Desmopressin dose requirements in patients with permanent arginine vasopressin deficiency: a tertiary center experience.

PURPOSE: The desmopressin daily dose requirement is highly variable among patients with arginine vasopressin (AVP) deficiency (i.e. central diabetes insipidus) and few studies to date have evaluated this topic, with often inconclusive results. The aim of our study was to identify clinical and biochemical predictors of such dose requirements in a cohort of patients with a confirmed diagnosis of permanent AVP deficiency who have good and stable control under substitutive treatment. METHODS: We retrospectively analyzed data of all patients with permanent AVP deficiency undergoing regular follow-up at our Division. Inclusion criteria were the presence of stable disease under therapy for at least 12 months and in good biochemical and clinical control. Patients with AVP deficiency who lacked intact thirst or had a disease duration of less than 12 months were excluded from the analysis. RESULTS: Out of the 132 patients initially screened, 96 patients (M/F 44/52; age 51 [37-63] years) met the inclusion criteria. Patients on nasal spray therapy (n = 8) had a significantly longer disease duration (p = 0.002) than patients treated with oral lyophilizate (n = 88). In the bivariate analysis, considering only patients treated with the sublingual formulation, the drug dose was correlated positively with estimated glomerular filtration rate (eGFR) and weight (r = 0.410, p < 0.001; r = 0.224, p = 0.036, respectively) and negatively with age (r = - 0.433, p < 0.001). In the multivariate regression analysis taking into account age, weight, and eGFR, only age emerged as a significant predictor of the required sublingual desmopressin dose (ß = - 1.426, p = 0.044). CONCLUSION: Our data suggest that patient age appears to be the primary factor associated with the daily sublingual desmopressin dose required to achieve adequate clinical and biochemical control in patients with permanent AVP deficiency.

Repeatedly non-diagnostic thyroid nodules: the experience of two thyroid clinics.

BACKGROUND: The clinical management of repeatedly non-diagnostic thyroid nodules (RNDNs) via fine needle aspiration cytology (FNAc) is a matter of debate because current recommendations and clinical practice are not based on high-quality evidence. Our purpose was to characterize RNDNs and evaluate their clinical management in our centers. METHODS: This retrospective observational study included 319 consecutive patients who underwent ultrasound (US-)guided FNAc in two Italian academic hospitals between 2016 and 2020 and had previous cytology non-diagnostic result (TIR1). Clinical management and anamnestic data were retrieved, and the cytological specimens and US exams were double-blindly reviewed by two pathologists and endocrinologists. RESULTS: The risk of RNDNs was significantly greater in hypoechogenic nodules (Odds Ratio [OR]=1.727, 95% confidence Interval [CI]: 1.090-2.735, P=0.02) and lower in nodules that had been recognized less than 10 years before (OR=0.349, 95% CI: 0.153-0.796, P=0.01). Clinicians chose to directly perform surgery on multinodular, intermediate-risk nodules (as per AACE/AME guidelines and EUTIRADS class 4), while larger (P<0.0001) and uninodular (P=0.03) lesions were further investigated with a third FNAc. Only 16 RNDNs were sent to surgery. Twelve nodules turned out to be benign goiters with a high rate of fibrosis, while only 3 were definitively malignant. However, retrospectively, all the malignant ones exhibited higher-risk ultrasound features and had an undetermined result (TIR3B) at the third cytological evaluation. CONCLUSIONS: In a real-life context, RNDNs exhibited a very low rate of malignancy and were mostly long-known goiters with regressive changes, as suggested by a hypoechoic pattern. Consequently, a clinical-US surveillance approach could be cautiously hypothesized, while greater attention could be given to larger and higher-US-risk (both as EUTIRADS 4-5 and AACE/AME intermediate- and high-risk classes) nodules.

Skeletal fragility in pituitary disease: how can we predict fracture risk?

