Spontaneous regression of Rathke's cleft cysts with conservative management: patient series.

BACKGROUND: Rathke's cleft cysts (RCCs) are benign fluid-filled cysts that develop in the pituitary gland because of the abnormal embryological development of Rathke's pouch. Most RCCs are small and asymptomatic; however, they can present with symptoms or documented growth, sometimes prompting surgical treatment. For smaller asymptomatic lesions, an unknown proportion demonstrates regression over time. This study describes 3 cases of spontaneous RCC regression. OBSERVATIONS: Three patients with a diagnosis of RCC demonstrated an average decrease of 78% in cyst volume over a mean interval of 3.7 months. One patient experienced the resolution of chronic headaches, whereas the other 2 patients had persistent headaches and endocrinopathies at follow-up. A systematic review included 9 studies that reported results from observational cohorts of patients with RCC, totaling 619 observed patients, with 158 (25.5%) patients demonstrating spontaneous cyst regression. In the patients with cyst regression, the majority had a resolution of symptoms. LESSONS: A substantial proportion of RCC patients managed nonsurgically demonstrated spontaneous regression. There is a role for the conservative management of RCCs in patients without significant symptoms, and surveillance should continue for a minimum of 5 years to confirm cyst stability. For patients undergoing planned surgery, same-day or recent imaging is recommended to prevent operating on involuted RCCs. https://thejns.org/doi/10.3171/CASE24268.

Endoscopic Endonasal Transsphenoidal Resection of Pituitary Adenomas in Patients Presenting With Monocular Blindness.

BACKGROUND AND OBJECTIVES: Suprasellar tumors, particularly pituitary adenomas (PAs), commonly present with visual decline, and the endoscopic endonasal transsphenoidal approach (EETA) is the primary management for optic apparatus decompression. Patients presenting with complete preoperative monocular blindness comprise a high-risk subgroup, given concern for complete blindness. This retrospective cohort study evaluates outcomes after EETA for patients with PA presenting with monocular blindness. METHODS: Retrospective analysis of all EETA cases at our institution from June 2012 to August 2023 was performed. Inclusion criteria included adults with confirmed PA and complete monocular blindness, defined as no light perception, and a relative afferent pupillary defect secondary to tumor mass effect. RESULTS: Our cohort includes 15 patients (9 males, 6 females), comprising 2.4% of the overall PA cohort screened. The mean tumor diameter was 3.8 cm, with 6 being giant PAs (>4 cm). The mean duration of preoperative monocular blindness was 568 days. Additional symptoms included contralateral visual field defects (n = 11) and headaches (n = 10). Two patients presented with subacute PA apoplexy. Gross total resection was achieved in 46% of patients, reflecting tumor size and invasiveness. Postoperatively, 2 patients experienced improvement in their effectively blind eye and 2 had improved visual fields of the contralateral eye. Those with improvements were operated within 10 days of presentation, and no patients experienced worsened vision. CONCLUSION: This is the first series of EETA outcomes in patients with higher-risk PA with monocular blindness on presentation. In these extensive lesions, vision remained stable for most without further decline and improvement from monocular blindness was observed in a small subset of patients with no light perception and relative afferent pupillary defect. Timing from vision loss to surgical intervention seemed to be associated with improvement. From a surgical perspective, caution is warranted to protect remaining vision and we conclude that EETA is safe in the management of these patients.

Management of growth hormone-secreting pituitary adenomas causing acromegaly: a practical review of surgical and multimodal management strategies for neurosurgeons.

This review aimed to highlight the history, diagnostic criteria, preoperative prognostic factors, surgical management, and multimodal adjuvant therapies recommended to provide a comprehensive and multifaceted understanding of and clinical approach to treating growth hormone-secreting pituitary adenomas (GHPAs) in patients with acromegaly. The authors collated and reviewed published studies, many written by skull base neurosurgeons, endocrinologists, and radiation oncologists with expertise in pituitary adenoma management, to produce a practical and contemporary update pertaining to the optimal management of acromegaly for neurosurgeons. Acromegaly is a debilitating disease for which surgery can be curative in more than two-thirds of patients. Recent rates of hormonal remission by the authors' group and others following the resection of GHPAs are on the order of 70%-80%, and these increase to more than 85% with the addition of medical therapy in a minority of patients who do not achieve remission with surgery alone. Most tumors are accessible via a direct endoscopic endonasal transsphenoidal approach, which can be augmented with a variety of extended approaches to gain access to suprasellar, clival, and parasellar compartments as needed. Preoperative growth hormone levels, cavernous sinus invasion, and pituitary adenoma consistency are important factors in determining the extent of resection. In most patients with residual or recurrent disease, medical therapy (e.g., somatostatin analogs and dopamine agonists) can be used to help achieve hormonal remission. Repeat surgery can be safely performed in most cases if needed, whereas stereotactic radiosurgery is usually reserved for medically resistant tumors in surgically inaccessible compartments. The neurosurgeon has a primary and often definitive role in the management of acromegaly. The involvement of an integrated and multidisciplinary team consisting of experts from neurosurgery, otolaryngology, endocrinology, and radiation oncology optimizes the chances for a biochemical cure, even in large and aggressive GHPAs.

