Search Results (13)

Background/Objectives: The management of pituitary adenomas involves balancing treatment efficacy with the risk of long-term morbidity, particularly treatment-induced hypopituitarism. While risk factors are qualitatively recognized, quantitative, individualized risk prediction tools for clinical practice are lacking. This study aims to evaluate and characterize the clinical features, hormonal profiles, and treatment outcomes of pituitary adenomas, and to develop and validate a pragmatic clinical prediction model for new-onset hypopituitarism. Methods: We conducted a retrospective cohort study of 215 patients diagnosed with pituitary adenomas, selected from 647 sellar lesions screened at a tertiary referral center between January 2010 and December 2020. Primary outcomes included adenoma size control, hormonal remission in functioning adenomas, and the development of new-onset hypopituitarism. A multivariable logistic regression model was developed to identify independent predictors of new-onset hypopituitarism, and its performance was assessed for discrimination and calibration. Results: The cohort consisted of 107 prolactinomas (49.8%), 77 non-functioning adenomas (35.8%), 18 GH-secreting (8.4%), and 8 ACTH-secreting (3.7%) adenomas, with a mean age of 43.2 ± 14.1 years and a female predominance (59.1%). At a median follow-up of 4.8 years, overall adenoma control was 92.1%. Radiotherapy achieved 100% adenoma control but was associated with the highest incidence of new hypopituitarism at 5 years (34.3%), significantly greater than medical therapy (5.6%, p < 0.001) and surgery (13.0%, p < 0.01). The final risk prediction model, incorporating treatment modality, baseline hypopituitarism, macroadenoma, age >50 years, and cavernous sinus invasion, demonstrated good discrimination (C-statistic = 0.82; 95% CI: 0.76–0.88) and excellent calibration (Hosmer–Lemeshow p = 0.42). Conclusions: Treatment modalities for pituitary adenomas have distinct risk–benefit profiles. Our validated, points-based risk model provides a transparent and clinically applicable tool to quantify an individual patient’s risk of developing hypopituitarism. This model can be integrated into clinical practice to facilitate shared decision-making and guide personalized surveillance strategies. Full article

Background/Objectives: Non-functional pituitary macroadenomas (NFPMA) are uncommon pituitary lesions that do not cause hormonal hypersecretion and are most often discovered at the macroadenoma stage. Consequently, they are more challenging to diagnose, often mimicking other non-secreting sellar masses, among which hypophysitis should be carefully considered. This study aimed to differentiate between non-functioning pituitary macroadenomas (NFPMA) and hypophysitis, two distinct sellar pathologies with overlapping MRI features, by developing a diagnostic score based on clinical, biological, and radiological criteria. Methods: We conducted a prospective study, including 56 patients with NFPMA and 16 patients with hypophysitis primarily of the lymphocytic subtype. A total of 31 clinical, biological, and radiological variables were analyzed using univariate and multivariate statistical methods to identify significant predictors and to establish a diagnostic score. Results: Nine significant criteria were identified: female sex, headaches, visual disturbances, corticotropic insufficiency, pituitary volume ≤ 7 cm³, loss of the posterior pituitary bright spot, cavernous sinus invasion, optic pathway compression, and pituitary stalk thickening. The established score demonstrated significant performance in predicting the diagnosis of hypophysitis (p < 0.001; Area Under the Curve = 0.967; 95% CI = 0.926–1). The sensitivity and specificity of this score were 93.8% and 87.5%, respectively, using a threshold ≥0.5. The median score was −2 (interquartile range = [−3.5; 0.5]), with extremes ranging from −6.5 to 9. Among these, pituitary stalk thickening emerged as a key diagnostic indicator. Conclusions: This simple and effective multi-parametric score enables rapid and accurate differentiation of hypophysitis from NFPMA, helping to avoid unnecessary surgical interventions and to improve the management of pituitary insufficiencies and may be especially valuable in settings when biopsy is unavailable or risky. Full article

Background/Objectives: This prospective study evaluates the relationship between the ganglion cell–inner plexiform layer (GCIPL), retinal nerve fiber layer (RNFL), and photopic negative response (PhNR) in patients with newly diagnosed pituitary macroadenomas over 12 months. Methods: A total of 40 patients (80 eyes) were included, divided into a treatment group of 27 patients (54 eyes), receiving pharmacological and/or surgical intervention, and an observation group of 13 patients (26 eyes), with non-functional pituitary adenomas (NFPAs) that did not require treatment. Results: Key findings indicate a significant improvement in best corrected visual acuity (BCVA) after 12 months in the treatment group (p = 0.02) and a significant reduction in RNFL thickness in multiple quadrants (p < 0.01). Moreover, PhNR amplitude and W-ratio significantly increased in the treatment group (p < 0.0001). In the observation group, only GCIPL Inferior (p = 0.0470) and PhNR W-ratio (p = 0.0015) showed significant differences. Between-group comparisons showed significant differences in RNFL Nasal quadrant at baseline (p = 0.0017) and after 12 months (p = 0.0150). PhNR amplitude and W-ratio also differed significantly between groups at 12 months (p = 0.0012 and p = 0.0016, respectively). Correlations between OCT and ERG parameters were weak at baseline and diminished over time. Conclusions: These findings suggest that GCIPL, RNFL, and PhNR analyses may be useful for monitoring disease progression and guiding treatment decisions in patients with pituitary macroadenomas. Full article