Pituitary hormones play a crucial role in regulating skeletal physiology, and skeletal fragility is a frequent complication of pituitary diseases. The ability to predict the risk of fracture events is crucial for guiding therapeutic decisions; however, in patients with pituitary diseases, fracture risk estimation is particularly challenging. Compared to primary osteoporosis, the evaluation of bone mineral density by dual X-ray absorptiometry is much less informative about fracture risk. Moreover, the reliability of standard fracture risk calculators does not have strong validations in this setting. Morphometric vertebral assessment is currently the cornerstone in the assessment of skeletal fragility in patients with pituitary diseases, as prevalent fractures remain the strongest predictor of future fracture events. In recent years, new tools for evaluating bone quality have shown promising results in assessing bone impairment in patients with pituitary diseases, but most available data are cross-sectional, and evidence regarding the prediction of incident fractures is still scarce. Of note, apart from measures of bone density and bone quality, the estimation of fracture risk in the context of pituitary hyperfunction or hypofunction cannot ignore the evaluation of factors related to the underlying disease, such as its severity and duration, as well as the specific therapies implemented for its treatment. Aim of this review is to provide an up-to-date overview of all major evidence regarding fracture risk prediction in patients with pituitary disease, highlighting the need for a tailored approach that critically integrates all clinical, biochemical, and instrumental data according to the specificities of each disease.

Sex-specific association of chronic proton pump inhibitor use with reduced bone density and quality.

CONTEXT: Chronic use of proton pump inhibitors (PPIs) has been associated with an increase in bone fragility. However, evidence on the effect of chronic PPI use on bone density is conflicting, and data on bone microarchitectural quality are scarce. OBJECTIVE: The primary aim of this study was to evaluate whether trabecular bone microarchitecture, assessed by trabecular bone score (TBS), is altered in chronic PPI users. The association between PPI use and bone density was also evaluated as a secondary endpoint. METHODS: We extracted individual patient data from the 2005-2008 cycles of the population-based National Health and Nutrition Examination Survey (NHANES), in which lumbar spine dual-energy X-ray absorptiometry (DXA) scans were acquired. TBS values were calculated from DXA images using a dedicated software. Multivariable linear regression analyses stratified by sex were performed to evaluate the association of chronic PPI use with TBS and bone mineral density (BMD), adjusting for relevant confounders. RESULTS: A total of 7478 subjects were included (3961 men, 3517 women). After adjustment for relevant confounders, chronic PPI use was associated with a worse bone health profile in men, with lower TBS (-0.039, 95%CI:[-0.058, -0.020], p<0.001), lumbar spine T-score (-0.27, 95%CI:[-0.49, -0.05], p=0.018), total hip T-score (-0.20, 95%CI:[-0.39, -0.01], p=0.038), and femoral neck T-score (-0.21, 95%CI:[-0.42, -0.01], p=0.045). Notably, the association between chronic PPI use and degraded TBS remained statistically significant even after further adjustment for BMD at lumbar spine and femoral neck (-0.026, 95%CI:[-0.039, -0.012], p=0.001). In contrast, no significant association was observed between chronic PPI use and either TBS or BMD in women. CONCLUSIONS: Chronic PPI use is associated with degraded trabecular bone quality in men, even after adjustment for BMD. No association was observed in women.

Rapid UHPLC-MS/MS measurement of pregnanediol 3-glucuronide in spot urine samples for detecting ovulation.

Biochemical confirmation of ovulation typically involves measuring serum progesterone levels during the mid-luteal phase. Alternatively, this information could be obtained by monitoring urinary excretion of conjugated metabolites of ovarian steroids such as pregnanediol 3-glucuronide (PDG) using immunoassay techniques that have methodological limitations. The aim of the present study was to develop a mass spectrometry (MS)-based method for the rapid and accurate measurement of urinary PDG levels in spot urine samples. A "dilute and shoot" ultra-high-performance liquid cromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed for measuring PDG urinary concentration with a 6-min analysis time. The method underwent validation in accordance with ISO 17025 documentation for quantitative methods, proving an efficient separation of PDG from other structurally similar glucuro-conjugated steroid metabolites and ensuring a sufficient sensitivity for detecting the target analyte at concentrations as low as 0.01 µg/mL. The validation protocol yielded satisfactory results in terms of accuracy, repeatability, intermediate precision, and combined uncertainty. Additionally, the stability of both the samples and calibration curves was also conducted. The application to real urine samples confirmed the method's capability to measure PDG levels throughout an entire menstrual cycle and detecting ovulation. The rapidity of the analytical platform would therefore enable high throughput analysis, which is advantageous for large cohort clinical studies.

