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Controversies in Thyroid Treatment


Patient Version

Hypothyroidism

The thyroid gland is a gland in the neck that makes hormones that control metabolism.
Thyroid hormone is active in many different tissues in the body, so symptoms of low thyroid can be diverse:
Fatigue
Weight gain
Feeling cold
Muscle aches
Depression, foggy thinking
Constipation
Dry skin and hair
“Thyroid hormone” is actually a collection of several hormones. The main circulating form of thyroid in the blood is T4, but the form that is actually active inside cells is T3, where one iodine has been removed from the T4 molecule.

Reasons for Low Thyroid Activity

Sometimes the gland itself can be damaged, such as in autoimmune thyroiditis (“Hashimoto’s”) or it may be removed surgically or damaged by radioactive iodine to treat other conditions, like thyroid cancer or Graves’ Disease.
In some people, the thyroid may be underactive because the brain and/or pituitary gland are not sending it the proper signals to produce thyroid hormone. This can happen after a head injury, because of some medications, like pain medications, or for other reasons.
In some people, the thyroid gland may be working normally but their body does not make good use of thyroid hormones, either because of stress, selenium deficiency, exposure to environmental chemicals (PCB’s, phthalates, BPA, etc.) or for other reasons.

Treating Hypothyroidism

Hypothyroidism (“Low thyroid”) can be treated with several different medications.

T4

The FDA approved treatment is levothyroxine, which is synthetic T4. For the majority of patients, this works well to control low thyroid symptoms, since it is inexpensive, widely available, has a long half-life so it can be taken once a day or even less often because blood levels stay pretty stable, and the body can convert it to T3.
For a subset of patients, however, the conversion to T3 is poor in some or all cells. There is no reliable blood test to detect this problem, because T3 may be normal in the blood but low in tissues, and it may be different in the brain than in the rest of the body. In those patients, symptoms will not be relieved with levothyroxine treatment, particularly psychiatric symptoms (depression, “brain fog”, etc.) In those patients, treatment options include synthetic T3 (Cytomel and other forms of liothyronine) and dessicated thyroid (ground up animal thyroid glands, with a mix of T3, T4 and other compounds as found in animal thyroid glands.)

T3 (Liothyronine, Cytomel)

The half-life of this hormone in the blood is short, 4-6 hours or so, so some patients feel a lot of side effects in the first few hours after taking a dose, and can “crash” partway through the day as it wears off. It generally works better to take it 3 times a day.

Dessicated thyroid – (Armour thyroid, Naturethroid, NP thyroid, WP thyroid and others.)

This is made from powdered thyroid glands (usually from pigs), and can include T1, T2 T3 and T4 as well as calcitonin.
For many people, this is a “smoother treatment” than the pure T3, with less up and down symptoms and better relief of their low thyroid symptoms. This has been used for 115 years under the US Pharmacopoeia, and is available from a number of different companies.
Dessicated thyroid is NOT FDA approved because it was already in common use before the current FDA approval mechanisms were in place, and the studies to introduce FDA approval are expensive. (As an example, when colchicine, a very old gout medicine, went through the FDA approval process in 2009 the cost went from about 10 cents per pill to $5 per pill; pancreatic enzymes also used to be as low as $20 -$40 per month and are now $500 per month or more.)

Risks/Side effects of thyroid treatment

Side effects to watch for include:
Racing heart or palpitations
Shaking hands
Feeling nervous or unable to sleep
Feeling too hot
Diarrhea
These risks may be higher with T3, either from dessicated thyroid or liothyronine, and are more common in elderly patients. The heart side effects in particular can be dangerous, so some caution is needed when using T3 in that group, however it is sometimes still necessary.

