Gender-affirming hormone therapy effect on cortisol levels in trans males and trans females.

PURPOSE: Previous studies have shown differences in baseline and stimulated cortisol levels between men and women. Whether this difference is secondary to sex hormones or to other factors, such as genetic or epigenetic changes, is unknown. We investigated the effect of gender-affirming hormone treatment (GAHT) on the hypothalamo-pituitary-adrenal axis of transgender subjects in an effort to throw light on this question. METHODS: Ten transgender males (TM) and eight transgender females (TF) underwent a low-dose (1 µg) adrenocorticotropic hormone (ACTH) stimulation test before and 6 months after GAHT initiation. Serum total, free and salivary cortisol (SC) levels were measured at baseline and at 20, 30 and 40 min. RESULTS: For the TM, all three levels were significantly lower at several time points after ACTH injection compared to pretreatment levels following 6 months of treatment (p < .05). Likewise, the overall SC response as calculated by the area under the curve was significantly lower (p = .0053). For the TF, the basal total cortisol (TC) level increased after 6 months of treatment (p < .01) while ACTH-stimulated SC levels decreased significantly. The basal ACTH levels were significantly lower following hormonal therapy (p < .001). CONCLUSION: Stimulated salivary cortisol levels decreased significantly after 6 months of GAHT in both male and female transgender subjects, possibly reflecting a decreased state of anxiety associated with treatment initiation. Additionally, basal and stimulated serum TC levels increased after hormonal treatment in the TF, probably secondary to the effect of oestrogen on cortisol-binding globulin.

Sublingual Estradiol Offers No Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study.

Purpose: Chronic gender-affirming hormone therapy (GAHT) with sublingual estradiol (SLE) has not been studied. We aimed to compare GAHT with SLE only, to combined oral (CO) estradiol and cyproterone acetate, in treatment-naive trans women. Methods: Twenty-two trans women enrolled into either the CO arm or the SLE-only arm (0.5 mg four times daily) in this 6-month prospective study. Anthropometric and laboratory variables were collected at baseline and 3 and 6 months. At the study beginning and end, body composition was measured by dual-energy X-ray absorptiometry and bioelectrical impedance, and gender dysphoria, sexual desire, and function were assessed by validated questionnaires. Results: Subjects in the SLE were older, 26.3±5.8 years versus 20.1±2.3 years, p=0.006. All anthropometric, body composition, and laboratory variables were identical at baseline. Although dysphoria appeared greater, and sexual function lower at baseline in the CO group, this canceled out after age adjustment. Both treatments induced similar biochemical and hormonal changes. Creatinine, hemoglobin and cholesterol decreased significantly, while testosterone was suppressed to the same level in both groups: 3.22 [1.47-5.0] nmol/L in the SLE group and 2.41 [0.55-8.5] nmol/L in the CO, p=0.65. Significant changes in body composition toward a more feminine body were noted in both groups. Dysphoria did not significantly improve in either group, while sexual desire and function decreased at six months in both, p<0.001. Conclusions: Both treatments achieved similar clinical changes. At this stage, SLE, which repeatedly induces alarming excursions of serum estradiol throughout the day, appears to offer no advantage over the CO approach.

Dysglycemia in non-functioning pancreatic neuroendocrine tumors (NF-PNET): Further insights into an under recognized entity.

Objective: Pancreatic neuroendocrine tumors (PNETs) are rare, but their incidence has risen significantly in recent years. Whereas diabetes mellitus (DM) is recognized in association with chronic pancreatitis and pancreatic cancer, it has not been well-characterized concerning non-functioning (NF)-PNETs.Study aim: to determine whether NF-PNETs are associated with DM/ Pre-DM and characterize the features of this putative association. Methods: Retrospective study to evaluate rate of Pre-DM /DM in subjects with NF-PNETs. Results: Study cohort of 129 patients with histologically confirmed NF-PNETs, ∼60% were men (M/F: 77/52). Abnormal glucose metabolism that preceded any treatment was seen in 70% of this cohort: overt DM in 34% and Pre-DM in 36% of the subjects. However, during follow-up, the overall prevalence rose to 80.6%, owing exclusively to newly diagnosed DM in subjects who received treatment.Patients with DM/Pre-DM were older (65 ± 11; 54 ± 14; p < 0.0001), the tumor was more commonly localized in the pancreatic body and tail (76.5% vs. 23.5% p = 0.03), while BMI (27 ± 6 vs. 28 ± 5 kg/m2), and tumor size (2.4 ± 2 vs. 2.9 ± 3.2 cm) were similar. The relative prevalence of DM in our cohort of NF-PNETs was 1.6 higher than that in the age and gender-adjusted general Israeli population (95 %CI: 1.197-2.212p = 0.03). Conclusions: We found a high rate of impaired glucose metabolism, either DM or Pre-DM, in a large cohort of NF-PNETs. The high prevalence of diabetes/pre-diabetes was unrelated to obesity or tumor size. This observation should increase awareness of the presence of DM on presentation or during treatment of "NF"-PNETs.

