www.drlowe.com--Thyroid Hormone Resistance--Fibromyalgia, Hypothyroidism, Thyroid Hormone Resistance

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The Metabolic Treatment
of Fibromyalgia
by Dr. John C. Lowe
Readers' Comments

Thyroid Hormone Resistance
[Q&As are placed in reverse chronological order. In other words,
the latest Q&As come first. Earlier ones are further down the page.]

Latest Updates to drlowe.com

December 21, 2002

Question: Great site! My problem is a little different. Over the past three years my TSH readings have ranged from 5.05 to 6.93. However, I have no hypothyroid symptoms whatsoever. My weight has remained constant for over 30 years (I'm a 55-year-old male) and I run five miles nearly every day. As a precaution to an even higher TSH reading, I went on 25 mcg of Levoxyl (T4). What a mistake! I’ve never felt right on thyroid medication (it makes me feel hyper) but even worse. My cholesterol, which normally is in the 170 to 180 range, shot up to 217, which, of course, is high. From what I’ve read on your site, it’s not uncommon for cholesterol to elevate on a low dose of T4. You don't have to convince me that T4 isn’t the way to go. My question is twofold: First, should I even concern myself with thyroid medication if I feel great with a TSH of 6? And Second, should I simply try a low dose of Armour? Thanks in advance.

Dr Lowe: Thanks for the compliment on our website. You didn't say whether the level of thyroid hormone in your blood is high-normal or high. If it is, you may have mild general resistance to thyroid hormone. In general resistance, most of the tissues of the body and brain, and perhaps all of them, are partially resistant to thyroid hormone. That is, the tissues don't respond as readily to thyroid hormone as do most other people's tissues. Because the patient's pituitary gland is partially resistant to thyroid hormone, it continues to secrete TSH until the blood level of thyroid hormone rises higher than normal. When the thyroid hormone level rises high enough, it begins to suppress the pituitary gland's production of TSH. As a result, the patient's TSH and thyroid hormone levels are either high-normal or high. Because the body tissues are also partially resistant, the high-normal blood level of thyroid hormone doesn't overstimulate them. So the person has normal metabolism and feels normal despite having fairly high TSH and thyroid hormone levels. I don’t know whether this is applies to you, but it is a possible mechanism.

The thyroid hormone preparation you took, T4 alone, is an extremely poor test to see whether you might benefit from thyroid hormone therapy. Nonetheless, taking thyroid hormone may be of no value to you. I say this for several reasons: You're apparently healthy, feel well, and have no evidence of deficient thyroid hormone regulation of your tissues, such as high cholesterol. It’s highly likely that your elevated cholesterol after starting to use Levoxyl resulted from the extremely small dose you were taking. That low a dose isn't likely to benefit anyone other than a very small pygmy. Moreover, you're correct—the small dose may impede metabolism and cause abnormalities such as your high cholesterol.

March 17, 2000

Question: You and your coauthors have written that many fibromyalgia patients are resistant to thyroid hormone. From what I've read, thyroid hormone resistance is hard to prove. How do you know when a patient is resistant to the hormone?

Dr. Lowe: If a patient has either "general" or "pituitary" resistance to thyroid hormone, this is indicated by the results of thyroid function tests. However, our studies suggest that perhaps 40% of fibromyalgia patients have "peripheral" tissue resistance to thyroid hormone—not pituitary or general resistance.

Patients who have peripheral tissue resistance to thyroid hormone have normal thyroid test results before treatment with thyroid hormone. So, we don't know that they have peripheral resistance until we've treated them with plain T3. (Of course, we treat them with T3 as part of more comprehensive metabolic rehabilitation). A three-part therapeutic outcome tells us which patients have peripheral resistance.

First, resistant patients recover from their hypothyroid-like symptoms and signs only with extraordinarily large dosages of T3 (called "supraphysiologic" dosages). Second, despite these large dosages—which might hospitalize a person who doesn't have tissue resistance—the patients have no indication of tissue overstimulation. (We use various objective tests to rule out overstimulation, such as serial EKGs and various biochemical tests. We also closely scrutinize patients and use various physical exam procedures such as the Achilles reflex test.) Third, although the patients have recovered from their symptoms and signs with high dosages that don't overstimulate them, lab tests show that they have extremely high blood levels of free T3.

If these patients did not have tissue resistance to thyroid hormone, the high blood levels of T3 would cause severe overstimulation (termed thyrotoxicosis). Hence, we know the patients' peripheral tissues are resistance to normal levels of thyroid hormone. Unfortunately, we don't know the mechanism of the tissue resistance. But we're determined to identify the mechanism through further studies.

