~Thyroid Deficiency

~Thyroid Deficiency
Reprinted with permission of Life Extension®.



The Thyroid Gland

The thyroid gland lies in the neck, just below the Adam's apple. It measures about 2 inches across and normally cannot be seen. It can barely be felt upon palpation. An enlarged thyroid, known as a goiter, can easily be detected by a physician upon examination. The thyroid gland secretes hormones which control the body's metabolic rate in two primary ways: by stimulating tissue response in the body to produce specialized proteins and by increasing cell oxygenation. To produce these vital hormones, the thyroid needs the element iodine, which is ingested from food and water.

The regulation of thyroid hormone levels is controlled by several mechanisms. The hypothalamus, located in the brain just above the pituitary gland, secretes thyrotropin-releasing hormone, which triggers the pituitary to release thyroid-stimulating hormone (TSH). When the amount of thyroid hormone in the blood reaches a certain level, the pituitary will produce less TSH; conversely, when the amount of thyroid hormone in the blood decreases to a certain level, the pituitary produces more TSH.

Thyroid Hormones

The thyroid gland secretes two significant hormones: thyroxine (T4) and triiodothyronine (T3). Approximately 93% of the hormone secreted by the thyroid is T4, with only 7% being T3.

In healthy people, almost all thyroxine is converted to triiodothyronine in the tissues. This means that the primary thyroid hormone finally delivered to and acting on tissues is T3. In normal health, maintenance of resting metabolism and excitability of membranes require between 35-50 mcg of T3 a day.

Thyroxine consists of two tyrosine molecules each binding two iodine constituents. The enzyme, 5-monodeiodinase, found in liver and in peripheral tissues, cleaves a single iodine from the outer tyrosine to create T3. Excess T4 is disposed of by action of a similar enzyme, which takes a single iodine from the inner tyrosine, and thus creates reverse T3, which is metabolically inactive.

Calcitonin (thyrocalcitonin) is another hormone secreted by the thyroid gland. Calcitonin maintains blood calcium levels by inhibiting bone breakdown and preventing excess calcium in the blood (hypercalcemia).

THYROID DEFICIENCY

  • Thyroid Deficiency in Obesity and Diabetes
  • Other Effects of Thyroid Deficiency


Because the thyroid stores a several weeks' supply of hormone, symptoms of deficiency may actually occur some time after the gland is damaged or compromised. Deficient production of thyroid hormone may reflect inadequate dietary iodine or autoimmune disease that attacks the glandular tissue.

In the absence of signs of frank thyroid disease, doctors often fail to properly assess thyroid function. Blood levels of TSH and T4 are helpful in some cases, but may be normal even in profound deficiency states.

The Achilles Tendon Reflex Recovery test and the Barnes Basal Temperature test may be helpful in disclosing cases of deficient conversion of T4 to T3. This is particularly important in evaluating systemic metabolic disorders such as obesity and metabolic diabetes. (The procedure for determining your basal temperature is given below in the text.)

Lowering the intake of calories (dieting) has the unfortunate consequence of diminishing production of T3, which in turn lowers the basal (resting) metabolic rate, which alone can lead to weight gain.

Thyroid Deficiency in Obesity and Diabetes

The enzyme that converts T4 to T3 is called 5-monodeiodinase. Unfortunately, this enzyme is inhibited in response to diminished caloric intake (dieting). That means that the fewer calories ingested, the lower the production of 5-monodeiodinase. This is the body's natural method of conserving fuel during shortage. Because "dieting" is not a natural state, it elicits the same physical reaction as famine--another reason why "eating less" will never effectively treat obesity. Deficient peripheral conversion of T4 to T3 is found almost universally in patients who become overweight.

The thyroid gland is located in the neck and measures about 2 inches across. Thyroxine (T4) and triiodothyronine (T3) stimulate energy metabolism in all the body's cells. Thyrocalcitonin, another thyroid hormone, regulates blood calcium levels by inhibiting bone breakdown. The parathyroid glands are located on the back of the thyroid gland. Parathyroid hormone (PTH) has the opposite effect of thyrocalcitonin. PTH increases blood calcium levels as needed by stimulating bone breakdown. (Anatomical Chart Company 2002®, Lippincott Williams & Wilkins)

Other Effects of Thyroid Deficiency

A thyroid deficiency (hypothyroidism) means that the thyroid gland is producing too little thyroid hormone. The symptoms of hypothyroidism are gradual and are sometimes mistaken for depression. Facial expressions become dull, the voice becomes hoarse, eyelids droop, and the face and eyes become puffy and swollen.

Hypothyroidism can cause a number of other conditions, such as allergies, skin problems, fatigue, nervousness, gaining or losing weight, brittle nails, dry skin, gastrointestinal problems (constipation), infertility, mental sluggishness, low immune function, depression, and intolerance to cold. Carpal tunnel syndrome has also been associated with thyroid deficiency.