Endocrinology specialty service for inpatients: an unmet growing need.

BACKGROUND: There is recent concern regarding the documented mismatch between demand and supply, vis-à-vis the growing need for trained endocrinologists unmet by parallel rise in the world workforce of endocrinologist. Due to the increasing complexity of disease in inpatients, in recent years we have experienced a growing demand for inpatient endocrine consults. Surprisingly, the need for the endocrinology subspecialty in the overall care of inpatients in the current setting of general hospitals has received little attention. METHODS: A retrospective analysis of endocrine consult service based on solicited consults carried out during 3 consecutive months. RESULTS: During 3 months, there were 767 consults, comprised of 156 diabetes referrals and 611 endocrine/metabolic consult requests. The 611 "non-glucocentric" consult requests were related to 295 inpatients (2.1 ± 2.7 consults/patient). Mean patient age was 58.9 ± .18 years (range 21-92), with some F/M preponderance (58/42%). Requests for endocrine consults were evenly distributed (49.8%, 50.2%) between internal medicine and surgery wards. Case distribution was as follows: thyroid 45.4%, calcium & bone 11.5%, pituitary 12%, adrenal 10% and all others 8.1-0.7%. The mean response time was 4.4 ± 2.7 h. The consults had a discernible effect on the patients' disease management in 60% of the patients. Of these, the consults modified the hospital treatment in 74%, the discharge treatment recommendations in 19% and the diagnosis in 7%. CONCLUSION: At a large medical center, endocrine consults were requested for ~ 3.3% of all admitted inpatients. The endocrine consults modified pre-consult diagnosis or treatment in ~ 60% of the cases. Contrary to its common image as an exclusively outpatient-based subspecialty, endocrinology practiced by specialists and endocrine trainees has a notable role in the daily care of inpatients admitted to a referral general hospital.

A Lymph Node Ratio Model for Prognosis of Patients with Pancreatic Neuroendocrine Tumors.

The objective of this study was to determine the prognostic value of lymph node (LN) involvement and the LN ratio (LNR) and their effect on recurrence rates and survival in patients with pancreatic neuroendocrine tumors (PNETs) undergoing surgery. This single-center retrospective study reviewed the medical records of 95 consecutive patients diagnosed with PNETs who underwent surgery at our medical center between 1997 and 2017. The retrieved information included patient demographics, pathology reports, treatments, and oncological outcomes. Results: 95 consecutive potentially suitable patients were identified. The 78 patients with PNETs who underwent surgery and for whom there was adequate data were included in the analysis. Their mean ± standard deviation age at diagnosis was 57.4 ± 13.4 years (range 20-82), and there were 50 males (64%) and 28 females (36%). 23 patients (30%) had LN metastases (N1). The 2.5- and 5-year disease-free survival (DFS) rates for the entire cohort were 79.5% and 71.8%, respectively, and their 2- and 5-year overall survival (OS) rates were 85.9% and 82.1%, respectively. The optimal value of the LNR was 0.1603, which correlated with the outcome (2-year OS p = 0.002 HR = 13.4 and 5-year DFS p = 0.016 HR = 7.2, respectively, and 5-year OS and 5-year DFS p = 0.004 HR = 9 and p = 0.001 HR = 10.6, respectively). However, the multivariate analysis failed to show that the LNR was an independent prognostic factor in PNETs. Patients with PNETs grade and stage are known key prognostic factors influencing OS and DFS. According to our results, LNR failed to be an independent prognostic factor.

Sperm parameters in Israeli transgender women before and after cryopreservation.

