What is Euthyroid Sick Syndrome (Nonthyroidal Illness Syndrome)?
Euthyroid sick syndrome, also called nonthyroidal illness syndrome, is a term that describes changes observed in the thyroid function tests given to patients in intensive medical care during serious illness. Even though it’s called a syndrome, it doesn’t refer to a specific set of symptoms. Instead, it explains significant changes in the body’s hormone regulator – the hypothalamic-pituitary-thyroid axis – seen in approximately 75% of hospitalized patients.
This condition is commonly observed in patients with serious illnesses, those not getting enough nutrients, and those who have had major surgeries. The most frequent hormonal changes seen in euthyroid sick syndrome are low levels of two hormones: total T3 and free T3. The levels of two other hormones – T4 and thyroid-stimulating hormone – can be low or normal.
What Causes Euthyroid Sick Syndrome (Nonthyroidal Illness Syndrome)?
Euthyroid sick syndrome is a condition that can be caused by various severe illnesses. These may include lung infections like pneumonia, severe lack of food from conditions like anorexia nervosa, severe body infection (sepsis), stress, past physical trauma (for example, a hip fracture), heart surgery, heart attack, cancer, severe burns, organ transplants, heart failure, exposure to extreme cold (hypothermia), inflammatory bowel disease, liver scarring (cirrhosis), major surgical operations, kidney failure, or a serious complication of diabetes known as diabetic ketoacidosis.
Recently, it has been found that people who have had a Covid-19 infection can also develop euthyroid sick syndrome. Interestingly, it was found that Covid-19 patients who had low levels of a hormone called T3 were more likely to have severe outcomes, even in the early stages of the disease.
Risk Factors and Frequency for Euthyroid Sick Syndrome (Nonthyroidal Illness Syndrome)
The most common irregularity, present in about 40% to 100% of cases, is the decrease of total T3 levels. Roughly 10% of patients in a hospital diagnosing a low level of TSH, a completely unrelated condition to thyroid diseases. This abnormality is most common in the severely sick patients. The chance of a person dying tends to align with their serum total T4 level. If the total T4 levels go down below 4 mcg/dL, the death chance is around 50%. And if the T4 levels drop below 2 mcg/dL, the likelihood of death exceeds 80%.
Signs and Symptoms of Euthyroid Sick Syndrome (Nonthyroidal Illness Syndrome)
Euthyroid sick syndrome is a condition related to the thyroid. Diagnosing this condition can be tricky because there are no specific symptoms related to it. Instead, this condition presents symptoms related to the cause of the problem. Interestingly, people who already have thyroid issues can also get euthyroid sick syndrome. If this happens, it can be difficult for doctors to tell if symptoms are from the original thyroid problem or from euthyroid sick syndrome. Therefore, care must be taken while diagnosing this so that the doctors do not confuse this syndrome with other thyroid-related diseases.
Testing for Euthyroid Sick Syndrome (Nonthyroidal Illness Syndrome)
Euthyroid sick syndrome is a condition characterized by abnormal thyroid function in individuals who aren’t diagnosed with thyroid disease. It is usually seen in hospitalized individuals who are critically ill. This syndrome could be broken down into four different categories:
1. Low T4 syndrome
2. Low T3 and low T4 syndrome
3. High T4 syndrome
4. Other abnormalities related to the thyroid
Majority of individuals with this syndrome, around 70% of hospitalized patients, show low levels of T3 in their blood. T3 is a hormone produced by the thyroid gland which plays a key role in the body’s control of energy production and use. Additionally, these individuals have high levels of a hormone called reverse T3 (rT3). RT3 is typically increased as a response to stress, starvation or critical illness. However, in patients with kidney failure, this might not be the case.
The low T3 and low T4 syndrome is usually found in those patients who are severely sick and in intensive care units. A decreased level of T4, another hormone secreted by the thyroid, can indicate a poor prognosis for the individual. In these patients, the level of a protein called thyroid binding globulin, which helps transport thyroid hormones in the blood, is typically normal, but the amount of free T4 (T4 not attached to this protein) is low.
The level of free T4 can also be reduced in patients who had received medications known to reduce the levels of thyroid-stimulating hormone (TSH), such as dopamine and steroids. Conditions like acute intermittent porphyria (a group of rare metabolic disorders) and chronic hepatitis can result in increased total T4 levels but normal free T4 levels.
Certain medications and substances such as amiodarone and radiocontrast agents used for imaging procedures can potentially increase both total and free T4 levels. These substances impair the body’s ability to convert T4 into T3, making T4 more available in the body. In patients with an autonomous thyroid nodule, this can potentially result in a hyperactive thyroid condition.
