Read this article in: Dutch
A Successful Approach to Underactive Thyroid Hormone Function
There is widespread dissatisfaction and frustration among people with underactive thyroid hormone function: The majority of them feel that their condition has been missed or that the treatment they are receiving has never really restored that function to normal or gotten their lives back to what they were before they became hypothyroid.2,3,4,5,6 This occurs despite the fact that the endocrinologists and thyroidologists who drive the teaching and treatment of this condition are intelligent people with many years of education and training in medicine, thyroid hormone function and the treatment of thyroid diseases.7
They even admit that this tragic situation exists but are, for various reasons, unable to re-think their approach sufficiently to effect the necessary changes in patient outcomes. We will try to ascertain what some of those reasons are and show that hypothyroidism can be treated satisfactorily, but the protocol is a well kept secret. This is a tragic situation because thyroid hormone function is extremely important for the metabolism of every cell in the body, including the brain, and people in whom this function is low suffer myriad possible negative consequences. These include elevated cholesterol14 and homocysteine levels and increased incidence of heart attacks,24 strokes, and peripheral vascular disease. Other adverse effects include infertility and miscarriages; low sex drive; impotence and erectile dysfunction;25,26 high blood pressure; physical and mental fatigue, sluggishness and apathy; lack of ambition and drive; abnormal weight gain and obesity; very dry skin, brittle nails and hair loss; constipation, often severe, with impaction; depression and mood swings; anxiety, memory loss, dementia and “Alzheimer’s”; cold-intolerance; insomnia; increased susceptibility to infections and possibly cancer, especially breast cancer; muscle and joint pains; digestive problems; increased allergies and rashes; personality issues; even lack of leadership ability.
The biggest losers in this neglectful situation are cardiovascular, infertile, elderly, memory loss, mood-disordered, chronically fatigued, insomniac and overweight patients.
An indication of the level to which hypothyroidism is underdiagnosed and undertreated, is revealed by the fact that I have never had to prescribe a statin drug to normalize anyone’s cholesterol, triglyceride or other lipid blood levels. I am treating them not with another drug, but with what they really need: optimal blood levels of the thyroid hormone(s) which they are lacking!
The Basics of Thyroid Physiology7
The thyroid gland is a butterfly-shaped gland that straddles the front of the windpipe and voice-box and that can be palpated (felt) with the fingers, especially if it is enlarged or has nodules or tumors in it. It secretes two main thyroid hormones into the blood stream, all the available L-Thyroxine (T4) and about 10 percent of the necessary Tri-Iodo-Thyronine or Lio-Thyronine (T3). These are manufactured in the gland from one molecule of the amino acid tyrosine and iodine—four iodine atoms per tyrosine molecule in the case of T4, and three iodine atoms in the case of T3.
Several minerals and other nutrients are also involved, in a supportive way, in the manufacture of these two thyroid hormones, so it pays to optimize their blood levels as well. These are iodine, of course, along with selenium, zinc and magnesium. Vitamin A is essential for production of thyroid hormone. Mercury, chlorine/chloride, fluorine/fluoride, perchlorate toxicity and excess copper—and even normal therapeutic levels of the mineral lithium-are known to decrease T4 and, especially, T3 levels. Therefore, the physician should do a blood test for these levels if there is any suspicion that these levels may be elevated (such as many silver fillings or high deep-sea fish consumption in the case of mercury; or living in a home with copper plumbing and no water-filtration system in the case of copper). Even certain foods such as soy and cabbage can reduce thyroid function. It seems that genetically modified soy is especially goitrogenic.
Only T3 is really active as thyroid hormone, T4 being a pre-hormone or pro-hormone which has to be converted, that is, de-iodinated to form the remaining necessary T3 in the tissues and cells before thyroid function can ensue. Brain cells may initially need to receive a good proportion of their supplies of thyroid hormones in the form of T4, before it is converted to T3 inside the cells of the brain, spinal cord and peripheral nerves, partly because T4 passes more readily through the choroid plexus (the “blood-brain barrier”) into the cerebrospinal fluid. But most T3 is present in the blood stream. The level of free or unbound T3—meaning unbound to serum proteins—by the accurate tracer-dialysis-method blood test, corresponds well to its function inside the tissues and cells of the body and brain.2
When the thyroid gland does not produce enough thyroid hormones (mostly T4, and some T3), a feedback mechanism in the pituitary gland (situated in a bony cage at the base of the skull) comes into play. This causes the pituitary gland to secrete increasing amounts of thyroid stimulating hormone (TSH or thyrotropin), which, as its name implies, stimulates the thyroid gland to produce more T4 and T3 hormones. There is also another endocrine organ, the hypothalamus, in the base of the brain, immediately above the pituitary gland, which can either stimulate or suppress the function of the pituitary gland in relation to thyroid function by the increased or decreased action of its thyrotropin-releasing hormone (TRH).
When all these types of hypothyroidism (thyroid underactivity) are taken into account (see sidebar below), my estimation is that 20 percent of the adult U.S. population suffers from some degree of hypothyroidism. This prevalence increases after middle age and into old age.
In practice, any combination of two or more of these types of hypothyroidism can occur simultaneously, confusing the diagnosis and the perception of the degree of hypothyroidism significantly. There does not need to be a known pathology in any of these glands or body tissues for the function of that gland or hormone to be compromised and leave the patient with the “bottom line” of low thyroid hormone function, as indicated by a low serum free-T3 level (especially when measured by the tracer-dialysis method, the only consistently accurate method). Much too often, when there is no known pathology in the pituitary or hypothalamus, and no definite chronic disease diagnosis, it is assumed that only primary hypothyroidism needs to be screened (and often only with a TSH test, the most likely test to be abnormal if only primary hypothyroidism is present).
