Redefining cerebellar assessment: A comprehensive review of the cerebellum's cognitive and affective roles and the efficacy of CCAS scales.

Background: Emerging research expands our understanding of the cerebellum beyond motor control to include cognitive, emotional, and autonomic functions. This review examines the cerebellum's complex role, spotlighting Schmahmann's syndrome, or cerebellar cognitive affective syndrome (CCAS), which impairs executive functions, language, and spatial processing. It emphasizes advancements in diagnosing CCAS and the imperative of developing superior diagnostic tools for managing cerebellar pathologies effectively. Methods: A comprehensive literature search was performed using databases such as PubMed, OVID Embase, and OVID Medline. Using the keywords "cerebellar cognitive, affective syndrome" and "Schmahmann syndrome," the search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines for systemic review, in which the selection process narrowed down an initial set of 54 articles to 12, focusing on the impact of the CCAS scale on diagnosing and understanding Schmahmann's syndrome. Results: The review's analysis confirms the cerebellum's roles in motor and cognitive functions and underscores the CCAS scale as a significant advancement in detecting cerebellar deficits, surpassing traditional assessments such as the mini-mental state examination and Montreal cognitive assessment. Conclusion: This review emphasizes the importance of understanding the cerebellum's involvement in cognition and emotion and the crucial role of the CCAS scale for identifying cerebellar impairments. It calls for better diagnostic tools to assess CCAS accurately and suggests enhancing the CCAS Scale to reflect cultural and educational diversity. This will improve the diagnosis and treatment of cerebellar disorders, promoting a comprehensive neurological perspective on the cerebellum's functions.

Elevated risk of recurrence and retreatment for silent pituitary adenomas.

PURPOSE: Pituitary adenomas are the most common tumor of the pituitary gland and comprise nearly 15% of all intracranial masses. These tumors are stratified into functional or silent categories based on their pattern of hormone expression and secretion. Preliminary evidence supports differential clinical outcomes between some functional pituitary adenoma (FPA) subtypes and silent pituitary adenoma (SPA) subtypes. METHODS: We collected and analyzed the medical records of all patients undergoing resection of SPAs or FPAs from a single high-volume neurosurgeon between 2007 and 2018 at Brigham and Women's Hospital. Descriptive statistics and the Mantel-Cox log-rank test were used to identify differences in outcomes between these cohorts, and multivariate logistic regression was used to identify predictors of radiographic recurrence for SPAs. RESULTS: Our cohort included 88 SPAs and 200 FPAs. The majority of patients in both cohorts were female (48.9% of SPAs and 63.5% of FPAs). SPAs were larger in median diameter than FPAs (2.1 cm vs. 1.2 cm, p < 0.001). The most frequent subtypes of SPA were gonadotrophs (55.7%) and corticotrophs (30.7%). Gross total resection (GTR) was achieved in 70.1% of SPA resections and 86.0% of FPA resections (p < 0.001). SPAs had a higher likelihood of recurring (hazard ratio [HR] 3.2, 95% confidence interval [95%CI] 1.6-7.2) and a higher likelihood of requiring retreatment for recurrence (HR 2.5; 95%CI 1.0-6.1). Subset analyses revealed that recurrence and retreatment were more both likely for subtotally resected SPAs than subtotally resected FPAs, but this pattern was not observed in SPAs and FPAs after GTR. Among SPAs, recurrence was associated with STR (odds ratio [OR] 9.3; 95%CI 1.4-64.0) and younger age (OR 0.92 per year; 95%CI 0.88-0.98) in multivariable analysis. Of SPAs that recurred, 12 of 19 (63.2%) were retreated with repeat surgery (n = 11) or radiosurgery (n = 1), while the remainder were observed (n = 7).There were similar rates of recurrence across different SPA subtypes. CONCLUSION: Patients undergoing resection of SPAs should be closely monitored for disease recurrence through more frequent clinical follow-up and diagnostic imaging than other adenomas, particularly among patients with STR and younger patients. Several patients can be observed after radiographic recurrence, and the decision to retreat should be individualized. Longitudinal clinical follow-up of SPAs, including an assessment of symptoms, endocrine function, and imaging remains critical.

