Pituitary tumors are rare in the pediatric population, accounting for less than 10% of childhood tumors. Craniopharyngiomas are the most common pediatric sellar lesions, but pituitary adenomas/PitNETs also occur, representing 2-8% of all sellar lesions. This study explores a decade of transsphenoidal microsurgery on pediatric patients, examining perioperative features including complications, clinical outcomes and anatomical peculiarities. This retrospective study included a total of 147 transsphenoidal surgeries performed by a single surgeon on 122 pediatric patients under the age of 18 between 2013 and 2023. Parameters assessed included age, gender, clinical hormone production, histopathological and radiographic parameters, surgical features, postoperative complications and recurrences rate. Among 122 pediatric patients with pituitary lesions, we found that craniopharyngiomas were the most common entity (34.4%), especially in children under 10 years old (58.6%). Pituitary adenomas/PitNETs accounted for 31.1% and were more prevalent in older children, with corticotrophic and lactotrophic adenomas being the most common subtypes. Younger patients needed significantly more time for surgery, with the longest durations observed in the 3-9 years age group and the shortest in the 16-17 years age group. Additionally, sphenoid sinus pneumatization increased with age and was inversely correlated with the duration of surgery. The current study is one of the largest to date on pediatric pituitary region lesions shedding light on demographic, clinical and histopathological features. The age-dependent distribution pattern highlights the prominence of craniopharyngiomas in younger patients, while PPAs became increasingly prevalent in those older than 10 years.

Abstract Corticotroph pituitary neuroendocrine tumours (PitNETs)/adenomas are heterogeneous sellar neoplasms. Currently established histopathological classification approaches are often considered limited in fully capturing the clinical and biological complexity of these tumours. Thus far, a molecular-based classification has not been established in corticotroph PitNETs. We compile molecular data of 270 corticotroph PitNETs (111 internal, 159 external), encompassing epigenome, transcriptome, and proteome profiles. Comprehensive integrative analyses are performed to identify, validate and characterise definitive molecular subgroups. Corticotroph PitNETs separate into four robust and clinicopathologically distinct molecular subgroups, which are broadly distinguishable by microscopy using SSTR1, GATA3 and SSTR5 immunohistochemistry. An integrated stratification model incorporating these molecular subgroups demonstrates significant prognostic utility. Our findings support the establishment of a refined molecular-based corticotroph PitNET classification, the full clinical value of which will require validation in prospective studies. To facilitate future research, we provide an easy-to-use epigenomic classifier for corticotroph PitNETs.

Acquired hypothalamic obesity (aHO) is a disease characterized by rapid, clinically significant, and persistent weight gain resulting from damage to hypothalamic structures. aHO is associated with substantial morbidity, increased mortality, and marked impairment in quality of life. Etiologies include craniopharyngioma and other space-occupying lesions of the sellar/parasellar region, neurosurgical procedures, cranial irradiation, and traumatic brain injury. A multidisciplinary panel comprising ten specialists in neuroendocrinology, neurooncology, and neurosurgery from Germany, Austria, and Switzerland convened in Frankfurt am Main, Germany, on November 10, 2025, to discuss contemporary challenges and advances in this field. aHO should be conceptualized and treated within the broader clinical entity of hypothalamic syndrome, a complex disorder involving multiple neuroendocrine deficiencies, disturbances of circadian regulation, impaired control of hunger, satiety, and thirst, altered thermoregulation, and a range of cognitive, sleep-related, and psychosocial dysfunctions. Long-term outcomes for affected individuals are frequently unfavorable, largely due to increased risks of metabolic syndrome, cardiovascular disease, profound reductions in health-related quality of life, and elevated rates of premature mortality. The management of hypothalamic syndrome remains particularly challenging. Pharmacological strategies, including dextroamphetamine and glucagon-like peptide-1 receptor agonists, have demonstrated potential benefits for weight and hyperphagia-related outcomes. Recently, preliminary findings from a prospective, randomized, placebo-controlled clinical trial (TRANSCEND) provided encouraging evidence for the efficacy of setmelanotide, a melanocortin-4 receptor agonist. This perspectives report reviews clinical advances in epidemiology, diagnostics, treatment, and follow-up of patients with aHO and outlines key directions for future research aimed at improving outcomes in this vulnerable population.

