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.

DXA assessment and fracture prevention in hormone positive breast cancer patients after treatment initiation with aromatase inhibitors: A registry-based cohort study.

Background: Several guidelines have been proposed to prevent aromatase inhibitors induced bone loss (AIBL), but there is scarce data on their endorsement in clinical practice. Aim: To assess bone health evaluation and fracture prevention in postmenopausal women with estrogen receptor (ER)-positive breast cancer after aromatase inhibitors (AI) initiation. Methods: An historical cohort analysis based on data from the cancer and osteoporosis Maccabi Health Services (MHS) registries from Jan 1st 2009 to Dec 31st 2020. Cases of estrogen receptor (ER)-positive breast cancer were extracted. Index date was set as the first aromatase inhibitors (AI) purchase. Variables such as age, BMI, smoking history, alcohol use, rheumatoid arthritis, diabetes, glucocorticosteroid use, previous fractures, BMD T-scores and purchases of AI and anti-resorptive agents were collected. Age under 50, previous cancer, prior major osteoporotic fractures and prior anti-resorptive treatment were exclusion criteria. Kaplan-Meier curves were generated to assess the time to outcomes. Multivariable Cox's proportional hazards survival model was performed. Results: A total of 8617 women initiating AI were eligible. The median follow up was 6.1 years. The mean (SD) age at index was 62.8 (9.2), the mean (SD) BMI was 29.1 (5.6). The mean (SD) T-score was -1.3 (1.2) at the lumbar spine, -1.5 (0.9) at the femoral neck and -1.0 (1.0) at the total hip. Twenty percent had type 2 diabetes, 8.1 % were active smokers, 3.8% had rheumatoid arthritis and 1.2% were exposed to glucocorticoids.A total of 37% and 53% underwent a DXA scan at 1 and 2 years from AI initiation, and 12% and 17% were prescribed an anti-resorptive agent at 1 and 2 years from index. Advanced age was associated with a higher rate of evaluation and treatment, while obesity and diabetes were associated with a lower rate. The cumulative incidence of a major osteoporotic fracture was 8.8 and 15.8 % at 5 and 10 years, respectively. Conclusions: Despite the excess risk of fractures, bone health assessment and preventive treatment are still partial and postponed in breast cancer AI treated patients. Strategies to ensure appropriate care are needed.

Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement.

This Consensus Statement from an international, multidisciplinary workshop sponsored by the Pituitary Society offers evidence-based graded consensus recommendations and key summary points for clinical practice on the diagnosis and management of prolactinomas. Epidemiology and pathogenesis, clinical presentation of disordered pituitary hormone secretion, assessment of hyperprolactinaemia and biochemical evaluation, optimal use of imaging strategies and disease-related complications are addressed. In-depth discussions present the latest evidence on treatment of prolactinoma, including efficacy, adverse effects and options for withdrawal of dopamine agonist therapy, as well as indications for surgery, preoperative medical therapy and radiation therapy. Management of prolactinoma in special situations is discussed, including cystic lesions, mixed growth hormone-secreting and prolactin-secreting adenomas and giant and aggressive prolactinomas. Furthermore, considerations for pregnancy and fertility are outlined, as well as management of prolactinomas in children and adolescents, patients with an underlying psychiatric disorder, postmenopausal women, transgender individuals and patients with chronic kidney disease. The workshop concluded that, although treatment resistance is rare, there is a need for additional therapeutic options to address clinical challenges in treating these patients and a need to facilitate international registries to enable risk stratification and optimization of therapeutic strategies.