Patients with HIV may experience different changes in their thyroid function, including increased T4 levels, decreased reverse T3 levels, but a normal T3 level and T3/T4 ratio.
Finally, it’s important to note that for individuals with euthyroid sick syndrome, imaging studies or thyroid biopsies are not necessary for diagnosis or management of the condition.
Treatment Options for Euthyroid Sick Syndrome (Nonthyroidal Illness Syndrome)
In general, patients with a condition known as ‘euthyroid sick syndrome’ don’t typically need thyroid hormone replacement. The main treatment focus is on managing the underlying medical condition causing the syndrome. However, it’s crucial to regularly monitor the thyroid function while the patient is in hospital.
Even after leaving the hospital, the patient’s thyroid might not function normally for several weeks. In such cases, where the patient seems well, it’s usually recommended to wait at least six weeks after hospital discharge before repeating thyroid function tests. This can help confirm whether the patient is experiencing thyroid dysfunction or whether the patient’s thyroid function has returned to normal, which indicates they have ‘euthyroid sick syndrome’.
If the thyroid tests are done sooner, the results might show an elevated level of thyroid-stimulating hormone (TSH), reflecting the recovery phase. This could be easily misunderstood as overt hypothyroidism – a condition where the thyroid does not produce enough hormones.
Recent research suggested that giving children thyroid hormone before heart surgery helped prevent ‘euthyroid sick syndrome’ and decreased certain heart-related complications, especially those related to lack of adequate blood supply (ischemia).
What else can Euthyroid Sick Syndrome (Nonthyroidal Illness Syndrome) be?
When looking at the health condition known as euthyroid sick syndrome, doctors must consider several other diagnoses that may have similar symptoms. These include:
- Hashimoto thyroiditis or an underactive thyroid (hypothyroidism)
- An overactive thyroid (hyperthyroidism) or thyrotoxicosis
- Panhypopituitarism (a condition where the pituitary gland doesn’t produce enough hormones)
- Thyroid dysfunction caused by the use of different medications. Examples of these include:
- Amiodarone therapy
- Dopamine
- Steroids
- Lithium
- Iodide
- Estrogen or Androgen use
- Antiseizure or opioid meds
In each case, the doctor would need to perform specific tests to confirm or rule out these possible diagnoses.
What to expect with Euthyroid Sick Syndrome (Nonthyroidal Illness Syndrome)
A low level of T3, a type of thyroid hormone, in the blood is linked with a longer hospital stay, the need for critical care, and the use of a machine to help with breathing in patients suffering from acute heart failure. Similarly, a low level of T4, another type of thyroid hormone, is also associated with poor outcomes in severely ill patients. Particularly, levels below 2 micrograms per deciliter have been connected with death rates of more than 80%.
A recent study from China found that higher levels of another thyroid hormone, known as reverse T3 (rT3), was linked with worse outcomes and was mainly seen in the most severely ill patients.
In reports on patients with Covid-19, the condition known as ‘euthyroid sick syndrome’ – where thyroid hormone levels are abnormal but the thyroid gland itself isn’t dysfunctional – was linked with a poor prognosis and worse outcomes, even in the early stages of the disease.
In case of patients with hip fractures, the presence of euthyroid sick syndrome was associated with an increased need for blood transfusions and the development of anemia (a condition where your blood has lower than normal red blood cells) after surgical repair.
Possible Complications When Diagnosed with Euthyroid Sick Syndrome (Nonthyroidal Illness Syndrome)
The issues that arise from euthyroid sick syndrome are generally related to the root cause of the condition rather than an issue with the thyroid gland itself. Once the original medical issue prompting the euthyroid sick syndrome is addressed and treated, the thyroid tests are expected to show normal results again, with no remaining thyroid function problems. If someone already has known thyroid condition, it’s very important to understand the current state of thyroid functionality. The understanding should be based on the symptoms experienced and results from a physical examination. That way, the thyroid condition can be properly treated.
Common Situations:
- Problems caused by the underlying issue of the syndrome rather than thyroid function
- The expectation of normal thyroid tests after treating the initial medical problem
- No leftover issues with thyroid function predicted
- Necessity of understanding the current thyroid function in patients with existing thyroid problems
- Need for treatment based on symptoms and physical examination results
Preventing Euthyroid Sick Syndrome (Nonthyroidal Illness Syndrome)
Patients should be informed if their thyroid tests come back abnormal. It’s important for them to follow up with their regular doctor to have these tests done again once they have recovered fully from their illness. Usually, they should wait at least six weeks after being in the hospital to take these tests again. If a patient’s thyroid hormone levels continue to be abnormal even after their initial sickness is gone, it’s important for them to undergo further testing on their thyroid function. This is to understand and identify any problems related only to the thyroid that require special assessment and the right treatment.