Endoscopic endonasal approach for MRI-Negative Cushing's microadenoma.

A 54-year-old male with a history of diabetes mellitus type 2 for 12 years and hypertension was seen in the clinic due to poorly controlled diabetes. Inferior petrosal sinus sampling (IPSS) confirmed Cushing's disease with primary adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma on the right. However, 3T and subsequent 7T MRI showed no visible tumor. An endoscopic transsphenoidal approach was selected to explore the pituitary gland and resect the presumed microadenoma. Tumor was identified in the lateral recess along the right medial cavernous sinus wall and gross-total resection (GTR) was performed. The normal pituitary gland was preserved, and the patient went into remission. The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2324.

Validation of Myc-Associated Protein X (MAX) regulation in growth hormone secreting and nonfunctional pituitary adenoma.

INTRODUCTION: Many patients with growth hormone-secreting pituitary adenoma (GHPA) fail to achieve biochemical remission, warranting investigation into epigenetic and molecular signatures associated with tumorigenesis and hormonal secretion. Prior work exploring the DNA methylome showed Myc-Associated Protein X (MAX), a transcription factor involved in cell cycle regulation, was differentially methylated between GHPA and nonfunctional pituitary adenoma (NFPA). We aimed to validate the differential DNA methylation and related MAX protein expression profiles between NFPA and GHPA. METHODS: DNA methylation levels were measured in 52 surgically resected tumors (37 NFPA, 15 GHPA) at ~100,000 known MAX binding sites derived using ChIP-seq analysis from ENCODE. Findings were correlated with MAX protein expression using a constructed tissue microarray (TMA). Gene ontology analysis was performed to explore downstream genetic and signaling pathways regulated by MAX. RESULTS: GHPA had more hypomethylation events across all known MAX binding sites. Of binding sites defined using ChIP-seq analysis, 1,551 sites had significantly different methylation patterns between the two cohorts; 432 occurred near promoter regions potentially regulated by MAX, including promoters of TNF and MMP9. Gene ontology analysis suggested enrichment in genes involved in oxygen response, immune system regulation, and cell proliferation. Thirteen MAX binding sites were within coding regions of genes. GHPA demonstrated significantly increased expression of MAX protein compared to NFPA. CONCLUSION: GHPA have significantly different DNA methylation and downstream protein expression levels of MAX compared to NFPA. These differences may influence mechanisms involved with cellular proliferation, tumor invasion and hormonal secretion.

Treatment of Cushing Disease With Pituitary-Targeting Seliciclib.

CONTEXT: Preclinical studies show seliciclib (R-roscovitine) suppresses neoplastic corticotroph proliferation and pituitary adrenocorticotrophic hormone (ACTH) production. OBJECTIVE: To evaluate seliciclib as an effective pituitary-targeting treatment for patients with Cushing disease (CD). METHODS: Two prospective, open-label, phase 2 trials, conducted at a tertiary referral pituitary center, included adult patients with de novo, persistent, or recurrent CD who received oral seliciclib 400 mg twice daily for 4 consecutive days each week for 4 weeks. The primary endpoint in the proof-of-concept single-center study was normalization of 24-hour urinary free cortisol (UFC; ≤ 50 µg/24 hours) at study end; in the pilot multicenter study, primary endpoint was UFC normalization or ≥ 50% reduction in UFC from baseline to study end. RESULTS: Sixteen patients were consented and 9 were treated. Mean UFC decreased by 42%, from 226.4 ± 140.3 µg/24 hours at baseline to 131.3 ± 114.3 µg/24 hours by study end. Longitudinal model showed significant UFC reductions from baseline to each treatment week. Three patients achieved ≥ 50% UFC reduction (range, 55%-75%), and 2 patients exhibited 48% reduction; none achieved UFC normalization. Plasma ACTH decreased by 19% (P = 0.01) in patients who achieved ≥ 48% UFC reduction. Three patients developed grade ≤ 2 elevated liver enzymes, anemia, and/or elevated creatinine, which resolved with dose interruption/reduction. Two patients developed grade 4 liver-related serious adverse events that resolved within 4 weeks of seliciclib discontinuation. CONCLUSION: Seliciclib may directly target pituitary corticotrophs in CD and reverse hypercortisolism. Potential liver toxicity of seliciclib resolves with treatment withdrawal. The lowest effective dose requires further determination.

