Journal of Endocrinological Investigation最新文献

Background: Hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by insufficient or absent secretion of parathyroid hormone (PTH), which results in hypocalcemia, hyperphosphatemia, and disruption of calcium phosphate homeostasis. Despite advances in understanding its pathophysiology and management, HypoPT remains a complex and impactful condition associated with significant morbidity, impaired quality of life, and long-term complications affecting the skeletal, renal, and neurological systems.

Methods: A literature search was performed on PubMed. Articles were selected based on their relevance to the main topic of the review, with particular attention to recent studies.

Results: This review provides a comprehensive synthesis of the current knowledge on HypoPT, addressing its epidemiology, underlying pathophysiological mechanisms, genetic and acquired etiologies, clinical manifestations, diagnostic strategies, and chronic disease-related complications. Emphasis is placed on the genetic spectrum of the disease, challenges of postsurgical management, and burden of conventional therapy, which often fails to fully restore mineral homeostasis and patient well-being. The evolving therapeutic landscape is detailed, highlighting advances from traditional calcium and active vitamin D supplementation to innovative PTH replacement strategies. Among these, palopegteriparatide and eneboparatide (phase 3 clinical trial ongoing) are reshaping treatment paradigms by enabling more physiological restoration of calcium-phosphate balance, reducing complications, and improving patient-centered outcomes, including renal function and quality of life.

Conclusions: By integrating clinical expertise with the latest research developments, this review offers an updated and holistic perspective on HypoPT management, aiming to support clinicians in delivering effective and individualized care to patients across the spectrum of disease severity.

Purpose: Patients with adamantinomatous craniopharyngiomas (aCP) often present hypothalamic involvement (HI) either by the tumor or therapeutic interventions, resulting in hypothalamic obesity (HyOb). This study aims to investigate how appetite sensations and orexigenic and anorexigenic hormones response may contribute to the HyOb pathogenesis in these subjects.

Subjects and methods: Fifteen patients with aCP submitted to surgical resection (31,1 ± 12 years; 9 women) and 15 controls (31 ± 11,7 years) paired by sex, age and BMI were included in this cross-sectional study. Leptin and adiponectin were measured in basal conditions (T0'). Glucose, insulin, ghrelin, GLP-1, and PYY levels were assessed at T0', T30', T60', T120', and T180' minutes after a standard meal test. Sensations of hunger, fullness and prospective food consumption were measured using a visual analogic scale at the same time points.

Results: Intergroup differences on appetite sensations and biochemical variables were not significant between patients with aCP and controls. Intragroup analyses revealed distinct post-meal dynamics: compared to matching controls, patients with aCP showed earlier increase in hunger, and decrease in fullness (both P = 0.005) and prospective food consumption (P = 0.06) ratings from T0' to T180'. There was a tendency towards higher fasting leptin concentrations (P = 0.06), while adiponectinemia was significantly lower (P = 0.002). Insulin and HOMA-IR (both P < 0.01) were higher at T180', whereas the anorexigenic hormones GLP-1 (P = 0.03) and PYY (P = 0.02) were higher at T120'. PYY and ghrelin showed earlier postprandial rise and fall, respectively, in patients with aCP.

Conclusions: Although intergroup differences were limited, our intragroup analyses revealed reduced satiety persistence and earlier appetite rebound, particularly in patients with HyOb and severe HI, providing new insights into the complex, multifactorial pathophysiology of HyOb associated with aCP.

Purpose: To evaluate the efficacy and safety of osilodrostat in patients with Ectopic Cushing syndrome (ECS).

Methods: A retrospective, multicenter, real-world study of patients with ECS treated with osilodrostat. The main efficacy endpoint was the proportion of patients who were complete responders (urinary free cortisol [UFC] < the upper limit of normal [ULN] or adrenal insufficiency development).

