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14-September-2008 18:02:48 - hormone resistance Thyroid hormone resistance Classification and external resources ICD-10 E07. OMIM 275200 188570 274300 DiseasesDB 31913 MeSH D018382 Thyroid hormone resistance describes 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. Contents 1 Causes 2 Incidence 3 Presentation 4 Diagnosis 5 Terminology 6 Claims of cause of fibromyalgia and chronic fatigue syndromes 7 Proposed treatment 8 References Causes The most common cause of the syndrome are mutations of the β beta form 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.1 Incidence Thyroid hormone resistance syndrome is rare, incidence is variously quotes as 1 in 50,000 or 1 in 40,000 live births. Presentation The syndrome can present with variable symptoms, even between members of the same family harboring the same mutation.2 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.3 An association with depression has been proposed.4 Diagnosis The characteristic blood test results for this disorder can also be found in other disorders for example TSH-oma pituitary adenoma, or other pituitary disorders. The diagnosis may involve identifying a mutation of the thyroid receptor, which is present in approximately 85% of cases.5 Yet, since discovery of resistance to thyroid hormones in the absence of thyroid hormone receptor beta mutations, lack of a mutation in a patient does not rule out resistance.6 Terminology Sometimes the phrase thyroid hormone resistance is used to identify cases where patients with autoimmune thyroid disorders respond poorly to normal doses of replacement thyroid hormone, this is thought to occur where patients have developed antibodies to thyroid hormones. Antibodies to thyroid hormones quite commonly occur in such disorders, and may interfere with the normal clinical assays used in monitoring such disorders, and in unusual cases may have further independent clinical significance. Claims of cause of fibromyalgia and chronic fatigue syndromes This section needs additional citations for verification. January 2008 The neutrality and factual accuracy of this section are disputed. Please see the relevant discussion on the talk page. March 2008 Recent evidence has come to light through the works of Dr. Samuel Refetoff,7not in citation given Dr. Roy Weisscitation needed and Dr. John C. Lowe,8 that thyroid hormone resistance is far more common than once suspected. Refetoff has linked thyroid hormone resistance with a variety of other diseases that many times mask the real problem because thyroid hormone resistance is not always detectable by blood work. Some forms of hormone resistance affect the conversion of T4 thyroid hormone to T3 and result in insufficient hormone reaching bodily tissues the at the cellular level. This type of conversion malfunction is not always detectable by blood tests which tell us how much hormone is circulating in the blood not what is reaching the tissues. Sometimes a reverse T3 will show that there is a conversion malfunction but in only one subset of the many groups of conversion malfunctions. What modern doctors are realizing is that a person may have a sever thyroid insufficiency without the blood tests indicating this. Dr. Lowe believes through extensive research, that fibromyalgia and chronic fatigue syndrome are frequently misdiagnoses of partial resistance to thyroid hormone. He and Dr. Dennis Wilson use T3 therapy with drugs such as Cytomel and compounded T3 in patients who may even have normal thyroid blood tests. The result is that these patients improve or even recover completely while their blood tests may indicate they are taking too much thyroid hormone. Since they must take more thyroid hormone than others, the result is an excess of thyroid hormone floating around in the blood stream, however what reaches the tissues is usually far less, in fact a normal amount. This shocks doctors who do not understand thyroid hormone resistance. Such doctors are under a mistaken belief that if the blood tests show thyrotoxicity too much thyroid hormone then it must be true, even though their patients cannot recover or feel well without this high dose. Doctors like Refetoff, Lowe, Berndtson, Wilson and Papernick have come to discover, that to bring their patients health and free them from their terrible symptoms, they must prescribe these large