Pituitary最新文献

Background: In a resource limited setting, cabergoline remains an important part of medical management in acromegaly patients with persistent disease after surgery. Response to medical treatment may depend on the receptor expression in these tumors.

Objectives: To study the dopamine receptor subtype2 (D2R) and somatostatin receptor subtypes2&5(SSTR2&SSTR5) expression in somatotropinomas by immunohistochemistry (IHC) and real time/quantitative polymerase chain reaction(qPCR). Also, to determine the relation between density of D2R expression and remission with cabergoline therapy.

Methods: This study included 30 patients with somatotropinomas who underwent surgery and had persistent disease post-surgery treated with cabergoline. Immunostaining and qPCR for D2R, SSTR2&5 were performed on archived GH secreting pituitary adenoma specimens. The clinical, biochemical and radiological details were collected from the hospital electronic medical records.

Results: D2R was the predominantly expressed receptor followed by SSTR2 and SSTR5. The median(range) duration of cabergoline therapy was 20(6-72) months. 23% (7/30) of patients achieved normalization of IGF-I or GH < 1ng/ml (random/post glucose suppression) with cabergoline. Subjects with baseline IGF-1 < 1.5 times the upper limit of normal were more likely to achieve remission with cabergoline. D2R mRNA expression was significantly higher in patients in remission. On ROC curve analysis, a D2R ^ΔΔ CT of 19.2 (19-fold higher expression compared to normal tissue) predicted remission with cabergoline with a sensitivity of 71% and specificity of 74% (AUC 0.745).

Conclusion: D2 receptor profiling of growth hormone secreting pituitary tumors and post-operative IGF-1 level at 3 months are helpful to predict response to medical treatment with cabergoline.

Purpose: This study aimed to develop a core outcome set (COS) for pituitary surgery to enhance the quality, efficiency and effectiveness of future pituitary adenoma surgery research.

Methods: Thirty-three outcomes were identified through a systematic review of pituitary adenoma surgery outcomes and a study on patient-reported measures. These were presented in an online survey to healthcare professionals (HCPs), patients and caregivers. In the first round, participants scored each outcome's importance on a 5-point scale (1-strongly disagree; 5-strongly agree) and could also suggest additional outcomes, which were reviewed and, if appropriate, added to existing domains. In the second round, participants re-scored the updated the list, considering group median and interquartile range scores from the previous round. Outcomes with a median score of 5 were included in the COS. A final live online consensus meeting discussed and voted on borderline outcomes (median scores 3-4).

Results: The first round received 95 responses (52% HCPs, 48% patients/caregivers). Of the 33 outcomes, 16 received a median score of 5 (strongly agree), three received 4.5 and 14 received 4 (agree). Round two received 87 responses (52% HCPs, 48% patients and caregivers). Of the 33 outcomes, 14 received a median ranking of 5, two received 4.5, 15 received 4 and two received 3 (neutral). The live meeting (attended by 12 participants: 5 HCPs, 6 patients, 1 caregiver), reached consensus on the final COS, which includes 7 domains: short-term surgical outcomes; nasal outcomes; ophthalmic outcomes; endocrine outcomes; quality of life and psychological outcomes; other short-term outcomes; and disease control outcomes.

Conclusion: We advocate for use of the COS in future pituitary surgery research.

Introduction: X-linked acrogigantism (X-LAG; OMIM: 300942) is a rare X-linked dominant, fully penetrant form of infancy-onset pituitary gigantism caused by Xq26.3 tandem duplications involving the GPR101 gene. All previously reported X-LAG-associated duplications disrupt the integrity of the resident topologically associating domain (TAD). This creates a neo-TAD, permitting ectopic chromatin interactions between GPR101 and centromeric pituitary enhancers postulated to lie between RBMX and VGLL1, and culminating in pituitary GPR101 misexpression and growth hormone excess. Conversely, none of the few previously reported cases of Xq26.3 duplications in unaffected individuals include the tissue-invariant TAD border that shields GPR101 from its centromeric enhancers. Preservation of this boundary has thus been considered synonymous with non-penetrance of X-LAG.

Methods: We examined a series of four family members from the same kindred with an incidentally detected GPR101-containing Xq26.3 duplication involving the invariant TAD border.

Results: Chromosome microarray demonstrated an interstitial chromosome Xq26.3 duplication: arr[GRCh37] Xq26.3(135,954,223 - 136,224,319)x2, including GPR101, the TAD invariant border and RBMX, but not VGLL1. None of the relatives with the Xq26.3 duplication exhibited evidence of growth hormone excess, making this the first unaffected family with a GPR101-containing Xq26.3 duplication involving the invariant TAD border. The predicted neo-TAD in this kindred excludes the VGLL1 region, which is present in all previously described X-LAG patients and absent in all previously described unaffected individuals with Xq26.3 duplications.

Conclusion: Our clinical findings suggest that TAD border involvement is not sufficient for X-LAG to develop, and implicates the VGLL1 region as likely the sole pituitary enhancer responsible for GPR101 misexpression and the X-LAG phenotype. Pending corroborative studies, this new insight into X-LAG pathogenesis may guide interpretation of future Xq26.3 duplications and counselling of families in whom such duplications are found.

Purpose: 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.

Methods: Surgical outcomes were retrospectively analyzed for 59 consecutive patients with prolactinomas who underwent endoscopic endonasal surgery between October 2018 and December 2024.

Results: 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.

Conclusion: 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.

Background: Adamantinomatous craniopharyngioma (ACP) is a histologically benign yet clinically aggressive intracranial tumor characterized by high recurrence rates. Fibroblast activation protein (FAP), a marker of cancer-associated fibroblasts (CAFs), is implicated in tumor progression and microenvironment remodeling. This study evaluates the prognostic significance of FAP and develops a radiomics-based model for non-invasive preoperative risk stratification.

Methods: Immunohistochemical analysis was performed on 54 ACP cases to assess FAP expression levels. Transcriptomic data from 110 ACP cases across two external databases were analyzed for differential gene expression and pathway enrichment. Immunofluorescence was conducted to determine the spatial correlation of FAP with angiogenic markers (VEGF, CD31, CD34). A radiomics model was developed using preoperative MRI data to predict FAP expression and validated for predictive performance.

Results: High FAP expression was associated with extracellular matrix remodeling, angiogenesis, and inflammatory pathway activation. Clinically, high-FAP tumors exhibited larger volumes (P = 0.044), more severe hypothalamic dysfunction (P = 0.001), and shorter progression-free survival (P = 0.03). Multivariate analysis identified high FAP expression (HR = 9.890, P = 0.0340) as an independent predictor of recurrence. Immunofluorescence confirmed the co-localization of FAP⁺ CAFs with angiogenic markers, suggesting a role in tumor recurrence. The radiomics model integrating T1/T2-weighted MRI features demonstrated robust performance in predicting FAP expression, with AUCs of 0.742 (training set),0.822 (internal validation set) and 0.686(external validation set).

Conclusions: FAP is a prognostic biomarker in ACP, with high expression indicative of increased recurrence risk. The radiomics model offers a non-invasive approach for preoperative risk stratification, potentially guiding surgical decision-making and anti-angiogenic therapeutic strategies.