The conventional approach to screening for, diagnosing, and treating hypothyroidism is to measure the TSH level only, or occasionally the T4 if the TSH level is “abnormal” according to an older, higher “normal range.” The usual treatment is T4 only, which physicians assume will always convert sufficiently into the active hormone, T3. In conventional treatment the T3 level is rarely if ever be measured, especially using new, more accurate methods. No wonder that most patients are dissatisfied with their treatment of hypothyroidism!
The only way to be sure that no form of hypothyroidism is present, when the patient exhibits suspicious symptoms of hypothyroidism, is to always measure the free-T3 serum level (preferably by the new, more accurate dialysis method) and the free-T4 level, in addition to the TSH level. When a low free-T3 level is not suspected or measured for, it will not be found, reinforcing the perception that low T3 levels, without abnormal T4 and TSH levels, are rare or insignificant. If the FT3 level is always measured, whenever thyroid function is tested, it will be found that a low T3 level is a common condition, leading to a lot of illness and death, while the patient is told that their thyroid function is normal (just because the TSH level, and perhaps a T4 level, is normal).9,10,11,12
Two Reasons for Timidity in Treating Thyroid Underactivity Optimally
The two commonly known negative effects of treating hypothyroidism with too much thyroid hormone are cardiac arrhythmias (dangerous irregular or rapid heartbeats) and osteoporosis (thinning and fragility of the bones). However, most such thyroid-induced incidents occurred at a time when it was the accepted treatment to push for supra-physiologic (above-normal) blood levels of T4 in order to obtain optimal thyroid function. It was only when a more sensitive TSH test was developed, which showed severe suppression of the TSH level in such patients, that practitioners realized that too much thyroid hormone may have been prescribed in many of these patients. The only way to be sure, in each individual case, would have been to obtain the free-T3 serum levels, which were not done in the reported cases!
So we have no way of knowing how many of those patients were really over-prescribed or how many had suppressed TSH levels for other reasons. Of course, those who developed cardiac arrhythmias and/or osteoporosis could have been over-prescribed thyroid hormones, although there are other causes of these conditions, such as deficiencies in minerals, vitamins, protein and other hormones, which are too often automatically “blamed” on excessive thyroid function instead.
In my opinion, fears of precipitating or aggravating osteoporosis are unwarranted. Evidence for these fears is equivocal as both natural and iatrogenic (treatment-caused) hypo- and hyperthyroidism may cause the condition.13 Apparently, under-treatment of either thyroid state is a risk factor as well. The objections about aggressive thyroid treatment causing or aggravating osteoporosis and cardiac arrhythmias are found (in my practice) not only to be overblown, but to be entirely non-existent when optimal corrections are made for certain mineral, vitamin, protein and sex- and growth-hormonal deficiencies.
If one always measures the free-T3 level, without any doses of the T3-containing prescription being missed in the 24 hours prior to the drawing of the blood, and the level is never too high for that patient’s age and medical condition, one can be certain that one is not contributing to cardiac arrhythmias and osteoporosis by over-prescribing thyroid hormones. But, if one hardly ever measures the FT3 level, and relies excessively on diagnosis based on the TSH level, one can easily assume that a suppressed or very low TSH level automatically means that either the patient is being over-treated with thyroid hormone or doesn’t need treatment at all, when low TSH levels may actually indicate pituitary or hypothalamic underfunction. The dose of thyroid hormone is then unnecessarily reduced, or the patient doesn’t get any at all, and the patient now suffers from what will be suboptimal thyroid function and inadequately treated thyroid underactivity, with all the attendant negative effects, including heart attack, stroke, peripheral vascular disease and premature death. T3 is more effective than T4 in lowering excess lipid levels and in decreasing the risk of coronary and cerebral arterial occlusion, even in patients who are merely slightly hypothyroid.14
Another reason physicians blame “overtreatment with thyroid hormone” for cardiac arrhythmias and osteoporosis or osteopenia is due to the fact that physicians do not use the more accurate blood tests for measuring magnesium, potassium and calcium, tests that reflect their true levels in the tissues and cells that they influence. The tests physicians normally use measure serum levels of magnesium and potassium but do not reflect their intracellular activity, which is where they exert their effects. Levels of magnesium, potassium and calcium in the red blood cells should be obtained, which do reflect their levels in the cells of the muscles and other tissues where they influence the neuromuscular activities of those tissues—heart and skeletal muscles being particularly pertinent, the former for cardiac arrhythmias and the latter for muscle cramps, spasms and “charley horses.” Consequently most physicians are at a loss to treat the latter as well, and often resort to quinine or drugs to stop this symptom artificially.
When the intracellular/red blood cell levels of magnesium and potassium are obtained, the physician realizes that many more people are deficient in these two anions – and much more severely so—than when the serum levels are measured. When these deficiencies are then taken care of, with large prescription doses of these minerals, patients are far less likely to respond negatively to high, or even high-normal, blood levels of thyroid hormones.
Similarly, the total serum calcium level is not a true reflection of the activity of calcium in the nerves, muscles and bones. It is the ionized calcium level that needs to be obtained. This level actually shows that more people are now running calcium levels that are too high, contributing to heart attacks, kidney stones, joint and tendon problems, etc., and that there is too much public emphasis on the need for calcium in most people.
Over-Reliance on TSH Levels
I kid you not: TSH is regarded as the most accurate measure of thyroid function simply because the test itself is very accurate for what it measures: The thyroid stimulating hormone is not a thyroid hormone and its level in the blood is an indirect test of thyroid function, influenced by many factors other than the amount of the thyroid hormone levels in the blood! It is assumed that because the TSH test is an accurate test for the substance that it measures, that it is an accurate gauge of thyroid function! As I said, the people making this judgment are intelligent people; I can only assume they have a mental blind spot about this.
