Ectopic ACTH by Carcinoid Tumor Mimicking Nelson Syndrome in a Patient with Bilateral Adrenalectomy

Introduction: Nelson syndrome has been reported in up to 25% of adults after bilateral adrenalectomy (BLA) for Cushing’s disease (CD). It usually manifests as an expanding pituitary mass, rising adrenocorticotropic (ACTH) hormone levels and, in many patients, the development of hyperpigmentation. We review the clinical course of a patient with rising ACTH levels after BLA for presumed CD. Although the diagnosis of Nelson syndrome was considered, he was found 9 years after BLA to have an ectopic ACTH secreting bronchial carcinoid tumor as a cause for the elevated ACTH levels. Case Description: A 35 year old male was evaluated at another institution in 2010 after he presented with weight gain, new onset hypertension, muscle weakness with multiple falls, depression, irritability and emotional lability. He was diagnosed with CD and was referred to a university center where he underwent trans-sphenoidal pituitary surgery in May 2011. An adenoma was seen on frozen section but not on the final pathology. He developed transient symptoms of adrenal insufficiency on the second post-operative day. Because of persistent hypercortisolism he underwent BLA in November 2011. We started following him in 2012 and signs of hypercortisolism gradually resolved. He appeared euadrenal on hydrocortisone 10 mg am, 5 mg 12 noon and 5 mg 6 pm and fludrocortisone 0.05 mg daily. ACTH levels increased from 54 pg/ml (6-50) in 2012 to 1024 pg/ml in 2019. He had no hyperpigmentation and MRI of the pituitary from 2014-20 did not show a pituitary mass. During an evaluation for COVID-19 infection in May 2020, a chest x ray revealed a right lower lobe lung mass measuring 3.3 x 2.0 cm. He underwent right lower lobe lung lobectomy in July 2020 and pathology revealed a carcinoid tumor-spindle cell pattern which stained strongly positive for ACTH and weakly positive for chromogranin. ACTH levels after the surgery decreased to 16.3 pg/ml. Discussion: Some authors have suggested that Nelson syndrome be considered in patients with BLA who have one of the following: an expanding pituitary mass or ACTH levels >500 p/ml at 3 different time points after surgery. This case highlights the need to consider ectopic ACTH syndrome as another cause for rising ACTH levels after BLA for CD especially in those patients who are not found to have a discreet adenoma after pituitary surgery.

Current Practices Surrounding Endonasal Skull Base and Pituitary Surgery during COVID-19 Pandemic: A Global Survey

INTRODUCTION: During the Sars-CoV-2 pandemic, Endoscopic Endonasal Surgery (EES) is feared to be a high-risk procedure for transmission of the COVID-19 virus. Nonetheless, data are lacking regarding the management of EES during this pandemic. METHODS: A web-based survey of skull base surgeons worldwide was conducted.Different practices by geographical regions and COVID-19 prevalence were analyzed. RESULTS: 135 unique responses were collected. Regarding the use of personal protection equipment (PPE), North America reported using more powered air-purifying respirators (PAPR) and Asia/Europe using more standard precautions. North America and Europe resorted more to reverse transcriptase polymerase chain reaction (RT-PCR) for screening asymptomatic patients. High prevalence countries showed a higher use of PAPR. The medium prevalence group reported lower RT-PCR testing for symptomatic cases and the high prevalence group used it significantly more in asymptomatic cases. 19 respondents reported healthcare personnel transmission of COVID-19 from EES, with a higher rate of transmission among countries classified as having a medium prevalence of COVID-19. These specific respondents (medium prevalence) also reported a lower use of airborne PPE. In the cases of healthcare transmission, the patient was reportedly asymptomatic 32% of the time. CONCLUSION: This survey gives an overview of EES practices during the Sars-CoV-2 pandemic. Intensified preoperative screening, even in asymptomatic patients, RT-PCR for all symptomatic cases, and an increased use of airborne PPE is associated with decreased reports of COVID-19 transmission during EES.