December 1, 1997

Question: I'm confused by the term "thyroid hormone resistance," which you invoke at the cellular level to explain why supraphysiologic levels of thyroid hormones are required to alleviate symptoms in some patients. My impression is that you've totally suppressed the TSH levels (TSH < 0.1) of your fibromyalgia patients who've required massive doses before they've responded. Is this true? But the explanation I see most commonly for "thyroid hormone resistance" suggests that TSH levels are normal—see, for example, the link (http://www.thyrolink.com/thyint/3-96int.htm#resist) which explains that, in cases of resistance, "administration of supraphysiologic doses of thyroid hormone fail to suppress TSH secretion."

Dr. Lowe: When supraphysiologic dosages of thyroid hormone fail to suppress TSH secretion, the patient has "general" resistance to thyroid hormone. This classification of thyroid hormone resistance is different from the one that manifests as fibromyalgia in many patients. The latter classification is termed "peripheral" resistance to thyroid hormone. I will explain the difference between general and peripheral resistance.

The classification of thyroid hormone resistance is based on whether (1) the pituitary gland and (2) the other tissues of the body (referred to as "peripheral" tissues) are involved in the patient's resistance. In general resistance, both the pituitary gland and the peripheral tissues are partially resistant to thyroid hormone. The patient's thyroid hormone levels are elevated, but his TSH level and his peripheral tissue metabolism are usually normal. Here's why:

In normal functioning of the hypothalamic-pituitary-thyroid axis, when the amount of thyroid hormone in the blood reaches an appropriate level, it then inhibits secretion of TSH by the pituitary gland (this is a normal "feedback" mechanism). But, when the pituitary tissue is resistant to thyroid hormone, much larger amounts are necessary to suppress TSH secretion. When the peripheral tissues are also partially resistant, large amounts of thyroid hormone are needed to "override" the resistance and drive the subnormal metabolism in the periphery to a higher, normal rate. Typically, when these large amounts of thyroid hormone (secreted by a thyroid gland stimulated by large amounts of TSH from a resistant pituitary) finally increase enough to normalize the metabolic rate of the patient's peripheral tissues, the pituitary tissue also finally responds to this amount by reducing its secretion of TSH into the normal range. Thus, patients with general resistance usually have clinically normal peripheral tissue metabolism with high levels of thyroid hormone in the blood, and a normalized level of TSH (finally suppressed only by the high blood levels of thyroid hormone). In this way, the circulating levels of thyroid hormone are kept high enough to override the peripheral tissue resistance (with normalized metabolism) and the pituitary resistance (with normalized TSH). In other words, many general resistance patients appear clinically normal except for the high thyroid hormone levels.

In peripheral resistance to thyroid hormone, only the peripheral tissues are resistant. The pituitary tissue responds normally to a normal amount of thyroid hormone in the blood, and it decreases its TSH output when the blood levels signal that it should do so. Normal blood levels of thyroid hormone, then, properly suppress pituitary gland release of TSH, and keep the circulating TSH levels normal. What's important to realize in this scenario is that the feedback between the pituitary gland and the thyroid gland is normal, and both glands secrete normal amounts of their respective hormones. But the normal thyroid hormone levels are insufficient to override the partial resistance of tissues other than the pituitary--that is the peripheral tissues. As a result, metabolism in the peripheral tissues is subnormal. To speed peripheral tissue metabolism up to normal, the peripheral resistance patient must use large dosages of thyroid hormone. But the effect of these large dosages on the normally responsive pituitary tissue is suppression of the TSH. Thus, secretion of TSH, and its circulating level, are extremely low.

Unfortunately, most physicians become alarmed when they measure the TSH level in such a patient and find it extremely low. Physicians have been taught that a low TSH level means only one thing in a patient taking thyroid hormone--the dosage is too high and is going to harm the patient. It will take some years for physicians to learn about peripheral resistance to thyroid hormone and to understand the odd test values these patients have when taking effective dosages of thyroid hormone. Patients with peripheral resistance must take TSH-suppressing dosages of thyroid hormone to have normal peripheral tissue metabolism. But there is nothing whatsoever harmful to these patients in having their TSH suppressed by these dosages of thyroid hormone. In fact, it would be harmful for most of them not to take such dosages. The adverse consequences include conditions such as fibromyalgia, chronic fatigue syndrome, and liver and cardiovascular diseases.