Telemedicine for Neurosurgery Consultations at a Pituitary Center of Excellence: Patient Preference and Willingness to Proceed with Surgery.

Objective The purpose of this study was to evaluate pituitary tumor patient satisfaction with telemedicine, patient preference for telemedicine, potential socioeconomic benefit of telemedicine, and patients' willingness to proceed with surgery based on a telemedicine visit alone. Method In total, 134 patients who had pituitary surgery and a telemedicine visit during the coronavirus disease 2019 (COVID-19) pandemic (April 23, 2020-March 4, 2021) were called to participate in a 13-part questionnaire. Chi-square, ANOVA, and Wilcoxon Rank Sum tests were used to determine significance. Result Of 134 patients contacted, 90 responded (67%). Ninety-five percent were "satisfied" or "very satisfied" with their telemedicine visit, with 62% stating their visit was "the same" or "better" than previous in-person appointments. Eighty-two percent of the patients rated their telemedicine visit as "easy" or "very easy." On average, patients saved 150 minutes by using telemedicine compared with patient reported in-person visit times. Seventy-seven percent of patients reported the need to take off from work for in-person visits, compared with just 12% when using telemedicine. Forty-nine percent of patients preferred in-person visits, 34% preferred telemedicine, and 17% had no preference. Fifty percent of patients said they would feel comfortable proceeding with surgery based on a telemedicine visit alone. Patients with both initial evaluation and follow-up conducted via telemedicine were more likely to feel comfortable proceeding with surgery based on a telemedicine visit alone compared with patients who had only follow-up telemedicine visits ( p = 0.051). Conclusion Many patients are satisfied with telemedicine visits and feel comfortable proceeding with surgery based on a telemedicine visit alone. Telemedicine is an important adjunct to increase access to care at a Pituitary Center of Excellence.

Surgery for acromegaly: Indications and goals.

Acromegaly is a disease that occurs secondary to high levels of GH, most often from a hormone-secreting pituitary adenoma, with multisystem adverse effects. Diagnosis includes serum GH and IGF-1 levels, and obtaining an MRI pituitary protocol to assess for a functional pituitary adenoma. Attempted gross total resection of the GH-secreting adenoma is the gold standard in treatment for patients with acromegaly for a goal of biochemical remission. Medical and radiation therapies are available when patients do not achieve biochemical cure after surgical therapy.

Cushing Disease: Medical and Surgical Considerations.

Cushing disease is a disorder of hypercortisolemia caused by hypersecretion of adrenocorticotropic hormone by a pituitary adenoma and is a rare diagnosis. Cushing disease presents with characteristic clinical signs and symptoms associated with excess cortisol, but diagnosis is difficult and often relies on repeated and varied endocrinologic assays and neuroradiologic investigations. Gold standard treatment is surgical resection of adrenocorticotropic hormone-secreting pituitary adenoma, which is curative. Patients require close endocrinologic follow-up for maintenance of associated neuroendocrine deficiencies and surveillance for potential recurrence. Medications, radiation therapy, and bilateral adrenalectomy are alternative treatments for residual or recurrent disease.

Modern Linear Accelerator-Based Radiotherapy Is Safe and Effective in the Treatment of Secretory and Nonsecretory Pituitary Adenomas.

