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Thyroid Regulation

Millions of Americans suffer from fatigue, weight gain, depression, and cognitive impairment. Many believe that they have no choice but to accept these seemingly “age-related” declines in quality of life.

Underactive thyroid (hypothyroidism) is often overlooked or misdiagnosed and can be the underlying cause of these symptoms. Patients and their doctors often disregard these common signs of thyroid hormone deficiency, mistaking them for normal aging.1

Overactive thyroid (hyperthyroidism) afflicts fewer people than hypothyroidism, yet the symptoms can be equally devastating. Subclinical hyperthyroidism, characterized by suppressed thyroid stimulating hormone (TSH) levels accompanied by normal thyroid hormones (T4 and T3) levels,2 has been associated with increased rates of cardiovascular disease; arrhythmia in particular.3 Overt hyperthyroidism compromises bone health,4 elevates blood glucose levels,5 and often causes anxiety.6

Fortunately, a simple blood test for TSH, T3 and T4 can reveal an underlying thyroid condition and help direct treatment to improve the symptoms.1, 2

In this protocol we will discuss the function and regulation of the thyroid gland, and the systemic implications of both hypothyroidism and hyperthyroidism. We will examine the importance of proper testing and interpretation of thyroid hormone levels and reveal natural approaches for maintaining optimal thyroid hormone levels.

Role of the Thyroid

The thyroid is a butterfly-shaped organ located just below the Adam’s apple in the neck. Made up of small sacs, this gland is filled with an iodine-rich protein called thyroglobulin along with the thyroid hormones thyroxine (T4) and small amounts of triiodothyronine (T3).

The primary function of these two hormones is to regulate metabolism by controlling the rate at which the body converts oxygen and calories to energy. In fact, the metabolic rate of every cell in the body is regulated by thyroid hormones, primarily T3.7

In healthy individuals the gland is imperceptible to the touch. A visibly enlarged thyroid gland is referred to as a goiter. Historically, goiter was most frequently caused by a lack of dietary iodine. 8 However, in countries where salt is iodized, goiter of iodine deficiency is rare.

Thyroid Regulation

The production of T4 and T3 in the thyroid gland is regulated by the hypothalamus and pituitary gland. To ensure stable levels of thyroid hormones, the hypothalamus monitors circulating thyroid hormone levels and responds to low levels by releasing thyrotropin-releasing hormone (TRH). This TRH then stimulates the pituitary to release thyroid stimulating hormone (TSH).9,10 When thyroid hormone levels increase, production of TSH decreases, which in turn slows the release of new hormone from the thyroid gland.

Cold temperatures can also increase TRH levels. This is thought to be an intrinsic mechanism that helps keep us warm in cold weather.11

Elevated levels of cortisol, as seen during stress and in conditions such as Cushing’s syndrome, lowers TRH, TSH and thyroid hormone levels as well.12,13

The thyroid gland needs iodine and the amino acid L-tyrosine to make T4 and T3. A diet deficient in iodine can limit how much T4 the thyroid gland can produce and lead to hypothyroidism.14

T3 is the biologically active form of thyroid hormone. The majority of T3 is produced in the peripheral tissues by conversion of T4 to T3 by a selenium-dependent enzyme. Various factors including nutrient deficiencies, drugs, and chemical toxicity may interfere with conversion of T4 to T3.15

Another related enzyme converts T4 to an inactive form of T3 called reverse T3 (rT3). Reverse T3 does not have thyroid hormone activity; instead it blocks the thyroid hormone receptors in the cell hindering action of regular T3.16

Ninety-nine percent of circulating thyroid hormones are bound to carrier proteins, rendering them metabolically inactive. The remaining “free” thyroid hormone, the majority of which is T3, binds to and activates thyroid hormone receptors, exerting biological activity.17 Very small changes in the amount of carrier proteins will affect the percentage of unbound hormones. Oral contraceptives, pregnancy, and conventional female hormone replacement therapy may increase thyroid carrier protein levels and, thereby, lower the amount of free thyroid hormone available.18