The other issue about the TSH test is the long time that it is taking most physicians, laboratories and medical journals to accept the newly recommended range of 0.3-2.5 as normal, which was set by the National Academy of Clinical Biochemistry (NACB), back in September 2002.15 Before that, the normal range was considered to be 0.40-5.00, based on a cohort of only twenty-seven hospital workers in Edinburgh, Scotland, set by Professor Anthony Toft, the lead researcher of that study. There was no evidence that this cohort of study subjects completely excluded anyone with mild hypothyroidism.
Based on several epidemiological studies showing that TSH levels above 2.5 mU/L were not normal, the hundreds of thyroid and lab experts from around the world who make up the NACB concluded that, rather than 0.45-4.5 or 5.0, the new range should be considered as 0.3-2.5. And of course this range only applies when there is a question of primary hypothyroidism on its own.
If there is any element of secondary, tertiary or non-thyroidal-illness (NTI) hypothyroidism present, then the normal range cannot be any higher than 0.01-1.00, in my opinion. In practice this is the range that I aim for in most of my treated cases of hypothyroidism, while keeping the FT4 and FT3 levels optimal for their age and medical condition—most often high-normal but scaled down from that to the mid-range or even slightly below that in frail, cardiac or very elderly patients.
In January 2003, the American Association of Clinical Endocrinologists suggested the range should be 0.40-3.04 and said that this lower range would now mean that 13 million more Americans would be treated for hypothyroidism annually. A year or two later, Carol Spencer, one of the top researchers of the Endocrine Society, and its reigning president at the time, Leonard Wartofsky, MD, MPH, suggested a range of 0.3-2.0 —which I had been using since I started treating hypothyroidism in 1989! Unfortunately, to this day, the labs and most treating physicians are still using the old, higher range. It should never be forgotten that these ranges apply only for the diagnosis of purely primary hypothyroidism. The range drops significantly for the other types, alone or in combination with primary hypothyroidism.
As a psychiatrist, I had already learned the importance of good thyroid function in mood disorders,11,16,17,18 memory loss and other mental conditions, even psychoses.19 It is known that depressed patients with low T3 levels cannot be helped to come out of their depressions by any means, including electroshock therapy, unless the T3 level is at least normalized, if not optimized to the high end of its normal range. This was a very important lesson to me. Also, several psychiatric researchers, including two of my teachers at the University of Toronto,16 proved that bipolar-disordered patients do much better when their T4 level is optimized to the high end of its normal range, or even slightly above its high end. And one of the best treatments for bipolar disorders, the mineral lithium, is known to lower thyroid function, especially the T3 function. T3 must be “watched like a hawk” during lithium treatment, and optimized if low.28 Depakote, and other anti-epileptic drugs used in the treatment of bipolar disorders also lower the T3 function in most patients, so the same advice applies.
“Alternative” Approaches to Hypothyroidism
Before the more accurate dialysis-method tests for Free-T3 and FT4 became available, Broda Barnes recommended a body temperature-measuring approach that could give some indication of possible thyroid hypo-function, though this is a non-specific approach; hypothyroidism, though the most common, is not the only cause of hypothermia. Temperature measuring was a useful tool at the time and may have enabled many cases that were missed by the blood testing measurements of the day to receive treatment, but now that we have the totally accurate dialysis Free-T3 and Free-T4 blood tests, there is much less need for that approach, except as an indicator to lay persons that they may be hypothyroid and should be investigated further for that possibility.
Since the early 1990s, Dennis Wilson, an MD in Florida, has been advocating a T3-only approach to the treatment of fatigue and low body temperatures that has been helpful in some patients.6 But it is puzzling as to why he should eschew T4 treatment altogether, especially since T3-only treatment lowers the T4 level to below or at the low-normal blood level and, as we know, the brain requires a good blood level of T4 to ensure sufficient crossing of the chronoid plexus (blood-brain barrier) by sufficient T4 for conversion to T3 in the brain cells. My suspicion is that many of Wilson’s patients, while attaining good physical thyroid function, remain deficient in the brain’s thyroid function for memory and mood.
More recently, John Lowe, DC, has come to the fore, through published articles,4 as an advocate of T3 treatment for chronic fatigue syndrome and fibromyalgia in patients with normal thyroid function, because of what he regards as thyroid resistance in the tissues of these patients. He does use and advocate T4 and T3 combination therapy in all hypothyroid patients.
In general, it can be said that most nutritional, integrative, wholistic, complementary, natural-medicine, anti-aging and alternative physicians are using the T4-T3 combination approach,20,5 rather than the T4-only approach that is still stubbornly used and recommended by most conventional physicians. I have some questions as to how diligently and regularly they are using the accurate blood tests mentioned above but I have no doubt, based on their reported outcomes, that in general their hypothyroid patients are doing much better than those of the conventional physicians. That is quite a lot to say, considering that most of them are not endocrinologists or even internists, supposedly those medical specialists who have board certifications in, and are in charge of, the diagnosis and treatment of thyroid conditions.
Even more unfortunate than the T4-only conventional approach is the fact that the specific brand usually recommended and prescribed is Synthroid. In the 1990s, the company manufacturing Synthroid commissioned University of California at the San Francisco Medical School to carry out tests on the biological consistency of the product and publish the results on the three sales-leading T4 brands at that time, Synthroid, Levoxyl, and Levothroid. It would appear that Boots, Synthroid’s manufacturer, was so confident that Synthroid would come out on top they were willing to pay for this research. However, when Synthroid only came in third, it turned out that they had not been so confident, business-wise, that they had not made sure to include a clause in the contract with UCSF stipulating that Boots would have the final say-so over publication of the article! The Journal of the American Medical Association (JAMA) accepted the article for publication but Boots put the kibosh on its printing!
