Resistance to thyroid hormone rth is a rare autosomal dominant inherited syndrome of reduced endorgan responsiveness to thyroid hormone. Pdf thyroid hormone resistance syndrome and pregnancy. Thyroid hormone th regulates metabolic processes essential for normal growth and development as well as regulating metabolism in the adult 28, 40, 189. Pituitary thyroid resistance syndrome showed that the trbeta molecule is not necessary for the upregulation of tsh, but is required for thyroid hormone to exert its full suppressive effect. Thyroid hormone resistance syndrome is a genetic disease determined by a mutation that modifies the configuration of the. The characteristic clinical feature is goitre without symptoms and metabolic consequences of thyroid hormone excess. Suppression therapy is used primarily in patients with thyroid cancer to prevent recurrence or progression of their cancer. The syndrome ofgeneralized thyroid hormone resistance gthrwasfirst describedbyrefetoffetal. 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. In the present case, he was diagnosed to have pituitary resistance to thyroid hormone as clinically he was thyrotoxic and he had raised free t4 and t3 but. But biological active is t3 so t4 is converted to t3 in peripheral tissues by the enzyme 5monodeiodinase and become active.
However, important pitfalls and difficult cases still exist. Voltaire said that in all nations, history is disfigured by fable and history proves that anything can be proved by history. It reflects resistance to thyroid hormone action in the hypothalamicpituitarythyroid hpt axis and is accompanied by variable refractoriness in peripheral tissues. The test to address sensitivity to thyroid hormone was performed using liothyronine 50 mcg x 3 day, 100 mcg x 3 day, 200 mcg x 3 days. Patients with thr have elevated serum free thyroxine. Hormone resistance syndromes can be broadly defined as reduced or absent endorgan responsiveness to a hormone.
Thyroid hormone resistance and pituitary enlargement after. Serum thyrotropin tsh levels were normal or slightly elevated and responded normally to the administration of thyrotropinreleasing hormone trh and ltriiodothyronine. Thyroid hormone resistance and periodic paralysis questioni am looking for assistance with the following case. 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. 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 aims of this study were to present 1 pedigree of.
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. Thyroid hormone treatment american thyroid association. Patients with thr have elevated serum free thyroxine ft4. The aim of this study was to investigate the effect of weight loss after bariatric surgery bs on resistance to thyroid hormones in patients with extreme obesity compared with a control group. We report a patient with inappropriate secretion of thyrotropin tsh and a pituitary mass. A case of resistance to thyroid hormone with chronic.
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. The diagnosis of thyroid hormone resistant syndromes thrs is based on abnormal thyroid hormone th laboratory tests. 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. Resistance to thyroid hormone an incidental finding. Thyroid hormone resistance and the value of genetics. A case of resistance to thyroid hormone diagnosed after. Only free and albuminbound thyroid hormone is biologically available to tissues. Thyroid hormone resistance wikimili, the free encyclopedia.
Patients with all rth all have nonsuppressed thyroidstimulating hormone tsh levels despite elevated free thyroxine ft4 and free. However, the sequence of recognition of thyroid hormone receptor mutations as a cause of resistance to thyroid hormone is not. Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births. It is characterized by the presence of elevated serum levels of the free thyroid hormones thyroxine t4 and triiodothyronine t3 with. Thyroid hormone resistance postgraduate medical journal.
Any discussion on thyroid resistance would be remiss in not mentioning dr. Thyroid hormone resistance is a rare condition characterised biochemically by elevated levels of free thyroid hormones t3 and t4, together with an inappropriately normal tsh concentration. Pdf the syndrome of impaired sensitivity to thyroid hormone, also known as. Interpretation of thyroid function tests the lancet. The disorder is characterized by elevated free thyroid hormone levels and partial resistance to thyroid hormone at the cellular level. Resistance to thyroid hormone rth, a syndrome of reduced. Resistance to thyroid hormone you and your hormones from. Genetic analysis identified a thyroid hormone receptor gene mutation t277i, making a diagnosis of resistance to thyroid hormone rth. The patient is thus hypothyroid in a clinical sense.
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 duration of thyroid hormone abnormality from november 2011 to april 2012 seemed to speak against thyroiditis. Patients with thr have elevated serum free thyroxine ft4, free triiodothyronine ft3, but normal or slightly elevated serum thyrotropin values. 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. Thyroid hormones ths exert marked effects on cardiac function that result from direct effects of the hormones on the cardiac myocyte as well as effects on the peripheral vasculature. Resistance to thyroid hormone rth is a syndrome involving reduced responsiveness of target tissues to thyroid hormone th 1.