Increased cardiometabolic risk and prevalence of ascending aorta dilation in patients with nonfunctioning adrenal incidentaloma: a retrospective propensity score-matched study.

The cardiometabolic implications of Non-Functioning Adrenal Incidentaloma (NFAI) is still matter of debate. This study takes a novel approach to analyze this association, accounting for the influence of various confounding factors. We present the findings of a retrospective, cross-sectional, and case-control study. Data from all NFAI patients in primary prevention, referred to the University of Turin between 2000 and 2023, were collected and compared with subjects without adrenal disease, using propensity score matching analysis. A total of 1997 patients were included (906 patients with NFAI; 1091 controls). Adrenal tumor group was associated with high levels of cardiovascular risk scores in both univariate and multiple linear regression analyses (Progetto CUORE: EC 11.00, 95% CI 2.72-44.46, p = 0.001; SCORE: EC 1.97, 95% CI 1.01-3.81, p = 0.046). Regarding cardiometabolic complications, multivariable logistic regression revealed an independent association between NFAI and ascending aorta dilation (OR 4.64, 95% CI 2.24-9.63, p = 0.000), after adjusting for age, sex, smoking status, metabolic syndrome, number of antihypertensive drugs, estimated glomerular filtration rate (eGFR), and normetanephrine levels. Propensity score matching analysis (1:1 matching ratio), based on the same logistic regression model, confirmed the association of NFAI with aortic dilation (ß = 0.083, 95% CI 0.008-0.157, p = 0.030). No significant associations were found with metabolic syndrome, type II diabetes, eGFR <60 mL/min/1.73 m2, microalbuminuria, atrial fibrillation, or hypertensive heart disease. This study suggests that patients with NFAI face increased cardiometabolic risk and high prevalence of ascending aorta dilation. Routine evaluation of NFAI patients should include thorough cardiovascular assessment and consideration of treatments aimed at reducing cardiovascular risk.

Asymmetric and symmetric dimethylarginine as markers of endothelial dysfunction in cerebrovascular disease: A prospective study.

BACKGROUND AND AIM: Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have been proposed as mediators of endothelial dysfunction. In this study, we aimed to investigate the diagnostic and prognostic role of ADMA and SDMA in acute cerebrovascular disease. METHODS AND RESULTS: A prospective case-control study was performed, enrolling 48 patients affected by ischemic stroke with no cardioembolic origin, 20 patients affected by TIA, 40 subjects at high cardiovascular risk and 68 healthy subjects. ADMA levels were significantly lower in high-risk subjects (18.85 [11.78-22.83] µmol/L) than in patients with brain ischemic event, both transient (25.70 [13.15-40.20] µmol/L; p = 0.032) and permanent (24.50 [18.0-41.33] µmol/L; p = 0.001). SDMA levels were different not only between high-risk subjects and ischemic patients, but also between TIA and stroke patients, reaching higher levels in TIA group and lower levels in stroke group (1.15 [0.90-2.0] vs 0.68 [0.30-1.07] µmol/L; p < 0.001). SDMA was also correlated with short-term prognosis, with lower levels in case of adverse clinical course, evaluated by type of discharge (p = 0.009) and need of prolonged rehabilitation (p = 0.042). CONCLUSIONS: The present study highlights the relationship between l-arginine, ADMA, SDMA and acute cerebrovascular events. Therefore, our results suggested a potential role of SDMA as a specific marker of transient ischemic damage and as a short-term positive prognostic marker.

Effectiveness of Copeptin, MR-proADM and MR-proANP in Predicting Adverse Outcomes, Alone and in Combination with Traditional Severity Scores, a Secondary Analysis in COVID-19 Patients Requiring Intensive Care Admission.

