Endocrine surgery during and after the COVID-19 epidemic: Expert guidelines from AFCE

The COVID-19 pandemic commands a major reorganisation of the entire French healthcare system. In France, general rules have been issued nationally and implemented by each healthcare centre, both public and private, throughout France. Guidelines drafted by an expert group led by the French-speaking Association of Endocrine Surgery (AFCE) propose specific surgical management principles for thyroid, parathyroid, endocrine pancreas and adrenal surgery during and after the COVID-19 epidemic.

# Introduction
The ongoing COVID-19 pandemic commands a major reorganisation of the entire French healthcare system [bib_ref] Technical Advisory Group for Infectious H. COVID-19: what is next for public..., Heymann [/bib_ref]. To respond to the present and expected influx of patients needhttps://doi.org/10.1016/j.jviscsurg.2020.04.018 1878-7886/ 2020 Elsevier Masson SAS. All rights reserved. ing a period of intensive care [bib_ref] High prevalence of obesity in severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) requiring..., Simonnet [/bib_ref] , the short-term priority has been directing available material and human resources toward sectors dispensing care for COVID-19 patients [bib_ref] Critical care utilisation for the COVID-19 outbreak in Lombardy, Italy: early experience..., Grasselli [/bib_ref] [bib_ref] Blueprint for restructuring a department of surgery in concert with the health..., Zarzaur [/bib_ref]. This policy has entailed the almost complete descheduling of non-urgent surgery [bib_ref] COVID-19: all non-urgent elective surgery is suspended for at least three months..., Iacobucci [/bib_ref]. More than a month now after the start of the epidemic, there is a pressing need to manage other health disorders not linked to COVID-19, but for which deferral of surgery until after the epidemic is over, could worsen prognosis or be life-threatening. It is also important to be thinking now about the conditions under which surgery can be resumed at a normal pace after the epidemic. General rules have been put out nationally and implemented by each healthcare centre, both public and private, throughout France. Specific guidelines have been proposed for visceral surgery [bib_ref] Strategy for the practice of digestive and oncological surgery during the COVID-19..., Tuech [/bib_ref]. Likewise, to meet their need for specific guidelines, the French-speaking Association of Endocrine Surgery (AFCE) brought together a group of experts to propose principles for the surgical management of thyroid, parathyroid, endocrine pancreas and adrenal pathologies during the COVID-19 epidemic and afterwards, for when surgical activity will be able to return gradually to its normal pattern. These guidelines were drafted in the light of the existing literature. They will be updated as knowledge advances.

## General principles for scheduling surgery during and after the covid-19 epidemic
Four scheduling levels were defined to help prioritise patients (these levels may change according to how the epidemic setting evolves) [fig_ref] Figure 1: General principles for scheduling endocrine surgery during and after the COVID-19 epidemic [/fig_ref] :
- urgent surgery that must be carried out as soon as possible because even a short deferral would be life-threatening; - semi-urgent surgery that can be deferred for a few weeks but not beyond 3 months without threat to life or adverse effects on cancer or functional prognosis; - high-priority elective surgery that can wait for several months but must be given scheduling priority as soon as the epidemic is over; - distant elective surgery that can be deferred until well after the epidemic is over, even more than 6 months, without compromising the indication.
For urgent surgery, the ratio of the benefits expected from surgery to the risks incurred by scheduling it dur-ing the epidemic must always be evaluated according to how both the national and local contexts are evolving, in particular the resources available: operating room, consumables and hospital capacities, particularly if intensive care may be needed. When surgery is prescribed in the epidemic setting, short hospital stays or outpatient care is recommended [bib_ref] At last a step forward toward ambulatory care for endocrine surgery in..., Brunaud [/bib_ref] , provided this does not increase the risk of rehospitalisation. To limit operating time and the risk of postoperative complications, the surgery should also be performed by one or more experienced surgeons. Even if no symptoms of COVID-19 are apparent, the risk of infection should be assessed beforehand as it may be associated with unfavourable prognosis [bib_ref] Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China, Liang [/bib_ref]. Any surgery on a patient infected or suspected of being infected must be performed according to the rules laid down by the hospital's hygiene teams and infectiologists.

