Endocrine Effects of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2)
Covid-19 has changed our world and medicine since its identification in late 2019. As we have seen infections spread across the globe, we continue to learn of the health impacts of this novel virus. The endocrine system is no exception. The involvement of the endocrine system has not been well-defined, but we do have several suggestions of involvement from experience with SARS-CoV1 and from around the world in SARS-CoV2.
Renin Angiotensin Aldosterone System (RAAS)
Angiotensive converting enzyme 2 (ACE2) is the receptor for entry of SARS-CoV2 into host cells. The renin angiotensin aldosterone system (RAAS) is well known as a usual feedback loop regulating volume and blood pressure status. This led to an early focus on the use of ACE-inhibitors, angiotensin receptor blockers and mineralocorticoid receptor antagonists. Also, understanding whether these predisposed patients will have worse outcomes with SARS-CoV2 since these medications increase expression of ACE2. However, ACE2 is part of the RAAS system that appears to have protective effects.
ACE2 is found in the lung, as well as the heart muscle cells and vascular cells, allowing SARS-CoV2 admission into those tissues. Then, ACE2 action is decreased by the virus. Since the ACE2 is protective, this removes protection from this inflammatory pathway. This allows the proinflammatory effects of the virus.
Since estrogen causes higher levels of ACE2, this may explain why premenopausal women have less severe SARS-CoV2 infections than men. The vascular expression of ACE2 may also explain the predisposition to clotting disorders that accompany COVID.
We also know that hypertension, obesity, and cardiovascular disease are risk factors for more severe SARS-Cov2 infections. It was noted that ACE inhibitors and ARB use allows lower risk of all-cause mortality and as they increase ACE2 expression, they may be beneficial in protecting from the decrease in ACE2 expression with SARS-CoV2. Therefore, it is not recommended to change anti-hypertensive therapy away from these agents with the current evidence.
Vitamin D is a negative regulator of the RAAS system. Treatment of vitamin D deficiency has been postulated to prevent COVID-19 infection, but this has not been proven. Multiple studies looking to show benefit in treating vitamin D deficiency to prevent other diseases have been disappointing and often are correlated with other factors. Patients with underlying vitamin D deficiency do not require any changes to their treatment unless their levels are inappropriate on treatment.
Treatment with glucocorticoids (specifically dexamethasone) in patients with SARS-CoV2 who are on ventilators was shown to decrease risk of death in one study, but it did not appear to improve outcomes in patients who did not require oxygen. Therefore, timing of use of steroids is critical.
Pituitary
SARS-CoV1 has an 80% genetic similarity to SARS-CoV2. In Co-V1 hypophysitis was noted. The theory is that SARS-CoV enters the brain through the olfactory bulb which has ACE2 receptors. Therefore, the mechanism of loss of smell and taste may allow entry into the CNS. This may lead to hypophysitis, with temporary central adrenal insufficiency and central hypothyroidism. The stress response may also lead to transient hyperprolactinemia.
Patients with underlying endocrine illness must be monitored very closely. For example, patients with underlying adrenal insufficiency must increase their steroid replacement to stress doses of replacement glucocorticoids. Sick day guidelines are to be followed and IV steroids must be given if patients are unable to maintain their oral intake of steroids or if they develop diarrhea.
Patients with diabetes insipidus also should have close monitoring of their sodium levels since electrolyte disturbances with COVID-19 are common. Patients on dopamine agonists for hyperprolactinemia, will need to be monitored if they require anti-viral medications in case of drug interactions. No treatment changes are required for patients on GH replacement for growth hormone deficiency.
Adrenal
Adrenal necrosis and vasculitis and immune infiltration of the adrenal were seen in autopsies in patients with SARS CoV1. Thus far, it has not been reported in SARS-CoV1, but vigilance is suggested. As above, adrenal insufficiency treatment with sick day guidelines are to be followed if patients with AI develop Covid-19.
Patients with Cushing’s syndrome may require anticoagulation or if critically ill, etomidate therapy.
Patients with pheochromocytoma or paraganglioma may require alpha blockade followed by beta-blockade.
Thyroid
Thyroiditis has been seen after recovery from Covid-19 with transient hyperthyroidism typically followed by hypothyroidism due to destruction of the follicular cells. Euthyroid sick syndrome is common in hospitalized patients, and this is no exception. Additionally, central hypothyroidism can be found.
There should not be any need for thyroid hormone dose adjustments for patients with hypothyroidism and COVID unless their labs indicate such.
Pancreas
Hyperglycemia is often seen in patients with SARS-CoV2. This is likely related to viral injury via ACE2 expression on islet cells. High glucose levels also glycosylate ACE2 leading to increased access of the virus to the cell. Stress hormones such as cortisol, growth hormone, adrenergic system lead to hyperglycemia. New reports of patients with type 1 DM after suffering SARS-CoV2 have been reported. Pancreatitis has not been a widespread problem in patients with SARS-CoV infections.
Insulin use in critical care situations is common and often typically managed. However, the access to patients in COVID units with high PPE needs has led to creative solutions with a movement to allow continuous glucose monitoring systems in hospital. Although this is not yet FDA approved, many innovative feasibility trials are underway.
Gonads
Impaired spermatogenesis and androgen synthesis have been reported with SARS infections and this would require follow-up after recovery.
Hypogonadism therapy in men may be temporarily held or moved to topical therapy. Topical estrogen is also less likely than oral estrogen to cause thrombosis risk.
Parathyroid
There do not appear to be direct effects on the parathyroid glands from SARS-CoV2. However, hypoparathyroid patients should maintain eucalcemia to avoid QT prolongation.
SARS-CoV2 continues to teach us new lessons in medicine and we continue to be aware of how it impacts each patient.
Moffitt COVID 19 Safety Measures:
All patients and staff entering Moffitt undergo temperature screening and questions about symptoms or recent requirements for quarantine. All those within Moffitt are required to wear masks. Special safety guidelines are also required pre-procedure since we know that patients with COVID19 who undergo surgery have worse outcomes. Therefore, testing before surgery is our standard process. We also test patients prior to radiation therapies and some chemotherapy regimens. We have limited visitors for outpatient visits. Family may attend appointments virtually. Inpatient visitors have been limited in number to avoid exposures to our fragile patients.
We have excellent access to COVID testing within Moffitt as our expert teams have developed in house SARS-CoV2 testing which is PCR based and has quick turnaround results.
Moffitt's renowned Head and Neck-Endocrine Oncology Department provides individualized treatment and supportive care to patients with cancers that affect the thyroid, adrenal and pituitary glands as well as other endocrine organs. Moffitt's endocrine cancer treatment team takes a multispecialty approach to endocrine cancer evaluation and treatment. To refer a patient to Moffitt, complete our online form or contact a physician liaison for assistance or support. As part of our efforts to shorten referral times as much as possible, online referrals are typically responded to within 24 - 48 hours.