Results: A total of 17 patients with ECS were identified. Most of the cases (88.2%, n = 15) were classified as severe Cushing´s syndrome (UFC > 5 ULN). Two patients received osilodrostat as first-line therapy, 9 as second line and 6 as a third line. Fourteen patients were treated with osilodrostat in monotherapy and 3 in combination with other treatments. The initial doses of osilodrostat ranged between 4 and 30 mg/day and the maximum doses between 4 and 60 mg/day. Response to osilodrostat was evaluated in 16 patients because one patient died few days (< 30) after the initiation of the treatment. We found that 88% (n = 14/16) were complete responders while 2 patients had partial response (UFC reduction > 50% but with no normalization). The median time to achieve hypercortisolism control was 4.5 weeks (range 1–12), and 40% of the cases had normal UFC after 1 month of treatment. Six patients developed adverse events associated with the use of osilodrostat: 3 had adrenal insufficiency, 1 QT prolongation and 1 deterioration of blood pressure control.

Conclusion: Overall, osilodrostat controls hypercortisolism in approximately 90% of the patients with ECS and severe hypercortisolism and with normalization of UFC in 40% of cases after just 4 weeks of treatment. Therefore, osilodrostat should be considered as first-line treatment in patients with ECS, especially in patients with severe hypercortisolism.

Background: Cancer survivors have been considered individuals who have completed anti-tumor treatment and are in "remission". However, the definition is increasingly seen as insufficient due to a significant number of patients living with chronic or stable disease, as a result of advanced therapies, and according to a recent definition, "survivors" are all people living with and beyond cancer. Breast, prostate, lung and colorectal cancers are the most frequent tumors diagnosed in Europe with an increasing population of survivors. The longer life expectancy has made it necessary to assess the health status, comorbidities, and complications in cancer patients, mainly in the age range of 20-50 years. In particular, the long-lasting hormonal therapies in hormone-sensitive tumors and the immunotherapies, that are changing the cancer clinical scenario, have opened a broad landscape of late endocrine/metabolic toxicities.

Purpose: The aim of the present manuscript is to evaluate the late endocrine-metabolic complications in survivors of young adult or adult-onset cancers in the most prevalent tumors, analyzing risk factors for endocrine/metabolic disease, attempting to provide a indications for long-term surveillance and treatment strategies.

Conclusions: This paper highlights the importance of recognizing endocrine and metabolic complications, as well as identifying key risk factors that can suggest a more effective surveillance and management.

Introduction: Unilateral adrenalectomy is a definitive treatment for patients with primary aldosteronism (PA), yet its long-term renal and metabolic consequences remain insufficiently characterized. This study aimed to evaluate the incidence, risk, and cumulative burden of chronic kidney disease (CKD)/renal impairment, hyperuricemia, and gout in patients undergoing adrenalectomy compared to matched controls.

Methods: We used the Longitudinal Generation Tracking Database (LGTD) from the Health and Welfare Data Science Center, Taiwan, which includes data from 2 million individuals insured since 2000. We identified 1,110 primary aldosteronism (PA) patients diagnosed between 2000 and 2019, excluding those with adrenal insufficiency or pre-existing hyperuricemia, gout, CKD, or plasma cell dyscrasia. The final cohort included 537 PA patients who underwent unilateral adrenalectomy, with a control group matched 4:1 using propensity scores based on age, gender, and comorbidities. Outcomes included new-onset CKD/renal impairment, hyperuricemia, and gout. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards models, and cumulative incidence was visualized via Kaplan-Meier plots.

Results: A total of 537 adrenalectomized PA patients and 2148 matched controls were analyzed. Compared with controls, the adrenalectomy group exhibited a significantly increased risk of CKD/renal impairment (aHR 2.07; 95% CI, 1.58-2.72; p < 0.0001) and gout (aHR 1.54; 95% CI, 1.02-2.32; p = 0.048), while the elevated risk of hyperuricemia did not reach statistical significance (aHR 1.92; 95% CI, 0.82-4.52; p = 0.424). Kaplan-Meier curves demonstrated a higher cumulative incidence of CKD and gout over a 20-year period in the adrenalectomy group, whereas the divergence in hyperuricemia incidence was less pronounced. Stratified analyses revealed age- and sex-specific risk variations, and antihypertensive medication adjustment post-adrenalectomy was associated with differential risk. Among adrenalectomized patients, metabolic comorbidities and aging were key predictors of adverse outcomes.

Conclusion: Patients with PA who undergo unilateral adrenalectomy are at increased long-term risk of CKD and gout. These findings underscore the need for vigilant renal and metabolic monitoring postoperatively, particularly in older patients and those with predisposing comorbidities.