CASE REPORT

Transsphenoidal pituitary tumor resection in a patient with pituitary apoplexy and simultaneous COVID-19 infection

Arun George, MD
Resident, Allegheny General Hospital
Allegheny Health Network, Pittsburgh, PA

Adam Yu Yuan, MD
Director of Neuroanesthesia, Allegheny General Hospital
Allegheny Health Network, Pittsburgh, PA

Adam Yu Yuan, MD
Arun George, MD

Introduction

The COVID-19 pandemic has been responsible for creating hurdles in healthcare and global disruption of routine hospital services, including canceling and delaying surgeries.1 Many of these surgeries, including pituitary tumor resection, are time-sensitive, especially in patients presenting with pituitary apoplexy in whom emergent surgery is recommended to improve neurological, endocrine, and oncological outcome.2

Case Description

A 58-year-old female presented with progressive worsening of her vision, fatigue, and intermittent headaches. About four months after symptoms started, an MRI of the brain showed a mass in the sella extending into the suprasellar region, about 1.8 x 1.5 x 2.4 cm compressing the optic chiasm and concerning for apoplexy. She was evaluated for bitemporal hemianopsia, decreased visual acuity, and color vision in her right eye.

The patient’s medical history was significant for hyperlipidemia, hypertension, and sleep apnea. She was vaccinated for COVID-19 with two doses of the Pfizer vaccine and was waiting to receive the booster.

She was started on dexamethasone and was scheduled for an elective transsphenoidal surgical resection of the pituitary mass six days later. Two days prior to the surgery, her COVID-19 test came back positive. She subsequently developed mild fatigue and sore throat, as well as worsening of her visual symptoms.

Discussions were held between the patient and clinicians involved to formulate a treatment plan considering her active COVID-19 infection and risk of deteriorating vision. With a major concern being the unknown complication of the surgical spread of the virus into the brain, it was decided surgery be delayed, and steroid dosing increased to protect her vision. The patient was aware of the risk of further vision deterioration but decided to delay the surgery to reduce the chances of COVID-associated complications. Aggressive treatment of COVID-19 was done according to CDC guidelines with medications, including monoclonal antibody therapy. Her COVID-19 symptoms significantly improved, and she underwent surgery seven days later than scheduled and was uneventful. N95 respirators, disposable gowns, and safety goggles were used by all personnel present in the operating room in addition to various logistical adjustments like intubating the patient in a pre-designated negative pressure room before transportation to the OR. The patient recovered post-operatively and was discharged four days later. She reported significant improvement in her vision bilaterally and recovered from her COVID symptoms as well.

Discussion

The overall effect of the virus on the central nervous system (CNS) and its neurological manifestations have been noted to be acute and chronic, which is anticipated to be a significant public health challenge.3 The purpose of this article is to focus on two major concerns:

  • Impact of the spread of the SARS-CoV-2 virus into the brain via the transsphenoidal approach.
  • Importance of having proper guidelines or timelines for surgery in patients who have symptomatic pituitary mass and COVID infection simultaneously.

Impact of the spread of the SARS-CoV-2 virus into the brain via the transsphenoidal approach

There are several routes suggested through which the virus enters the CNS. Transcribial, trans-synaptic, and hematogenous and/or lymphatic routes are a few to be described in that context. We focus mainly on the transcribial route, which describes the spread of the infection from the olfactory epithelium through the cribriform plate into the subarachnoid space.4 The virus utilizes angiotensin-converting enzyme – 2 (ACE 2) and TMPRSS2 as the main docking receptor. Proteolytic processing of spike protein by the transmembrane protein serin is required for efficient cell entry.5 It is well known that the nasopharynx is a major site of infection for SARS-CoV-2.6  Both ACE2 and TMPRSS2 have been identified in the nasal mucosa confirming their presence on the olfactory epithelium.7 This is the same epithelium breached for access into the sella during transsphenoidal surgeries. Other routes described for viral entry into the CNS include through the median eminence of the hypothalamus and regions of the brain with fenestrae or leaky blood-brain barrier in the capillary wall and by infected immune cells which transport the virus into CNS.8,9