Microscopic (MTS) or endoscopic transsphenoidal surgeries (ETS) are two main well established approaches for the management of sellar pathologies in contemporary established approaches for the management of sellar pathologies in contemporary neurosurgical practice. Exoscopic transsphenoidal surgery (ExTS), which employs a 4K 3D camera system (Orbeye, Olympus), has recently emerged as a promising alternative; however, its role in the management of Rathke’s cleft cysts (RCC) remains unclear. This study aimed to evaluate the surgical characteristics and clinical outcomes of ExTS in patients with RCC and to compare these results with those achieved using the more widely established microscopic transsphenoidal surgery (MTS) technique. We performed a retrospective analysis of electronic medical records of all transsphenoidal operations conducted between July 2013 and May 2022 at the University Medical Center Hamburg-Eppendorf. 125 patients with RCC after a defined type of transsphenoidal surgery were included. Mean operative duration was similar between groups (78.5 ± 21.7 min vs. 73.1 ± 26.7 min, p = 0.20). Complication and recurrence rates did not differ significantly between MTS and ExTS (16.7

BACKGROUND:Recurrence after successful pituitary surgery remains a challenge in the management of patients with Cushing's disease, with no reliable predictors of long-term outcome. Pathogenic somatic USP8 variants are found in one third of cases and their association with recurrence is unclear. The aim of this study was to determine the association between USP8 status and postoperative outcome. METHODS:This international, retrospective, longitudinal study was done in eight tertiary centres in east Asia, Europe, and North America. We reviewed clinical records and genetic information of patients with clinically diagnosed and pathologically confirmed Cushing's disease who underwent first pituitary surgery in any of the participating centres between Jan 1, 1989, and April 1, 2024. Inclusion criteria were postoperative follow-up of at least 3 months after first pituitary surgery, known postsurgical outcome, and tissue availability or known USP8 status. The primary outcomes were recurrence and time to recurrence after first surgery. We assessed recurrence-free intervals and recurrence risk using survival analysis, multivariate logistic regression, and Cox proportional hazards models. FINDINGS:We retrospectively retrieved and examined clinical records from 558 patients, 123 of whom were excluded. 360 (83%) of 435 patients were female and 75 (17%) were male. We detected USP8 variants in 195 (45%) cases. Recurrence was recorded in 66 (18%) of 371 patients in immediate remission. Risk of recurrence depended on USP8 status and tumour size. Patients with USP8-variant microadenomas and USP8-variant macroadenomas had similar cumulative hazards for recurrence, so they were considered as a single risk group. 10-year recurrence rate was higher for USP8-variant tumours (36·8%, 95% CI 23·7-47·7) than for wildtype microadenomas (15·0%, 4·9-24·0; adjusted p=0·016) but was lower than for wildtype macroadenomas (44·5%, 26·2-58·2; adjusted p=0·025). Patients with USP8-variant tumours (hazard ratio 2·41, 95% CI 1·19-4·87; p=0·014) or wildtype macroadenomas (4·48, 2·11-9·52; p<0·0001) had significantly higher risk of recurrence than patients with wildtype microadenomas, even after adjusting for age, postoperative nadir serum cortisol, tumour invasion, and ethnicity or centre. INTERPRETATION:Combined USP8 genotype-tumour size identified patients at increased risk of recurrence, particularly in largely heterogeneous groups of patients with non-invasive tumours or low postoperative serum cortisol not considered high risk in standard care. Implementing this combined genetic-clinical stratification could provide more accurate risk assessment, indicate those at higher risk of recurrence, and ultimately personalise long-term follow-up in patients with Cushing's disease. FUNDING:Deutsche Forschungsgemeinschaft, National Natural Science Funds of China, and CAMS Innovation Fund for Medical Sciences.