BACKGROUND: The application of fertility preservation, initially intended for oncological patients prior to gonadotoxic treatment, has extended in recent years to transgender and gender-non-conforming individuals undergoing therapy for gender compatibility. OBJECTIVES: To examine semen quality and survival in transgender women pursuing semen cryopreservation in the presence or absence of gender-affirming hormonal medication. MATERIALS AND METHODS: In this retrospective cohort study, we reviewed data of 74 consecutive transgender women presenting for semen cryopreservation at a single center between 2000 and 2019. Semen parameters before and after cryopreservation were compared to a control group composed of 100 consecutive sperm bank donor candidates. A subgroup analysis of subjects who had used gender-affirming hormonal treatment was also performed. RESULTS: Compared to the control group, transgender women had lower total sperm count (144.0 vs. 54.5 million, respectively, p < 0.001), lower sperm motility percentage (65.0% vs. 51.0%, respectively, p < 0.001), and lower total motile sperm count (94.0 vs. 27.0 million, respectively, p < 0.001). Values were further decreased in transgender women who had received hormonal treatment before sperm cryopreservation. Post-thawing motility rate remained lower in the transgender group compared to the control group (20.0% vs. 45.0%, respectively, p < 0.001), and the total motile count remained lower as well (2.7 vs. 9.0 million, respectively, p < 0.001). Following sperm cryopreservation, the post-thaw decreases in total motile sperm count were higher in the transgender group compared with the control group (91.5% vs. 90.0%). Further subdivision in the transgender group showed that the decrease in total motile sperm count was lower for transgender women who did not use gender-affirming hormonal treatment compared to those who did (-89.7% vs. -92.6%, respectively, p < 0.01). DISCUSSION AND CONCLUSION: Sperm parameters in transgender women are poor compared to candidates for sperm donation representing the general population. Specimens collected after discontinuation of gender-affirming hormone treatments were further impaired. Moreover, post-thawing sperm total motile count, motility, and overall sperm survival were reduced in transgender women.

Why fertility preservation rates of transgender men are much lower than those of transgender women.

RESEARCH QUESTION: What are the fertility preservation rates of transgender women and transgender men, and what are the factors that affect their decision-making? DESIGN: This prospective study included 97 transgender women and 91 transgender men referred to the Gender Clinic of the study medical centre's Endocrinology Institute and to the Gan Meir Community Health Care Centre. The responders completed a 28-item questionnaire during 2018. RESULTS: Most of the transgender women and transgender men wished to parent a child (67.4% and 61.9%, respectively, P = 0.447), but only 40.4% of the transgender women and 5.8% of the transgender men used fertility preservation (P < 0.001). The main reasons for not pursuing fertility preservation were unwillingness to postpone gender-affirming treatment (58.8% and 74.0%, respectively, P = 0.076), preference to adopt a child (58.8% and 60.9%, respectively, P = 0.818) and cost (44.9% and 60.9%, respectively, P = 0.086). Factors related to the fertility preservation process itself were specifically chosen by transgender men compared with transgender women as the reason for not pursuing this treatment, including distress caused by the fertility preservation technique (60.3% versus 29.3%, respectively, P = 0.006), fear of gender dysphoria caused by hormonal treatment (63.5% versus 28.3%, P = 0.002) and concern over the attitude of medical staff (44% versus 19%, P = 0.027). CONCLUSIONS: Fertility preservation rates were considerably lower among transgender men than transgender women, strongly related to the fertility preservation process itself. Finding ways to overcome the obstacles confronted by transgender individuals, especially transgender men, will enhance their future biological parenting.

Transgender men's preferences when choosing obstetricians and gynecologists.

BACKGROUND: Transgender men are a marginalized population with unique health care needs. However, their usage of health services is low because of considerable discrimination. A major factor in their avoidance is patient-provider interactions. METHODS: This cross-sectional study included 102 transgender men who anonymously completed a 55-item questionnaire in clinic, between 10/2017 and 01/2019. In addition, 92 transgender women filled out the part about family physician's preferences. We examined which characteristics transgender men prefer in their obstetricians/gynecologists in order to promote their usage of healthcare services. RESULTS: A small majority of the transgender men (54.1%) had no gender preference for their obstetrician/gynecologist, while 42.9% preferred a female obstetrician/gynecologist and 3.1% preferred a male obstetrician/gynecologist. Most transgender men with a same-gender preference preferred female obstetricians/gynecologists for both invasive procedures (e.g., pelvic examination, 97.4%) and non-invasive procedures (e.g., cesarean section, 60%). The reasons for preferences regarding invasive procedures were feeling comfortable, embarrassment and feeling that female obstetricians/gynecologists are gentler. Transgender men who preferred female obstetricians/gynecologists ranked ability (90.5%), sexual tolerance (92.9%) and gender identity tolerance (90.5%) as the top three desirable qualities of obstetricians/gynecologists, while the responders who did not prefer female ranked ability (94.6%), experience (92.9%) and knowledge (92.9%) as the top three qualities. Transgender men with female preferences considered female obstetricians/gynecologists to be more accepting of gender identity compared to the responders that did not prefer females (47.5% vs. 9.1%, P < .001).. CONCLUSION: A small majority of the transgender men exhibited no gender preference when choosing an obstetrician/gynecologist, although 42.9% preferred females. The latter choice was associated with the assumption that female obstetricians/gynecologists are more tolerant towards their transgender men patients. Educating the medical staff about their special needs and establishing dedicated SGM centers staffed with high percentages of female healthcare providers are highly recommended.

