Journal of Endocrinological Investigation最新文献

Introduction: This Position Statement presents the recommendations of the Italian Society of Endocrinology (SIE) to identify patients with Cushing's syndrome in specific clinical settings. We set two overarching research questions: 1. Which subjects should be screened ("who" should be screened)? 2. Which is the most appropriate first-line test ("how" to screen) for screening? All suggestions/recommendations are evidence-based and directed at endocrinologists and other physicians who deal with patients who have presumptive Cushing's syndrome.

Methods: The recommendations, developed by a SIE committee, were formulated based on eight short-reviews commissioned to experts of the SIE Pituitary and Adrenal Clubs. These short reviews, published in a special issue of the Journal of Endocrinological Investigation, reported a comprehensive review of the literature, and each of them answered the two research questions (who and how to screen for hypercortisolism) in a specific population: (1) patients with type 2 diabetes mellitus or obesity; (2) patients with arterial hypertension; (3) children and adolescents; (4) women with hyperandrogenism and/or menstrual irregularities; (5) patients with osteoporosis and/or fractures; (6) patients with mood disorders; (7) patients with adrenal and pituitary incidentaloma; (8) patients with unusual infections or thrombotic events. Finally, 24 recommendations were formulated, based on the quality of available evidence.

Conclusions: The evidence-based Position Statement provides clear and pragmatic advice regarding "who" and "how" to screen for Cushing's syndrome. The suggestions/recommendations are developed for all health care providers, not only endocrinologists, to raise awareness on the diagnosis of Cushing's syndrome.

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.