Development and validation of a prediction model for consistency of pituitary adenoma: the PiTCon score.

PURPOSE: Pituitary adenomas (PAs) usually have a soft consistency, facilitating gross total resection. However, 5-13% of PAs with fibrous consistency are challenging to remove entirely and are accompanied by greater morbimortality. This study aims to identify the clinical and radiological characteristics that correlate with PA fibrous consistency preoperatively. A simple scoring system has been proposed to predict incidence of fibrous PAs. MATERIALS AND METHODS: Consecutive interventions (226) were analyzed, all performed through an endoscopic endonasal transsphenoidal approach. Univariable and multivariable logistic regression analysis was performed. Hosmer-Lemeshow test and receiver operating characteristic (ROC) curves were assessed to evaluate the model. A point scoring system (PiTCon) was derived based on the multivariable regression model. Our study aimed to identify the clinical and radiological characteristics that correlate with fibrous tumor consistency preoperatively. RESULTS: The best diagnostic accuracy for predicting PA consistency consisted of five predictive factors: age, compressive symptoms, panhypopituitarism, craniocaudal extension of the PA in mm, and prior surgery. The multivariable model achieved good discrimination with an area under the curve (AUC) of the ROC curve being 0.82 and the 95% CI 0.76 to 0.88. Internal validation yielded an optimism-adjusted C-statistic of 0.80 (95% CI 0.74 to 0.86). A point scoring system (PiTCon score) was designed using the best predictive model. CONCLUSIONS: PA consistency can be estimated preoperatively regarding clinical and radiological characteristics. We propose a point-based scoring system (PiTCon score) that can better guide neurosurgeons in clinical decision-making and surgical risk assessment and help establish and describe patient prognosis.

Differences in clinical, hormonal, and radiological presentation and in surgical outcomes in patients presenting with and without pituitary apoplexy. A multicenter study of 245 cases.

PURPOSE: To compare the clinical, hormonal, and radiological presentation and surgical outcomes of patients with macroadenomas presenting with pituitary apoplexy and patients not presenting pituitary apoplexy. METHODS: Multicentre retrospective study of patients presenting with macroadenomas and pituitary apoplexy in three Spanish tertiary hospitals between 2008 and 2022. We selected as control group (non-pituitary apoplexy), patients with pituitary macroadenomas without apoplexy who underwent pituitary surgery between 2008 and 2020. RESULTS: A total of 60 patients with apoplexy and 185 without apoplexy were enrolled. Patients with pituitary apoplexy were more frequently men (70% vs. 48.1%, p = 0.003), had higher prevalence of hypertension (43.3% vs. 26.0%, p = 0.011) and of obesity (23.3% vs. 9.7%, P = 0.007), were under treatment with anticoagulants more commonly (11.7% vs. 4.3%, P = 0.039) and had larger (27.5 ± 11.03 vs. 23.6 ± 12.55 mm, p = 0.035) and invasive pituitary macroadenomas more frequently (85.7% vs. 44.3%, P < 0.001) than those without apoplexy. Surgical remission was more frequent in patients with pituitary apoplexy than those without apoplexy (OR 4.55, P < 0.001), but they developed new pituitary deficits (OR 13.29, P < 0.001) and permanent diabetes insipidus (OR 3.40, P = 0.022) more commonly. However, visual improvement (OR 6.52, p < 0.001) and complete pituitary function recovery (OR 2.37, P < 0.001) was more common in patients without apoplexy. CONCLUSION: Surgical resection is more common in patients presenting with pituitary apoplexy than those without apoplexy; however, visual improvement and complete recovery of pituitary function is more common in patients without apoplexy. The risk of new pituitary deficits and permanent diabetes insipidus is higher in patients with apoplexy than in those without it.

