Thyroid Hormone Resistance (Refetoff Syndrome)

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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.[1] 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.[4] 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.[citation needed]

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.[6] Mutations in MCT8 and SECISBP2 have also been associated with this condition.[7]

Source: Wikipedia


  1.  Jump up to:a b Refetoff S, DeWind LT, DeGroot LJ (1967). “Familial syndrome combining deaf-mutism, stuppled epiphyses, goiter and abnormally high PBI: possible target organ refractoriness to thyroid hormone”. J. Clin. Endocrinol. Metab27 (2): 279–94. doi:10.1210/jcem-27-2-279. PMID 4163616.
  2. Weiss RE, Dumitrescu A, Refetoff S (2010). “Approach to the patient with resistance to thyroid hormone and pregnancy”J. Clin. Endocrinol. Metab95 (7): 3094–102. doi:10.1210/jc.2010-0409. PMC 2928892. PMID 20610605.
  3. Refetoff S, Bassett JH, Beck-Peccoz P, Bernal J, Brent G, Chatterjee K, et al. (March 2014). “Classification and proposed nomenclature for inherited defects of thyroid hormone action, cell transport, and metabolism”Eur Thyroid J3 (1): 7–9. doi:10.1159/000358180. PMC 4005262. PMID 24847459.
  4. Hauser P, Zametkin AJ, Martinez P, et al. (1993). “Attention deficit-hyperactivity disorder in people with generalized resistance to thyroid hormone” (PDF). N. Engl. J. Med328 (14): 997–1001. doi:10.1056/NEJM199304083281403. hdl:2318/1646358. PMID 8450877.
  5. Fardella CE, Artigas RA, Gloger S, Jiménez M, Carvajal CA, Krall PM, Quiroz D, Campino C, Mosso LM (June 2007). “Refractory depression in a patient with peripheral resistance to thyroid hormone (RTH) and the effect of triiodothyronine treatment”. Endocrine31 (3): 272–8. doi:10.1007/s12020-007-0042-7. PMID 17906375. S2CID 19503692.
  6. Beato-Víbora P, Arroyo-Díez J, Rodríguez-López R (March 2013). “Thyroid hormone resistance caused by a novel deleterious variant of the thyroid hormone receptor beta gene”. Eur. J. Obstet. Gynecol. Reprod. Biol167 (1): 118–9. doi:10.1016/j.ejogrb.2012.11.001. PMID 23195042.
  7. Jump up to:a b Refetoff S, Dumitrescu AM (2007). “Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination”. Best Pract. Res. Clin. Endocrinol. Metab21 (2): 277–305. doi:10.1016/j.beem.2007.03.005. PMID 17574009.
  8. Bottcher Y, Paufler T, Stehr T, Bertschat FL, Paschke R, Koch CA (2007). “Thyroid hormone resistance without mutations in thyroid hormone receptor beta”. Med. Sci. Monit13 (6): CS67–70. doi:10.12659/MSM.484143. PMID 17534237.
  9. Lafranchi SH, Snyder DB, Sesser DE, Skeels MR, Singh N, Brent GA, Nelson JC (September 2003). “Follow-up of newborns with elevated screening T4 concentrations”. J. Pediatr143 (3): 296–301. doi:10.1067/S0022-3476(03)00184-7. PMID 14517508.

Featured photo: Mikael Häggström/Wikipedia

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