Hypothyroidism: Sensitive diagnosis and optimal treatment (of all types and grades)
Hypothyroidism: Sensitive diagnosis and optimal treatment (of all types and grades)
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While overt hypothyroidism is easily diagnosed by physicians, the primary illness can be less apparent in its early or so-called subclinical stages (Ross, 1991a; Arem, 1999); and secondary and tertiary (Pinchera et al, 1991) and non-thyroidal illness/ euthyroid-sick syndrome (Palazzo & Suter, 1990; Chopra, 1997; DeGroot, 1999) hypothyroidism are also overlooked by the current conventional diagnostic approach, which frequently relies exclusively on the ultrasensitive serum thyroid stimulating hormone (TSH) level. It is important to recognize that the ultrasensitive TSH is an indirect test with a normal range that is useful for diagnosing grades 1 and 2 primary hypothyroidism only (see The Grades of Primary Hypothyroidism, below). In the United States, an FT4 level is sometimes obtained, and occasionally a total-T3 level, but an FT3 level, the only accurate indicator of this much-more-active hormones function, is rarely obtained.
Patients with subclinical hypothyroidism who have the qualifying proposed serum thyroid hormone profile discussed below, almost always have multiple classical symptoms and signs of hypothyroidism. As one authorship has stated, The presence or absence of symptoms, in both hypothyroidism and subclinical hypothyroidism, depends more on the clinician than on the patient. (Fowler & Stubbs, 1992). In other words, even subclinical hypothyroid patients have symptoms (making the term a misnomer); it is just that the physician frequently doesnt elicit the symptoms and signs. This view is backed by the papers of Staub et al, and Zulewski et al, respectively, which clearly showed significant changes in a clinical symptom index, the Billewicz scale, in subclinically hypothyroid women of mean age 50, compared to age-matched controls (Staub et al, 1992); and showed significant correlation with serum free thyroxine and TSH levels (Zulewski et al, 1997).
Many physicians regard hypothyroidism as far more common than is generally acknowledged. This article will detail how patients who are being treated are actually undertreated, because of excessive reliance on the ultrasensitive serum TSH level for monitoring, and the use of a single thyroid hormone, thyroxine (T4), in its treatment. Additionally, there are excessive fears of precipitating or aggravating osteoporosis. Evidence for this is equivocal and shared by concerns of both natural and iatrogenic hypo- and hyperthyroidism causing it (Adlin et al, 1991; Ross, 1991b; Franklyn et al, 1994; Hart, 1995; Uzzan et al, 1996; Bauer et al, 1997) (and, presumably, undertreatment of either being a risk factor as well). The conservative American College of Physicians has recently found enough evidence of the widespread nature of hypothyroidism to recommend that, and since women are 9 times more likely than men to become hypothyroid, women over 50 years of age should be screened for it once every 5 years (Helfand & Redfern, 1998). In an editorial rebuttal, renowned thyroidologist David Cooper argues for a more aggressive approach to case-finding, and treatment of milder degrees of hypothyroidism (Cooper, 1998) and cites powerful support (Surks & Ocampo, 1996; Arem & Escalante, 1996), including the American Thyroid Association (Singer et al, 1995).
A recent estimate of the widespread prevalence of primary hypothyroidism suggests a figure of 9-10% in the United States. This estimate was limited only to active, uncorrected grades 1 and 2 primary hypothyroidism, based on a survey of serum TSH levels on 26,000 adults at a health fair (Ridgway, Canaris, et al, 1997). Only about 10% of those thus identified as hypothyroid admitted to being diagnosed and ~ by definition, inadequately! ~ treated, despite the long_term health risks associated with the condition. Results of the study were presented at the Oct. 1997 annual meeting of the American Thyroid Association held in Colorado Springs and are presumably in medical press. These researchers also discovered a strong relationship between an underactive thyroid and elevated serum cholesterol levels, as other workers also have (Fowler & Stubbs, 1992; Hart, 1995; Dillman, 1991; Miura et al, 1994; Dullaart et al, 1995).