Aerosolization risk during endoscopic transnasal surgery: a prospective qualitative and quantitative microscopic analysis of particles spreading in the operating room.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic represents the greatest public health emergency of this century. The primary mode of viral transmission is droplet transmission through direct contact with large droplets generated during breathing, talking, coughing, and sneezing. However, the virus can also demonstrate airborne transmission through smaller droplets (< 5 µm in diameter) generated during various medical procedures, collectively termed aerosol-generating procedures. The aim of this study was to analyze droplet contamination of healthcare workers and splatter patterns in the operating theater that resulted from endoscopic transnasal procedures in noninfected patients. METHODS: A prospective nonrandomized microscopic evaluation of contaminants generated during 10 endoscopic transnasal procedures performed from May 14 to June 11, 2020, in the same operating theater was carried out. A dilution of monosodium fluorescein, repeatedly instilled through nasal irrigation, was used as a marker of contaminants generated during surgical procedures. Contaminants were collected on detectors worn by healthcare workers and placed in standard points in the operating theater. Analysis of number, dimensions, and characteristics of contaminants was carried out with fluorescence microscopy. RESULTS: A total of 70 samples collected from 10 surgical procedures were analyzed. Liquid droplets and solid-tissue fragments were identified as contaminants on all detectors analyzed. All healthcare workers appeared to have been exposed to a significant number of contaminants. A significant degree of contamination was observed in every site of the operating room. The mean (range) diameter of liquid droplets was 4.1 (1.0-26.6) µm and that of solid fragments was 23.6 (3.5-263.3) µm. CONCLUSIONS: Endoscopic endonasal surgery is associated with the generation of large amounts of contaminants, some of which measure less than 5 µm. All healthcare workers in the surgical room are exposed to a significant and similar risk of contamination; therefore, adequate personal protective equipment should be employed when performing endoscopic endonasal surgical procedures.

COVID-19 and hypopituitarism.

Besides the pulmonary manifestations caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), an emerging endocrine phenotype, which can heavily impact on the severity of the syndrome, has been recently associated with coronavirus disease 2019 (COVID-19). Patients with pituitary diseases or the pituitary gland itself may also be involved in COVID-19 clinical presentation and/or severity, causing pituitary apoplexy.Moreover, hypopituitarism is frequently burdened by several metabolic complications, including arterial hypertension, hyperglycemia, obesity and vertebral fractures, which have all been associated with poor outcomes and increased mortality in patients infected by SARS-CoV-2.This review will discuss hypopituitarism as a condition that might have a bidirectional relationship with COVID-19 due to the frequent presence of metabolic comorbidities, to the direct or indirect pituitary damage or being per se a potential risk factor for COVID-19. Finally, we will address the current recommendations for the clinical management of vaccines in patients with hypopituitarism and adrenal insufficiency.

Safety of Endoscopic Transsphenoidal Pituitary Surgery during the COVID-19 Pandemic and Comparison to the Pre-Pandemic Era.

Objective The COVID-19 pandemic has caused significant disruption to the surgical care of patients with pituitary tumors. Guidance issued early during the pandemic suggested avoiding transnasal approaches to minimize risks of transmitting COVID-19 to health care professionals involved in these procedures. Methods This observational, single-center study compares results of endoscopic transsphenoidal approach (TSA) for pituitary tumors since the start of the pandemic to a pre-pandemic period. Anesthetic time, surgical time, and complication rates were compared. Newly acquired COVID-19 infections and transmission rates to patients and staff were reviewed. Data were analyzed by using the independent t -test, Mann-Whitney U test, and Pearson Chi-square test, significance set at p <0.05. Results Over a 12-month period, a total of 50 and 69 patients underwent endoscopic TSA for pituitary tumor during and before the pandemic, respectively. All patients tested negative for COVID-19 preoperatively. Median duration of anesthesia was 35 minutes (interquartile range [IQR]: 22) during the pandemic and 25 minutes (IQR: 8, p = 0.0002) pre-pandemic. Median duration of surgery was 70 minutes (IQR: 28) during the pandemic and 79 minutes (IQR: 33.75, p = 0.126) pre-pandemic. There were no statistically significant differences between intraoperative CSF leaks and complication rates. No staff members tested positive for COVID-19. Three patients tested positive for COVID-19 postdischarge, but the infections were community acquired. Conclusion In contrast to published guidelines, adequate preoperative testing, a multidisciplinary approach and the implementation of standardized protocols and vaccination against COVID-19 allow for endoscopic transsphenoidal surgery to be performed safely in patients with pituitary pathology during the pandemic.

Aerosolisation in endonasal endoscopic pituitary surgery.

PURPOSE: To determine the particle size, concentration, airborne duration and spread during endoscopic endonasal pituitary surgery in actual patients in a theatre setting. METHODS: This observational study recruited a convenience sample of three patients. Procedures were performed in a positive pressure operating room. Particle image velocimetry and spectrometry with air sampling were used for aerosol detection. RESULTS: Intubation and extubation generated small particles (< 5 µm) in mean concentrations 12 times greater than background noise (p < 0.001). The mean particle concentrations during endonasal access were 4.5 times greater than background (p = 0.01). Particles were typically large (> 75 µm), remained airborne for up to 10 s and travelled up to 1.1 m. Use of a microdebrider generated mean aerosol concentrations 18 times above baseline (p = 0.005). High-speed drilling did not produce aerosols greater than baseline. Pituitary tumour resection generated mean aerosol concentrations less than background (p = 0.18). Surgical drape removal generated small and large particles in mean concentrations 6.4 times greater than background (p < 0.001). CONCLUSION: Intubation and extubation generate large amounts of small particles that remain suspended in air for long durations and disperse through theatre. Endonasal access and pituitary tumour resection generate smaller concentrations of larger particles which are airborne for shorter periods and travel shorter distances.