Six years later, the Wall Street Journal published this scandalous story and Boots was forced to go ahead and allow the publication of the article. But to this day, due to physician loyalty from years of “wining and dining,” Synthroid is still one of the top two thyroxine (T4) products in sales in the U.S., despite costing a lot more. The other top seller now is Levoxyl, which won the three-way comparison test. This story is one egregious example of the business collaboration between pharmaceutical companies, on the one hand, and physicians, medical journals and medical schools, on the other, which is in place to serve the interests of these three powerful parties at the expense of the patients and the public.
The series of companies that have owned the Synthroid brand at various times (Boots, Knowles and now Abbott Labs) has also been heavily involved in the campaign to get T4-only as the only accepted treatment for all forms of hypothyroidism, despite the fact that (1) the thyroid gland produces T3 as well as T4; (2) patients on T3 and T4 do better and are much more satisfied with their treatment; and (3) three, out of the four types of hypothyroidism clearly require T3 as well as T4, in their treatment; and (4) there is not one shred of evidence that T4/T3 combination treatment – the only, and very successful, type of treatment for hypothyroidism during the first 60 years of this therapy (in the form of desiccated animal thyroid tissue)—has any disadvantages when its use is understood and its monitoring is accurate. The companies making the other two brand names, Levoxyl (King Pharmaceuticals, which also makes Cytomel, the leading T3-only brand) and Levothroid (Forest, which also makes Armour Thyroid and Thyrolar, the natural and synthetic, respectively, T4/T3 combo products), are not involved in the T4-only campaign as they have diversified their portfolios to include T3-containing products. These have been both scientifically and commercially beneficial decisions on their part. The T4-only campaign has been almost totally successful in keeping T3 and T4/T3 combo products out of many other countries, including Australia, Israel and Spain (despite the Escobar-Morreale research team in Madrid, which showed that the addition of T3 to the T4 treatment was necessary to restore to normal the brain function of rats whose thyroid glands had been removed or destroyed).21
In spite of the fact that neither Boots nor Knowles is in business any longer (at least under those names), due to public outcry, the medical profession is still largely in the Synthroid camp with regard to brand names—and has even allowed its scientific judgment to be skewed on the issue of T4-only treatment by this pharma industry giant.
When I first started treating hypothyroidism, in 1989, there were several very bad generic products on the market that produced inferior results and blood levels. That is no longer the case. This is one area where some praise for the FDA is in order, though they went overboard in banning Euthroid—and may go overboard again, in a much worse way, banning all non-T4-only products, if Sidney Wolfe, MD, the misguided Public Citizen advocate, attains a high enough position in it to impose his view on the organization.
Pushing the T4-Only Approach to Treatment
Toward the end of 2003 a rash of papers appeared in the October issue of the Journal of Clinical Endocrinology and Metabolism, along with an editorial by Kaplan and others,31 and an article in the December issue of the Journal of the American Medical Association,32 showing that the substitution of T3 for some of the T4 in T4-only-treated hypothyroid patients produced no benefit. However, these study patients’ T3 and T4 serum levels were even less optimized than those of the 33 patients in a 1999 paper by Bunevicius and others, published in the New England Journal of Medicine, which had found significant benefits33 – and which these newer papers were obviously intended to counteract. In addition, the patients in the 1999 study often ended up on a lower total daily intake of thyroid hormone (T3 and T4 combined) was their treatment.
Using patients with suboptimized serum T3 and T4 levels is no way to try to prove the futility of T3 treatment—not only for primary hypothyroidism patients but even less so for patients who have one of the other types of hypothyroidism, either as the sole cause of their hypothyroidism or as an additional cause of their total hypothyroid picture. There is no way to justify withholding the addition of T3 to secondary, tertiary and NTI hypothyroidism patients, because in them the T3 is the lower of the two thyroid hormones.
In these latter types of hypothyroidism there is a strong tendency for the free T3 level (determined by the dialysis method) to lag behind the dialysis free T4 level (determined by the dialysis method). This is partly because of the lack of TSH (which drives the conversion of T4 to T3), but may also be due to peripheral interference with the 5′-deiodinase enzyme’s conversion/deiodination of T4 to T3, which occurs in NTI hypothyroidism. It is telling that the Kaplan editorial indicated a marked note of despair that an ideal treatment for all the symptoms of hypothyroidism will ever be found! Considering the flawed assumption on which the editorial and the articles were based, it is not at all surprising to me that optimal treatment is an elusive goal to these researchers and opinion-makers!
If practitioners would simply switch their focus from “optimizing” TSH to truly optimizing the dialysis-tested free T3 and free T4 serum levels, they would achieve, as I have, this laudable goal in virtually all their patients!
Fortunately, the pendulum has already started to swing back toward evidence for the efficacy of the addition of T3 to T4 treatment. In 2002, an “old guard” resister of the combination approach, the same Anthony Toft who originally set the “normal range” for TSH, recanted and expressed openness to the idea that, at least in some patients, the addition of T3 to T4 treatment may well be beneficial and may be the only way to optimize thyroid function. He said: “It would appear that the treatment of hypothyroidism is about to come full circle.”27 Other researchers followed. We see this in two articles published in the first half of 2005, one by Sararvanan and others published in the February issue of the Journal of Clinical Endocrinology and Metabolism and involving 697 primary hypothyroid patients,30 and the other by Appelhof and others published in the May issue of the same journal and involving 141 primary hypothyroid patients.29 The Appelhof paper compared the outcomes for two different ratios of T4 to T3; 5:1 and 10:1. It is notable that the patients receiving the higher amounts of T3 reported the most satisfaction with their results, especially in weight loss.
Unfortunately, both studies were still operating under the flawed assumption that whatever amount of T3 was added to any patient’s treatment, an equivalent amount of T4 had to be subtracted. Using my approach, the T4 dosage would have been increased in many patients due to its level still being suboptimal prior to the addition of T3 being added. Because of the feedback loop in which a high T3 level would suppress the TSH level, which would then cause the T4 level to drop because of less stimulation by TSH, the addition of T3 would have actually lowered the total amount of T4 in the blood stream, thus requiring additional amounts of T4. On the increased intake of T4 and the addition of T3, these patients would have really experienced improved thyroid function and physical and mental well-being, and not just the minimal improvements noted in these articles.