Impaired aldosterone response to ACTH without hypoaldosteronism: An unrecognized secretory pattern in search of clinical implications.

CONTEXT: Aldosterone has been recently characterized as a 'stress hormone'. Stress per se elicits a sizable rise in aldosterone secretion, which could be replicated by the administration of a low dose (0.03-1 µg, IV) of adrenocorticotropic hormone (ACTH). Whether or not the aldosterone response to ACTH could be selectively impaired, that is, in association with intact cortisol response, is presently unknown. OBJECTIVE: To determine whether or not the aldosterone response to low dose of ACTH is impaired in subjects referred to assess the hypothalamic-pituitary-adrenal axis (HPA). DESIGN: Retrospective analysis. SETTING: Outpatient referral endocrine day care centre. PATIENTS: One hundred and ninety-five consecutive subjects who underwent the low dose (1 µg) ACTH test, in whom decreased cortisol reserve was suspected due to former/present glucocorticoid excess, pituitary disease or/and unexplained weakness. MAIN OUTCOME MEASURES: The outcome was the detection of lack of aldosterone response, defined as a rise <111 pmol/l. RESULTS: In all, 46/195 subjects had subnormal aldosterone response as compared with 52/195 subjects showing diminished cortisol response. Nine subjects had combined deficient aldosterone and cortisol response. In the 37 subjects with isolated subnormal aldosterone response common associations were the use of exogenous glucocorticoids, mostly prednisone (n = 16); former Cushing disease (n = 2); nonfunctioning pituitary adenoma (n = 8); hypothyroidism (n = 11); the use of statins (n = 11), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (n = 6), sex steroids in transgenders and orthostatic hypotension (n = 3). Twenty-seven percent (25/93) of the subjects with recent exposure to glucocorticoids had impaired aldosterone response to ACTH. CONCLUSION: Blunted aldosterone response to ACTH in the absence of hypoaldosteronism was seen in ~27% of subjects referred for HPA assessment using the low dose 1 µg ACTH test. Exposure to glucocorticoid excess was often linked to this impairment, independent of the cortisol response to ACTH.

Low-Dose Cyproterone Acetate Treatment for Transgender Women.

BACKGROUND: Transgender women with intact gonads receive lifelong hormonal treatment to suppress physiologic androgen production, the optimal efficacious and safe cyproterone acetate (CPA) dose has not been established. AIM: To assess the effectiveness and safety of low-dose (10-20 mg/day) compared with high-dose (50-100 mg/day) CPA treatment. METHODS: We conducted a historical cohort study of transgender women treated at a tertiary center for transgender health. OUTCOME MEASURES: Serum levels of testosterone, estradiol, prolactin, gonadotrophins, liver enzymes, and lipids. RESULTS: There were 38 transgender women in the low-dose group and 26 in the high-dose group. Age (median 24.9 years, interquartile range [IQR] 21-30 vs 25 years, IQR 19-35) and follow-up time (median 12 months, IQR 6-23 vs 15 months, IQR 12-36) were similar in the low- and high-dose groups, respectively. Serum gonadotropins and testosterone were suppressed to a similar level at all time points in both groups. Prolactin levels increased significantly in both groups, however, with a more substantial increase in the high- vs the low-dose group (804 ± 121 vs 398 ± 69 mIU/ml at 12 months, respectively, P = .004). Total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglyceride levels were not significantly affected by the dose. CLINICAL IMPLICATIONS: We suggest an adjustment of current clinical practice guidelines to recommend lower doses of CPA for the treatment of transgender women. STRENGTHS & LIMITATIONS: This is the first demonstration that low-dose CPA treatment of transgender women is effective. Limitations include a relatively small sample and retrospective study design. CONCLUSION: Low-dose CPA treatment of transgender women is as effective as high-dose treatment and possibly safer. Zohar NE, Sofer Y, Yaish I, et al. Low-Dose Cyproterone Acetate Treatment for Transgender Women. J Sex Med 2021;18:1292-1298.

Comparison of Equations Estimating Resting Metabolic Rate in Older Adults with Type 2 Diabetes.