## Thyroid and parathyroid surgery thyroid cancers
Differentiated thyroid cancers most often have an excellent prognosis [bib_ref] Thyroid cancer, Cabanillas [/bib_ref] , and there is no high level of proof supporting an optimal surgery deferral time [fig_ref] Figure 2: Principles for scheduling thyroid cancers during and after the COVID-19 epidemic [/fig_ref]. During the epidemic, any thyroid tumour suspected of malignancy (Bethesda 5 or 6) must be discussed at a multidisciplinary team (MDT) meeting. When there are clinical or paraclinical signs pointing to an aggressive form of cancer (recurrent nerve palsy, local invasion with esophageal, vascular or tracheal involvement, massive lymph nodes infiltration [bib_ref] American Thyroid Association management guidelines for adult patients with thyroid nodules and..., Haugen [/bib_ref] , surgery must be programmed as semi-urgent. If anaplastic, poor differentiated thyroid carcinoma or lymphoma is suspected, a surgical biopsy must be performed before any surgery is undertaken. If either of these diagnoses is confirmed, an appropriate treatment with corticoids and/or chemotherapy must be proposed as first line therapy [bib_ref] Effect of primary treatment on survival in anaplastic thyroid carcinoma, Besic [/bib_ref]. If there is no loco-regional aggressiveness, deferral of surgery for differentiated carcinoma will depend on lymph node and tumour size. A tumour size greater than or equal to 2 cm and/or associated with lymph nodes can be deferred without risk until the epidemic is over but must then be given priority and scheduled within the following 3 months. Tumours smaller than 2 cm in size, with no ganglion metastases, can be deferred until well after the end of the epidemic. Although the prognosis of medullary thyroid carcinoma (MTC) is slightly less favourable than that of follicular differentiated thyroid cancer [bib_ref] Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma, Jr [/bib_ref] , the care deferral guidelines given above still hold.

## Benign thyroid disorders
Most thyroidectomies for benign lesions can be deferred without risk [fig_ref] Figure 3: Principles for scheduling surgery for benign thyroid disorders during and after the... [/fig_ref]. However, specific situations can require semi-urgent scheduling, e.g. thyrotoxicosis (Graves's disease, toxic nodules, toxic goiters, iatrogenic hyperthyroidism) resistant to or poorly controlled by synthetic anti-thyroid (SAT) agents [bib_ref] The Graves' disease, consensus of the French Society of Endocrinology, Bartes [/bib_ref]. In this situation, lithium, potassium perchlorate, and if this fails, plasmapheresis may be useful to normalise levels of triiodothyronine (T3) and control those of thyroxine (T4) at the time of surgery. Non-suspect goiters responsible for severe compressive symptoms (inspiratory dyspnea due to tracheal compres- sion, dysphagia due to esophageal compression, superior vena cava syndrome due to deep vein compression) must also be scheduled for semi-urgent surgery before the epidemic ends.

## Hyperparathyroidism
Surgical treatment of primary hyperparathyroidism (HPT) is generally not urgent [fig_ref] Figure 4: Principles for scheduling parathyroid surgery during and after the COVID-19 epidemic [/fig_ref] [bib_ref] A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery, Silverberg [/bib_ref]. In the COVID-19 epidemic setting, its scheduling depends on the presence or absence of severe hypercalcemia, defined by a very high level of blood calcium > 3.5 mmol/L (140 mg/L) [bib_ref] Parathyroidectomy for hypercalcemic crisis: 40 years' experience and long-term outcomes, Cannon [/bib_ref] , and/or the presence of clinical complications-acute pancreatitis secondary to HPT, brown tumour, calciphylaxis, fracture osteopenia, heart rhythm disorders (QT shortening on ECG, bradycardia with risk of asystole) with cardiac insufficiency [bib_ref] Parathyroidectomy for hypercalcemic crisis: 40 years' experience and long-term outcomes, Cannon [/bib_ref] [bib_ref] Calciphylaxis due to hyperparathyroidism, Roy [/bib_ref] [bib_ref] The association of primary hyperparathyroidism with pancreatitis, Bai [/bib_ref]. In all cases, hypocalcemic treatment must first be given. In the epidemic setting, the use of cinacalcet is recommended [bib_ref] Cinacalcet hydrochloride maintains long-term normocalcemia in patients with primary hyperparathyroidism, Peacock [/bib_ref]. In cases of severe hypercalcemia, surgery must be scheduled as semi-urgent, without waiting for the epidemic to end, or as urgent when it escapes control by the medical treatment. If there is no severe hypercalcemia, surgery can be deferred without risk until the epidemic is over. These guidelines are valid for cases of genetically determined primary HPT. For tertiary HPT, the blood calcium threshold defining severe hypercalcemia must be lowered to 2.8 mmol/L to protect renal grafts (nephrocalcinosis, acute tubular necrosis, lithiasis) and bone and vascular impact [bib_ref] Tertiary hyperparathyroidism: is less than a subtotal resection ever appropriate? A study..., Pitt [/bib_ref] [bib_ref] Characteristics of persistent hyperparathyroidism after renal transplantation, Yamamoto [/bib_ref]. For secondary HPT, surgical treatment is not recommended during the epidemic because of the higher risk of COVID-19 infection in dialysed patients [bib_ref] Minimising the risk of COVID-19 among patients on dialysis, Ikizler [/bib_ref]. When indicated, surgery must be scheduled as a priority in the three months following the epidemic in cases of disabling bone pain, brown tumour or temporary contraindication for renal transplant [bib_ref] Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder..., Ketteler [/bib_ref].