doses. Interestingly, aside from the blood test results, thyroid hormone resistance patients do not experience the symptoms of thyrotoxicity such as diahhreah, hives, hair loss, heart palpitations and nervousness and in fact do experience the symptoms of hypothyroidism if they are not medicated with these high doses of T3. Dr. Refetoff has also noted that there are many cases that present thyroid hormone resistance without the genetic mutation. Nobody knows what causes thyroid hormone resistance in these patients but doctors have discussed the possility of environmental toxicities, stealth viruses, mutated bacteria, systemic fugal infection and others. Dr. Marshall has invented a protocol for Sarcoidosis and autoimmune disease that is proving to free many thyroid hormone resistant patients from their symptoms and their large doses of medication. His research would indicate that there is an autoimmune manlfunction causing thyroid hormone resistance. However, thyroid hormone resistance is suspected to occur in 1%-3% of the entire female population if Dr. Lowe is correct in his belief that Fibromyalgia is thyroid hormone resistance. Dr. Refetoff believes that many people with ADD have thyroid hormone resistance which would cover another large chunck of the population. In fact, it is unknown how many people have it, but we now know that it is not a rare disorder as once was believed. The other symtoms that indicate a person may have thyroid hormone resistance include but are not limited to: low body temperature, blood pressure problems, chronic fatigue, constipation, fibromyalgia or widespread pain, weight gain, memory problems, cognitive dysfunction, asthma or allergies, and all other symptoms commonly associated with either Hashimoto's thyroiditis and/or regula hypothyroidism, and/or regular hyperthyroidism. The symptoms of this illness are many but the only way to really know if you have it, is to work with a doctor on a therapeutic trial of the thyroid hormone therapy. If a person cannot achieve homoeostasis without large doses of T3 or T4, then she/he may have thyroid hormone resistance. Dr. Refetoff has studied people who needed 1000mcg of T4 and 500mcg of T3 before feeling well. These are doses that would kill a normal person and yet for those with thyroid hormone resistance, living without these supraphysiologic doses feels like death. Proposed treatment Treatment varies vastly from person to person but what is common to all are the high doses of thyroid hormone necessary before a patient feels well. First, treatments can be desiccated or synthetic. Then, they can be either T3, T4 or combination T3/T4 drugs. Dr. Lowe has published the most extensive guidelines for properly medicating those with thyroid hormone resistance. Also note, that not all tissues absorb thyroid hormone at the same rate. The heart for example, may absorb at a higher rate than the lungs and muscles. This means, patients may need other drugs to supplement this difference in absorption rate. For many, this includes a beta blocker to reduce stimulation on the heart and allow for a higher hormone dose to better alleviate muscle or lung resistance. It is a balancing act that can only be adjusted by your symptoms and medical tests. Desiccated thyroid is made from pig hormones. It is usually a cheaper drug and it is considered natural. An additional note is that according to Dr. Lowe, many people with thyroid hormone resistance cannot assimilate desiccated thyroid drugs like naturthroid and armour. This has to do with the extra conversion the body must go through to assimilate desiccated thyroid. This group of people will do far better on synthetic thyroid drugs. Furthermore, desiccated thyroid is a combination T3/T4 drug and does not allow for the fine tuning involved if a patient's optimal ratio is different than that compounded into the drug. For example, armour thyroid has a ration of T4/T3 of 4/1. But people with thyroid hormone resistance may not improve without a ratio of 2/1 or even 1/1. This cannot be achieved with desiccated thyroid alone. Many patients recover with only T3 or only T4. These patients will take drugs like synthroid or levoxy for T4 and cytomel or time released compounded T3 for the T3. Those on T3 drugs who find the drugs too stimulating can switch to a time released mechanism to prolong the benefits of the T3 drug which is typically out of the system