Optimal treatment should not revolve on answering the question, “What is the best type of thyroid medication to use?” The best approach, one I have used very successfully since 1989 in over 5,000 patients,22 does not advocate any one prescription medication for all cases but has the goal of optimizing the free serum levels of both the T3 and T4 thyroid hormones (measured by the dialysis methods). The physician should use in treatment whatever combination of both thyroid hormones produces this result. (In a minority of cases, this will be T4 alone.) This is true regardless of whether the treatment results in a TSH level below its normal range. If such a result occurs, it simply means that the patient’s TSH feedback loop is not functioning properly, or else it would not be suppressed below normal when the T4 and T3 thyroid hormone levels are not elevated.
Unless the FT3 level in a new case is significantly higher than the FT4 level, it is not optimally helpful to treat with T4-only replacement. If the patient has a high TSH level (TSH drives T4-to-T3 conversion) and still cannot directly produce enough T3 from his or her thyroid gland and from the conversion of T4 to T3 peripherally, then that patient will not convert enough T3 from T4-only treatment after the TSH level drops.
The conventional approach to the treatment of hypothyroidism assumes that T4-only preparations convert peripherally to T3 in fairly standard amounts and at fairly standard rates. If that does not occur, it is considered to be because of extrathyroidal illness “which is of no concern to the physician charged with correcting thyroid dysfunction.” But, the clinical experience of always measuring free T3 and free T4 serum levels shows that this assumed scenario is not true for the majority of patients. At least 80 percent of my patients have required some T3 in treatment (always prescribed for two or three times per day), in addition to T4, for their free T3 and free T4 serum levels to be optimized.
Consistent measuring of both the FT3 and FT4 blood levels in all hypothyroid patients who are on T4-only therapy will very rapidly dispel the myth of adequate conversion (as well as the myth of “purely extra-thyroidal causes” of low T3 levels). A certain minority of hypothyroid patients do convert enough T4 to T3 at a sufficient rate for T4-only treatment to be effective in producing an adequate FT3 serum level. However, as stated above, the majority (80 percent) of patients require some combination of T3 and T4 to optimize FT3 and FT4 levels. Once these levels are optimized, the patient’s health and performance improve.
Optimizing both the FT3 and FT4 levels usually requires one of the following: (1) a combined T4/T3 preparation; (2) separate T4 and T3 preparations; or (3) a combination of T4 and T4/T3 preparation. Desiccated whole hog thyroid (such as Armour Thyroid or one of its generics, like Naturethroid) is a good, relatively inexpensive starting point for the fixed combination T4/T3 treatment. Since it contains the short-acting T3 hormone, it should always be prescribed to be taken after breakfast and supper (in the twice-daily regimen) to reduce the rapidity of onset and prolong the duration of its action.
The major shift in thinking for most physicians is to recognize that desiccated thyroid hormone should be taken not just once a day, but at least twice daily after meals. An alternative would be dosages taken three times daily (every eight hours) without regard to meal times. If desiccated thyroid alone does not optimize both hormones’ free levels, additional T4 (or, less often, T3) treatment can be added in order to achieve the goal. If synthetic thyroid hormones are used exclusively, an estimated amount of T4 would be taken once daily along with an estimated amount of T3 to be taken twice daily, after breakfast and supper (or as described above, every eight hours without regard to meal times). Thyrolar is a synthetic T4/T3 combo preparation, with T4 and T3 in the same ratios as that of desiccated pig thyroid extract; it should also be taken two to three times per day because of the short half-life of the T3 component.
Once optimal T3 and T4 hormone replacement has been achieved, the ultra-sensitive TSH remains useful as a gauge of optimal thyroid function only if it is still in the low end of its normal range, or it may go below the low end of the range (down to 0.01 mU/L). If this occurs, thyroid function will have been optimized by the yardstick of both the TSH level and the dialysis tested FT3 and FT4 levels.
As one who has both a personal and a perfectionist interest in optimal thyroid function rather than “normal” function, my view is that the only satisfactory optimization is the one just described. It remains to be decided, in certain rare cases in which the TSH needs to be suppressed below 0.01 mU/L for the dialysis FT3 and FT4 levels to be optimized, whether to accept suboptimal free T3 and free T4 levels or a sub-0.01 mU/L TSH level. My own preference would be for the latter, except in frail or cardiacarrhythmic patients.
A small number of large or overweight thyroid hormone-resistant patients, usually women, may need up to 6-9 grains of Armour Thyroid per day (or the equivalent of thyroxine, counting 0.1 mg of T4 as equivalent to 1 grain); or a combination of the two. These patients seem to represent some form of thyroid hormone resistance syndrome, as described by Refetoff.23
Patients who already take Armour Thyroid (or one of its generic equivalents) in once per day dosages should be advised to split their doses immediately, according to the twice- to thrice-daily regimen described in several sections above. Then, the Free-T3 levels obtained in blood monitoring of the treatment would be much more meaningful in terms of the all-important T3 fraction of the thyroid function.
The Types of Hypothyroidism7
PRIMARY HYPOTHYROIDISM: This occurs when the primary problem is in the thyroid gland itself, which does not produce sufficient T4 and T3 to drive the metabolism of the cells of the body and brain. The feedback mechanism with the pituitary gland then kicks in—if the pituitary and hypothalamus are functioning properly—causing increased secretion into the blood stream of TSH, with blood level rising above its normal range. This mechanism may be sufficient, at least at first, to keep the levels of T4 and T3 in the blood high enough, at least by day, to be in their normal ranges. At night, when all functions diminish, including pituitary function, T4 and/ or T3 levels may drop below their normal ranges and all the metabolic functions that depend on the thyroid hormones may not occur adequately at night. The most common cause of primary hypothyroidism is autoimmune (Hashimoto’s) thyroiditis, an autoimmune disease in which the immune system attacks the thyroid tissue, usually causing it to become underactive. Occasionally the opposite occurs and overactive thyroid function, hyperthyroidism, or Graves’ disease is the result.
