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Generalized Resistance to Thyroid Hormone

Tess Thompson

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The thyroid gland in humans is responsible for the synthesis and secretion of thyroid hormones thyroxine (T4) and triiodothyronine (T3). These hormones circulate through the blood and are used by every cell in the body. High or low levels of these hormones are the primary reason behind many thyroid problems.

The pituitary gland located in the brain secretes a thyroid-stimulating hormone (TSH), which controls the secretion of thyroid glands. The release of TSH depends upon the feedback from free thyroxine and triiodothyronine circulating in the blood. This essentially means that if the thyroid hormone levels are inadequate, the TSH level is increased to ensure more production, and the TSH levels are suppressed if thyroid hormones are more than adequate to reduce the level of production of thyroid hormones. Thyroid hormone resistance is a rare thyroid condition of high serum levels of free T3 and T4 with non-suppressed TSH. This leads to a situation where sometimes thyroid dysfunction may not be reflected in laboratory reports.

The most common cause of resistance to thyroid hormones is changes in the genetic structure (mutations) of the preliminary form of thyroid hormone receptor (TR-beta). A receptor is a cellular structure that is meant for mediation between a chemical agent (hormones in this case) and the physiological response.

Another cause of thyroid hormone resistance that has been discovered recently is a mutation in the thyroid hormone transporters. To initiate physiological response from cells, thyroid hormones must first enter them. Recent studies refute the earlier theory that thyroid hormones diffuse passively across plasma membrane. It is now understood that thyroid hormones actually cross plasma membrane of cells through various transporters. Mutations, in an important thyroid hormone transporter, MCT8, have been associated with thyroid hormone resistance.

The third possible cause has been found to be a defect in metabolism of the thyroid hormones. This leads to a deficient conversion of T4 to T3.

Symptoms of thyroid hormone resistance largely depend upon the underlying cause. Mutations in MCT8 may cause mental retardation and lack of normal tension in muscular tissue. It may also manifest as confusing lab reports of thyroid function tests. Mutations in TR-beta may not affect normal thyroid functioning, but can manifest as symptoms of a thyroid problem, hypothyroidism. Improper metabolism of thyroid hormones is reflected in short stature and delayed bone age (mismatch of chronological age and bone development).

There are many cases where laboratory reports of thyroid function tests do not support the symptoms of thyroid problems in patients. These discrepancies are explained with the discovery of resistance to thyroid hormones, especially mutations in MCT8.