Intrasellar Arachnoid Diverticulae as a Risk Factor for Intraoperative Cerebrospinal Fluid Leakage in Patients Undergoing Endoscopic Transsphenoidal Surgery.

BACKGROUND AND OBJECTIVES: Intrasellar arachnoid diverticulae can often be identified on preoperative imaging in patients undergoing endoscopic transsphenoidal surgery. The objective of this study was to characterize arachnoid diverticulae both qualitatively and quantitatively in a large institutional cohort of patients with pituitary tumors and to evaluate its association with intraoperative cerebrospinal fluid (CSF) leak. METHODS: Preoperative imaging studies of 530 patients who underwent primary endoscopic transsphenoidal resection of pituitary tumors were examined both quantitatively and qualitatively for the presence of an intrasellar arachnoid diverticulum. A matched cohort analysis was performed to compare patients with a "significant" (>50% sellar depth) diverticulum with those with nonsignificant/no diverticulum. Morphologically, diverticulae were separately classified as Type 1 (ventral CSF cleft with no tumor/gland tissue between sellar face and infundibulum) or Type 2 (central CSF cleft with tumor/gland tissue between sellar face and infundibulum). RESULTS: Arachnoid diverticulae were noted in 40.2% of cases, and diverticulum depth was linearly correlated with tumor size and body mass index. A significant diverticulum was identified in 66 cases (12.5%) and was significantly associated with the functional tumor subtype (P = .005) and intraoperative CSF leak (P < .001). Type 1 clefts were associated with nonfunctional pathology (P = .034) and the presence of suprasellar extension (P = .035) and tended to be deeper than Type 2 clefts (P < .001), with a higher incidence of intraoperative CSF leak (P = .093). On logistic regression analysis, only the presence of a significant diverticulum was independently associated with intraoperative CSF leak (odds ratio 4.545; 95% CI 2.418-8.544; P < .001). CONCLUSION: The presence of an intrasellar arachnoid diverticulum should alert the surgeon to an elevated risk of intraoperative CSF leak during transsphenoidal surgery for pituitary tumors. A relatively limited surgical exposure tailored to the craniocaudal extent of the sellar pathology should be considered in these patients.

Morphological Classification of Pituitary Tumors With Suprasellar Extension.

BACKGROUND AND OBJECTIVES: The objective of this study was to study the association among various morphological parameters and surgical outcomes in pituitary macroadenomas with suprasellar extension. METHODS: MRI studies of 160 patients undergoing endoscopic transsphenoidal resection of pituitary macroadenomas with suprasellar extension were reviewed. In the coronal plane, tumors were classified into Type 1 (dome-shaped, no constriction at the level of diaphragma sellae) and Type 2 (dumbbell-shaped, with constriction at the level of diaphragma sellae). Based on the dome-to-neck ratio (D/Nr), Type 2 tumors were further classified as Type 2A (wide neck; D/Nr >1 and <1.3) and Type 2B (narrow neck; D/Nr ≥1.3). Surgical outcomes and complications were analyzed using a logistic regression model. Overall extent of resection (EOR) and presence of residual sellar-suprasellar tumor was separately assessed in all patients with available postoperative MRI (n = 149). RESULTS: There were 108 Type 1 tumors and 26 patients each in the Type 2A and Type 2B subgroups. Tumor subtype was significantly associated with tumor size (P < .001), intraoperative cerebrospinal fluid leak (P < .001), EOR (P < .001), postoperative suprasellar residual tumor (P < .001), and postoperative complications, including diabetes insipidus (P = .005) and visual worsening (P = .003). On multivariate analysis, after adjusting for confounders, Type 2B tumors were negatively associated with EOR (odds ratio [OR] 0.22; 95% CI 0.07-0.68; P = .008) and associated with the presence of postoperative suprasellar residual tumor (OR 18.08; 95% CI 5.20-62.89; P < .001), intraoperative cerebrospinal fluid leak (OR 5.33; 95% CI 1.89-14.99; P = .002), and postoperative diabetes insipidus (OR 4.89; 95% CI 1.67-14.35; P < .001). CONCLUSION: Preoperative tumor classification based on D/Nr is clinically and surgically relevant, and Type 2B macroadenomas are significantly associated with lower rates of gross total resection and higher rates of postoperative complications after endoscopic transsphenoidal resection.