BACKGROUND: Adjuvant radiotherapy (RT) can help achieve local control (LC) and reduce hormonal overexpression for pituitary adenomas (PAs). Prior reports involved Gamma Knife or older linear accelerator (LINAC) techniques. The aim of this study was to report long-term outcomes for modern LINAC RT. METHODS: Institutional retrospective review of LINAC RT for PAs with minimum 3 years of magnetic resonance imaging follow-up was performed. Hormonal control was defined as biochemical remission in absence of medications targeting hormone excess. LC defined using Response Evaluation Criteria in Solid Tumors on surveillance magnetic resonance imaging. Progression-free survival defined as time alive with LC without return of or worsening hormonal excess from secretory PA. Kaplan-Meier and Cox proportional hazard models used. RESULTS: From 2003 to 2017, 140 patients with PAs (94 nonsecretory, 46 secretory) were treated with LINAC RT (105 fractionated RT, 35 radiosurgery) with median follow-up of 5.35 years. Techniques included fixed gantry intensity-modulated radiotherapy (51.4%), dynamic conformal arcs (9.3%), and volumetric modulated arc therapy (39.3%). Progression-free survival at 5 years was 95.3% for secretory tumors and 94.8% for nonsecretory tumors. Worse progression-free survival was associated with larger planning target volume on multivariable analysis (hazard ratio 2.87, 95% confidence interval 1.01-8.21, P = 0.049). Hormonal control at 5 years was 50.0% and associated with higher dose to tumor (hazard ratio 1.05, 95% confidence interval 1.02-1.09, P = 0.005) and number of surgeries (hazard ratio 1.74, 95% confidence interval 1.05-2.89, P = 0.032). Patients requiring any pituitary hormone replacement increased from 57.9% to 70.0% after RT. CONCLUSIONS: Modern LINAC RT for patients with PAs was safe and effective for hormonal control and LC. No difference in LC was noted for functional versus nonfunctional tumors, possibly owing to higher total dose and daily image guidance.

Functioning Crooke Cell Adenomas: Case Series and Literature Review.

BACKGROUND: Crooke cell adenomas (CCAs) are rare, potentially aggressive pituitary adenomas. Data regarding prevalence and clinical course are sparse. METHODS: We performed a retrospective review of 59 consecutive functioning corticotroph adenomas operated on between October 2017 and November 2020 and a literature review of CCA publications since 1991. RESULTS: The prevalence of CCAs among functioning corticotroph adenomas at our institution was 8.5% (5/59). In the 4 other surgical case series, prevalence of CCAs was 0%-6.8%. Our patients (4 women and 1 man, mean age 46 ± 11 years) presented with hypercortisolism (3/5), with vision loss (1/5), and incidentally (1/5). All patients had elevated adrenocorticotropic hormone (151 ± 54 pg/mL) and urinary free cortisol (830 ± 796.5 µg/day). Radiologically, 3 tumors were macroadenomas and 2 had cavernous sinus invasion. All patients achieved biochemical remission at 3 months postoperatively. One patient with a giant pituitary adenoma underwent fractionated radiation for residual tumor. During follow-up (range, 3.1-31.0 months), no patients had evidence of radiological or biochemical recurrence. The literature review identified 22 functioning corticotroph adenomas with outcome data. Additional treatments included reoperation (50%), radiation (59%), bilateral adrenalectomy (23%), and temozolomide (36%). CONCLUSIONS: We found a higher CCA prevalence among functioning adrenocorticotropic hormone adenomas after implementation of the 2017 World Health Organization classification. In our series and the literature, most CCAs were macroadenomas with high adrenocorticotropic hormone levels. Postoperative outcomes were excellent in our series, while some cases from the literature were refractory to standard treatments. Larger clinical and molecular studies are needed to identify patients at risk.

Racial Disparities in Acromegaly and Cushing's Disease: A Referral Center Study in 241 Patients.