in 2-4 hours. With a time released drug it can stay in the system longer and will reduce the crash when the drug runs out. T4 stays in the system longer but it does not always convert to active usable T3. For this reason, some people do better on combination T4 and T3 therapy. Thyrolar is a combination synthetic drug that many prefer. However, if a patient does not feel optimal on thyrolar it may be that he/she needs to independently adjust the T3 and T4 to a different ration than that compounded into the drug. Some people take their thyroid dose all at one time in the morning. Others must divide the dose into two or three daily doses. References ^ 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. Metab. 21 2: 277-305. doi:10.1016/j.beem.2007.03.005. PMID 17574009. ^ 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. Metab. 27 2: 279-94. PMID 4163616. ^ Hauser P, Zametkin AJ, Martinez P, et al 1993. Attention deficit-hyperactivity disorder in people with generalized resistance to thyroid hormone. N. Engl. J. Med. 328 14: 997-1001. doi:10.1056/NEJM199304083281403. PMID 8450877. ^ Fardella CE, Artigas RA, Gloger S, et al 2007. Refractory depression in a patient with peripheral resistance to thyroid hormone RTH and the effect of triiodothyronine treatment. Endocrine 31 3: 272-8. doi:10.1007/s12020-007-0042-7. PMID 17906375. ^ 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. Monit. 13 6: CS67-70. PMID 17534237. ^ Tjørve E, Tjørve KM, Olsen JO, Senum R, Oftebro H 2007. On commonness and rarity of thyroid hormone resistance: a discussion based on mechanisms of reduced sensitivity in peripheral tissues. Med. Hypotheses 69 4: 913-21. doi:10.1016/j.mehy.2006.12.056. PMID 17383828. ^ Refetoff S 2008. Resistance to thyroid hormone: one of several defects causing reduced sensitivity to thyroid hormone. Nat Clin Pract Endocrinol Metab 4 1: 1. doi:10.1038/ncpendmet0703. PMID 18084342. ^ Jackie Grosch Yellin; Lowe, John W. 2000. The Metabolic Treatment of Fibromyalgia. McDowell Publications. ISBN 0-914609-02-5. v d e Endocrine pathology: endocrine diseases E00-35, 240-259 Pancreas/ glucose metabolism Diabetes mellitus types: type 1, type 2, MODY, complications: coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy Hypoglycemia - Hyperinsulinism - Zollinger-Ellison syndrome - insulin receptor Rabson-Mendenhall syndrome - Insulin resistance Hypothalamic/ pituitary axes Pituitary Hyperpituitarism Acromegaly, Hyperprolactinaemia, SIADH Hypopituitarism Sheehan's syndrome, Kallmann syndrome, Growth hormone deficiency, Diabetes insipidus Adiposogenital dystrophy - Empty sella syndrome - Pituitary apoplexy - ACTH deficiency Thyroid Hypothyroidism Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre, Myxedema Hyperthyroidism Graves disease, Toxic multinodular goitre, Teratoma with thyroid tissue or Struma ovarii Thyroiditis De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's thyroiditis Euthyroid sick syndrome - Thyroid hormone resistance - Thyroid nodule Parathyroid Hypoparathyroidism Pseudohypoparathyroidism - Hyperparathyroidism Primary, Secondary, Tertiary Adrenal Adrenocortical hyperfunction: Cushing's syndrome Nelson's syndrome, Pseudo-Cushing's syndrome - Hyperaldosteronism Conn syndrome, Bartter syndrome CAH Lipoid, 3β, 11β, 17α, 21α Adrenal insufficiency Addison's disease, Waterhouse-Friderichsen syndrome - Hypoaldosteronism Gonads ovarian Polycystic ovary syndrome, Premature ovarian failure testicular 5-alpha-reductase deficiency, 17-beta-hydroxysteroid dehydrogenase deficiency general Hypogonadism, Delayed puberty, Precocious puberty Other Androgen insensitivity syndrome - Autoimmune polyendocrine syndrome - Carcinoid syndrome - Gigantism - Short stature Laron syndrome, Psychogenic dwarfism - Multiple endocrine neoplasia 1, 2 - Progeria - Woodhouse-Sakati syndrome - thymus Abscess of thymus, Thymus hyperplasia see also congenital, neoplasia Retrieved from http://en..org/wiki/Thyroid_hormone_resistance Categories: Thyroid disease | Genetic disordersHidden categories: Articles needing additional references from January 2008 | Accuracy disputes from March 2008 | NPOV disputes from March 2008 | All articles with statements | Articles with statements since January 2008 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch This page was last modified on 22 June 2008, at 17:30
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