Pituitary adenoma or neuroendocrine tumour: the need for an integrated prognostic classification.

In the 2022 fifth edition of the WHO Classification of Endocrine Tumours and of Central Nervous System Tumours, pituitary adenomas are reclassified as neuroendocrine tumours (NETs). This change confers an oncology label to neoplasms that are overwhelmingly benign. A comprehensive clinical classification schema is required to guide prognosis, therapy and outcomes for all patients with pituitary adenomas. Pituitary adenomas and NETs exhibit some morphological and ultrastructural similarities. However, unlike NETs, pituitary adenomas are highly prevalent, yet indolent and rarely become malignant. This Perspective presents the outcomes of an interdisciplinary international workshop that addressed the merit and clinical implications of the classification change of pituitary adenoma to NET. Many non-histological factors provide mechanistic insight and influence the prognosis and treatment of pituitary adenoma. We recommend the development of a comprehensive classification that integrates clinical, genetic, biochemical, radiological, pathological and molecular information for all anterior pituitary neoplasms.

Metastatic pituitary tumors: an institutional case series.

PURPOSE: Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined. METHODS: We present an institutional case series of patients treated for pituitary carcinomas over a 30-year period from 1992 to 2022. A systematic review was conducted to identify prior case series of patients with pituitary carcinomas. RESULTS: Fourteen patients with a mean age at pituitary carcinoma diagnosis of 52.5 years (standard deviation [SD] 19.4) met inclusion criteria. All 14 patients had tumor subtypes confirmed by immunohistochemistry and hormone testing, with the most common being ACTH-producing pituitary adenomas (n = 12). Patients had a median progression-free survival (PFS) of 1.4 years (range 0.7-10.0) and a median overall survival (OS) of 8.4 years (range 2.3-24.0) from pituitary adenoma diagnosis. Median PFS and OS were 0.6 years (range 0.0-2.2) and 1.5 years (range 0.1-9.6) respectively upon development of metastases. Most patients (n = 12) had locally invasive disease to the cavernous sinus, dorsum sellae dura, or sphenoid sinus prior to metastasis. Common sites of metastasis included the central nervous system, liver, lung, and bone. In a pooled analysis including additional cases from the literature, treatment of metastases with chemotherapy or a combination of radiation therapy and chemotherapy significantly prolonged PFS (p = 0.02), while failing to significantly improve OS (p = 0.14). CONCLUSION: Pituitary carcinomas are highly recurrent, heterogenous tumors with variable responses to treatment. Multidisciplinary management with an experienced neuro-endocrine and neuro-oncology team is needed given the unrelenting nature of this disease.

Postoperative Serum Cortisol and Cushing Disease Recurrence in Patients With Corticotroph Adenomas.

CONTEXT: In Cushing disease, the association between the rate of serum cortisol decline and recurrent disease after corticotroph adenoma removal has not been adequately characterized. OBJECTIVE: To analyze postoperative serum cortisol and recurrence rates in Cushing disease. METHODS: Patients with Cushing disease and pathology-confirmed corticotroph adenoma were retrospectively studied. Cortisol halving time was estimated using exponential decay modeling. Halving time, first postoperative cortisol, and nadir cortisol values were collected using immediate postoperative inpatient laboratory data. Recurrence and time-to-recurrence were estimated and compared among cortisol variables. RESULTS: A total of 320 patients met inclusion/exclusion criteria for final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 25 months (95% CI, 19-28 months), and 62 patients had ≥ 5 years follow-up time. Higher first postoperative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first postoperative cortisol ≥ 50 µg/dL were 4.1 times more likely to recur than those with a first postoperative cortisol < 50 µg/dL (HR 4.1, 1.8-9.2; P = .0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, P = .18). Patients with a nadir cortisol ≥2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, P < .0001). CONCLUSION: Postoperative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first postoperative cortisol and cortisol halving time, a nadir < 2 µg/dL showed the strongest association with long-term remission and typically occurs within the first 24 to 48 hours after surgery.

