Glucose metabolism outcomes after pituitary surgery in patients with acromegaly.

AIM: To investigate the impact of pituitary surgery on glucose metabolism and to identify predictors of remission of diabetes after pituitary surgery in patients with acromegaly. METHODS: A national multicenter retrospective study of patients with acromegaly undergoing transsphenoidal surgery for the first time at 33 tertiary Spanish hospitals (ACRO-SPAIN study) was performed. Surgical remission of acromegaly was evaluated according to the 2000 and 2010 criteria. RESULTS: A total of 604 acromegaly patients were included in the study with a total median follow up of 91 months (interquartile range [IQR] 45-163). At the acromegaly diagnosis, 23.8% of the patients had diabetes mellitus (DM) with a median glycated hemoglobin (HbA1c) of 6.9% (IQR 6.4-7.9) [51.9 mmol/mol (IQR 46.4-62.8)]. In the multivariate analysis, older age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), dyslipidemia (OR 5.25, 95% CI 2.81 to 9.79), arthropathy (OR 1.39, 95% CI 2.82 to 9.79), and higher IGF-I levels (OR 1.30, 95% CI 1.05 to 1.60) were associated with a greater prevalence of DM. At the last follow-up visit after surgery, 21.1% of the DM patients (56.7% of them with surgical remission of acromegaly) experienced diabetes remission. The cure rate of DM was more common in older patients (hazard ratio [HR] 1.77, 95% CI 1.31 to 2.43), when surgical cure was achieved (HR 2.10, 95% CI 1.01 to 4.37) and when anterior pituitary function was not affected after surgery (HR 3.38, 95% CI 1.17 to 9.75). CONCLUSION: Glucose metabolism improved in patients with acromegaly after surgery and 21% of the diabetic patients experienced diabetes remission; being more frequent in patients of older age, and those who experienced surgical cure and those with preserved anterior pituitary function after surgery.

Clinical presentation and surgical outcomes of very large and giant pituitary adenomas: 80 cases in a cohort study of 306 patients with pituitary adenomas.

PURPOSE: To identify differences in the presentation and surgical outcomes between very large (30-39 mm) and giant (≥ 40 mm) (LARGE group) pituitary adenomas (PAs) compared to the smaller group (< 30 mm) (non-LARGE group). METHODS: Eighty patients with very large (n = 44) or giant (n = 36) PAs and 226 patients in the non-LARGE group who underwent tumor resection by pituitary surgery between 2008 and 2023 were studied. Hormonal, radiological, ophthalmological, and pathological data, and surgical outcomes were evaluated. RESULTS: Preoperatively, patients of the LARGE group presented more frequently with visual impairment (82.5% vs. 22.1%, P < 0.001) and with pituitary apoplexy (15.0% vs. 2.7%, P < 0.001) than the non-LARGE group. Moreover, the LARGE group were more commonly associated with preoperative panhypopituitarism (28.8% vs. 6.2%, P < 0.001). This group presented cavernous sinus invasion more frequently (71.3% vs. 23.9%, P < 0.001). The non-LARGE group achieved surgical cure more often than the LARGE group (79.7% vs. 50.0%, P < 0.001), and the rate of major complications was higher in the latest (8.8% vs. 1.3%, P < 0.004). CONCLUSIONS: PAs ≥ 30 mm are most frequently accompanied by hormonal dysfunction, cavernous sinus invasion, and visual impairment. All this implies lower resection rates and higher postoperative complications than the smaller adenomas, posing a real surgical challenge.

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.

Craniopharyngioma in the Elderly: A Multicenter and Nationwide Study in Spain.