SECONDARY (OR PITUITARY) HYPOTHYROIDISM: This occurs when there is no problem within the thyroid gland itself but the pituitary gland, from which the thyroid gland expects a normal amount of TSH in order to produce a normal amount of T4 and T3 hormones, does not secrete adequate amounts of TSH. In this scenario, the free T4 and T3 serum levels will be below normal and the TSH level will be below or at the low end of its normal range. The thyrotropin-releasing hormone (TRH) level, if tested, would show an increase but is ineffective in raising the TSH level from the malfunctioning pituitary gland.
TERTIARY, CENTRAL OR HYPOTHALAMIC HYPOTHYROIDISM: This occurs when there is no malfunction within the thyroid or pituitary glands but there is inadequate secretion of TRH by the hypothalamus to keep the pituitary gland secreting enough TSH to produce enough T4 and T3 from the thyroid gland. This can occur in depression. T4, T3, TSH and TRH levels would all be low, and the thyroid functional level would be determined by the free T3 level (preferably by the dialysis method).
NON-THYROIDAL-ILLNESS (NTI) HYPOTHYROIDISM: This occurs when there is no problem in the thyroid, pituitary or hypothalamic glands but another illness in the body that interferes with the peripheral or tissue conversion of T4 into T3. T4, TSH and TRH levels are all normal but the serum free-T3 level, depicting the only active thyroid hormone level, is low. In an acute cardiac or pulmonary or other life-threatening condition, it may be temporarily advantageous for the body’s metabolism to be slowed by a low circulating level of free T3, so T3 treatment may not be indicated at that point. But, when chronic, non-life-threatening conditions, like chronic fatigue syndrome, chronic liver and other diseases, cause a low free T3 serum level, there is no advantage to the body and brain’s metabolism being slowed and T3—or combination T4/ T3 treatment—is usually not only beneficial but even essential in restoring normal energy and function to that person’s body and brain tissues.8
Some Reasons Why T3 Is Not Measured and Prescribed Much More Often
Much of the reason has to do with the physiology of the T3 hormone versus the T4 hormone.7 Whereas T4 is long-acting, with a half-life of a week, T3 is short-acting, with a half-life of 8-12 hours, depending on whether it is taken on an empty stomach or after meals. So T4 produces a more stable and consistent blood level; a blood test showing a certain T4 level can be relied upon to stay relatively stable, no matter when it is measured. However, I have found, over a 20-year time-period, in over 5,000 patients, that the free-T3 level does not fluctuate as much as is commonly believed. Also, it is important to understand the dynamics of testing in relation to the previous couple of doses of T3-containing thyroid hormone preparation.
If one or two doses of T4 are missed, the blood level will not be much different than if those doses had been taken. But if one, and even more so, if two doses of a T3-containing preparation are missed in the 24 hours prior to the blood draw, the blood level could be extremely low, indicating the patient needs a lot more T3 when in fact the level may have been normal, even optimal, while they were taking the prescribed doses regularly. It is lack of knowledge and sensitivity to the wide fluctuations in the serum level of T3, depending on the timing of doses and blood draws, that has led to the fear that endocrinologists have for using T3 and/ or T4/T3 combination preparations. One T4/T3 combo, Euthroid, an excellent product in my opinion, was even taken off the market by the FDA some years ago because physicians did not know how to take into account the time at which their measurements of the T3 hormone should be done in relation to the last 2 doses, in patients taking this product.
Secondly, the T3 level is affected by non-thyroidal factors such as stress, other diseases, several metal/mineral levels (such as lithium, mercury, copper and aluminum), the patient’s degree of arousal and activity, etc. It is wrong to assume that if T3 is low only because of another disease or non-thyroidal factor, then it is not the concern of the endocrinologist but of the specialist covering the other disease or factor! And rarely is it ever communicated to the other specialist that “their disease or factor” is lowering the patient’s thyroid function, or what might be done to remedy the low T3 level. Endocrinologists and internists need to accept responsibility for their patient’s thyroid function as measured in the FT3 level, and not just the apparent normality or abnormality of the thyroid, pituitary and hypothalamus glands.
Lastly, for many years, available blood tests for the T3 hormone were not as accurate as those for T4 or TSH level. In the past 10-15 years, the tracer-dialysis method for measuring T3 has been available, although it costs 8-10 times as much as the non-dialysis test. Because it is so crucial to ascertain exact thyroid function, there is no excuse for not having this accurate test performed; it is not at all expensive when compared to many other tests that are run much more commonly, such as MRIs and CAT Scans. It only costs about $80 and is covered by health insurance. Instead of getting this crucial information, many physicians still have these concepts of unreliability and expense in their heads and they are foregoing the accurate measurement of the crucial T3 level, which depicts the actual level of thyroid function.
Dennis Wilson, MD, was a practicing physician in Longwood, Florida in the ealry 1990s who noticed that many fatigued and low-body-temperature patients had low T3 levels (often with normal T4 and TSH levels). Instead of realizing that these were patients with the three other types of hypothyroidism than primary hypothyroidism, he proposed a new syndrome, which he called Wilson’s Syndrome (a name that had already been taken by a metabolic disease in which there is the accumulation of too much copper in parts of the eyes, liver and blood stream). His treatment, instead of a combination of T4 and T3 (so that the T4 level can be maintained as a source of newly-converted T3, when necessary, especially for the brain) was to prescribe high doses of T3 only. This treatment takes care of most of the physical needs of patients, in regard to thyroid function, but tends to leave their cognitive and other brain functions neglected. I don’t see any benefit in leaving out T4 altogether, especially as it is already the “junior partner” in the desiccated thyroid and Thyrolar preparations (which raise the T3 level more than the T4 level).