Thyroid Dysfunction


In hyperthyroidism, the thyroid gland produces too much thyroid hormone, which can significantly accelerate the body's metabolism. Typical symptoms of hyperthyroidism include sudden weight loss, a rapid heartbeat, sweating, nervousness or irritability. Hyperthyroidism affects about one percent of the population.19

Extreme hyperthyroidism, or thyrotoxicosis, can culminate in what’s referred to as “thyroid storm”.20 In this medical emergency, patients suffer from elevated heart rates and blood pressure, extreme exhaustion, and high fever. Thyroid storm sharply increases a patient’s risk for stroke and heart attack, and is fatal for up to 50% of patients, even with the best medical care.21

Hyperthyroidism: What you need to know

Hyperthyroidism is usually caused by Graves’ disease characterized by symptoms such as rapid heartbeat, sweating, nervousness, tremors, muscle weakness, sleep difficulties, increased appetite and sudden weight loss.22 Affected individuals can also experience thyroid storm—a potentially deadly medical emergency.23

Medical Treatment of Grave’s disease 24

  • Anti-thyroid drugs, such as methimazole or proplythiouracil, inhibit the production of T3.
  • Radioactive iodine, which causes destruction of the overactive thyroid gland.
  • Surgical removal of the thyroid gland (thyroidectomy).
  • Βeta-blockers may be used to control the high blood pressure and increased heart rate associated with hyperthyroidism.

Nutritional Support of Hyperthyroidism

  • Increased thyroid activity increases loss of L-carnitine through the urine. Individuals suffering from hyperthyroidism may, therefore, require supplemental L-carnitine.25
  • L-carnitine supplementation helped prevent or reverse muscle weakness and other symptoms in individuals suffering from hyperthyroidism. Clinical trials have shown that doses of 2,000-4,000 mg/day of L-carnitine are helpful in individuals who suffer from hyperthyroidism.26
  • Passion flower (Passiflora incarnata ) and valerian (Valeriana officinalis) are botanicals that have a calming effect on the nervous system27,28 and thus may help control the symptoms of an overactive thyroid.


Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormones, characterized by a reduction in metabolic rate. The main symptoms of hypothyroidism are fatigue, weakness, increased sensitivity to cold, constipation, unexplained weight gain, dry skin, hair loss or coarse dry hair, muscle cramps and depression. However, most symptoms take years to develop. The slower the metabolism gets, the more obvious the signs and symptoms will become. If hypothyroidism goes untreated, the signs and symptoms could become severe, such as a swollen thyroid gland (goiter), slow thought processes, or dementia. 29

Subclinical hypothyroidism, an often under-diagnosed thyroid disorder, manifests as elevated TSH, normal T4 and normal T3 levels.30 Individuals with subclinical hypothyroidism are at greater risk for developing overt hypothyroidism.31 An August 2010 study reported that 8.3% of women with no history of thyroid disease suffer from subclinical hypothyroidism.32 An article in the American Family Physician in 2005 estimated that about 20% of women over the age of 60 suffer from subclinical hypothyroidism.33

There is evidence that the standard blood TSH test reference range may cause many cases of hypothyroidism to be missed. Most physicians accept a reference range for TSH between 0.45 and 4.5 mU/L to indicate normal thyroid function. In reality, though, a TSH reading of more than 2.0 may indicate lower-than-optimal thyroid hormone levels.34

According to a study reported in Lancet, various TSH levels that fall within normal range are associated with adverse health outcomes.26

  • TSH greater than 2.0: increased 20-year risk of hypothyroidism and increased risk of thyroid autoimmune disease
  • TSH between 2.0 and 4.0: hypercholesterolemia and cholesterol levels decline in response to T4 therapy
  • TSH greater than 4.0: greater risk of heart disease