Routine statins use is associated with less adverse outcome in patients above 70 years of age admitted to hospital with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to multiorgan insufficiency and death, particularly among the older adults. Statins have been suggested as potentially protective drugs due to their pleotropic effects, but the actual benefit of statin use among the older population in this setting is not clear. This study aimed to evaluate the association between preadmission statin use and the presentation and clinical outcomes of hospitalized COVID-19 patients older than 70 years of age. METHODS: A historical cohort study of all patients above 70 years of age who were hospitalized with COVID-19 infection in a large academic hospital between March and August 2020 was performed. The association between preadmission statin use and patients' presentation and adverse outcome was studied. Adverse outcome was defined as any of the following: shock, invasive or non-invasive ventilation, organ insufficiency, myocardial infarction, cerebrovascular accident, in-hospital or 30-day post-admission mortality, hospital stay longer than the median length of stay of all COVID-19 patients, referral to nursing home or rehabilitation center. RESULTS: Seventy-two (44%) of the 163 studied patients (median age 82 years, 45% males) had been preadmission treated with statins. The statin-treated patients (STP) had a higher prevalence of diabetes (40% vs 24%, p = 0.028) and cardiovascular disease (58% vs. 34%, p = 0.002). Seventy two percent of the STP had adverse outcome, compared to 86% of the non-STP (p = 0.033). After adjustment for potential confounders, prior statin use was associated with decreased risk for an adverse outcome (odds ratio = 0.4, 95% confidence interval 0.18-0.92, p = 0.03). CONCLUSIONS: The preadmission use of statins was associated with a lower risk of adverse outcome in older adults hospitalized with COVID-19. Continuation of statin treatment might be implemented for risk reduction of adverse outcomes in the older population in the era of new SARS-CoV-2 variants and less effective vaccines.

Sex hormones, insomnia, and sleep quality: Subjective sleep in the first year of hormone use in transgender persons.

STUDY OBJECTIVES: Transgender persons can use gender-affirming hormone therapy (GAHT) to align their physical appearance with their identified gender. Many transgender persons report poor sleep, but the effects of GAHT on sleep are unknown. This study examined the effects of a 12 months of GAHT use on self-reported sleep quality and insomnia severity. METHODS: A sample of 262 transgender men (assigned female at birth, started masculinizing hormone use) and 183 transgender women (assigned male at birth, started feminizing hormone use), completed self-report questionnaires on insomnia (range 0-28), sleep quality (range 0-21) and sleep onset latency, total sleep time and sleep efficiency before start of GAHT and after 3, 6, 9, and 12 months of GAHT. RESULTS: Reported sleep quality showed no clinically significant changes after GAHT. Insomnia showed significant but small decreases after 3 and 9 months of GAHT in trans men (-1.11; 95%CI: -1.82; -0.40 and -0.97; 95%CI: -1.81; -0.13, respectively) but no changes in trans women. In trans men, reported sleep efficiency decreased by 2.8% (95%CI: -5.5%; -0.2%) after 12 months of GAHT. In trans women, reported sleep onset latency decreased by 9 min (95%CI: -15; -3) after 12 months of GAHT. CONCLUSIONS: These findings show that 12 months of GAHT use did not result in clinically significant changes in insomnia or sleep quality. Reported sleep onset latency and reported sleep efficiency showed small to modest changes after 12 months of GAHT. Further studies should focus on underlying mechanisms by which GAHT could affect sleep quality.

Refractory nonfunctioning pituitary adenomas.

Non-functioning pituitary adenomas (NFPAs) comprise silent tumors of different pituitary lineages that tend to escape early detection and present as invasive macroadenomas with symptoms of mass effect. Incomplete surgical resection is common and may be followed by significant rates of subsequent remnant progression. Pituitary tumors are defined as refractory when resistance to optimal standard therapies including surgery, radiotherapy, and medical treatment is documented. In the absence of approved medications for the treatment of NFPAs, the last criterion to classify these tumors as refractory is ill defined. Silent corticotroph and null cell adenomas have been reported, albeit not in all studies, to be larger and recur more often compared with silent gonadotroph tumors. Nevertheless, it is currently unknown if certain NFPA subtypes are more often refractory using well defined criteria. The response rate to temozolomide is lower in NFPA compared to that seen in functioning tumors. Refractory NFPAs present a significant diagnostic and therapeutic challenge and are associated with increased morbidity and mortality rates.

Revisiting Age Criterion for Surgery in Asymptomatic Primary Hyperparathyroidism.

