Thyroid Failure:Hashimoto’s Disease

When I was a resident in medical training a woman arrived in the emergency room in a coma. She had been living alone and, according to neighbors, sitting in a chair in her apartment for weeks. Her clinical state was like one of hibernation, with very low pulse, blood pressure and temperature. Her hair was like thin and brittle, her skin scaly and dry, her face puffy and her legs thickened by a waxy swelling called myxedema. She was in the final stages of thyroid gland failure, myxedema coma. Early in the course of her illness, when symptoms were probably mild and ill-defined, no one had realized she was “hypothyroid.” Later, when thyroid hormone levels had fallen to dangerous lows, she was too slow mentally and physically to seek help. By the time she arrived in the ER she was on the brink of death from Hashimoto’s disease, an autoimmune inflammation of the thyroid gland, or thyroiditis. Hashimoto’s disease was the first recognized disease caused by the immune system attacking some part of the body, and is the most common cause of thyroid gland failure in the USA.

Hashimoto’s disease affects at least one in every 1000 people in the US, women more frequently than men.  Though the thyroid disease was first described in 1912, and is now known to be caused by the production of antibodies against thyroid hormone producing enzymes and proteins, there is still no known way to prevent it. The only risk factor is a family history of a similar problem. Some environmental factors such as high iodine intake and viral infections may play a role in triggering the process in genetically susceptible individuals. In Hashimoto’s disease, the antibodies gradually destroy the gland’s hormone producing follicles. Most often, the thyroid gradually and irregularly enlarges as the follicles are replaced by inflammatory tissue. While the bumpy neck bulge created is similar to a goiter, the latter is smoother and more regular in shape and a sign of an overworking but non-inflamed thyroid gland which is getting insufficient dietary iodine.

In Hashimoto’s disease, subtle physical symptoms often precede the development of an enlarged thyroid gland. Since thyroid hormone facilitates all metabolism and energy production in every part of the body, inadequate amounts of the hormone cause a host of vague symptoms which are often excused as simply the byproduct of life style inadequacies such as too little sleep, poor diet, lack of exercise and stress. The symptoms include fatigue, weight gain, depression and anxiety, inability to stay warm, joint and muscle aches and pains, constipation, slow pulse, coarse and thinning hair, puffiness, irregular menstrual periods, and inability to conceive. In some people, gland enlargement never occurs. And though the underlying problem is inflammatory, the thyroid gland is not tender.

Because of the vague nature of the symptoms that bring a patient with Hashimoto’s thyroiditis to the doctor, because the thyroid gland may not be enlarged and because the screening blood test for total thyroid hormone level may fall within a normal range, many other diagnoses are often entertained before the correct one is made. These include depression, anxiety, chronic fatigue syndrome and subclinical infection. In addition, because hypothyroidism drives cholesterol and weight up, attention gets diverted to heart disease and other components of the metabolic syndrome.

But once suspicion of Hashimoto’s has been raised, the problem is easily identified by blood tests for antibodies to an enzyme called thyroid peroxidase and to a thyroid hormone binding protein called thyroglobulin and a test for a pituitary gland hormone called TSH, or thyroid stimulating hormone.  TSH rises as thyroid function fails and the pituitary gland attempts to stimulate it to keep producing thyroid hormone.

Some patients need thyroid scans and biopsies of any suspicious gland areas to rule out the very rare possibility that a lump in the gland is cancerous. A general medical evaluation is also helpful since low thyroid hormone can accelerate cardiovascular disease and since the autoimmune dysfunction underlying Hashimoto sometimes occurs in association with other autoimmune disorders such as celiac disease, Type 1 diabetes, adrenal gland insufficiency, autoimmune gastritis with Vitamin B12 deficiency, rheumatoid arthritis, lupus, and some clotting disorders that may cause either bruising or clot formation in blood vessels.

If other autoimmune problems are not found, the therapy for Hashimoto’s thyroiditis is as easy as taking one pill a day, usually a synthetic thyroid hormone called levothyroxine. Prior to the development of synthetic thyroid hormone, a desiccated powder made from pig thyroid glands was the only treatment available and it is still preferred by a significant number of patients. A controlled study done in 2013 to determine whether there was any scientific evidence for treatment preference showed that both synthetic thyroid hormone and desiccated thyroid hormone are equally effective in raising thyroid hormone levels and returning TSH levels to normal, but that desiccated thyroid hormone resulted in slightly greater weight loss.