Vascular anomalies in patients with growth hormone-secreting pituitary adenomas: illustrative case report and systematic review of the literature.

PURPOSE: Endonasal resection is the first-line treatment for patients harboring growth hormone (GH)-secreting pituitary adenomas. The complexity of the parasellar neurovascular structures makes pre-operative diagnostic imaging essential to understanding the anatomy of this region. We aimed to describe vascular anomalies in acromegalic patients and emphasize their relevance for surgery and preoperative planning. METHODS: A systematic review following the PRISMA statement was performed in July 2021. RESULTS: Thirty-three studies were evaluated. Elevated GH and insulin-like growth factor-1 (IGF-1) levels are linked to the occurrence of cardiovascular risk factors. This is attributed to endothelial dysfunction, mainly caused by changes in flow-mediated dilatation (FMD), which is probably the main cause of vascular anomalies in acromegaly. The occurrence of protrusions of the internal carotid artery (ICA) (35-53%), a narrow intercarotid distance, and an asymmetrical course was described. In 13-18% of acromegalic patients, the presence of an intracerebral aneurysm could be reported (incidence in the general population:0.8-1.3%). The selected studies were however performed with a small patient sample (range:1-257). We present a case report of a 57y/o male patient with anomalies of the ICA ("kissing carotid arteries") harboring a GH-secreting adenoma, which was resected via an endoscopic endonasal approach. CONCLUSIONS: There is an association between acromegaly and endothelial dysfunction, which increases cardiovascular risk factors and vascular anomalies. Preoperative vascular imaging, e.g., CT angiography, should be implemented as a standard to identify patients at risk and estimate surgical morbidity. However, no evidence-based recommendations exist so far, so future studies are necessary.

Hajek and Hirsch: Otolaryngology Pioneers of Endonasal Transsphenoidal Pituitary Surgery.

OBJECTIVE: To evaluate the historical descriptive origins of the extracranial transnasal transsphenoidal route to the sphenoid sinus and sella turcica focusing on the works of two otolaryngologists: Markus Hajek (1861-1941) and Oskar Hirsch (1877-1965). DATA SOURCES: A collection of primary references of author publications, and contemporary references and textbooks. REVIEW METHODS: Primary references were reviewed with specific focus on surgical routes to the sphenoid sinus and sella turcica. Chronology was cross-referenced with contemporary publications by contemporaries. Translations from German were conducted by author AM when necessary. RESULTS: Markus Hajek elegantly described the surgical approach to the posterior ethmoids and sphenoid sinus in 1904 using a transnasal route. Building on this foundation, Oskar Hirsch described the fully extracranial endonasal transethmoid transsphenoidal approach in 1909. He was first to describe surgical entrance to the sella using this exclusively unilateral endonasal route, which he demonstrated on a cadaver. He reports performing this procedure on a live patient in April, 1910, under local anesthesia in stages over 5 weeks. For better exposure, Hirsch consolidated his method with Killian's submucosal window resection of the posterior nasal septum allowing for bilateral access to the sphenoid sinus and sella, and completed a single stage procedure on a patient in June 1910. CONCLUSION: Oskar Hirsch was the first to describe and perform a stepwise surgical approach to the sella using an exclusively extracranial, endonasal, transethmoid, and transsphenoidal approach. He built upon his mentor Markus Hajek's approaches to the posterior ethmoid cells and sphenoid sinus. LEVEL OF EVIDENCE: NA: Background information, synthesis from multiple sources emphasizing factual information Laryngoscope, 133:807-813, 2023.

A national stratification of the global macroeconomic burden of central nervous system cancer.

