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.

Trends in endoscopic and microscopic transsphenoidal surgery: a survey of the international society of pituitary surgeons between 2010 and 2020.

PURPOSE: This comparative survey of surgical practice patterns between 2010 and 2020 aims to elicit trends in practice patterns for transsphenoidal surgery and to identify areas for improvement. METHODS: Web-based surveys were sent to the International Society of Pituitary Surgeons via a membership listserv in 2010 and 2020. These 33-item surveys collected information on demographics, surgical approach, perceived advantages and disadvantages, and recommendations for improvements. Statistical analyses were conducted using the Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables. RESULTS: There were 51 respondents in 2010 and 82 respondents in 2020. The majority were full-time academic surgeons from the United States or Europe. Preference for a purely endoscopic technique increased from 43% in 2010 to 87% in 2020. Preference for routinely working with an otolaryngologist or second neurosurgeon increased from 35 to 51%. Most surgeons (74%) reported that they were more likely to achieve a greater extent of resection with the endoscope, though 51% noted increased operating time. The most commonly rated advantage (34%) of endoscopic TSS was fewer postoperative nasoseptal perforations; the most commonly (34%) rated disadvantage was more postoperative complications, including cerebrospinal fluid leak. Respondents were divided on whether microscopic TSS should continue to be taught in residency. Many (32%) advocated for improved endoscopic instrumentation and team training. CONCLUSION: Endoscopic TSS is now the clearly preferred method for surgery amongst a cohort of higher-volume academic neurosurgeons. This trend is likely to continue, and this provides guidelines for future training.

Do Most Patients With a Spontaneous Cerebrospinal Fluid Leak Have Idiopathic Intracranial Hypertension?

BACKGROUND: The association between cerebrospinal fluid (CSF) leaks at the skull base and raised intracranial pressure (ICP) has been reported since the 1960s. It has been suggested that spontaneous CSF leaks might represent a variant of idiopathic intracranial hypertension (IIH). We review the evidence regarding the association between spontaneous CSF leaks and IIH, and the role of ICP in the pathophysiology of nontraumatic skull base defects. We also discuss the management of ICP in the setting of CSF leaks and IIH. EVIDENCE ACQUISITION: References were identified by searches of PubMed from 1955 to September 2018 with the terms "idiopathic intracranial hypertension" and "cerebrospinal fluid leak." Additional references were identified using the terms "pseudotumor cerebri," "intracranial hypertension," "benign intracranial hypertension," and by hand search of relevant articles. RESULTS: A CSF leak entails the egress of CSF from the subarachnoid spaces of the skull base into the surrounding cavitary structures. Striking overlaps exist regarding demographic, clinical, and radiological characteristics between IIH patients and those with spontaneous CSF leaks, suggesting that some (if not most) of these patients have IIH. However, determining whether a patient with spontaneous CSF leak may have IIH may be difficult, as signs and symptoms of raised ICP may be obviated by the leak. The pathophysiology is unknown but might stem from progressive erosion of the thin bone of the skull base by persistent pulsatile high CSF pressure. Currently, there is no consensus regarding the management of ICP after spontaneous CSF leak repair when IIH is suspected. CONCLUSIONS: IIH is becoming more widely recognized as a cause of spontaneous CSF leaks, but the causal relationship remains poorly characterized. Systematic evaluation and follow-up of patients with spontaneous CSF leaks by neuro-ophthalmologists will help clarify the relation between IIH and spontaneous CSF leaks.

Angiotensin receptor blockade: a novel approach for symptomatic radiation necrosis after stereotactic radiosurgery.

Preclinical evidence suggests angiotensin blockade therapy (ABT) decreases late radiation toxicities. This study aims to investigate the association between ABT and symptomatic radiation necrosis (SRN) following stereotactic radiosurgery (SRS). Resected brain metastases (rBM) and arteriovenous malformation (AVM) patients treated with SRS from 2002 to 2015 were identified. Patients in the ABT cohort were on therapy during SRS and at 1-month follow up. Kaplan Meier method and cumulative incidence model were used to analyze overall survival (OS) and intracranial outcomes. 228 consecutive patients were treated with SRS: 111 with rBM and 117 with AVM. Overall, 51 (22.4%) patients were in the ABT group: 32 (28.8%) in the rBM and 19 (16.2%) in AVM cohorts. Baseline characteristics were similar, except for higher Graded Prognostic Analysis (3-4) in the rBM (ABT: 25.0% vs. non-ABT: 49.0%, p = 0.033) and median age in the AVM (ABT: 51.4 vs. non-ABT: 35.4, p < 0.001) cohorts. In both populations, OS and intracranial efficacy (rBM-local control; AVM-obliteration rates) were statistically similar between the cohorts. ABT was associated with lower 1-year SRN rates in both populations: rBM, 3.1 versus 25.3% (p = 0.003); AVM, 6.7 vs. 14.6% (p = 0.063). On multivariate analysis, ABT was a significant predictive factor for rBM (HR: 0.17; 95% CI 0.03-0.88, p = 0.035), but did not reach statistical significance for AVM (HR: 0.36; 95% CI 0.09-1.52, p = 0.165). ABT use appears to be associated with a reduced risk of SRN following SRS, without detriment to OS or intracranial efficacy. A prospective trial to validate these findings is warranted.

