Vitamins and Hormones最新文献

{"title":"Cyclic Cushing's syndrome.","authors":"Elisabeth Nowak","doi":"10.1016/bs.vh.2026.02.004","DOIUrl":"10.1016/bs.vh.2026.02.004","url":null,"abstract":"<p><p>While physiological cortisol secretion follows a regulated circadian rhythm, pathological excess as in endogenous Cushing's syndrome is characterised by increased and dysregulated cortisol concentrations. While subtle fluctuations occur in virtually all patients with Cushing's syndrome, cyclic Cushing's syndrome (cCS) represents a sub-entity defined by alternating periods of biochemical hypercortisolism (\"peaks\") and spontaneous intervals of physiological or even suppressed cortisol concentrations (\"troughs\"). These oscillations may occur over days to years and are usually unpredictable in frequency or amplitude. CCS is one of the most diagnostically challenging variants of hypercortisolism, which frequently leads to discordant biochemical test results, misclassifications, and prolonged diagnostic latency. Furthermore, diagnostic procedures performed during eucortisolaemic phases may yield false results, occasionally resulting in unnecessary investigations or inappropriate surgical interventions. Recognition of cyclicity is therefore essential in patients presenting with recurrent or fluctuating Cushingoid features and inconsistent biochemical findings. Establishing the diagnosis requires serial hormonal profiling combined with careful clinical correlation. Once confirmed, management should follow established principles for the underlying aetiology, while accounting for the temporal variability in cortisol excess that complicates timing of invasive diagnostic procedures, such as bilateral petrosal sinus sampling, and medical therapy. This chapter provides a concise, clinically oriented review of the epidemiology, etiology, diagnostic approach, and management strategies of cCS, aiming to support clinicians in recognising and effectively managing this complex and often underdiagnosed disorder.</p>","PeriodicalId":51209,"journal":{"name":"Vitamins and Hormones","volume":"132 ","pages":"235-241"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New molecular markers of response to medical therapy in acromegaly.","authors":"Aina Raventós, Joan Gil, Montserrat Marques-Pamies, Paula de Pedro-Campos, Carmín Puente de la Vega, Antonio Picó, Cristina Lamas, Elías Delgado, Edelmiro Menéndez, Guillermo Serra, Ignacio Bernabéu, Rocio Villar, Jordi Ferri, Karla Mariaca, Rebeca Martínez, Mónica Marazuela, Marta Araujo-Castro, Betina Biagetti, Mireia Jordà, Elena Valassi, Manel Puig-Domingo","doi":"10.1016/bs.vh.2025.10.006","DOIUrl":"10.1016/bs.vh.2025.10.006","url":null,"abstract":"<p><p>The management of pituitary neuroendocrine tumors (PitNETs) is shifting toward a personalized medicine approach, supported by the identification of biomarkers that can guide individualized surgical and medical strategies. In acromegaly, medical therapy with somatostatin receptor ligands (SRLs), dopamine agonists, and GH receptor antagonists represent the cornerstone of treatment in patients with persistent disease after surgery or when surgery cannot be performed. However, therapeutic outcomes are highly variable, reflecting the substantial heterogeneity of somatotropinomas. The classical approach, which considers clinical factors, radiological features, and histological subtypes, continues to play a role but remains insufficient to reliably identify treatment response with high accuracy. New approaches such as those based on functional testing and omics sciences-including genomics, epigenomics, transcriptomics, and proteomics-are showing superiority in identifying determinants of treatment response. Although current evidence is growing, these approaches are still considered in the research field but are slowly being introduced in clinical practice. In this chapter, we review the available molecular and functional markers of response to medical therapy in acromegaly and discuss how to include them in the clinical ground for advancing precision medicine in this disease.</p>","PeriodicalId":51209,"journal":{"name":"Vitamins and Hormones","volume":"131 ","pages":"265-292"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth hormone: Synthesis and regulation.","authors":"Pedro Iglesias, Fernando Guerrero-Pérez","doi":"10.1016/bs.vh.2025.10.001","DOIUrl":"10.1016/bs.vh.2025.10.001","url":null,"abstract":"<p><p>Growth hormone (GH) plays an essential role in the regulation of postnatal growth and metabolism through both direct and GH-IGF-1 axis-mediated mechanisms. GH action involves a complex interplay of endocrine, paracrine and autocrine signals that affect multiple tissues and organs. This review addresses the molecular and physiological fundamentals of GH secretion and action, as well as the multiple factors that modulate it, including central and peripheral signals, metabolic variables, physiological and pharmacological states. The relevance of GH receptor signaling and intracellular pathways involved in tissue response is discussed, as well as the mechanisms of hormone resistance that may arise in different clinical contexts. GH secretion, which is pulsatile, is subject to strict regulation by the hypothalamic-pituitary system, involving GHRH, somatostatin and ghrelin, together with negative feedback from GH and IGF-1. In addition, factors such as sleep, nutrition, stress, age or sex contribute significantly to its physiological variability. The implications of the somatotropic axis in pathological conditions such as GH deficiency, acromegaly or GH insensitivity syndromes are also explored.