Thyroid hormone resistance syndrome thrs is a rare autosomal dominant or recessive disorder that occurs in familial and sporadic cases. The syndrome ofgeneralized thyroid hormone resistance gthrwasfirst describedbyrefetoffetal. Resistance to thyroid hormone rth is a dominantly inherited condition of impaired tissue responsiveness to thyroid hormone th. A case of resistance to thyroid hormone with thyroid cancer resistance to thyroid hormone rth is an autosomal dominant hereditary disorder that is difficult to diagnose because of its rarity and variable clinical features. The characteristic clinical feature is goitre without symptoms and metabolic consequences of thyroid hormone. Peripheral resistance to thyroid hormones genetic and rare. Thyroid hormone resistance syndrome thrs is a rare disorder with increased concentrations of free thyroxine ft4 and triiodothyronine ft3, but normal or slightly increased thyroidstimulating hormone tsh. This is a common cause of feeling like crap because when this happens in your body, the cells arent absorbing and utilizing thyroid. Thyroid hormone resistance postgraduate medical journal. Resistance to thyroid hormone is a rare genetic condition where some body tissues do not respond normally to thyroid hormones produced by the thyroid gland. Thyroid hormone resistance syndrome due to mutations in. Of variable severity, the presence of goiter, tachycardia, hyperactivity, or abnormal findings on routine laboratory tests usually lead to further investigation and, ultimately, the diagnosis of rth.
The syndrome of impaired sensitivity to thyroid hormone, also known as syndrome of thyroid hormone resistance, is an inherited condition that occurs in 1 of 40,000 live births characterized by a reduced responsiveness of target tissues to thyroid hormone due to mutations on the thyroid hormone receptor. Resistance to thyroid hormone rth is a rare disorder characterized by variable tissue hyporesponsiveness to thyroid hormone, usually caused by mutations in the thyroid hormone receptor beta tr. The disorder has an autosomal dominant or recessive pattern of inheritance. The most common forms of thyroid hormone resistance are caused by mutations of the thyroid hormone receptor beta gene. Seminal studies have highlighted the contribution of thyroid hormone associated derangements to the incidence of insulin resistance, wherein a partial thyroidectomy was associated with improvements in insulin resistance and restored glucose tolerance in diabetic subjects with hyperthyroidism 9, 57, 64, 70. The mutant receptor has lower binding affinity for thyroid hormone and, as a consequence. Its major cause, found in more than 3,000 individuals, is mutations in the th receptor. The aims of this study were to present 1 pedigree of. Mar 20, 20 only free and albuminbound thyroid hormone is biologically available to tissues.
Resistance to thyroid hormone rth is most often due to point mutations in. Treatment of resistance to thyroid hormoneprimum non nocere. The clinical manifestation includes reduced responsiveness of the targeted tissues pituitary andor surrounding to thyroid hormone, which leads to increased concentrations of free thyroxine ft 4 and triiodothyronine ft 3, but normal or. Hypothyroidism and resistance to thyroid hormone panel. Background resistance to thyroid hormone is characterised by a lack of response of peripheral tissues to the active form of thyroid hormone triiodothyronine, t3.
Pituitary resistance to thyroid hormone prth is defined as resistance to the action of thyroid hormone that is more severe in the pituitary than at the peripheral tissue level. A case of resistance to thyroid hormone with thyroid cancer. A thyroid hormone receptor mutation that dissociates thyroid hormone regulation of gene expression in vivo. Resistance to thyroid hormone rth is caused by reduced target tissue response to thyroid hormone, resulting in the loss of the normal feedback mechanism that suppresses the secretion of thyrotropin tsh.
Thyroid hormone receptors and resistance to thyroid. Pubmed is a searchable database of medical literature and lists journal articles that discuss generalized resistance to thyroid hormone. The characteristic clinical feature is goitre without symptoms and metabolic consequences of thyroid hormone excess. The first report of the condition appeared in 1967. Proceedings of the national academy of sciences 2009. Genetic and clinical features of 42 kindreds with resistance to thyroid hormone. It has been reported that the serum of patients with rth is free of autoantibodies against thyroglobulin tg and thyroid peroxidase tpo, except in rare cases where coincidental. A case of partial end organ resistance to thyroid hormone in congenital hypothyroidism is described, with evidence of an alteration in tsh threshold to feedback inhibition by thyroid hormone. Conventional medicine, in years past, has tried, often without success, and sometimes with undesirable side effects, to simply plug in to the thyroid pathway with various and sundry combinations of synthetic thyroxine t4 and triiodothyronine t3.