Optical coherence tomography retinal ganglion cell complex analysis for the detection of early chiasmal compression.

PURPOSE: To report patients with sellar tumors and chiasmal compression with normal visual fields, who demonstrate damage to the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) on optical coherence tomography (OCT). METHODS: Seven patients with sellar tumors causing mass effect on the optic chiasm without definite visual field defect, but abnormal GCC are described. GCC/RNFL analyses using Cirrus-OCT were classified into centiles based on the manufacturer's reference range. RESULTS: In seven patients with radiologic compression of the chiasm by a sellar tumor, OCT-GCC thickness detected compressive chiasmopathy before visual defects became apparent on standard automated visual field testing. Without OCT, our patients would have been labelled as having normal visual function and no evidence of compressive chiasmopathy. With only OCT-RNFL analysis, 3/7 patients would still have been labelled as having no compression of the anterior visual pathways. CONCLUSIONS: These patients show that OCT-GCC analysis is more sensitive than visual field testing with standard automated perimetry in the detection of compressive chiasmopathy or optic neuropathy. These cases and previous studies suggest that OCT-GCC analysis may be used in addition to visual field testing to evaluate patients with lesions compressing the chiasm.

Comprehensive evaluation of thyrotropinomas: single-center 20-year experience.

PURPOSE: To present a single-center 20-year experience with operated thyrotropinomas, including prevalence, clinical, biochemical and histological characteristics, and postoperative outcomes. METHODS: Retrospective series of histopathologically-proven thyrotropinomas (1993-2013), divided in two groups: A (active, central hyperthyroidism) and B (silent, no hyperthyroidism). RESULTS: Of 1628 operated pituitary adenomas, 20 were ß-TSH-positive (1.2%). In increments of 5 years, proportion of thyrotropinomas was 1, 1, 0.04 and 1.77% respectively. Median follow-up was 10.4 months (1.2-150). Group A: 6 patients (5 men), age 41 ± 12 years presented with hyperthyroidism (3), pituitary incidentaloma (2) and acromegaly (1). Tumor diameter was 2.1 ± 1.2 cm, FT4 2.68 ± 2.73 ng/dL; TSH 6.50 ± 3.68 µIU/mL. Glycoprotein alpha subunit (GSU) was uniformly elevated. Two patients had biochemical evidence of acromegaly. Tumors were plurihormonal (5 GH-positive); none atypical. Postoperative euthyroidism was achieved in 4 of 6 patients (66%). Group B: 14 patients (7 men), age 47 ± 14 years presented with acromegaly (6), mass effect (4), incidentaloma (3) and galactorrhea (1). Tumor diameter was 2.0 ± 1.0 cm. Free T4 (1.00 ± 0.24 ng/dL) and TSH (2.02 ± 1.65 mIU/L) were lower than in group A (p < 0.01). GSU was elevated in all tested cases. Nine patients had biochemical evidence of acromegaly. Tumors were plurihormonal (12 GH-positive); none atypical. Gross total resection was achieved in 12 of 14 (86%), and 1 (7%) recurred. CONCLUSION: In our series, more thyrotropinomas were operated in recent years. These tumors were often plurihormonal with heterogenous clinical presentation and frequent GH co-secretion. Surgical outcomes were good but long-term follow up is necessary.

SIGNIFICANT ELEVATION OF GROWTH HORMONE LEVEL IMPACTS SURGICAL OUTCOMES IN ACROMEGALY.

OBJECTIVE: Transsphenoidal adenomectomy (TSA) is first-line treatment for acromegaly. Our aim was to determine the impact of pre-operative biochemical parameters on the outcomes of surgery. METHODS: Retrospective case series of 79 consecutive acromegalics operated between 1994 and 2013. Inclusion criteria were: first TSA, pathology-confirmed growth hormone (GH) adenoma, and follow-up >3 months. Biochemical remission was defined as normal insulin-like growth factor 1 (IGF-1) without adjuvant therapy during follow-up. RESULTS: Median follow-up was 35.4 months (range, 3 to 187 months). Logistic regression analysis showed that the best model to predict long-term remission included the following pre-operative markers: GH, tumor diameter, and cavernous sinus invasion (CSI) (area under the curve, 0.933). A threshold GH of 40 ng/mL was associated with long-term remission (sensitivity, 97%; specificity, 42%). Group A (GH >40 ng/mL) comprised 19 patients (9 men); age, 43 ± 13 years; tumor diameter, 2.7 ± 1.0 cm; 73.7% with CSI; and pre-operative median GH, 77.8 ng/mL (interquartile range [IQR], 66.7 to 107.0 ng/mL). Three patients (15%) in group A achieved remission at 3 months, but 2 patients recurred during follow-up. Group B (GH ≤40 ng/mL) comprised 60 patients (25 men); age, 47 ± 13 years; tumor diameter, 1.6 ± 1.0 cm; 35% with CSI, preoperative median GH, 6.9 ng/mL (IQR, 3.4 to 16.9 ng/mL). Thirty-five patients (58%) in group B achieved remission at 3 months without recurrence during follow-up. Group A had larger tumors and a higher proportion of tumors with CSI (P<.05). CONCLUSION: Both GH and IGF-1 should be measured pre-operatively, as highly elevated GH levels negatively impact long-term surgical remission. This strategy allows early identification of patients who require adjuvant therapy and may decrease time to biochemical control.