The altered thyroid function of obesity may be due to a mild acquired resistance to the thyroid hormone. Patients with thr have elevated serum free thyroxine ft 4, free triiodothyronine ft 3, but normal or slightly elevated serum thyrotropin values. In about 85% of cases, a mutation in thrb, the gene coding for thyroid receptor. This leads the thyroid gland to make a normal, but completely ineffectual, amount of thyroid hormone that cannot function in the body. 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 syndrome due to mutations in. Typically, despite the high serum thyroid hormone levels, tsh release occurs with stimulation by trh. Hyperthyroidism, excess thyroid hormone, promotes a hypermetabolic state characterized by increased resting. The most common category is resistance to thyroid hormone rth, a syndrome characterized by reduced intracellular action of. On evaluation, she had increased free thyroxine and tsh levels, normal serum glycoprotein. Here, we describe the first patients identified with a mutation in thra that affects both tr. The aim of this research is to study a pediatric case of resistance to thyroid hormone rth and its clinical manifestation. All were clinically euthyroid but all had goiters and markedly increased serum thyroid hormone levels. Treatment of resistance to thyroid hormoneprimum non.
Although she had been treated for biochemical hyperthyroidism with thyroid surgery and radioiodine ablation, she had never complained of specific symptoms or demonstrated signs of overt thyroid dysfunction. Thyroid hormone resistance thr is a rare syndrome of reduced end organ sensitivity. As a consequence, higher concentrations of free thyroid hormone are required for hormone to bind to the receptor. In general, the relative tissuespecific distribution of tr. Thyroid hormone resistance and its management ncbi. Thyroid hormone resistance endocrinology cmc in vellore. The most common forms of thyroid hormone resistance are caused by mutations of the thyroid hormone receptor beta gene.
Resistance to thyroid hormone rth is a dominantly inherited condition of impaired tissue responsiveness to thyroid hormone th. This class of conditions is due to a defect in th action resistance to thyroid hormone, rth, t4 transport into the cell thyroid hormone cell transport defect, thctd or metabolism of t4 to the active hormone, t3 thyroid. 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. Increased t3 and t4, determined by a compensatory tsh elevation.
Resistance to thyroid hormone rth, is a rare genetic disease. Thyroid hormone resistance syndrome caused by heterozygous. Thyroid hormone resistance an overview sciencedirect. Resistance to thyroid hormone caused by a mutation in. Thyroid resistance as valid as insulin resistance, yet. Rth is a disorder characterised by elevated thyroid hormones, failure to suppress pituitary tsh secretion and variable refractoriness to hormone action in peripheral tissues.
Thyroid hormone resistance and pregnancy kane 2003. Recently, individual reports described the first patients with thyroid hormone receptor. 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. For complete coverage of this and related areas in endocrinology, visit the free online webtextbook, resistance to thyroid hormone rth, a syndrome of reduced responsiveness of target tissues to thyroid hormone th was identified in 1967 1. The syndrome of resistance to thyroid hormone rth is characterized by elevated circulating levels of free thyroid hormones together with nonsuppressed pituitary tsh secretion. The condition is usually the result of a mutation in the t3 binding domain of. The characteristic clinical feature is goitre without symptoms and metabolic consequences of thyroid hormone. Thyroid hormone resistance also released in the stress response are inflammatory immune cells called cytokines, which make thyroid receptors less sensitive to thyroid hormones.
Diagnosis is based on persistent elevations of serum free t4 and often t3 levels. Fortunately, the thyroid glands resistance can be overridden with skyhigh levels of thyroid hormone in. 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. Insulin resistance and normal thyroid hormone levels. Among the amount of thyroid hormone production and release t4 is approximately 95% and t3 is 5%. 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. A clinicians guide to understanding resistance to thyroid hormone.
Although patients with gthrare relatively refractory to the. It seemed that resistance to thyroid hormone was definite possibility. There are two genes that express the major thyroid hormone receptor isoforms. Mutations in both these genes have given rise to resistance to thyroid hormone rth syndromes rth. 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. It may be associated with no symptoms or with features of both an overactive and underactive thyroid. Resistance to thyroid hormone rth, a syndrome of reduced endorgan responsive. 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 thyroid hormone resistance have elevated free triiodothyronine ft3 andor free thyroxine ft4 with inappropriately normal or. Endocrine abnormalities are common in obesity, including altered thyroid function. Patients with rth have elevated serum free thyroxine ft4 and free triiodothyronine ft3.
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