Thyroid hormone resistance syndrome is a quite unusual thyroid disease - in its course, patients may experience symptoms of hyperthyroidism and hypothyroidism at the same time. This disease is caused by various genetic mutations that interfere with the activity of one of the thyroid hormone receptors - the variety of mutations makes the clinical picture of the thyroid hormone resistance syndrome in different patients completely different.
Thyroid hormone resistance syndromewas first described in 1967 by Samuel Refetoff, hence the other name of the disease, i.e.Refetoff syndrome. Yet another term for this problem isThyroid Hormone Sensitivity Syndrome .
The thyroid hormone resistance syndrome occurs with a similar frequency in men and women. The exact statistics of its prevalence are not known due to the fact that this disease is simply very rare - so far, only over 1000 cases of the syndrome have been described. According to available statistics, Refetoff's syndrome is found in 1 in 40,000 live births.
Thyroid Hormone Resistance Syndrome: Causes
The main problem that occurs in patients with thyroid hormone resistance syndrome is dysfunction of the thyroid hormone receptors. Their occurrence is caused by mutations in genes encoding thyroid hormone receptors. Refetoff's syndrome is inherited autosomal dominant - this means that a parent suffering from this entity has a 50% risk that his offspring will also suffer from the same disease. Mutations in these genes can be really diverse - so far over 100 different mutations related to the thyroid hormone resistance syndrome have been described. Due to the fact that the underlying cause of Refetoff's syndrome are defects in the genetic material, classically this disease runs in families.
Abnormal receptor activity for hormones such as thyroxin (T4) and triiodothyronine (T3) is the direct cause of the thyroid hormone resistance syndrome. It is for this reason that patients' tissues show a reduced sensitivity to thyroid gland hormones, but it should be emphasized that this does not apply to all tissues of the human body.
Mutations related to Refetoff syndromeThey relate to one of the several forms of thyroid hormone receptor, which is TRβ2. This type of receptor is characteristic of the pituitary gland, while in other tissues for which the functioning of thyroid hormones is also very important, other types of receptors for thyroid hormones are found. This is the case, for example, in the case of skeletal muscle cells and heart muscle cells in which TRα1 receptors are found. This type of differentiation in thyroid hormone receptors is responsible for the specific symptoms in the course of thyroid hormone resistance syndrome - they may be symptoms suggesting both hyperthyroidism and hypothyroidism.
Thyroid Hormone Resistance Syndrome: Symptoms
Due to, inter alia, Since the thyroid hormone resistance syndrome is caused by various gene mutations, the course of the disease in different patients can be completely different. The most characteristic deviation that appears in this disease is the increased amounts of thyroid hormones (T3 and T4) in the blood. Interestingly, an excess of thyroxine and triiodothyronine does not necessarily have to be accompanied by a disturbance in the amount of pituitary thyrotropin (TSH) in the blood. Physiologically, as the amount of T3 and T4 in the body increases, there is a decreased release of TSH from the pituitary gland. Meanwhile, in the case of Refetoff's syndrome, such a phenomenon is not observed, in patients the level of TSH usually has a value that corresponds even to the upper limits of the norm.
It would seem that since in the course of the thyroid hormone resistance syndrome the body circulates increased amounts of thyroid gland hormones, patients should develop symptoms of hyperthyroidism. In this case, the patient's tissues - or at least some of them - are not sensitive to these substances, and this is what distinguishes Refetoff's syndrome from hyperthyroidism. The most common symptom in patients with thyroid hormone resistance syndrome is goiter, i.e. enlargement (sometimes even of considerable size) the thyroid gland. Another, also common symptom of Refetoff's syndrome is tachycardia (the heart rate accelerates due to the fact that the thyroid hormone receptors present in its cells function properly and the excess of thyroid hormones in the body promotes tachycardia). In patients suffering from this disease, various emotional disorders are also encountered.
There are other problems associated with the thyroid hormone resistance syndrome, such as:
- disorders resembling the attention deficit hyperactivity disorder (ADHD)
- immune system dysfunction (viawhich in patients have relatively frequent infections, such as pharyngitis or ear infections)
- mental retardation
- short stature
- low body weight (especially in children with thyroid hormone resistance syndrome)
Thyroid Hormone Resistance Syndrome: Diagnosis
In the diagnosis of Refetoff syndrome, laboratory tests are the most important. In patients with this unit, the aforementioned, significantly increased levels of thyroxine and triiodothyronine in the blood are detected.
The thyroid hormone resistance syndrome, however, requires differentiation from other conditions that may also lead to thyroid dysfunction, such as TSH-secreting pituitary adenoma. For this reason, patients may undergo imaging tests (e.g. magnetic resonance imaging of the head to exclude the presence of a pituitary tumor), as well as specific laboratory tests. In the case of the latter, the TRH (thyreoliberin) test is used. In patients suffering from the thyroid hormone resistance syndrome, the release of TSH increases after administering them TRH. In turn, in patients with pituitary adenoma secreting TSH, this relationship no longer occurs.
The final confirmation that the patient suffers from the thyroid hormone resistance syndrome can be obtained by conducting genetic tests and detecting genetic mutations related to this unit.
Thyroid Hormone Resistance Syndrome: Treatment
As surprising as it may be, some patients with Thyroid Hormone Resistance Syndrome do not require treatment. This possibility is due to the fact that in some patients the reduced sensitivity of tissues to thyroid hormones is sufficiently compensated by the significantly increased secretion of hormones by the thyroid gland.
In patients whose symptoms are extremely severe, treatment with thyroid hormones in high doses may be used, in addition, some patients are given tyratricol (this drug, among others, stimulates thyroid hormone receptors). When ailments such as tachycardia or hyperactivity in patients become severe, treatment with beta-blockers may be used. Sources: Tolulope O Olateju, Mark P J Vanderpump, "Thyroid hormone resistance", Ann Clin Biochem 2006; 43: 431-440, on-line access: http://journals.sagepub.com/doi/pdf/10.1258/000456306778904678Thyroid Hormone Resistance, generalized, autosomal dominant; GRTH, OMIM disease database, on-line access: https://www.omim.org/entry/188570InternaSzczeklik 2022, pub. Practical Medicine
About the authorBow. Tomasz NęckiA graduate of the medical faculty at the Medical University of Poznań. An admirer of the Polish sea (most willingly strolling along its shores with headphones in his ears), cats and books. In working with patients, he focuses on always listening to them and spending as much time as they need.