Measuring resting metabolic rate (RMR) is time-consuming and expensive, and thus various equations for estimating RMR have been developed. This study's objective was to compare five equations in elderly people with type 2 diabetes (T2DM). RMR was measured in 90 older adults (≥65 years) with T2DM (mean body mass index (BMI) of 31.5 kg/m2), using indirect calorimetry. Results were compared to four frequently used equations (those of Cunningham, Harris and Benedict, and Gougeon developed for young adults with T2DM, and that of Lührmann, which was developed for the elderly), in addition to a new equation developed recently at the Academic College at Wingate (Nachmani) for overweight individuals. Estimation accuracy was defined as the percentage of subjects with calculated RMR within ±10% of measured RMR. Measured RMR was significantly underestimated by all equations. The equations of Nachmani and Lührmann had the best estimation accuracy: 71.4% in males and 50.9% in females. Skeletal muscle mass, fat mass, hemoglobin A1c (HbA1c), and the use of insulin explained 70.6% of the variability in measured RMR. RMR in elderly participants with T2DM was higher than that calculated using existing equations. The most accurate equations for this specific population were those developed for obesity or the elderly. Unbalanced T2DM may increase caloric demands in the elderly. It is recommended to adjust the RMR equations used for the target population.

Components of metabolic syndrome in patients with multiple myeloma and smoldering multiple myeloma.

BACKGROUND: The prevalences of diabetes mellitus and hypertension, both of which are components of metabolic syndrome, are known to be increased among patients with multiple myeloma (MM), but remain undetermined among patients with smoldering MM (SMM). METHODS: Changes in various components of metabolic syndrome were investigated during the follow-up of patients with either MM or SMM compared to healthy controls. The data of 153 patients (105 with MM and 48 with SMM) and 138 controls were accessed from our medical center's records between 2008 and 2015. We analyzed the patients' data at diagnosis (baseline) and after 1, 3, and 5 years of follow-up. RESULTS: Patients with SMM had a significantly higher prevalence of diabetes, hypertension, and dyslipidemia at baseline compared to controls. A multivariate Cox regression analysis revealed a higher risk to develop dyslipidemia after 1, 3, and 5 years of follow-up among the SMM patients. The MM patients had a higher risk to develop diabetes after 1 year, hypertension after 5 years, and dyslipidemia after 1, 3, and 5 years of follow-up. CONCLUSIONS: These data demonstrate that patients with SMM and those with MM are more prone to develop various components of metabolic syndrome, and they stress the importance of following-up metabolic syndrome components in both groups of patients.

Differential Endocrine and Metabolic Effects of Testosterone Suppressive Agents in Transgender Women.

OBJECTIVE: Suppression of testosterone secretion and/or action in transgender women using cyproterone acetate (CPA), spironolactone, or gonadotropin-releasing hormone analogues (GA) is achieved through various mechanisms. Our objective was to characterize possible differential effects of these compounds on metabolic and endocrine variables. METHODS: We conducted a historic cohort study of transgender patients treated in a tertiary referral center. A longitudinal analysis of treatment naïve patients and a cross-sectional analysis of the whole cohort at the last visit was carried out. RESULTS: Among 126 transgender women (75 treatment-naïve), CPA was the predominant androgen suppressive therapy (70%), followed by spironolactone (17.6%), and GA (10.2%). Among those who were treatment-naïve, the increase in serum prolactin levels over baseline was greater at 3 months following CPA initiation (mean change 397 ± 335 mIU/L) than following spironolactone (20.1 ± 87 mIU/L) or GA initiation (64.6 ± 268 mIU/L; P = .0002). Prolactin levels remained higher in the CPA-treated group throughout follow-up, irrespective of estradiol levels, which were similar between the groups. A worse metabolic profile was associated with treatment with CPA than with spironolactone or GA. In the CPA compared to the spironolactone and GA groups, high-density lipoprotein-cholesterol levels were lower (47.1 ± 10.4, 54.4 ± 12.2, and 60.3 ± 13, respectively; P = .0076), while body mass index levels (24.3 ± 5, 21.7 ± 2.3, and 20.7±3.1 kg/m2; P = .03), and systolic (117 ± 12.1, 109 ± 12.2, and 105 ± 13.3mm Hg; P = .01) and diastolic (74 ± 9, 65.6 ± 5.5, and 65.4 ± 11 mm Hg; P = .0008) blood pressure levels were higher at the last visit. CONCLUSION: Treatment of transgender women with CPA was associated with hyperprolactinemia and a worse cardiovascular risk profile than treatment with spironolactone or GA. ABBREVIATIONS: BMI = body mass index; CPA = cyproterone acetate; E2 = estradiol; FSH = follicle-stimulating hormone; GA = gonadotropin-releasing hormone analogues; LH = luteinizing hormone.

