Hypothyroidism: Diagnosis & Treatment

Google and the UCSF Department of Medicine commissioned me to write a Knol entitled “Hypothyroidism.” I’ve included some excerpts here, but you may wish to see the entire knol, which provides more details and includes sections on hypothyroidism in children and pregnant women as well as myxedema crisis.

Manifestations of Hypothyroidism:

Most adults with hypothyroidism complain of fatigue, weight gain, and feeling cold. But the symptoms of hypothyroidism vary considerably among individuals and most people will have only a few of them.

Other common manifestations include: slow heart rate (bradycardia), high blood pressure, cold intolerance, fatigue, depression, mental dullness, puffiness in face or extremities, headache, slow speech, hoarse voice, heavy menstrual periods, joint and muscle pains, tingling feelings (paresthesias), carpal tunnel syndrome, hair breakage and thinning, brittle nails, decreased perspiration and dry skin, skin pallor or yellowing, weight gain. There also may be an enlarged thyroid gland (goiter), due to stimulation of the gland by TSH and also by Hashimoto thyroiditis (see below), which can cause the thyroid to develop a firm “rubbery” texture, making it easier to see or feel in the neck.

Uncommon symptoms of hypothyroidism include: trouble swallowing (dysphagia), breast milk secretion when not nursing (galactorrhea), shortness of breath, pneumonia, weight loss, decreased appetite, absent menstrual periods (amenorrhea), psychosis, sensitivity to narcotics and other drugs, reduced consciousness and coma.

Causes of Hypothyroidism in Adults:

Hashimoto thyroiditis (autoimmune thyroiditis) is the most common cause of hypothyroidism. Dr. Hakaru Hashimoto, a Japanese surgeon, first described the condition in 1912. It’s an autoimmune condition in which the body’s immune system is turned against the thyroid. White blood cells (B lymphocytes) invade the thyroid gland, such that the condition is also known as chronic lymphocytic thyroiditis. Meanwhile, the immune system makes antibodies (immune proteins) that are directed against the thyroid gland. Such antithyroid antibodies are found in the blood of about 10% of adults in the USA, but only a minority of these individuals develop hypothyroidism. Hashimoto thyroiditis is usually a chronic condition that can eventually damage the thyroid and cause hypothyroidism.

Autoimmune thyroiditis has a strong genetic component. Other members of the family are more likely to have hypothyroidism or hyperthyroidism (Graves disease) and may have other autoimmune conditions as well. Although autoimmune thyroiditis can occur at any age and in either sex, it typically affects women. The sexual disparity is striking, with a female:male ratio of 10:1. Hashimoto’s thyroiditis can be caused by the drugs lithium, amiodarone, and interferon. Dietary iodine supplementation also appears to increase the risk of autoimmune thyroiditis and hypothyroidism.

Although hypothyroidism from Hashimoto’s thyroiditis is usually permanent, up to 11% of patients experience a remission after several years. There are two causes for such a remission: 1) The Hashimoto thyroiditis may improve spontaneously for no apparent reason; 2) A stimulating antibody (Thyroid Stimulating Immunoglobulin, TSI) is produced that stimulates the thyroid’s TSH receptors, overwhelming the destructive effects of concurrent Hashimoto thyroiditis and causing the thyroid to produce more thyroid hormone. If the thyroid gland produces excessive amounts of thyroid hormone, the result is autoimmune hyperthyroidism, a condition known as Graves disease. Most people with Graves disease have concurrent Hashimoto thyroiditis.

People with autoimmune thyroiditis have an overactive immune system that attacks their thyroid gland, but may attack other organs as well. Sjöegren syndrome (dry eyes & mouth, usually mild) can occur fairly often, due to autoimmunity against the salivary and lacrimal glands. Celiac disease, autoimmunity against the intestine (provoked by gluten, wheat) is also seen commonly. Vitiligo (patches of white skin) can also occur. Patients may also develop antibodies against other endocrine glands, such that a person with hypothyroidism from autoimmune thyroiditis is somewhat more prone to develop autoimmune adrenal insufficiency, autoimmune hypoparathyroidism (low serum calcium), or autoimmune type 1 diabetes mellitus. When more than one endocrine gland is damaged by autoimmunity, it is termed polyglandular autoimmune syndrome.

Other causes of hypothyroidism include: thyroid surgery, and external beam radiation therapy to the head/neck region for treatment of cancer or skin conditions. Radioiodine (131I), received for treatment or from nuclear fallout, can also cause hypothyroidism. Chemotherapy for cancer can also cause hypothyroidism. Additional causes of hypothyroidism include chronic hepatitis, certain drugs (propylthiouracil, methimazole, sulfonamides, interleukin-2), and sunitinib (Sutent chemotherapy). In addition, iodine deficiency can cause hypothyroidism and goiter; certain foods (turnips, cassava) can aggravate iodine deficiency and are known as goitrogens. Finally hypopituitarism (loss of function in the frontal lobe of the pituitary gland) can cause hypothyroidism, due to a deficiency of TSH.