Serious Thoughts About Iodine
It is well known that the original cause of most cases of hypothyroidism was iodine deficiency.7 In an effort to deal with that issue in a cost-effective manner, public health officials called for the substitution of iodized salt for non-iodized salt on all our grocery store shelves. This measure has taken the edge off the iodine deficiency problems of yesteryear—although not by any means completely, as good measurements of both organic and inorganic iodine levels in patients’ blood or urine would show. But has anyone in thyroidology stopped to recognize the fact that we have actually substituted many more cases of autoimmune thyroiditis and primary hypothyroidism for the relatively fewer cases of iodine deficiency hypothyroidism that existed previously?
Could the mechanism for this phenomenon be that we used the wrong form of iodine—inorganic instead of organic— as a food supplement, and that this harsh form of iodine actually damages the thyroid tissue enough to trigger our immune systems to react against it? I believe this is a question that, at the very least, deserves serious consideration and investigation. I have laid out this case to physicians and researchers who have focused on iodine deficiency, and who recommend taking Lugol’s liquid iodine or Iodoral tablets—which contains inorganic potassium iodide as well as organic iodine—but none of them has responded. Iodide is inorganic and harsh, burning flesh and other living matter with which it comes into contact; iodine is organic and gentle, usually cushioned or bound to proteins or other organic matter, providing the benefits of iodine to living matter without the harsh burning interactive effect.
In the mean time, I am recommending that my patients forego the iodized salt on the shelves of their grocery stores and use genuine 80-mineral sea salt instead, which also tastes much better! And, if their organic iodine serum level is low (measured at Boston University’s Iodine Research Lab), to take 4-6 drops of organic iodine (such as Thyactin by TriMedica) after breakfast and supper daily (8-12 drops per day) rather than Lugol’s liquid iodine or Iodoral tablets.
A Summary of Thyroid Medications
|Chemical or Generic Name||Trade or Brand Names|
|L-Thyroxine/ Levo-Thyroxine/ T4||Levoxyl, Levothroid, Synthroid, Unithroid|
|Tri-Iodo-Thyronine/ Lio-Thyronine/ T3||Cytomel, Cynomel|
|T4/T3 Combination Medication||Thyrolar (in grains, analogous to the strengths of Desiccated Porcine Thyroid)|
|Chemical or Generic Name||Trade or Brand Names|
|Desiccated Porcine Thyroid Extract (USP)
(In Grains or Mg, 60mg = 1grain)
|Armour Thyroid, the original, now by Forest,
Westhroid (both by Western Research Labs)
Tests for Thyroid and Related Functions
|Free-Thyroxine (T4), by Direct Dialysis method||0.8-2.7ng/dL||The only accurate T4 level|
|Free Triiodothyronine (T3), by Tracer Dialysis||2.3-5.2ng/dL||The only accurate T3 level
and the only true measure of thyroid function
|Thyroid Stimulating Hormone (TSH) serum level||0.3-2.5 mIU/L||A relative or indirect test,
not definitive of thyroid function.
|Total Thyroxine (T4) serum level||4.0-12.0ug/dL||Inaccurate test of pre-hormone|
|Free-Thyroxine (T4), non-dialysis method||0.7-1.8ng/dL||Less accurate than dialysis test|
|Total Tri-Iodo-Thyronine (T3) serum level||100-240ng/dL||Inaccurate test for T3 activity|
|Free Triiodothyronine (T3), Non-dialysis method||2.3-5.2ng/dL||Less accurate than dialysis test|
|T3 Resin Uptake||25-39%||Primitive, inaccurate T3 test|
|T7 or Free Thyroxine Index/ FTI (T3U x T4 level)||1.0-4.0||Slightly better than T3U test|
|Microsomal TPO Antibodies Titer||<35 units=”" td=”">|
|Organic (Protein-bound) Iodine level||8.0-16.0||The only level that is necessary|
|Inorganic Iodide level||1.0-4.0||Valuable if too high, indication to avoid inorganic iodine (iodide)|
|Total Iodine level||9.0-20.0||Mixed conglomeration of the 2|
|Selenium serum level||140-280||Normal level needed|
|Zinc level||70-150||Normal level needed|
|Copper level||70-150||Make sure not too high|
|Mercury level||<5 br=”">||Make sure not too high|
|Aluminum level||<7 br=”">||Make sure not too high|
Note: I treat metal and mineral toxicities with with oral chelation pills, available from supplement companies.
- Dommisse, J.V.: Hypothyroidism: Sensitive diagnosis and optimal treatment of all types and grades – A Comprehensive Hypothesis, based on a review of the standard and ‘alternative’ literature and extensive clinical experience. Thyroid Science 3(2):H1-14,2008,www.ThyroidScience.com/Hypotheses.
- Arem, R.: The Thyroid Solution: A Mind-Body Program for Beating Depression and Regaining Your Emotional and Physical Health. NewYork, Ballantine Books/ Random House, June 1999.
- Ridgway, E.C., Canaris, G., et al.: Thyroid disease often undiagnosed. Reuters Wire Service, New York, Oct. 1997. [Later published in a medical journal.]
- Lowe, J.C., Garrison, R.L., Reichman, A.J., et al.: Effectiveness and safety of T3 (triiodothyronine) therapy for euthyroid fibromyalgia: A double-blind placebo-controlled response-driven crossover study. Clin. Bull. Myofascial Ther.,2(2/3):31-57,1997.
- Shames, R.L. and Shames, K.H.: Thyroid Power. New York, Harper Resource, 2001.
- Wilson, D.: A Doctor’s Manual for Wilson’s Syndrome. Summerfield, FL (PO Box 539), The Wilson’s Syndrome Foundation, 1992.