Corticotroph pituitary neuroendocrine tumors (PitNETs) expressing adrenocorticotropic hormone (ACTH) can lead to Cushing’s disease (CD). In contrast, silent corticotroph PitNETs also produce ACTH but lack clinical or biochemical signs of hypercortisolism and have been associated with a more aggressive clinical course. The mechanisms underlying the divergent secretory behavior between overt and silent tumors remain incompletely understood. In overt cases, impaired negative feedback regulation has been linked to reduced glucocorticoid receptor (GR) expression, whereas silent tumors often retain GR expression and an intact feedback loop, potentially explaining the absence of overt hypercortisolism. We hypothesized that tumor-intrinsic neural signaling contributes to this differential hormonal activity. Using reference-based deconvolution of bulk DNA methylation profiles, we inferred cellular composition and classified TPIT-positive tumors according to neural lineage signatures. Samples were stratified into high- and low-neural subgroups based on hypomethylated CpG sites and expression of genes involved in synaptic integration. Clinically, silent corticotroph PitNETs presented with significantly larger tumor volumes. Methylation-based deconvolution revealed that silent phenotypes exhibited a significantly higher neural score, indicating increased neuronal lineage characteristics. These tumors also showed enriched neuronal and astrocytic signatures and reduced stem cell components. Immune deconvolution demonstrated that silent tumors were enriched in CD8⁺ T cells, neutrophils, and NK cells, contrasting with the immunosuppressive microenvironment in overt CD. Notably, peripheral basal cortisol levels negatively correlated with CD8⁺ T cell signatures, suggesting cortisol-mediated immune suppression in overt cases. These findings define silent TPIT-positive PitNETs as a distinct clinical and molecular subtype characterized and highlight the potential contribution of neural and immune cell interactions to the clinical behavior of corticotroph tumors.

INTRODUCTION: The incidental finding of pituitary microadenomas (PmAs) is increasingly common due to the widespread use of MRI. To date, no comprehensive volumetric analyses of PmAs growth patterns have been conducted. A greater understanding of how these lesions progress could influence an array of management strategies, including frequency of imaging and the use of surgical versus conservative medical intervention. METHODS: Patients who underwent = 2 pituitary MRIs for suspected PmAs were identified retrospectively across 4 referral centers worldwide. Patient demographics, presenting symptoms, clinical variables, MRIs, and treatment course were collected and analyzed. RESULTS: A total of 447 patients (Male = 126; 28.2%) referred to the 4 centers from 2003 to 2022 were identified. Median age at first MRI was 43 years [IQR 32–54]. Median number of MRIs per patient was 3 [IQR 2–5] and median follow-up time was 55 months [IQR 29–100]. 300 PmAs (67.1%) were solid, 102 (22.8%) were cystic, 47 (10.5%) were uncertain, and 24 (5.4%) were mixed. At baseline, median suspected tumor volume was 45 mm 3 [15–103]. 77 patients (17.2%) presented with subclinical hyperpituitarism, most often hyperprolactinemia, while 67 (15.0%) experienced hypopituitarism such as hypogonadism, hypothyroidism, and growth hormone deficiency. During follow-up, new onset hyperpituitarism was detected in 20 patients (4.5%) along with hypopituitarism in 9 (2.0%). During the study period, 225 patients (50.3%) had no change in suspected PmA growth, 144 (32.2%) had a decreased size, and 101 (22.6%) had an increased size. 80 patients (17.9%) received medical therapy and 48 (10.7%) underwent transsphenoidal surgery. CONCLUSIONS: With the forthcoming volumetric analysis, we hope to gain further insights into predictors of long-term volumetric evolution of PmAs to improve patient management.