A comprehensive review with potential significance during skull base and neck operations, Part II: glossopharyngeal, vagus, accessory, and hypoglossal nerves and cervical spinal nerves 1-4.

Knowledge of the possible neural interconnections found between the lower cranial and upper cervical nerves may prove useful to surgeons who operate on the skull base and upper neck regions in order to avoid inadvertent traction or transection. We review the literature regarding the anatomy, function, and clinical implications of the complex neural networks formed by interconnections between the lower cranial and upper cervical nerves. A review of germane anatomic and clinical literature was performed. The review is organized into two parts. Part I discusses the anastomoses between the trigeminal, facial, and vestibulocochlear nerves or their branches and other nerve trunks or branches in the vicinity. Part II deals with the anastomoses between the glossopharyngeal, vagus, accessory and hypoglossal nerves and their branches or between these nerves and the first four cervical spinal nerves; the contribution of the autonomic nervous system to these neural plexuses is also briefly reviewed. Part II is presented in this article. Extensive and variable neural anastomoses exist between the lower cranial nerves and between the upper cervical nerves in such a way that these nerves with their extra-axial communications can be collectively considered a plexus.

Anastomoses between lower cranial and upper cervical nerves: a comprehensive review with potential significance during skull base and neck operations, part I: trigeminal, facial, and vestibulocochlear nerves.

Descriptions of the anatomy of the neural communications among the cranial nerves and their branches is lacking in the literature. Knowledge of the possible neural interconnections found among these nerves may prove useful to surgeons who operate in these regions to avoid inadvertent traction or transection. We review the literature regarding the anatomy, function, and clinical implications of the complex neural networks formed by interconnections among the lower cranial and upper cervical nerves. A review of germane anatomic and clinical literature was performed. The review is organized in two parts. Part I concerns the anastomoses between the trigeminal, facial, and vestibulocochlear nerves or their branches with any other nerve trunk or branch in the vicinity. Part II concerns the anastomoses among the glossopharyngeal, vagus, accessory and hypoglossal nerves and their branches or among these nerves and the first four cervical spinal nerves; the contribution of the autonomic nervous system to these neural plexuses is also briefly reviewed. Part I is presented in this article. An extensive anastomotic network exists among the lower cranial nerves. Knowledge of such neural intercommunications is important in diagnosing and treating patients with pathology of the skull base.

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.

Acromegaly as a cause of 1,25-dihydroxyvitamin D-dependent hypercalcemia: case reports and review of the literature.

Growth hormone excess has been associated with hypercalciuria and nephrolithiasis. Hypercalcemia in acromegaly is rare and usually due to coexistent primary hyperparathyroidism. To report two cases of 1,25-dihydroxyvitamin D (1,25 (OH)(2) D)-dependent hypercalcemia in cromegaly. A 50 year-old female with 2 years history of hypercalcemia presented with features of acromegaly. Serum calcium (Ca) was 10.9 mg/dl (8.6-10.2), parathyroid hormone (PTH) 20 pg/ml (10-65), PTH-related peptide undetectable, and 1,25 (OH)(2) D 119 pg/ml (15-75). Insulin-like growth factor 1 (IGF1) was 911 ng/ml (49-292) and growth hormone (GH) 14.5 ng/ml (0.03-10). MRI showed a 1.7 cm pituitary tumor. Transsphenoidal adenectomy (TSA) resulted in normalization of IGF1, GH, Ca, and 1,25 (OH)(2) D (50 pg/ml) and complete tumor resection. A 52-year-old female was diagnosed with visual field deficits on routine exam. MRI showed a 3 cm invasive pituitary macroadenoma. IGF1 was 416 ng/ml (87-238) and GH 75.8 (0-6.0) ng/ml. Incidentally, she was found with high Ca of 10.8 mg/dl (8.9-10.3) associated with PTH 19 pg/ml and 1,25 (OH)(2) D66 pg/ml. Postoperatively, IGF1 and GH remained abnormal (440 and 12.8 ng/ml, respectively), while MRI showed parasellar tumor residue. Ca remained high (10.1-11.1 mg/dl), along with elevated 1,25 (OH)(2) D level (81.3 pg/ml). In both cases, other causes of hypercalcemia were ruled out. We present 2 cases of 1,25 (OH)(2) D-dependent hypercalcemia associated with growth hormone excess. Complete resection of tumor produced biochemical remission of acromegaly and normalization of calcium and 1,25 (OH)(2) D levels, while incomplete resection was associated with persistent 1,25 (OH)(2) D-dependent hypercalcemia. Acromegaly should be considered a cause of 1,25 (OH)(2) D-dependent hypercalcemia.

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.

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.

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.

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.

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.

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.