Thyroid resistance as valid as insulin resistance, yet. In general, the relative tissuespecific distribution of tr. The syndrome of resistance to thyroid hormone, misdiagnosed. Aug 19, 2014 patients with mutations in thrb present with resistance to thyroid hormone.
This is a common cause of feeling like crap because when this happens in your body, the cells arent absorbing and utilizing thyroid hormone. However, the sequence of recognition of thyroid hormone receptor mutations as a cause of resistance to thyroid hormone is not as suggested in the editorial by dr. Generalized resistance to thyroid hormone genetic and. Thyroid hormone secretion suppresses the expression of thyroid stimulating hormone tsh, both of which are strictly controlled by a negative feedback loop between the hypothalamuspituitary and thyroid. For physicians of patients taking thyroid hormones mildmoderate thyroid insufficiency is quite common and is an unrecognized cause of depression, obesity, high cholesterol, cold intolerance, atherosclerosis, chronic fatigue, and fibromyalgia. Thyroid hormone resistance syndrome caused by heterozygous.
This disorder can easily be confused with graves disease and result in inappropriate treatment for hyperthyroidism, as was the case in three of our patients. The syndrome of impaired sensitivity to thyroid hormone isth is a condition of decreased tissue sensitivity to thyroid hormone action usually caused by germline mutations of the thyroid hormone receptor beta thrb gene. About 85% of patients with rth are harboring mutations in thyroid hormone receptor beta tr. This is a case of a woman who was diagnosed with resistance to thyroid hormone after total thyroidectomy for thyroid cancer. So you might be taking thyroid hormone and your lab work might all look great, but you still feel like they just scraped you off the tires of a.
Impaired biologic activity of the hormone impaired activity of the hormone is caused by mutations or posttranscriptional modifications that result in production of an abnormal hormone molecule. About 1 in 5,000 babies is born with congenital hypothyroidism, in which the thyroid fails to grow. Sep 15, 2017 there are two genes that express the major thyroid hormone receptor isoforms. Very interesting case study on thryoid hormone resistance. I have been diagnosed with partial peripheral tissue resistance to thyroid hormone and currently take 350 mg of cytomel. Resistance to thyroid hormonebeta rthbeta is a rare inherited syndrome characterized by variable reduced tissue responsiveness to the intracellular action of triiodothyronine t3, the active form of the thyroid hormone. Thyroid hormone receptors and resistance to thyroid hormone.
Authors present an eightmonthold infant with poor linear growth. Only free and albuminbound thyroid hormone is biologically available to tissues. Thyroid hormone resistance syndrome is a genetic disease determined by a mutation that modifies the configuration of the. Thyroid hormone resistance an overview sciencedirect topics. In this article, we present a case of resistance to thy roid hormones, in. The most common category is resistance to thyroid hormone rth, a syndrome characterized by reduced intracellular action of. Resistance to thyroid hormone rth is an inherited syndrome of reduced tissue responsiveness to thyroid hormone t3 caused by mutations in the thyroid hormone receptor beta trbeta. The monarch initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers.
Fortunately, the thyroid glands resistance can be overridden with skyhigh levels of thyroid hormone in the form of cytomel. Pdf thyroid hormone resistance syndrome and pregnancy. Resistance to thyroid hormones rth is a syndrome characterized by reduced response to thyroid. Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, r243q and r243w, with marked impairment of function that cannot be explained by altered in vitro 3,5,3. These findings suggest that thyroid hormone resistance in this patient is not due to a decrease in either the affinity or the number of specific nuclear t 3 receptors. Monarchs tools are designed to make it easier to compare the signs and symptoms phenotypes of different diseases and discover common features.
