In thyroid hormone resistance, enough thyroid hormones are produced, but they cannot adequately affect the pituitary gland or peripheral organs. The cause is a genetic defect of thyroid hormone receptors. The clinical picture of thyroid hormone resistance is highly variable.
What is thyroid hormone resistance?
In thyroid hormone resistance, the two thyroid hormones, thyroxine (T4) and triiodothyroxine (T3), are not sufficiently effective. There are two forms of thyroid hormone resistance. There is general peripheral thyroid hormone resistance and isolated thyroid hormone resistance to the pituitary gland or the other organs. Thyroid hormones are produced in the follicular epithelial cells of the thyroid gland. They are represented by two hormones such as thyroxine (T4) or the more effective triiodothyroxine (T3). Both hormones regulate energy metabolism and cell growth. They are therefore essential for life. They act via receptors on the pituitary gland and other peripheral organs. They have no effect on the brain, spleen and testes, but in all other organs and tissues they increase metabolism. Furthermore, they have an influence on the activity of the endocrine glands. They exert this influence through the pituitary gland. They regulate sugar metabolism by increasing insulin production and stimulate the activity of the adrenal glands. They are also known to influence sex hormones.
Causes
So-called receptors are necessary for the activity of thyroid hormones. The molecules dock onto these receptors and can thus develop their effectiveness. However, if the receptors are defective or insufficiently effective due to a mutation, there is thyroid hormone resistance despite sufficient hormone concentrations. In most cases, the mutation is inherited in an autosomal dominant manner. Since the thyroid hormones cannot bind sufficiently to the receptors, their effectiveness is limited. Due to this low effectiveness, the body produces even more thyroid hormones. Therefore, in thyroid hormone resistance, the concentration of thyroid hormones is increased. Effectively, with the increased hormone concentration, function can be normal, increased, or decreased. This results in a variable clinical picture, which accordingly can only be treated individually. The hormone thyrotropin (TSH) is normal or slightly elevated. TSH is also called thyroid-stimulating hormone. It is produced in the anterior pituitary gland and is responsible for regulating thyroid hormone production. When thyroid hormone concentrations are low, the concentration of thyrotropin increases, which stimulates the thyroid gland to produce hormones. If the thyroid hormone concentration is increased, the concentration of TSH decreases. Subsequently, the concentration of thyroid hormones also decreases. This regulatory mechanism no longer functions properly in thyroid hormone resistance. Even with additional administration of thyroid hormones, the concentration of TSH does not decrease, because despite hormone administration, its effectiveness does not continue to increase. Two different genes encode the thyroid receptors. One is the THRA gene from chromosome 17 and the other is the THRB gene from chromosome 3. Mutations on either or both of these genes can result in a defect in thyroid hormone receptors, which leads to thyroid hormone resistance.
Symptoms, complaints, and signs
The appearance in thyroid hormone resistance varies. It depends on whether there is hypothyroidism, hyperthyroidism, or even normal thyroid function. Depending on the severity of the defect in the receptors, the effectiveness of the thyroid hormones also varies. Patients usually develop goiter. Often there is hyperactivity, learning and hearing disorders, cardiac arrhythmias or developmental disorders of the central nervous system and skeleton. Even within the family, the symptoms of the disease may vary. Distinguishable are general resistance and pituitary resistance. In generalized resistance, thyroid function may be normal despite elevated hormone levels. However, hypothyroidism is also found. In pituitary thyroid hormone resistance, TSH production increases because the regulatory circuit does not function despite elevated thyroid levels.However, elevated TSH levels produce even more elevated thyroid hormone levels, which can then affect the other organs and cause hyperthyroidism.
Diagnosis and disease progression
To diagnose thyroid hormone resistance, thyroid hormone and TSH levels are examined. Both thyroid hormone levels are elevated. TSH is either normal or moderately elevated. When T4 is administered, there is no reduction in TSH levels. If thyroid hormone action is normal, administration of thyroid hormone should result in an immediate decrease in TSH levels.
Complications
The symptoms and complications of thyroid hormone resistance are relatively dependent on whether the thyroid gland is affected by hypothyroidism or hyperthyroidism. However, both malfunctions have a very negative effect on the daily life and quality of life of the affected person, so that treatment is necessary. In most cases, a goiter develops. Furthermore, most of those affected also suffer from hyperactivity and thus from concentration disorders. This can have a very negative effect on learning behavior, especially in children, and possibly lead to disturbed development. Disorders of the heart can also occur due to thyroid hormone resistance and must be examined in this context. The malfunction of the thyroid gland usually has a negative effect on the internal organs, so that these can also be damaged. Treatment of thyroid hormone resistance is usually carried out without complications. Those affected are dependent on taking hormones. This can completely limit and alleviate the symptoms. In most cases, however, patients are dependent on lifelong therapy. With early diagnosis and successful treatment, the patient’s life expectancy is not negatively affected by this disease.