Objective: To investigate whether copeptin, MR-proADM and MR-proANP, alone or integrated with the SOFA, MuLBSTA and SAPS II scores, are capable of early recognition of COVID-19 ICU patients at increased risk of adverse outcomes. Methods: For this predefined secondary analysis of a larger cohort previously described, all consecutive COVID-19 adult patients admitted between March and December 2020 to the ICU of a referral, university hospital in Northern Italy were screened, and clinical severity scores were calculated upon admission. A blood sample for copeptin, MR-proADM and MR-proANP was collected within 48 h (T1), on day 3 (T3) and 7 (T7). Outcomes considered were ICU and in-hospital mortality, bacterial superinfection, recourse to renal replacement therapy (RRT) or veno-venous extracorporeal membrane oxygenation, need for invasive mechanical ventilation (IMV) and pronation. Results: Sixty-eight patients were enrolled, and in-hospital mortality was 69.1%. ICU mortality was predicted by MR-proANP measured at T1 (HR 1.005, 95% CI 1.001-1.010, p = 0.049), although significance was lost if the analysis was adjusted for procalcitonin and steroid treatment (p = 0.056). Non-survivors showed higher MR-proADM levels than survivors at all time points, and an increase in the ratio between values at baseline and at T7 > 4.9% resulted in a more than four-fold greater risk of in-hospital mortality (HR 4.417, p < 0.001). Finally, when considering patients with any reduction in glomerular filtration, an early copeptin level > 23.4 pmol/L correlated with a more than five-fold higher risk of requiring RRT during hospitalization (HR 5.305, p = 0.044). Conclusion: Timely evaluation of MR-proADM, MR-proANP and copeptin, as well as changes in the former over time, might predict mortality and other adverse outcomes in ICU patients suffering from severe COVID-19.

Mild hyponatremia is not associated with degradation of trabecular bone microarchitecture despite bone mass loss.

CONTEXT: Hyponatremia is associated with increased risk of osteoporosis and fractures. The impact of hyponatremia on non-invasive indices of bone quality, however, is unknown. OBJECTIVE: To evaluate whether trabecular bone microarchitecture, assessed non-invasively by trabecular bone score (TBS), is altered in patients with hyponatremia. METHODS: We conducted a cross-sectional analysis of the population-based 2005-2008 cycles of the National Health and Nutrition Examination Survey (NHANES), in which TBS measurement was performed. The main outcome measures were TBS values and bone mineral density (BMD) T-scores at the lumbar spine, total hip and femoral neck. RESULTS: A total of 4204 subjects aged 50 years or older were included (4041 normonatremic, 163 hyponatremic - 90.8% with mild hyponatremia). Univariate analyses did not show any difference in TBS between patients with and without hyponatremia (1.308 ± 0.145 vs 1.311 ± 0.141, p = 0.806). Hyponatremic subjects had lower BMD T-score at total hip (-0.70 ± 1.46 vs -0.13 ± 1.32, p < 0.001) and femoral neck (-1.11 ± 1.26 vs -0.72 ± 1.14, p = 0.004), while no difference was observed at lumbar spine (-0.27 ± 1.63 vs -0.31 ± 1.51, p = 0.772). After adjustment for relevant confounders, hyponatremia was confirmed as an independent predictor of lower BMD T-score at the total hip (ß=-0.20, 95%CI:[-0.39, -0.02], p = 0.029), while the significance was lost at the femoral neck (p = 0.308). Again, no association between hyponatremia and lumbar spine BMD (p = 0.236) or TBS (p = 0.346) was observed. CONCLUSIONS: Hyponatremia, at least in mild forms, is not associated with a degradation of trabecular microarchitecture, assessed non-invasively by TBS. An independent association between hyponatremia and loss of bone mass is confirmed, particularly at the total hip.

Prolactin-secreting tumors, dopamine agonists and pregnancy: a longitudinal experience of a tertiary neuroendocrine center.

PURPOSE: Prolactin (PRL)-secreting tumours are associated with infertility and can be reverted by dopamine agonist (DA) therapy. The suspension of DA is recommended once pregnancy is established, as all DAs cross the placenta. The aim of the study was to evaluate the rate of maternal-foetal complications in women treated with cabergoline (CAB) or bromocriptine (BRM) for prolactinoma during gestation and the effect of pregnancy on prolactinoma progression. METHODS: This was a retrospective observational study involving 43 women affected by prolactinoma who became pregnant during therapy with CAB or BRM for a total of 58 pregnancies. For each patient, medical records were analysed by integrating the data with outpatient or telephone interview. RESULTS: At the time of conception, 18 women were in the BRM group, while 40 were in CAB group. No differences were found in obstetric or neonatal outcomes between the two groups. There was a significant difference (p = 0.046) in child complications reported in maternal interview found exclusively in the CAB group. No further confounding factors were detected. Disease remission rate after the first pregnancy was 42.9% and the main predictor was a lower PRL nadir before pregnancy (p = 0.023). No difference was detected between the two groups in terms of tumor remission. Breastfeeding did not modify the outcome. CONCLUSION: Foetal exposure to DAs during the first weeks of embryogenesis is not associated with a greater risk of complications. The transient and mild developmental disorders recorded resolved spontaneously and the prevalence was substantially overlapping with that observed in the general population.