The current conventional approach to diagnosis does not allow for optimal diagnosis and treatment. We propose a new approach that is more logical and perspicacious, and which imitates the basic physiology of thyroid function. This approach includes attention to grade-3 primary hypothyroidism, subtle forms of secondary/ pituitary and tertiary/ hypothalamic central hypothyroidism, and many cases of nonthyroidal-illness hypothyroidism. We also submit the view that most treated cases are in fact undertreated, and propose here a logic-supported treatment-approach that eliminates this situation. It goes without saying that, if true, undiagnosed, untreated and undertreated cases of hypothyroidism would cause massive morbidity, mortality, and suffering.
Broda Barness book Hypothyroidism: The Unsuspected Illness (1976) is used by many natural medicine physicians in their approach to hypothyroidism in the US. The book suggests that 64 diseases are caused or aggravated by (mostly-undiagnosed) hypothyroidism, and that hypothyroidism afflicts approximately 40% of the population. The 40%-figure seems high but, if successfully-treated grades 1 and 2 primary, all grade-3 primary, subtle forms of secondary and tertiary, and many cases of non-thyroidal-illness hypothyroidism are added to the 10% of the population uncovered in the health fair survey (above) who are either untreated or inadequately treated grades 1 and 2 primary hypothyroidism cases, the figure must surely jump to at least 20%, of which only a small percentage is being treated.
The validity of the euthyroid sick syndrome was first questioned in the 1980s. It had become common for psychiatrists to find that, in refractorily_depressed patients who had been passed as euthyroid by endocrinologists, serum T3 levels were low (Joffe et al, 1985) and T3 administration, more so than T4, actually enhanced the effectiveness of the antidepressants (Joffe & Singer, 1990). In 1990, Palazzo and Suter (Palazzo & Suter, 1990) also published their earlier questioning of the so-called euthyroidism of the sick euthyroid patients they were seeing in an intensive-care unit.
Measuring both the FT3 and FT4 serum level on all patients since l988, in both diagnostic screening and treatment-monitoring, has usually shown a large disparity between these two levels (unpublished data). Including T3 in the treatment (unless the patient had a life_threatening or cardiac-arrhythmic illness, in which a low T3 serum level may have been life_saving by keeping their metabolism and/or heart-rate low) invariably enabled patients to lose their classic hypothyroid symptoms, just as described in the literature (Dommisse, 1991 & 1993; Arem, 1999)) ~ something they had not been able to do with T4-only treatment, even when the FT4 level had been pushed to the maximum, or even beyond (Cooke et al, 1992). In most cases, it is important for both FT4 and FT3 levels to be optimized with whatever combination of T4 and T3 is necessary in treatment. This objective necessitated the use of both T3- as well as T4-containing preparations in the management of the vast majority of all hypothyroid patients. Gelenberg reported the same phenomenon in a psychiatric newsletter (1992). In 1997 IJ Chopra, contributor to some of the best papers and textbooks on thyroidology, published his paper on The euthyroid sick syndrome: Is it a misnomer? (Chopra, 1997). And, in early 1999, Leslie deGroot, another highly published thyroidologist, has published his own recent misgivings about the current dismissive approach to low free-T3 and -T4 serum levels in non-thyroidal illness/ euthyroid sick syndrome (DeGroot, 1999).
There are currently 4 categories of hypothyroidism that are often not being diagnosed as such, and therefore go untreated: (1) grade_3 primary; (2) subtle secondary/ pituitary without identifiable pituitary tumor or disease; (3) subtle tertiary/ hypothalamic in depression, chronic fatigue and other chronic illnesses; and (4) many cases of non-thyroidal illness/ euthyroid sick syndrome in which the low FT3 (and sometimes even FT4) level is counter-productive and not life-saving. The remaining categories, grades 1 and 2 primary hypothyroidism, are very often undertreated.