It is characterized by the presence of elevated serum levels of the free thyroid hormones thyroxine t4 and triiodothyronine t3 with. Reduced sensitivity to thyroid hormones rsth is a rare disease that affects about 3,000 indi viduals, belonging to about. Similarly, numerous cases of resistance to thyroid hormone rth and the corresponding mutations in the genes encoding human thyroid. Thr is differentiated from thyroid stimulating hormone tsh secreting pituitary adenoma by history of. Mutations in the genes that encode the thyroid hormone receptors thrs,thra and thrb, result in resistance to thyroid hormone disorders. Voltaire said that in all nations, history is disfigured by fable and history proves that anything can be proved by history. Among the amount of thyroid hormone production and release t4 is approximately 95% and t3 is 5%. My editorial was a brief overview of the idea of failure to respond well to hormones and was aimed at putting the concept of resistance to thyroid hormone in context. End organ resistance to thyroid hormone has been described for a number of years. Thyroid and weight does extreme obesity affect thyroid hormone absorption. Most of the reported mutations have been detected in the thyroid hormone receptor. Syndromes of thyroid hormone resistance emconsulte. A case of resistance to thyroid hormone diagnosed after. I have been on the gamoot of different medications and after 3 months it seemed they woould lose their effec.
Now available in pdf format for saving and printing and web page format for viewing online. Partial end organ resistance to thyroid hormone in congenital. The first person to diagnose me was the wonderful late dr, john c lowe who has since passed away. The patient is thus hypothyroid in a clinical sense. Resistance to thyroid hormone with a mutation of the. Mutations in both these genes have given rise to resistance to thyroid hormone rth syndromes rth. Resistance to thyroid hormone rth is a dominantly inherited condition of impaired tissue responsiveness to thyroid hormone th 16. They usually have elevated thyroid hormones and a normal or elevated thyroid. It has been reported that the serum of patients with rth is free of autoantibodies against thyroglobulin tg and thyroid peroxidase tpo, except in rare cases where coincidental autoimmune. Seminal studies have highlighted the contribution of thyroid hormoneassociated derangements to the incidence of insulin resistance, wherein a partial thyroidectomy was associated with improvements in insulin resistance and restored glucose tolerance in diabetic subjects with hyperthyroidism 9, 57, 64, 70. He defines thyroid hormone resistance as a type 2 format of hypothyroidism, much as insulin resistance occurs in prestage to diabetes type 2, and explains that it has more to do with.
Resistance to thyroid hormone rth is most often due to point mutations in the i. Todays health tip is about thyroid hormone resistance. Generalized resistance to thyroid hormone genetic and rare. It is often secondary, so the tsh is normal, but the ft4 and ft3 levels are low in the reference ranged. It may be associated with no symptoms or with features of both an overactive and underactive thyroid. Thyroid hormone resistance endocrinology cmc in vellore. The syndrome of resistance to thyroid hormone rth is characterized by elevated circulating levels of free thyroid hormones together with nonsuppressed pituitary tsh secretion. Description of the thyroid hormone resistance syndrome illustrated. Wondisford, in handbook of neuroendocrinology, 2012. It reflects resistance to thyroid hormone action in the hypothalamicpituitary thyroid hpt axis and is accompanied by variable refractoriness in peripheral tissues. A clinicians guide to understanding resistance to thyroid. The magnitude of rth is caused by mutations in the thyroid hormone receptor beta tr. A case of resistance to thyroid hormone diagnosed after total thyroidectomy for thyroid cancer mariko aoyama department of surgery, tokushima municipal hospital abstract.
Resistance to thyroid hormone with a mutation of the thyroid. Partial end organ resistance to thyroid hormone in. Increased t3 and t4, determined by a compensatory tsh elevation. About 1 in 5,000 babies is born with congenital hypothyroidism, in which the thyroid fails to grow normally and cannot produce enough hormone. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone. A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for peripheral resistance to thyroid. But biological active is t3 so t4 is converted to t3 in peripheral tissues by the enzyme 5monodeiodinase and become active. Treatment of resistance to thyroid hormoneprimum non. Patients with thr have elevated serum free thyroxine ft4, free triiodothyronine ft3, but normal or slightly elevated serum thyrotropin values. If you have problems viewing pdf files, download the latest version of. Tissue responses to thyroid hormone in a kindred with resistance to thyroid hormone harboring a commonly occurring mutation in the thyroid hormone receptor beta gene p453t.