Endoscopic endonasal approach to pituitary adenomas: Impact on adenohypophyseal function. Study of 231 cases / Abordaje endoscópico endonasal en adenomas hipofisarios: impacto en la función adenohipofisaria. Estudio de 231 casos

Purpose To identify presurgical and surgical factors associated with the development of hypopituitarism and its recovery after endoscopic endonasal transsphenoidal (EET) resection of pituitary adenomas (PAs). Methods Retrospective study of patients with PAs operated by the same neurosurgeon through an EET approach in two Spanish tertiary hospitals in ten years. Results 242 pituitary surgeries performed in 231 patients were analyzed. In the 154 surgeries performed in 146 patients with non-functioning PAs (NFPAs), 46.8% (n=72) presented presurgical hypopituitarism. After PAs resection, 41 of these (56.9%) normalized pituitary function and 11 of 82 patients with preoperative normal function (13.4%) developed new pituitary deficits. Patients with preoperative visual impairment (OR=3.9, p=0.046) and operated in the first four years of the neurosurgeon's learning curve (OR=5.7, p=0.016) presented a higher risk of developing postoperative hypopituitarism.Of the 88 surgeries in 85 patients with functioning PAs (FPAs), 23.9% presented presurgical hypopituitarism, and 47.6% of those recovered after surgery. 9% of the cases with preoperative normal function developed new pituitary deficit/s. Diabetic patients presented a higher risk of persistence of hypopituitarism (OR=10.5, p=0.024). Patients with presurgical visual impairment (OR=30.0, p=0.010) and PAs>3cm (OR=14.0, p=0.027) had higher risk of developing new pituitary deficits. Conclusion Approximately 50% of patients with PAs and preoperative hypopituitarism recover pituitary function after EET surgery. 10% of patients with normal function develop new deficits. Patients with NFPAs with visual involvement and operated in the first four years of neurosurgeon's learning curve, and FPAs patients with presurgical visual impairment and tumor size>3cm have a higher risk of postoperative hypopituitarism. (AU)

Objetivo Identificar factores prequirúrgicos y quirúrgicos asociados con el desarrollo de hipopituitarismo y de su recuperación tras la resección transesfenoidal endoscópica endonasal (TEE) de adenomas hipofisarios (AH). Métodos Estudio retrospectivo de pacientes con AH intervenidos mediante abordaje TEE en dos hospitales terciarios por el mismo neurocirujano a lo largo de diez años. Resultados Se analizaron 242 cirugías hipofisarias realizadas 231 pacientes. De las 154 cirugías realizadas en 146 pacientes con AH no funcionantes (AHNF), el 46,8% (n=72) presentó hipopituitarismo prequirúrgico. Tras la resección del AH, 41 de los 72 pacientes (56,9%) normalizaron la función hormonal y 11 de 82 pacientes con función preoperatoria normal (13,4%) desarrollaron nuevos déficits hormonales. Los pacientes con afectación visual preoperatoria (OR=3,9, p=0,046) y operados en los primeros cuatro años de la curva de aprendizaje del neurocirujano (OR=5,7, p=0,016) presentaron mayor riesgo de desarrollar hipopituitarismo posoperatorio.De las 88 cirugías realizadas en 85 pacientes con AH funcionantes (AHF), el 23,9% presentó hipopituitarismo prequirúrgico y el 47,6% de los que presentaban hipopituitarismo se recuperaron tras la cirugía. El 9% de los pacientes con función preoperatoria normal desarrollaron nuevos déficits hormonales. Los pacientes diabéticos presentaron mayor riesgo de persistencia del hipopituitarismo (OR=10,5, p=0,024). Los pacientes con afectación visual prequirúrgica (OR=30,0, p=0,010) y AH>3cm (OR=14,0, p=0,027) presentaron un mayor riesgo de desarrollar nuevos déficits hormonales. Conclusión Aproximadamente el 50% de los pacientes con AH e hipopituitarismo preoperatorio recuperan la función hipofisaria después de la cirugía TEE. El 10% de los pacientes con función normal desarrollan nuevos déficits. Los pacientes con AHNF con afectación visual y operados en los primeros cuatro años de la curva de aprendizaje del neurocirujano ... (AU)

Endoscopic endonasal approach to pituitary adenomas: Impact on adenohypophyseal function. Study of 231 cases.

