Pubmed is a searchable database of medical literature and lists journal articles that discuss generalized resistance to thyroid hormone. Thyroid hormone treatment american thyroid association. Also, resistance to thyroid hormones is characterized by variable phenotypes. Thyroid hormones are important determinants of glucose homeostasis. Thyroid hormone resistance syndrome thrs is a rare autosomal dominant or recessive disorder that occurs in familial and sporadic cases. 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. Patients with thr have elevated serum free thyroxine ft4. Patients with thr have elevated serum free thyroxine ft4, free triiodothyronine ft3, but normal or slightly elevated serum thyrotropin values. Thyroid resistance can be the cause of many symptoms, such as acne, allergies, arthritis, asthma, chronic fatigue syndrome, chronic pain, depression, fibromyalgia, headaches, obesity, panic attacks, let alone being an important component to such health issues as attention deficit disorder add, and even dementia. Thyroid hormone resistance an overview sciencedirect topics. Reversible pituitary enlargement in the syndrome of. A clinicians guide to understanding resistance to thyroid hormone. Variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum tsh.
The first report of the condition appeared in 1967. Thyroid hormone resistance and the value of genetics. It has been suggested that both autosomal dominant and recessive forms exist because of different mutations in the same gene. The most common forms of thyroid hormone resistance are caused by mutations of the thyroid hormone receptor beta gene. The syndrome of resistance to thyroid hormone rth is a pathologic condition in which patients show decreased sensitivity to thyroid hormone due to gene mutations. Suppression therapy is used primarily in patients with thyroid cancer to prevent recurrence or progression of their cancer. 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. This leads the thyroid gland to make a normal, but completely ineffectual, amount of thyroid hormone that cannot function in the body. 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. We describe the syndrome of thyroid hormone resistance presenting in identical twins. 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. Hypothyroidism in these patients is partly overcome by the increased thyroid hormone levels. Treatment of resistance to thyroid hormoneprimum non.
Thyroid hormone resistance an overview sciencedirect. A study on assessment of thyroid stimulating hormone and. Coexistence of thyroid hormone resistance syndrome, pituitary. Reduced sensitivity to thyroid hormones rsth is a rare disease that affects about 3,000 indi viduals, belonging to about. Since then, others have used clinical, biochemical, and molecular studies to identify many examples of hormone resistance with mutations in their corresponding receptors. Resistance to thyroid hormone rth occurs in rare patients and its clinical presentation is considerably different than that seen in the usual hyperthyroid patient. This resistance is based on mutations in receptors. Fortunately, the thyroid glands resistance can be overridden with skyhigh levels of thyroid hormone in the form of cytomel. Fortunately, the thyroid glands resistance can be overridden with skyhigh levels of thyroid hormone. Mar 01, 2019 the syndrome of thyroid hormone resistance rth is a rare condition of the endocrine system in which the sensitivity of the target tissues to thyroid hormone th is decreased.
Patients with thr have elevated serum free thyroxine ft 4, free triiodothyronine ft 3, but normal or slightly elevated serum thyrotropin values. Rth is caused by mutations in the trb gene located on chromosome 3. Tissues in patients with rth are resistant to the action of t3 to the extent this gene is expressed in cells involved. Thyroid hormone resistance syndrome caused by heterozygous a. Resistance to thyroid hormone rth, a syndrome of reduced responsiveness of target tissues to thyroid hormone th was identified in 1967 1. Fuller albright first showed that pseudohypoparathyroidism represented a form of hormone resistance syndrome 75 years ago. Resistance to thyroid hormone you and your hormones from. Mutations in both these genes have given rise to resistance to thyroid hormone rth syndromes rth.
An inherited autosomal recessive trait, characterized by peripheral resistance to thyroid hormones and the resulting elevation in serum levels of thyroxine and triiodothyronine. These include chronic emotional or physical stress, chronic illness, diabetes, insulin resistance, obesity, leptin resistance, depression, chronic fatigue syndrome, fibromyalgia, pms, and both dieting and weight gain. Resistance to thyroid hormone associated with a novel mutation of the thyroid. Of interest, as in this case, is pituitary resistance to thyroid hormone. Generalized thyroid hormone resistance gthr refers to a syndrome characterized by elevated circulating lev els of free thyroid hormones, resistance to thyroid hormone action, and inappro priately normal or. Thyroid resistance as valid as insulin resistance, yet. 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. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone.
The characteristic clinical feature is goitre without symptoms and metabolic consequences of thyroid hormone excess. Thyroid hormone resistance postgraduate medical journal. Distinct single amino acid substitutions in the ligand binding domain of the beta form of the thyroid hormone receptor have been described in two kindreds with this disorder. Common symptoms reported by people with thyroid hormone resistance. Thyroid hormone resistance syndrome due to mutations in. It may be associated with no symptoms or with features of both an overactive and underactive thyroid. Resistance to thyroid hormone rth is a rare autosomal dominant inherited syndrome of reduced endorgan responsiveness to thyroid hormone.
