~Thyroid Deficiency, Part 2 - Treatment Strategies

~Thyroid Deficiency, Part 2 - Treatment Strategies
Reprinted with permission of Life Extension®.

INNOVATIVE DRUG STRATEGIES

  • Armour Thyroid
  • Cytomel
  • Thyrolar


Armour Thyroid

Armour thyroid (Thyrar), Nathroid, and Westhroid are prescription medications that contain desiccated thyroid derived from the thyroid gland of the pig. Natural thyroid extracts have been used since 1892 and were approved by the FDA in 1939. Armour thyroid and most other natural glandular preparations are made to standards approved by the United States Pharmacopoeia (U.S.P.), which ensures that its potency is accurately stated on the label.

Natural thyroid extracts were largely replaced in clinical medicine by levothyroxine (Synthroid). Most physicians are reluctant to prescribe natural glandulars because they are told that they are impure and inconsistent from dose to dose. If your physician requires more information on natural glandulars, contact the Broda O. Barnes Research Foundation listed in the summary.

An article in the New England Journal of Medicine described a study in which patients with hypothyroidism showed greater improvements in mood and brain function if they received treatment with Armour thyroid rather than Synthroid (thyroxine). The authors also detected biochemical evidence that thyroid hormone action was greater after treatment with Armour thyroid. The patients who were on Armour thyroid had significantly higher serum concentrations of sex hormone-binding globulin; having higher concentrations of sex hormone-binding globulin is not a favorable event (Bunevicius et al. 1999).

Cytomel

Liothyronine (Cytomel, Triostat) is a synthetic form of T3 that was approved by the FDA in 1954. It is preferred over Synthroid (synthetic T4) by many doctors because it does not require conversion in the body (T4 must be converted to T3, the metabolically active form). For this reason, the Life Extension Foundation recommends Cytomel instead of synthetic T4 medication.

The standard dose of Cytomel is 25 mcg orally once daily, increasing by 12.5 mcg every 1-2 weeks if required. Approximately 15-37.5 mcg of Cytomel is equal to 60 mg of desiccated thyroid.

An article in the New England Journal of Medicine reports on the results of research comparing the effects of thyroxine alone with those of thyroxine plus triiodothyronine (Cytomel) in 33 patients with hypothyroidism. The combination group scored higher on six of the 17 tests of cognitive performance and assessments of mood. The authors stated: "Treatment with thyroxine plus triiodothyronine improved the quality of life for most patients" (Bunevicius et al. 1999). Gupta et al. (2001) showed a link between low serum T3 levels and patient mortality in elderly hospitalized patients.

Thyrolar

Liotrix (Thyrolar) is a mixture of synthetic T4 and T3 in a 4:1 ratio by weight used to treat hypothyroidism. The standard dose is initially 30 mg orally perday, with an increased dose every 2-3 weeks if clinical response indicates. Most patients will require 60-120 mg perday. Approximately 60 mg of Thyrolar is equal to 60 mg of desiccated thyroid.

DRUG SIDE EFFECTS AND INTERACTIONS

Because the various thyroid drugs have similar actions, the side effects, contraindications, and drug interactions are almost identical for each.

Adverse reactions to thyroid medications include many of the signs of hyperthyroidism, including:

  • Heat intolerance, fever, diaphoresis (sweating)
  • Headache, insomnia, irritability, tremor
  • Menstrual irregularity, amenorrhea
  • Palpitations, angina, atrial fibrillation, heart failure, sinus tachycardia
  • Nausea and vomiting, diarrhea, anorexia, weight loss
  • Alopecia (hair loss)


Thyroid medications interact with several classes of medications:

  • Cholestyramine (colestipol) decreases the efficacy of thyroid preparation. The doses should be separated by 4-6 hours.
  • Estrogens can produce a decrease in thyroid agent effectiveness secondary to increased thyroid-binding globulins.
  • Anticoagulant effect of anticoagulant drugs is increased.
  • Beta-blockers may have decreased effectiveness.
  • Digoxin clearance decreases with hypothyroidism; when corrected with thyroid hormone, clearance returns to normal.
  • Theophylline's clearance is decreased with hypothyroidism; when corrected with thyroid hormone, clearance returns to normal.


