{"title":"Metabolic complications and their mechanisms in patients with craniopharyngioma","authors":"Eva Marie Erfurth , Hermann L. Müller","doi":"10.1016/j.beem.2025.101999","DOIUrl":"10.1016/j.beem.2025.101999","url":null,"abstract":"<div><div>After diagnosis of craniopharyngioma, patients frequently develop a rapid weight gain leading to morbid hypothalamic obesity due to disease- and/or treatment-associated hypothalamic lesions. Hypothalamic obesity should be diagnosed and treated in the context of hypothalamic syndrome. Hypothalamic syndrome includes neuroendocrine deficiencies, disruption of circadian rhythm, disturbed hunger-satiety and thirst feelings, temperature dysregulation, and neurocognitive, sleep and psychosocial behavioral problems. Long-term prognosis is frequently impaired by increased risk for metabolic syndrome, cardiovascular problems, severe impairments of health-related quality of life, and premature mortality. Treatment of hypothalamic syndrome is challenging. Recently, an algorithm for personalized, risk-specific treatment of hypothalamic syndrome has been published. Dextro-amphetamines and other central stimulating agents as well as glucagon-like peptide-1 receptor (GLP-1R) agonists may cause weight loss. Bariatric surgery is effective. However, non-reversible procedures are controversial due to ethical and legal considerations in minors. Hypothalamus-sparing treatment strategies and research on novel therapeutic agents for hypothalamic syndrome are warranted.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 5","pages":"Article 101999"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Georgia Ntali (Consultant Endocrinologist and Honorary Medical Research Fellow in Endocrinology) , Taufiq Khan (Spesialist Registrar in Neurosurgery) , Niki Karavitaki (Professor of Endocrinology and Honorary Consultant Endocrinologist) , Georgios Tsermoulas (Consultant Neurosurgeon and Honorary Associate Professor in Neurosurgery)
{"title":"Ectopic craniopharyngiomas","authors":"Georgia Ntali (Consultant Endocrinologist and Honorary Medical Research Fellow in Endocrinology) , Taufiq Khan (Spesialist Registrar in Neurosurgery) , Niki Karavitaki (Professor of Endocrinology and Honorary Consultant Endocrinologist) , Georgios Tsermoulas (Consultant Neurosurgeon and Honorary Associate Professor in Neurosurgery)","doi":"10.1016/j.beem.2025.102047","DOIUrl":"10.1016/j.beem.2025.102047","url":null,"abstract":"<div><div>Craniopharyngiomas (CPs) are rare embryonic malformational tumours of the sellar/parasellar region, classified by the World Health Organization (WHO) 5th edition as grade 1 tumours. They may arise anywhere on the path of embryonic cell migration between the midline sphenoid bone and the floor of the sella turcica. On rare occasions, they can be found remotely in areas like the nasopharynx, the orbit, the posterior fossa, the brain parenchyma and the spine. Such ectopic CPs may present as primary in an atypical location, or as secondary, which represent distant recurrence after initial surgical excision in an orthotopic location. The pathogenesis of primary and secondary ectopic CPs is considered distinct, reflecting differences in developmental biology versus tumour dissemination. Primary ectopic CPs are thought to arise either from embryologically misplaced tissue or from genetically driven tumourigenesis outside the sella. Pathogenesis of secondary ectopic CPs reflects tumour cell dissemination through surgical tract implantation, cerebrospinal fluid (CSF) seeding or meningeal seeding. Ectopic cases pose unique diagnostic and therapeutic challenges. In this review which encompasses 97 cases (42 primary and 55 secondary ectopic CPs) published during the period, 2000–2025, we discuss the pathogenesis, clinical presentation, diagnosis and management of these distinctive tumours.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 5","pages":"Article 102047"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jose Mario Gonzalez-Meljem (Assistant Professor) , Lei Cao (Paediatric and Adult Neurosurgeon, Associate Professor) , John Richard Apps (Associate Clinical Professor and Paediatric Neuro-Oncologist) , Juan Pedro Martinez-Barbera (Professor of Developmental Biology and Cancer)
