Introduction:
- The euthyroid sick syndrome, also known as nonthyroidal illness syndrome, refers to significant alterations in thyroid function tests observed in critically ill patients, particularly in the medical intensive care unit.
- It is not a distinct syndrome but rather a manifestation of changes in the hypothalamic-pituitary-thyroid axis, affecting about 75% of hospitalized patients.
- This condition is commonly associated with severe critical illness, calorie deprivation, and major surgical procedures.
Causes:
- Euthyroid sick syndrome can be triggered by various critical illnesses, including:
- Pneumonia
- Starvation
- Sepsis
- Stress
- Trauma (e.g., hip fracture)
- Cardiopulmonary bypass
- Myocardial infarction
- Malignancies
- Burns
- Organ transplantations
- Congestive cardiac failure
- Hypothermia
- Inflammatory bowel disease
- Cirrhosis
- Major surgery
- Renal failure
- Diabetic ketoacidosis
- Reports have also linked it to Covid-19 infection.
Pathophysiology:
- The mechanisms contributing to euthyroid sick syndrome are multifactorial and include:
- Presence of thyroid-binding hormone inhibitors in serum and tissues, hindering thyroid hormone binding to thyroid-binding proteins.
- Cytokines like interleukin 1, interleukin 6, tumor necrosis factor-alpha, and interferon-beta affecting the hypothalamus and pituitary glands, inhibiting TSH (thyroid-stimulating hormone), TRH (thyroid-releasing hormone), thyroglobulin (TG), T3, and thyroid-binding globulins (TBG) production.
- Reduction in type 1 deiodinase activity and increased activity of type 2 and type 3 deiodinase in critically ill patients.
- Inhibition of 5′-monodeiodination, leading to decreased serum total T3 levels due to factors like high serum cortisol, exogenous corticosteroid therapy, and certain medications (e.g., amiodarone, propranolol).
- Serum albumin binding to fatty acids, displacing thyroid hormones from thyroid-binding globulin.
- Drugs like aspirin and heparin impairing protein binding of thyroid hormones, resulting in reduced total T3 and T4 levels and temporary elevation of free T3 and T4 levels.
Prevalence and Common Patterns:
- Low serum total T3 levels are the most common abnormality, occurring in about 70% of hospitalized patients.
- Reverse T3 (rT3) levels are elevated in ESS, mainly due to decreased activity of type I iodothyronine 5′-monodeiodinase.
- Low T3 and low T4 patterns are observed in the most critically ill patients, often associated with a poor prognosis.
- ESS can be explained by the presence of thyroid-binding hormone inhibitors in circulation.
Medications and Other Influences:
- Medications like dopamine and steroids can reduce free T4 levels, especially when they promote decreased TSH levels.
- Acute intermittent porphyria and chronic hepatitis can increase thyroid-binding globulin levels, affecting free T4 and total T4 levels.
- Amiodarone and radiocontrast agents can increase total T4 and free T4 levels, potentially causing hyperthyroidism.
Unique Variations in Special Populations:
- HIV patients may exhibit variations in thyroid function, including increased T4 and TBG levels, decreased reverse T3, and normal T3 levels.
- No imaging studies or thyroid biopsies are necessary for ESS evaluation or management.
Treatment / Management:
- Thyroid hormone replacement is generally not needed in ESS.
- Focus on treating the underlying medical illness.
- Periodic monitoring of thyroid function in hospitalized patients.
- Repeat thyroid function tests no earlier than six weeks post-hospitalization to distinguish between ESS and overt thyroid dysfunction.
Differential Diagnosis:
- Consider differential diagnoses like Hashimoto thyroiditis, hyperthyroidism, panhypopituitarism, and drug-induced thyroid dysfunction.
Prognosis:
- Low T3 and T4 levels correlate with longer hospital stays, ICU admissions, and the need for mechanical ventilation.
- Elevated rT3 levels are associated with worse outcomes, especially in severely ill patients.
- ESS has been linked to poor prognosis in Covid-19 patients and complications in cases like hip fractures.
Complications:
- Complications are primarily related to the underlying causes of ESS and not thyroid gland malfunction.
- Once the initial medical issue causing ESS is treated, thyroid function typically normalizes.
- Patients with known thyroid problems require careful evaluation for appropriate treatment based on symptomatology and physical examination findings.
Managing the Impact of Anesthesia and Surgery
Anesthesia and surgery can potentially worsen existing Sick Euthyroid Syndrome (SES) or Non-Thyroidal Illness Syndrome (NTIS) in some patients, although it primarily depends on various factors, including the patient’s overall health, the type of surgery, and the anesthesia used. Here are some considerations:
- Severity of Illness: The development and progression of SES are closely related to the severity of the underlying illness. If a patient with SES undergoes surgery for a non-critical condition or a minor procedure, it may not significantly worsen the syndrome. However, in cases of major surgeries or in critically ill patients, the stress and trauma of surgery can exacerbate SES.
- Anesthetic Agents: Some anesthetic agents, particularly drugs like opioids, can affect the hypothalamic-pituitary-thyroid axis and thyroid function. This may contribute to the worsening of SES during and after surgery. Anesthesia providers should choose medications carefully, considering their potential impact on thyroid hormones.
- Stress Response: Surgery is a significant physiological stressor that can lead to alterations in thyroid function, even in individuals without pre-existing thyroid issues. This stress response can further affect patients with SES, potentially worsening their condition.
- Monitoring and Management: Anesthesiologists should be aware of a patient’s thyroid status, especially if SES is known or suspected. Proper monitoring of thyroid function and close management during surgery can help mitigate potential exacerbation of SES.
- Postoperative Care: The recovery period following surgery is critical. Patients with SES may need continued monitoring and management of their thyroid function to ensure any worsening is promptly addressed. This includes evaluating and adjusting any thyroid medications if necessary.
- Underlying Condition: It’s essential to address the primary reason for surgery and ensure that it doesn’t contribute to worsening SES. For example, if surgery is required due to an infection or other illness causing SES, successful treatment of the underlying condition can improve thyroid function.
In summary, anesthesia and surgery can potentially worsen existing Sick Euthyroid Syndrome, especially in patients undergoing major procedures or those who are critically ill. Anesthesiologists and surgical teams should be aware of a patient’s thyroid status, carefully choose anesthetic agents, and provide appropriate monitoring and postoperative care to minimize the impact on thyroid function and overall patient well-being.