Pituitary Center Research

Abstract

Selection of the safest and most effective surgical approach for complex skull base lesions is a matter of great relevance and significant controversy. A combination of endoscopic endonasal and transcranial approaches for complex skull base pathology is underinvestigated. We aim to analyze our experience with combination of endonasal endoscopic and transcranial approaches, either simultaneously or as staged procedures.Thirty-two patients underwent a combined strategy. Patients were divided into simultaneous or staged group. Lesions were classified according to pathology and skull base compartments. Primary endpoints were rationale for selection of approaches, clinical outcomes, extent of resection, and postoperative complications in both groups.Twenty-two patients underwent a simultaneous strategy, and 10 a staged approach. Gross-total resection was achieved in 11 patients (50%) in the simultaneous group and in 5 patients (50%) in the staged group. Cerebrospinal fluid leak occurred in 1 out of 22 cases (4.5%) in the simultaneous group, and in 3 out of 10 cases (30%) in the staged group (P = .043). Preoperative neurological deficits improved in 5 out of 9 patients in the simultaneous group and 5 out of 9 in the staged group.Our study showed that, except for cerebrospinal fluid leak rates, there were no main significant differences between performing both approaches simultaneously or staged. Selection of the strategy depends on the characteristics of the lesion and surgical team. When complex lesions expand from the central skull base into anterior, middle, or posterior regions, a combination strategy can provide favorable results.

View details for DOI 10.1227/ons.0000000000001825

View details for PubMedID 41201316

Abstract

OBJECTIVE: The primary objective of this study was to elaborate on the surgical anatomy and technical nuances of pituitary transposition techniques and assess their clinical application, enhancing both the safety and efficacy of endonasal approaches to the retrosellar and interpeduncular regions.METHODS: Twenty-two colored silicone-injected specimens were dissected stepwise via an endoscopic endonasal approach. A comprehensive assessment of pituitary transposition techniques, including anatomical landmarks, surgical nuances, and transposition distances, was performed. Their clinical relevance was presented using illustrative cases.RESULTS: The following pituitary transposition techniques were established according to their relationship with the dual-layered sellar dura and the extent of pituitary gland mobilization: extradural (involves elevating the dura from the sellar floor, allowing limited access to the lower dorsum sellae and superior pituitary gland mobilization [mean vertical transposition distance ± SD of 2.4 ± 0.7 mm]); interdural transsellar (outer dural layer is incised at the sellar face and floor, improving access to the dorsum sellae and facilitating further superior pituitary gland mobilization [mean vertical transposition distances of 4.1 ± 0.8 mm at the midline and 4.9 ± 0.7 mm at the lateral aspect]); interdural transcavernous (outer dural layer is opened at the anterior wall of the cavernous sinus [CS] for superomedial pituitary gland mobilization with direct transcavernous access to the posterior clinoid process [mean vertical transposition distances of 3.6 ± 0.6 mm at the midline and 6.8 ± 0.7 mm at the lateral aspect, mean horizontal transposition distance of 3.8 ± 0.7 mm]); extended interdural transcavernous (interdural approach is extended into the clinoidal space by transecting the caroticoclinoid ligament, maximizing exposure for challenging posterior clinoidectomy [mean vertical transposition distances of 5.5 ± 0.9 mm at the midline and 8.7 ± 0.9 mm at the lateral aspect, mean horizontal transposition distance of 7.2 ± 0.8 mm]); intradural hemitransposition (involves opening both dural layers at the sellar face, dissecting the pituitary gland away from the medial wall of the CS on the selected side, and enabling ipsilateral paramedian exposure of the dorsum sellae and retrosellar and retroinfundibular regions); full intradural (pituitary gland is dissected away from the medial wall of the CS bilaterally, facilitating its horizontal and vertical mobilization and providing comprehensive access to the dorsum sellae and bilateral retrosellar and retroinfundibular regions; transection of the diaphragm enhances suprasellar access); and pituitary gland sacrifice (complete removal, offering unimpeded access to the retrosellar and retroinfundibular regions).CONCLUSIONS: Seven pituitary transposition techniques based on dural opening, gland mobilization, and approach extent are described herein. Selecting the appropriate technique, guided by the affected anatomical regions, pathology type, and preoperative pituitary gland function, is crucial for optimal surgical outcomes.