The effect of circuit resistance training, empagliflozin or "vegeterranean diet" on physical and metabolic function in older subjects with type 2 diabetes: a study protocol for a randomized control trial (CEV-65 trial).

BACKGROUND: Treatment of the older diabetic individual comprises a therapeutic challenge. Currently little scientific evidence exists depicting the best approach to type 2 diabetes treatment in this growing sub-population of patients. The purpose of this study is to assess the effects of a modified plant-based Mediterranean diet ("vegeterranean" diet), circuit resistance training (CRT) and empagliflozin, separately or in combination, on body composition and physical function in older subjects with type 2 diabetes. The rationale for this study is to assess three interventions associated with a negative energy/caloric balance (increased caloric use in exercise, caloric restriction in the "vegeterranean" diet and caloric wasting by glycosuria with empagliflozin), their interaction and effect on body composition and physical function. METHODS: One hundred and twenty men and women ≥65 years of age with type 2 diabetes, and low levels of physical activity will be randomized (1:1:1 manner, gender stratified) for 10 weeks to one of 3 parallel arms: CRT consisting of 3 home sessions/week; ad-libitum plant-based Mediterranean diet (limited consumption of eggs, dairy and fish, avoidance of red meat and poultry) or empagliflozin 10 mg/day. After 10 weeks CRT will be added to the empagliflozin and diet arms for an additional 10 weeks. Allocation concealment and blinding of primary outcome assessors will be implemented. Efficacy will be determined by assessment of lean body mass, body weight, frailty and functional status, sarcopenia, HbA1c and quality of life questionnaires. Safety will be evaluated by routine monitoring of adverse events. This study was approved by the Tel-Aviv Sourasky Medical Center Institutional Review Board. DISCUSSION: The combination and comparison of these diverse interventions to metabolic control may lead to better understanding of their mechanism of action with potential clinical implications in older individuals. Also, this study will provide evidence of the effectiveness of these interventions on delaying the progression from diabetes to sarcopenia and/or frailty. TRIAL REGISTRATION: ClinicalTrials.gov PRS: NCT03560375 . Last registration date (last update): 06/06/2018. The trial was a-priori registered before actual recruitment of subjects.

Increment in Dietary Potassium Predicts Weight Loss in the Treatment of the Metabolic Syndrome.

BACKGROUND: In the treatment of obesity/metabolic syndrome, dietary measures traditionally focus on reducing carbohydrate/fat-related caloric intake. The possibility that changes in potassium consumption may be related to the achieved weight loss has not been previously explored. METHODS: Sixty-eight participants, with a mean age of 51.6 ± 11.0 years (F/M-30/38), who fulfilled the ATPIII criteria for the metabolic syndrome (MS) were enrolled into a 1-year intensive multidisciplinary program. Nutritional recommendation consisted of a moderate low calorie/high protein Mediterranean diet. Baseline assessment included clinical and biochemical profiling, and body composition. Nutritional components were registered over 7 days before and at the end of 1 year of treatment. RESULTS: Mean baseline body mass index (BMI) was 35 ± 4 kg/m², which declined by 9.4 ± 0.1% after one year of combined intervention. Linear stepwise regression analysis revealed that 45% of the predicted variance of the % decline in BMI was related to increased consumption of dietary potassium (ß = -0.865) and caproic acid (ß = -0.423) and reduction in the consumption of dietary vitamin B6 (ß = 0.542), calcium (ß = 0.335), total carbohydrates (ß = 0.239) and total caloric intake (ß = 0.238; p < 0.001). Notably, the strongest correlate of the decline in BMI was the increase in dietary potassium intake (ß = -0.865). Subjects whose achieved decrease in BMI was above the average (n = 30) increased potassium intake by 25% as compared to an increase in dietary potassium intake of only 3% by those whose decline in BMI was below the average (n = 36; p < 0.05). The change in dietary potassium was related to the percent increase in dietary protein (r = 0.433; p < 0.001). CONCLUSION: An increase in dietary potassium consumption is a previously unrecognized predictor of the achieved reduction in BMI in a weight-loss-oriented multidisciplinary intervention in obesity/MS. Prospective trials are underway to confirm this post-hoc finding.

Long-term effects of proximal small bowel exclusion by duodenal-jejunal bypass liner on weight reduction and glycemic control in diabetic patients.