Background/Objectives: Spindle cell oncocytomas (SCOs) of the pituitary gland are rare tumors often misdiagnosed for nonfunctioning pituitary macroadenomas. Although classified as grade 1, they are often challenging in terms of diagnosis and treatment. Pituitary SCOs harbor peculiar features such as hypervascularity and stronger adherence to surrounding structures, with increased risk of hemorrhage, partial resection, and significantly higher recurrence rate. Almost 100 cases have been reported so far. The role of surgery is still crucial for the decompression of the optic chiasm as well as for achieving diagnosis. However, given the higher tendency of recurrence, the role of postoperative radiotherapy has been investigated over the last few years. Case presentation: Here, we reported a case of a 48-year-old female with a pituitary SCO treated at our institution, in which we focused on diagnosis, treatment, and follow-up. Conclusions: This type of tumor presents a challenge related to its higher vascularity and strong adherence to the surrounding structures. Adjuvant radiotherapy is something that should be considered, especially when gross total resection is not achieved, and finally, SCOs require diligent follow-up to monitor for any signs of disease recurrence or progression. Full article

(1) Background: Pituitary adenomas are benign tumors comprising about 18% of all intracranial tumors, and they often require surgical intervention. Differentiating pituitary tissue from adenoma during surgery is crucial to minimize complications. We hypothesized that using ICG dye would reduce the hormonal complication rates. (2) Methods: A prospective randomized study (February 2019–October 2023) included 34 patients with non-functional macroadenomas of the pituitary gland randomly assigned to receive intraoperative ICG or be in the control group. All underwent endoscopic endonasal transsphenoidal surgery. Pituitary function was assessed preoperatively, immediately postoperatively, and 3–6 months postoperatively. Adenohypophysis function was evaluated with hormonal tests (Cosyntropin stimulation test, TSH, fT3, fT4, prolactin, IGF-1, FSH, LH, and testosterone in men) and neurohypophysis function with fluid balance, plasma and urine osmolality, and serum and urinary sodium. (3) Results: Of the 34 patients (23 men, 11 women; average age 60.9 years), 5.9% in the ICG group developed diabetes insipidus postoperatively, compared to 23.5% in the control group. Adenohypophysis function worsened in 52.9% of the ICG group and in 35.3% of the control group. (4) Conclusions: Our study did not confirm the benefits of using ICG in these surgeries. Further research with a larger sample is needed. Full article

Pituitary adenomas (PAs) are the third most common brain tumors in adults right after meningiomas and gliomas. Taking into account their hormonal activity in vivo, they can be divided in functioning PAs, which secrete hormones, and nonfunctioning pituitary adenomas (NFPAs), which are not associated with increased hormone secretion. We present the case of a man diagnosed with pituitary apoplexy. A transsphenoidal surgery was performed with subtotal removal of the mass. Pituitary hormones were measured before and after the procedure on several occasions, showing always normal PRL values, so he was diagnosed with a clinically NFPA. Two years later, the patient noticed a visual deficit. A new magnetic resonance imaging study was performed, showing adenomatous recurrence, and the patient underwent a new surgery. After this, hormonal evaluation revealed high levels of PRL on several occasions. After treatment with cabergoline was started, PRL levels normalized, the visual deficit improved, and there was a slight adenoma reduction. This case report represents an exception to the paradigm that in the presence of a macroadenoma and normal PRL levels (avoiding the “hook effect”), a prolactinoma can be discarded. Moreover, it stresses the importance of comprehensive, regular, and lifelong surveillance of patients with NFPAs and the close monitoring of serum PRL. Full article