Thyroid medications are contraindicated in:

  • Cardiac disease, acute myocardial infarction
  • Hyperthyroidism, thyrotoxicosis
  • Hypoadrenalism
  • Tartrazine sensitivity (a food coloring, FD&C Yellow No. 5)


Absorption of thyroid medications is impaired by:

  • Iron sulfate
  • Calcium pills (Tums and Os-Cal)
  • Aluminum hydroxide antacids
  • Phenytoin (Dilantin), carbamazepine (Tegretol), rifampin, cholestyramine, sucralfate


NATURAL SUPPLEMENTS

  • Iodine
  • Tyrosine
  • Selenium
  • Dehydroepiandrosterone
  • Thyroid & L-Tyrosine Complex
  • Soy


Natural supplements for thyroid problems include vitamin A; vitamin B complex; B12; and the vitamins C, and E; as well as coenzyme Q10; and especially the minerals magnesium, manganese, selenium, and zinc, all of which can be found in ample amounts in the Life Extension Mix. Deficiencies of any of these minerals can prevent the conversion of T4 to T3 and should be corrected. Sufficient protein iodine and especially the amino acid tyrosine are necessary to make T4 in the thyroid gland.

Treatment of autoimmune hypothyroidism (Hashimoto's) and euthyroid sick syndrome is based upon the underlying disorder.

Iodine

Thyroid hormones are made by adding iodine molecules. Hence, a dietary deficiency of iodine can be a cause of hypothyroidism. Iodine is found in kelp and other seaweeds and seafood. It is also available in iodized salt. Those who suffer from autoimmune thyroid disease, such as Hashimoto's thyroiditis or Graves' disease, may want to avoid taking extra iodine because this disorder is not due to iodine deficiency and will not be of much help. For some it may irritate the thyroid and make matters worse.

Tyrosine

Tyrosine is a precursor of thyroid hormone and the neurotransmitters dopamine, norepinephrine, and epinephrine. A deficiency of tyrosine leads to hypothyroidism and low adrenal function. The recommended daily amount of tyrosine is about 1 gram perday for adults (Marz 1997).

Selenium

Selenium assists in removing toxins from the body through the enzyme glutathione peroxidase. Selenium is readily available in many foods, such as asparagus, grains, garlic, and mushrooms. Many agricultural areas, however, are extremely deficient in selenium. Research has linked selenium with thyroid function. One study found that the combination of both iodine and selenium deficiency was particularly toxic to the thyroid gland (Contempre et al. 1995).

A recent study in Belgium used selenium (20-60 mcg perday) to treat 18 children with congenital hypothyroidism. Supplementation with selenium caused a 74% increase in plasma selenium and normalized the levels of TSH. The authors concluded that selenium improves the thyroid hormone feedback system and improves the conversion of T4 to active T3 (Chanoine et al. 2001).

Another article described the use of selenium in three cases of hypothyroidism in children. After only 4 weeks of supplementation, they saw a marked improvement of all clinical symptoms and a return to normal metabolism (Pizzulli et al. 2000).

A double-blind, placebo-controlled study of 36 elderly subjects conducted in Italy found a linear correlation between selenium levels and T4 (as well as the ratio of T3:T4). Reduced conversion of T4 to T3 causes an overt hypothyroid condition that is common in the elderly. The main result of the study was a significant improvement in selenium levels and a decrease in the T4 levels in selenium-treated subjects (Olivieri et al. 1995).

Dehydroepiandrosterone (DHEA)

DHEA, a hormone that enhances the body's metabolic functioning, may also be deficient in individuals with hypothyroidism (Tagawa et al. 2000). A DHEA blood test should be administered to achieve optimal dosing (see the DHEA-Pregnenolone Precautions in the DHEA Replacement Therapy protocol for more detailed information).

Thyroid & L-Tyrosine Complex

Thyroid & L-Tyrosine Complex by Enzymatic Therapy combines thyroid tissue, the amino acid tyrosine, and synergistic trace minerals that must be present for endocrine gland functions, especially the thyroid. The thyroid gland needs iodine and L-tyrosine to produce hormones that control the body's metabolism. The trace minerals manganese, zinc, copper, and molybdenum included in the formula are involved with specific enzymes linked to endocrine glandular processes.

Soy

The effect of soy on thyroid function is currently a controversial topic. Some believe that soy increases metabolic rate and thyroid function. Several recent articles, however, have noted problems with people taking soy supplements.

One study identified the mechanism of soy's effect on thyroid function. Genistein and daidzein, the isoflavones in soy, inhibited thyroid peroxidase by acting as alternative substrates (Divi et al. 1997).