</p>","PeriodicalId":51209,"journal":{"name":"Vitamins and Hormones","volume":"131 ","pages":"1-23"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiometabolic comorbidities in overt Cushing's syndrome.","authors":"Laura González Fernández, Rogelio García Centeno","doi":"10.1016/bs.vh.2026.02.006","DOIUrl":"10.1016/bs.vh.2026.02.006","url":null,"abstract":"<p><p>Endogenous Cushing's syndrome (CS) is characterized by chronic glucocorticoid excess that drives a severe cardiometabolic phenotype responsible for most morbidity and mortality associated with the disorder. Cortisol excess induces a constellation of metabolic derangements-including visceral adiposity, insulin resistance, hypertension, dyslipidemia, and ectopic fat deposition-that closely mirror and amplify the components of metabolic syndrome. These abnormalities result from widespread glucocorticoid actions on adipose tissue, liver, skeletal muscle, pancreas, vasculature, and the heart, mediated through genomic, nongenomic, and local tissue-specific mechanisms such as altered AMPK signaling and dysregulated 11β-HSD activity. Cardiovascular disease represents the leading cause of death in CS, with increased risks of myocardial infarction, stroke, heart failure, and venous thromboembolism. Structural and functional cardiovascular changes-including arterial stiffness, endothelial dysfunction, concentric left ventricular hypertrophy, myocardial fibrosis, and coronary microvascular impairment-are frequently observed and often only partially reversible. Although biochemical remission leads to improvement in many metabolic and cardiovascular parameters, substantial residual cardiometabolic risk persists, with high rates of persistent hypertension, dyslipidemia, glucose abnormalities, central adiposity, and prothrombotic imbalance. Long-term mortality remains elevated even decades after cure, particularly in patients with prolonged hypercortisolism or coexisting cardiometabolic disease. The recognition that overt CS constitutes an accelerated model of metabolic syndrome underscores the need for early diagnosis, prompt cortisol normalization, and aggressive long-term management of cardiovascular and metabolic comorbidities.</p>","PeriodicalId":51209,"journal":{"name":"Vitamins and Hormones","volume":"132 ","pages":"317-344"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical manifestations of primary aldosteronism and cardiometabolic risk.","authors":"Eider Pascual-Corrales, José Manuel Ruiz-Cánovas, Marta María Pérez Peña","doi":"10.1016/bs.vh.2025.08.002","DOIUrl":"10.1016/bs.vh.2025.08.002","url":null,"abstract":"<p><p>Primary aldosteronism (PA) is the most common cause of secondary hypertension and is increasingly recognized as a spectrum disorder, ranging from subclinical to overt forms. Clinical manifestations include hypertension, often resistant, and may be accompanied by hypokalemia. Beyond BP elevation, PA is associated with a disproportionately high risk of cardiovascular and metabolic complications compared to essential hypertension, including coronary artery disease, arrhythmias, heart failure, left ventricular hypertrophy, stroke, metabolic syndrome and impaired glucose metabolism. The negative effects of aldosterone excess induce greater target organ damage than seen in primary hypertension, including arterial stiffness, cardiac remodeling, and renal dysfunction. Targeted treatments such as mineralocorticoid receptor (MR) antagonists and adrenalectomy have demonstrated efficacy in reducing these risks and improving patient outcomes. Therefore, early detection and management of PA are essential for preventing long-term cardiovascular and metabolic complications.