Background: The prediction of the regrowth potential of pituitary adenomas after surgery is challenging. The genome-wide DNA methylation profiling of pituitary adenomas may separate adenomas into distinct methylation classes corresponding to histology-based subtypes. Specific genes and differentially methylated probes involving regrowth have been proposed, but no study has linked this epigenetic variance with regrowth potential and the clinical heterogeneity of nonfunctioning pituitary adenomas. This study aimed to investigate whether DNA methylation profiling can be useful as a clinical prognostic marker. Methods: A DNA methylation analysis by Illumina’s MethylationEPIC array was performed on 54 pituitary macroadenomas from patients who underwent transsphenoidal surgery during 2007–2017. Twelve patients were excluded due to an incomplete postoperative follow-up, degenerated biobank-stored tissue, or low DNA methylation quality. For the quantitative measurement of the tumor regrowth rate, we conducted a 3D volumetric analysis of tumor remnant volume via annual magnetic resonance imaging. A linear mixed effects model was used to examine whether different DNA methylation clusters had different regrowth patterns. Results: The DNA methylation profiling of 42 tissue samples showed robust DNA methylation clusters, comparable with previous findings. The subgroup of 33 nonfunctioning pituitary adenomas of an SF1-lineage showed five subclusters with an approximately unbiased score of 86%. There were no overall statistically significant differences when comparing hazard ratios for regrowth of 100%, 50%, or 0%. Despite this, plots of correlated survival estimates suggested higher regrowth rates for some clusters. The mixed effects model of accumulated regrowth similarly showed tendencies toward an association between specific DNA methylation clusters and regrowth potential. Conclusion: The DNA methylation profiling of nonfunctioning pituitary adenomas may potentially identify adenomas with increased growth and recurrence potential. Larger validation studies are needed to confirm the findings from this explorative pilot study. Full article

Post-operative tumour progression in patients with non-functioning pituitary neuroendocrine tumours is variable. The aim of this study was to use machine learning (ML) models to improve the prediction of post-operative outcomes in patients with NF PitNET. We studied data from 383 patients who underwent surgery with or without radiotherapy, with a follow-up period between 6 months and 15 years. ML models, including k-nearest neighbour (KNN), support vector machine (SVM), and decision tree, showed superior performance in predicting tumour progression when compared with parametric statistical modelling using logistic regression, with SVM achieving the highest performance. The strongest predictor of tumour progression was the extent of surgical resection, with patient age, tumour volume, and the use of radiotherapy also showing influence. No features showed an association with tumour recurrence following a complete resection. In conclusion, this study demonstrates the potential of ML models in predicting post-operative outcomes for patients with NF PitNET. Future work should look to include additional, more granular, multicentre data, including incorporating imaging and operative video data. Full article

Clinically-relevant pituitary adenomas occur in about 1:1000 of the general population, but only about 5% occur in a known genetic or familial setting. Familial isolated pituitary adenomas (FIPA) are one of the most important inherited settings for pituitary adenomas and the most frequent genetic cause is a germline mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene. AIP mutations lead to young-onset macroadenomas that are difficult to treat. Most are growth hormone secreting tumors, but all other secretory types can exist and the clinical profile of affected patients is variable. We present an overview of the current understanding of AIP mutation-related pituitary disease and illustrate various key clinical factors using examples from one of the largest AIP mutation-positive FIPA families identified to date, in which six mutation-affected members with pituitary disease have been diagnosed. We highlight various clinically significant features of FIPA and AIP mutations, including issues related to patients with acromegaly, prolactinoma, apoplexy and non-functioning pituitary adenomas. The challenges faced by these AIP mutation-positive patients due to their disease and the long-term outcomes in older patients are discussed. Similarly, the pitfalls encountered due to incomplete penetrance of pituitary adenomas in AIP-mutated kindreds are discussed. Full article

miR-17-5p and E2F1 have been described as deregulated in cancer, but they have scarcely been studied in pituitary neuroendocrine tumours (PitNETs). This study evaluates the relationship of E2F1 and miR-17-5p with the invasiveness and proliferation of PitNETs. In this cross-sectional descriptive study, we evaluated the expression of E2F1, MYC, and miR-17-5p by quantitative real time PCR analysis in 60 PitNETs: 29 gonadotroph (GT), 15 functioning somatotroph (ST), and 16 corticotroph (CT) tumours, of which 8 were silent (sCT). The clinical data were collected from the Spanish Molecular Register of Pituitary Adenomas (REMAH) database. We defined invasiveness according to the Knosp classification and proliferation according to a molecular expression of Ki-67 ≥ 2.59. E2F1 was more expressed in invasive than in non-invasive tumours in the whole series (p = 0.004) and in STs (p = 0.01). In addition, it was overexpressed in the silent subtypes (GTs and sCTs; all macroadenomas) and normoexpressed in the functioning ones (fCTs and STs; some microadenomas). miR-17-5p was more expressed in proliferative than in non-proliferative tumours (p = 0.041) in the whole series but not by subtypes. Conclusions: Our study suggests that in PitNETs, E2F1 could be a good biomarker of invasiveness, and miR-17-5p of proliferation, helping the clinical management of these tumours. Full article