{"title":"Decoding craniopharyngioma: From mechanisms to therapy","authors":"Jose Mario Gonzalez-Meljem (Assistant Professor) , Lei Cao (Paediatric and Adult Neurosurgeon, Associate Professor) , John Richard Apps (Associate Clinical Professor and Paediatric Neuro-Oncologist) , Juan Pedro Martinez-Barbera (Professor of Developmental Biology and Cancer)","doi":"10.1016/j.beem.2025.102051","DOIUrl":"10.1016/j.beem.2025.102051","url":null,"abstract":"<div><div>Research from the last 15 years has profoundly advanced our understanding of craniopharyngioma, a challenging tumour of the sella. Genetically and histologically distinct subtypes — adamantinomatous (ACP) and papillary (PCP) — have been decoded. ACP is primarily driven by CTNNB1 mutations, leading to β-catenin accumulation and WNT pathway activation, while PCP is characterized by BRAF-V600E mutations. Sophisticated ACP mouse models and human studies have proposed a mechanism of senescence-driven pathogenesis in which senescent epithelial cells secrete growth and inflammatory factors that orchestrate a tumour-promoting microenvironment through paracrine signalling. Single-cell RNA sequencing has confirmed this view and revealed intricate tumour ecosystems. These foundational insights are now directly informing novel therapies. Promising targeted approaches, including BRAF/MEK inhibitors for PCP and small molecules disrupting the senescence-associated secretory phenotype (SASP) in ACP are transitioning from bench to bedside, heralding a new biology-driven era for patients.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 5","pages":"Article 102051"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura van Iersel Paediatric resident in training , Jiska van Schaik Paediatric resident in training , Hanneke M. van Santen Professor of Paediatric Endocrinology
{"title":"Growth hormone replacement therapy in childhood-onset craniopharyngioma","authors":"Laura van Iersel Paediatric resident in training , Jiska van Schaik Paediatric resident in training , Hanneke M. van Santen Professor of Paediatric Endocrinology","doi":"10.1016/j.beem.2025.101998","DOIUrl":"10.1016/j.beem.2025.101998","url":null,"abstract":"<div><div>Tumour- or treatment related growth hormone (GH) deficiency is often observed in children diagnosed or treated for childhood onset craniopharyngioma (cCP). Adequate and timely GH replacement therapy (GHRT) is important to improve growth velocity and final height during childhood. GHRT may be continued through adulthood due to its beneficial effects on metabolic health, bone health, mental health and quality of life. The current evidence suggests no increased risk for tumour progression or recurrence, secondary neoplasms or mortality in cCP patients receiving GHRT. In children with newly diagnosed cCP, GHRT may be initiated as early as three months after initial surgery to ameliorate linear growth and metabolic disturbances. The potential long-term effects of early initiation of GHRT as well GHRT with long-acting GH preparations are topics for future research.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 5","pages":"Article 101998"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The management of hypothalamic obesity in craniopharyngioma","authors":"Paul Dimitri","doi":"10.1016/j.beem.2025.102018","DOIUrl":"10.1016/j.beem.2025.102018","url":null,"abstract":"<div><div>Hypothalamic obesity (HO) is a severe, treatment-refractory metabolic disorder resulting from hypothalamic injury secondary to craniopharyngioma directly or from its surgical resection. Characterised by dysregulated energy balance from disruption of complex hypothalamic neuroregulatory circuits, hyperphagia, and reduced sympathetic tone, HO arises due to impaired leptin-melanocortin signalling and autonomic dysfunction. Conventional lifestyle modifications remain largely ineffective, necessitating pharmacotherapeutic approaches targeting neuroendocrine and metabolic pathways. Amelioration of sleep disturbances and pituitary dysfunction serve as an important foundation for management of HO. The use of dextroamphetamine in some HO patients has proved effective. Emerging therapies include melanocortin-4 receptor (MC4R) agonists such as setmelanotide, which restore anorexigenic signalling, glucagon-like peptide-1 (GLP-1) receptor agonists that enhance satiety and energy expenditure, and combination strategies integrating adrenergic modulation (Tesomet). Despite promising preliminary data, long-term efficacy and safety profiles require further validation. Optimizing precision medicine approaches incorporating polypharmacotherapy and neuroendocrine modulation may redefine therapeutic paradigms for HO management.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 5","pages":"Article 102018"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Georgia Ntali (Consultant endocrinologist and Honorary Medical Research Fellow) , Abdul Muktadir Shafi , Niki Karavitaki
