Background: Acromegaly is characterized by impaired bone quality and increased fracture risk. However, due to the pathophysiology of acromegalic osteopathy, bone mineral density (BMD) does not represent a reliable predictor for fragility fractures in this setting. Trabecular bone score (TBS) has been recently evaluated as an alternative index of skeletal fragility in acromegalic patients. However, no conclusive data are still available in this regard. Methods: PubMed/Medline, EMBASE, Cochrane Library, Ovid, and CINAHL databases were systematically searched until June 2022 for studies reporting data either about the comparison of TBS values between acromegalic patients and non-acromegalic controls or about the relationship – within acromegalic patients – between TBS values and fracture risk. Effect sizes were pooled through a random-effect model. Results: Eight studies were eligible for inclusion in the meta-analysis, encompassing 336 acromegalic patients and 490 non-acromegalic controls. Overall, TBS was significantly lower in acromegalic patients compared to controls (−0.089, 95% CI: [−0.111, −0.067], p < 0.01), irrespective of acromegaly disease activity and gonadal status. With respect to fracture risk, TBS was significantly lower in acromegalic patients with vertebral fractures than in those without (−0.099, 95% CI: [−0.166, −0.032], p < 0.01). Conclusion: In this meta-analysis, we specifically assessed the role of TBS as an index of bone quality and fracture risk in patients with acromegaly. Our results support the notion that TBS could be of value in the assessment and management of skeletal fragility in acromegalic patients, especially in light of the poor information provided in this setting by BMD.
8 June 2020 in Journal of Endocrinological Investigation
Approximately 60% of acromegaly patients are not adequately controlled by first-generation somatostatin receptor ligands. This multicenter retrospective study aimed to identify the most relevant biomarkers specific for the Italian acromegaly population. Resistant patients were enrolled consecutively based on time of neurosurgery, while responders were collected in a 1:2 ratio. Clinical characteristics and T2-intensity on MRI scans at diagnosis were retrospectively re-evaluated. Histological analyses of CAM5.2 granulation patterns and SSTR2 expression were centrally performed. Sixty-three resistant patients and thirty-three responders were enrolled. A low-grade SSTR2 expression was the most relevant predictor of resistance identified (OR 4.58, p = 0.013), even considering CAM5.2 immunohistochemistry (OR 2.65, p = 0.047). T2-iso/hyperintense pattern on MRI was also associated with a 3.3-fold greater probability of poor response to medical treatment (p = 0.027), as well as a young age at diagnosis (OR 0.96, p = 0.035). In those patients treated only after neurosurgery due to persistent GH-hypersecretion (51, 53.1%) the absence of any appreciable adenomatous remnant on postoperative MRI was associated with a negligible risk of resistance (OR 0.04, p = 0.003). In the Italian acromegaly population, a low-grade SSTR2 expression seems to be the most relevant predictor of resistance to first-generation somatostatin receptor ligands, followed by a SG/intermediate cytokeratin pattern and a T2-iso/hyperintense MRI signal.
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.
Introduction: In type 2 diabetes mellitus (T2DM), the antidiuretic system participates in the adaptation to osmotic diuresis further increasing urinary osmolality by reducing the electrolyte-free water clearance. Sodium glucose co-transporter type 2 inhibitors (SGLT2i) emphasize this mechanism, promoting persistent glycosuria and natriuresis, but also induce a greater reduction of interstitial fluids than traditional diuretics. The preservation of osmotic homeostasis is the main task of the antidiuretic system and, in turn, intracellular dehydration the main drive to vasopressin (AVP) secretion. Copeptin is a stable fragment of the AVP precursor co-secreted with AVP in an equimolar amount.Aim: To investigate the copeptin adaptive response to SGLT2i, as well as the induced changes in body fluid distribution in T2DM patients.Methods: The GliRACo study was a prospective, multicenter, observational research. Twenty-six consecutive adult patients with T2DM were recruited and randomly assigned to empagliflozin or dapagliflozin treatment. Copeptin, plasma renin activity, aldosterone and natriuretic peptides were evaluated at baseline (T0) and then 30 (T30) and 90 days (T90) after SGLT2i starting. Bioelectrical impedance vector analysis (BIVA) and ambulatory blood pressure monitoring were performed at T0 and T90.Results: Among endocrine biomarkers, only copeptin increased at T30, showing subsequent stability (7.5 pmol/L at T0, 9.8 pmol/L at T30, 9.5 pmol/L at T90; p = 0.001). BIVA recorded an overall tendency to dehydration at T90 with a stable proportion between extra- and intracellular fluid volumes. Twelve patients (46.1%) had a BIVA overhydration pattern at baseline and 7 of them (58.3%) resolved this condition at T90. Total body water content, extra and intracellular fluid changes were significantly affected by the underlying overhydration condition (p < 0.001), while copeptin did not.Conclusion: In patients with T2DM, SGLT2i promote the release of AVP, thus compensating for persistent osmotic diuresis. This mainly occurs because of a proportional dehydration process between intra and extracellular fluid (i.e., intracellular dehydration rather than extracellular dehydration). The extent of fluid reduction, but not the copeptin response, is affected by the patient’s baseline volume conditions.Clinical trial registration: Clinicaltrials.gov, identifier NCT03917758.
27 November 2020 in Journal of Endocrinological Investigation
Purpose: Vasoplegia often complicates on-pump cardiac surgery. Systemic inflammatory response induced by extracorporeal circulation represents the major determinant, but adrenal insufficiency and postoperative vasopressin deficiency may have a role. Pathophysiological meaning of perioperative changes in endocrine markers of hydro-electrolyte balance has not still fully elucidated. Objectives of the present research study were to estimate the incidence of vasoplegia in a homogeneous cohort of not severe cardiopathic patients, to define the role of presurgical adrenal insufficiency, to evaluate copeptin and NT-proBNP trends in the perioperative. Methods: We conducted a prospective cohort study in the cardiac intensive care unit of a tertiary referral center. We evaluated 350 consecutive patients scheduled for cardiac surgery; 55 subjects completed the study. Both standard and low-dose corticotropin stimulation tests were performed in the preoperative; copeptin and NT-proBNP were evaluated in the preoperative (T0), on day 1 (T1) and day 7 (T2) after surgery. Results: Nine subjects (16.3%) developed vasoplegic syndrome with longer bypass and clamping time (p < 0.001). Reduced response to low-dose ACTH test was not associated to vasoplegia. Preoperative copeptin > 16.9 pmol/L accurately predicted the syndrome (AUC 0.86, 95% CI 0.73–0.94; OR 1.17, 95% CI 1.04–1.32). An evident correlation was observed at 7 days postoperative between NT-proBNP and copeptin (r 0.88, 95% CI 0.8–0.93; p < 0.001). Conclusion: Preoperative impaired response to low-dose ACTH stimulation test is not a risk factor for post-cardiotomic vasoplegia; conversely, higher preoperative copeptin predicts the complication. On-pump cardiac surgery could be an interesting model of rapid heart failure progression.