Testing for Hypothyroidism:

When the thyroid gland fails, the brain’s hypothalamus/pituitary senses the diminished levels of thyroid hormone in the blood and secretes more Thyroid Stimulating Hormone (TSH). Therefore, an elevated serum TSH level is the most sensitive test for hypothyroidism (exception: hypopituitarism). In addition, with hypothyroidism, the serum free T4 (FT4) level is usually low or low normal. Both the TSH and FT4 levels are determined by testing blood samples. The blood can be drawn at any time of day and fasting is not required.

To screen for Hashimoto’s (autoimmune) thyroiditis, blood is assayed (tested) for antithyroid antibodies: anti-thyroperoxidase (TPO) antibodies, and anti-thyroglobulin (TG) antibodies.

Treatment for Adults with Hypothyroidism:

Treatment for hypothyroidism first became available in 1892, when sheep thyroid glands were fried and eaten to treat this condition. This was not particularly palatable or successful. In 1900, a thyroid preparation was first introduced in the United States as desiccated (dried) sheep’s thyroid that had been freed from fat, cleaned, dried, and powdered. It could be made into tablets whose dosage was measured as weight in an old measurement called grains, where 1 grain (not to be confused with the word gram) is equivalent to 60 milligrams (mg). However, the original desiccated thyroid preparations differed in potency from batch to batch, although they have become more reliable and continue to be available. Synthetic thyroxine was developed to be a more reliable thyroid medication.

Synthetic thyroxine (T4) is the thyroid medication that is preferred by most clinicians for treating patients with hypothyroidism. There are several thyroxine formulations and many dosage strengths. Most formulations have accurate amounts of thyroxine in their tablets. However, the bioavailability (absorption) of the different manufacturer’s thyroxine formulations can differ slightly. Therefore, it’s best for hypothyroid patients to be consistent and to take the same brand name of thyroxine or the same manufacturer’s generic thyroxine. It’s also best to take thyroxine with water in the morning on an empty stomach. Certain drugs (eg, iron) interfere with the absorption of thyroxine and certain conditions change the thyroxine dosage requirement: increased (pregnancy) or decreased (eg, menopause); please see my knol for more information.

While receiving thyroxine replacement therapy, most people’s symptoms of hypothyroidism resolve fully. Serum TSH (thyroid stimulating hormone) levels are used to monitor the adequacy of oral thyroxine replacement. The required dosage of thyroxine varies considerably, from 0.25 mcg/d to 300 mcg/d. The thyroid dosage is adjusted to keep the serum TSH level between 0.4 mU/L and 2.0 mU/L, which is generally considered to be an optimal level. For example, if the serum TSH remains above 2.0 mU/L, the dosage of thyroid hormone may need to be increased. Similarly, if the serum TSH is low, the thyroid dosage may need to be reduced. If someone is unable to eat for a prolonged period, thyroxine may be given intravenously at a daily dose of about 75% of their usual oral dose.

Some treated hypothyroid individuals continue to have hypothyroid-type symptoms (e.g., fatigue, weight gain), despite having normal serum TSH and FT4 levels. In such cases, it’s important to consider whether other conditions or drugs might be responsible. However, if hypothyroid symptoms continue without another explanation, it is reasonable to try a slightly higher dosage of thyroid hormone replacement, unless there are contraindications such as angina or atrial fibrillation. The increased dosage may be continued if there is clear clinical benefit and no symptoms/signs of hyperthyroidism. In such cases, I check serum T3 or free T3 levels to ensure that they are in the low-normal or mid-normal range.

In the United States, most clinicians (including me) prescribe pure T4 preparations. However, since the normal thyroid gland secretes both T4 and T3, studies have compared pure T4 thyroid preparations to combined T4/ T3 preparations; these studies have yielded conflicting results. A disadvantage of combined T4/ T3 preparations is that the T3 component peaks a few hours after taking the pill, with transiently elevated serum T3 levels. Nevertheless, some patients state that they feel better when taking combined T4/ T3 preparations. A Dutch double-blind study of 141 hypothyroid individuals found that some patients preferred T4 /T3 over pure T4 preparations and that serum TSH levels were sometimes suppressed on the preferred doses. Other studies have shown no advantage of combined T4/ T3 therapy over pure T4 therapy, when the serum TSH is kept normal. For more information, please see my knol:

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