Summary about Disease
Resistance to Thyroid Hormone (RTH) is a rare genetic disorder in which the body's cells do not respond normally to thyroid hormone. This can lead to a complex and variable presentation, with individuals experiencing symptoms of both hyperthyroidism (overactive thyroid) and hypothyroidism (underactive thyroid) or sometimes no symptoms at all. The body produces normal or elevated levels of thyroid hormone, but the tissues are less responsive, leading the pituitary gland to produce more TSH (thyroid-stimulating hormone) in an attempt to stimulate thyroid hormone action.
Symptoms
Symptoms of RTH can vary widely among individuals, even within the same family. Common symptoms include:
Hyperthyroidism-like symptoms: Rapid heart rate (tachycardia), anxiety, tremor, excessive sweating, heat intolerance, hyperactivity, difficulty concentrating, diarrhea.
Hypothyroidism-like symptoms: Fatigue, constipation, growth retardation (in children), delayed bone age, learning disabilities, goiter (enlarged thyroid gland).
Other symptoms: ADHD-like behavior, hearing loss, and in rare cases, cardiac arrhythmias. Some individuals may be completely asymptomatic.
Causes
RTH is primarily caused by mutations in the THRB gene, which provides instructions for making the thyroid hormone receptor beta (TRβ). These receptors are responsible for mediating the effects of thyroid hormone in various tissues throughout the body. Mutations in *THRB* impair the receptor's ability to bind to thyroid hormone and/or to properly interact with other proteins involved in gene regulation. The disorder is usually inherited in an autosomal dominant pattern, meaning that only one copy of the mutated gene is sufficient to cause the condition. *De novo* mutations (new mutations arising spontaneously) can also occur. Rarely, mutations in the *THRA* gene, encoding the thyroid hormone receptor alpha (TRα), can also cause a different form of RTH.
Medicine Used
Treatment for RTH is complex and individualized, aiming to alleviate specific symptoms and normalize TSH levels without causing excessive thyroid hormone effects.
Triiodothyronine (T3): In some cases, high doses of T3 may be used to overcome the resistance to thyroid hormone, particularly when hypothyroidism-like symptoms predominate. This is used with extreme caution.
Beta-blockers: These medications, such as propranolol, can help manage hyperthyroidism-like symptoms like rapid heart rate, anxiety, and tremor.
Other medications: Medications to treat ADHD-like symptoms, constipation, or other specific issues may be prescribed as needed.
Thyroid hormone analogs: Selikreon (Sobetirome) is a selective TRβ agonist that is designed to target the receptor without causing the negative effects of thyroid hormone. (Note: Selikreon may not be approved or available in all countries.)
Is Communicable
No, Resistance to Thyroid Hormone is not communicable. It is a genetic disorder caused by mutations in the THRB or *THRA* gene and is not spread from person to person.
Precautions
Because RTH is a genetic condition, the main precautions are related to genetic counseling and family planning. Individuals with RTH should be aware of the 50% risk of passing the condition on to their children if it is an autosomal dominant condition.
How long does an outbreak last?
RTH is not an "outbreak" type of disease; it is a chronic genetic condition. Individuals with RTH have the condition throughout their lives. The severity of symptoms can vary over time and may be influenced by factors such as age, stress, and other medical conditions.
How is it diagnosed?
Diagnosis of RTH typically involves a combination of clinical evaluation, laboratory testing, and genetic testing.
Clinical Evaluation: A doctor will assess the patient's symptoms, medical history, and family history.
Laboratory Testing: Blood tests will measure thyroid hormone levels (T4 and T3) and TSH. In RTH, T4 and T3 levels are often elevated or in the upper normal range, while TSH is inappropriately normal or elevated.
Genetic Testing: Genetic testing of the THRB gene is used to confirm the diagnosis by identifying mutations associated with RTH. Testing for *THRA* gene mutations may be considered in rare cases.
Timeline of Symptoms
The timeline of symptoms can vary greatly depending on the individual and the severity of their RTH. Some individuals may present with symptoms in infancy or early childhood, while others may not be diagnosed until adulthood. Symptoms can fluctuate over time.
Important Considerations
Individualized Treatment: Management of RTH requires a personalized approach, as symptoms and responses to treatment can vary significantly.
Careful Monitoring: Regular monitoring of thyroid hormone levels and TSH is essential to adjust treatment as needed.
Endocrinologist Expertise: Management of RTH is best handled by an endocrinologist with experience in thyroid disorders.
Genetic Counseling: Genetic counseling can provide information about the inheritance pattern of RTH and the risk of passing the condition on to future generations.
Avoid unnecessary thyroid surgery or radioactive iodine treatment. These procedures should generally be avoided, as they can worsen the effects of the hormone resistance.