OBJECTIVE: To revisit the current age criterion (50 years) for surgical candidacy in patients diagnosed with asymptomatic primary hyperparathyroidism (PHPT). STUDY DESIGN: A predictive model relying on past publications using the electronic databases "PubMed," "Embase," "Medline," and "Google Scholar." SETTING: Hypothetical large cohort. METHODS: A Markov model was constructed, based on relevant literature, to compare 2 potential treatment algorithms for asymptomatic PHPT patients, parathyroidectomy (PTX), and observation. The various potential health states were characterized for the 2 treatment options and included potential surgical complications, end-organ deterioration, and death. A 1-way sensitivity analysis was performed to calculate the quality-adjusted life year (QALY) gains of both strategies. A Monte-Carlo simulation for 30,000 subjects was performed and cycled per annum. RESULTS: On the basis of the model's assumptions, the QALY value for the PTX strategy was 19.17 versus 17.82 for the observation strategy. The incremental QALY gains for various ages according to the sensitivity analyses for PTX in comparison to observation were: 2.84 QALY for 40-year-old patients, 2.2 QALY for 50-year-old patients, 1.81 QALY for 55-year-old patients, 1.35 QALY for 60-year-old patients, and 0.86 QALY for 65-year-old patients. The incremental QALY is below 0.5 after the age of 75 years. CONCLUSION: This study found PTX to be advantageous for asymptomatic PHPT patients older than the current age criterion of 50 years. The calculated QALY gains support a surgical approach for medically fit patients in their 50s. The current guidelines for the surgical treatment of young asymptomatic PHPT patients should be revisited by the next steering committee.

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.

Lower incidence of hip fractures among elderly Ethiopian immigrants to Israel: first assessment from the Israel National Trauma Registry (INTR) 2011-2020.

The incidence hip fractures (HF) among Ethiopian immigrants is unknown. In Israel, the incidence of HF among Ethiopian immigrants aged ≥ 50 years between 2011 and 2020 was lower than in the general Israeli population, but possibly on the rise. These data should be confirmed in other countries where the Ethiopian diaspora has settled. PURPOSE: The incidence of osteoporotic fractures in the aging Ethiopian population that immigrated to Western countries has not been reported. This study sought to provide a first assessment of the incidence of hip fractures in Ethiopian immigrants in Israel, as a proxy for osteoporosis in this population. METHODS: This is an epidemiologic study of the incidence of hip fractures (HF) in people aged ≥ 50 years in Israel, between 2011 and 2020. Data were extracted from the Israel National Trauma Registry (INTR). Annual age-adjusted HF incidence rates (IR), and standardized incidence ratios (SIR) among Ethiopian-born (EB) relative to non-EB subjects (others) were computed. RESULTS: During the study period, among subjects age ≥ 50 in the INTR, only 20.1% of the EB suffered a HF, in contrast to 32.3% of subjects from other origins (P < 0.0001). Although EB subjects were generally younger than their non-EB counterparts, the age at which they sustained a HF was similar: 80.45 ± 11.7 years for EB vs. 79.44 ± 10.32 years, P = 0.19. EB men were more likely to sustain a HF, as they represented 41.8% of all HF in their respective group, in comparison with 33.6% for others (P = 0.02). Annual IR of HF were lower for EB subjects throughout the study. Despite an initial rise in the SIR, these were also lower for most of the period. CONCLUSIONS: In Israel, EB subjects ≥ 50 years still enjoy protection from HF. Our data require confirmation from other Western countries where the Ethiopian diaspora is aging. If a secular upward trend is observed, contributing risk factors should be identified to enable preventative measures.

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.

The Effects of Metabolism Tracker Device (Lumen) Usage on Metabolic Control in Adults with Prediabetes: Pilot Clinical Trial.

