Nonthyroidal-illness syndrome is not a disease in its own right, but occurs in the setting of serious illness or starvation. It characterizes an alteration in the metabolism of thyroid hormones in the presence of normal thyroid function. The significance of non-thyroidal illness syndrome is not yet fully understood.
What is nonthyroidal-illness syndrome?
Nonthyroidal-illness syndrome (NTIS) or TACITUS syndrome is characterized by altered metabolism of thyroid hormones in the presence of normal thyroid function. Therefore, it is also called euthyroid sick syndrome. It never occurs in isolation, but always in association with severe courses of disease, as well as in states of starvation. The significance of this syndrome for the organism is not yet clear. The altered metabolism could develop to protect the organism against the extremely severe courses of the disease. However, it could also be a secondary disorder. In any case, in critically ill individuals, this syndrome is generally associated with a worse prognosis. Nonthyroidal Illness Syndrome is composed of several components, not all of which may always occur simultaneously. There are three main components and several other components. Even the major components may appear singly or in combination. It is spoken of a characteristic allostatic constellation of the thyrotropic control loop. An allostatic constellation describes an adaptation of the body to chronic stress. The main components of non-thyroidal illness syndrome include central hypothyroidism (low-THS syndrome), impaired binding of thyroid hormones to the corresponding plasma proteins, and reduced formation of T3 from T4 with increased conversion of T4 to rT3 (low-T3 syndrome). The first component denotes a general deficiency of thyroid hormones, as occurs in hypothyroidism. Furthermore, the existing thyroid hormones are limited in their effect due to impaired binding to the plasma proteins. In addition, the conversion of thyroxine (T4) by deiodination into the more effective triiodothyronine (T3) is impeded in favor of its conversion into the inactive rT3. Like T3, the molecule rT3 also contains three iodine atoms. However, it is iodinated in exactly the opposite way as T3 and is therefore inactive. Other components include impaired uptake of thyroid hormones into target cells and decreased effectiveness of thyroid hormone receptors. Very rarely, non-thyroidal illness syndrome presents with such courses as low-T4 syndrome, low-T3-low-T4 syndrome, high-T4 syndrome, or high-T3 syndrome. However, it is difficult to detect the individual components of the syndrome.
Causes
The causes and pathogenesis for nonthyroidal illness syndrome are also not fully understood. Inflammatory processes, which may occur in the context of various diseases, are discussed for the decreased conversion of T4 to T3. Thus, proinflammatory cytokines, glucocorticoids, and certain metabolites are thought to be responsible for these processes. It is also possible that liver parenchymal damage in the context of a corresponding underlying disease leads to inhibition of deiodination. Liver parenchymal damage could also be the cause of reduced binding of thyroid hormones to plasma proteins simply because fewer albumins are present. Endocrine causes such as decreased leptin levels or endotoxins from bacteria have been considered as causes of central hypothyroidism. These influences could trigger local hyperdeiodation, which in turn reduces the production of TRH via the endocrine regulatory circuit. TRH (thyrotropin releasing hormone) is produced in the hypothalamus and sets the target value for the concentration of thyroid hormones. If less TRH is present, less thyroid hormone is produced. The increased production of rT3 instead of T3 possibly serves the accumulation of halogens, which includes iodine, in the defense cells in order to be able to perform better defense work in sepsis, among other things. Serious diseases that can trigger non-thyroidal illness syndrome include liver cirrhosis, cardiac insufficiency, myocardial infarction, chronic renal insufficiency, diabetic ketoacidosis, sepsis or burns.Fasting states, malnutrition, or malnutrition in the setting of anorexia nervosa can also cause nonthyroidal illness syndrome.
Symptoms, complaints, and signs
The symptoms of this syndrome are difficult to recognize because they occur in the setting of other serious underlying conditions. Usually, they are similar to those of hypothyroidism. Metabolism is greatly reduced, so that all bodily functions run on low flame. It is possible that the organism thus protects itself from overload in order to be able to cope with the other challenges of the underlying diseases.
Diagnosis and course of the disease
The diagnosis of non-thyroidal illness syndrome is usually very difficult. Because it is masked by the symptoms of the corresponding underlying disease, only the hormone levels of free thyroid hormones can provide clues. Thus, the basal hormone levels of FT4, FT3 and TSH are usually decreased, although there is a large gray area. The concentration of rT3 is usually elevated.
Complications
Usually, the nonthyroidal illness syndrome itself is a complication. This complaint can be difficult to recognize because the symptoms and complaints are relatively nonspecific and not particularly characteristic. However, those affected suffer from the symptoms of hypothyroidism. The patient suffers from permanent fatigue and exhaustion. The ability of the affected person to cope with stress also decreases considerably with non-thyroidal illness syndrome, so that heavy physical activities or sporting activities are usually no longer possible. Thus, the quality of life of the affected person is considerably limited and reduced by the non-thyroidal-illness syndrome. The body is also no longer able to fight off various infections and inflammations properly, so that infections and inflammations can occur more frequently. Treatment of non-thyroidal illness syndrome is usually carried out with the help of thyroid hormones. There are no particular complications for the patient. However, most sufferers are dependent on prolonged therapy, as the disease cannot be completely curtailed. However, the life expectancy of the affected person is not reduced by the non-thyroidal illness syndrome. However, the further course of this disease also strongly depends on the underlying disease.