Aerosolization in Endoscopic Sinus Surgery and Risk Mitigation in the COVID-19 Era: A Scoping Review.

Objective The continually evolving coronavirus disease 2019 (COVID-19) pandemic has created a dire need for rapid reorganization of health care delivery within surgical services. Ensuing initial reports of high infection rates following endoscopic sinus and skull base surgery, various expert and societal guidelines have emerged. We hereby provide a scoping review of the available literature on endoscopic sinus and skull base surgery, exploring both the risk of aerosolization and expert recommendations on surgical management during the pandemic. Methods A literature search of the PubMed database was performed up until May 9th, 2020. Additionally, websites and published statements from otolaryngology associations were searched for recommendations. This scoping review followed the guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta Analyses Extension for Scoping Reviews. Results A total of 29 peer-reviewed publications and statements from expert recommendations or professional associations were included. Current expert guidance relies mainly on scarce, anecdotal evidence, and two cadaveric studies, which have demonstrated potential aerosolization during transnasal surgery. General consensus exists for delaying surgery when possible, ascertaining COVID-19 status preoperatively and donning of adequate personal protective equipment by all operating room staff (including at minimum an N95 mask). Cold, nonpowered surgical instruments are deemed the safest, while thermal instruments (electrocautery and laser) and high-speed drills should be minimized. Conflicting recommendations emerge for use of microdebriders. Conclusion Endoscopic sinus and skull base surgery impart a potential risk of aerosolization. Hence, surgical indications, protective measures for health care workers, and surgical instrumentation must be adapted accordingly in the COVID-19 context.

The nose lid for the endoscopic endonasal procedures during COVID-19 era: technical note.

BACKGROUND: COVID-19 pandemic has disrupted the global health systems worldwide. According to the tremendous rate of interhuman transmission via aerosols and respiratory droplets, severe measures have been required to contain contagion spread. Accordingly, medical and surgical maneuvers involving the respiratory mucosa and, among them, transnasal transsphenoidal surgery have been charged of maximum risk of spread and contagion, above all for healthcare professionals. METHOD: Our department, according to the actual COVID-19 protocol national guidelines, has suspended elective procedures and, in the last month, only three patients underwent to endoscopic endonasal procedures, due to urgent conditions (a pituitary apoplexy, a chondrosarcoma causing cavernous sinus syndrome, and a pituitary macroadenoma determining chiasm compression). We describe peculiar surgical technique modifications and the use of an endonasal face mask, i.e., the nose lid, to be applied to the patient during transnasal procedures for skull base pathologies as a further possible COVID-19 mitigation strategy. RESULTS: The nose lid is cheap, promptly available, and can be easily assembled with the use of few tools available in the OR; this mask allows to both operating surgeon and his assistant to perform wider surgical maneuvers throughout the slits, without ripping it, while limiting the nostril airflow. CONCLUSIONS: Transnasal surgery, transgressing respiratory mucosa, can definitely increase the risk of virus transmission: we find that adopting further precautions, above all limiting high-speed drill can help preventing or at least reducing aerosol/droplets. The creation of a non-rigid face mask, i.e., the nose lid, allows the comfortable introduction of instruments through one or both nostrils and, at the same time, minimizes the release of droplets from the patient's nasal cavity.

Pituitary surgery during Covid-19: a first hand experience and evaluation.

PURPOSE: During the Covid-19 pandemic every hospital has had to change its internal organization. Different institutions have highlighted the risks connected with endoscopic endonasal surgery. The goal of this paper is to illustrate the feasibility of pituitary region surgery during the SARS-CoV-2 pandemic. METHODS: After two negative Covid tests were obtained, three patients with macro GH-secreting tumors, and two patients with micro ACTH-secreting tumors resistant to medical treatment underwent surgery during the pandemic. During the surgery, every patient was treated as if they were positive. RESULTS: Neither operator, nor patient have developed Covid symptoms. The two neurosurgeons performing the operations underwent two Covid swab, which resulted negative. CONCLUSIONS: Pituitary surgery is a high risk non-urgent surgery. However, the method described has so far been effective and is safe for both patients and healthcare providers.