Ultra-high field 7 T MRI localizes regional brain volume recovery following corticotroph adenoma resection and hormonal remission in Cushing's disease: A case series.

Background: Cushing's disease (CD) is defined by glucocorticoid excess secondary to the increased section of corticotropin by a pituitary adenoma. Magnetic resonance imaging (MRI) studies performed at 1.5 or 3 Tesla (T) have demonstrated correlations between regional changes in brain structure and the progression of CD. In this report, we examine the changes in brain volume following corticotroph pituitary adenoma resection using ultra-high field 7 T MRI to increase the accuracy of our volumetric analyses. Methods: Thirteen patients were referred to the endocrinology clinic at our institution from 2017 to 2020 with symptoms of cortisol excess and were diagnosed with ACTH-dependent endogenous Cushing syndrome. Five patients had follow-up 7 T imaging at varying time points after a transsphenoidal resection. Results: Symmetrized percent change in regional volumes demonstrated a postoperative increase in cortical volume that was relatively larger than that of cerebral white matter or subcortical gray matter (percent changes = 0.0172%, 0.0052%, and 0.0120%, respectively). In the left cerebral hemisphere, the medial orbitofrontal, lateral orbitofrontal, and pars opercularis cortical regions experienced the most robust postoperative percent increases (percent changes = 0.0166%, 0.0122%, and 0.0068%, respectively). In the right cerebral hemisphere, the largest percent increases were observed in the pars triangularis, rostral portion of the middle frontal gyrus, and superior frontal gyrus (percent changes = 0.0156%, 0.0120%, and 0.0158%). Conclusion: Cerebral volume recovery following pituitary adenoma resection is driven by changes in cortical thickness predominantly in the frontal lobe, while subcortical white and gray matter volumes increase more modestly.

Association between socioeconomic status and presenting characteristics and extent of disease in patients with surgically resected nonfunctioning pituitary adenoma.

OBJECTIVE: The aim of this study was to evaluate the association between zip code-level socioeconomic status (SES) and presenting characteristics and short-term clinical outcomes in patients with nonfunctioning pituitary adenoma (NFPA). METHODS: A retrospective review of prospectively collected data from the University of Southern California Pituitary Center was conducted to identify all patients undergoing surgery for pituitary adenoma (PA) from 2000 to 2021 and included all patients with NFPA with recorded zip codes at the time of surgery. A normalized socioeconomic metric by zip code was then constructed using data from the American Community Survey estimates, which was categorized into tertiles. Multiple imputation was used for missing data, and multivariable linear and logistic regression models were constructed to estimate mean differences and multivariable-adjusted odds ratios for the association between zip code-level SES and presenting characteristics and outcomes. RESULTS: A total of 637 patients were included in the overall analysis. Compared with patients in the lowest SES tertile, those in the highest tertile were more likely to be treated at a private (rather than safety net) hospital, and were less likely to present with headache, vision loss, and apoplexy. After multivariable adjustment for age, sex, and prior surgery, SES in the highest compared with lowest tertile was inversely associated with tumor size at diagnosis (-4.9 mm, 95% CI -7.2 to -2.6 mm, p < 0.001) and was positively associated with incidental diagnosis (multivariable-adjusted OR 1.72, 95% CI 1.02-2.91). Adjustment for hospital (private vs safety net) attenuated the observed associations, but disparities by SES remained statistically significant for tumor size. Despite substantial differences at presentation, there were no significant differences in length of stay or odds of an uncomplicated procedure by zip code-level SES. Patients from lower-SES zip codes were more likely to require postoperative steroid replacement and less likely to achieve gross-total resection. CONCLUSIONS: In this series, lower zip code-level SES was associated with more severe disease at the time of diagnosis for NFPA patients, including larger tumor size and lower rates of incidental diagnosis. Despite these differences at presentation, no significant differences were observed in short-term postoperative complications, although patients with higher zip code-level SES had higher rates of gross-total resection.