When should one go to the doctor?
If hormonal symptoms occur or if there are recurrent general illnesses such as fever or gastrointestinal complaints, a doctor should be consulted. Nonspecific signs of illness that occur over months or years may indicate nonthyroidal illness syndrome. This is a serious change in the thyroid hormone metabolism, which must be clarified by a doctor in any case. Medical advice is needed at the latest when signs of a disease of the internal organs are noticed. Non-thyroidal illness syndrome often occurs after operations or in connection with malnutrition. People who regularly take medication or have suffered physical trauma are also among the risk groups and should see their family doctor if the described signs of illness occur. If dizziness, palpitations or severe malaise occur, emergency medical services should be contacted. In case of doubt, the affected person must be taken to a hospital. Non-thyroidal illness syndrome is treated by a thyroid doctor. This may be an internist or specified specialist. Individual symptoms may be investigated and treated by the appropriate specialist in consultation with the primary care physician.
Treatment and therapy
Treatment of non-thyroidal illness syndrome is highly controversial. There is a question as to whether general substitution therapy with thyroid hormones is at all useful or even harmful. It is true that the body suffers from an undersupply of energy. However, this could be the purpose of the altered metabolism of thyroid hormones in the severity of the underlying disease. The organism should be protected from overload. Although studies have shown that substitution with thyroid hormones improves the cardiac output of patients, it does not improve their chance of survival. The non-thyroidal illness syndrome can only be treated successfully in the context of the therapy of the underlying disease.
Outlook and prognosis
Non-thyroidal illness syndrome is not a disease in its own right. Therefore, no generally valid prognosis can be made for the further development of health. The patient’s overall situation and the underlying disease present must be considered to provide an outlook for future health changes. The syndrome is only diagnosed in people suffering from severe diseases. Often, severe organic damage is already present, which brings an unfavorable prognosis. The quality of life is limited and the patient may require intensive medical care or long-term therapy. In most cases, recovery is achieved only with a great deal of effort as well as an immense change in life circumstances. If the underlying disease cannot be successfully treated, the patient is threatened with premature death. Only if this leads with the medical possibilities to an improvement of the general health condition, an alleviation of the complaints is observed altogether. In the case of irreversible organ damage, there is often a need for a donor organ so that changes can occur. Transplantation is associated with other serious complications and side effects. If everything proceeds without significant disturbances, an improvement in health is possible. Patients must undergo regular check-ups even if the course of the disease is favorable. The metabolic system as well as the general functioning of the organs must be examined. Often, drug support is necessary in the long term.
Prevention
Because nonthyroidal illness syndrome is not a disease in its own right, there can be no recommendation for its prevention. However, the risk for the occurrence of each of the underlying diseases can generally be prevented by a healthy lifestyle with a balanced diet, physical activity, and avoidance of alcohol and smoking.
Follow-up
In most cases, only a few or limited follow-up measures are available to those affected by nonthyroidal illness syndrome. First and foremost, the affected person’s state of hunger must be ended. Only then can recovery take place, although a complete cure is not always possible. Therefore, in the case of non-thyroidal illness syndrome, a physician should be contacted immediately to prevent further deterioration of the symptoms or, in the worst case, death of the affected person. As a rule, these patients are dependent on taking various preparations or medicines. It is always important to ensure that the correct dosage is taken and that the medication is taken regularly in order to alleviate the symptoms. All the doctor’s instructions should be followed. Furthermore, regular checks and examinations of the thyroid gland are very important in the case of non-thyroidal illness syndrome. The further course of the disease depends very much on the time of diagnosis and the severity of the symptoms, so that a general prediction is not possible. However, in some cases, the life expectancy of the affected person is reduced by this disease.
What you can do yourself
This disease always occurs only in conjunction with other diseases, some of them severe, which must be treated in the first place. Supportively, affected patients can try to keep the consequences of their non-thyroidal illness syndrome as low as possible. For example, it is advisable to maintain a normal body weight and to reduce existing excess weight. Several dietary options are available for this purpose, which must be discussed with the physician who is also treating the underlying disease. Since non-thyroidal illness makes it more difficult to fight off infections, it is important to have a strong immune system. Eighty percent of all immune cells are located in the intestine, so attention should be paid to a healthy intestinal flora. This can be achieved not only by eating a fresh, low-fat, high-fiber diet, but also by getting as much exercise as possible, following a regular daily routine, and getting a good night’s sleep. The intake of probiotics has also proven to be helpful. These are living microorganisms that are introduced into the intestine via oral ingestion, where they multiply and help to build up healthy intestinal flora. High-dose probiotics are available over-the-counter in pharmacies.It may be very stressful for patients to suffer from both an underlying disease and non-thyroidal illness syndrome, especially since the latter also dampens the joy of exercise. This group of patients might find relief with adjunctive psychotherapy.
