Newly discovered Pituitary Adenoma in the Emergency Center during the COVID-19 Pandemic in Serbia: Treatment and Early Postoperative Outcome (preprint)

Introduction:Pituitary tumors represent 10-15% of all intracranial tumors. Clinical manifestations depend on the size of the tumor such as microadenoma, macroadenoma or giant adenoma, and type of the tumor (secreting or non-secreting). Surgical treatment of pituitary adenoma can be managed via transcranial or transsphenoidal approach. Depending on the approach, there is a possibillity of postoperative complications such as meningitis, pneumocephalus, liquorrhea, transient diabetes insipidus and ect. Aim:The aim of this study was to establish the frequency of newly discovered pituitary tumors in the Emergency Center, University Clinical Center Of Serbia, during the COVID-19 pandemic in Serbia, and early postoperative complications in patients treated with an endoscopic and microscope transsphenoidal approach. Material and methods: During the time period during the pandemic, the study contains 119 patients, from January 1, 2020 to March 1, 2023, of which 64 are male (53.8%) and 55 are female (46.2%), age range is 14 to 85 years with a mean of 52.10. As for statistical analysis, assessment of frequency rate and relative numbers were used as methods of descriptive statistics. Results:Macroadenoma was present in 95 patients (79.83%), microadenoma in 22 patients (18.49%), and giant adenoma in 2 patients (1.69%). Transient DI developed postoperatively in 11 patients (9.24%). The average duration of hospitalization after surgery was 8 days. Conclusion: The duration of hospitalization depends on numerous factors where the COVID-19 pandemic can serve as an example for future similar crisis situations so that better organization and preoperative preparation of patients can be implemented.

Pituitary apoplexy and COVID-19 vaccination: a case report and literature review.

A 50-year-old man was admitted to our hospital for vomit, nausea, diplopia, and headache resistant to analgesic drugs. Symptoms started the day after his third COVID-19 mRNA vaccine (Moderna) whereas SARS-CoV-2 nasal swab was negative. Pituitary MRI showed recent bleeding in macroadenoma, consistent with pituitary apoplexy. Adverse Drug Reaction was reported to AIFA (Italian Medicines Agency).A stress dexamethasone dose was administered due to the risk of adrenal insufficiency and to reduce oedema. Biochemistry showed secondary hypogonadism; inflammatory markers were elevated as well as white blood cells count, fibrinogen and D-dimer. Pituitary tumour transsphenoidal resection was performed and pathology report was consistent with pituitary adenoma with focal haemorrhage and necrosis; we found immunohistochemical evidence for SARS-CoV-2 proteins next to pituitary capillaries, in the presence of an evident lymphocyte infiltrate.Few cases of pituitary apoplexy after COVID-19 vaccination and infection have been reported. Several hypotheses have been suggested to explain this clinical picture, including cross-reactivity between SARS-CoV-2 and pituitary proteins, COVID-19-associated coagulopathy, infection-driven acutely increased pituitary blood demand, anti-Platelet Factor 4/heparin antibodies development after vaccine administration. Ours is the first case of SARS-CoV-2 evidence in pituitary tissue, suggesting that endothelial infection of pituitary capillaries could be present before vaccination, possibly due to a previous asymptomatic SARS-CoV-2 infection. Our case underlines that SARS-CoV-2 can associate with apoplexy by penetrating the central nervous system, even in cases of negative nasal swab. Patients with pituitary tumours may develop pituitary apoplexy after exposure to SARS-CoV-2, therefore clinicians should be aware of this risk.

Pituitary apoplexy in the aftermath of a SARS-CoV-2 infection: a case series from Amiens University Hospital.

Objective: Since the outbreak of the COVID-19 pandemic, several cases of pituitary apoplexy (PA) following a SARS-CoV-2 infection have been described in several countries. Here, we describe a case series of PA occurring in the aftermath of a SARS-CoV-2 infection to alert physicians about possible neuro-endocrinological damage caused by the virus that can lead to visual sequelae and hypopituitarism. Design and methods: We retrospectively identified all the adult patients treated at Amiens University Hospital between March 2020 and May 2021 for PA confirmed by cerebral imaging and following an RT-PCR-confirmed SARS-CoV-2 infection. Results: Eight cases (six women, two men) occurred between March 2020 and May 2021 and were reviewed in this study. The mean age at diagnosis was 67.5 ± 9.8 years. Only one patient had a 'known' non-functional pituitary macroadenoma. The most common symptom of PA was a sudden headache. Brain imaging was typical in all cases. Only two patients required decompression surgery, whereas the others were managed conservatively. The clinical outcome was favorable for all patients but without recovery of their pituitary deficiencies. There was no diabetes insipidus. Conclusion: This case series, the largest in the literature, reinforces the strength, consistency, and coherence of the association between SARS-CoV-2 infection and PA. Our study provides support for the hypothesis that SARS-CoV-2 may be a new precipitating factor for PA. It is essential that practitioners be alerted about possible pituitary disease due to the virus so that such patients are recognized and appropriately managed, hence improving their prognosis.