OBJECTIVE: Country-by-country estimates of the macroeconomic disease burden of central nervous system (CNS) cancers are important when determining the allocation of resources related to neuro-oncology. Accordingly, in this study the authors investigated macroeconomic losses related to CNS cancer in 173 countries and identified pertinent epidemiological trends. METHODS: Data for CNS cancer incidence, mortality, and disability-adjusted life years (DALYs) were collected from the Global Burden of Disease 2019 database. Gross domestic product data were combined with DALY data to estimate economic losses using a value of lost welfare approach. RESULTS: The mortality-to-incidence ratio of CNS cancer in 2019 was 0.60 in high-income regions compared to 0.82 in Sub-Saharan Africa and 0.87 in Central Europe, Eastern Europe, and Central Asia. Welfare losses varied across both high- and low-income countries. Welfare losses attributable to CNS cancer in Japan represented 0.07% of the gross domestic product compared to 0.23% in Germany. In low- and middle-income countries, Iraq reported welfare losses of 0.20% compared to 0.04% in Angola. Globally, the DALY rate in 2019 was the same for CNS cancer as for prostate cancer at 112 per 100,000 person-years, despite a 75% lower incidence rate, equating to CNS cancer welfare losses of 182 billion US dollars. CONCLUSIONS: Macroeconomic losses vary across high- and low-income settings and appear to be region specific. These differences may be explained by differences in regional access to screening and diagnosis, population-level genetic predispositions, and environmental risk factors. Mortality-to-incidence ratios are higher in low- and middle-income countries than in high-income countries, highlighting possible gaps in treatment access. Quantification of macroeconomic losses related to CNS cancer can help to justify the spending of finite resources to improve outcomes for neuro-oncological patients globally.

The Hitchhiker Position in Endoscopic Pituitary Surgery.

BACKGROUND: Technically and ergonomically correct positioning is essential in endoscopic transsphenoidal pituitary surgery. OBJECTIVE: To propose a safe, ergonomic approach to conduct endoscopic endonasal pituitary and skull base surgery in large patients without sacrificing important aspects of current standard practice. METHODS: The patient's right arm is outstretched and secured in a supine position, with the primary surgeon standing in the axillary area. Considerations include maintaining comfort, immobility, anesthesia access, endotracheal tube fixation, intravenous lines, thorax elevated 25° to 30° for optimization of respiration, free and exposed abdomen for fat graft, legs positioned with no sciatic stretch or venous strain, and the patient's head in parallel with the surrounding area to sustain a strict midline. RESULTS: Ten patients who underwent transsphenoidal pituitary tumor resections conducted using the hitchhiker position from October 2019 to June 2021 comprised our study cohort. The patients' mean height was 168.70 ± 9.29 cm, their mean weight was 114.35 ± 19.32 kg, and their mean body mass index was 40.19 ± 6.39 kg/m 2 . Twenty percent (n = 2) patients had a body mass index classified as "obesity class 1," 50% (n = 5) as "obesity class 2," and 30% (n = 3) as "extreme obesity class 3." The primary surgeon consistently reported decreased bodily strain and improved ergonomic access to the surgical site using the hitchhiker position. CONCLUSION: The hitchhiker position offers the opportunity to improve both patient and physician well-being in the context of endoscopic pituitary surgery.

Ergonomics in Endoscopic Transsphenoidal Surgery: A Survey of the North American Skull Base Society.

