Thyroid hormone resistance

Thyroid hormone resistance describes a rare syndrome where the thyroid hormone levels are elevated but the thyroid stimulating hormone (TSH) level is not suppressed, or not completely suppressed as would be expected.

Causes
The most common cause of the syndrome are mutations of the β (beta) form (THRB gene) of the thyroid hormone receptor, of which over 100 different mutations have been documented.

Mutations in MCT8 and SECISBP2 have also been associated with this condition.

Incidence
Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births.

Presentation
The syndrome can present with variable symptoms, even between members of the same family harboring the same mutation. Typically most or all tissues are resistant to thyroid hormone, so despite raised measures of serum thyroid hormone the individual may appear euthyroid (have no symptoms of over- or underactivity of the thyroid gland). The most common symptoms are goiter and tachycardia. It has also been linked to some cases of attention deficit hyperactivity disorder (ADHD), although the majority of people with that diagnosis have no thyroid problems.

An association with depression has been proposed.

Diagnosis
The characteristic blood test results for this disorder can also be found in other disorders (for example TSH-oma (pituitary adenoma), or other pituitary disorders). The diagnosis may involve identifying a mutation of the thyroid receptor, which is present in approximately 85% of cases.

Yet, since discovery of resistance to thyroid hormones in the absence of thyroid hormone receptor beta mutations, lack of a mutation in a patient does not rule out resistance.

Terminology
Sometimes the phrase thyroid hormone resistance is used to identify cases where patients with autoimmune thyroid disorders respond poorly to normal doses of replacement thyroid hormone. This is thought to occur where patients have developed antibodies to thyroid hormones. Antibodies to thyroid hormones quite commonly occur in such disorders, and may interfere with the normal clinical assays used in monitoring such disorders, and in unusual cases may have further independent clinical significance.