## Technical aspects of neck surgery
Uni-or bilateral cervicotomy is the approach recommended for the surgical treatment of thyroid or parathyroid pathologies in the epidemic setting, so as to limit operating time and complication risk [bib_ref] Is it possible to limit the risks of thyroid surgery, Daher [/bib_ref]. Surgery requiring a thoracic or mediastinal approach and/or postoperative intensive care [bib_ref] Morbidity of total thyroidectomy for substernal goiter: a series of 70 patients, Tabchouri [/bib_ref] must be deferred whenever possible until after the epidemic is over. Endoscopic surgical approaches, with or without robotic assistance, are not recommended [bib_ref] Extracervical approaches to thyroid surgery: evolution and review, Sephton [/bib_ref]. If there is no dysphonia, laryngoscopy before or after surgery is not recommended [bib_ref] COVID-19 pandemic: effects and evidence-based recommendations for otolaryngology and head and neck..., Kowalski [/bib_ref] because of the high risk of airborne SARS-CoV-2 transmission during such examination [bib_ref] SARS-CoV-2 viral load in upper respiratory specimens of infected patients, Zou [/bib_ref]. Neuromonitoring of the inferior laryngeal nerve is recommended:
- to make sure the neuromuscular apparatus of the larynx is functioning before and after surgery [bib_ref] Does intraoperative neuromonitoring of recurrent nerves have an impact on the postoperative..., Mirallie [/bib_ref] ; - to reduce the risk of bilateral recurrent nerve palsy that can require intensive care and interruption of surgery if the signal is lost during the dissection of the first side [bib_ref] International neural monitoring study group guideline 2018 part I: staging bilateral thyroid..., Schneider [/bib_ref].
Peroperative PTH assay is possible but must not increase time spent in the operating room. The usual guidelines for the prevention and/or management of postoperative hypocalcemia remain unchanged during the epidemic [bib_ref] Randomised controlled trial of alfacalcidol supplementation for the reduction of hypocalcemia after..., Genser [/bib_ref].

## Neuroendocrine tumours of the pancreas
In the epidemic setting, the indication for the surgical treatment of a neuroendocrine tumour of the pancreas must be discussed in an MDT meeting to assess the balance between the risks of surgery and its oncological and/or secretory benefits [fig_ref] Figure 5: Principles for scheduling surgery for neuroendocrine tumours of the pancreas during and... [/fig_ref] [bib_ref] ENETS consensus guidelines update for gastroduodenal neuroendocrine neoplasms, Delle Fave [/bib_ref]. The management of Grade 3 carcinomas (poorly differentiated) has already been the subject of guidelines as part of the French National Digestive Oncology Thesaurus, and the COVID-19 epidemic does not change the usual guidelines favouring chemotherapy or neoadjuvant radio-chemotherapy [bib_ref] ENETS consensus guidelines for high-grade gastroenteropancreatic neuroendocrine tumours and neuroendocrine carcinomas, Garcia-Carbonero [/bib_ref]. A pancreatectomy may be indicated when a curative resection can be considered after clinical and morphological reassessment [bib_ref] Pancreatic neuroendocrine tumours: the impact of surgical resection on survival, Hill [/bib_ref] , in which case surgery is scheduled as semi-urgent before the epidemic has ended. Patients with a well-differentiated neuroendocrine tumour of the pancreas (Grades G1, G2 or G3), that is nonsecretory, can be deferred until well after the epidemic is over. If there is an associated secretory syndrome, a medical treatment should first be given [bib_ref] ENETS consensus guidelines for the management of patients with digestive neuroendocrine neoplasms:..., Jensen [/bib_ref]. If this treatment fails to control the secretory syndrome satisfactorily, pancreatectomy must be scheduled as semi-urgent before the end of the epidemic. If the medical treatment is effective, surgery can be deferred until well after the epidemic has ended. When technically possible, laparoscopy is recommended for left pancreatectomies and enucleations to minimise postoperative impact on respiratory function and hospital length of stay [bib_ref] Strategy for the practice of digestive and oncological surgery during the COVID-19..., Tuech [/bib_ref] [bib_ref] The association of primary hyperparathyroidism with pancreatitis, Bai [/bib_ref].