Objective Different surgical set-ups for endoscopic transsphenoidal surgery (ETS) have been described, but studies on their ergonomics are limited. The aim of this article is to describe present trends in the ergonomics of ETS. Design and Participants A 33-question, web-based survey was sent to North American Skull Base Society members in 2018 and 116 responded to it (16% of all members). Most respondents were from North America (76%), in academic practice (87%), and neurosurgeons (65%); they had more than 5 years of experience in ETS (73%), had received specific training (66%), and performed at least 5 procedures/mo (55%). Results Mean reported time for standard and complex procedures were 3.7 and 6.3 hours, respectively. The patient's body is usually positioned in a straight, supine position (84%); the head is in a neutral position (46%) or rotated to the side (38%). Most surgeons perform a binostril technique, work with a partner (95%), and operate standing (94%), holding suction (89%) and dissector (83%); sometimes the endoscope is held by the primary surgeon (22-24%). The second surgeon usually holds the endoscope (72%) and irrigation (42%). During tumor removal most surgeons stand on the same side (65-66%). Many respondents report strain at the dorsolumbar (50%) or cervical (26%) level. Almost one-third of surgeons incorporate a pause during surgery to stretch, and approximately half exercise to be fit for surgery; 16% had sought medical attention for ergonomic-related symptoms. Conclusion Most respondents value ergonomics in ETS. The variability in surgical set-ups and the relatively high report of complaints underline the need for further studies to optimize ergonomics in ETS.

Changes in the Options for Management of Prolactin Secreting Pituitary Adenomas.

Objectives Initial therapy for the management of prolactinomas has long been maintained to be medical, consisting of a dopamine agonist. These therapies may have troublesome side effects, and some prolactinomas are resistant to medical therapy regarding lowering prolactin levels or shrinking the tumor. These issues have revived interest in surgery for prolactin-secreting adenomas as an early therapeutic option. We report our analysis of surgery for prolactin microadenomas in women, using the transsphenoidal endoscopic approach. Design We reviewed a contemporary series of 33 women (mean age = 31.8 years) with microprolactinomas who underwent early surgical intervention, which was a three-dimensional transnasal transsphenoidal endoscopic operation. Setting The study was conducted at a tertiary academic referral center for pituitary tumors. Main Outcome Measures Preoperative and postoperative prolactin. Results Overall, 28 patients had received preoperative dopamine agonists, 24 of these experienced a variety of drug-related side effects, and 4 had tumors that were resistant to lowering prolactin or tumor shrinkage. Preoperative prolactin levels averaged 90.3 ng/mL (range = 30.7-175.8 ng/mL). We observed a 94% normalization rate in postoperative prolactin (mean = 10.08 ng/mL, range = 0.3-63.1 ng/mL). During the follow-up (mean = 33.9 months), five patients had elevated prolactin; four required reinitiation of medical therapy, two had surgical reexploration, and none received radiation therapy. Complications included syndrome of inappropriate antidiuretic hormone secretion ( n = 3), transient diabetes insipidus ( n = 1), postoperative epistaxis ( n = 1), and fat graft site infection ( n = 1). Conclusion This review supports the consideration of transsphenoidal surgery as an early intervention for some women with prolactin-secreting microadenoma. Indications include significant side effects of medical therapy and tumors that do not respond to standard medical management.

A Surgical Perspective on the Association between Cystic Lesions of the Pineal Gland (Descartes' Seat of the Soul) and the Pituitary (the Master Gland).

Introduction Rene Descartes (1596-1650), the famous philosopher and scientist, identified the pineal gland as the only cerebral structure not represented bilaterally, the "seat of the soul"; and the source of rational thought. Pineal cysts (PCs) are often incidentally identified in MRI studies, with a reported prevalence of 1 to 4.3%. Rathke cleft cysts (RCCs) are pituitary lesions accounting for <1% of intracranial masses. There are scant data in the literature addressing any association between these two midline cystic lesions. Methods We reviewed the medical records of patients presenting at our institution from April 2008 through February 2020, whose records indicated a diagnosis of RCC, and those whose records included pineal lesions. Our objective was to evaluate the association between these two midline lesions. Brain MRI studies were reviewed for the presence of PCs; only patients with PCs that measured ≥5 mm in diameter were included. Results We identified 116 patients with RCCs, and 34 patients with PCs, treated from April 2008 through February 2020. Among the RCC group, 14/116 patients (12%) had PCs. Among the PC group, 3/34 patients (8.8%) had RCCs. Overall, 17 patients (11.3%) had concomitant RCCs and PCs. The mean maximal diameter of the PCs was 7.5 mm (range = 5-17 mm), whereas the mean maximal diameter of RCCs was 13 mm (range = 5-40 mm). Conclusion The incidental diagnosis of cystic lesions of the pineal and pituitary gland is increasingly reported, primarily because of advances in current diagnostic modalities. Our data demonstrated no clear consensual association between pineal and pituitary cysts.