If left untreated, hypothyroidism can cause anemia, low body temperature, and heart failure. A life-threatening condition known as myxedema coma may ensue in which respiration slows, seizures occur, and blood flow to the brain decreases. Exposure to cold, infections, tranquilizing drugs, and trauma can trigger myxedema coma.

There is some evidence that low T3 levels may be associated with breast cancer. A study in Molecular Carcinogenesis (Gonzalez-Sancho et al. 2002) stated that T3 down-regulated the expression of T1, a gene that is over-expressed in human breast adenocarcinomas. The study concluded that T3 reduced the proliferation of mammary epithelial cells and inhibited the expression of cyclin D1 and T1 genes. Another study in the Annals of Medicine (Smyth 1997) indicated that although the exact mechanism for the association between thyroid and breast cancer is not quite clear, there is the possibility that the presence of thyroid abnormalities may influence breast cancer progression, and this should stimulate awareness into the coincidence of the two disorders. Finally, according to the World Health Organization, 45.5% of patients with a breast carcinoma had thyroid enlargement compared with only 10.5% of controls. Antithyroid peroxidase autoantibodies were twice as common in breast cancer patients as in controls. These findings provide evidence of a relationship between thyroid disease and breast carcinoma, although the mechanisms require further study (Shering et al. 1996).

EPIDEMIOLOGY

Thyroid deficiency generally affects women who are over the age of 40, but it can also affect men and teenagers, especially if it runs in the family. The elderly are particularly susceptible to undiagnosed or subclinical hypothyroidism. Hypothyroidism is also associated with pernicious anemia (vitamin B12 deficiency) and insulin-dependent diabetes.

CAUSES

  • Risk Factors


Hashimoto's thyroiditis is the most common form of hypothyroidism, presenting with an enlarged thyroid gland that becomes nonfunctional, with the active parts of the gland deteriorating after several years. Hashimoto's thyroiditis is a chronic inflammation of the thyroid gland thought to be caused by autoimmune factors. Other forms of autoimmune disease are common, including pernicious anemia, rheumatoid arthritis, systemic lupus erythematosus (SLE), and Sjögren's syndrome. Schmidt's syndrome refers to hypothyroidism with other endocrine disorders, including Addison's disease (adrenal insufficiency), hypoparathyroidism, and diabetes mellitus, all of which may be autoimmune in nature.

Euthyroid sick syndrome is hypothyroidism, associated with a severe systemic illness, that causes decreased peripheral conversion of T4 to T3, an increased conversion of T3 to the inactive reverse T3, and decreased binding of thyroid hormones. Conditions commonly associated with this syndrome include fasting, starvation, protein-calorie malnutrition, general surgical trauma, myocardial infarction, chronic renal failure, diabetic ketoacidosis, anorexia nervosa, cirrhosis, thermal injury, and sepsis. Once the underlying cause is treated, the condition is usually resolved.

Treatment for hyperthyroidism, which includes administering radioactive iodine and surgical removal of the thyroid gland, may also result in hypothyroidism.

In many undeveloped countries, where there is a chronic lack of iodine in the diet, goitrous hypothyroidism resulting from an underactive thyroid gland is common. Hypothyroidism resulting from a lack of dietary iodine has disappeared in the United States.

Drugs that may produce hypothyroidism as an adverse reaction include amiodarone (Cordarone), colchicine (Colsalide), fluoxetine (Prozac), interferon-alfa (Alferon N, Intron A, Roferon A), lithium (Eskalith, Lithobid), methimazole (Tapazole), potassium iodide, KI (Pima, SSKI), and propylthiouracil.

Risk Factors

  • Smoking
  • Lead
  • Homocysteine


Smoking. Smoking has also been identified as a risk factor for hypothyroidism, but the reason for the association is unknown (Nystrom et al. 1993).

Lead. Hypothyroidism may also be caused by occupational exposure to lead (Lasisz et al. 1992).

Homocysteine. A recent study measured the plasma homocysteine levels in 50 hypothyroid and 46 hyperthyroid patients. They found that plasma homocysteine concentrations increased in hypothyroidism and decreased in hyperthyroidism. They also found that restoration of the euthyroid state (by drug treatment) decreased both homocysteine and creatinine in hypothyroid patients and increased both homocysteine and creatinine in hyperthyroid patients. Folate levels were found to be lower in the hypothyroid group when compared with the hyperthyroid group. They proposed that a higher creatinine clearance in hyperthyroidism could partially explain the changes in homocysteine. A similar study found the same relationship between homocysteine and hypothyroidism, but the authors believed it was due to decreased hepatic levels of enzymes involved in the remethylation pathway of homocysteine (Nedrebo et al. 1998; Hussein 1999; Catargi et al. 1999; Diekman et al. 2001).