CONTEXT: Acromegaly (ACM) and Cushing's disease (CD) are caused by functioning pituitary adenomas secreting growth hormone and ACTH respectively. OBJECTIVE: To determine the impact of race on presentation and postoperative outcomes in adults with ACM and CD, which has not yet been evaluated. METHODS: This is a retrospective study of consecutive patients operated at a large-volume pituitary center. We evaluated (1) racial distribution of patients residing in the metropolitan area (Metro, N = 124) vs 2010 US census data, and(2) presentation and postoperative outcomes in Black vs White for patients from the entire catchment area (N = 241). RESULTS: For Metro area (32.4% Black population), Black patients represented 16.75% ACM (P = .006) and 29.2% CD (P = .56). Among the total 112 patients with ACM, presentations with headaches or incidentaloma were more common in Black patients (76.9% vs 31% White, P = .01). Black patients had a higher prevalence of diabetes (54% vs 16% White, P = .005), significantly lower interferon insulin-like growth factor (IGF)-1 deviation from normal (P = .03) and borderline lower median growth hormone levels (P = .09). Mean tumor diameter and proportion of tumors with cavernous sinus invasion were similar. Three-month biochemical remission (46% Black, 55% White, P = .76) and long-term IGF-1 control by multimodality therapy (92.3% Black, 80.5% White, P = .45) were similar. Among the total 129 patients with CD, Black patients had more hypopituitarism (69% vs 45% White, P = .04) and macroadenomas (33% vs 15% White, P = .05). At 3 months, remission rate was borderline higher in White (92% vs 78% Black, P = 0.08), which was attributed to macroadenomas by logistic regression. CONCLUSION: We identified disparities regarding racial distribution, and clinical and biochemical characteristics in ACM, suggesting late or missed diagnosis in Black patients. Large nationwide studies are necessary to confirm our findings.

The genomic profiling and MAMLD1 expression in human and canines with Cushing's disease.

BACKGROUND: Cushing's disease (CD) is defined as hypercortisolemia caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (corticotroph PA) that afflicts humans and dogs. In order to map common aberrant genomic features of CD between humans and dogs, we performed genomic sequencing and immunostaining on corticotroph PA. METHODS: For inclusion, humans and dog were diagnosed with CD. Whole exome sequencing (WES) was conducted on 6 human corticotroph PA. Transcriptome RNA-Seq was performed on 6 human and 7 dog corticotroph PA. Immunohistochemistry (IHC) was complete on 31 human corticotroph PA. Corticotroph PA were compared with normal tissue and between species analysis were also performed. RESULTS: Eight genes (MAMLD1, MNX1, RASEF, TBX19, BIRC5, TK1, GLDC, FAM131B) were significantly (P < 0.05) overexpressed across human and canine corticotroph PA. IHC revealed MAMLD1 to be positively (3+) expressed in the nucleus of ACTH-secreting tumor cells of human corticotroph PA (22/31, 70.9%), but absent in healthy human pituitary glands. CONCLUSIONS: In this small exploratory cohort, we provide the first preliminary insights into profiling the genomic characterizations of human and dog corticotroph PA with respect to MAMLD1 overexpression, a finding of potential direct impact to CD microadenoma diagnosis. Our study also offers a rationale for potential use of the canine model in development of precision therapeutics.

Pituitary society expert Delphi consensus: operative workflow in endoscopic transsphenoidal pituitary adenoma resection.

PURPOSE: Surgical workflow analysis seeks to systematically break down operations into hierarchal components. It facilitates education, training, and understanding of surgical variations. There are known educational demands and variations in surgical practice in endoscopic transsphenoidal approaches to pituitary adenomas. Through an iterative consensus process, we generated a surgical workflow reflective of contemporary surgical practice. METHODS: A mixed-methods consensus process composed of a literature review and iterative Delphi surveys was carried out within the Pituitary Society. Each round of the survey was repeated until data saturation and > 90% consensus was reached. RESULTS: There was a 100% response rate and no attrition across both Delphi rounds. Eighteen international expert panel members participated. An extensive workflow of 4 phases (nasal, sphenoid, sellar and closure) and 40 steps, with associated technical errors and adverse events, were agreed upon by 100% of panel members across rounds. Both core and case-specific or surgeon-specific variations in operative steps were captured. CONCLUSIONS: Through an international expert panel consensus, a workflow for the performance of endoscopic transsphenoidal pituitary adenoma resection has been generated. This workflow captures a wide range of contemporary operative practice. The agreed "core" steps will serve as a foundation for education, training, assessment and technological development (e.g. models and simulators). The "optional" steps highlight areas of heterogeneity of practice that will benefit from further research (e.g. methods of skull base repair). Further adjustments could be made to increase applicability around the world.

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

The WHO Classification of Endocrine Tumours designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.

Rare Case of a Disappearing Pituitary Adenoma During the Coronavirus Disease 2019 (COVID-19) Pandemic.