There is another and separate problem brought on by these overly broad normal ranges for TSH. People already diagnosed and being treated for hypothyroidism are often not taking correct doses of thyroid replacement hormone. A November 2010 study reported that about 37% of people being treated for hypothyroidism were taking incorrect doses, about half too much and another half too little hormone.35

Consequences of Hypothyroidism

Gastrointestinal problems: Hypothyroidism is a common cause of constipation. Constipation in hypothyroidism may result from diminished motility of the intestines. In some cases, this can lead to intestinal obstruction or abnormal enlargement of the colon.36 Hypothyroidism is also associated with decreased motility in the esophagus, which causes difficulty swallowing, heartburn, indigestion, nausea, or vomiting. Abdominal discomfort, flatulence, and bloating occur in those with small intestinal bacterial growth secondary to poor digestion.31

Depression and psychiatric disorders: Panic disorders, depression, and changes in cognition are frequently associated with thyroid disorders.37 Hypothyroidism is often misdiagnosed as depression.38 A study published in 2002 suggests that that thyroid function is especially important for bipolar patients: “Our results suggest that nearly three-quarters of patients with bipolar disorder have a thyroid profile that may be suboptimal for antidepressant response.” 39

Cognitive decline: Patients with low thyroid function can suffer from slowed thinking, delayed processing of information, difficulty recalling names, etc.40 Patients with subclinical hypothyroidism show signs of decreased working memory,41 and decreased speed of sensory and cognitive processing.42 An evaluation of thyroid hormones along with TSH may help avoid misdiagnosis as being depressed. 43

Cardiovascular Disease: Hypothyroidism and subclinical hypothyroidism are associated with increased levels of blood cholesterol, increased blood pressure, and increased risk of cardiovascular disease. 44 Even those with subclinical hypothyroidism were almost 3.4 times as likely to develop cardiovascular disease than those with healthy thyroid function.45

  • High blood pressure: Hypertension is relatively common among patients with hypothyroidism. In a 1983 study, 14.8% of patients with hypothyroidism had high blood pressure, compared with 5.5% of patients with normal thyroid function. 46 “Hypothyroidism has been recognized as a cause of secondary hypertension. Previous studies … have demonstrated elevated blood pressure values. Increased peripheral vascular resistance and low cardiac output has been suggested to be the possible link between hypothyroidism and diastolic hypertension.” 47
  • High cholesterol and atherosclerosis: “Overt hypothyroidism is characterized by hypercholesterolemia and a marked increase in low-density lipoproteins (LDL) and apolipoprotein B” 48 These changes accelerate atherosclerosis, which causes coronary artery disease.43 The risk of heart disease increases proportionally with increasing TSH, even in subclinical hypothyroidism.49 Hypothyroidism that is caused by autoimmune reactions is associated with stiffening of the blood vessels. 50 Thyroid hormone replacement may slow the progression of coronary heart disease by inhibiting the progression of plaques.51,52
  • Homocysteine: Treating hypothyroid patients with thyroid hormone replacement might attenuate homocysteine levels, an independent risk factor for cardiovascular disease: “A strong inverse relationship between homocysteine and free thyroid hormones confirms the effect of thyroid hormones on homocysteine metabolism.” 53
  • Elevated C-reactive protein: Overt and subclinical hypothyroidism are both associated with increased levels of low-grade inflammation, as indicated by elevated C-reactive protein (CRP). A 2003 clinic study observed that CRP values increased with progressive thyroid failure and suggested it may count as an additional risk factor for the development of coronary heart disease in hypothyroid patients. 54

Metabolic Syndrome: In a study of more than 1,500 subjects, researchers found that those with metabolic syndrome had statistically significantly higher TSH levels (meaning lower thyroid hormone output) than healthy control subjects. Subclinical hypothyroidism was also correlated with elevated triglyceride levels and increased blood pressure. Slight increases in TSH may put people at higher risk for metabolic syndrome. 55