PURPOSE: To identify presurgical and surgical factors associated with the development of hypopituitarism and its recovery after endoscopic endonasal transsphenoidal (EET) resection of pituitary adenomas (PAs). METHODS: Retrospective study of patients with PAs operated by the same neurosurgeon through an EET approach in two Spanish tertiary hospitals in ten years. RESULTS: 242 pituitary surgeries performed in 231 patients were analyzed. In the 154 surgeries performed in 146 patients with non-functioning PAs (NFPAs), 46.8% (n=72) presented presurgical hypopituitarism. After PAs resection, 41 of these (56.9%) normalized pituitary function and 11 of 82 patients with preoperative normal function (13.4%) developed new pituitary deficits. Patients with preoperative visual impairment (OR=3.9, p=0.046) and operated in the first four years of the neurosurgeon's learning curve (OR=5.7, p=0.016) presented a higher risk of developing postoperative hypopituitarism. Of the 88 surgeries in 85 patients with functioning PAs (FPAs), 23.9% presented presurgical hypopituitarism, and 47.6% of those recovered after surgery. 9% of the cases with preoperative normal function developed new pituitary deficit/s. Diabetic patients presented a higher risk of persistence of hypopituitarism (OR=10.5, p=0.024). Patients with presurgical visual impairment (OR=30.0, p=0.010) and PAs>3cm (OR=14.0, p=0.027) had higher risk of developing new pituitary deficits. CONCLUSION: Approximately 50% of patients with PAs and preoperative hypopituitarism recover pituitary function after EET surgery. 10% of patients with normal function develop new deficits. Patients with NFPAs with visual involvement and operated in the first four years of neurosurgeon's learning curve, and FPAs patients with presurgical visual impairment and tumor size>3cm have a higher risk of postoperative hypopituitarism.

Clinical relevance of tumor consistency in pituitary adenoma.

PURPOSE: To review the clinical relevance of pituitary adenoma (PA) consistency and its relationship to clinical presentation, radiologic and histopathological characteristics, and surgical outcomes. BACKGROUND: PA consistency is a critical factor influencing operative planning, surgical outcomes, and patient counseling. There is no validated classification of PA consistency in the literature, and there are no current preoperative variables capable of predicting it. REVIEW: We conducted a thorough literature review of the Medline, Embase, Web of Science, and Cochrane Library databases. The inclusion criteria were all articles that described PA consistency and correlated it with preoperative aspects, radiological, pathological, and operative findings, or clinical outcomes. DISCUSSION: Although most authors differentiate easily aspirated (soft) tumors from those that are not (fibrous, might require prior fragmentation), there is no universally accepted PA consistency classification. Fibrous PA tends to be hypointense on T2WI and has lower apparent diffusion coefficient (ADC) values. Fibrous tumors seemed to present higher invasion into neighboring structures, including the cavernous sinus. Several articles suggest that dopamine agonists could increase PA consistency and that prior surgery and radiotherapy also make PA more fibrous. The anatomopathological studies identify collagen as being mainly responsible for fibrous consistency of adenomas. CONCLUSIONS: Preoperative knowledge of PA consistency affords the neurosurgeon substantial benefit, which clearly appears to be relevant to surgical planning, risks, and surgery outcomes. It could also encourage the centralization of these high complexity tumors in reference centers. Further studies may be enhanced by applying standard consistency classification of the PA and analyzing a more extensive and prospective series of fibrous PA.

Radiological Knosp, Revised-Knosp, and Hardy-Wilson Classifications for the Prediction of Surgical Outcomes in the Endoscopic Endonasal Surgery of Pituitary Adenomas: Study of 228 Cases.

PURPOSE: To evaluate which radiological classification, Knosp, revised-Knosp, or Hardy-Wilson classification, is better for the prediction of surgical outcomes in the endoscopic endonasal transsphenoidal (EET) surgery of pituitary adenomas (PAs). METHODS: This is a retrospective study of patients with PAs who underwent EET PA resection for the first time between January 2009 and December 2020. Radiological cavernous sinus invasiveness was defined as a Knosp or revised-Knosp grade >2 or a grade E in the Hardy-Wilson classification. RESULTS: A total of 228 patients with PAs were included. Cavernous sinus invasion was evident in 35.1% and suprasellar extension was evident in 74.6%. Overall, surgical cure was achieved in 64.3% of patients. Surgical cure was lower in invasive PAs than in non-invasive PAs (28.8% vs. 83.1%, p < 0.0001), and the risk of major complications was higher (13.8% vs. 3.4%, p = 0.003). The rate of surgical cure decreased as the grade of Knosp increased (p < 0.001), whereas the risk of complications increased (p < 0.001). Patients with Knosp 3B PAs tended to achieve surgical cure less commonly than Knosp 3A PAs (30.0% vs. 56.0%, p = 0.164). Similar results were observed based on the invasion and extension of Hardy-Wilson classification (stage A-C 83.1% vs. E 28.8% p < 0.0001, grade 0-II 81.1% vs. III-IV 59.7% p = 0.008). The Knosp classification offered the greatest diagnostic accuracy for the prediction of surgical cure (AUC 0.820), whereas the invasion Hardy-Wilson classification lacked utility for this purpose (AUC 0.654). CONCLUSION: The Knosp classifications offer a good orientation for the estimation of surgical cure and the risk of complications in patients with PAs submitted to EET surgery. However, the invasion Hardy-Wilson scale lacks utility for this purpose.