INTRODUCTION: Prediabetes is a risk factor for type 2 diabetes mellitus (T2DM). However, it may be reversed via lifestyle changes. Lumen is a novel handheld device that measures exhaled CO2 producing results in agreement with those of indirect calorimetry when assessing metabolic fuel usage. The aim of this study was to examine the effects of following Lumen's personalized, measurement-guided lifestyle intervention program on anthropometric and metabolic variables in adults with prediabetes. METHODS: A 12-week single-arm intervention study was conducted in 27 participants. Body composition and blood markers were measured at the start and end of the study. Each participant took a daily morning (fasted) measurement and received feedback on their metabolic state (i.e., their degree of fat vs. carbohydrate oxidation). Participants were then provided with personalized daily guidelines for their carbohydrate, fat, and protein consumption, along with recommended lifestyle changes. RESULTS: Intention-to-treat analysis revealed a significant decrease in body weight (5.99 kg, p < 0.001), comprising a significant reduction in percentage body fat (2.93%, p < 0.001) and waist circumference (6.23 cm, p < 0.001). Significant reductions were also observed in glycated hemoglobin A1c (0.27%, p < 0.001), triglycerides (0.45 mg/dL, p < 0.001), and systolic blood pressure (0.5 mm Hg, p < 0.05). CONCLUSION: In a 12-week pilot study of participants with prediabetes, Lumen usage significantly improved multiple metabolic parameters, demonstrating its potential to deliver better clinical outcomes for patients with T2DM and metabolic syndrome.

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.

Levoketoconazole treatment in endogenous Cushing's syndrome: extended evaluation of clinical, biochemical, and radiologic outcomes.

Objective: This extended evaluation (EE) of the SONICS study assessed the effects of levoketoconazole for an additional 6 months following open-label, 6-month maintenance treatment in endogenous Cushing's syndrome. Design/Methods: SONICS included dose-titration (150-600 mg BID), 6-month maintenance, and 6-month EE phases. Exploratory efficacy assessments were performed at months 9 and 12 (relative to the start of maintenance). For pituitary MRI in patients with Cushing's disease, a threshold of ≥2 mm denoted change from baseline in the largest tumor diameter. Results: Sixty patients entered EE at month 6; 61% (33/54 with data) exhibited normal mean urinary free cortisol (mUFC). At months 9 and 12, respectively, 55% (27/49) and 41% (18/44) of patients with data had normal mUFC. Mean fasting glucose, total and LDL-cholesterol, body weight, BMI, abdominal girth, hirsutism, CushingQoL, and Beck Depression Inventory-II scores improved from the study baseline at months 9 and 12. Forty-six patients completed month 12; four (6.7%) discontinued during EE due to adverse events. The most common adverse events in EE were arthralgia, headache, hypokalemia, and QT prolongation (6.7% each). No patient experienced alanine aminotransferase or aspartate aminotransferase >3× upper limit of normal, Fridericia-corrected QT interval >460 ms, or adrenal insufficiency during EE. Of 31 patients with tumor measurements at baseline and month 12 or follow-up, the largest tumor diameter was stable in 27 (87%) patients, decreased in one, and increased in three (largest increase 4 mm). Conclusion: In the first long-term levoketoconazole study, continued treatment through a 12-month maintenance period sustained the early clinical and biochemical benefits in most patients completing EE, without new adverse effects.

Validation of a multi-frequency bioelectrical impedance analysis device for the assessment of body composition in older adults with type 2 diabetes.

BACKGROUND: Aging and type 2 diabetes (T2DM) are associated with an increased risk of sarcopenia. Diagnosis of sarcopenia is commonly done using dual-energy X-ray absorptiometry (DXA) in specialized settings. Another available method for assessing body composition is direct segmental multi-frequency bioelectrical impedance analysis (DSMF-BIA). Here, we examine the accuracy of a DSMF-BIA (InBody-770) for assessing body composition in older adults with T2DM when compared to DXA. METHODS: Eighty-four obese/overweight older adults (49 women, 71 ± 5 years) with T2DM who were recruited for the CEV-65 study and had both DSMF-BIA and DXA assessments at baseline were included. The analysis included Bland-Altman plots and intra class correlation coefficients. Sub-analyses were performed according to gender and following 10 weeks of interventions (diet, circuit training, and Empagliflozin). RESULTS: The leg lean mass results according to DSMF-BIA and DXA were 14.76 ± 3.62 kg and 15.19 ± 3.52 kg, respectively, with no difference between devices according to Bland-Altman analyses (p = 0.353). Assessment of appendicular skeletal mass index did not differ between DSMF-BIA and DXA (7.43 vs. 7.47 kg/m2; p = 0.84; ICC = 0.965, p < 0.0001; mean difference -0.068, p = 0.595). Gender and treatment interventions did not modify the accuracy of the DSMF-BIA when compared to DXA. CONCLUSIONS: In older adults with T2DM the degree of agreement between DSMF-BIA and DXA, was high, supporting the use of DSMF-BIA to measure muscle mass.

