Thyroid hormone resistance syndrome (THRS) is a rare genetic disorder characterized by a reduced sensitivity of body tissues to thyroid hormone. According to researchers, this syndrome affects approximately 1 in 40,000 to 50,000 individuals globally. Unlike many other thyroid disorders that affect women disproportionately, THRS affects men and women equally.
In this article, we will learn about the:
What causes thyroid hormone resistance syndrome?
Thyroid hormone receptors are proteins that are widely distributed throughout the body and bind to triiodothyronine (T3), the active form of thyroid hormone to trigger its effects. These receptors are particularly abundant in the cells of the liver, heart, muscles, and bones.
The thyroid hormone receptor alpha (THRA) and thyroid hormone receptor beta (THRB) genes are the main genes responsible for producing thyroid receptors found in various tissues of the body.
Approximately 85% of THRS cases are associated with mutations in the THRB gene. These mutations are typically inherited in an autosomal dominant pattern, meaning a parent with the mutation has a 50% chance of passing it to their offspring. The genetic mutations can alter the structure or function of the thyroid hormone receptors, which is why they become less responsive to thyroid hormone.
What are the types of thyroid hormone resistance syndrome?
There are two main types of this disorder, namely generalized resistance to thyroid hormone (GRTH) and pituitary resistance to thyroid hormone (PRTH).
1. Generalized Resistance to Thyroid Hormone (GRTH)
GRTH involves a widespread insensitivity to thyroid hormones affecting multiple tissues throughout the body. Most individuals with GRTH are clinically euthyroid, meaning they do not exhibit overt symptoms despite having elevated thyroid hormone levels. This is because the body compensates for the reduced sensitivity by producing more thyroid hormones to achieve a nearly normal thyroid function across different tissues. However, some individuals with GRTH may show a mix of symptoms of both hypothyroidism and hyperthyroidism because different tissues vary in their sensitivity to thyroid hormones.
2. Pituitary Resistance to Thyroid Hormone (PRTH)
PRTH is characterized by resistance primarily localized to the pituitary gland. In this type, the pituitary gland does not respond appropriately to the feedback mechanisms of thyroid hormones, resulting in elevated TSH (thyroid-stimulating hormone) levels despite high levels of circulating thyroid hormone.
What are the symptoms of thyroid hormone resistance syndrome?
The symptoms of THRS can vary depending on the severity of the condition and which tissues are affected. THRS often doesn’t cause any noticeable symptoms, particularly in the generalized form. Some people, however, may have mild or even severe symptoms.
Here are some possible symptoms of THRS:
- Developmental delays (particularly in children)
- Unexplained weight gain or difficulty losing weight
- Fatigue
- Feeling cold (intolerance to cold)
- Irregular menstrual periods
- Slow heart rate (bradycardia)
- Fast heart rate (tachycardia)
- Goiter (enlarged thyroid gland)
It’s important to note that these symptoms can also be caused by other conditions, so it’s important to see a doctor for proper diagnosis.
How is thyroid hormone resistance syndrome diagnosed?
THRS can be challenging to diagnose due to many reasons such as its similarity to other conditions, asymptomatic cases, and mixed symptoms. Because many individuals with GRTH are clinically euthyroid (do not exhibit obvious symptoms), there’s a high likelihood of a delayed diagnosis.
Moreover, standard thyroid function tests may show high levels of thyroid hormones along with normal or slightly elevated TSH levels. This is the opposite of what you would expect in hyperthyroidism, where TSH is typically suppressed. For this reason, thyroid function tests alone are not enough to diagnose THRS as the results require careful interpretation and follow-up testing to rule out other causes of thyroid dysfunction
Generally, diagnosing THRS involves a combination of clinical evaluation and laboratory tests, including:
- Thyroid Function Tests: These blood tests measure levels of TSH, T4, and T3. In THRS, TSH levels are usually within the normal range or slightly elevated, despite high levels of T4 and T3.
- Genetic testing: This can confirm mutations in the THRB or THRA gene and is particularly useful in ambiguous cases.
- Specialized tests: The thyrotropin-releasing hormone (TRH) stimulation test, for instance, can help differentiate PRTH from other conditions such as TSH-secreting Pituitary Adenomas (TSHomas). This is necessary as both conditions show elevated TSH levels with high thyroid hormone levels. Also, imaging studies, such as MRI, may also be needed to exclude TSHomas, adding to the diagnostic process’s complexity and cost.
How is thyroid hormone resistance syndrome managed?
Although there is no cure for THRS, many patients (who are asymptomatic) actually do not require treatment. This is because the body can compensate for the reduced sensitivity by producing higher levels of thyroid hormones.
Symptomatic treatment, however, focuses on managing specific symptoms. For instance, beta-blockers can be used to control tachycardia, while triiodothyroacetic acid (TRIAC) may be used to reduce thyroid hormone levels. TRIAC is a synthetic analog of T3, mimics its effects, and binds even more strongly to the thyroid hormone receptors in specific tissues like the pituitary gland. This helps to normalize the levels of TSH produced by the pituitary gland.
Living with THRS
Individuals with THRS often lead normal lives. However, regular medical follow-up is essential to manage the condition effectively, especially for children and those who are symptomatic. Being well-informed about THRS can also help patients and their families navigate the challenges associated with this disorder.
Key takeaways
- Thyroid hormone resistance syndrome is a complex and rare condition requiring careful diagnosis and tailored treatment strategies.
- Genetic testing plays a vital role in confirming the diagnosis and guiding treatment, while ongoing research continues to enhance our understanding and management of this disorder.
- Although it is a lifelong condition, with appropriate diagnosis and tailored management, individuals with THRS can maintain a good quality of life.
- Management of THRS aims to address symptoms and normalize TSH levels when possible.