LC-MS/MS measurement of endogenous steroid hormones and phase II metabolites in blood volumetric absorptive microsampling (VAMS) for doping control purposes.

BACKGROUND: Volumetric Absorptive Microsampling (VAMS) is emerging as a valuable technique in the collection of dried biological specimens, offering a potential alternative to traditional sampling methods. The objective of this study was to assess the suitability of 30 µL VAMS for the measurement of endogenous steroid hormones. METHODS: A novel LC-MS/MS method was developed for the quantification of 18 analytes in VAMS samples, including main endogenous free steroids and phase II metabolites of androgens. The method underwent validation in accordance with ISO/IEC 17025:2017 and World Anti-Doping Agency (WADA) requirements. Subsequently, it was applied to authentic VAMS samples obtained from 20 healthy volunteers to assess the stability of target analytes under varying storage conditions. RESULTS: The validation protocol assessed method's selectivity, matrix effect, extraction recovery, quantitative performance, carry-over and robustness. The analysis of authentic samples demonstrated the satisfactory stability of monitored steroids in VAMS stored at room temperature, 4 °C, -20 °C and -80 °C for up to 100 days and subjected to up to 3 freezing-thawing cycles. CONCLUSIONS: The validated LC-MS/MS method demonstrated its suitability for the measurement of steroids in dried blood VAMS. The observed stability of steroidal compounds suggests promising prospects for future applications of VAMS, both in anti-doping contexts and clinical research.

Evaluating adherence, tolerability and safety of oral calcium citrate in elderly osteopenic subjects: a real-life non-interventional, prospective, multicenter study.

BACKGROUND: Osteoporosis is a common concern in the elderly that leads to fragile bones. Calcium supplementation plays a crucial role in improving bone health, reducing fracture risk, and supporting overall skeletal strength in this vulnerable population. However, there is conflicting evidence on the safety of calcium supplements in elderly individuals. AIM: The aim of this study was to evaluate the adherence, safety and tolerability of calcium citrate supplementation in elderly osteopenic subjects. METHODS: In this non-interventional, prospective, multicenter study, subjects received daily 500 mg calcium citrate supplementation for up to one year. Adherence was calculated based on compliance and persistence. Safety was assessed through adverse reactions (ARs), deaths, and clinical laboratory evaluations. RESULTS: A total of 268 Caucasian subjects (91.4% female, mean age 70 ± 4.5 years) participated in the study. Mean adherence to treatment was 76.6 ± 29.5% and half of subjects had an adherence of 91% and ~ 33% of participants achieved complete (100%) adherence. ARs were reported by nine (3.9%) subjects, primarily gastrointestinal disorders, with no serious ARs. The frequency of all adverse events (including ARs) was significantly higher in subjects with adherence of < 80% (41.6%; 32/77) vs. those with adherence ≥ 80% (11%; 16/145, p < 0.0001). Both systolic and diastolic blood pressure decreased from baseline to follow-up visit (change of -2.8 ± 13.9 mmHg, p = 0.0102 and -2.1 ± 10.4 mmHg, p = 0.0116, respectively). CONCLUSION: This study demonstrated favorable adherence to calcium citrate supplementation in elderly osteopenic subjects. The occurrence of ARs, though generally mild, were associated with lower adherence to calcium supplementation.

Radiomic Analysis in Pituitary Tumors: Current Knowledge and Future Perspectives.

