dysregulation on body composition in men affected by DM-associated late-onset hypogonadism (LOH).Methods: Fourteen subjects affected by FH (FH-LOH) and 18 subjects not affected (N-LOH) were studied. Clinical, hormonal, and body composition measures were considered.Results: The 2 groups had comparable age and weight. FH-LOH patients had lower levels of total (2 ± 0.27 ng/mL versus 2.31 ± 0.26 ng/mL; P = .003) and free (39.5 ± 6.44 pg/mL versus 46.8 ± 7.23 pg/mL; P = .005) (median, 38.7 &lsqb;interquartile range, 36.1 to 41.3] pg/mL versus median, 46.1 &lsqb;interquartile range, 40.4 to 52.7] pg/mL) testosterone compared to N-LOH patients. Abdominal fat amount was greater in FH-LOH than in N-LOH patients, even after adjustment for total testosterone. None of the bivariate correlations between body composition measures and hormonal variables were significant in N-LOH. Conversely, in FH-LOH, cortisol area under the curve (AUC) was found to be positively and significantly correlated with trunk (r = 0.933; P<.001) and abdominal fat (r = 0.852; P<.001) and negatively with lean leg (r = -0.607; P = .021). All of these associations were further confirmed upon linear regression analysis in FH-LOH (respectively, unstandardized β = 10.988 &lsqb;P<.001]; β = 1.156 &lsqb;P<.001]; β = -7.675 &lsqb;P = .021]). Multivariate regression analysis confirmed AUC cortisol as a predictor of trunk and abdominal fat in FH-LOH.Conclusion: Dysregulation of the HPA axis in LOH-associated DM seems to be involved in abdominal fat accumulation.Abbreviations:ACTH = adrenocorticotropic hormoneAUC = area under the curveCRH = corticotropin-releasing hormoneCT = computed tomographyDEXA = dual-energy X-ray absorptiometryDM = diabetes mellitusFH = functional hypercortisolismFH-LOH = subjects affected by functional hypercortisolismFSH = follicle-stimulating hormoneHPA = hypothalamic-pituitary-adrenalLH = luteinizing hormoneLOH = late-onset hypogonadismN-LOH = subjects not affected by functional hypercortisolismOST = overnight low-dose dexamethasone suppression testSHBG = sex hormone–binding globulinUFC = urinary free cortisol