Soy-based infant formulas have been associated with an increased incidence of autoimmune thyroid disease and diabetes when compared with breast-fed infants (Fort et al. 1986; Fort et al. 1990).

Soy supplements should be avoided by hypothyroid patients because they increase the amount of thyroxine needed to attain clinical effect (Bell et al. 2001; Jabbar et al. 2001).

DIETARY RECOMMENDATIONS

Some foods contain goitrogenic substances that prevent the utilization of iodine. Goitrogens are found in sweet potato, cabbage, cauliflower, turnips, rutabaga, rapeseed oil (canola), cassava, pine nuts, mustard, millet, soybeans, and peanuts. The actual content of goitrogens in these foods, however, is quite low, and cooking inactivates them.

THE PROBLEM WITH CURRENT REFERENCE RANGES

How to best diagnose thyroid deficiency has been a long-standing medical controversy. Conventional doctors rely on thyroid blood tests, whereas alternative physicians look for signs and symptoms of thyroid deficiency. An article in The Lancet revealed surprising findings about reference ranges that may alter the way physicians assess individual thyroid status.

Before The Lancet article is discussed, the reader should be reminded of the serious consequences of a thyroid hormone deficiency. Aging people encounter a variety of ailments that doctors often attribute to problems other than thyroid deficiency. Some of the most noticeable symptoms caused by low thyroid are poor concentration, memory disturbances, cold hands and feet, accumulation of excess body fat, difficulty in losing weight, menstrual problems, dry skin, thin hair, and low energy levels. Some specific disorders related to thyroid deficiency include depression, elevated cholesterol, migraine headaches, hypertension, and infertility (Stanosz 1992; Saito et al. 1994; Vierhapper 1997; Michalopoulou et al. 1998; Pop et al. 1998; Lincoln et al. 1999; Krassas 2000; Hagen et al. 2001; Spierings 2001).

Broda O. Barnes was a physician-scientist who dedicated more than 50 years of his life to researching, teaching about, and treating thyroid and related endocrine dysfunctions. In his book entitled Hypothyroidism: The Unsuspected Illness, Dr. Barnes described more than 47 symptoms that may be related to poor thyroid function. During his many years of research and practice, Dr. Barnes condemned conventional doctors who ignored obvious clinical manifestations of thyroid deficiency. According to Dr. Barnes: "The development and use of thyroid function blood tests left many patients with clinical symptoms of hypothyroidism undiagnosed and untreated."

In lieu of blood tests, Dr. Barnes advocated that patients measure their temperature upon awakening. If the temperature is consistently below normal ranges, this is indicative of a thyroid deficiency. The Barnes Basal Temperature test, which appears earlier in this protocol, provides specific instructions on how best to measure your body temperature in order to assess thyroid hormone status.

Dr. Barnes believed that 40% of the adult population suffered from thyroid deficiency. Based on the percentage of adults now taking prescription drugs to treat depression, elevated cholesterol, and high blood pressure, Dr. Barnes' observations about the epidemic of thyroid deficiency may now have been validated.

The Lancet is one of the most prestigious scientific journals in the world. It often reports new medical findings that defy conventional wisdom. According to the August 3, 2002, issue of The Lancet, the problem with thyroid blood tests may be caused by inadequate laboratory reference ranges that fail to reflect what the optimal level of thyroid hormone should be in a particular individual (Dayan et al. 2002).

The Life Extension Foundation has discussed the issue of faulty laboratory reference ranges for many years. The problem is that for many blood tests, the laboratories provide a wide range that represents "average" populations, rather than what the optimal level should be to maintain good health.

Back in the 1960s, for instance, the upper reference range for cholesterol extended up to 300 (mg/dL). This number was based on a statistical calculation indicating that it was "normal" to have total cholesterol levels as high as 300. At that time, it was also "normal" for men to suffer fatal heart attacks at relatively young ages. As greater knowledge accumulated about the risk of heart attack and high cholesterol, the upper limit of the reference range gradually dropped to the point where it is now 200 (mg/dL) (ADVANCEDATA).

The same situation occurred with homocysteine reference ranges. Up until recently, it was considered normal to have a homocysteine blood reading as high as 15 (mcmoles/L) (Mahanonda et al. 2001). Most reference ranges now provide a chart showing that homocysteine levels above 7 increase risk of heart attack and stroke (Robinson et al. 1995).