Growth hormone secreting pituitary adenomas show distinct extrasellar extension patterns compared to nonfunctional pituitary adenomas.

PURPOSE: Patterns of extension of pituitary adenomas (PA) may vary according to PA subtype. Understanding extrasellar extension patterns in growth hormone PAs (GHPA) vis-a-vis nonfunctional PAs (NFPAs) may provide insights into the biology of GHPA and future treatment avenues. METHODS: Preoperative MR imaging (MRI) in 179 consecutive patients treated surgically for NFPA (n = 139) and GHPA (n = 40) were analyzed to determine patterns of extrasellar growth. Extension was divided into two principal directions: cranio-caudal (measured by infrasellar/suprasellar extension), and lateral cavernous sinus invasion (CSI) determined by Knosp grading score of 3-4. Suprasellar extension was defined as tumor extension superior to the tuberculum sellae- dorsum sellae line, and inferior extension as invasion through the sellar floor into the sphenoid sinus or clivus. Categorical analysis was performed using Fisher's exact test. RESULTS: GHPAs were overall more likely to remain purely intrasellar compared to NFPA (50% vs 26%, p < 0.001). GHPAs, however, were 7 times more likely to exhibit isolated infrasellar extension compared to NFPA (20% vs 2.8%, p = 0.001). Conversely, NFPAs were twice as likely to exhibit isolated suprasellar extension compared to GHPA (60% vs 28%, p < 0.001), as well as combined suprasellar/infrasellar extension (25% vs 3%, p = 0.011). There were no overall differences in CSI between the two subgroups. DISCUSSION: GHPA and NFPA demonstrate distinct extrasellar extension patterns on MRI. GHPAs show proclivity for inferior extension with bony invasion, whereas NFPAs are more likely to exhibit suprasellar extension through the diaphragmatic aperture. These distinctions may have implications into the biology and future treatment of PAs.

Evaluating the predictive value of comorbidity indices in pituitary surgery: a mixed-effects modeling study using the Nationwide Readmissions Database.

OBJECTIVE: Although pituitary adenomas (PAs) are common intracranial tumors, literature evaluating the utility of comorbidity indices for predicting postoperative complications in patients undergoing pituitary surgery remains limited, thereby hindering the development of complex models that aim to identify high-risk patient populations. We utilized comparative modeling strategies to evaluate the predictive validity of various comorbidity indices and combinations thereof in predicting key pituitary surgery outcomes. METHODS: The Nationwide Readmissions Database was used to identify patients who underwent pituitary tumor operations (n = 19,653) in 2016-2017. Patient frailty was assessed using the Johns Hopkins Adjusted Clinical Groups (ACG) System. The Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI) were calculated for each patient. Five sets of generalized linear mixed-effects models were developed, using as the primary predictors 1) frailty, 2) CCI, 3) ECI, 4) frailty + CCI, or 5) frailty + ECI. Complications of interest investigated included inpatient mortality, nonroutine discharge (e.g., to locations other than home), length of stay (LOS) within the top quartile (Q1), cost within Q1, and 1-year readmission rates. RESULTS: Postoperative mortality occurred in 73 patients (0.4%), 1-year readmission was reported in 2994 patients (15.2%), and nonroutine discharge occurred in 2176 patients (11.1%). The mean adjusted all-payer cost for the procedure was USD $25,553.85 ± $26,518.91 (Q1 $28,261.20), and the mean LOS was 4.8 ± 7.4 days (Q1 5.0 days). The model using frailty + ECI as the primary predictor consistently outperformed other models, with statistically significant p values as determined by comparing areas under the curve (AUCs) for most complications. For prediction of mortality, however, the frailty + ECI model (AUC 0.831) was not better than the ECI model alone (AUC 0.831; p = 0.95). For prediction of readmission, the frailty + ECI model (AUC 0.617) was not better than the frailty model alone (AUC 0.606; p = 0.10) or the frailty + CCI model (AUC 0.610; p = 0.29). CONCLUSIONS: This investigation is to the authors' knowledge the first to implement mixed-effects modeling to study the utility of common comorbidity indices in a large, nationwide cohort of patients undergoing pituitary surgery. Knowledge gained from these models may help neurosurgeons identify high-risk patients who require additional clinical attention or resource utilization prior to surgical planning.

Use of predictive spatial modeling to reveal that primary cancers have distinct central nervous system topography patterns of brain metastasis.