A Novel Intraoperative Ultrasound Probe for Transsphenoidal Surgery: First-in-human study.

Background. Ultrasound has been explored as an alternative, less bulky, less time-consuming and less expensive means of intraoperative imaging in pituitary surgery. However, its use has been limited by the size of its probes relative to the transsphenoidal corridor. We developed a novel prototype that is more slender than previously reported forward-viewing probes and, in this report, we assess its feasibility and safety in an initial patient cohort. Method. The probe was integrated into the transsphenoidal approach in patients with pituitary adenoma, following a single-centre prospective proof of concept study design, as defined by the Innovation, Development, Exploration, Assessment and Long-Term Study (IDEAL) guidelines for assessing innovation in surgery (IDEAL stage 1 - Idea phase). Results. The probe was employed in 5 cases, and its ability to be used alongside the standard surgical equipment was demonstrated in each case. No adverse events were encountered. The average surgical time was 20 minutes longer than that of 30 contemporaneous cases operated without intraoperative ultrasound. Conclusion. We demonstrate the safety and feasibility of our novel ultrasound probe during transsphenoidal procedures to the pituitary fossa, and, as a next step, plan to integrate the device into a surgical navigation system (IDEAL Stage 2a - Development phase).

Resolution of pituitary microadenoma after coronavirus disease 2019: a case report.

BACKGROUND: This report describes the case of a patient whose pituitary microadenoma resolved after he contracted coronavirus disease 2019. To our knowledge, this is one of the first reported cases of pituitary tumor resolution due to viral illness. We present this case to further investigate the relationship between inflammatory response and tumor remission. CASE PRESENTATION: A 32-year-old man in Yemen presented to the hospital with fever, low blood oxygen saturation, and shortness of breath. The patient was diagnosed with coronavirus disease 2019. Past medical history included pituitary microadenoma that was diagnosed using magnetic resonance imaging and secondary adrenal insufficiency, which was treated with steroids. Due to the severity of coronavirus disease 2019, he was treated with steroids and supportive care. Three months after his initial presentation to the hospital, brain magnetic resonance imaging was performed and compared with past scans. Magnetic resonance imaging revealed changes in the microadenoma, including the disappearance of the hypointense lesion and hyperintense enhancement observed on the previous scan. CONCLUSIONS: Pituitary adenomas rarely undergo spontaneous resolution. Therefore, we hypothesized that tumor resolution was secondary to an immune response to coronavirus disease 2019.

Apoplexy in a previously undiagnosed pituitary macroadenoma in the setting of recent COVID-19 infection.

Pituitary apoplexy is an endocrine emergency, which commonly presents as hypopituitarism. Prompt diagnosis and treatment can be both life and vision saving. There are a growing number of published case reports postulating a link between COVID-19 and pituitary apoplexy. We report the case of a 75-year-old man who presented with a headache and was later diagnosed with hypopituitarism secondary to pituitary apoplexy. This occurred 1 month following a mild-to-moderate COVID-19 infection with no other risk factors commonly associated with pituitary apoplexy. This case, therefore, supplements an emerging evidence base supporting a link between COVID-19 and pituitary apoplexy.

Coronavirus Disease 2019 and Pituitary Apoplexy: A Single-Center Case Series and Review of the Literature.

BACKGROUND: Pituitary apoplexy (PA) is a rare, but life-threatening, condition characterized by pituitary infarction and hemorrhage, most often in the setting of a preexisting adenoma. The risk factors and mechanisms associated with PA are poorly understood. Although neurovascular manifestations of coronavirus disease 2019 (COVID-19) infection have been documented, its association with PA has not yet been determined. METHODS: From a prospectively collected database of patients treated at a tertiary care center for pituitary adenoma, we conducted a retrospective medical record review of PA cases during the COVID-19 pandemic from March 2020 to December 2020. We also conducted a literature review to identify other reported cases. RESULTS: We identified 3 consecutive cases of PA and concomitant COVID-19 infection. The most common symptoms at presentation were headache and vision changes. The included patients were successfully treated with surgical decompression and medical management of the associated endocrinopathy, ultimately experiencing improvement in their visual symptoms at the latest follow-up examination. COVID-19 infection in the perioperative period was corroborated by polymerase chain reaction test results in all the patients. CONCLUSIONS: With the addition of our series to the literature, 10 cases of PA in the setting of COVID-19 infection have been confirmed. The present series was limited in its ability to draw conclusions about the relationship between these 2 entities. However, COVID-19 infection might represent a risk factor for the development of PA. Further studies are required.