Patients with thr have elevated serum free thyroxine. This syndrome is caused by mutations of gene thrb encoding the thyroid hormone receptors beta in target cells. The variable clinical phenotype in thyroid hormone resistance. Hypothyroidism and resistance to thyroid hormone panel.
Each form of resistance manifests itself differently regarding. The syndrome of resistance to thyroid hormone, misdiagnosed. Resistance to thyroid hormone rth is a dominantly inherited condition of impaired tissue responsiveness to thyroid hormone th. More than individuals have been identified with thyroid hormone resistance, of which 85% had thyroid hormone beta receptor mutation. The syndrome ofgeneralized thyroid hormone resistance gthrwasfirst describedbyrefetoffetal. We report pituitary enlargement after radioiodine ablation in a patient with elevated thyroid hormones and features of hyperthyroidism. 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. Ravi1, sadaria roshni gokaldas2 1md, professor and head, department of biochemistry, kempegowda institute medical sciences, banashankari 2nd stage, bangalore 560070, india.
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. Increased t3 and t4, determined by a compensatory tsh elevation. Metabolic syndrome ms is clustering obesity, hypertension, dyslipidemia and insulin resistance. Tsh increase was shown to be associated with increased cholesterol and triglycerides and with decreased hdlc. About hypothyroidism and resistance to thyroid hormone primary congenital hypothyroidism is a permanent thyroid hormone deficiency that is present from birth. Peripheral thyroid hormone conversion and its impact on tsh and metabolic activity worsened in numerous conditions. Pdf thyroid hormone resistance syndrome and pregnancy. The aims of this study were to present 1 pedigree of. Thyroid hormone resistance syndrome thrs is a rare disorder with increased concentrations of free thyroxine ft4 and triiodothyronine ft3, but normal or slightly increased thyroid stimulating hormone tsh. Thyroid hormones thyroxine t4 and triiodothyronine t3 regulate many cellular processes in virtually every type of tissue. Thyroid hormone regulation of metabolism physiological. It is a pathology affecting several members of the same family, given its transmission in an autosomal dominant mode. The disorder is characterized by elevated free thyroid hormone levels and partial resistance to thyroid hormone at the cellular level.
Recently, individual reports described the first patients with thyroid hormone receptor. Thyroid hormone resistance syndrome caused by heterozygous. Thyroid hormone resistance syndrome semantic scholar. Treatment of resistance to thyroid hormoneprimum non nocere. Pdf thyroid hormone resistance rth is a rare autosomal dominant disorder, characterized clinically by goiter and biochemically by elevated. The phenotype is heterogeneous and ranges from highly symptomatic to subclinical.
Because the syndrome of generalized resistance to thyroid hormones involves both the pituitary and peripheral tissues, a compensatory increase in thyroid hormone synthesis and release means that exogenous thyroid hormone treatment is not usually required to maintain a euthyroid state. The thyroid hormone deficiency or mutation of deiodinase, which is the regulator of thyroid hormone metabolism, has also been shown to induce obesity and insulin resistance. Within the sphere of subclinical hypothyroidism, or an underactive thyroid, this phenomenon can be called thyroid hormone resistance syndrome, just like in prediabetes, this initial phase towards full blown diabetes can be caused by insulin resistance syndrome, better known as syndrome x. Thyroid hormone resistance thr is a rare genetic syndrome in which tissue sensitivity to thyroid hormones is decreased, determining high levels of serum. 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. Thyroid hormone resistance syndromes hormone resistance. Ms is a status where most features of hypothyroidism can be seen. Pdf pituitary thyroid resistance syndrome researchgate. There are two genes that express the major thyroid hormone receptor isoforms. The syndrome of thyroid hormone resistance rth is a rare condition of the endocrine system in which the sensitivity of the target tissues to thyroid hormone th is decreased. Background resistance to thyroid hormone is characterised by a lack of response of peripheral tissues to the active form of thyroid hormone triiodothyronine, t3. A study on assessment of thyroid stimulating hormone and insulin resistance inwomen with polycystic ovarian syndrome b. 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. The syndrome ofgeneralized thyroid hormone resistance.