OBJECTIVE: Brain metastasis is the most common intracranial neoplasm. Although anatomical spatial distributions of brain metastasis may vary according to primary cancer subtype, these patterns are not understood and may have major implications for treatment. METHODS: To test the hypothesis that the spatial distribution of brain metastasis varies according to cancer origin in nonrandom patterns, the authors leveraged spatial 3D coordinate data derived from stereotactic Gamma Knife radiosurgery procedures performed to treat 2106 brain metastases arising from 5 common cancer types (melanoma, lung, breast, renal, and colorectal). Two predictive topographic models (regional brain metastasis echelon model [RBMEM] and brain region susceptibility model [BRSM]) were developed and independently validated. RESULTS: RBMEM assessed the hierarchical distribution of brain metastasis to specific brain regions relative to other primary cancers and showed that distinct regions were relatively susceptible to metastasis, as follows: bilateral temporal/parietal and left frontal lobes were susceptible to lung cancer; right frontal and occipital lobes to melanoma; cerebellum to breast cancer; and brainstem to renal cell carcinoma. BRSM provided probability estimates for each cancer subtype, independent of other subtypes, to metastasize to brain regions, as follows: lung cancer had a propensity to metastasize to bilateral temporal lobes; breast cancer to right cerebellar hemisphere; melanoma to left temporal lobe; renal cell carcinoma to brainstem; and colon cancer to right cerebellar hemisphere. Patient topographic data further revealed that brain metastasis demonstrated distinct spatial patterns when stratified by patient age and tumor volume. CONCLUSIONS: These data support the hypothesis that there is a nonuniform spatial distribution of brain metastasis to preferential brain regions that varies according to cancer subtype in patients treated with Gamma Knife radiosurgery. These topographic patterns may be indicative of the abilities of various cancers to adapt to regional neural microenvironments, facilitate colonization, and establish metastasis. Although the brain microenvironment likely modulates selective seeding of metastasis, it remains unknown how the anatomical spatial distribution of brain metastasis varies according to primary cancer subtype and contributes to diagnosis. For the first time, the authors have presented two predictive models to show that brain metastasis, depending on its origin, in fact demonstrates distinct geographic spread within the central nervous system. These findings could be used as a predictive diagnostic tool and could also potentially result in future translational and therapeutic work to disrupt growth of brain metastasis on the basis of anatomical region.

Treatment strategies for giant pituitary adenomas in the era of endoscopic transsphenoidal surgery: a multicenter series.

OBJECTIVE: Given the anatomical complexity and frequently invasive growth of giant pituitary adenomas (GPAs), individually tailored approaches are required. The aim of this study was to assess the treatment strategies and outcomes in a large multicenter series of GPAs in the era of endoscopic transsphenoidal surgery (ETS). METHODS: This was a retrospective case-control series of 64 patients with GPAs treated at two tertiary care centers by surgeons with experience in ETS. GPAs were defined by a maximum diameter of ≥ 4 cm and a volume of ≥ 10 cm3 on preoperative isovoxel contrast-enhanced MRI. RESULTS: The primary operation was ETS in all cases. Overall gross-total resection rates were 64% in round GPAs, 46% in dumbbell-shaped GPAs, and 8% in multilobular GPAs (p < 0.001). Postoperative outcomes were further stratified into two groups based on extent of resection: group A (gross-total resection or partial resection with intracavernous remnant; 21/64, 33%) and group B (partial resection with intracranial remnant; 43/64, 67%). Growth patterns of GPAs were mostly round (11/14, 79%) in group A and multilobular (33/37, 89%) in group B. In group A, no patients required a second operation, and 2/21 (9%) were treated with adjuvant radiosurgery. In group B, early transcranial reoperation was required in 6/43 (14%) cases due to hemorrhagic transformation of remnants. For the remaining group B patients with remnants, 5/43 (12%) underwent transcranial surgery and 12/43 (28%) underwent delayed second ETS. There were no deaths in this series. Severe complications included stroke (6%), meningitis (6%), hydrocephalus requiring shunting (6%), and loss or distinct worsening of vision (3%). At follow-up (mean 3 years, range 0.5-16 years), stable disease was achieved in 91% of cases. CONCLUSIONS: ETS as a primary treatment modality to relieve mass effect in GPAs and extent of resection are dependent on GPA morphology. The pattern of residual pituitary adenoma guides further treatment strategies, including early transcranial reoperation, delayed endoscopic transsphenoidal/transcranial reoperation, and adjuvant radiosurgery.