BACKGROUND: Exclusion of the proximal gut from nutrient absorption entails significant metabolic benefits. The duodenal-jejunal bypass liner (DJBL) is the first endoscopic device that excludes the first part of the gut by covering it. OBJECTIVES: To assess weight and glycemic control at the end of treatment and after 1 year of follow-up. SETTING: Bariatric endoscopy service in a tertiary medical center. METHODS: Diabetic patients were treated with DJBL and followed prospectively between 2013 and 2016. Data were collected during scheduled visits. RESULTS: Out of 51 patients treated, 39 completed at least 9 months with the device. Complications were recorded for the entire cohort. Percent of total weight loss was 15.05% ± 6.0% after 12 months of treatment (P < .001 versus baseline). Twelve months postretrieval, percent of total weight loss decreased to 8.75% ± 5.07% (P < .001 versus baseline). Patients with baseline body mass index ≥35 kg/m2 experienced greater percent total weight loss changes over time (P < .001). There was a significant effect on hemoglobin A1C levels over time (P = .003), and the nadir was reached at 9 months of treatment (median 6.05% versus 7.20% at baseline, P < .001). Insulin users had consistently higher median hemoglobin A1C values compared with insulin nonusers (P < .001). Adverse events were experienced by 12 of 51 patients (23.5%), of which 4 cases (7.8%) were severe. CONCLUSIONS: Proximal bowel bypass by DJBL is an effective tool for weight reduction and glycemic control. Metabolic achievements are partially preserved at 1 year after device removal. Because DJBL entails a considerable rate of side effects, strategies to mitigate them are warranted.

Human sex hormone-binding globulin does not provide metabolic protection against diet-induced obesity and dysglycemia in mice.

BACKGROUND: Sex hormone-binding globulin (SHBG) is the main transporter of sex hormones in most vertebrates. Low SHBG levels have been linked to increased risk for diabetes and metabolic syndrome. Polymorphisms of the SHBG gene linked to low SHBG protein levels also strongly predicted increased risk of type 2 diabetes, thus raising the possibility that SHBG may play a role in the pathogenesis of insulin resistance and diabetes. AIM: To examine whether expression of human SHBG in mice may ameliorate the development of diabetes and metabolic syndrome in response to a high-fat diet (HFD). METHODS: Transgene mice expressing a human SHBG transgene (SHBG+) (N = 10/11; males/females) and their wild type littermates (N = 12/8; males/females) were fed HFD for 4.5 months. RESULTS: HFD induced comparable obesity in control and SHBG+ mice. Male transgenes had higher muscle mass after 2-3.5 months HFD (0.43 ± 0.028 (n = 4) vs 0.38 ± 0.053 g (n = 7), P = 0.05). Fasting blood glucose, as well as insulin or HOMA-IR, was not different in transgenic vs wild-type males after 4-5 months HFD. Female transgenes had higher fasting glucose (152 ± 29 (n = 7) vs 115 ± 27 mg/dL, P = 0.01 (n = 8)), but mean insulin and HOMA-IR were not different. Likewise, insulin tolerance test and intra-peritoneal glucose tolerance test (GTT) were not different. Finally, SHBG+ mice were not different from controls in terms of liver enzymes, serum triglyceride levels and blood pressure. CONCLUSION: In mice with diet-induced obesity, human SHBG did not protect against development of obesity or dysglycemia.

GENDER DETERMINES SERUM FREE CORTISOL: HIGHER LEVELS IN MEN.

OBJECTIVE: Because only the free fraction of serum cortisol can readily access glucocorticoid receptors, we investigated whether or not a gender-related difference in serum free cortisol (FC) exists in the basal and adrenocorticotropic hormone (ACTH)-stimulated state. METHODS: Serum total cortisol (TC) and FC were measured in 323 subjects (175 men; 148 women). Additionally, the low-dose 1-µg ACTH test was performed in 56 subjects (30 women, 26 men). Subjects were healthy volunteers, recruited in a preventive medicine screening program and an outpatient clinic. RESULTS: Overall, basal serum TC and FC level were ~18 and ~33%, respectively, higher in men than in women (TC, 14.5 ± 0.33 µg/dL vs. 12.3 ± 0.33 µg/dL; P<.0001; FC, 0.68 ± 0.02 µg/dL vs. 0.51 ± 0.02 µg/dL; P<.0001). The higher FC in men relative to women was apparent across a wide age range (17 to 86 years) and persisted after adjustment for age and body mass index. The FC fraction (%FC, out of TC) was concordantly higher in men (5.4 ± 0.09% vs. 4.8 ± 0.3%; P = .046). FC was not related to the estimated menopausal status (women age below and above 47, 50, or 53 years). ACTH-stimulated FC levels were significantly higher in men compared to women, as reflected by the area under the response curve (49.4 ± 3.4 µg × min vs. 39.6 ± 2.2 µg × min; P = .0014). CONCLUSION: Gender is an unrecognized determinant of serum FC in humans. The possibility of lifelong exposure to the higher bioactive fraction of cortisol under basal conditions or daily stress involving ACTH stimulation should be further investigated in the context of gender-related phenotypic features such as "android" (visceral) fat deposition and longevity. ABBREVIATIONS: ACTH = adrenocorticotropic hormone BMI = body mass index CBG = cortisol-binding globulin FC = free cortisol HPA = hypothalamic-pituitary-adrenal TC = total cortisol.