View details for DOI 10.3171/2025.3.JNS242358

View details for PubMedID 40680307

Abstract

To assess surgical outcomes in patients with prolactinomas treated surgically with contemporary endoscopic endonasal techniques within the context of recent advances in transcavernous approaches and shifts towards surgery as a primary treatment option alongside dopamine agonists.Surgical outcomes were retrospectively analyzed for 59 consecutive patients with prolactinomas who underwent endoscopic endonasal surgery between October 2018 and December 2024.The cohort included 42 (71%) patients with macroprolactinomas and 32 (54%) patients with cavernous sinus (CS) invasion, including 14 (24%) with isolated medial wall invasion and 18 (31%) with CS compartment invasion. Median follow-up was 19 months (interquartile range = 10-38). Overall, 82% of patients demonstrated normoprolactinemia within three days of surgery and 80% (74% macroprolactinoma, 94% microprolactinoma) achieved biochemical remission at last follow-up. Adjuvant dopamine agonist treatment and/or radiation increased the long-term remission rate to 86% overall and to 83% for macroprolactinomas. Among patients for whom total resection (vs. debulking) was the primary surgical goal, long-term biochemical remission was achieved in 84% of patients (88% with adjuvant therapy). One operative complication with no neurological sequelae occurred in a patient with a giant invasive adenoma. Permanent arginine vasopressin deficiency was observed in three patients and transient diplopia was observed in four patients.The addition of endoscopic transcavernous approaches for prolactinoma resection can be safe and effective in selected patients after multidisciplinary evaluation when performed by an experienced neurosurgical team, providing further support for the wider adoption of surgery in the management of prolactinomas.

View details for DOI 10.1007/s11102-025-01545-w

View details for PubMedID 40593194

View details for PubMedCentralID 10259306

Abstract

With their growing experience in endoscopic transcavernous approaches, the authors have observed that pituitary adenomas have distinct patterns of invasion into the medial wall of the cavernous sinus (MWCS). In this study, they aimed to describe the different patterns of MWCS invasion and their relevance for pituitary surgery.Based on a review of 144 patients with 159 cavernous sinus (CS) explorations, the authors described three patterns of MWCS invasion: focal invasion, wall thickening, and wall destruction. Demographics, previous surgery, size, hormonal status, consistency, CS compartment invasion, invasion of the carotico-clinoid ligament (CCL), carotid adherence, gross-total resection (GTR) of intracavernous tumor, endocrinological remission (ER), and complications (vascular injury, cranial nerve palsy, CSF leakage, and hematoma) were evaluated.The most frequent pattern of MWCS invasion was wall destruction (47.2%), followed by wall thickening (28.9%) and focal invasion (23.9%). All cases of focal invasion were contained within the wall, whereas 59% of the wall-thickening and 100% of the wall destruction cases had intracavernous tumor (p < 0.001). Overall, GTR was achieved in 87.4% of cases and ER was achieved in 80.6% with surgery alone. Focal invasion was most associated with functioning adenomas (92%) and low Knosp grade (95%). Invasion of the CCL, adherence of the MWCS to the carotid artery, and fibrous consistency were found in 15%-20% of cases. GTR was achieved in all cases and ER in 93% with no complications associated with MWCS resection. Wall thickening was also found predominantly in functioning adenomas (83%) with low Knosp grade (72%), and often in recurrent cases (46%). Carotid adhesion was significantly more frequent (61%), as was CCL invasion (44%) and fibrous consistency (46%). GTR was achieved in 98% and ER in 82%, with transient postoperative diplopia in 7% of cases, all with intracavernous tumor. Wall destruction occurred almost exclusively in macroadenomas (96%) with high Knosp grades (59%) and no hormonal secretion (55%). Invasion of the CCL, fibrous consistency, and carotid adherence were found in less than one-third of the cases. GTR was achieved in 75% and ER in 65%, with postoperative diplopia in 11% of cases.Pituitary adenomas may invade the MWCS in three distinct patterns, each with particular tumor characteristics and a differential degree of technical difficulty and clinical outcomes.

