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.

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.

OBJECTIVE: Our aim was to characterise a cohort of patients with Cushing\'s disease (CD) who did not present pituitary adenoma in magnetic resonance imaging (MRI), needing a catheterisation of the inferior petrosal sinus (CIPS), and to study the pathological findings of the pituitary gland in these subjects after transsphenoidal surgery in order to establish the aetiology of CD. Furthermore, we evaluated possible differences in the features of the diagnosis between hyperplasia and adenoma.
METHODS: We included 16 subjects. 17 CIPS were done. Hormonal parameters were measured using standard methods. A microscopic histochemical study following standard procedures and immunohistochemical analysis was performed. The diagnostic criteria for adenoma and hyperplasia were based on the WHO classification.
RESULTS: One patient was excluded for presenting an ACTH-producing bronchial neuroendocrine tumour. The 15 subjects with CD have a positive CIPS test indicating hypophyseal ACTH production. After transsphenoidal surgery, 12 patients showed a microadenoma and three (20%) a corticotroph cell hyperplasia. We found four recurrences after the transsphenoidal surgery (26%), with a mean time for recurrence of 105 months. We found that recurrence was more frequent in subjects with hyperplasia, and in those subjects with lower right/left ACTH ratio.
CONCLUSIONS: Our study, which was focused on patients with CD with no pituitary adenoma detected by MRI and a positive CRH test after CIPS, has found that 20% showed corticotroph cell hyperplasia as the cause of CD. Right/left ACTH ratio after CIPS was useful to differentiate adenoma from hyperplasia. This finding may have important prognostic and treatment implications. More studies are necessary to confirm our result.

OBJECTIVE: 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.

BACKGROUND: Inferior petrosal sinus sampling (IPSS) is indicated in the diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing\'s syndrome (CS), especially when the results of the initial diagnostic tests are discordant.
OBJECTIVE: To describe the patients who underwent this invasive functional test in a tertiary hospital.
METHODS: This was an observational study of a retrospective cohort of patients with ACTH-dependent CS and IPSS between 2004 and 2019. We determined their epidemiological, hormonal, radiological and functional characteristics, and evaluated their diagnostic capacity and optimal cut-off points to differentiate between Cushing\'s disease (CD) and ectopic Cushing\'s syndrome (ECS).
RESULTS: 23 patients were evaluated, of which 65.2% were women with the average age of 42 (36-62) years. ACTH secretion of pituitary origin was evident in 82.6% of the patients and of ectopic origin in 17.4%. Plasma cortisol, urinary free cortisol, and ACTH levels were higher in patients with ECS. Regarding IPSS, the baseline central/peripheral ACTH gradient detected 89.5% of patients with CD and after stimulation with CRH, 100%. The optimal cut-off points in the diagnosis of CD were 2.06 at baseline and 2.49 after CRH stimulation.
CONCLUSIONS: IPSS with CRH stimulation is a test with a high diagnostic accuracy for correctly classifying patients with CD and ECS. The cut-off points of the gradients may be different from the classic ones. Therefore, we recommend that each center perform its own evaluation.

OBJECTIVE: 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.

BACKGROUND: In the past few years, stereotactic radiosurgery (SRS) has been suggested as a good alternative, second line therapy for the management of patients with ACTH-secreting pituitary adenomas. A retrospective study has been conducted in order to evaluate the efficacy and safety of this treatment in these patients.
METHODS: Data were collected on all patients treated with SRS for an ACTH-secreting pituitary adenoma between 1996 and 2008, and with at least one year of follow-up. An analysis was carried out by analysing the return to normal of the hormone levels and clinical improvement rates (including Cushing signs, arterial hypertension), as well as adverse effects, and disease relapse. A return to normal of the 24 hour urinary free cortisol (24-UFC) levels (<100 μg/day) without any ACTH-secretion suppressor drug treatment, was considered as cure or improvement.
RESULTS: A total of 30 patients were treated with SRS, of which 24 were included in the analysis. They all had high 24-UFC levels before the treatment. Cure was achieved in 12 (50%) in a mean of 28 months, and in other 3 patients 24-UFC levels returned to normal with treatment with ketoconazole after the SRS. Cushing signs improved in all cases, as well as arterial hypertension in 13 out of 14 cases. There were relapses after cure consolidation. As far as adverse effects, it should be mentioned that there were 9 cases of new pituitary hormonal dysfunction (the most frequent being hypothyroidism), one radionecrosis, and one case of visual field defect impairment. Radiation-related neoplasm was not detected in any of the cases.
CONCLUSIONS: SRS is an effective treatment for those patients with ACTH-secreting pituitary adenoma in whom surgery has failed, or in those that are not good candidates for it. It showed good rates of hormone levels returning to normal, as well as clinical disease control and a low level of adverse effects.

