Euthyroid sick syndrome is a change in the level of thyroid hormones that is not associated with thyroid disease. It occurs in several variants: a decrease in T3, a decrease in T3 and T4, an increase in T3 and T4, a decrease or increase in TSH. There are no symptoms of thyroid dysfunction. To diagnose of disease, an echography of the thyroid gland is performed, a study of the thyroid status. The appointment of hormone replacement treatment in most cases is considered inappropriate. The level of thyroid hormones normalizes after the treatment of the underlying disease.
ICD 10
E07.8 Other specified thyroid diseases
Meaning
Euthyroid sick syndrome has several alternative names: the syndrome of non-thyroid diseases, the syndrome of pseudodisfunction of the thyroid gland, the syndrome of euthyroid weakness. It develops against the background of severe somatic pathologies in the absence of an organic lesion of the thyroid gland. The syndrome has been studied since 1968, when for the first time thyroid hormone fluctuations were detected in athletes that were not associated with thyroid or pituitary dysfunction. Depending on the cause, the frequency of euthyroid sick syndrome (ESS) varies from 10 to 65%.
Causes
Euthyroid sick syndrome is a somatogenically caused changes in the concentration of thyroid and thyroid-stimulating hormone (TSH) in the absence of primary damage to the endocrine glands. With ESS, the metabolism and transport of thyroid hormones, as well as the regulation of their secretion, are disrupted. The causes of this phenomenon are the following conditions:
- Severe diseases. Pseudodisfunction of the thyroid gland can develop in pathologies of the gastrointestinal tract (stomach ulcer, NUC, functional dyspepsia, IBS), lungs (pneumonia, COPD, tuberculosis), heart and blood vessels (myocardial infarction, CHF, stroke), joints (rheumatoid arthritis, osteoarthritis), kidneys (terminal CRF), endocrinopathies (DM 1 and 2 types), etc. Cases of euthyroid sick syndrome in infections (viral hepatitis, AIDS, sepsis) are described. ESS occurs with hereditary erythrocytosis, gestosis in pregnant women.
- Drug intoxication. Thyroid status may change under the influence of medications: corticosteroids, amiodarone, salicylates, anticoagulants, diuretics, estrogens, lithium preparations. There are cases of ESS caused by the introduction of iodine-containing radiopaque drugs.
- Injuries and stresses. Severe traumatic brain injuries, blood loss, massive burns, hypothermia, dehydration, and starvation can provoke euthyroid sick syndrome. A number of studies indicate the role of heavy physical exertion in professional athletes, psychoemotional stress, PTSD, irradiation of head and neck tumors in the occurrence of ESS.
Premature infants, ICU patients, hemodialysis patients, and oncological patients are at risk for the development of euthyroid weakness syndrome.
Pathogenesis
Deioding violation
The mechanism underlying the euthyroid sick syndrome remains poorly understood, but there are several theories on this. One of them proceeds from the fact that the transformation of T4 into T3 in target tissues in non-thyroid diseases is disrupted due to a decrease in the activity of the enzymes deiodinases of iodothyronines of the 1st (D1), 2nd (D2) and 3rd types (D3). D1 by deioding promotes the conversion of T4 into active T3 or reverse T3 (rT3). D2 regulates the intracellular level of biologically active T3 and its interaction with receptors in target tissues. D3 produces the reverse T3 from T4.
The balance of iodothyronine deiodinases is extremely important for maintaining normal thyroid status. In various critical conditions, the levels of D1 and D2 tend to decrease, and the level of D3 increases. This causes a decrease in T4 and an increase in rT3.
Violation of GGT regulation
Another mechanism of the euthyroid sick syndrome is associated with a violation of the regulation of thyroid hormones along the hypothalamic-pituitary-thyroid system (HPTS). It is known that HPTS plays an important role in the adaptation of the body in response to stress and extreme environmental influences. Thyrotropin-releasing hormone of the hypothalamus (tyroliberin, TRH) activates the synthesis of thyroid-stimulating hormone by the anterior pituitary gland, and TSH stimulates the secretion of thyroxine by thyroid cells. Iodothyronines, in turn, inhibit the synthesis of TSH by negative feedback.
In conditions of short–term stress, serotonin blocks the synthesis of TRH and TSH, and norepinephrine stimulates it. At the same time, iodothyronines suppress the production of serotonin and norepinephrine. In a prolonged stressful situation, the secretion of ACTH and cortisol increases, which causes a decrease in thyroxine production.
Cytokine imbalance
One theory links euthyroid sick syndrome with an increase in cytokine levels in response to inflammation. It has been proven that with ESS, the production of interleukins 1, 6, 8, TNF-alpha increases, and the synthesis of anti-inflammatory IL-10 decreases. At the same time, the higher the content of pro-inflammatory cytokines in the blood serum, the lower the T3 level.