BACKGROUND: Craniopharyngioma (CP) is a rare tumor in the elderly whose clinical features and prognosis are not well known in this population. AIM: To evaluate the clinicopathological features and therapeutic outcomes of CP diagnosed in the elderly. PATIENTS AND METHODS: This was a retrospective, multicenter, national study of CP patients diagnosed over the age of 65 years and surgically treated. RESULTS: From a total of 384 adult CP patients, we selected 53 (13.8%) patients (27 women [50.9%], mean age 72.3 ± 5.1 years [range 65-83 years]) diagnosed after the age of 65 years. The most common clinical symptoms were visual field defects (71.2%) followed by headache (45.3%). The maximum tumor diameter was 2.9 ± 1.1 cm. In most patients, the tumor was suprasellar (96.2%) and mixed (solid-cystic) (58.5%). The surgical approach most commonly used was transcranial surgery (52.8%), and more than half of the patients (54.7%) underwent subtotal resection (STR). Adamantinomatous CP and papillary CP were present in 51 and 45.1%, respectively, with mixed forms in the remaining. Surgery was accompanied by an improvement in visual field defects and in headaches; however, pituitary hormonal hypofunction increased, mainly at the expense of an increase in the prevalence of diabetes insipidus (DI) (from 3.9 to 69.2%). Near-total resection (NTR) was associated with a higher prevalence of DI compared with subtotal resection (87.5 vs. 53.6%, p = 0.008). Patients were followed for 46.7 ± 40.8 months. The mortality rate was 39.6% with a median survival time of 88 (95% CI: 57-118) months. DI at last visit was associated with a lower survival. CONCLUSION: CP diagnosed in the elderly shows a similar distribution by sex and histologic forms than that diagnosed at younger ages. At presentation, visual field alterations and headaches are the main clinical symptoms which improve substantially with surgery. However, surgery, mainly NTR, is accompanied by worsening of pituitary function, especially DI, which seems to be a predictor of mortality in this population.

Deep Brain Stimulation in Posttraumatic Tremor: A Series of Cases and Literature Review.

BACKGROUND: Posttraumatic tremor (PTT) is the most frequent movement disorder secondary to cranioencephalic trauma and can be persistent and disabling. OBJECTIVES: We review and assess the efficacy of deep brain stimulation (DBS) at the VIM/VOP/ZI (ventralis intermedius/ventrooralis posterior/zona incerta) complex level for the treatment of PTT. METHODS: During the period from 1999 to 2014, 5 patients diagnosed with PTT were selected who had experienced a major deterioration in their quality of life without improvement during medical treatment for more than 1 year. They underwent surgery for DBS at the VIM/VOP/ZI complex level, and the modified tremor scale before and after surgery was used for their follow-up. RESULTS: Each patient showed improvements in their symptoms after DBS compared with baseline, which was moderate (II) in 2 cases and marked (III) in the other cases. All of the improvements were maintained with chronic DBS, without tremor rebound. CONCLUSIONS: Stimulation of the contralateral VIM/VOP/ZI complex resulted in a noticeable improvement in tremor and recovery of independence in basic daily activities in patients with PTT.

Exploring risk factors of severe pituitary apoplexy: Insights from a multicenter study of 71 cases.

PURPOSE: To identify clinical and radiological factors associated with a higher risk of developing a severe pituitary apoplexy (PA). METHODS: Multicenter retrospective study of patients presenting with clinical PA in three Spanish tertiary hospitals of Madrid between 2008 and 2022. We classified PA as severe when presenting with an altered level of consciousness (Glasgow Coma Scale (GCS) < 15) or visual involvement. RESULTS: A total of 71 PA cases were identified, of whom 80.28% (n = 57) were classified as severe PA. The median age was 60 (18 to 85 years old) and 67.6% (n = 48) were male. Most patients had macroadenomas, except for one patient with a microadenoma of 9 mm. Headache was the most common presenting symptom (90.1%) and anticoagulation was the most frequent predisposing risk factor, but it was not associated with a higher risk for severe PA (odds ratio [OR] 1.13 [0.21-5.90]). Severe cases were associated with male gender (OR 5.53 [1.59-19.27]), tumor size >20 mm (OR 17.67 [4.07-76.64]), and Knosp grade ≥2 (OR 9.6 [2.38-38.73]). In the multivariant analysis, the only variables associated with a higher risk for severe PA were tumor size and Knosp grade. Surgery was more common in severe PA than in non-severe (91.2% vs. 64.3%, P = 0.009). CONCLUSION: A tumor size >20 mm and cavernous sinus invasion are risk factors for developing a severe PA. These risk factors can stratify patients at a higher risk of a worse clinical picture, and subsequently, more need of decompressive surgery.

Pegvisomant and pasireotide in PRL and GH co-secreting vs GH-secreting Pit-NETs.

The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

Differences between GH and PRL co-secreting and GH-secreting pituitary adenomas. A series of 604 cases.

PURPOSE: To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). METHODS: Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). RESULTS: GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. CONCLUSIONS: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

Executive summary of the expert consensus document from the Spanish Society of Neurosurgery and the Spanish Society of Endocrinology and Nutrition: Clinical recommendations on the perioperative management of pituitary tumors.