Background: Here, we compared the toxicity profiles of contemporary stereotactic radiosurgery (SRS), modern fractionated radiotherapy (FRT), and transsphenoidal surgery used to treat nonfunctioning pituitary macroadenomas. Methods: We included the data of patients with nonfunctioning pituitary macroadenomas. To compare treatment outcomes, the patients were categorized groups 1 (those receiving modern FRT), 2 (those receiving contemporary SRS), and 3 (those receiving transsphenoidal surgery). The multivariable Cox proportional hazards regression analysis was performed to yielded adjusted hazard ratios (aHRs) and their 95% CIs for local recurrence in groups 2 and 3 compared with group 1. Results: We included the data of 248 patients with nonfunctioning pituitary macroadenomas. The analytical results revealed no significant differences in second primary brain or head and neck cancer, hypopituitarism, or optic nerve injury between the three cohorts. The multivariable Cox proportional hazards regression analysis revealed that compared with group 1, the aHRs (95% CIs) for stroke risk in groups 2 and 3 were 0.37 (0.14–0.99) and 0.51 (0.31–0.84), respectively. Conclusion: Contemporary SRS and transsphenoidal surgery for nonfunctioning pituitary macroadenoma treatment have equivalent toxicity profiles. However, modern FRT for nonfunctioning pituitary macroadenoma treatment might considerably increase stroke risk. Full article

Background: To compare the effects of contemporary stereotactic radiosurgery (SRS), modern fractionated radiotherapy (FRT), and transsphenoidal surgery on nonfunctioning pituitary macroadenoma. Methods: We enrolled patients with nonfunctioning pituitary macroadenoma. To compare treatment outcomes, the patients were categorized into three groups according to the treatment modality: group 1, patients receiving modern FRT; group 2, patients receiving contemporary SRS; and group 3, patients receiving transsphenoidal surgery. Results: In total, 548 patients with nonfunctioning pituitary macroadenoma were selected for our study. Univariate and multivariate Cox regression analysis results indicated that the treatment modalities were significant independent prognostic factors. In multivariable Cox proportional hazard regression analysis, the adjusted hazard ratios (aHR; 95% confidence interval (CI)) of local recurrence were 0.27 (0.10–0.91) and 1.95 (1.25–2.37) for the SRS and transsphenoidal surgery cohorts, respectively, in comparison with the FRT cohort. The aHR (95% CI) of all-cause mortality was 1.03 (0.68–1.56) for the transsphenoidal surgery cohort in comparison with the FRT cohort, without statistical significance. However, the aHR (95% CI) of all-cause mortality was 0.36 (0.15–0.85) for the SRS cohort in comparison with the FRT cohort. Conclusion: Contemporary SRS has optimal effects on local recurrence and survival compared with modern FRT and transsphenoidal surgery. Modern FRT is associated with more favorable local control and equal survival compared with transsphenoidal surgery. Full article

Background: The use of fractionated stereotactic radiotherapy (FSRT) has evolved with technical advances in noninvasive immobilization, radiation delivery, and image guidance. The application of FSRT to pituitary tumours is aimed at reducing toxicity through improved dose conformality and reduced treatment margins. The aim of the present paper is to report our own experience and to review the published data on FSRT for pituitary macroadenomas. Methods: Between September 2000 and October 2005, 13 patients with pituitary macroadenoma underwent FSRT at our institution. In 12 patients, radiotherapy treatment followed surgical resection (transsphenoidal resection in 8, frontal craniotomy in 3, and multiple transsphenoidal resections followed by craniotomy in 1). In 4 patients, the tumours were functional (2 adrenocorticotropic hormone–secreting, 1 prolactinoma, and 1 growth hormone–secreting); the tumours in the remaining patients were clinically non-secretory. Before radiation, 3 patients had panhypopituitarism, and 6 patients had visual field defects. All patients were treated with FSRT using non-coplanar micro–multileaf collimation portals. A median dose of 50.4 Gy (range: 45–60 Gy) was prescribed to the 76.9%–95.2% isodose surface and delivered in 1.8-Gy fractions. The median planning target volume (gross tumour plus 3 mm) was 33.5 cm³ (range: 3.2–75 cm³). Results: After a median follow-up of 24 months (range: 6–60 months), local control was 100%. One patient achieved clinical complete response. Treatment was well tolerated acutely for all patients. Neither radiation-induced optic neuropathy nor any radiation-related endocrine dysfunction was observed in our patients. Conclusions: In accordance with published series, we found FSRT to be safe and effective in the management of large pituitary macroadenomas. Full article