We present a case of a 28-year-old woman with a history of severe headaches and pituitary insufficiency. She was found to have a large, enhancing, sellar mass consistent with a pituitary adenoma. The patient's surgical care was delayed due to the coronavirus disease 2019 (COVID-19) pandemic, and follow-up imaging revealed spontaneous involution of the sellar mass. Spontaneous involution of pituitary masses has been described but not often encountered in clinical practice. This case highlights that follow-up imaging is necessary when scheduling elective surgeries during the COVID-19 pandemic.

Spontaneous Skull Base Cerebrospinal Fluid Leaks and Their Relationship to Idiopathic Intracranial Hypertension.

BACKGROUND: The association between spontaneous skull base cerebrospinal fluid (CSF) leaks and idiopathic intracranial hypertension (IIH) has been suggested, but its significance remains unclear. OBJECTIVE: To estimate the prevalence of IIH in spontaneous skull base CSF leak patients. METHODS: Systematic collection of demographics, neuro-ophthalmic and magnetic resonance imaging evaluation of spontaneous skull base CSF leak patients seen pre- and post-leak repair in one neuro-ophthalmology service. Patients with preexisting IIH were diagnosed with definite IIH if adequate documentation was provided; otherwise, they were categorized with presumed IIH. Classic radiographic signs of intracranial hypertension and bilateral transverse venous sinus stenosis were recorded. RESULTS: Thirty six patients were included (age [interquartile range]: 50 [45;54] years; 94% women; body mass index: 36.8 [30.5;39.9] kg/m2), among whom six (16.7%, [95% confidence interval, CI]: [6.4;32.8]) had a preexisting diagnosis of definite or presumed IIH. Of the remaining 30 patients, four (13.3%, 95%CI: [3.8;30.7]) had optic nerve head changes suggesting previously undiagnosed IIH, while one was newly diagnosed with definite IIH at initial consultation. One out of 29 patients with normal findings of the optic nerve head at presentation developed new onset papilledema following surgery (3.4%, 95%CI: [0.1;17.8]) and was ultimately diagnosed with definite IIH. Overall, the prevalence of definite IIH was 19.4% (95%CI: [8.2;36.0]). CONCLUSION: Striking demographic overlap exists between IIH patients and those with spontaneous CSF leak. Definite IIH was present in approximately 20% of our patients. However, its true prevalence is likely higher than identified by using classic criteria. We therefore hypothesize that an active CSF leak serves as an auto-diversion for CSF, thereby "treating" the intracranial hypertension and eliminating characteristic signs and symptoms at initial presentation.

Risk Factors for Rhinosinusitis After Endoscopic Transsphenoidal Adenomectomy.

OBJECTIVE: Patients undergoing endoscopic transsphenoidal adenomectomy (eTSA) for pituitary tumors are at risk for postoperative complications, including rhinosinusitis. We aimed to determine if preoperative sinonasal disease is a risk factor for postoperative rhinosinusitis (PRS). STUDY DESIGN: Retrospective review. SETTING: Tertiary academic center in U.S. SUBJECTS AND METHODS: Patients with a diagnosis of pituitary adenoma who underwent eTSA between 2007-2016. PRS patients were matched to non-PRS patients or sex, age, tumor size, skull base reconstruction with intranasal tissue grafting, and concurrent septoplasty. Groups were statistically analyzed for potential preoperative risk factors of sinonasal disease (patient-reported, radiographic, endoscopic). RESULTS: 49 of 987 patients who underwent eTSA developed PRS (44.9% male, 71.4% Caucasian, mean age 49.3y). On analysis of individual risk factors, there was a significantly higher proportion of patients with a history of prior sinonasal surgery in the PRS group than the non-PRS group (25.5% vs. 6.5%, p = 0.01); however, this group difference became insignificant on multivariate analysis. There were no significant group differences with regard to history of sinus infections, nasal symptoms, seasonal allergies, radiographic abnormalities, or sinonasal disease on endoscopy. CONCLUSION: This is the first study to investigate preoperative sinonasal disease as a risk factor for PRS after eTSA. The risk factors considered did not demonstrate definitive risk for PRS, although a history of prior sinonasal surgery should be investigated further.