Postoperative GH and Degree of Reduction in IGF-1 Predicts Postoperative Hormonal Remission in Acromegaly.

Purpose: Determine predictive factors for long-term remission of acromegaly after transsphenoidal resection of growth hormone (GH)-secreting pituitary adenomas. Methods: We identified 94 patients who had undergone transsphenoidal resection of GH-secreting pituitary adenomas for treatment of acromegaly at the USC Pituitary Center from 1999-2019 to determine the predictive value of postoperative endocrine lab values. Results: Patients underwent direct endoscopic endonasal (60%), microscopic transsphenoidal (38%), and extended endoscopic approaches (2%). The cohort was 63% female and 37% male, with average age of 48.9 years. Patients presented with acral enlargement (72, 77%), macroglossia (40, 43%), excessive sweating (39, 42%), prognathism (38, 40%) and frontal bossing (35, 37%). Seventy-five (80%) were macroadenomas and 19 (20%) were microadenomas. Cavernous sinus invasion was present in 45%. Available immunohistochemical data demonstrated GH staining in 88 (94%) and prolactin in 44 (47%). Available postoperative MRI demonstrated gross total resection in 63% of patients and subtotal resection in 37%. Most patients (66%) exhibited hormonal remission at 12 weeks postoperatively. Receiver operating characteristic (ROC) curves demonstrated postoperative day 1 (POD1) GH levels ≥1.55ng/mL predicted failure to remit from surgical resection alone (59% specificity, 75% sensitivity). A second ROC curve showed decrease in corrected insulin-like growth factor-1 (IGF-1) levels of at least 37% prognosticated biochemical control (90% sensitivity, 80% specificity). Conclusion: POD1 GH and short-term postoperative IGF-1 levels can be used to successfully predict immediate and long-term hormonal remission respectively. A POD1 GH cutoff can identify patients likely to require adjuvant therapy to emphasize clinical follow-up.

Consensus on diagnosis and management of Cushing's disease: a guideline update.

Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants. During the meeting, concise summaries of the recorded lectures were presented, followed by small group breakout discussions. Consensus opinions from each group were collated into a draft document, which was reviewed and approved by all participants. Recommendations regarding use of laboratory tests, imaging, and treatment options are presented, along with algorithms for diagnosis of Cushing's syndrome and management of Cushing's disease. Topics considered most important to address in future research are also identified.

Cure and Hormonal Control After Prolactinoma Resection: Case Series and Systematic Review.

CONTEXT: Surgical management of prolactinomas is an important treatment for patients intolerant of dopamine agonist therapy. However, predictors of postoperative outcomes remain unclear. OBJECT: While transsphenoidal surgical resection (TSSR) is important second-line therapy in prolactinoma patients, predictors of surgical cure and biochemical remission following TSSR remain sparse. METHODS: A retrospective review of prolactinoma patients undergoing TSSR at the USC Pituitary Center from 1995 to 2020 was conducted. Participants were categorized as surgical cure (normalization of serum prolactin without medical treatment), surgical noncure, biochemical control (prolactin normalization with or without adjuvant therapy), and nonbiochemical control. A systematic review of the outcomes of surgically managed prolactinomas was performed. RESULTS: The 40 female and 16 male participants had an average age of 35.6 years. Prior treatment included transsphenoidal resection (6, 11%) and dopamine agonist treatment (47, 84%). The 40 macroadenomas and 15 microadenomas exhibited suprasellar extension (24, 43%) and parasellar invasion (20, 36%). Fifteen (27%) were purely intrasellar. Gross total resection was achieved in 25 patients (45%) and subtotal in 26 (46%). Surgical cure was achieved in 25 patients (46%) and biochemical control in 35 (64%). Surgical cure was more likely in smaller, noninvasive tumors, those that were fully resected, and patients with lower preoperative (< 1000 ng/mL) and immediately postoperative (< 7.6 ng/mL) prolactin levels. Ten of 26 patients (38%) undergoing adjuvant therapy achieved biochemical control, which was less likely in men and those with higher preoperative prolactin or invasive tumors. CONCLUSION: Surgical resection of prolactinomas is a safe procedure that, when offered judiciously, can achieve symptom and/or biochemical control in a majority of patients. A variety of predictors may be useful in advising patients on likelihood of postoperative remission.

Silent corticotroph pituitary adenomas: clinical characteristics, long-term outcomes, and management of disease recurrence.