Pituitary tumors (PT) account for 15% of intracranial tumors affect 10.7%-14.4% of the population although the incidence of clinically relevant PT is 5.1 cases/100,000 inhabitants. Surgical treatment is indicated in PTs with hormone hypersecretion (except for prolactin-producing PTs) and those with local compressive or global neurological symptoms. Multidisciplinary care, is essential for patients with PTs, preferably delivered in a center of excellence and based on a well-defined care protocol. In order to facilitate and standardize the clinical procedures for this type of tumor, this document gathers the positioning of the Neuroendocrinology Knowledge Area of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Society of Neurosurgery (SENEC) on the management of patients with PTs and their preoperative, surgical and postoperative follow-up.

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.

Presurgical predictive factors of surgical remission in Cushing's disease. Study of 32 cases.

PURPOSE: Identify presurgical factors associated with surgical remission in Cushing's disease (CD). METHODS: All the patients with ACTH-dependent Cushing's Syndrome in follow-up at our centre between 2014-2021 (n=40) were identified. Those patients with CD diagnosis who underwent transsphenoidal surgery by the same neurosurgeon (n=32) were included. Surgical remission was defined as plasma cortisol <1.8µg/dl and normal or low urinary free cortisol (UFC) after surgery. RESULTS: Sixty-three per cent (n=20) were women, and the mean age at diagnosis was 42.3±17.9 years. Six patients had macroadenomas, 17 had microadenomas, and in the other 9 patients, no pituitary lesion was identified on the MRI. Seven patients were previously operated on in another centre. Surgical remission was achieved in 75% (n=24). Only three patients experienced recurrence. No association between pre-surgical demographic (age, sex, comorbidities) or hormonal (UFC, ACTH, late-night salivary cortisol levels) characteristics and the probability of surgical remission was observed. The only variable associated with a greater chance of remission was the presurgical visualisation of the adenoma on MRI (OR 8.3, P=0.02). It was also observed that patients with a history of a previous pituitary surgery had a lower tendency to achieve remission, although statistical significance was not reached (OR 0.17, P=0.09). CONCLUSIONS: In our experience, 75% of patients with CD achieved biochemical cure after the intervention. Surgical remission was up to eight times more frequent in those patients in whom the adenoma was visualised before the intervention, but no other presurgical predictive factors of cure were identified.

Diagnosis and Therapeutic Management of Ventricular Gangliogliomas: An Illustrated Review.

BACKGROUND: Gangliogliomas (GGs) are extremely rare benign neoplasms frequently located within the temporal lobe that usually present with seizures. GGs growing predominantly within the ventricular system (VGGs) are even more infrequent, so definite conclusions concerning their diagnosis and therapeutic management are lacking. METHODS: A retrospective review of case reports of VGGs was performed from the introduction of modern imaging techniques, including 4 new illustrative cases treated in our department. RESULTS: Thirty-four cases were collected. Ages ranged from 10 to 71 years (mean, 26.62 years), and 55.9% were male. Most patients developed symptoms related to high intracranial pressure. The lateral ventricles were predominantly involved (58.8%). Obstructive hydrocephalus was observed in 54.5% of patients. Cystic degeneration and calcification were frequently observed. Surgical treatment was carried out in all cases. Morbidity and mortality were 17.6% and 2.9%, respectively. Gross total tumor resection was achieved in 64.5% of patients. Four patients experienced tumor dissemination along the neural axis. More than 90% of patients maintained a good functional status at last follow-up. CONCLUSIONS: Despite their low incidence, a diagnosis of VGGs should be considered in young male adults who progressively develop intracranial hypertension, caused by a ventricular mass showing signs of cystic degeneration and calcification. Maximal and safe surgical resection represents the gold standard for the treatment of symptomatic VGGs, although total removal is frequently precluded by difficulties in defining appropriate tumor boundaries. Adjuvant radiotherapy should be considered if an incomplete resection was carried out, especially in World Health Organization grade III neoplasms.

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.

Giant Non-Functioning Pituitary Adenoma: Clinical Characteristics and Therapeutic Outcomes.