PANCREATIC INCIDENTALOMA: DIFFERENTIATING NONFUNCTIONING PANCREATIC NEUROENDOCRINE TUMORS FROM INTRAPANCREATIC ACCESSORY SPLEEN.

OBJECTIVE: To improve the preoperative assessment of pancreatic incidentalomas (PIs) by analysis of 1 index case and characterization of the published features of intrapancreatic accessory spleen (IPAS) compared to pancreatic neuroendocrine tumor (PNET). METHODS: A search of the literature using the online database MEDLINE. RESULTS: In all, 46 cases of IPAS have been described to date: 17 were "presumed" as IPAS based on technetium-99m (Tc-99m) scanning, fine-needle aspiration (FNA) stain for CD8, or contrast-enhanced sonography; 29 were misdiagnosed as PNET and underwent surgery. The pancreatic lesions were 1) mostly solitary; 2) solid on imaging; 3) well defined; 4) located predominantly at the pancreatic tail; 5) not exceeding 3 cm in the largest diameter; 5) all detected in adults (22-81 years); 6) not related to sex. In subjects referred for surgery, standard imaging studies/imaging protocols did not differentiate between IPAS and PNET. FNA was performed in 5/46 cases, all of which were false-positive for PNET. Immunohistochemical staining for T-cells on FNA material and specific imaging features (characteristic arciform splenic enhancement pattern on dynamic computed tomography [CT]; nuclear scintigraphies with radioisotope specifically trapped by splenic tissue [Tc-99m]) or contrast-enhanced sonography offered valuable clues. Still, distal pancreatectomy and splenectomy was carried out in 72%, and the rest had distal pancreatectomies. CONCLUSION: IPAS should be considered before surgery in patients with PIs. A new practical algorithm is presented for better preoperative evaluation of such lesions; it combines the recognition of early indicators and sequential consideration of cytologic and imaging features to decrease the hazards of unnecessary major surgery. ABBREVIATIONS: CT = computed tomography EUS = endoscopic ultrasound FNA = fine-needle aspiration HDRBC = heat-damaged red blood cells IPAS = intrapancreatic accessory spleen MRI = magnetic resonance tomography NF-PNET = nonfunctioning pancreatic neuroendocrine tumor PET = positron emission tomography PNET = pancreatic neuroendocrine tumor PI = pancreatic incidentalomas SPIO = superparamagnetic iron oxide Tc-99m = technetium-99m.

Multidisciplinary Treatment of the Metabolic Syndrome Lowers Blood Pressure Variability Independent of Blood Pressure Control.

Blood pressure (BP) variability (BPV) contributes to target organ damage independent of BP. The authors examined the effect of a 1-year multidisciplinary intervention on BPV in patients with the metabolic syndrome (MetS) as defined by criteria from the Third Report of the Adult Treatment Panel. Forty-four nondiabetic patients underwent clinical and biochemical profiling, 24-hour ambulatory BP monitoring (ABPM), body composition, carotid intima-media thickness, and carotid-femoral pulse wave velocity (PWV). The intervention targeted all MetS components. BPV was assessed by the standard deviation of daytime systolic BP derived from ABPM. Patients with low and high BPV (lower or higher than the median daytime standard deviation of 11.6 mm Hg) did not differ in regards to systolic and diastolic BP, age, fasting glucose, glycated hemoglobin, and body mass index, but the high-variability group had higher values of low-density lipoprotein and leg fat. The 1-year intervention resulted in weight reduction but not BP-lowering. BPV declined in the high-variability group in association with lowering of PWV, C-reactive protein, glycated hemoglobin, alanine aminotransferase, asymmetric dimethylarginine, and increased high-density lipoprotein cholesterol. A multidisciplinary intervention independent of BP-lowering normalized BPV, lowered PWV, and enhanced metabolic control.