View details for DOI 10.3171/2025.3.JNS242823

View details for PubMedID 40577846

Abstract

The carotidoclinoidal ligament (CCL) spans from the medial wall of the cavernous sinus (MWCS) to the internal carotid artery (ICA) and anterior clinoid process. In endoscopic endonasal transcavernous surgery, safe transection of the CCL requires not only knowledge of its typical anatomy, but also an understanding of its possible variations. The aim of this study was to analyze the anatomical variations of the CCL and the patterns of CCL invasion by pituitary adenomas (PAs).This investigation comprised an anatomical and a clinical study. Endonasal dissections of 20 specimens (40 sides) were performed to investigate CCL variations. A retrospective analysis of 145 patients with PA invading the CS (160 CS sides) was conducted to report the incidence and patterns of CCL invasion.The CCL was present in all investigated sides (n = 40). In the coronal plane, 1 CCL branch was found in 20 sides (50.0%) and ≥ 2 CCL branches were found in 20 sides (50.0%). The main CCL branch was defined as the medial continuation of the proximal dural ring, marking the transition from the cavernous to the paraclinoidal ICA segment. When additional accessory CCL branches were present, they attached to the paraclinoidal ICA (n = 17, 53.1%), the horizontal cavernous ICA segment (n = 10, 31.3%), and/or the anterior genu of the cavernous ICA (n = 5, 15.6%). The CCL most commonly attached to the upper (n = 29, 72.5%) and middle third (n = 26, 65.0%) of the MWCS. In the axial plane, the CCL was found to be a fenestrated membrane in 29 sides (72.5%) and an intact membrane in 11 sides (27.5%). All CCLs attached to at least the anterior third of the MWCS. Additionally, some CCLs attached to the middle third (n = 23, 57.5%) and/or the posterior third (n = 17, 42.5%). The CCL was connected to the inferior parasellar ligament in 14 sides (35.0%). Among all PAs invading the CS, the CCL was invaded in 36 cases (22.5%). Two patterns of CCL invasion were identified: 1) tumor adherent to and infiltrating the CCL fibers (n = 30, 83.3%), and 2) CCL thickened due to tumor growth within and along the fibers (n = 6, 16.7%).This study represents a comprehensive analysis of the anatomical variations and patterns of invasion of the CCL, which is particularly relevant for the safe and effective resection of PA invading the CS.

View details for DOI 10.3171/2025.3.JNS242768

View details for PubMedID 40577843

Abstract

BACKGROUND: Underdiagnosis and the absence of a condition-specific diagnostic code have made the economic burden of adult growth hormone deficiency (AGHD) difficult to capture. This study measured all-cause and disease-specific healthcare utilization and costs of AGHD among individuals stratified by diagnosis status and receipt of growth hormone (GH) treatment.METHODS: Adults meeting ≥1 of the following criteria (1/1/2017-12/31/2021): diagnosis of hypopituitarism or related condition, ≥3 pituitary hormone deficiencies, ≥3 pituitary hormone treatments, or ≥1GH prescription were identified in the Veradigm Network EHR linked to claims. Individuals were stratified by GH level on or before the earliest qualifying event: confirmed (GH < 3ng/mL), at-risk (no test result), ruled-out (GH ≥ 3ng/mL). Confirmed and at-risk individuals were segmented by GH treatment. An age and gender-matched control cohort without AGHD was identified. Healthcare utilization and costs were measured in the 12-month post-index period. Multivariable modeling compared all-cause and AGHD-related healthcare costs, excluding cost of GH, among diagnosis- or treatment status-stratified cohorts while adjusting for baseline characteristics.RESULTS: Among 54,310 individuals at risk for AGHD and 268 with confirmed AGHD, 3.1% and 9.7% received GH treatment, respectively. Study subjects were, on average, 50years old and majority female. Adjusted all-cause healthcare costs were higher among at-risk individuals (cost ratio [95% confidence interval]: 2.37 [2.26-2.49]) and among confirmed individuals (2.11 [1.52-3.43]) compared to controls. Adjusted annual AGHD-related costs were lower among confirmed individuals compared to at-risk individuals (0.62 [0.52-0.76]) and among treated individuals compared to untreated individuals (0.55 [0.47-0.64]) for those initiating GH therapy.CONCLUSIONS: All-cause healthcare costs were higher among individuals with confirmed AGHD or at risk for AGHD than among adults without GHD. After excluding the cost of GH therapy, lower adjusted AGHD-related costs were associated with both a confirmed AGHD diagnosis and receipt of GH treatment.

View details for DOI 10.1080/13696998.2025.2548741

View details for PubMedID 40826813

Abstract

Nuclear reprogramming of somatic cells into a pluripotent status has the potential to create patient-specific pluripotent stem cells (iPSCs) for regenerative medicine. Currently, however, the epigenetic mechanisms underlying this pluripotent reprogramming are poorly understood. To delineate this epigenetic regulatory network, we utilized a chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to identify long noncoding RNAs (lncRNAs) embedded in the 3-dimensional intrachromosomal architecture of stem cell core factor genes. By combining CRIST-seq and RNA-seq, we identified Osilr9 (Oct4-Sox2 interacting lncRNA 9) as a pluripotency-associated lncRNA. Osilr9 expression was associated with the status of stem cell pluripotency in reprogramming. Using shRNA knockdown, we showed that this lncRNA was required for the optimal maintenance of stem cell pluripotency. Overexpression of Osilr9 induced robust activation of endogenous stem cell core factor genes in fibroblasts. Osilr9 participated in the formation of the intrachromosomal looping required for maintenance of pluripotency. After binding to the Oct4 promoter, Osilr9 recruited the DNA demethylase TET1, leading to promoter demethylation. These data demonstrate that Osilr9 is a critical chromatin epigenetic modulator that coordinates the promoter activity of core stem cell factor genes, highlighting the critical role of pluripotency-associated lncRNAs in stem cell pluripotency and reprogramming.

