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Hypothyroidism results from deficient production of thyroid hormone by the thyroid gland. Since the thyroid hormones regulate metabolism in every cell of the body, a deficiency can affect virtually all body functions. Deficiency of thyroid hormones can result from lack of stimulation by the pituitary gland, defective hormone synthesis or impaired cellular conversion of T4 to T3. (1,2) No matter what the cause, symptoms such as low energy, fatigue, cold hands and feet, muscle pain, depression and cognitive deficits are common.
A Brief Review of Thyroid Physiology - The thyroid gland is composed of follicle cells which secrete hormone and surround a viscous substance called colloid. Neurons terminate on the blood vessels in the thyroid gland and on the follicle cells themselves. Acetylcholine and catecholamines directly affect follicle secretion. Thyroid hormone (TH), made up of thyroxine (T4) and triiodothyronine (T3), is regulated through a negative-feedback loop between the hypothalamus, anterior pituitary and thyroid gland. The hypothalamus releases TRH (thyrotropin-releasing hormone), which stimulates the release of TSH (thyroid stimulating hormone) from the anterior pituitary. TSH binds to receptors on the thyroid gland and causes an immediate release of stored TH, an increase in iodine uptake and an increase in TH synthesis. The release of TH inhibits further release of TRH and TSH. (2)
Active transport of iodide (inorganic form of iodine) into the thyroid gland is the first step in TH synthesis. Before it can be used to form TH, the iodide must be oxidized to iodine by the enzyme thyroidal peroxidase within the follicular cell (2). Thyroglobulin, a large glycoprotein synthesized in the follicle, is released into the colloid where iodine then combines with the tyrosine residues in the thyroglobulin, catalyzed by the enzyme thyroperoxidase (TPO), to form either monoiodotyrosines (MIT) with one iodine attached or diiodotyrosines (DIT) with two iodines attached. Once iodinated tyrosine residues have been formed, there is a coupling of these iodotyrosines to form iodothyronines. Either two DITs combine to form T4 (~90%) or one MIT combines with one DIT to form T3 (~10%). Both forms are released into the circulation where they are transported to the tissues bound to carrier proteins. (2,3) Only about 1-5% is unbound, or "free", and metabolically active (5).
In the body tissues, T4 is converted to T3, the more active hormone, by 5'deiodinase enzymes. The iodine can be removed from T4 either by the action of type I and type II deiodinases which results in active T3, or by the action of type III deiodinases which results in the inactive rT3. Type I and type II deiodinases are selenoenzymes which are dependant on adequate levels of selenium to function optimally (3,4,11). T3 is up to eight times more active than T4 and rT3 has less than 1% of the activity of T4 (3,4). Therefore T3 and rT3 are "increase" and "decrease" hormonal messages.
To affect metabolism in the cell, T3 must first bind to its receptor in the cell and then that T3-receptor complex must then bind and activate specific DNA sequences in the cells nucleus. This T3-nuclear receptor-transcription depends on heterodimerization of the T3 receptor with retinoic acid receptors in the nucleus prior to transcription so adequate vitamin A metabolism may also be necessary (3).
Etiology of Hypothyroidism - Primary hypothyroidism is caused by an inherent inability of the thyroid gland to produce a sufficient amount of thyroid hormone. About 95% of overt hypothyroidism is primary. In the past, the most common cause of primary hypothyroidism was iodine deficiency, but with the advent of iodized salt, this is rare in the US and industrialized countries (1). In the US, currently the most common cause is Hashimoto's thyroiditis, an autoimmune disease resulting in lymphocytic infiltration and destruction of thyroid tissue by anti-thyroid antibodies (2,6). The second most common cause is referred to as "post-theraputic hypothyroidism" due to surgery or radiation therapy for hyperthyroidism (6). However, primary hypothyroidism can also result from genetic defects, inhibition by drugs or chemicals, cancer, and iodine deficiency or excess.
In any case, the loss of functional tissue leads to a decrease production of TH to which the pituitary responds with an increased production of TSH which increases the synthesis of thyroglobulin, which may lead to thyroid enlargement (possibly as it tries to trap iodine if there is deficiency) and goiter results (1,2,6,7,8). Laboratory tests reveal elevated TSH with decreasing levels of TH reflective of the severity of the hypothyroidism (5,7). Maintenance of T3 levels until the late stages of hypothyroidism is accomplished by both increased secretion of T3 by the thyroid and increased conversion of T4 to T3 in the peripheral tissues. (7)
Secondary hypothyroidism is due to inadequate stimulation of a normal thyroid gland by TSH from the pituitary. Most commonly, this is the result of pituitary tumors (or their treatment) or trauma but can also occur at the level of the hypothalamus. Lab tests will reveal very low TSH levels along with low levels of TH.
Cellular hypothyroidism is a third, less common, cause that results when the HPT axis is intact but symptoms of hormone deprivation result from a disorder in the peripheral tissues that reduce their responsiveness to TH (TH resistance) or that inactivate the hormone (massive infantile hemangioma) (3,7). Lab tests will reveal normal TSH and hormones but there will be low functional thyroid activity (low BMR, low temp) (1). There may be decreased peripheral conversion of T4 to T3, increased conversion of T4 to rT3 or decreased binding to TBG. (6) Sometimes referred to as "euthyroid sick syndrome", this could also reflect mutations in either the thyroid hormone receptor genes or polymorphisms in the deiodinase enzymes.(3)
Subclinical hypothyroidism may represent the first signs of dysfunction in the progressive development of thyroid disease. It is characterized by increased levels of TSH with normal levels of thyroid hormone (3,4,7). Roos et al looked at the association between thyroid function and components of the metabolic syndrome and found that low normal free T4 levels were significantly associated with increased insulin resistance (9). Another recent study by Uzunlulu et al looked at the prevalence of subclinical hypothyroidism in patients with metabolic syndrome and found that thyroid function affected metabolic syndrome parameters including cholesterol, HDL, triglycerides, blood pressure and blood sugar (10).