OBJECTIVE: Silent corticotroph adenomas (SCAs) are a distinct subtype of nonfunctioning pituitary adenomas (NFAs) that demonstrate positive immunohistochemistry for adrenocorticotropic hormone (ACTH) without causing Cushing's disease. SCAs are hypothesized to exhibit more aggressive behavior than standard NFAs. The authors analyzed their institution's surgical experience with SCAs in an effort to characterize rates of invasion, postoperative clinical outcomes, and patterns of disease recurrence and progression. The secondary objectives were to define the best treatment strategies in the event of tumor recurrence and progression. METHODS: A retrospective analysis of patients treated at the authors' institution identified 100 patients with SCAs and 841 patients with NFAs of other subtypes who were treated surgically from 2000 to 2019. Patient demographics, tumor characteristics, surgical and neuroimaging data, rates of endocrinopathy, and neurological outcomes were recorded. Cohorts of patients with SCAs and patients with standard NFAs were compared with regard to these characteristics and outcomes. RESULTS: The SCA cohort presented with cranial neuropathy (13% vs 5.7%, p = 0.0051) and headache (53% vs 42.3%, p = 0.042) compared to the NFA cohort, despite similar rates of apoplexy. The SCA cohort included a higher proportion of women (SCA 60% vs NFA 45.8%, p = 0.0071) and younger age at presentation (SCA 50.5 ± 13.3 vs NFA 54.6 ± 14.9 years of age, p = 0.0082). Reoperations were comparable between the cohorts (SCA 16% vs NFA 15.7%, p = 0.98). Preoperative pituitary function was comparable between the cohorts with the exception of higher rates of preoperative panhypopituitarism in NFA patients (2% vs 6.1%, respectively; p = 0.0033). The mean tumor diameter in SCA patients was 24 ± 10.8 mm compared to 26 ± 11.3 mm in NFA patients (p = 0.05). Rates of cavernous sinus invasion were higher in the SCA group (56% vs 49.7%), although this result did not reach statistical significance. There were no significant differences in extent of resection, intraoperative CSF leak rates, endocrine or neurological outcomes, or postoperative complications. Ki-67 rates were significantly increased in the SCA cohort (2.88 ± 2.79) compared to the NFA cohort (1.94 ± 1.99) (p = 0.015). Although no differences in overall rates of progression or recurrence were noted, SCAs had a significantly lower progression-free survival (24.5 vs 51.1 months, p = 0.0011). Among the SCA cohort, progression was noted despite the use of adjuvant radiosurgery in 33% (n = 4/12) of treated tumors. Adequate tumor control was not achieved in half (n = 6) of the SCA progression cohort despite radiosurgery or multiple resections. CONCLUSIONS: In this study, to the authors' knowledge the largest surgical series to assess outcomes in SCAs to date, the findings suggest that SCAs are more biologically aggressive tumors than standard NFAs. The progression-free survival duration of patients with SCAs is only about half that of patients with other NFAs. Therefore, close neuroimaging and clinical follow-up are warranted in patients with SCAs, and residual disease should be considered for early postoperative adjuvant radiosurgery, particularly in younger patients.

The role of reoperation after recurrence of Cushing's disease.

Surgical failure or recurrence of Cushing's disease can be treated with medical therapy, radiotherapy, adrenalectomy, and/or repeat transsphenoidal surgery, all of which have their respective benefits and drawbacks. Redo transsphenoidal surgery has been shown to achieve at least short-term remission in about 40-80% of patients and is associated with low rates of morbidity and near-zero mortality, albeit higher rates of postoperative hypopituitarism, diabetes insipidus, and cerebrospinal fluid leak than initial resection. Despite this, recurrence may ensue in 50% of patients. When selecting patient candidates for reoperation, many predictors of postoperative outcomes have been proposed including imaging characteristics, histopathological staining, intraoperative tumor visualization, and tumor size, however no single predictor consistently predicts outcomes. Redo transsphenoidal surgery should be performed by an experienced pituitary surgeon and patients should be followed at a tertiary care center by a multidisciplinary team consisting of an experienced endocrinologist and neurosurgeon to monitor closely for remission and recurrence.

Safety and Effectiveness of the Direct Endoscopic Endonasal Approach for Primary Sellar Pathology: A Contemporary Case Series of More Than 400 Patients.