Incidentally detected acromegaly: single-center study of surgically treated patients over 22 years.

Acromegaly is a rare disease associated with comorbidities that are common in the general population. Most patients undergo screening for classic phenotypical (CP) or mass effect manifestations. By retrospective review of pituitary tumor surgeries performed between 1994 and 2016 (1836), we identified patients with acromegaly (112). Main presentations were: CP (43%), mass effect (26%), incidentally detected (ID) tumors (17%), and other (14%). We compared the ID and CP groups regarding prevalence, clinical, biochemical, radiological and histopathological characteristics, and postoperative outcomes. The prevalence of ID among all surgeries increased after 2011 from 0.6% to 1.9% (p=0.01), while prevalence of CP remained stable (2.8% and 2.33%, p=0.65). Almost half of ID (47.4%) presented with otolaryngological manifestations. The ID and CP groups were similar regarding age, gender, comorbidities (hypertension, diabetes, hypopituitarism), tumor diameter and cavernous sinus invasion. Median insulin-like growth factor (IGF-1) and growth hormone (GH) levels were lower in the ID than CP (p<0.05 and p=0.07). Patients younger than 40 had smaller tumors in the ID than CP, while the opposite was true for older patients. The 3-month biochemical remission rates were similar (68% ID and 58% CP). A similar number of patients had normal IGF-1 at last follow-up (89.5% ID and 81.25% CP) after surgery alone and multimodality treatment. In conclusion, an increased number of patients with GH-secreting adenomas were ID in recent years. Education of physicians other than endocrinologists regarding presentation and comorbidity clustering may lead to an earlier diagnosis of acromegaly and improved outcomes.

Sheltered Neurosurgery During COVID-19: The Emory Experience.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) pandemic has directly and indirectly impacted health care systems, including residency programs. Social distancing, cancellation of elective cases, and staff re-deployment have compromised clinical and academic teaching. We describe the neurosurgical experience at Emory University during the COVID-19 pandemic and the impact of COVID-19-related policies on resident experience. METHODS: We retrospectively reviewed all neurosurgical cases performed at Emory University Hospital between March 16, the day cancellation of elective cases was effective, and April 15, 2020, and the same period in the preceding 3 years. For the study period, we collected the number of cases and their distribution by subspecialty along with total hospital charges. RESULTS: Compared with an average of 606 cases performed during the study period over the past 3 years, only 145 neurosurgical cases were performed between March 16 and April 15, 2020, which corresponds to an 80% reduction in case volume and 66% decrease in hospital revenue in 2020. When divided by subspecialty, the most significant reduction was observed in functional (84%; P < 0.01) followed by spine (78%; P < 0.01) surgery, although all subspecialties were significantly impacted. Assessing junior resident experience, we observed a significant reduction in number of neurosurgical admissions (47%; P < 0.01) and bedside procedures (59%; P < 0.01) in the study period in 2020 compared with the past 3 years, with no significant reduction in number of consultations (17%; P > 0.1). CONCLUSIONS: Even at academic centers that were not hugely impacted by the COVID-19 pandemic, prophylactic and preparedness measures still exhibited an unprecedented toll on neurosurgical resident and fellow experience.

Status of Pituitary Surgery During the COVID-19 Pandemic.

Even in ideal circumstances, the performance of safe and effective endoscopic transsphenoidal pituitary surgery requires complicated orchestration of care amongst multiple medical and surgical teams in the preoperative, intraoperative, and postoperative settings. The current COVID-19 pandemic further complicates this highly orchestrated effort. Healthcare systems around the globe are working to adapt to the rapidly changing healthcare landscape as information about the SARS-CoV-2 virus is discovered and disseminated. The nature of the transsphenoidal corridor exposes the pituitary surgery team to increased risk of virus exposure.