+, above upper normal limit; N, within normal reference range; -, below lower normal limit.
Clinical symptoms - The characteristic sign of severe, chronic hypothyroidism is myxedema. Myxedema is the result of the build up of a protein-mucopolysaccharide complex that binds water and produces a non-pitting edema especially around the eyes, hands and feet. It also causes a thickening of the tongue and mucous membranes of the laryngeal and pharyngeal area causing hoarseness and slurred speech. (2)
The symptoms of hypothyroidism usually have an insidious onset and the patient may be unaware of them for years before reaching the stage of myxedema although a more sudden onset can be expected if the hypothyroidism is brought about by surgery or radiation. Decreased levels of thyroid hormone leads to a general decrease in the metabolism of fats, proteins and carbohydrates and often result in weight gain, dyslipidemia and an increased risk of cardiovascular disease. Dry skin and hair, brittle nails and significant hair loss are common, and along with a poor tolerance to cold may be some of the first symptoms. Loss of libido, menstrual abnormalities, constipation, muscle weakness and joint stiffness are predominant features although depression, weakness and fatigue are usually early symptoms as well. A decrease in basal body temperature found by an early morning axillary temperature of less than 97 degrees Farenheit has been promoted by Dr. Broda Barnes MD as functional measure of decreased thyroid activity (1,7).
Alternative treatments - Allopathic treatment for hypothyroidism involves medication with either T4, T3 or both. Alternative treatment focuses on supporting thyroid function by supplying nutrients necessary for the synthesis of thyroid hormone as well as for the cellular conversion of T4 to T3 while being aware of foods that can interfere. Additionally, emphasis is placed on reducing anti-thyroid antibodies by eliminating potential food antigens that can induce antibodies capable of cross-reacting with the thyroid (3). The importance of exercise in stimulating thyroid hormone secretion, increasing tissue sensitivity to those hormones and decreasing stress is significant. The goal of the alternative approach is to avoid the necessity for exogenous hormones or, failing that, to lower the requirement for exogenous hormone as much as possible. With that in mind, an alternative approach would: (3)
- Provide precursors for thyroxine synthesis. Adequate iodine is essential for the synthesis of thyroid hormones and can be supplied by iodized salt and/or sea vegetables such as bladderwrack, kelp or focus (16). While tyrosine itself doesn't appear to have a beneficial effect on raising thyroid hormones (3), adequate protein in the diet is important.
- Support conversion of T4 to T3. Selenium, zinc and copper are cofactors for the deiodinase enzymes that convert T4 to T3 (1,17,18). Cortisol interferes with the conversion to T3 and results in conversion to inactive rT3 (3) so adaptogens would be appropriate for those under stress (4).
- Optimize cellular metabolism. Provide adequate vitamin A and zinc to promote proper receptor binding for nuclear transcription (3,18,20).
- Reduce antithyroid antibodies. Eliminating foods with known sensitivity as well as potential food antigens caused by foods such as wheat (gluten) and dairy (casein) decreases the chance for cross reactions with the thyroid gland (3,4,12). There is a strong correlation between celiac disease and autoimmune thyroiditis so a gluten free diet is often therapeutic (21.22). Additionally, vitamin D appears to help regulate immune sensitivity and may help protect against the development of autoantibodies. (3,12,19)
- Avoid excessive intake of goitrogens. Goitrogens are foods that can induce iodine deficiency by combining with iodine and making it unavailable for use by the thyroid (1,3,12). Foods such as broccoli, cabbage, cauliflower, Brussels sprouts, turnips, walnuts, almonds and soy are considered goitrogenic. Cooking usually neutralizes the goitrogens in these foods and eating nuts and soy in limited amounts while ensuring adequate intake of iodine and selenium should eliminate any problem. (4,12,13)
- Encourage routine exercise. Exercise stimulates thyroid hormone synthesis, tissue sensitivity and decreases stress, which can interfere with the conversion to active T3. (3,23)
Sue Dieffenbach, MS, CCN, RN, is founder of the PerkUp! Health Center in Poway, CA and has been a nutritional consultant aligned with the principles of functional medicine for over 10 years.
1. Pizzorno J, Murray M Textbood of Natural Medicine p.1329-1334
2. McCance K, Huether S Pathophysiology 4th Edition p. 635-638
3. Bland J, Nutritional Endocrinology- Breakthrough Approaches for Improving Adrenal and Thyroid Function 2002 syllabus p.82-117, p.165-167
4. Rakowski R, New Strategies for Improving Adrenal and Thyroid Function 2002 syllabus
5. Pagana & Pagana, Mosby's Manual of Diagnostic and Laboratory Tests 3rd Edition p.487-511
6. Merck Manual 15th Edition p. 802-806
8. Guyton, Textbook of Medical Physiology 7th Ed. p. 906
9. 9. Roos, A et al. Thyroid Function is Associated with Components of the Metabolic Syndrome in Euthyroid Subjects J Clin Endocrin Metab. Nov. 7, 2006
10. Uzunlulu M et al. Prevalence of Subclinical Hypothyroid in Patients with Metabolic Syndrome Endocrine Journal Nov. 14, 2006
11. 11, Kohrle, J The Deiodinase Family: Selenoenzymes regulating thyroid hormone availability Cellular and Molecular Life Sciences 57 (2000). p. 1853-1863
13. Shames R Thyroid Power p.167
21. http://www.springerlink.com/content/xv2h3k42n19gu6g5/ autoimmune
23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&lis... zinc, exercise and thyroid function
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