Our myxedema coma patient survived, though her management was difficult because of the severity of her hypothyroidism. Under the autoimmune attack of Hashimoto’s thyroiditis, the thyroid gland is a victim of a very slow war of attrition as more and more of its structure is replaced by inflammatory cells and scar tissue.  The fall-off in hormone production is slow, and the body adapts to lower and lower levels of thyroid hormone until all systems finally begin shutting down. At that point, re-introducing high levels of thyroid hormone can be dangerous to heart function. The correction must occur gradually, as the decline did, underscoring the importance of detecting thyroid gland failure early, before it takes such a metabolic toll. Even when discovered early, the establishment of appropriate hormone dose and the reversal of symptoms may take some time and patience. The hormone must be taken for the rest of a long and otherwise normal life.


Iodine: An Unfinished Story

In these days of high tech medicine it is easy to forget that some of the most effective and efficient health interventions are simple and cheap. One example is the addition of iodine to salt, an idea which began in the early 1900s with experimental trials in schoolchildren living in what was then known as the “goiter belt” of the USA. In that region surrounding the Great Lakes, many children developed enlarged thyroid glands called goiters.  A goiter is a sign of iodine deficiency.  So successful were the trials of iodine-supplemented diets that, by the 1930s, 90% of residents of the Great Lakes region used iodized salt and goiter rates in the region had plummeted.  Now, 70% of the world’s population uses iodized salt.

Iodine as an essential element

When iodine is in short supply, thyroid glands grow large in an attempt to harvest as much of the vital element as possible from the blood.  Iodine is necessary for making thyroid hormone and thyroid hormone is crucial for normal development and metabolism.  Pregnant women who have  low iodine levels and insufficient thyroid hormone often miscarry their babies or produce babies who are deaf, mentally-retarded  and stunted in growth.  In children and adults, iodine and thyroid hormone deficiencies cause fatigue, weight gain, lowered IQ levels, mental apathy and numerous metabolic abnormalities.  Regular intake of iodine is a simple preventive measure for a host of serious problems.

Unequal distribution

Iodine exists in an inorganic form in soil and water and makes its way into the plants and animals that we consume by combining with larger carbon-containing molecules.  In its inorganic form, iodine is a water-soluble salt which washes out of soil easily, especially in areas where the land is rocky and exposed. Where soil is iodine deficient, so are crops, unless supplemented with iodine containing fertilizers.  In contrast to its variable presence in soil, iodine is much more uniformly distributed in salt water seas.  Algae, kelp and other seawater plants, as well as saltwater fish and shell fish are the most reliable natural sources of dietary iodine, while iodine concentrations in land based plants depend on the amount of iodine in soil that supports them.  Terrestrial animals supply iodine proportional to the iodine in their food sources. Egg yolks are a good iodine source, because, like people, chickens develop goiters, and chicken feed is supplemented with iodine. Dairy products are also good sources. Cattle feed was originally supplemented with iodine to prevent hoof rot, and and because of the supplemented feed, iodine is secreted in the milk the cows produce.

Iodine and breast tissue

Milk contains iodine because mammary gland tissue, like thyroid gland tissue, accumulates iodine. The fact that iodine is found in human breast tissue, where it has no known function, has prompted studies of the element’s relationship to breast health.  Japanese women have low rates of breast cancer and fibrocystic breast disease compared to American women, and their regular iodine consumption via seaweed is high, perhaps 25x higher than the recommended daily iodine consumption in the US. Studies on the treatment of fibrocystic breast disease with iodine supplements have been promising but so far a direct relationship between breast disease and iodine consumption has not been proven.

Iodine supplementation?

Even if high dietary iodine content has something to do with low breast cancer rates among Japanese women, translating this information to attempts to prevent breast cancer is not a straightforward task. While it is clear that iodine supplementation prevents goiter, hypothyroidism and cognitive impairment, it is also clear that increasing iodine intake is not risk free, particularly in people who are accustomed to low levels of dietary iodine.  The thyroid gland, when faced with insufficient iodine in the blood, becomes a ruthless scavenger, extracting every last iodine molecule it can find. When iodine levels in the blood suddenly increase because of supplementary iodine intake, some thyroid glands will actually grow in size, pump out excessive thyroid hormone and even develop cancerous nodules. It may be that Japanese women can tolerate high amounts of iodine because it has never been in short supply for them. Caution and careful follow-up are always advisable when supplementing the diet with iodine in the form of tablets, drops or multivitamins.