DIAGNOSIS

  • Barnes Basal Temperature Test


Overt hypothyroidism is easy to diagnose by a simple blood test. Low levels of T3 and T4 are signs that you do not have enough thyroid hormones. An elevated TSH is a sign of thyroid deficiency. When your TSH is high, it means the pituitary gland is trying to make the thyroid gland produce more hormones. Patients with euthyroid sick syndrome, however, have a normal TSH.

Hashimoto's thyroiditis is diagnosed by high titers of antithyroid (antimicrosomal) antibodies. High titers of antibody against thyroglobulin (TG) and thyroid peroxidase (TPO) are present in most patients.

If, however, someone is suffering from the classic symptoms of thyroid deficiency but has normal test results, the thyroid slowdown could be slight or age- related and is not easily detected by a blood test. Thyroid deficiency often mimics many symptoms associated with old age. One way to determine a thyroid deficiency is to have your physician test for a substance called transthyretrin (also known as prealbumin). Thyroid hormone is carried through the bloodstream and brain by transthyretrin. Even when all other hormones are normal, a low level of trans-thyretrin could mean that you are not producing enough thyroid hormones and that it is not being delivered to the cells.

Another sensitive laboratory test to measure thyroid deficiency is the TRH (thyrotropin-releasing hormone) stimulation test. It can show whether a patient is suffering from an underactive thyroid even when routine thyroid tests reveal nothing. The patient's level of TSH is measured through a blood test, then the patient is given an injection of TRH (a harmless synthetic hormone, modeled after the TRH secreted by the hypothalamus gland in the brain); 25 minutes later blood is drawn and the TSH is measured again. If the measures from the second TSH blood test are high (above 15), then the patient's thyroid is underactive.

The TRH injection stimulates the brain's pituitary gland, which produces TSH and regulates the thyroid. If the thyroid is under-functioning, the pituitary gland will secrete excess TSH.

Barnes Basal Temperature Test

Another way of detecting a possible thyroid deficiency is to take your basal body temperature. Place a thermometer at your bedside, and as soon as you wake up before you step out of bed, place the thermometer under your arm for at least 3 minutes. If you are T3 deficient, you will find your basal temperature to be below 97.8°F (normal throughout the day is 98.6°F). If your first-thing-in-the-morning temperature is consistently low, it likely means that your basal (resting) metabolic rate is also low.

Record the time, date, and temperature every morning for 2 weeks to show your doctor. In addition to following up with blood tests, your doctor can determine the patency of your deep tendon reflexes, especially the time it takes your Achilles tendon to recover after first elicitation.

CONVENTIONAL TREATMENTS

  • Synthroid
  • Unithroid
  • Levoxyl


Synthroid

Conventional treatment calls for the oral replacement of deficient thyroid hormones. A synthetic form of T4 (Synthroid, Levothroid, Levothyroxine) is most often administered. Treatment, especially in older people, begins with low doses of thyroid hormone because serious side effects may occur with too large a dose. The dose is gradually increased until TSH levels in the blood return to normal. The medication must usually be taken for life.

Synthroid is the third most popular drug prescribed in the United States, being taken by 8 million people. The drug was introduced in 1955 without FDA approval. Recently the safety, stability, and efficacy of this drug have come under fire. In April 2001 the FDA denied Abbott Laboratory's request that Synthroid be allowed to bypass a new drug application and be declared "generally recognized as safe and effective." Instead the FDA stated that Synthroid "had a history of problems with potency and stability" and required Abbott to file the necessary application and study results by August 14, 2001, for official review and approval. Final review and approval was granted by the FDA in July 2002. A condition of approval was that Abbott is required to "develop an analytical method for the determination of impurities and degradation products in the drug substance and the drug product" by July 31, 2003.

Several studies have questioned the effectiveness of levothyroxine and other synthetic T4 drugs for various treatments of thyroid disorders. One study evaluating its ability to suppress the number of nodules in patients with multinodular euthyroid goiter showed limited effectiveness in reduction of nodules. This study also indicated it was ineffective for body weight reduction in obese patients (Imbrogno et al. 2001).

For some patients, hypothyroidism symptoms persist despite standard thyroxine replacement therapy. Thyroxine therapy was no more effective than placebo in improving cognitive function and psychological well-being in patients with symptoms of hypothyroidism, despite thyroid function tests falling well within the reference range (Pollock et al. 2001; Walsh et al. 2001).

Unithroid

Unithroid (levothyroxine), previously known as Thyrox, was approved by the FDA on August 22, 2000, as the first FDA-approved levothyroxine (synthetic T4) drug on the market. Many physicians are recommending that their patients switch from other non-FDA-approved drugs (such as Synthroid) to Unithroid.

Levoxyl

On May 25, 2001, Levoxyl received FDA approval as the second levothyroxine drug. Many patients prefer Levoxyl because of its lower price.

Continued . . .
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