## Adrenal lesions
In the epidemic setting, the indication for the surgical treatment of an adrenal lesion must be discussed at an MDT meeting to assess the balance of risk and its oncological and/or secretory benefits [fig_ref] Figure 6: Principles for scheduling surgery for adrenal tumours during and after the COVID-19... [/fig_ref].
Lesions suspected to be malignant (adrenal cortical carcinoma, metastases) must undergo surgery when they are considered resectable [bib_ref] European Society of Endocrine Surgeons (ESES) and European Network for the Study..., Gaujoux [/bib_ref] [bib_ref] Adrenocortical carcinoma: impact of surgical treatment, Mirallie [/bib_ref]. In cases of secretory syndrome, prior management by a medical treatment is recommended (metyrapone, ketoconazole). Surgery must be scheduled as semi-urgent, before the end of the epidemic, in an expert centre [bib_ref] Adrenalectomy Risk Score: an original preoperative surgical scoring system to reduce mortality..., Caiazzo [/bib_ref]. Chromaffin lesions (pheochromocytoma and/or paraganglioma) must first receive an appropriate anti-hypertension treatment (alpha-blocking agents, beta-blocking agents, calcium inhibitors), and be monitored by an experienced care team [bib_ref] Pheochromocytoma and paraganglioma, Neumann [/bib_ref]. If this treatment controls the secretory syndrome, close monitoring can be continued until the adrenalectomy, which will be scheduled as a priority when the epidemic ends. If this treatment fails to control the secretory syndrome satisfactorily, surgery can be scheduled as semi-urgent, before the epidemic ends, in an experienced centre.
For other secretory adrenal lesions (in particular, hypercorticism and hyperaldosteronism), an appropriate medical treatment (steroidogenesis inhibitors, anti-aldosterone) must first be implemented. If the secretory syndrome is not controlled or if impact is marked, adrenalectomy can be scheduled as semi-urgent during the epidemic. In other cases, adrenalectomy can be scheduled well after the epidemic has ended. During the epidemic, laparoscopy remains the preferred approach for adrenalectomy. Conversely, for suspect lesions and/or those larger than 10 cm, laparotomy is recommended [bib_ref] Long-term survival after adrenalectomy for stage I/II adrenocortical carcinoma (ACC): a retrospective..., Donatini [/bib_ref].

## Postoperative follow-up in the epidemic setting
Postoperative follow-up consultations must be maintained during the epidemic. Tele-consultation is recommended to ensure continuity of care while limiting the risks of coronavirus propagation in healthcare centres. For a consultation in which a diagnosis of cancer or a therapeutic strategy is to be announced, some form of video exchange is recommended. Whenever possible, blood tests and imaging must be performed outside hospitals.
In a situation where medical drugs of major therapeutic importance may be in short supply, patients, who are dependent on a hormone substitution treatment, should be reminded never to interrupt their treatment longer than 24 h for corticoids [bib_ref] Adrenal insufficiency, Arlt [/bib_ref] , longer than 48 h for calcium [bib_ref] Heath 3rd H. Hypocalcemic emergencies, Reber [/bib_ref] , and longer than one week for thyroid hormones [bib_ref] Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a..., Clyde [/bib_ref].

# Disclosure of interest
The authors declare that they have no competing interest.
[fig] Figure 1: General principles for scheduling endocrine surgery during and after the COVID-19 epidemic. [/fig]
[fig] Figure 2: Principles for scheduling thyroid cancers during and after the COVID-19 epidemic. * Loco-regional aggressiveness defined as the presence of recurrent nerve paralysis, local invasion with esophageal, vascular or tracheal involvement, or massive ganglion infiltration. (Anapl = anaplastic, Lymph: lymphoma; MDT: multidisciplinary team). [/fig]
[fig] Figure 3: Principles for scheduling surgery for benign thyroid disorders during and after the COVID-19 epidemic. * Synthetic anti-thyroid agents, lithium, potassium perchlorate, plasmapheresis. (Med TTT = medical treatment). [/fig]
[fig] Figure 4: Principles for scheduling parathyroid surgery during and after the COVID-19 epidemic. Blood calcium > 3.5 mmol/L and/or presence of clinical complications (acute pancreatitis secondary to HPT, brown tumour, calciphylaxis fracture osteopenia, cardiac rhythm disorder with heart failure). * Hydration, calcimimetic (Med TTT = medical treatment). [/fig]
[fig] Figure 5: Principles for scheduling surgery for neuroendocrine tumours of the pancreas during and after the COVID-19 epidemic. * Diazoxide, proton pump inhibitor, somatostatin analogues, (TTT med: medical treatment; MDT: multidisciplinary team). [/fig]
[fig] Figure 6: Principles for scheduling surgery for adrenal tumours during and after the COVID-19 epidemic. * Steroidogenesis inhibitors (metyrapone, ketoconazole), anti-hypertensive agents (alpha-blocking drugs, beta-blocking drugs, calcium inhibitors), anti-aldosterone diuretics, (Med TTT:medical treatment, pheochr: pheochromocytoma; MDT: multidisciplinary team). [/fig]