It is not just blood laboratory reference ranges that fail to provide physicians and patients with optimal numbers. For example, when your blood pressure is checked, a diastolic number up to 90 (mmHg) is considered normal. Yet a diastolic blood pressure reading greater than 85 is associated with an increased stroke risk. A high percentage of people over age 60 have diastolic readings greater than 85, and this is the age group most vulnerable to stroke (Hansson et al. 1998). So when your doctor checks your blood pressure and says it is normal, your response should be that "normal" is not good enough because it is also normal for people over age 60 to suffer a stroke. Instead, you should ask your doctor what is the "optimal" range. In the case of diastolic blood pressure, taking steps to keep it at 85 or below could greatly reduce long-term vascular damage. It is important to note that midlife hypertension predisposes people to stroke later in life, so keeping blood pressure readings in optimal ranges is important at any age.

Scientists are now examining epidemiological data related to thyroid hormone reference ranges, and their findings indicate that it may be time to change the way laboratories report their TSH results.

THE THYROID STIMULATING HORMONE (TSH) TEST

  • Defying the Reference Ranges
  • Measuring Thyroid Hormone Levels


The standard blood test used to determine thyroid gland hormone output is the TSH test. When there is a deficiency in thyroid hormone, the pituitary gland releases more TSH to signal the thyroid gland to produce more hormones.

When the TSH test is in normal range, doctors usually assume that the thyroid gland is secreting enough thyroid hormone. The question raised by The Lancet authors, however, is whether today's reference range for TSH reflects optimal thyroid hormone status.

The TSH reference range used by many laboratories is between 0.2-5.5 (mU/L). A greater TSH number is indicative of a thyroid hormone deficiency. That is because the pituitary is over-releasing TSH based on lack of thyroid hormone in the blood. Any reading more than 5.5 alerts a doctor to a thyroid gland problem and that thyroid hormone therapy may be warranted.

The trouble is that the TSH reference range is so broad that most doctors will look at a TSH reading as low as 0.2 and think it is as normal as a 5.5 reading. The difference between 0.2-5.5, however, is an astounding 27-fold. It would seem almost absurd to think that a person could be in an optimal state of thyroid health anywhere along this 27-fold parameter, that is, TSH readings between 0.2-5.5.

A review of published findings about TSH levels reveals that readings of more than 2.0 may be indicative of adverse health problems related to insufficient thyroid hormone output. One study showed that individuals with TSH values of more than 2.0 have an increased risk of developing overt hypothyroid disease over the next 20 years (Vanderpump et al. 1995). Other studies show that TSH values greater than 1.9 indicate abnormal pathologies of the thyroid, specifically autoimmune attacks on the thyroid gland itself that can result in significant impairment (Hak et al. 2000).

More ominous was a study s14howing that TSH values of more than 4.0 increase the prevalence of heart disease, after correcting for other known risk factors (Hak et al. 2000). Another study showed that administration of thyroid hormone lowered cholesterol in patients with TSH ranges of 2.0-4.0, but had no effect in lowering cholesterol in patients whose TSH range was between 0.2-1.9 (Michalopoulou et al. 1998). This study indicates that in people with elevated cholesterol, TSH values of more than 1.9 could indicate that a thyroid deficiency is the culprit causing excess production of cholesterol, whereas TSH levels below 2.0 would indicate no deficiency in thyroid hormone status.

Doctors routinely prescribe cholesterol-lowering drugs to patients without properly evaluating their thyroid status. Based on the evidence presented to date, it might make sense for doctors to first attempt to correct a thyroid deficiency (based on a TSH value over 1.9) instead of first resorting to cholesterol-lowering drugs.

In a study to evaluate psychological well-being, impairment was found in patients with thyroid abnormalities who were nonetheless within "normal" TSH reference ranges (Pollock et al. 2001).