Reproductive system problems: In women, hypothyroidism is associated with menstrual irregularities and infertility.56 Proper treatment can restore a normal menstrual cycle and improve fertility. 57

Fatigue and weakness: The well known and common symptoms of hypothyroidism, such as chilliness, weight gain, paresthesia (tingling or crawling sensation in the skin) and cramps are often absent in elderly patients compared with younger patients, fatigue and weakness are common in hypothyroid patients.58

Testing Thyroid Function

Thyroid stimulating hormone (TSH) level is the most common test for screening for thyroid dysfunction. In the last decade the diagnostic strategy for using TSH measurements has changed as a result of the sensitivity improvements in these assays. It is now recognized that the TSH measurement is a more sensitive test than T4 for detecting both hypo- and hyperthyroidism. 59 As a result, some countries now promote a TSH-first strategy for diagnosing thyroid dysfunction in patients. 60

In 2008 many labs adopted the reference range for TSH, 0.45 to 4.50 μIU/mL, recommended by both the Endocrine Society and the American Medical Association. Although this range is an improvement over the previous 0.45-5.5 mIU/L, it is still considered too broad by many clinicians. 59, 60, 61

The American Association of Clinical Endocrinologists now recommends an upper limit of 3.0 mIU/L.61 The guidelines for diagnosing thyroid disease from The National Academy of Clinical Biochemistry point out that “more than 95% of normal individuals have TSH levels below 2.5 [mIU/L].. 62 This panel suggests that the upper limit of TSH should be reduced to 2.5 mIU/L.63

On the other hand, current studies also suggest that TSH values below the normal range may represent thyroid hormone excess and, in elderly patients, might be associated with an increased risk of death due to cardiovascular disease. 64, 65

Life Extension suggests an optimal level of TSH between 1.0 and 2.0 mIU/L, as some studies have noted that a TSH above 2.0 may be associated with adverse cardiovascular risk factors. 26 In addition, a TSH between 1.0 and 2.0mIU/L has been associated with the lowest subsequent incidence of abnormal thyroid function.66

However, while a measure of TSH alone is a useful screening tool in assessing thyroid function, Life Extension advocates additional testing, including Free T3 and T4 levels, to provide a more complete evaluation of the thyroid.

Note: TSH values do fluctuate with time of day, infection, and various other factors. In a 2007 survey published in the Archives of Internal Medicine, values spontaneously returned to normal in more than 50% of patients with abnormal TSH levels when the test was repeated at a later date.67 No single measurement of TSH should be considered diagnostic.

Basal Body Temperature: An alternative method for assessing thyroid status that was widely used in the past, before the development of accurate thyroid function blood tests, is the basal body temperature test. The temperature is taken when the body is at complete rest, immediately after waking and before beginning any activity. The normal basal temperature is 97.6-98.2ºF, and some alternative practitioners believe that a 5-day consecutive temperature reading below 97.6 ºF is indicative of hypothyroidism. One study showed a significant correlation between the basal body temperature and low thyroid function in whiplash patients. The authors of this study conclude that basal body temperature “seems to be a sensitive screening test, in combination with laboratory analysis, for the hypothyroidism seen after whiplash trauma.”68 However, there are many reasons for alteration of basal body temperature, a thyroid panel blood test should be taken to accurately evaluate the thyroid function.

Tests for T4 and T3: Thyroid hormones can be tested in both their free and protein-bound forms. Tests for the protein-bound forms and unbound form of T4 or T3 are generally referred to as Total T4 or Total T3 respectively; unbound forms are called Free T4 and Free T3. Each of these tests gives information about how the body is making, activating, and responding to thyroid hormone. Levels of free T3 and T4 will be below normal in clinical hypothyroidism. In subclinical hypothyroidism the TSH will be elevated while the thyroid hormone levels are still in the normal reference range.