Other mechanisms
In addition to these, there are other mechanisms that explain the occurrence of euthyroid sick syndrome in certain cases:
- changes in the expression of thyroid hormone receptors in various conditions (increase in CRF, decrease in injuries, sepsis);
- changes in the concentration of thyroid hormone carrier proteins, including a decrease in the level of thyroxine-binding globulin;
- ESS is a normal adaptive reaction of the body, which allows optimizing metabolic processes in extreme conditions (for example, during fasting).
Classification
Depending on the level of thyroid and thyroid – stimulating hormone in clinical endocrinology , there are four types of euthyroid sick syndrome:
- Type 1 (low T3 syndrome). There is an isolated decrease in T3 total. by 60%, T3 St. – by 40%. The production of T4 and TTG remains within the normal range. This variant of ESS is associated with a violation of deioding processes. It occurs with ketoacidosis, CHF, endotoxicosis, etc.
- Type 2 (low T4 syndrome). It is characterized by a simultaneous decrease in both thyroxine (T4) and triiodothyronine (T3). It is caused by a violation of the binding of thyroid hormones. Prognostically, the most unfavorable option. It is often detected with terminal CRF.
- Type 3 (high T4 syndrome). Accompanied by an increase in T4 total and T3 mod . It occurs in patients with liver pathology, pulmonary tuberculosis, due to taking drugs.
- Type 4 (TSH anomaly syndrome). It occurs in two variants: a decrease in thyrotropin (subtype 4A) and an increase in thyrotropin (subtype 4B). Reflect the reaction of the pituitary gland to a stressful situation for the body (myocardial infarction, pneumonia). They can meet in isolation or successively replace each other.
Symptoms
Euthyroid sick syndrome has no clinical manifestations. There are no signs of thyroid dysfunction (hypothyroidism, thyrotoxicosis). The thyroid status corresponds to euthyroidism. The symptoms of a severe systemic disease come to the fore: acute coronary syndrome, infection, trauma, starvation, post-surgical conditions, etc.
The hormonal level normalizes as the causal disease resolves. It may take from several weeks to several months for thyroid hormone levels to return to normal. It is important to remember that the prognosis of the underlying pathology is directly dependent on the concentration of thyroid hormones.
Diagnostics
The main purpose of the diagnosis is to differentiate the euthyroid sick syndrome from the true dysfunction of the thyroid gland and pituitary gland. To do this, patients with abnormalities in the content of thyroid hormones should be consulted by an endocrinologist and examined according to the following scheme:
- Analysis of hormonal status. All patients are examined for levels of TSH, total and free fractions of T3 and T4, T‑Uptake, titer of At to TPO. Depending on the values obtained, the type and severity of the euthyroid sick syndrome are determined. It may also be necessary to study interleukin status, gonadotropin levels, ACTH, cortisol.
- Ultrasound of the thyroid gland. Echography allows you to determine the size of the thyroid gland, to identify the absence or presence of organic thyropathies (nodular, cystic formations, calcifications, diffuse changes).
Differential diagnosis
Based on the totality of the obtained data (laboratory, instrumental), differential diagnosis of non-thyroid and thyroid pathology is carried out. The diagnoses of exclusion with altered values of thyroid and thyroid – stimulating hormones are:
- hyperthyroidism associated with diffuse or nodular toxic goiter, subacute thyroiditis, etc.;
- hypothyroidism caused by iodine deficiency, thyroid hypoplasia, autoimmune thyroiditis, hypopituitarism, etc.
Treatment
The attitude of clinicians to the need for medical correction of thyroid imbalance in ESS is ambiguous. Most studies demonstrate the absence of a positive effect from the administration of thyroid hormone preparations and thyrostatics. It is believed that the main efforts should be directed to the therapy of the underlying disease.
Nevertheless, there is evidence of favorable results of the use of levothyroxine and triiodothyronine in euthyroid sick syndrome in patients with chronic heart failure. It is likely that the decision on the appropriateness of hormone replacement therapy should be made individually in each clinical case, taking into account many factors.
Prognosis and prevention
Euthyroid sick syndrome occurs in severe non-thyroid pathologies leading to functional shifts in the synthesis and metabolism of thyroid hormones. ESS itself does not pose a threat to health, but it is an important prognostic factor for the course and outcome of a background disease: the more severe it is, the more significant the thyroid imbalance. The 2nd type of thyroid pseudodisfunction is considered the most unfavorable.
To eliminate hormonal shifts, it is necessary to revise drug therapy, intensive treatment of causal pathology, elimination of stress factors. Patients with detected euthyroid sick syndrome are shown periodic monitoring of hormonal parameters until their normalization.