- Braverman, L.E. and Utiger R.D., eds.: Werner and Ingbar’s ‘The Thyroid’: A Fundamental and Clinical Text, 8th ed.. Philadelphia, Lippincott Williams & Wilkins, 2000.
- DeGroot, L.J.: Dangerous dogmas in medicine: The nonthyroidal illness syndrome. J. Clin. Endocrinol. Metab., 84(1):151-164,1999.
- Dommisse, J.V.:T3 is at least as important as T4 in all cases of hypothyroidism. J.Clin. Psychi.,54(7):277-278, 1993
- Gelenberg, A.J.: T3+T4=success. Biological Therapies in Psychi. Nsltr., 15(4):14, 1992.
- Joffe, R., Blank, D.W., Post, R.M., and Uhde, W.: Decreased triiodothyronines (T3) in depression: A preliminary report. Biological Psychi., 20-922-925, 1985.
- Joffe, R.T. and Singer, W: A comparison of triiodothyronine (T3) and thyroxine (T4) in the potentiation of tricyclic antidepressants. Psychiatric Res., 32:241-251, 1990.
- Uzzan, B., Campos, J., Cucherat, M., et al.: Effects on bone mass of long-term treatment with thyroid hormones: A meta-analysis. J. Clin. Endocrinol. Metab., 81(12):4278-4289, 1996.
- Dullaart, R.P., vanDoormaal, J.J., Hoogenberg, K., and Sluiter, W.J.: T3 rapidly lowers plasma lipoprotein-A, apo-B and LDL-cholesterol in hypothyroid subjects. Neth. J. Med., 46(Apr):179-184, 1995.
- Devers, L.M., Spencer, C.A., and Cooper, D.S., eds.: Laboratory Medicine Practice Guidelines: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease. Washington, DC, National Academy of Clinical Biochemistry (www.nacb.org), Sept. 18, 2002.
- Stancer, H.C. and Persad, E.: Treatment of intractable rapid-cycling manic-depressive disorder with levothyroxine. Arch. Gen. Psychi., 39:311-312, 1982.
- Whybrow, P.C.: The therapeutic use of triiodothyronine (T3) and high-dose thyroxine (T4) in psychiatric disorder. Acta Medica Austriaca, 21(2):47-52, 1994.
- Cooke, R.G., Joffe, R.T., and Levitt, A.J.: T3 augmentation of antidepressant treatment in T4-replaced thyroid patients. J. Clin. Psychi. 53(1,Jan):16-18, 1992.
- Logothetis, J.: Psychotic behavior as the initial indicator of adult myxedema. J. Nerv. Ment. Dis., 136:561-568, 1963.
- Teitelbaum, J., Bird, B., Greenfield, R., et al.: Effective treatment of chronic fatigue syndrome (CFS) and fibromyalgia (FMS) – A randomized double-blind placebo-controlled intent-to-treat study. J. Chron. Fatigue Syn., 8:2, 2001.
- Escobar-Morreale, H.F., del Rey, F.E., Obregon, M.J., and de Escobar, G.M.: Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat. Endocrinology,137(6):2490-2502, 1996.
- Dommisse, J.V.: Unpublished clinical data, 1989-2008.
- Refetoff, S.: Thyroid hormone resistance syndromes. In Werner and Ingbar’s ‘The Thyroid’: A Fundamental and Clinical Text, 6th ed. Edited by L.E. Braverman and R.D. Utiger, Philadelphia, J.B. Lippincott, 1991, pp.1280-1294.
- LeMar, H.J., West, S.G., Garrett, C.R., et al.: Covert hypothyroidism presenting as a cardiovascular even. Am. J. Med., 91(Nov):549-552, 1991.
- Renshaw, D.C.: Therapeutic rounds: A case of primary impotence due to grade-2 hypothyroidism and a marginal free testosterone level in a 29-year-old man. Clin. Therapeutics, 7(3):309,390,1985
- Wortsman, J., Rosner, W., and Dufau, M.L.: Abnormal testicular function in men with primary hypothyroidism. Am. J. Med., 82(Feb):207-212, 1987.
- Toft, A.D.: T3/T4 combination therapy. Endocrine Abstracts, 3(April):S40, 2002.
- Dommisse, J.V.: Pseudotumor cerebri in two patients with lithium-induced hypothyroidism. J. Clin. Psychi., 52(5):239, 1991.
- Appelhof, B.C., Fliers, E., Wekking, E.M., Schene, A.H., Huyser, J., et al.: Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: A double-blind, randomized, controlled clinical trial. J. Clin. Endocrinol. Metab., 90(5):26662674, 2005.
- Saravanan, P., Simmons, D.J., Greenwood, R., Peters, T.J., and Dayan, C.M.: Partial substitution of thyroxine (T4) with tri-iodothyronine in patients on T4 replacement therapy: Results of a large community-based randomized controlled trial. J. Clin. Endocrinol. Metab., 90(2):805-812, 2005.
- Kaplan, M.M., Sarne, D.H., and Schneider, A.B.: In search of the impossible dream?: Thyroid hormone replacement therapy that treats all symptoms in all hypothyroid patients (Editorial). J. Clin. Endocrinol. Metab., 88:4540-4542, 2003.
- Clyde, P.W., Harari, A.E., Getka, E.J., and Mahamed Shakir, K.M.: Combined levothyroxine plus liothyronine compared with levothyroxine alone inprimary hypothyroidism: A randomized controlled trial. J.A.M.A., 290(Dec.):2952-2958, 2003.
- Bunevicius, R., Kazanavicius, G., Zalinkevicius, R., and Prange, A.J.: Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. New Eng. J. Med., 340:424-429, 1999.
This article appeared in Wise Traditions in Food, Farming and the Healing Arts, the quarterly journal of the Weston A. Price Foundation, Summer 2009.