When should you see a doctor?
The symptoms of thyroid hormone resistance are individual and cannot be precisely narrowed down. Basically, a doctor is needed as soon as the affected person experiences suffering in everyday life, feels unwell over a longer period of time or changes appear that trigger a deterioration in the quality of life. In the case of problems in coping with everyday life, a decrease in mental performance, restlessness or hyperactivity, a doctor should clarify the cause of the complaints. If learning difficulties become apparent, if the usual requirements can no longer be met, or if there are changes in mood, the affected person needs help. Weight fluctuations, libido disorders or psychological irregularities indicate hormonal imbalances in the organism. Blemished skin, brittle nails and hair growth disorders are further signs of health impairment. Swelling in the area of the thyroid gland indicates an enlargement of the organ and should be clarified. If the affected person can perceive changes through his or her own palpation, a doctor should be consulted. If there is a feeling of tightness in the throat or chest, or if there are problems with swallowing or breathing, the patient should be examined and treated. The enlargement of the thyroid gland can lead to shortness of breath and thus cause anxiety. In addition, the oxygen supply to the organism is reduced, which results in increased heart activity. A doctor should therefore be consulted even if the heart is racing.
Treatment and therapy
Treatment of thyroid hormone resistance depends on the symptoms that occur. If there is general thyroid hormone resistance, thyroid function may be normal. Then no therapy is necessary. If the value is too low, T4 must be given in such a concentration that is necessary for normal thyroid function. This varies in each individual case. In case of pituitary thyroid hormone resistance, only the pituitary gland is affected by the resistance. All other organs react normally to the thyroid hormones. In this case, since TSH levels are elevated via the pituitary disruption of the hormone regulatory circuit, thyroid hormone levels are also elevated. All organs affected by thyroid hormones except the pituitary gland respond to the elevated levels in the form of hyperthyroidism. In these cases, the first attempt is to reduce the TSH levels. If this is unsuccessful, complete removal of the thyroid gland is often the only alternative.Subsequent substitution therapy is influenced by the clinical picture.
Prevention
Because the inheritance of thyroid hormone resistance is usually autosomal dominant, individuals with the disease who wish to have children should seek human genetic counseling. In this form of inheritance, 50 percent of the disease is transmitted to the offspring. However, autosomal recessive inheritance has also been discovered and should be revealed by human genetic testing.
Follow-up
Thyroid hormone resistance is usually congenital. The problems can vary because the target cells do not respond adequately to the thyroid hormones that are actually present. Because thyroid hormone resistance is not usually considered a disease that heals after acute treatment, it cannot be assumed to be a mere follow-up condition. Follow-up care in conjunction with treatment is usually required for life. However, the effects may change or alternate. Therefore, regular visits to a specialist, in this case an endocrinologist, are indispensable. Depending on the course of the disease, tests of certain blood parameters are indispensable at fixed intervals, as well as sonographic imaging of the thyroid gland itself, since goiter may develop. Depending on the course of the disease, a certain lifestyle or diet may be indicated for the patient. This may refer in particular to abstaining from iodine. The endocrinologist will provide appropriate guidance in this regard and, if necessary, refer the patient for nutritional counseling. Since a lifelong treatment is to be assumed regularly, no aftercare can take place after a healing, this would be conceivable only in individual cases with later developed illnesses of the hypophysis. Then, the aftercare refers to the control of hormone levels and the necessary drug support of a normal metabolism.
What you can do yourself
In the case of thyroid hormone resistance, there are no self-help options to achieve a cure for the disorder. The symptoms of this disorder are manifold, but they can be partially alleviated by specific training or exercise sessions. In the case of an existing learning disorder, it is possible to work continuously on an improvement without a doctor by means of therapies that are specifically tailored to the needs of the patient. Together with a therapist, an individual training plan is created, which can be expanded and continued independently at home. If the patient is a child, legal guardians and relatives should help to complete the learning training. This promotes the patient’s quality of life and social togetherness. Since concentration may be disturbed, the exercise sessions should be tailored to the patient’s capabilities and needs. Situations of excessive demands should be avoided. In addition, goals and successes achieved should be praised and appreciated accordingly. To prevent psychological stress, the patient should be informed sufficiently and at an early stage about his physical and mental abnormalities. Open discussions and the clarification of existing questions can help to cope better with the disease in everyday life. In addition, comprehensive education about further development over the lifespan is advisable.