In our review of literature, we did not come across studies reporting the effects of direct inoculation of the brain from surgical shedding. One can speculate that the SARS CoV-2 virus may attach to the brain tissue during surgical shedding, just as it does in case of a leaky blood-brain barrier, especially when there is a breach in the olfactory epithelium of the nasopharynx during the transsphenoidal approach to the pituitary. From various reports, Constanino summarized that SARS- CoV 2 virus does infect the brain tissue causing neuronal death, but CSF and autopsy data did not provide any proof of direct CNS infection.3 In summary, we feel that more research may be beneficial to identify an ideal timeline for safely proceeding with the breech of the nasopharyngeal epithelium during transsphenoidal surgery in COVID-positive patients in whom the olfactory epithelium of the nasopharynx is a major site of infection for the SARS-CoV-2 virus.

Importance of having proper guidelines or timelines for surgery in patients who have symptomatic pituitary mass and COVID infection simultaneously

In terms of the timing of surgery, various factors need to be considered, including but not limited to risk to patients from indirect COVID complications and risk of transmission to operating room personnel. The American Association of Neurological surgeons emphasized that transsphenoidal surgeries on patients who have the COVID-19 infection presented a higher risk of transmission to operating room staff than other surgeries.10 Some early reports out of China and Italy showed an increased COVID-19 infection rate seen among teams performing aerosol-generating procedures such as those involving the sinus.11,12,13 Some early reports out of Wuhan even suggest that a significant number of physicians infected and died were otolaryngologists, anesthesiologists, critical care doctors, and ophthalmologists.14 During the peak of the first wave, the Neurosurgery Society of Australasia recommended that serious consideration be given to avoid the transsphenoidal approach due to the extremely high viral transmission risk.15   But the benefits of the transsphenoidal approach still make it the preferred approach by most neurosurgeons.

This brings us to our next question, how much more risk does transsphenoidal surgery being one that produces aerosols and involves a breach of the high viral load containing nasopharynx put on the operating room personnel? Patel et al. stated that endonasal surgery for COVID-19 positive patients with pituitary tumors should be considered a high-risk procedure. They recommended testing for the infection 48 hours prior to transsphenoidal surgery. Several neurosurgical groups across the world were undertaking only urgent transsphenoidal surgeries and postponing elective ones.16 On the contrary, Zhu et al. argue that the possibility of aerosols originating in nostrils escaping suction and being inhaled subsequently by operating room personnel is rare. They suggest that performing these surgeries in negative pressure operating rooms with sufficient PPE followed by post-operative quarantine would suffice to proceed with surgery, especially the emergent ones such as patients with pituitary apoplexy.17

The Centers for Disease Control and Prevention (CDC) has currently delegated most restrictions on how to provide healthcare during the COVID-19 infection to local health departments and individual institutions.18 They recommend that these restrictions be based on potential harm on delaying the treatment and risk to health care workers and community transmission. COVID-19 has permeated through all facets of healthcare and will potentially continue to do so for an unknown period. Hence, it is vital to formulate a strategy providing high-quality and safe management of patients infected with COVID-19. Most healthcare teams agree with strategies of postponing elective cases, but the best timeline remains controversial for urgent cases. We did not come across any evidence-based study for patients who are in the acute phase of COVID-19 infection requiring urgent surgery for a pituitary tumor and suggest that it must be studied further. It is important to keep in mind that pituitary tumors deteriorate quickly, and patients may present with mass effects like visual deterioration, headaches, hypopituitarism, and hormonal hypersecretion.19 Timing of pituitary surgeries would be crucial, and setting guidelines would be extremely beneficial. In our case, both patient and the treating team were concerned about potential life-threatening effects COVID-19 presented even though the surgery was required urgently. Our team took measures to best delay the progress of the tumor and proceed with surgery when the viral load and infectivity reduced.

Our report aims to emphasize the possibility of direct inoculation of the CNS by the SARS-CoV-2 virus during transsphenoidal surgery and emphasize the importance of a timeline for patients with symptomatic pituitary mass and concomitant COVID-19 infection. These guidelines would be beneficial for the treating teams as well as patients encountering this complex situation. It is of utmost importance to communicate, reassure, and include patients in structuring the plan for their management.