</p>","PeriodicalId":51209,"journal":{"name":"Vitamins and Hormones","volume":"130 ","pages":"69-104"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mild autonomous cortisol secretion: Diagnosis.","authors":"Leonor Pinto, Sara Donato","doi":"10.1016/bs.vh.2026.02.005","DOIUrl":"10.1016/bs.vh.2026.02.005","url":null,"abstract":"<p><p>Mild autonomous cortisol secretion (MACS) is the most frequent hormonal alteration identified in patients with adrenal incidentalomas and is characterized by adrenocorticotropic hormone (ACTH)-independent cortisol hypersecretion in the absence of specific clinical features of Cushing syndrome. Growing evidence indicates that even mild degrees of cortisol excess are associated with increased cardiometabolic morbidity, including hypertension, type 2 diabetes mellitus, dyslipidemia, and obesity, as well as skeletal fragility, frailty and excess mortality. Diagnosis relies primarily on biochemical evaluation, with the 1-mg dexamethasone suppression test as the cornerstone, complemented by confirmation of ACTH independence. However, hormonal testing is subject to important limitations. Management strategies include individualized consideration of adrenalectomy, conservative treatment with target treatment of associated comorbidities, or selected use of medical therapies targeting cortisol secretion or action. Despite increasing recognition of the clinical relevance of MACS, optimal risk stratification and identification of patients most likely to benefit from surgery remain challenging, highlighting the need for validated biomarkers and well-designed prospective randomized trials. This chapter reviews current concepts in the pathophysiology and genetic background of MACS, its clinical consequences, diagnostic challenges and evolving therapeutic strategies.</p>","PeriodicalId":51209,"journal":{"name":"Vitamins and Hormones","volume":"132 ","pages":"243-272"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular profile of Cushing's syndrome.","authors":"Clara González-Pérez, Sergio Pedraza-Arevalo, Justo P Castaño, Alejandro Ibáñez-Costa","doi":"10.1016/bs.vh.2026.04.003","DOIUrl":"10.1016/bs.vh.2026.04.003","url":null,"abstract":"<p><p>Cushing's syndrome comprises a heterogeneous group of disorders characterized by chronic excess of glucocorticoid release from adrenal glands, caused by altered adrenal function or by ACTH hypersecretion from pituitary or ectopic sources. Advances in high-throughput molecular profiling have substantially refined our understanding of the mechanisms underlying endogenous hypercortisolism. This chapter provides an integrated overview of the genetic, transcriptomic, and epigenetic alterations driving both ACTH-dependent and ACTH-independent forms of the disease. Hypothalamic-pituitary-adrenal axis regulation of cortisol homeostasis is controlled by complex feedback circuits involving glucocorticoid receptor signaling, transcriptional POMC regulation, and multilayered neuroendocrine inputs. Disruption of these regulatory networks represents a central event in disease pathogenesis. In corticotroph adenomas, recurrent somatic mutations in USP8, USP48, and BRAF converge on enhanced POMC transcription and ACTH secretion, while aggressive tumors frequently harbor alterations in TP53 and ATRX. Transcriptomic and spatial profiling reveal lineage-defined tumor identities alongside significant intratumoral heterogeneity, whereas epigenetic mechanisms-including DNA methylation, miRNA dysregulation, and chromatin remodeling-fine-tune hormone secretion and glucocorticoid feedback resistance. Ectopic ACTH-secreting neuroendocrine tumors exhibit a distinct molecular profile characterized by epigenetic reactivation of POMC through promoter hypomethylation and context-dependent transcriptional reprogramming, independent of canonical pituitary lineage factors. In contrast, ACTH-independent Cushing's syndrome is predominantly driven by constitutive activation of the cAMP/PKA pathway in adrenal lesions, most commonly through activating PRKACA mutations, with additional contributions from GNAS and CTNNB1. Adrenocortical carcinoma displays a more complex genomic landscape involving IGF2 overexpression, Wnt/β-catenin activation, and tumor suppressor alterations, reflecting its malignant phenotype. These molecular insights have direct clinical implications, enabling refined disease classification, improved prognostic stratification, and the identification of actionable therapeutic targets, including EGFR, MAPK, PKA, and glucocorticoid receptor-associated pathways. Collectively, the integration of multi-omics approaches is redefining the conceptual framework of Cushing's syndrome and paving the way toward precision medicine strategies in endocrine oncology.</p>","PeriodicalId":51209,"journal":{"name":"Vitamins and Hormones","volume":"132 ","pages":"291-316"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aldosterone & cortisol cosecretion.","authors":"Pol Candela, Carme Figueredo, Felicia A Hanzu","doi":"10.1016/bs.vh.2025.10.009","DOIUrl":"10.1016/bs.vh.2025.10.009","url":null,"abstract":"<p><p>Mild autonomous cortisol co-secretion (MACS) in primary aldosteronism (PA)-referred to as Connshing syndrome, C-PA, or MACS-PA-has emerged as a clinically significant adrenal disorder that substantially influences the prognosis and management of PA. In this chapter, a comprehensive overview of current knowledge and recent advances in the pathophysiology, diagnosis, and clinical impact of Connshing syndrome is presented, highlighting its importance for personalized treatment strategies and improved patient outcomes.