Dietary iodine in the age of dietary angst

Obtaining enough iodine through the diet should be possible in almost all circumstances, especially because of the wisdom of public health policies regarding iodine.  Nevertheless, some eating trends in health in the closing decades of the 20thC have again raised public health concerns about iodine intake.   Assessments of body iodine content are made by measuring urinary iodine levels, since the body extracts as much iodine as it needs and excretes the rest in urine. But individual measurements are so variable that averages of all people tested are used to estimate the iodine status in a given geographic area.  Between 1971 and 2001, American iodine intake dropped dramatically then leveled off at half of the 1971 levels.

What happened over the last few decades?   Americans began getting much more of their salt in the form of the un-iodized salt in processed foods. Many people began avoiding salt altogether, some quite unnecessarily. Sea salt appeared on the grocery store shelves as part of the natural and organic food trends.   It is also possible that the 1971 levels of iodine consumption were artificially high. Studies in the 1970s showed that iodine-containing sanitizers were raising iodine levels in cows’ milk. Practices changed and milk iodine levels returned to normal.   Between the 1960s and 1980s, iodine was used in dough making and bread supplied 25% of the iodine consumed during that period.*  Perhaps the baseline measurements of iodine intake in the early 1970s were unnecessarily high. Perhaps intakes in 2001 and since  are adequate, at least to prevent goiters from developing. But the fact that Japanese people ingest far higher levels of iodine from whole food sources without ill effect suggests that we can tolerate more. Stay tuned.


*Note: Iodine in the Nuclear Age

In the wake of the atmospheric nuclear testing period, the government mandated the use of iodine containing oxidizing agents for dough conditioning in commercial baking. The iodine in the bread  competed  in the diet for uptake into the thyroid gland with radioactive iodine isotopes generated in  the wake of atmospheric nuclear testing. Saturating the thyroid gland with normal iodine is standard practice when radioactive iodine in the atmosphere  is a threat, as it was after the Chernobyl disaster. Taken within 8 hours after, or 48 hours prior to a nuclear disaster, iodine can prevent accumulation of radioactive iodine in the thyroid gland and thus prevent radiation damage to the gland. Pills to be taken in the event of a nuclear catastrophe are simply potassium iodide.

Thyroid Ups and Downs

Early in her husband’s presidency, first lady Barbara Bush began to lose weight. Her eyes became, in her own words “horrible and puffy” looking.” She had developed an autoimmune thyroid gland problem called Graves’ Disease. A few months later, the Bush‘s dog Millie came down with another autoimmune disease – lupus. The next spring, the president became ill with weight loss and a rapid, irregular heartbeat. Like Barbara he had Graves’ disease. Conspiracy theorists blamed Saddam Hussein for this outbreak of autoimmune disease in the White House, but thyroid experts saw nothing but coincidence. They admit, though, that they do not know what triggers antibody attacks against the thyroid gland, the most common cause of thyroid disease.

The many and varied symptoms of thyroid disease
Symptoms of thyroid disease most often involve effects of the hormones the gland makes. Thyroid hormone stokes the fire of metabolism, setting the rate of energy usage in every cell of the body and determining the basal metabolic rate (number of calories burned at complete rest).
Too much thyroid hormone causes hyperthyroidism; too little creates hypothyroidism. Extreme cases of either problem are easy to diagnose, but milder excess or deficiency states are much trickier and more common (an estimated 7-10% of adults have thyroid abnormalities). Hyperthyroid patients lose weight, become intolerant of warm environments and sweat profusely. Hair becomes thin and fine. The heart beats too fast and blood pressure rises, while muscles feel weak and hands shake. Sleep becomes elusive. On the hypothyroid end of the spectrum, lack of thyroid hormone banks the metabolic fires and drops the heat. Patients feel cold and become constipated. Incoming energy gets stored as fat; weight and cholesterol levels climb. Lethargy encroaches on daytime hours, and ambition and mental quickness decline. Both under and overactive glands can be enlarged and even visible as swellings just under the Adam’s apple.

