Nikhil Prasad Fact checked by:Thailand Medical News Team Jul 31, 2025 1 day, 22 hours, 43 minutes ago
Thailand Medical News: As the global medical community continues to unravel the multifaceted impacts of COVID-19, emerging research highlights a significant yet under-discussed complication: Euthyroid Sick Syndrome (ESS), also known as nonthyroidal illness syndrome (NTIS). This condition, characterized by abnormal thyroid function tests in critically ill patients without pre-existing thyroid disease, has been increasingly observed in individuals hospitalized with severe COVID-19 and even in individuals with mild infections. This
Thailand Medical News exclusive report explores the connection between COVID-19 and Euthyroid Sick Syndrome (ESS), shedding light on its implications for patient prognosis and clinical management.
COVID-19 Causes Euthyroid Sick Syndrome
What is Euthyroid Sick Syndrome?
Euthyroid Sick Syndrome is not a true thyroid disorder but rather a state of altered thyroid hormone levels typically triggered by severe illness, starvation, or major surgeries. It manifests as a disruption in the hypothalamic-pituitary-thyroid (HPT) axis, leading to low levels of triiodothyronine (T3) and, in more severe cases, thyroxine (T4), while thyroid-stimulating hormone (TSH) levels typically remain normal or low. Unlike hypothyroidism, ESS does not reflect thyroid gland dysfunction but is an adaptive or maladaptive response to critical illness. Common symptoms mimic hypothyroidism, including fatigue, muscle weakness, and cold intolerance, but these are often overshadowed by the underlying disease. ESS is observed in approximately 75% of hospitalized COVID-19 patients with severe conditions, making it a critical marker for assessing disease severity.
How COVID-19 Triggers Euthyroid Sick Syndrome (ESS)
The link between COVID-19 and ESS stems from the virus’s profound impact on multiple organ systems, including the endocrine system. SARS-CoV-2, the virus responsible for COVID-19, may influence thyroid function through several mechanisms. Firstly, the virus can directly target thyroid cells, which express high levels of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), key entry points for SARS-CoV-2. Studies have detected viral particles in the thyroid follicular epithelium of deceased COVID-19 patients, suggesting direct glandular damage. Secondly, the cytokine storm—a hallmark of severe COVID-19—characterized by excessive release of pro-inflammatory cytokines like IL-6 and TNF-α, disrupts thyroid hormone metabolism. These cytokines suppress T3 production and increase reverse T3 (rT3), a hormonally inactive metabolite, contributing to the low T3 state typical of ESS. Additionally, medications like corticosteroids, commonly used in severe COVID-19 cases, further suppress TSH secretion and T4-to-T3 conversion, exacerbating ESS.
Clinical Implications and Prognosis
Research indicates that ESS in COVID-19 patients is a significant prognostic indicator. A 2020 study in Changsha, China, found that 27.52% of 149 COVID-19 patients exhibited ESS, with those patients showing higher levels of inflammatory markers like C-reactive protein (CRP) and
procalcitonin (PCT). These individuals faced longer hospitalizations, increased need for mechanical ventilation, and higher mortality rates compared to non-ESS patients. Another study from 2021 at Sheba Medical Centre in Israel reported that patients with the lowest free T3 (FT3) levels had a mortality rate of 40%, compared to 5.9% in those with higher FT3 levels. ESS has also been associated with severe respiratory insufficiency and increased ICU admissions, underscoring its role as a marker of disease severity even in mild cases. The presence of ESS in pediatric patients with multisystem inflammatory syndrome in children (MIS-C) further highlights its relevance across age groups.
Mechanisms and Pathophysiology
The pathophysiology of Euthyroid Sick Syndrome (ESS) in COVID-19 is complex. The virus’s interaction with ACE2 receptors on thyroid cells may cause direct damage, while systemic inflammation alters deiodinase enzyme activity, reducing T4-to-T3 conversion and increasing rT3 production. Cortisol, elevated during acute infection, further suppresses TSH and T3 levels. Some researchers hypothesize that ESS represents a stress-induced response, potentially protective in conserving energy during critical illness, while others suggest it may reflect maladaptive changes. The role of thyroid hormone binding proteins and transport mechanisms is also disrupted, contributing to the characteristic low T3 and normal-to-low T4 and TSH profile.
Management and Future Directions
Currently, there is no consensus on treating Euthyroid Sick Syndrome (ESS) in COVID-19 patients, as thyroid hormone replacement remains controversial. Some studies suggest T3 supplementation may benefit select patients, but others argue it could disrupt the body’s adaptive response. Clinicians are advised to monitor thyroid function tests closely, particularly FT3, as a prognostic tool. Future research is needed to clarify whether ESS is a direct result of viral damage or a secondary response to systemic inflammation, and to explore targeted therapies that address underlying mechanisms without interfering with the body’s natural response to critical illness.
Public Health Implications
In geolocations, where COVID-19 continues to challenge healthcare systems, recognizing ESS as a complication could improve patient triage and management. Hospitals and doctors are encouraged to incorporate routine thyroid function testing for hospitalized COVID-19 patients to identify those at risk of poorer outcomes. Awareness of ESS could also guide public health strategies, emphasizing the need for early intervention in severe cases to mitigate long-term complications.
Conclusion
The association between COVID-19 and Euthyroid Sick Syndrome underscores the virus’s far-reaching effects on the endocrine system. As research continues to evolve, understanding ESS’s role in disease prognosis could enhance clinical decision-making and improve outcomes for patients worldwide. For now, healthcare providers must remain vigilant, using thyroid function tests as a critical tool in managing severe COVID-19 cases.
References
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