Grades of Primary Hypothyroidism
A patient is considered to have grade-1 primary hypothyroidism when their serum FT4 level (and possibly the FT3 level) is below the normal range and the ultra-sensitive TSH is above its normal range . Grade-2 primary hypothyroidism is diagnosed when the FT4 and FT3 levels are in the lower half of their normal ranges but the sensitive TSH is elevated above its normal range of approx. 0.5-4.2 mIU/L. Many physicians have also come to recognize a grade-3 hypothyroidism: Free-T4, Free-T3 and sensitive TSH all in their normal ranges but the TRH -stimulated TSH jumps up >20 points within 30 minutes. Since the advent of the ultra-sensitive TSH, it has been realized that the TRH-stimulation of the TSH is not necessary (Nicoloff & Lopresti, 1991), since it became apparent that a positive TRH-stimulated TSH test is equivalent to an ultra-sensitive basal-TSH in the higher part of its normal range, and signifies grade-3 hypothyroidism. Only about 5% of the physicians in the US treat grade-3 hypothyroidism and the authors are proud to count themselves among them because they have virtually never had a case that did not respond positively, in numerous ways, to their correction of that state. The current conventional approach appears to be tailor-made for many unpleasant surprises; just as one example, covert/ subclinical/ grade-3 hypothyroidism can present initially as a myocardial infarction.
Another condition that is increasingly becoming regarded as not necessarily always free of thyroidal functional effects is the euthyroid-sick/ non-thyroidal illness syndrome. In this condition the FT3 level (and sometimes the total-T3 level or the FT4 level or Free Thyroxine Index ~ FTI/ T7) is below normal and the TSH is normal or even low-normal (Nicoloff & Lopresti, 1991). This is not due to pituitary or hypothalamic problems but due to other extrathyroidal illness. It is important not to over-treat this condition when it is present in acute cardio-arrhythmic or other severe potentially life-threatening illness because in these cases the low FT3 (or FT4 or FTI) may be potentially life-saving, by lowering the metabolic and/or cardiac rate. However, the majority of so-called euthyroid sick cases these days appear to occur in chronic ambulatory conditions, such as fatigue or depression, in which the low FT3 level not only is not helpful but is actually harmful and is helping to perpetuate the fatigued or depressed state.
Also, psychiatrists have known for a long time that, even in the absence of diagnosed hypothyroidism, low T3 levels are actually causative factors in depression (Joffe, 1985). The depression is rendered refractory by this low T3 state and will frequently not respond to antidepressant medication unless T3 is used to augment the antidepressant medication. In bipolar-affective-disordered/ manic-depressive patients, leading psychiatrists have advocated and successfully used thyroid hormone treatment, especially supra-physiologic doses of T4, to help reduce the frequency and severity of the moodswings. In approximately one-sixth of individuals on lithium therapy, the thyroid function is lowered to a frankly-hypothyroid level (Barsano, 1991). There may be substantial numbers of other patients who should be considered to be rendered hypothyroid by this medication when a more-inclusive definition of hypothyroidism is used. So, many of the psychiatric cases who are regarded as euthyroid may in fact be cases of grade-3 primary hypothyroidism, secondary or tertiary hypothyroidism, or of euthyroid sick syndrome hypothyroidism. The term euthyroid sick is now being openly disputed, meaning that the T3 used in augmenting antidepressant treatment may in fact be a back-door entry to the thyroid treatment of refractorily-depressed hypothyroid patients (Cooke et al, 1992), until now regarded as euthyroid by the current approach to diagnosis.
The Current Standard and Alternative Approaches
Two current popular reference texts on the thyroid and endocrinology Braverman & Utiger, 1991; Greenspan & Rappoport, 1991) point to the great functional importance of T3 thyroid hormone. It is 9 times more physiologically active, in comparison to the T4 hormone. The T4 hormone merely serves as a pro_hormone or pre-hormone, with the possible exception of brain-function, which may require a significant amount of T4 for its optimal function because T4 is transported through the choroid plexus and T3 is not (Whybrow, 1991; Whybrow, 1994). Despite this broad agreement on the roles of the two thyroid hormones, when it comes to diagnosis, these texts often only advocate the ultra-sensitive serum TSH level and, sometimes, a FT4 or a Free Thyroxine Index/ FTI/ T7 (but no FT3 level). And these experts recommend the sole use of T4 for treatment in nearly all cases.