Apr 15, 2020 patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone. The mutant tr molecules have either reduced affinity for t 3 or impaired interaction with one of the cofactors involved in the mediation of th action 10. Yagi h, pohlenz j, hayashi y, sakurai a, refetoff s. Since response to the authentic hormone is normal, this circumstance is a pseudoresistance. With a few exceptions, rth is caused by mutations in the tr. More recently mutations in the thra gene were found to produce a different phenotype owing to the distinct tissue distribution of this th receptor. This leads the thyroid gland to make a normal, but completely ineffectual, amount of thyroid hormone that cannot function in the body. However, it may be due to excessive ingestion of thyroid hormone or, rarely, thyroid hormone production from an ectopic site, as seen in struma ovarii. Thyroid hormone resistance an overview sciencedirect. Resistance to thyroid hormone rth rth is inherited in an autosomal dominant manner and usually caused by a mutation in the thyroid hormone receptor beta trb. Patients with thr have elevated serum free thyroxine ft 4, free triiodothyronine ft 3, but normal or slightly elevated serum thyrotropin values. It reflects resistance to thyroid hormone action in the hypothalamicpituitarythyroid hpt axis and is accompanied by variable refractoriness in peripheral tissues. Thyroid hormone resistance thr is a rare syndrome of reduced end organ sensitivity.
Variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum tsh. About hypothyroidism and resistance to thyroid hormone primary congenital hypothyroidism is a permanent thyroid hormone deficiency that is present from birth. These mutations cluster in three different hot spot in the t3. A clinicians guide to understanding resistance to thyroid hormone.
Click on the link to view a sample search on this topic. Impaired sensitivity to thyroid hormone previously known as reduced sensitivity to thyroid hormone describes any process that interferes with the effectiveness of thyroid hormone and includes defects in thyroid hormone action, transport, or metabolism. However, the sequence of recognition of thyroid hormone receptor mutations as a cause of resistance to thyroid hormone is not. Quantitative assessment of pituitary resistance to thyroid hormone from plots of the logarithm of thyrotropin versus serum free thyroxine index. In about 85% of cases, a mutation in thrb, the gene coding for thyroid receptor. Pdf the syndrome of impaired sensitivity to thyroid hormone, also known as syndrome of thyroid hormone resistance, is an inherited condition that. Recently, individual reports described the first patients with thyroid hormone receptor. Thyroid hormone resistance syndrome caused by heterozygous a. Resistance to thyroid hormone you and your hormones from. My editorial was a brief overview of the idea of failure to respond well to hormones and was aimed at putting the concept of resistance to thyroid hormone in. A clinicians guide to understanding resistance to thyroid hormone due to receptor mutations in the tr. Resistance to thyroid hormone annals of internal medicine. Fortunately, the thyroid glands resistance can be overridden with skyhigh levels of thyroid hormone in. Pdf format for saving and printing clinical thyroidology for patients july 2011 volume 4 issue 7 pdf file, 880 kb table of contents web format.
Rth was originally described in 1967, and is inherited as an autosomal dominant disorder. Although patients with gthrare relatively refractory to the. The mutant trb is unable to bind t3 or interact with other factors that are necessary for thinduced gene transcription. Thyroid hormone resistance and its management ncbi. A case of resistance to thyroid hormone diagnosed after total. Sep 29, 2011 thyroid hormone secretion suppresses the expression of thyroid stimulating hormone tsh, both of which are strictly controlled by a negative feedback loop between the hypothalamuspituitary and thyroid. Thyroid hormone resistance also resistance to thyroid hormone rth, and sometimes refetoff syndrome 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. A case of resistance to thyroid hormone with chronic. Cardiac involvement in thyroid hormone resistance the. Treatment of resistance to thyroid hormone primum non nocere.
1522 1068 1042 39 1005 348 773 1253 1128 1442 763 846 542 884 577 1373 1456 362 315 271 1215 17 840 453 343 941 775 729 1115 117 349 1229 713