Thyroid Hormone Resistance (Refetoff Syndrome) also resistance to thyroid hormone (RTH) describes a rare syndrome in which the thyroid hormone levels are elevated but the thyroid-stimulating hormone (TSH) level is not suppressed, or not completely suppressed as would be expected. It was discovered by Samuel Refetoff, M.D. in 1969. He was born in Bulgaria and immigrated to Canada, and often referred to as the father of translational thyroidology.
Refetoff identified two other syndromes: resistance to thyrotropin (RTSH) and the inherited defect that affects the metabolism of thyroid hormones through mutations in SECISBP2 gene.
The Thyroid Hormone Resistance (Refetoff Syndrome) 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.
Normal thyroid hormone function requires normal thyroid hormone transport across cell membrane, appropriate deiodination, thyroid hormone nuclear receptor, thyroid hormone response elements, co-activators, co-repressors, and normal histone acetylation. Any abnormalities in this chain can result in thyroid hormone resistance and it has not been as well studied as the various forms of insulin resistance.
The most well-known cause of the Thyroid Hormone Resistance (Refetoff Syndrome) 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.
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