Characterization of a paradoxical post-operative increase in serum cortisol in Cushing disease.

PURPOSE: In Cushing disease, early post-operative serum cortisol fluctuations have not been adequately characterized, and their association with initial remission and recurrence is unclear. METHODS: A retrospective cohort study of patients with Cushing disease was conducted at two institutions. A "riser" was defined a priori as a paradoxical increase in serum cortisol with an immediate incremental increase in serum cortisol over three consecutive cortisol draws separated by roughly 6-h (definition 1). Post hoc analyses used a definition of two consecutive increases (definition 2). Risers were compared to non-risers for initial remission and time-to-recurrence. RESULTS: A total of 505 patients with Cushing disease were screened, and 469 had adequate data for group assignment. Analysis of post-operative cortisol showed a subgroup of "risers" with a frequency of 3.6% for definition 1 and 42.6% for definition 2. In these patients, cortisol levels were significantly higher until approximately 36 h post-operatively, and cortisol had a significantly longer mean serum half-life. In the post hoc analysis, definition 2 risers had a lower remission rate compared to non-risers (162/196, 82.7%, versus 243/264, 92.0%) with an odds ratio of 0.41 (0.23-0.73; p = 0.003). For both definitions, recurrence was similar between groups. CONCLUSIONS: We found that almost half of Cushing disease patients experienced a temporary increase in serum cortisol level during the early post-operative period. Serum cortisol half-life was longer, and the remission rates were lower, however, recurrence rates were similar to non-risers.

Alcohol intake and risk of pituitary adenoma.

BACKGROUND: The association between alcohol intake and incidence of pituitary adenoma has not been reported previously. We examined this association in three large, prospective cohort studies. METHODS: Using data from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-Up Study, we computed multivariable-adjusted hazard ratios (MVHR) and 95% confidence intervals (CI) for pituitary adenoma by levels of alcohol intake using Cox proportional hazards regression. RESULTS: We identified 292 incident cases of pituitary adenoma (225 among women, 67 among men) among 235,973 participants with 6,548,732 person-years of follow-up. Compared with intake of ≤ 0.5 g/day, cumulative average alcohol intake in all categories was associated with reduced risk of pituitary adenoma (MVHR = 0.60, 95% CI 0.43-0.83 for 0.5-≤ 2 g/day, MVHR = 0.57, 95% CI 0.41-0.79 for > 2.0-≤ 8.0, MVHR = 0.70, 95% CI 0.47-1.04 for > 8.0-≤ 15.0, and MVHR = 0.51, 95% CI 0.32-0.83 for > 15.0 g/day). Significant inverse findings were present in women and were similar but non-significant in men. For specific alcoholic beverages, inverse associations were statistically significant for total wine (MVHR = 0.58, 95% CI 0.43-0.79 comparing 0.5-≤ 2 to ≤ 0.5 g/day), red wine (MVHR = 0.65, 95% CI 0.46-0.92 comparing 0.5-≤ 2 to ≤ 0.5 g/day), and white wine (MVHR = 0.72, 95% CI 0.53-0.97 comparing 0.5-≤ 2 to ≤ 0.5 g/day). Results were consistent using baseline intake, recent intake, and with an 8-year lag. CONCLUSION: In three prospective cohorts, compared to almost no consumption, alcohol consumption was associated with reduced risk of pituitary adenoma. Sensitivity analyses suggest that these results are unlikely to be the result of reverse causation or diagnostic bias.

Epidemiology of common and uncommon adult pituitary tumors in the U.S. according to the 2017 World Health Organization classification.

