COVID-19 affects many organs of the body. The endocrine system is particularly vulnerable because of the expression of the angiotensin-converting enzyme 2 (ACE2) receptor in various endocrine glands. In 2020, Canadian researchers reported that ACE2 is the entry port that allows COVID-19 into cells, thus making certain endocrine glands susceptible to functional disruption or destruction by the virus.
Margarita Ramirez-Vick, MD
Early in the pandemic, for example, it became evident that people with diabetes experienced more severe symptoms and were at greater risk for complications and even death. A more recent study, published March 21 in The Lancet Diabetes & Endocrinology, reported that COVID-19 significantly raises the risk for diabetes by about 40% at 1 year, as reported in Medscape.
As we learned more about the disease, numerous reports documented the impact of COVID-19 on other endocrine glands, such as the thyroid, pituitary, and gonads.
People With Diabetes and COVID-19 Are at Higher Risk
Regardless of the presence of a diabetes diagnosis at the time of infection with COVID, a meta-analysis of observational studies found that hyperglycemia at the time of hospitalization greatly predisposed individuals to increased illness severity and mortality.
Scheen and colleagues found that people with diabetes were two to three times more likely to be hospitalized with COVID-19 and the mortality rate was twice that of people without diabetes. People with diabetes who had COVID-19 also tended to develop extreme hyperglycemia associated with an excessive release of counterregulatory hormones.
Among patients on insulin, COVID-19 triggered a rapidly progressive increase of insulin requirements and therefore more severe insulin resistance, seemingly associated with levels of inflammatory cytokines. Although there seems to be a relationship between poor metabolic control and severity of infection, the level of hyperglycemia at the time of hospital admission may be an even more important risk factor than A1c levels.
In a multicenter US study that looked exclusively at hospitalized patients with type 1 diabetes, those older than 40 had worse outcomes with worse metabolic control and more diabetes-related complications than younger patients. The most common comorbidity was obesity.
The jury has also been out on whether COVID-19 can trigger new-onset diabetes, especially in children. The CoviDIAB registry aims to establish the extent and characteristics of new-onset, COVID-19–related diabetes.
Thyroid Disruption and COVID-19
COVID-associated subacute thyroiditis has been reported in several case series. Patients presented with low thyroid-stimulating hormone and high free T4 levels, sometimes weeks after the resolution of COVID-19 (Brancatella et al; Ruggeri et al; Asfuroglu Kalkan and Ates; Ippolito et al).
An Italian study found that patients with COVID-19 who required greater intensive care had a higher prevalence of lower thyroid-stimulating hormone values or overt thyrotoxicosis that did not necessarily present with typical neck pain or lymphocytosis. A retrospective study of 58 patients with thyrotoxicosis found higher interleukin-6 levels in those who developed thyrotoxicosis during the acute phase of infection, suggesting that a more severe inflammatory response was a main contributing factor.
Although subacute thyroiditis is known to be caused by viral infections, the apparent higher incidence among patients with COVID-19 suggests this may be secondary to a combination of direct cellular damage and the exaggerated inflammatory response during infection. Current evidence indicates that thyroid dysfunction returns to normal after the acute phase of infection.
Other thyroid ailments that have been reported as possibly related to COVID-19 include relapse of Graves' disease or its onset 6-8 weeks after infection. Less often, hypothyroidism related to infection has been reported. Preexisting autoimmune thyroid disease does not appear to make patients more vulnerable to COVID-19.
COVID-19 Affects Reproductive Organs
Leydig cells in the testicles express ACE2 receptors and thus can be susceptible to damage by COVID-19.
A study found that up to 10% of infected men may experience testicular pain during the acute episode, and another study found that as many as 20% developed orchitis for up to a month after infection. Erectile dysfunction also appears to be more frequent among previously infected patients.
In a survey of 1031 Irish women, almost half had frequent menstrual irregularities after COVID-19; however, there is no clear evidence of the virus affecting ovarian hormones.
Pituitary Apoplexy and COVID-19
The pituitary gland shows lower expression of the ACE2 receptor than some other endocrine glands. Nevertheless, several case reports have been published on the occurrence of pituitary apoplexy during the acute phase of COVID-19. Most of these patients had other predisposing factors, such as pregnancy and preexisting macroadenoma or microadenomas; however, other studies found no risk factors (Ghosh et al; Soloro-Pidel et al).
Of note, COVID can precipitate a prothrombotic state, which is a risk factor for apoplexy.
Adrenal Insufficiency and COVID-19
Secondary adrenal insufficiency may be provoked by the frequent use of glucocorticoids as standard therapy in patients hospitalized with COVID-19. Beyond this, a few cases of new-onset primary adrenal insufficiency have been reported (Heidarpour et al; Hashim et al).
Although cases of adrenal infarction have been reported during acute COVID, other underlying conditions that are not related to COVID-19 could also be predisposing factors.
Conclusion
The endocrine glands affect physiologic processes throughout the body. The vulnerability of these glands to COVID-19 can manifest as an array of signs and symptoms that we in the healthcare professions must watch for.
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