Cost

Many insurance companies are now refusing to cover natural dessicated thyroid because it is not FDA approved. If you want to switch to levothyroxine we are happy to work with you on that, and recommend watching for return of symptoms, especially fatigue, depression and brain fog.
If you want to continue your current dessicated thyroid, talk to your pharmacist about the cost if you pay without insurance. We are also carrying Nature-throid at Full Circle to make this more affordable. Typical costs are under $10 per month once we know your dose:
Naturethroid32.5 mg60 pills$11.61
65 mg30 pills$6.86
81.25 mg60 pills$15.24


Health Care Provider Version

Treatment with Thyroid Hormones with “Normal” Blood Tests

Pituitary down-regulation

Altered conversion from T4 to T3 in cells

Resistance to binding at the thyroid receptor

(NTIS Nonthyroidal Illness Syndrome(external link), previously known as the Euthyroid sick syndrome) is well-described in the medical literature and is particularly receiving attention in recent years in the critical care literature. This is believed to represent both hypothalamic-pituitary axis dysfunction (thus a “normal” TSH in the presence of clinical hypothyroidism) as well as altered peripheral metabolism(external link) of tetraiodothyronine (production of rT3 instead of T3 in tissues) and perhaps changes in hormone binding. In addition, there are environmental causes(external link) of thyroid hormone resistance at the receptor level in our modern world . As one example, PCB’s actually cause mental retardation in the developing fetus by interfering with thyroid hormone binding to its receptor or gene activation normally induced by thyroid hormone.

The result of all of these factors is that often in persons with other illnesses (autoimmune disease, chronic fatigue syndrome, chronic infection), or even after significant weight loss or other stressors, there will be a clinical syndrome consistent with hypothyroidism (cold intolerance, constipation, dry skin, depression, etc.) without clear laboratory evidence of hypothyroidism. In this situation, I often have people measure basal body temperatures as a nonspecific indicator, and if these run low in conjunction with suggestive symptoms, I will give a trial of therapy of thyroid hormone replacement. If there is no improvement in symptoms, we consider that a failed trial and stop the hormones. If symptoms improve on the thyroid hormone, we then monitor for toxicity and decrease the dose if the TSH is suppressed. I have found this to make a significant difference in the quality of life for many of my patients, and feel it is safe as long as laboratory monitoring is performed. If patients are feeling well, many of them later can taper off the thyroid replacement, after the underlying illness that triggered the syndrome has been addressed.

Treatment of Hypothyroidism with Armour or Dessicated Thyroid rather than Levothyroxine

Another controversial point is the use of armour thyroid rather than levothyroxine for thyroid hormone replacement. The medical literature is split as to whether there is any benefit to providing a mixture of T3 with T4 as opposed to pure T4 replacement therapy. A 1999 study(external link) published in the New England Journal of Medicine found improved control of symptoms of hypothyroidism, particularly psychiatric symptoms, with combination therapy. Other studies have shown no difference, but many of those studies have excluded participants with a history of depression.
There are unrelated studies in the psychiatric literature(external link) reporting the use of liothyronine(cytomel, pure T3) for the augmentation of antidepressant therapy, even in persons who are clinically euthyroid, often with dramatic results (up to doubling of the response rate compared to the placebo group). There is also a body of literature addressing genetic polymorphisms (external link)in the D1, D2, and D3 iodothyronine deiodinases and their impact on thyroid function and hormone levels, confirming a plausible basis for genetic differences in the handling of thyroid hormones.

I have found, and the above studies support this, that many patients feel fine on levothyroxine, in which case I am happy to continue this as their primary thyroid replacement. There is a significant subset of patients, however, often those with chronic dysthymia or depression, who notice an improvement in symptom control when placed on armour thyroid instead.
One issue with armour thyroid is that the ratio of T3:T4 is 1:5, whereas a more normal ratio in humans is often 1:10. Laboratory monitoring of patients on armour will thus often reveal a low free T4 with a normal TSH, and if symptoms are controlled I will leave this as is. Some patients feel symptoms of excessive thyroid replacement (palpitations, nervousness, shaky hands, etc.) related to the high T3, however, and in those patients I will generally switch to levothyroxine or, in a few patients (and myself!), use a combination of the two to more closely approximate normal thyroid physiology.
Connie Basch, M.D March 2008

There are many more sites on the web supporting this view. I appreciated this one(external link), which I ran into recently