BACKGROUND: Giant pituitary adenoma (≥4 cm) is a rare tumor whose clinical features and prognosis are not well known. AIM: To evaluate the clinical characteristics and therapeutic outcomes of giant non-functioning PA (gNFPA). PATIENTS AND METHODS: A retrospective multicenter study of gNFPA patients diagnosed in a 12-year period was performed. In each patient, clinical data and therapeutic outcomes were registered. RESULTS: Forty patients (24 men, age 54.2 ± 16.2 years) were studied. The maximum tumor diameter [median (interquartile range)] was 4.6 cm (4.1-5.1). Women had larger tumors [4.8 cm (4.2-5.4) vs. 4.5 cm (4.0-4.9); p=0.048]. Hypopituitarism [partial (n=22, 55%) or complete (n=9, 22.5%)] at diagnosis was present in 77.5% of the patients. Visual field defects were found in 90.9%. The most used surgical technique was endoscopic endonasal transsphenoidal (EET) surgery (n=31, 77.5%). Radiotherapy was used in 11 (27.5%) patients (median dose 50.4 Gy, range 50-54). Thirty-seven patients were followed for 36 months (10-67 months). Although more than half of these patients showed tumor persistence (n=25, 67.6%), tumor size was significantly reduced [0.8 cm (0-2.5); p<0.001]. At last visit, 12 patients (32.4%) showed absence of tumor on MRI. Hypopituitarism rate was similar (75.0%), although with significant changes (p<0.001) in the distribution of the type of hypopituitarism. The absence of tumor at the last visit was positively associated with positive immunohistochemical staining for FSH (p=0.01) and LH (p=0.006) and negatively with female sex (p=0.011), cavernous sinus invasion (p=0.005) and the presence of Knosp grade 4 (p=0.013). CONCLUSION: gNFPAs are more frequent in men but tumors are larger in women. Surgical treatment is followed by a complete tumor resection rate of approximately 30%. Positive immunostaining for gonadotropins is associated with tumor absence at last revision, while female sex and invasion of the cavernous sinuses with tumor persistence.

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.

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.

Presurgical predictive factors of surgical remission in Cushing's disease. Study of 32 cases.

PURPOSE: Identify presurgical factors associated with surgical remission in Cushing's disease (CD). METHODS: All the patients with ACTH-dependent Cushing's Syndrome in follow-up at our centre between 2014-2021 (n=40) were identified. Those patients with CD diagnosis who underwent transsphenoidal surgery by the same neurosurgeon (n=32) were included. Surgical remission was defined as plasma cortisol <1.8µg/dl and normal or low urinary free cortisol (UFC) after surgery. RESULTS: Sixty-three per cent (n=20) were women, and the mean age at diagnosis was 42.3±17.9 years. Six patients had macroadenomas, 17 had microadenomas, and in the other 9 patients, no pituitary lesion was identified on the MRI. Seven patients were previously operated on in another centre. Surgical remission was achieved in 75% (n=24). Only three patients experienced recurrence. No association between pre-surgical demographic (age, sex, comorbidities) or hormonal (UFC, ACTH, late-night salivary cortisol levels) characteristics and the probability of surgical remission was observed. The only variable associated with a greater chance of remission was the presurgical visualisation of the adenoma on MRI (OR 8.3, P=0.02). It was also observed that patients with a history of a previous pituitary surgery had a lower tendency to achieve remission, although statistical significance was not reached (OR 0.17, P=0.09). CONCLUSIONS: In our experience, 75% of patients with CD achieved biochemical cure after the intervention. Surgical remission was up to eight times more frequent in those patients in whom the adenoma was visualised before the intervention, but no other presurgical predictive factors of cure were identified.

Multidisciplinary protocol of preoperative and surgical management of patients with pituitary tumors candidates to pituitary surgery.

The optimal planning of preoperative diagnosis, management and treatment of pituitary tumors (PT) candidates to pituitary surgery (PS) requires a multidisciplinary approach involving a team of endocrinologists, neurosurgeons, ENT, neuro-ophthalmologists and neuroradiologists with experience in pituitary diseases. Such teams improve surgical results, minimize complications and facilitate their correct treatment if occurring, and optimize the hormonal, ophthalmological and radiological preoperative and follow-up evaluation. We have developed a clinical practice protocol for patients with PT who are candidates to PS based on the most recent national and international guidelines and the relevant literature regarding PT published in the last years. The protocol has been elaborated by a multidisciplinary team of a Spanish Pituitary Tumor Center of Excellence (PTCE) that includes at least one neurosurgeon, ENT, neuroradiologist, neuro-ophthalmologist, endocrine pathologist and endocrinologist specialized in pituitary diseases. We elaborated this guideline with the aim of sharing our experience with other centers involved in the perioperative and surgical management of PT thereby facilitating the management of patients undergoing PS.