COVID-19 Testing in the Era of Modern Neurosurgery: Mitigating Risk in Our Vulnerable Patient Populations.

BACKGROUND: The respiratory illness identified as coronavirus disease 2019 (COVID-19) has resulted in a pandemic illness that has changed the face of healthcare. As the COVID-19 pandemic continues, patients have continued to require neurosurgical interventions, and the endoscopic endonasal approach for surgery has continued to be a mainstay treatment of pituitary tumors and anterior skull base lesions. METHODS: We sought to highlight the current lack of recommendations regarding testing protocols for neurosurgical patients. RESULTS: We implemented a novel testing protocol for our patient populations at increased risk and have proposed a model that can be used at other institutions to mitigate the risk of complications associated with some forms of COVID-19 testing. CONCLUSION: Patients with anterior skull base defects may be at risk with current COVID-19 testing protocols, and may benefit from alternative specimen collection strategies.

Case Report: SARS-CoV-2 Infection in a Child With Suprasellar Tumor and Hypothalamic-Pituitary Failure.

In early 2020, a novel coronavirus leading to potentially death was discovered. Since then, the 2019 coronavirus disease (COVID-19) has spread to become a worldwide pandemic. Beyond the risks strictly related to the infection, concerns have been expressed for the endocrinological impact that COVID-19 may have, especially in vulnerable individuals with pre-existing endocrinological health conditions. To date new information is emerging regarding severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in children but the literature is still scarce concerning this infection in patients with intracranial malignant neoplasms. We report a 9-year-old child infected with SARS-CoV-2 and recent diagnosis of suprasellar non-germinomatous germ cell tumor also suffering from diabetes insipidus and hypothalamic-pituitary failure (hypothyroidism, adrenal insufficiency, hypothalamic obesity and growth hormone deficiency) and its clinical course. The patient remained asymptomatic for the duration of the infection without requiring any change in the replacement therapeutic dosages taken before the infection. We then discuss the proposed approach to treat a pediatric patient with SARS-CoV-2 infection and hypothalamic-pituitary failure and we include a review of the literature. Our report suggests that SARS-CoV-2 infection is usually mild and self-limiting in children even those immunocompromised and with multiple endocrinological deficits. Patients are advised to keep any scheduled appointments unless informed otherwise.

Neuro-ophthalmic presentation of COVID-19 disease: A case report.

COVID-19 is a respiratory virus, which has affected various organ systems as well. Here we report a neuro-ophthalmic presentation of pituitary apoplexy under the setting of COVID-19 infection in a middle-aged man who presented to ophthalmic emergency with sudden bilateral loss of vision along with a history of fever past 10 days. There was sluggishly reacting pupils and RT-PCR for COVID was positive. Imaging pointed the diagnosis as pituitary macroadenoma with apopexy. In view of pandemic situation, patient was given symptomatic treatment as per the protocols and stabilized. Vision also showed improvement to some extent and the patient is awaiting neurosurgery.

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.

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.

[Pituitary tumor resection in a patient with SARS-CoV-2 (COVID-19) infection. A case report and suggested airway management guidelines]. / Assistência perioperatória de paciente com infecção pelo SARS­CoV­2 (COVID­19) submetido a ressecção de tumor de hipófise urgente. Relato de caso e diretrizes para manejo de via aérea.

The 2020 pandemic caused by the novel coronavirus, COVID-19, had its headquarters in China. It causes Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and presents a broad spectrum of clinical manifestations, ranging from entirely asymptomatic through severe acute respiratory failure and death. Presuming a significant quantity of ventilator-dependent patients, several institutions strategically delayed elective surgeries. Particularly procedures performed involving the nasal mucosa, such as a transsphenoidal approach of the pituitary gland, considering the tremendous level of viral shedding. Nevertheless, critical cases demand expeditious resolution. Those situations are severe pituitary apoplexy, declining consciousness level, or risk of acute visual loss. This case presents a successful urgent perioperative management of a 47 year-old male COVID-19 positive patient who presented to the Emergency Department with a left frontal headache that culminated with diplopia, left eye ptosis, and left visual acuity loss after 5 days. Transsphenoidal hypophysectomy was uneventfully performed, and the patient was discharged from the hospital on postoperative day four. It additionally describes in detail the University of Mississippi Medical Center airway management algorithm for patients infected with the novel coronavirus who need emergent surgical attention.

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.