Presurgical somatostatin receptor ligand treatment does not affect tumor consistency in GH-secreting pituitary macroadenomas.

PURPOSE: To evaluate whether presurgical treatment using long-acting somatostatin receptor ligands (SRL) may change pituitary tumor consistency and improve surgical outcome in GH-secreting pituitary macroadenomas. METHODS: Retrospective study of 40 patients with GH-secreting pituitary macroadenomas operated for the first time by endoscopic transsphenoidal approach. Tumor consistency was evaluated intraoperatively and then correlated with histopathological fibrosis parameters and surgical outcomes. Surgical remission was reported based on the 2010 criteria. RESULTS: The mean tumor size of GH-secreting macroadenomas was of 16.9 ± 8.2 mm and 25 were invasive pituitary adenomas (PAs). Presurgical treatment with long-acting SRL was performed in 17 patients (11 lanreotide, 6 octreotide). The cure rate was higher in those patients pre-treated with monthly doses ≥30 mg of octreotide or ≥90 mg of lanreotide than in those treated with lower doses or untreated (8/11 (72.7%) vs 11/29 (37.9%), P = 0.049). However, although the proportion of soft tumors increased as higher doses of SRL were considered in the pre-treated group, no statistical significance was reached, even when the highest approved monthly doses were used (6/6 (100%) vs 23/34 (67.7%), P = 0.102). Moreover, we found that the remission rate was similar between fibrous and soft tumors (P = 0.873) and also of surgical complications (P = 0.859), despite of the higher prevalence of Knosp >2 (P = 0.035) and very large PA (P = 0.025) in fibrous tumors than in soft tumors. CONCLUSIONS: Although presurgical treatment with high doses of SRL was associated with a 2.2-fold greater chance of surgical remission, this benefit was not related with changes in tumor consistency induced by the presurgical treatment.

Status and clinical and radiological predictive factors of presurgical anterior pituitary function in pituitary adenomas. Study of 232 patients.

PURPOSE: To investigate the status of preoperative anterior pituitary function in patients undergoing pituitary adenoma (PA) resection and to identify factors associated with preoperative anterior pituitary dysfunction (APD). METHODS: Patients with functioning and nonfunctioning PAs who underwent pituitary adenoma resection for first time, from January 2009 to December 2019 were analyzed. RESULTS: Total sample included 232 patients; 123 (53.2%) females, mean age at diagnosis was 53.3 years. Sixty-three percent presented as nonfunctioning PAs and 37.1% as functioning PAs. Eighty-eight percent were macroadenomas and 34.9% had cavernous sinus invasion. APD was demonstrated in 36.2% (n = 84) of the patients. The FSH/LH deficit was the most frequent anterior pituitary deficit (31.9%); followed by ACTH (18.1%); TSH (16.4%) and GH (13.8%). We identified as independent risk factors of APD, male sex (OR = 6.1, 95% CI = 3.3-11.0); age (OR = 1.03 for each year, 95% CI = 1.01-1.04), diabetes mellitus (OR = 3.5, 95% CI = 1.63-7.69), pituitary apoplexy presentation (OR = 4.3, 95% CI = 1.3-14.5) and tumor size (OR = 1.06 for each mm, 95% CI = 1.04-1.09). Nonfunctioning PAs (NFPA) had higher risk of APD than functioning PAs (FPA) (OR = 2.8 (95% CI = 1.5-5.0), but these differences disappeared after adjusted by tumor size (OR adjusted by tumor size = 1.7, 95% CI = 0.9-3.3). The tumor size with the highest diagnostic accuracy to predict hypopituitarism was 22 mm (sensitivity of 61.9% and specificity of 70.1%). CONCLUSION: More than one third of PAs candidates for surgery had APD. The male sex, diabetes, an older age, pituitary apoplexy, and larger PAs were risk factors of APD. Hence, in these patients, the hormonal study should be prioritized and the need for dynamic tests must be carefully assessed.