View details for DOI 10.1016/j.ymthe.2022.12.010

View details for PubMedID 36523163

Abstract

CONTEXT: Supraphysiological serum insulin-like growth-factor-I (IGF-I) concentrations have been a matter of concern in children treated with growth hormone (GH) because high IGF-I levels were associated with risk of later disease in former epidemiological studies.OBJECTIVE: To determine whether a single IGF-I measurement reliably reflects lifetime IGF-I exposure we evaluated intraindividual longitudinal tracking of IGF-I and IGF-binding-protein-3 (IGFBP-3) levels and we estimated cumulative lifetime exposure to IGF-I in healthy and GH-treated individuals.METHODS: We included 6,459 healthy participants (cross-sectional=5,326; longitudinal=1,133) aged 0----76 years (9,963 serum samples) and nine patients born small-for-gestational-age (SGA) with 238 serum samples during GH treatment.Intraindividual tracking of IGF-I and IGFBP-3 (SDS) was determined by intraclass correlation coefficients (ICC). Cumulative lifetime IGF-I exposure was estimated by area under the curve of the predicted SDS-trajectory from 0-76 years.RESULTS: For IGF-I (SDS), ICCs were 0.50 (95% CI: 0.47-0.53) for male and 0.53 (0.50-0.56) for female participants. Lifetime IGF-I exposure was significantly higher in female (mean 12,723±3,691 SD) than in male participants (12,563±3,393); p=0.02. In SGA children, treatment with GH increased the lifetime exposure to IGF-I from 9,512±1,889 to 11,271±1,689, corresponding to an increase in lifetime IGF-I trajectory from -0.89 SD±0.57 to -0.35 SD±0.49.CONCLUSION: Since IGF-I and IGFBP-3 levels track throughout life, a single measurement reliably reflects lifetime exposure. GH therapy increased the lifetime exposure to IGF-I only slightly and it remained below the average lifetime exposure in the reference population.

View details for DOI 10.1210/clinem/dgac605

View details for PubMedID 36250350

Abstract

The molecular circuitry that causes stem cells to exit from pluripotency remains largely uncharacterized. Using chromatin RNA in situ reverse transcription sequencing, we identified Peln1 as a novel chromatin RNA component in the promoter complex of Oct4, a stem cell master transcription factor gene. Peln1 was negatively associated with pluripotent status during somatic reprogramming. Peln1 overexpression caused E14 cells to exit from pluripotency, while Peln1 downregulation induced robust reprogramming. Mechanistically, we discovered that Peln1 interacted with the Oct4 promoter and recruited the DNA methyltransferase DNMT3A. By de novo altering the epigenotype in the Oct4 promoter, Peln1 dismantled the intrachromosomal loop that is required for the maintenance of pluripotency. Using RNA reverse transcription-associated trap sequencing, we showed that Peln1 targets multiple pathway genes that are associated with stem cell self-renewal. These findings demonstrate that Peln1 can act as a new epigenetic player and use a trans mechanism to induce an exit from the pluripotent state in stem cells.

View details for DOI 10.1083/jcb.202009134

View details for PubMedID 35171230

Abstract

BACKGROUND: A specific 3-dimensional intrachromosomal architecture of core stem cell factor genes is required to reprogram a somatic cell into pluripotency. As little is known about the epigenetic readers that orchestrate this architectural remodeling, we used a novel chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to profile long noncoding RNAs (lncRNAs) in the Oct4 promoter.RESULTS: We identify Platr10 as an Oct4 - Sox2 binding lncRNA that is activated in somatic cell reprogramming. Platr10 is essential for the maintenance of pluripotency, and lack of this lncRNA causes stem cells to exit from pluripotency. In fibroblasts, ectopically expressed Platr10 functions in trans to activate core stem cell factor genes and enhance pluripotent reprogramming. Using RNA reverse transcription-associated trap sequencing (RAT-seq), we show that Platr10 interacts with multiple pluripotency-associated genes, including Oct4, Sox2, Klf4, and c-Myc, which have been extensively used to reprogram somatic cells. Mechanistically, we demonstrate that Platr10 helps orchestrate intrachromosomal promoter-enhancer looping and recruits TET1, the enzyme that actively induces DNA demethylation for the initiation of pluripotency. We further show that Platr10 contains an Oct4 binding element that interacts with the Oct4 promoter and a TET1-binding element that recruits TET1. Mutation of either of these two elements abolishes Platr10 activity.CONCLUSION: These data suggest that Platr10 functions as a novel chromatin RNA molecule to control pluripotency in trans by modulating chromatin architecture and regulating DNA methylation in the core stem cell factor network.

View details for DOI 10.1186/s13059-021-02444-6

View details for PubMedID 34412677