INTRODUCTION: Although first-line prolactinoma (PL) management typically involves dopamine agonists (DAs), the role of surgery as a primary therapeutic is being reconsidered given the undesirable side effects of long-term DAs. METHODS: Patients surgically treated for PL from January 2017 through December 2020 were identified. Preoperative characteristics and postoperative outcomes were assessed. Multivariate models adjusting for tumor characteristics and surgery complexity identified factors predictive of complications and long-term adverse outcomes. RESULTS: Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PLs were macroadenomas. Most PLs were managed microscopically (69.9%) and fewer endoscopically (29.0%). Although 29.8% of patients experienced at least one early postoperative complication, most were minor (39.3%), with less being major complications (4.4%). The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. Based on available data on follow-up, disease remission on long-term follow-up imaging was achieved in 94.8% of cases, and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. Upon multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly prohibitive against long-term endocrinological cure. Knosp classification was highly predictive of residual tumor or PL recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). CONCLUSIONS: Our results evaluate a modern, multicenter, global series of patients treated for PL. This data serves as a benchmark to compare with DAs and demonstrates that surgery offers high rates of remission with low rates of complications and recurrence. It may be reasonable to consider surgery as an alternative to DAs.

Background and Objectives: Skull base reconstruction is a crucial step during transsphenoidal surgery. Sphenoid mucosa is a mucosal membrane located in the sphenoid sinus. Preservation and lateral shifting of sphenoid mucosa as sphenoid mucosal flap (SMF) during the transsphenoidal exposure of the sella may be important for later closure. This is the first systematic review to evaluate the utility of sphenoid mucosal flap for sellar reconstruction after transsphenoidal surgery. Materials and Methods: A systematic literature search was performed in January 2023: Cochrane, EMBASE, PubMed, Scopus, and Web of Science. The following keywords and their combinations were used: "sphenoid mucosa", "sphenoid sinus mucosa", "sphenoid mucosal flap", "sphenoid sinus mucosal flap". From a total number of 749 records, 10 articles involving 1671 patients were included in our systematic review. Results: Sphenoid sinus mucosa used to be applied for sellar reconstruction as either a vascularized pedicled flap or as a free flap. Three different types of mucosal flaps, an intersinus septal flap, a superiorly based flap and an inferiorly based flap, were described in the literature. Total SMF covering compared to partial or no SMF covering in sellar floor reconstruction resulted in fewer postoperative CSF leaks (p = 0.008) and a shorter duration of the postoperative lumbar drain (p = 0.003), if applied. Total or partial SMF resulted in fewer local complications (p = 0.012), such as fat graft necrosis, bone graft necrosis, sinusitis or fungal infection, in contrast to no SMF implementation. Conclusions: SMF seems to be an effective technique for skull base reconstruction after transsphenoidal surgery, as it can reduce the usage of avascular grafts such as fat along with the incidence of local complications, such as fat graft necrosis, bone graft necrosis, sinusitis and fungal infection, or it may improve the sinonasal quality of life by maintaining favorable wound healing through vascular flap and promote the normalization of the sphenoid sinus posterior wall. Further clinical studies evaluating sphenoid mucosal flap preservation and application in combination with other techniques, particularly for higher-grade CSF leaks, are required.

Introduction: The diagnosis of pituitary microprolactinomas is often obscured by relatively low levels of elevated prolactin compared to macroprolactinomas. This may lead to varying patterns of medical therapy versus observation. We sought to correlate prolactin levels in suspected microprolactinomas with tumor volumes and clinical outcomes.