Defying the Reference Ranges

The authors of The Lancet study stated that "the emerging epidemiological data begin to suggest that TSH concentrations above 2.0 (mU/L) may be associated with adverse effects." The authors prepared a chart based on previously published studies that provide guidance when interpreting the results from TSH blood tests. Here are three highlights from their chart that may be useful in ascertaining what your TSH values really mean:

  1. TSH greater than 2.0: Increased 20-year risk of hypothyroidism and increased risk of thyroid autoimmune disease (Vanderpump et al. 1995)
  2. TSH greater than 4.0: Greater risk of heart disease (Hak et al. 2000)
  3. TSH between 2.0-4.0: Cholesterol levels decline in response to thyroxine (T4) therapy (Michalopoulou et al. 1998)


Despite presenting these intriguing findings, The Lancet authors stated that more studies were needed to define optimal TSH level as between 0.2-2.0 instead of between 0.2-5.5. For a health-conscious person, however, this type of precise information provides an opportunity to correct a medical condition that has been unresponsive to mainstream therapies or possibly to prevent disorders from developing in the first place.

This means if you have depression, heart disease, high cholesterol, chronic fatigue, poor mental performance, or any of the many other symptoms associated with thyroid deficiency, you may want to ask your doctor to "defy the reference ranges" and try different thyroid replacement therapeutic approaches.

Measuring Thyroid Hormone Levels

TSH is just one blood test that doctors use to assess thyroid status. Other blood tests measure the actual amount of thyroid hormone found in the blood.

The primary hormone secreted by the thyroid gland is called thyroxine (T4). The T4 is then converted in the peripheral tissues into metabolically active triiodo-thyronine (T3). Doctors often test for TSH and T4 together, but this may not accurately reflect thyroid deficiency in tissues throughout the body. One study found that psychological well-being could be improved if T3 (e.g., the drug Cytomel) were added to T4 (e.g., the drug Synthroid) therapy, while maintaining thyroid function broadly within the standard reference ranges (Bunevicius et al. 1999; Walsh et al. 2001). What this means is that even when TSH and T4 blood tests are within normal ranges, a person can still be deficient in peripheral T3 and benefit from Cytomel therapy.

Because T3 is the metabolically active form of thyroid hormone, some physicians use it exclusively in lieu of T4 drugs like Synthroid. The FDA's recent notice to ban synthetic T4 drugs like Synthroid because of inconsistent potencies helps to validate a statement made by Broda Barnes more than 50 years ago: "Patients taking thyroid replacement therapy have much better improvement of symptoms with natural desiccated thyroid hormone rather than synthetic thyroid hormones."

Although the FDA has found many problems in T4 drugs, the T3 drug Cytomel has produced consistent clinical results and is not a subject of the FDA's proposed ban. Dr. Barnes fought the drug companies against synthetic T4 drugs for years and recommended desiccated thyroid (Armour) drugs as the therapy of choice for most patients.

An article in the New England Journal of Medicine described a study in which patients with hypothyroidism showed greater improvements in mood and brain function if they received treatment with Armour thyroid rather than Synthroid (thyroxine). The authors also detected biochemical evidence that thyroid hormone action was greater after treatment with Armour thyroid (Toft 1999).

Thyroid deficiency occurs when the thyroid gland under-produces the hormones thyroxine (T4) and triiodothyronine (T3) needed to regulate the body's metabolic rate. In some individuals, the thyroid does not properly convert T4 to T3, the metabolically active form. Supplementation with synthetic or animal-derived thyroid hormone is necessary to return hormone levels to normal.

Synthetic hormone supplementation, prescribed by a physician, includes synthetic T4 (Synthroid, Unithroid, and Levoxyl), synthetic T3 (Cytomel), and a combination of synthetic T3 and T4 (Thyrolar).

Natural glandulars (by prescription), such as Armour Desiccated Thyroid Hormone, Nathroid, and Westhroid, derived from the thyroid gland of the pig, contain T4 and T3, and most closely resemble natural human thyroid hormone.

Suggested supplements and their dosages follow:

  1. Iodine, 1 mg perday
  2. Selenium, 200-600 mcg perday
  3. Tyrosine, 500-1000 mg perday
  4. Melatonin, 300 mcg-6 mg at bedtime
  5. DHEA, 25 mg 1-3 times perday (refer to DHEA Replacement Therapy protocol)
  6. CoQ10, 100-200 mg daily
  7. Life Extension Mix for vitamin A, vitamin B complex, magnesium, manganese, selenium, and zinc, to be taken as directed
  8. Thyroid & L-Tyrosine Complex, 2 capsules 3 times daily


For more information, contact the Thyroid Foundation of America, (800) 832-8321. For more information on natural glandulars or the basal body temperature test, contact the Broda O. Barnes, M.D. Research Foundation, P.O. Box 98, Trembly, CT 06611, (203) 261-2101.
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