Pituitary and sellar region tumours account for 10-15% of intracranial benign tumours, with pituitary adenoma being the most common one. In this article, a review is presented on 9 years of experience in surgical treatment using an endoscopic approach of sellar region lesions. The main features of our surgical technique will be explained, as well as the results in clinical and hormonal terms.
A retrospective analysis was conducted on 200 patients operated on due to sellar lesions by the same neurosurgeon (J.E.) using an endoscopic endonasal transsphenoidal approach between February 2006 and February 2015. The cases excluded were, those requiring extended approaches of the skull base, as well as craniopharyngiomas, inflammatory, metastatic, or malignant lesions.
Of the 200 patients treated (59.5% women, mean age of 51.7 years, range: 18-82 years old), there were: 7 Rathke cysts and 193 adenomas (26 micro-adenomas and 165 macro-adenomas). All of them sub-classified according to the degree of invasion of the cavernous sinus (Knosp 0, 1, and 2: 129 cases and Knosp 3 and 4: 71 cases). Total resection was achieved in 143 patients (71.5%), subtotal resection in 39 (19.5%), and partial resection in 18 (9%). In the group of higher occupancy of the cavernous sinus (Knosp 3 and 4) complete resection was achieved in 55.5% (40 of 71 patients). Hormonal remission was achieved in 34 patients with acromegaly (85%), 23 patients with prolactinomas (76%), and 30 patients with Cushing\'s disease (86%).
The results obtained in our series, due to the centralisation of pathology and experience, are comparable to those achieved in pituitary surgery reference centres. Early surgical exploration of cerebrospinal fluid leaks reduces the risk of post-surgical meningitis.

OBJECTIVE: Treatment of Cushing\'s disease poses interesting dilemmas in clinical practice. The aim of our study was to analyze the outcomes of the different treatments, the control and recurrence rates, and the complications derived from them.
METHODS: Data were collected from the clinical records of 22 patients over 18 years of age (86.4% women). They had been diagnosed with Cushing\'s disease between 2000 and 2012, and were monitored at Complejo Hospitalario Universitario-Albacete, Hospital Virgen de la Salud-Toledo Hospital General Universitario de Ciudad Real, Hospital Virgen de la Luz-Cuenca, Hospital Nuestra Señora del Prado-Talavera de la Reina, and Complejo Hospitalario la Mancha Centro-Alcázar de San Juan.
RESULTS: Surgery was the treatment of choice in all patients. Biochemical cure was achieved in 72.2% of patients. Nine patients developed in the early postoperative period diabetes insipidus, which became in 2 patients only. Surprisingly, 3 patients with normal postoperative neurohypophyseal function later developed permanent diabetes insipidus. New hormone deficiencies occurred in 7 patients. Seventeen patients received ketoconazole before surgery (5 of them after surgery also), and 70% of them achieved normal urinary free cortisol levels. Three patients also received radiotherapy, and all of them were cured after a median follow-up of 85.5 months; they developed no tumors or other complications.
CONCLUSIONS: Our study reports the outcomes of management of Cushing\'s disease in non-reference centers for this disease, possibly giving a realistic picture of standard clinical practice for the condition in Spain.

BACKGROUND: Pituitary adenomas account for approximately 15% of intracranial benign tumors. The neurosurgical results achieved since the endoscopic endonasal transsphenoidal (EET) approach was introduced in our center in 2005 are reported here.
METHODS: A retrospective analysis of 121 patients with sellar lesions (58% females, age 55.7 ± 16 years, range 18-82) who underwent EET surgery from February 2005 to January 2012 and were followed up for a mean time of 4.58 years (range 1.08-8.58).
RESULTS: Six Rathke cleft cysts (3 intra-suprasellar, 1 intrasellar, 2 suprasellar); 114 pituitary adenomas (16 microadenomas, 98 macroadenomas), and 1 case of normal MRI were included. Baseline findings included hormonal changes in 59 patients (48,7%) and visual field changes in 38 patients (31%); in 7 patients (5.8%), clinical presentation was pituitary apoplexy. Complete resection was achieved in 77 patients (63.6%), subtotal resection in 29 (23.9%), and partial resection in 15 (12.3%). In patients with Grade 3 and 4 cavernous sinus invasion, resection was subtotal in 30% (12/39) and complete in 46% (18/39). Hormonal remission was achieved in 16 patients with Cushing disease (84%), 18 patients with prolactinoma (78.2%), and 18 patients with acromegaly (85,7%). There were 12 cases (9%) of cerebrospinal fluid leak, 4 cases of diabetes insipidus, and 3 cases with transient SIADH/hyponatremia. Seven patients developed panhypopituitarism. Postoperative mortality rate was 2.4%. One hundred and three patients (85.3%) were discharged from the hospital less than 48 hours after surgery.
CONCLUSIONS: Our results are similar to those reported by renowned pituitary units. Results achieved using an endoscopic approach in pituitary neurosurgery are better than those of microneurosurgery for cavernous sinus invasion.