Radiomic analysis has emerged as a valuable tool for extracting quantitative features from medical imaging data, providing in-depth insights into various contexts and diseases. By employing methods derived from advanced computational techniques, radiomics quantifies textural information through the evaluation of the spatial distribution of signal intensities and inter-voxel relationships. In recent years, these techniques have gained considerable attention also in the field of pituitary tumors, with promising results. Indeed, the extraction of radiomic features from pituitary magnetic resonance imaging (MRI) images has been shown to provide useful information on various relevant aspects of these diseases. Some of the key topics that have been explored in the existing literature include the association of radiomic parameters with histopathological and clinical data and their correlation with tumor invasiveness and aggressive behavior. Their prognostic value has also been evaluated, assessing their role in the prediction of post-surgical recurrence, response to medical treatments, and long-term outcomes. This review provides a comprehensive overview of the current knowledge and application of radiomics in pituitary tumors. It also examines the current limitations and future directions of radiomic analysis, highlighting the major challenges that need to be addressed before a consistent integration of these techniques into routine clinical practice.

Are prolactin levels efficient in predicting a pituitary lesion in patients with hyperprolactinemia?

PURPOSE: Data regarding the presence of a prolactin (PRL) threshold above which a pituitary magnetic resonance imaging (MRI) is mandatory in patients with hyperprolactinemia (hyperPRL) are controversial and derived primarily from studies focused on female populations. Aim of our study was to evaluate in a cohort of patients of both sexes with confirmed hyperPRL, the possible correlation between PRL values and the presence of pituitary abnormalities. METHODS: We retrospectively analyzed data from patients who underwent serial PRL sampling at our Division between January 2015 and December 2022. Patients diagnosed with monomeric hyperPRL at serial sampling and with subsequent contrast-enhanced MRI results available for the pituitary region were included in the study. Exclusion criteria were prior pituitary disease, severe renal insufficiency, liver cirrhosis, uncompensated primary hypothyroidism and ongoing therapy with hyperprolactinemic drugs. Physiological causes of hyperPRL were also ruled out. RESULTS: Out of the 1253 patients who underwent serial PRL sampling, 139 patients (101 women and 38 men) met the inclusion criteria: 106 (76.3%) patients had some form of pituitary disease, with microlesions observed in 69.8%, macrolesions in 25.5% and other findings in 4.7% of subjects. PRL values showed a modest accuracy in predicting the presence of a pituitary abnormality and the best cut-offs identified were >25 µg/L (AUC 0.767, p = 0.003) and >44.2 µg/L (AUC 0.697, p < 0.001) in men and women, respectively; however, if only patients with PRL values > 500 µg/L were excluded from the analysis, as they were already supposed to harbor a macroprolactinoma, PRL levels were not able to predict the presence of a macrolesion neither in men nor women. CONCLUSION: Given the high prevalence of pituitary abnormalities in patients of both sexes with hyperPRL at serial sampling, performing a pituitary imaging in all cases of hyperPRL, even if mild, appears to be a cautious choice.

Relacorilant, a Selective Glucocorticoid Receptor Modulator in Development for the Treatment of Patients With Cushing Syndrome, Does Not Cause Prolongation of the Cardiac QT Interval.

OBJECTIVE: To assess the effect of relacorilant, a selective glucocorticoid receptor modulator under investigation for the treatment of patients with endogenous hypercortisolism (Cushing syndrome [CS]), on the heart rate-corrected QT interval (QTc). METHODS: Three clinical studies of relacorilant were included: (1) a first-in-human, randomized, placebo-controlled, ascending-dose (up to 500 mg of relacorilant) study in healthy volunteers; (2) a phase 1 placebo- and positive-controlled thorough QTc (TQT) study of 400 and 800 mg of relacorilant in healthy volunteers; and (3) a phase 2, open-label study of up to 400 mg of relacorilant administered daily for up to 16 weeks in patients with CS. Electrocardiogram recordings were taken, and QTc change from baseline (ΔQTc) was calculated. The association of plasma relacorilant concentration with the effect on QTc in healthy volunteers was assessed using linear mixed-effects modeling. RESULTS: Across all studies, no notable changes in the electrocardiogram parameters were observed. At all time points and with all doses of relacorilant, including supratherapeutic doses, ΔQTc was small, generally negative, and, in the placebo-controlled studies, similar to placebo. In the TQT study, placebo-corrected ΔQTc with relacorilant was small and negative, whereas placebo-corrected ΔQTc with moxifloxacin positive control showed rapid QTc prolongation. These results constituted a negative TQT study. The model-estimated slopes of the concentration-QTc relationship were slightly negative, excluding an association of relacorilant with prolonged QTc. CONCLUSION: At all doses studied, relacorilant consistently demonstrated a lack of QTc prolongation in healthy volunteers and patients with CS, including in the TQT study. Ongoing phase 3 studies will help further establish the overall benefit-risk profile of relacorilant.