PURPOSE: To examine the contemporary epidemiology of adult pituitary tumors with a particular focus on uncommon tumor types, using the 2017 WHO Classification of pituitary tumors. METHODS: Adult patients presenting with a pituitary or sellar tumor between 2004 and 2017 were identified from the U.S. National Cancer Database, with tumor type categorized according to the 2017 WHO classification. Descriptive epidemiological statistics were evaluated and reported for all pituitary tumor types and subtypes. RESULTS: 113,349 adults with pituitary tumors were identified, 53.0% of whom were female. The majority of pituitary tumors were pituitary adenomas (94.0%), followed by craniopharyngiomas (3.8%). Among pituitary adenomas, whereas 71.6% of microadenomas presented in females, only 46.7% of macroadenomas and 41.3% of giant adenomas did (p < 0.001). For craniopharyngiomas, 71.2% were adamantinomatous and 28.8% were papillary, with adamantinomatous tumors associated with Black non-Hispanic race/ethnicity (ORadj = 2.44 vs. White non-Hispanic, 99.9 %CI = 1.25-4.75, p < 0.001) in multivariable analysis. The remaining 0.7% (n = 676) of pathology-confirmed pituitary tumor types were composed of: 21% tumors of the posterior pituitary, 16% chordomas, 11% pituitary carcinomas (i.e. adenohypophyseal histology with metastasis; herein most frequently to bone), 10% meningiomas, 8% germ cell tumors, 7% hematolymphoid (largely DLBCLs), and 4% neuronal/paraneuronal (largely gangliogliomas). Pituitary carcinomas and posterior pituitary tumors demonstrated a male predilection (62.2% and 56.0%, respectively), whereas sellar meningiomas predominated in females (84.1%). Age, race/ethnicity, tumor size, and overall survival further varied across uncommon pituitary tumor types. CONCLUSIONS: Our findings provide a detailed contemporary dissection of the epidemiology of common and uncommon adult pituitary tumors in the context of WHO2017.

Oral Contraceptive and Menopausal Hormone Therapy Use and Risk of Pituitary Adenoma: Cohort and Case-Control Analyses.

CONTEXT: No prospective epidemiologic studies have examined associations between use of oral contraceptives (OCs) or menopausal hormone therapy (MHT) and risk of pituitary adenoma in women. OBJECTIVE: Our aim was to determine the association between use of OC and MHT and risk of pituitary adenoma in two separate datasets. METHODS: We evaluated the association of OC/MHT with risk of pituitary adenoma in the Nurses' Health Study and Nurses' Health Study II by computing multivariable-adjusted hazard ratios (MVHR) of pituitary adenoma by OC/MHT use using Cox proportional hazards models. Simultaneously, we carried out a matched case-control study using an institutional data repository to compute multivariable-adjusted odds ratios (MVOR) of pituitary adenoma by OC/MHT use. RESULTS: In the cohort analysis, during 6 668 019 person-years, 331 participants reported a diagnosis of pituitary adenoma. Compared to never-users, neither past (MVHR = 1.05; 95% CI, 0.80-1.36) nor current OC use (MVHR = 0.72; 95% CI, 0.40-1.32) was associated with risk. For MHT, compared to never-users, both past (MVHR = 2.00; 95% CI, 1.50-2.68) and current use (MVHR = 1.80; 95% CI, 1.27-2.55) were associated with pituitary adenoma risk, as was longer duration (MVHR = 2.06; 95% CI, 1.42-2.99 comparing more than 5 years of use to never, P trend = .002). Results were similar in lagged analyses, when stratified by body mass index, and among those with recent health care use. In the case-control analysis, we included 5469 cases. Risk of pituitary adenoma was increased with ever use of MHT (MVOR = 1.57; 95% CI, 1.35-1.83) and OC (MVOR = 1.27; 95% CI, 1.14-1.42) compared to never. CONCLUSION: Compared to never use, current and past MHT use and longer duration of MHT use were positively associated with higher risk of pituitary adenoma in 2 independent data sets. OC use was not associated with risk in the prospective cohort analysis and was associated with only mildly increased risk in the case-control analysis.