Current medical treatment and perspective in gonadotroph tumors.

Gonadotroph cell adenoma is the most common clinically nonfunctioning pituitary adenoma; and is pathologically defined by immunopositivity for SF-1, GATA2 and ER-α. Most tumors also stain for follicle stimulating hormone and luteinizing hormone ß-subunits, but are usually hormonally silent and discovered incidentally or due to local mass effects. Complete transsphenoidal resection should be attempted when surgery is indicated. Post-surgical treatment can include radiation of the tumor remnant and medical treatment. Among medical treatments, dopamine agonists show the best evidence for preventing the need for recurrent surgery or radiation, and should be considered in patients with relatively bulky remnants or who have high risk features associated with tumor progression. Temozolomide is indicated for aggressive adenomas and carcinomas. Less well-established treatments include somatostatin receptor ligands, peptide receptor radionucleotide therapy and immunomodulatory agents.

Resistant prolactinomas: a case series of 26 patients.

PURPOSE: Prolactin (PRL)-secreting tumors are the most common functional pituitary adenomas. They usually respond to dopamine agonist (DA) treatment, with PRL normalization and adenoma shrinkage. Our aim was to characterize patients with prolactinoma resistant to DA treatment. METHODS: This retrospective case series included patients diagnosed with DA-resistant prolactinomas between 1993-2017 in three medical centers. Resistance was defined as PRL levels above three times the upper limit of normal (ULN) despite a weekly dose of ≥2 mg cabergoline (CAB). Clinical and biochemical information, and response to treatment, were retrieved from medical records. RESULTS: Twenty-six patients were identified; 20 males. Of 25 macroadenomas, three were giant tumors (>40 mm) and 15 (57.7%) were invasive. The mean age at diagnosis was 31.8 ± 14.9 years (range: 13-62). The median maximal CAB dose was 3.5 mg/week (IQR, 2.5-5). Half the patients received only CAB in escalating doses, nine received CAB and underwent transsphenoidal surgery, and four underwent surgery and radiotherapy in addition to CAB treatment. PRL levels at baseline between patients treated only with CAB and those operated were (91.6 [51.1-296.7] vs. 73.1 [22.6-170.9] XULN p = 0.355), and under maximal CAB dose PRL levels between patients treated only with CAB and those operated were similar (5.77 [1.27-11.27] vs 5.27 (2.9-26) XULN p = 0.317). At the last visit patients who received combined therapy achieved lower PRL levels than those treated with DA only (5.22 [1.7-21.6] vs 1.1 [0.44-3.99] XULN p = 0.017) PRL normalization was attained in seven patients and levels below 3 × ULN in fourteen patients; the overall response was 56%. CONCLUSIONS: Resistant prolactinomas usually require a multi-modal treatment strategy. We were able to control 14/25 (56%) of resistant tumors.

The ENIGI (European Network for the Investigation of Gender Incongruence) Study: Overview of Acquired Endocrine Knowledge and Future Perspectives.

Literature on the efficacy and safety of gender-affirming hormonal treatment (GAHT) in transgender people is limited. For this reason, in 2010 the European Network for the Investigation of Gender Incongruence (ENIGI) study was born. The aim of this review is to summarize evidence emerging from this prospective multicentric study and to identify future perspectives. GAHT was effective in inducing desired body changes in both trans AMAB and AFAB people (assigned male and female at birth, respectively). Evidence from the ENIGI study confirmed the overall safety of GAHT in the short/mid-term. In trans AMAB people, an increase in prolactin levels was demonstrated, whereas the most common side effects in trans AFAB people were acne development, erythrocytosis, and unfavorable changes in lipid profile. The main future perspectives should include the evaluation of the efficacy and safety of non-standardized hormonal treatment in non-binary trans people. Furthermore, long-term safety data on mortality rates, oncological risk, and cardiovascular, cerebrovascular and thromboembolic events are lacking. With this aim, we decided to extend the observation of the ENIGI study to 10 years in order to study all these aspects in depth and to answer these questions.