RTH; thyroid hormone resistance; THR. It can be subdivided into different forms – either generalised resistance to thyroid hormone or pituitary (central) resistance to thyroid hormone.
Resistance to thyroid hormone is a condition in which some body tissues do not respond normally to the thyroid hormones thyroxine and triiodothyronine (they are ‘resistant’). Blood levels of thyroid hormones are elevated because the pituitary gland (which controls hormone production from the thyroid gland) is not appropriately shut off by thyroid hormone. Thyroid hormone overproduction can lead to enlargement of the thyroid gland (goitre). Peripheral tissues are either resistant or remain sensitive to high levels of thyroid hormones resulting in features of both an under- and over-active thyroid.
Usually thyroid hormones carry out their role by interacting with a receptor in the various target cells in the body. In resistance to thyroid hormone, these receptors are abnormal, meaning that the thyroid hormones cannot act normally on cells and bring about their usual effects. There are two types of thyroid hormone receptor: alpha and beta. Tissues of the body contain differing proportions of alpha and beta receptors. Resistance to thyroid hormone is usually caused by a genetic mutation resulting in a defective beta receptor. Tissues in the body respond differently to high thyroid hormone levels depending on the relative amount of alpha versus beta receptor contained in that tissue. Thus, tissues containing mainly normal alpha receptors can exhibit features of thyroid overactivity, whereas tissues with mainly defective beta receptors are resistant to hormone action and can show features associated with thyroid underactivity.
The symptoms of thyroid hormone resistance vary depending on the severity of the abnormality with the thyroid hormone receptor. Hence, some patients might have no symptoms if they have a milder, partial resistance because they can overcome this by increasing the amount of thyroid hormones they make. This mild condition is sometimes referred to as ‘generalised resistance to thyroid hormone’.
Some patients might have signs of an underactive thyroid if their receptors respond very little to thyroid hormones. These include raised cholesterol levels, feeling tired and a tendency to be overweight (see the article on hypothyroidism for more information). However, there can also be some symptoms of an overactive thyroid, especially a fast heart rate (see the article on hyperthyroidism for more information). This is because the heart has few beta receptors and more of the normal alpha receptors that respond normally to the increased levels of thyroid hormone.
Most people with this condition develop an enlarged thyroid gland (goitre). This occurs because of the need to make more thyroid hormones than normal.
In children, there can be failure to grow, more frequent ear, nose and throat infections, attention deficit hyperactivity disorder (ADHD), learning disability and hearing loss.
Resistance to thyroid hormone is rare, affecting around 1 in every 40,000–50,000 people. It affects men and women equally. It may be diagnosed at any age although the blood test will be abnormal from birth.
The condition is inherited from one or other parent in over 80% of individuals. A person with resistance to thyroid hormone has a 50% chance of passing it on to each child.
The first step is to do a simple blood test called a thyroid function test. This usually shows high levels of thyroid hormones (thyroxine and triiodothyronine) along with a normal or slightly high level of thyroid stimulating hormone (TSH). This abnormal test is also seen in those patients with thyroid hormone resistance and no symptoms. This pattern of results can also be seen in several other situations. These include incorrect laboratory measurement of thyroid hormones due to interfering antibodies or abnormal thyroid hormone binding proteins in the blood; or a pituitary condition called a TSH-secreting pituitary adenoma.
The laboratory will check the test results carefully to exclude interference with measurement or a problem with circulating binding proteins. A TSH-secreting pituitary adenoma can be excluded by doing a blood test called ‘alpha subunit’ and a magnetic resonance imaging (MRI) scan of the brain. A test called a thyrotropin-releasing hormone test is also usually carried out to differentiate resistance to thyroid hormone from TSH-secreting pituitary adenoma. This is done in hospital but only takes a morning. It involves taking an initial blood sample followed by an injection of thyrotropin-releasing hormone, then further blood tests over an hour. Blood will also be taken to look for abnormalities of the thyroid hormone beta receptor by genetic testing. Family members may also be asked to have thyrotropin-releasing hormone checked.
After these investigations, if the diagnosis is still not clear, a triiodothyronine suppression test may be required. This involves taking a high dose of the thyroid hormone triiodothyronine for eight to 10 days with blood tests to measure hormone levels before and afterwards.
Genetic testing can provide a definitive confirmation, though it is likely that not all variants are known.
Many people with resistance to thyroid hormones have abnormal blood tests but no symptoms. They do not require any treatment. Children will need extra assessment to check they are growing and developing normally.
Patients who have symptoms of hypothyroidism (underactive thyroid) are treated with levothyroxine tablets – a synthetic version of thyroxine given to replace the sub-optimal level of thyroid hormone. Once the levothyroxine is absorbed in the bloodstream, it is converted to triiodothyronine, which is the active hormone that the tissues and cells require. Combination treatment with levothyroxine and triiodothyronine is not recommended because there is no clear evidence in research studies that it is more beneficial than levothyroxine alone. The treatment needs to be monitored with regular blood tests.
Drugs to slow the heart rate (e.g. a beta-blocker) may be prescribed for patients who have a fast heart beat because of the high levels of thyroid hormones.
Sometimes a drug called TRIAC, which mimics the action of thyroid hormone in specific tissues (i.e. the pituitary, liver), can be used to treat patients with resistance to thyroid hormone.
Beta-blockers, TRIAC and thyroxine are usually well tolerated with few side-effects. If high doses of thyroid hormones are required to compensate for the resistance, this can sometimes cause a fast heart rate requiring extra treatment with a beta-blocker.
Rarely, the very high levels of thyroid hormones can cause growth and related problems in an unborn child and this requires careful monitoring. Women who have resistance to thyroid hormones should speak to their specialist before becoming pregnant.
Resistance to thyroid hormone comes with an increased likelihood of thinning of the bones (osteoporosis) so monitoring of bone density is carried out in adult patients.
There is no evidence that any specific dietary modification can help in resistance to thyroid hormone.
British Thyroid Foundation may be able to provide advice and support to patients and their families dealing with resistance to thyroid hormone.
Last reviewed: Nov 2021