Trabecular bone score as a marker of skeletal fragility across the spectrum of chronic kidney disease: a systematic review and meta-analysis.

CONTEXT: The impairment of bone microarchitecture is a key determinant of skeletal fragility in patients with chronic kidney disease (CKD). Trabecular bone score (TBS) has been developed as a reliable non-invasive index of bone quality. However, its utility in this setting is still debated. OBJECTIVE: The aim of this systematic review and meta-analysis was to summarize the available evidence about TBS as a marker of skeletal fragility across the spectrum of CKD. METHODS: PubMed/Medline, EMBASE and Cochrane Library databases were systematically searched until July 2023 for studies reporting data about TBS in patients with CKD. Effect sizes were pooled through a random-effect model. RESULTS: Compared to controls, lower TBS values were observed in CKD patients not on dialysis (-0.057, 95%CI:[-0.090, -0.024], p < 0.01), in dialysis patients (-0.106, 95%CI:[-0.141, -0.070], p < 0.01) and in kidney transplant recipients (KTRs) (-0.058, 95%CI:[-0.103, -0.012], p = 0.01). With respect to fracture risk, TBS was able to predict incident fractures in non-dialysis patients at unadjusted analyses (hazard ratio (HR) per standard deviation decrease: 1.45, 95%CI:[1.05,2.00], p = 0.02), though only a non-significant trend was maintained when fully adjusting the model for FRAX® (HR = 1.26, 95%CI:[0.88,1.80], p = 0.21). Dialysis patients with prevalent fractures had lower TBS values compared to unfractured ones (-0.070, 95% CI:[-0.111, -0.028], p < 0.01). Some studies supported a correlation between TBS and fracture risk in KTRs, but results could not be pooled due to the lack of sufficient data. CONCLUSIONS: CKD patients are characterized by an impairment of bone microarchitecture, as demonstrated by lower TBS values, across the whole spectrum of kidney disease. TBS can also be helpful in the discrimination of fracture risk, with lower values being correlated with a higher risk of prevalent and incident fractures.

Bone safety of dual-release hydrocortisone in patients with autoimmune primary adrenal insufficiency.

Background: Conventional glucocorticoids (C-GC) replacement regimens have a detrimental effect on skeletal health in patients with adrenal insufficiency (AI), ultimately leading to an increased fracture risk. The novel dual-release hydrocortisone (DR-HC) formulations are characterized by a more favourable safety profile on various clinical endpoints. Data comparing the impact of C-GC and DR-HC on bone, however, are scarce. Methods: Twenty-seven patients with autoimmune primary AI (PAI; 13 treated with C-GC and 14 treated with DR-HC) were evaluated to compare bone-related parameters between the two treatment groups. Results: No significant differences between the two treatments groups were observed with respect to bone turnover markers. Patients treated with C-GC showed a lower bone mineral density (BMD) at lumbar spine (LS; 0.791 ± 0.195 vs. 0.942 ± 0.124 g/cm2, p=0.025) and at femoral neck (FN; 0.633 ± 0.114 vs. 0.716 ± 0.088 g/cm2, p=0.045). Moreover, they were characterized by a lower trabecular bone score (TBS; 1.236 ± 0.035 vs. 1.383 ± 0.030, p=0.004) and by a higher mean number of vertebral fractures per patient (0.75 vs. 0 fractures, p=0.002). TBS was the best predictor of fracture risk, with a pseudo-R2 of 0.593; moreover, at mediation analysis, it was able to fully explain the observed detrimental effect of C-GC, compared to DR-HC, on fracture risk. Conclusions: These results suggest that DR-HC is associated with less bone-related complications compared to C-GC in patients with PAI. Moreover, TBS seems to play a pivotal role in the mediation of the relationship between glucocorticoid treatment regimens and fracture risk.