Reverse T3: Certain individuals with apparently normal T4 and T3 hormone levels still display the classic symptoms of hypothyroidism. This may be due to an excessive production of reverseT3 (rT3). rT3 is inactive and may interfere with the action of T3 in the body. Stress and extreme exercise may play a role in lowering thyroid hormone action by suppressing production of TSH and T3 and elevating rT3 levels.69,70

Autoimmune antibodies: When evaluating the thyroid it is also important to consider that the most common cause of overt hypothyroidism in the United States is an autoimmune disorder known as Hashimoto’s thyroiditis.71 In this condition the body produces antibodies to the thyroid gland and damage the gland. Hashimoto’s thyroiditis is diagnosed by standard thyroid testing in conjunction with testing for the presence of these antibodies called antithyroglobulin antibodies (AgAb) and thyroperoxidase antibodies (TPOAb). Some people with celiac disease or sensitivity to gluten are at increased risk for developing autoimmune thyroid disease and should be evaluated.72

Elevated thyroid antibodies are often associated with chronic urticaria, also called hives. Studies report that as many as 57.4% of patients with hives have the presence of anti-thyroid antibodies.73,74 An August 2010 paper suggests that treatment with T4 improves the itching associated with urticaria, but did not advise treatment with T4 unless the patient was hypothyroid. 75

Additional testing: Sometimes biopsy or enzymatic studies are required to establish a definite diagnosis for thyroid dysfunction. Major abnormalities of the thyroid gland detected in physical exam can be further assessed by ultrasound or a procedure known as scintigraphy.

Hypothalamic pituitary axis (HPA): There is an intimate relationship between the thyroid, the adrenal glands and the sex hormones.76 If hypothyroidism is suspected, an evaluation of the adrenal glands as well as the sex hormones is suggested.

Hypothyroidism: What you need to know

  • Thyroid diseases occur about five times more frequently in women than in men. As many as 20% of women over 60 years old have subclinical hypothyroidism.77
  • If untreated, chronic hypothyroidism can result in myxedema coma, a rare, life-threatening condition. Mental dysfunction, stupor, cardiovascular collapse, and coma can develop after the worsening of chronic hypothyroidism as well.78
  • An autoimmune disease called Hashimoto’s thyroiditis is the most common cause of low thyroid function in the US. The body’s immune system mistakenly attacks the thyroid tissue impairing the ability to make hormones.79 Hypothyroidism caused by Hashimoto's disease is treated with thyroid hormone replacement agents.
  • Hashimoto’s disease usually causes hypothyroidism, but may also trigger hyperthyroid symptoms.80
  • Hyperthyroidism is usually caused by Graves’ disease, in which antibodies are produced that bind to TSH receptors in the thyroid gland, stimulating excess thyroid hormone production.20
  • The distinction between Hashimoto’s thyroiditis and Graves’ disease may not be as important as once thought. In 2009 researchers wrote that, “Hashimoto's and Graves' disease are different expressions of a basically similar autoimmune process, and the clinical appearance reflects the spectrum of the immune response in a particular patient.”81 The two diseases can overlap causing both thyroid gland stimulation and destruction simultaneously or in sequence.82 Some clinicians consider the two conditions different presentations of the same disease.83 About 4% of patients with Graves’ disease displayed some symptoms of Hashimoto’s thyroiditis during childhood.84
  • Pregnant women are especially at risk for hypothyroidism. During pregnancy, the thyroid gland produces more thyroid hormone than when a woman is not pregnant,85 and the gland may increase in size slightly.
  • Uncontrolled thyroid dysfunction during pregnancy can lead to preterm birth, mental retardation, and hemorrhage in the postpartum period. 86 It is important to work closely with a physician to monitor thyroid function during pregnancy.
  • Tests to diagnose and monitor hypothyroidism include: Thyroid Stimulating Hormone (TSH), Total T4, Total T3, Free T4 (fT4), Free T3 (fT3), Reverse T3 (rT3), Thyroid peroxidase antibody (TPOAb), Thyroglobulin antibody (TgAb)




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