{"title":"Mortality in craniopharyngiomas: Data from the last two decades","authors":"Georgia Ntali (Consultant endocrinologist and Honorary Medical Research Fellow) , Abdul Muktadir Shafi , Niki Karavitaki","doi":"10.1016/j.beem.2025.102049","DOIUrl":"10.1016/j.beem.2025.102049","url":null,"abstract":"<div><div>Craniopharyngiomas are rare epithelial tumours arising along the path of the craniopharyngeal duct. They are histologically benign but potentially clinically aggressive tumours due to their invasive behaviour and high recurrence rates. Patients with craniopharyngioma have a high burden of comorbidities which could affect their long-term survival. Studies published in the last 20 years and reporting on standardized mortality ratios (SMR) have demonstrated high mortality (SMRs ranging between 2.45 and 12.2), as also proposed in older reports. Cardiovascular, respiratory diseases and infections are main causes of death. Apart from older age at diagnosis, data on other predictors of mortality are not consistent requiring further elucidation.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 5","pages":"Article 102049"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariska Peck (Academic Foundation Programme Doctor) , Paul Connelly (Consultant in Endocrinology) , Angela K. Lucas-Herald (Senior Lecturer in Child Health, Honorary Consultant in Paediatric Endocrinology)
{"title":"Cardiometabolic outcomes of early onset hypogonadism in males","authors":"Mariska Peck (Academic Foundation Programme Doctor) , Paul Connelly (Consultant in Endocrinology) , Angela K. Lucas-Herald (Senior Lecturer in Child Health, Honorary Consultant in Paediatric Endocrinology)","doi":"10.1016/j.beem.2025.102004","DOIUrl":"10.1016/j.beem.2025.102004","url":null,"abstract":"<div><div>Testosterone is an important vascular hormone, with multiple effects reported on the vasculature. As such, boys and men with early onset hypogonadism may have altered cardiovascular function, with the potential to result in adverse cardiometabolic outcomes in adulthood. Given the fact that cardiovascular changes in the young can affect future cardiovascular health, there is a need to better understand the influence of androgens on the vasculature in those with conditions such as 46, XY Disorders of Sex Development and Klinefelter Syndrome. This review summarises what is known about hypogonadism and the effects of testosterone supplementation in adults with hypogonadism, as well as what is currently understood in those with early onset hypogonadism specifically. A number of research gaps persist in this area and there is a need for international collaborative studies to address these for future generations of affected individuals.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102004"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Agnethe Berglund , Simon Chang , Marie Lind-Holst , Kirstine Stochholm , Claus Højbjerg Gravholt
{"title":"The epidemiology of disorders of sex development","authors":"Agnethe Berglund , Simon Chang , Marie Lind-Holst , Kirstine Stochholm , Claus Højbjerg Gravholt","doi":"10.1016/j.beem.2025.102002","DOIUrl":"10.1016/j.beem.2025.102002","url":null,"abstract":"<div><div>During recent years the epidemiology of disorders of sex development (DSD) has been more clearly delineated. Here, we provide a detailed and up-to-date synopsis of the epidemiology of DSD, incorporating the latest body of knowledge in the field for sex chromosome DSD (Turner, Klinefelter, 47,XXX, and 47,XXY syndrome, and 45,X/46,XY mosaicism) as well as for 46,XX DSD and 46,XY DSD focusing on females with congenital adrenal hyperplasia (CAH), males with 46,XX DSD, females with Mayer-Rokitansky-Küster-Hauser syndrome and females with 46,XY DSD. Despite not fitting directly within the Chicago Consensus classification for DSD, we also include the few epidemiological studies addressing ambiguous genitalia. We show that epidemiological studies have improved our understanding of DSD and led to sound estimates of prevalence, have detailed morbidity and mortality patterns and have for some conditions also shed light on the impact on socioeconomic achievements.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102002"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Differences & disorders of sex development: A focus on outcomes","authors":"S. Faisal Ahmed , Olaf Hiort","doi":"10.1016/j.beem.2025.102029","DOIUrl":"10.1016/j.beem.2025.102029","url":null,"abstract":"","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102029"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}