The confirmation of the thyroid gland’s role in symptoms comes from blood tests that measure thyroid hormone levels. Extreme cases are easy to diagnose. Milder cases, with less impressive symptoms and “borderline” blood tests are trickier. Mild symptoms overlap many of life’s normal patterns that are unrelated to thyroid hormone: weight, blood pressure and cholesterol tend to go up with age; sedentary people frequently feel cold and constipated; women at menopause would sometimes like to abolish indoor heating, and physical and mental energy are always subject to lifestyle, happiness, and drug effects. The opinion of an endocrinologist is particularly helpful in interpreting borderline thyroid symptoms and lab values.
Thyroxin or T4 (with four iodine molecules) comes from the thyroid gland. Tri-iodothyronine (T3) comes from T4 when one iodine molecule is split off. Thyroid stimulating hormone (TSH), made in the pituitary gland, is like a thermostat that regulates how much T4 the thyroid gland makes. When T4 is too high, TSH goes down. When T4 is too low, TSH goes up. So hypothyroid patients have high TSH and low T4, and hyperthyroid patients have low TSH and high T4.
Symptoms suggesting hyperthyroidism, combined with high-normal T4 and T3 and low- normal TSH prompt further tests to look directly at the thyroid gland. Thyroid scans employ radioactive iodine and distinguish between glands that overproduce in all areas, ones that have nodules of overproduction, and enlarged glands that no longer make any hormone. Measurement of three different types of anti-thyroid antibodies further narrows the diagnosis.

The problems with the tests
Not all labs use the same ranges of normal values. Some rely on broad TSH ranges found in a random selection of apparently healthy people (0.32 -5.0 µIU/ml). Other labs use a much narrower range (.34-2.5µIU/ml) found in people who have been screened to rule out thyroid disease. So if you see a doctor who uses the first range and your TSH is 4.5, you might be told just to watch your weight, get better sleep, take a little blood pressure medicine and be rechecked in 6 months or a year. A doctor using the second might would give you a prescription for thyroid hormone. Treatment of hypothyroidism in these gray areas might normalize the blood tests without producing any clinically identifiable benefits. Nevertheless, it is wise to follow up on iffy test results because, over time, thyroid conditions may declare themselves further.

Autoimmune thyroid disease
Graves Disease and Hashimoto’s thyroiditis, caused by different types of antibodies, are the most common causes of thyroid problems and tend to run in families. In Graves ’ disease, the antibodies may also attack eye muscles and make them swell, producing the characteristic bulging eyes that Barbara Bush complained about. Graves disease most often begins with a hyperthyroid state that requires treatment to suppress overproduction of thyroid hormone or to obliterate the gland by radiation, producing hypothyroidism that requires treatment; sometimes Graves’ improves on its own but then goes on to hypothyroidism. Hashimoto’s disease most commonly bypasses the clinical hyperthyroid phase altogether and is the most common cause of hypothyroidism.

Iodine deficiency
Lack of dietary iodine once caused many cases of hypothyroidism. The word cretin (slang for dunce, idiot) originated in a mountainous French region where iodine deficient soil and lack of iodine-rich seafood resulted in a high incidence of mental and physical retardation from hypothyroidism in babies. Thyroid hormone and the dietary iodine required to make it are critical for normal growth and development, especially of the brain. In modern societies babies are screened and treated for hypothyroidism, and iodized salt makes this essential element easily available so this once frequent deficiency is much less common.

Oral, synthetic versions of T3 and T4, or “natural” versions made from batches of pig thyroid glands make failing thyroid glands easily treatable. Synthetic versions are easier to regulate than are the natural ones. Finding the proper dose to return the blood tests to the normal range is often much easier than finding the dose and timing of pills that improves symptoms. The latter process is an inexact science that sometimes results in too much hormone effect.
Overactive glands are treated with medicines that shut them down, sometimes with radioactive iodine that kills the glandular cells and sometimes with surgery to remove the entire gland. The latter two treatments always produce hypothyroidism which then requires treatment with replacement hormones.
One study on thyroid disease prevalence estimates that there are 13,000,000 Americans with undiagnosed thyroid problems. Thyroid tests are now part of routine blood work, more problems will be caught and treated earlier, and more will be learned about triggers for autoimmune thyroid problems – eventually putting at least one conspiracy theory to rest.

Notes on less Common Thyroid Conditions

Lumps in the thyroid: These are common and most are benign nodules or cysts; sometimes they produce thyroid hormone and cause hyperthyroidism.

Viral thyroiditis (also known as sub-acute thyroiditis): self-limited illness with several weeks of hyperthyroidism, followed by several weeks of hypothyroidism, and then recovery of normal function.

Thyroid cancer: Uncommon. Rarely produces thyroid hormone so usually the diagnosis results from evaluation of lump in the neck or hoarseness; results from radiation exposure – as once was the practice for treating acne.

Pituitary Gland Tumors: Pituitary failure to produce TSH causes hypothyroidism; very rarely the pituitary overproduces TSH and causes hyperthyroidism.

Dietary Hyperthyroidism: At least one outbreak of hyperthyroidism came from meat contaminated with animal thyroid glands. Another rare cause is sudden, excessive iodine supplementation in a patient with underlying thyroid disease .

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