BACKGROUND: The direct endoscopic endonasal approach (EEA) has become the primary technique used for resection of sellar pathology, meriting investigation into the risk factors for complications and predictors of postoperative outcomes after direct EEA. METHODS: We retrospectively analyzed the patient and tumor characteristics from 404 patients who had undergone direct EEA for sellar pathology at the USC Pituitary Center from September 2011 to December 2019. RESULTS: Of the 404 pathologic entities included, 349 (86%) were pituitary adenomas (PAs), 29 (7%) were Rathke cleft cysts, and 26 (6%) were other sellar lesions. The mean lesion diameter was 2.3 cm, with 34 microadenomas (10%) and 315 macroadenomas (90%). Cavernous sinus invasion was present in 39% of the PAs. No patient died. The surgical complications included internal carotid artery injury without neurological sequelae (0.2%), vision loss (0.7%), meningitis (0.7%), cerebrospinal fluid leak (4%), epistaxis (4%), sinusitis (1%), transient cranial nerve paresis (0.5%), and postoperative abscess (0.25%). New hypopituitarism developed in 3%. Gross total resection was achieved in 208 PA cases (58%). Clinical improvement of headaches and visual deficits were reported for 67% and 76% of cases, respectively. Hormonal remission was achieved in 82% of patients with functional PAs. The median hospital stay was 2 days, with 34 patients (8%) readmitted within 30 days and 10 (3%) undergoing early reoperation. Disease recurrence or progression developed in 10% and was less likely in the case of gross total resection and apoplexy. CONCLUSION: In the present, large, consecutive, mostly single-surgeon series, the patients experienced clinical improvement in most preoperative symptoms and had low rates of perioperative morbidity. We have demonstrated that direct EEA can be efficiently, safely, and successfully performed by a neurosurgical team.

Melanoma metastasis to a nonfunctioning pituitary macroadenoma: illustrative case.

BACKGROUND: Metastases to the central nervous system are often multiple in number and typically favor the gray-white matter junction. Collision tumors, defined as the coexistence of two morphologically different tumors, such as metastases to a known pituitary adenoma (PA), are exceedingly rare. Only a few reported cases of metastases to a PA exist in the literature. OBSERVATIONS: The authors present the case of a 64-year-old man with a known history of stage IV metastatic melanoma who was found to have hypermetabolic activity in the sellar region on surveillance positron emission tomography. On laboratory evaluation, he had clear evidence of pituitary axis dysfunction without diabetes insipidus. Subsequent magnetic resonance imaging showed a 2.4-cm sellar mass with features of a pituitary macroadenoma and internal hemorrhage, although no clinical symptoms of apoplexy were noted. He underwent a transsphenoidal endoscopic endonasal approach for resection of the sellar lesion. Final pathology showed a collision tumor with melanoma cells intermixed with PA cells. LESSONS: Histological analysis verified the rare presence of a collision tumor of a melanoma metastasis to a nonfunctional pituitary macroadenoma. Metastasis to a preexisting PA, although rare, should be considered in the differential diagnosis in patients with sellar lesions and a known cancer history.

Discrepancies in the Recommended Management of Adrenal Incidentalomas by Various Guidelines.

PURPOSE: Adrenal incidentalomas are being discovered with increasing frequency, and their discovery poses a challenge to clinicians. Despite the 2002 National Institutes of Health consensus statement, there are still discrepancies in the most recent guidelines from organizations representing endocrinology, endocrine surgery, urology and radiology. We review recent guidelines across the specialties involved in diagnosing and treating adrenal incidentalomas, and discuss points of agreement as well as controversy among guidelines. MATERIALS AND METHODS: PubMed®, Scopus®, Embase™ and Web of Science™ databases were searched systematically in November 2019 in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to identify the most recently updated committee produced clinical guidelines in each of the 4 specialties. Five articles met the inclusion criteria. RESULTS: There is little debate among the reviewed guidelines as to the initial evaluation of an adrenal incidentaloma. All patients with a newly discovered adrenal incidentaloma should receive an unenhanced computerized tomogram and hormone screen. The most significant points of divergence among the guidelines regard reimaging an initially benign appearing mass, repeat hormone testing and management of an adrenal incidentaloma that is not easily characterized as benign or malignant on computerized tomography. The guidelines range from actively recommending against any repeat imaging and hormone screening to recommending a repeat scan as early as in 3 to 6 months and annual hormonal screening for several years. CONCLUSIONS: After reviewing the guidelines and the evidence used to support them we posit that best practices lie at their convergence and have presented our management recommendations on how to navigate the guidelines when they are discrepant.