The diagnosis of pituitary microprolactinomas is often obscured by relatively low levels of elevated prolactin compared to macroprolactinomas. This may lead to varying patterns of medical therapy versus observation. We sought to correlate prolactin levels in suspected microprolactinomas with tumor volumes and clinical outcomes. This was a multicenter retrospective study of patients with pituitary microadenomas with baseline prolactin levels > 18ng/ml for males and > 30ng/ml for females. A linear-mixed model was used to depict changes in tumor volume over time. There were 65 patients with a mean tumor volume of 95.9mm3 and mean prolactin level of 59.4ng/ml. There were significantly higher prolactin levels in patients with tumors above the mean volume versus below (74.0 versus 53.4ng/ml, p = 0.027). 26 patients were observed, 31 were treated with anti-dopaminergic therapy, and 8 had surgery. There were significantly greater baseline prolactin levels for patients who were treated surgically (mean 86.4ng/ml) than those treated medically (mean 61.7 g/ml) or observed (mean 48.5ng/ml) (p = 0.02). Among the 26 patients who were surveilled, 13 patients demonstrated spontaneous tumor shrinkage, 12 remained stable, and 1 patient’s tumor grew but was lost to follow-up. Linear mixed modeling demonstrated a statistically significant rate of tumor shrinkage over time of 3.67mm3/year (p = 0.03). When analyzing patients who were observed versus those requiring surgery after initially being surveilled, there were significantly greater baseline PRL/volume ratios in surgical patients versus those observed (8.1 ng/ml/mm3 versus 2.4 ng/ml/mm3, p = 0.025). Suspected microprolactinomas may demonstrate more convincingly elevated prolactin levels when measuring over 95.9mm3. Tumors with baseline prolactin levels over 50ng/ml may be more inclined to undergo medical treatment. In tumors with levels below 50ng/ml, it may be reasonable to undergo surveillance as these tumors tend to spontaneously shrink over time. In tumors that are surveilled, an elevated baseline PRL/volume ratio of > 8 ng/ml/mm3 may be indicate serial tumor growth that may necessitate medical and/or surgical intervention.

Prolactinoma account to the most common pituitary adenomas and current therapy regime constitutes of dopamine agonist therapy (DA) and surgery in selected cases [17]. Due to tumor fibrosis induced by previous DA therapy, surgical removal can be challenging though. Therefore, this study investigates how preoperative DA usage influences perioperative treatment and surgical outcome in prolactinoma and aims to ascertain whether a specific subgroup of prolactinoma patients could derive greater benefit from exclusive surgical intervention. We retrospectively analyzed n = 159 surgically treated and histologically confirmed prolactinomas in the sella region from 2013–2022 in our institution. Clinical, radiological and surgical features were analyzed. Univariate and multivariate analyses were performed. Out of total of 159 prolactinoma patients, 83.6

Pituitary neuroendocrine tumors (PitNETs) are classified according to cell lineage, which requires immunohistochemistry for adenohypophyseal hormones and the transcription factors (TFs) PIT1, SF1, and TPIT. According to the current WHO 2022 classification, PitNETs with co-expression of multiple TFs are termed "plurihormonal". Previously, PIT1/SF1 co-expression was prevailingly reported in PitNETs, which otherwise correspond to the somatotroph lineage. However, little is known about such tumors and the WHO classification has not recognized their significance. We compiled an in-house case series of 100 tumors, previously diagnosed as somatotroph PitNETs. Following TF staining, histopathological features associated with PIT1/SF1 co-expression were assessed. Integration of in-house and publicly available sample data allowed for a meta-analysis of SF1-associated clinicopathological and molecular features across a total of 270 somatotroph PitNETs. The majority (74%, 52/70) of our densely granulated somatotroph PitNETs (DGST) unequivocally co-expressed PIT1 and SF1 (DGST-PIT1/SF1). None (0%, 0/30) of our sparsely granulated somatotroph PitNETs (SGST) stained positive for SF1 (SGST-PIT1). Among DGST, PIT1/SF1 co-expression was significantly associated with scarce FSH/LH expression and fewer fibrous bodies compared to DGST-PIT1. Integrated molecular analyses including publicly available samples confirmed that DGST-PIT1/SF1, DGST-PIT1 and SGST-PIT1 represent distinct tumor subtypes. Clinicopathological meta-analyses indicated that DGST-PIT1 respond more favorably towards treatment with somatostatin analogs compared to DGST-PIT1/SF1, while both these subtypes show an overall less aggressive clinical course than SGST-PIT1. In this study, we spotlight that DGST with co-expression of PIT1 and SF1 represent a common, yet underrecognized, distinct PitNET subtype. Our study questions the rationale of generally classifying such tumors as "plurihormonal", and calls for a refinement of the WHO classification. We propose the term "somatogonadotroph PitNET".

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