</p>","PeriodicalId":51209,"journal":{"name":"Vitamins and Hormones","volume":"130 ","pages":"289-312"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential diagnosis of ACTH-dependent Cushing's syndrome: Biochemical, imaging, and predictive approaches.","authors":"Wilfredo Antonio Rivera-Martínez, Carlos Esteban Builes-Montaño, Alejandro Román-González, Carlos Alfonso Builes-Barrera, María Johana Ramírez-Castaño, Johnayro Gutiérrez-Restrepo","doi":"10.1016/bs.vh.2026.03.002","DOIUrl":"10.1016/bs.vh.2026.03.002","url":null,"abstract":"<p><p>Endogenous hypercortisolism remains a high-stakes diagnostic challenge in which delays or misclassification drive excess morbidity and mortality. This chapter synthesizes an evidence-based, physiology-anchored approach to the differential diagnosis of ACTH-dependent Cushing's syndrome, integrating clinical phenotyping, first-line biochemistry, dynamic testing, imaging, and invasive confirmation. We first outline bedside features that raise or lower the pre-test probability of Cushing disease (CD) versus ectopic ACTH syndrome (EAS). Then, the initial laboratory tests (nocturnal salivary cortisol, 24-h urinary free cortisol, low-dose dexamethasone suppression, ACTH) and their pathophysiological correlates are reviewed. For dynamic tests, we summarize indications and interpretation of CRH, desmopressin, and high-dose dexamethasone suppression, highlighting their value as composites rather than stand-alone arbiters. The imaging section prioritizes 3 T dynamic pituitary MRI for CD and thin-slice CT for suspected EAS, with targeted use of ^68Ga-SSTRPET/CT (ectopic NETs), ^18F-FDG (high-grade biology), ^18F-DOPA (PPGL), and emerging pituitary-targeted PET tracers as adjuncts. When non-invasive data are discordant or indeterminate, bilateral inferior petrosal sinus sampling (BIPSS) remains the reference: verify selectivity (prolactin IPS:peripheral > 1.8) and apply ACTHIPS:peripheral cut-offs (≥ 2 basal or ≥ 3 post-stimulus), with optional optimized thresholds and prolactin-adjusted ratios in suboptimal flow. Finally, we propose a step-by-step diagnostic algorithm that sequences these elements pragmatically and discuss predictive models as complementary tools to prioritize testing and resource use.</p>","PeriodicalId":51209,"journal":{"name":"Vitamins and Hormones","volume":"132 ","pages":"151-200"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential diagnosis between endogenous Cushing´s syndrome and pseudo-Cushing.","authors":"Ahmed Alaa Abdul-Aziz","doi":"10.1016/bs.vh.2026.04.002","DOIUrl":"10.1016/bs.vh.2026.04.002","url":null,"abstract":"<p><p>The differentiation between pathological Cushing's syndrome (CS) and pseudo-Cushing's states, also termed non-neoplastic hypercortisolism (NNH), remains one of the biggest challenges in clinical endocrinology. NNH is defined as a reversible condition of clinical and/or biochemical hypercortisolism resulting from persistent activation of the hypothalamic-pituitary-adrenal (HPA) axis by a secondary, non-tumorous etiology. Prevalent conditions such as major depressive disorder, chronic alcoholism, obesity, and eating disorders are frequent causes. Neuropsychiatric disorders drive HPA axis hyperactivity via corticotropin-releasing hormone (CRH) excess and impaired glucocorticoid feedback, while metabolic states often feature tissue-specific amplification of cortisol action via 11β-hydroxysteroid dehydrogenase type 1. Critically, emerging evidence suggests that even functional hypercortisolism may actively contribute to cardiometabolic and neuropsychiatric morbidity, underscoring the importance of accurate discrimination. Clinical evaluation, though essential, is often insufficient, as specific catabolic signs may be absent and metabolic features are common to both entities. Consequently, refined biochemical dynamic tests are pivotal. This review synthesizes evidence on key second-line tests: the combined dexamethasone-CRH test, the desmopressin (DDAVP) test, which exploits aberrant vasopressin receptor expression on corticotroph adenomas and demonstrates high specificity; the combined dexamethasone-DDAVP test, offering a robust and practical alternative; and the 4 mg intravenous dexamethasone suppression test. Radiological studies have no role in this specific differential. A systematic, stepwise diagnostic approach-prioritizing thorough clinical assessment, followed by validated dynamic testing-is imperative to avoid misdiagnosis and ensure appropriate management for both true CS and clinically significant NNH.</p>","PeriodicalId":51209,"journal":{"name":"Vitamins and Hormones","volume":"132 ","pages":"127-149"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}