References:

  • Lancet Rheumatology. Too long to wait: the impact of COVID-19 on elective surgery. Lancet Rheumatol. 2021;3(2):e83.
  • Bonicki W, Kasperlik-Załuska A, Koszewski W, Zgliczyński W, Wisławski J. Pituitary apoplexy: endocrine, surgical and oncological emergency. Incidence, clinical course and treatment with reference to 799 cases of pituitary adenomas. Acta neurochirurgica. 1993 Jan 1;120(3-4):118-22.
  • Iadecola C, Anrather J, Kamel H. Effects of COVID-19 on the nervous system. Cell. 2020 Aug 19
  • Chen, Xiangliang, et al. “A systematic review of neurological symptoms and complications of COVID-19.” Journal of neurology (2020): 1-11.
  • Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. cell. 2020 Apr 16;181(2):271-80.
  • Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, Niemeyer D, Jones TC, Vollmar P, Rothe C, Hoelscher M. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020 May;581(7809):465-9.
  • Brann DH, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K, Gong B, Chance R, Macaulay IC, Chou HJ, Fletcher RB, Das D. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Science advances. 2020 Jul 31;6(31):eabc5801.
  • Kaur C, Ling EA. The circumventricular organs. Histology and histopathology. 2017 Feb 8;32(9):879-92.
  • Bergmann CC, Lane TE, Stohlman SA. Coronavirus infection of the central nervous system: host–virus stand-off. Nature Reviews Microbiology. 2006 Feb;4(2):121-32.
  • Zammar S, Simon S. Covid-19 and neurosurgery. American association of neurological surgeons.
  • Lu D, Wang H, Yu R, Yang H, Zhao Y. Integrated infection control strategy to minimize nosocomial infection of coronavirus disease 2019 among ENT healthcare workers. J. Hosp. Infect. 2020; 104: 454–5.Tran K, Cimon K, Severn M, Pessoa-Silva CL, Conly J. Aerosol gen- erating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review. PLoS One 2012; 7: e35797.
  • Tran K, Cimon K, Severn M, Pessoa-Silva CL, Conly J. Aerosol gen- erating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review. PLoS One 2012; 7: e35797.
  • Zou L, Ruan F, Huang M et al. SARS-CoV-2 viral load in upper respira- tory specimens of infected patients. N. Engl. J. Med. 2020; 382: 1177–9.
  • https://www.bloomberg.com/news/articles/2020-03-17/europe-s-doctors-getting-sick-like-in-wuhan-chinese-doctors-say?fbclid=IwAR2ds9OWRxQuMHAuy5Gb7ltqUGMZNSojVNtFmq3zzcSLb_bO9aGYr7URxaI. Accessed March 21, 2020.
  • Mitchell RA, King JA, Goldschlager T, Wang YY. Impact of COVID‐19 on pituitary surgery. ANZ journal of surgery. 2020 Jun 1.
  • Patel ZM, Fernandez-Miranda J, Hwang PH, Nayak JV, Dodd R, Sajjadi H & Jackler RK. Letter: Precautions for endoscopic transnasal skull base surgery during the COVID-19 pandemic. Neurosurgery 2020 nyaa125. (https://doi.org/10.1093/neuros/nyaa125)
  • Zhu W, Huang X, Zhao H, Jiang X. A COVID-19 patient who underwent endonasal endoscopic pituitary adenoma resection: a case report. Neurosurgery. 2020 Aug 1;87(2):E140-6.
  • Centers for Disease Control and Prevention. Framework for Health- care Systems Providing Non- COVID-19 Clinical Care During the COVID-19 Pandemic. Accessed October 3, 2020. https://www.cdc. gov/coronavirus/2019-ncov/hcp/framework-non-COVID-care.html
  • Melmed S. Pituitary-tumour endocrinopathies. New England Journal of Medicine 2020 382 937–950. (https://doi.org/10.1056/ NEJMra1810772)

 

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