Thyroid hormone resistance syndrome rth is a rare disorder characterized by elevated levels of circulating free thyroid hormones, inappropriate tsh secretion, and reduced peripheral tissue responses to iodothyronine action. Patients with rth have elevated serum free thyroxine ft4 and free triiodothyronine ft3 concentrations and normal or slightly elevated serum thyroid stimulating hormone tsh level. Thyroid hormone resistance and its management ncbi. Clinical features, physical exam findings and the study protocol in a woman with rth are presented. The patient is thus hypothyroid in a clinical sense. Different mutations have been identified in the triiodothyron. Diagnosis of the syndromes of thyroid hormone resistance relies mainly on thyroid function tests and in most cases, confirmation with genetic testing. To exert its functions, thyroid hormone needs to bind to thyroid hormone receptor alpha tr. Rth syndrome resistance to thyroid hormone syndrome. Thyroid function, hypothyroidism, tsh, goitre introduction resistance to thyroid hormone rth is an inherited condition that is being recognized and reported more frequently now than in the past. The mutant trb is unable to bind t3 or interact with other factors that are necessary for thinduced gene transcription.
Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births. Each mutation is associated with a distinctive syndrome. The most common category is resistance to thyroid hormone rth, a syndrome characterized by reduced intracellular action of t3, the active thyroid hormone. In about 85% of cases, a mutation in thrb, the gene coding for thyroid receptor. Thyroid hormone resistance and periodic paralysis4 june 2015. 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.
Peripheral thyroid hormone conversion and its impact on. However, mutations that affect the th receptors are called dominantnegative mutations. Resistance to thyroid hormones rth is a syndrome characterized by reduced response to thyroid hormones with variable degrees of resistance in target tissues. 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. About 1 in 5,000 babies is born with congenital hypothyroidism, in which the thyroid fails to grow normally and cannot produce enough hormone. Serum thyrotropin tsh levels were elevated despite normal circulating thyroid hormones, suggesting inappropriate tsh secretion associated either with a tsh secreting pituitary adenoma or resistance to thyroid hormone rth.
An early report proposed various mechanisms including defects in th transport, metabolism and action 2. The synthesis of thyroid hormones is controlled by hypothalamic. In general, the relative tissuespecific distribution of tr. The second entity, the thyroid hormone resistance syndrome, is that encountered in our young patient. Thyroid hormone resistance syndrome due to mutations in the. Thyroid hormone th regulates metabolic processes essential for normal growth and development as well as regulating metabolism in the adult 28, 40, 189.
Weintraub the gene for generalized thyroid hormone resistance has been mapped to the cerbap thyroid hormone receptor on chromosome 3 in multiple kindreds. 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. Multiple genetic factors in the heterogeneity of thyroid. Indeed, hormone resistance due to mutations in many nuclear hormone.
It is well established that thyroid hormone status correlates with body weight and energy expenditure 80, 127, 143. Generalized resistance to thyroid hormone grth, autosomal dominant and autosomal recessive, is also caused by mutation in the thrb gene. Treatment of thyroid hormone resistance remains a challenge, especially in severely affected individuals, such as the rare homozygotes. Rth was first identified in 1967 as a syndrome of reduced endorgan responsiveness to thyroid hormone 5 and was subsequently associated with mutations in the gene encoding the beta form. It is characterized by the presence of elevated serum levels of the free thyroid hormones thyroxine t4 and triiodothyronine t3 with. Thyroid hormone resistance endocrinology cmc in vellore. The diverse effects of thyroid hormone include regulation of growth, control of basal metabolic rate, enhanced myocardial contractility, and functional differentiation of the central nervous system. Generalized resistance to thyroid hormone genetic and. 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. Jun 04, 2015 thyroid hormone resistance and periodic paralysis questioni am looking for assistance with the following case. Licensed under creative commons attribution cc by reduce visceral fat mass, with resultant improvement in insulin resistance 18. Thyroid hormone resistance thr is a rare syndrome of reduced end organ sensitivity. This clinical syndrome is characterized by reduced tissue sensitivity to thyroid hormone. Hormone resistance syndromes can be broadly defined as reduced or absent endorgan responsiveness to a hormone.
Patients with this inherited condition produce inordinate levels of thyroid hormone because their negative feedback loop at the pituitary gland is metaphorically snipped. Click on the link to view a sample search on this topic. Thyroid hormone resistance syndrome is a genetic disease determined by a mutation that modifies the configuration of the. Resistance to thyroid hormone rth is a syndrome characterized by elevated serum thyroid hormone th levels and. Discussion the prevalence of resistance to thyroid hormone is unknown but is thought to be low, probably 1 in 50,000 live births. The characteristic clinical feature is goitre without symptoms and metabolic consequences of thyroid hormone. Resistance to thyrotropin or thyroid stimulating hormone rtsh can be defined as decreased responsiveness to thyroid stimulating hormone tsh characterized by high tsh with normal but. Thyroid hormone resistance syndrome oxford medicine. Although patients with gthrare relatively refractory to the. The substitution of arginine by tryptophan in the b isoform of the thyroid hormone. A case of resistance to thyroid hormone with chronic. Thyroid hormone resistance is 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. Rth is typically characterised by an increased level of serum free t 3 ft 3, free t 4 ft 4, and a nonsuppressed level of thyroid stimulating hormone tsh.
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