This paper will present evidence for the inclusion of the FT3 (and FT4) level in all thyroid screening and monitoring. It will also support the strategy of including T3 thyroid hormone, together with T4, in the treatment of most cases of primary, secondary, tertiary and non-thyroidal-illness hypothyroidism. This is implied by Escobar-Morreale et al with their discovery of the inadequate reversal of post-ablative hypothyroidism in rats by T4-only treatment (1996). If the TSH, FT4 and FT3 levels serve any diagnostic function at all, they do so only as an integral group of tests, each of which is in a reciprocal relationship to the others. The Escobar-Morreale study demonstrated that adding T3 to the replacement regimen did restore euthyroidism to rat tissues.
The major theoretical and practical reasons for the T4-only treatment-approach in the past centered around the greater stability of the T4 blood level, in comparison to the T3 level, which has wider diurnal and post_dose fluctuations (Chopra, 1991). The inaccuracy of the older tests for the T3 hormone also contributed to this perspective. However, the diurnal variation of T3 in the untreated human is fairly low; and twice_daily dosage of all treatment preparations containing T3 eliminates this objection in treated cases. Additionally, newer technology has provided the ready availability of the very accurate FT3 and FT4 blood levels (Stockigt, 1991). These factors have erased the validity of the current conventional approach. They have also removed the validity of the non-specific basal-temperature-recording alternative diagnostic and monitoring method of Broda Barnes, as described in his 1976 book (Barnes, 1976).
The traditional, older tests of thyroid function, the serum total-T4, T3 uptake, free thyroxin index (FTI, also known as T7?), total-T3, and T3_by_RIA tests should be abandoned because they are inaccurate and unreliable as gauges of thyroid function (Stockigt, 1991). Physicians in Britain, South Africa and several other countries already did so, years ago. While the richest and most medically-advanced nation in the world is adversely influencing peoples thyroid health, in a penny-wise, pound-foolish way, by sticking to these cheaper, outdated, inaccurate tests ~ or limiting the blood-testing to a single, indirect, fallible measurof thyroid function, the ultrasensitive TSH test.
The most common conventional way to diagnose hypothyroidism is with an ultra-sensitive TSH that is elevated beyond the so-called normal reference range. For most labs, this upper limit of the normal range is about 4.0 to 4.5 mU/L. This is thought to reflect the anterior pituitarys sensing of inadequate thyroid hormone levels in the blood or in its own cells, which would be consistent with grades 1 and 2 primary hypothyroidism. This will undoubtedly diagnose the severest grades of primary hypothyroidism, but it is far too limited a measure, and large numbers of patients who have some other form or degree of hypothyroidism will be missed. This strategy will fail to detect secondary and tertiary hypothyroidism because TSH is not elevated in these conditions; it will fail to detect the euthyroid sick syndrome for the same reason; and it will miss grade-3 primary hypothyroidism because the normal range for TSH has been set too high to identify this condition.
Two controversial alternative physicians have also become associated with a focus on T3. The first was Dennis Wilson, MD, of Florida (1992). He noticed, in the early 90s, that many patients with chronic fatigue and other similar symptoms had low basal body temperature, a la Broda Barnes, and low T3 levels (actually low total-T3 levels, a less accurate depictor of the T3 status than the FT3 level). He dubbed this condition Wilsons Syndrome (inappropriately-so because this name is readily confusable with Wilsons Disease, which is a disorder of copper metabolism named after a different physician, a long time ago). He treated them with a slightly-longer-acting form of T3-only, and said most of them improved significantly. He contended that, after a few months, the T3 could often be discontinued and some of the patients would not relapse into the low-T3 state, presumably because the supply of T3 had broken the vicious cycle of the low T3 level that had caused a breakdown in the peripheral conversion of T4 to T3. [It is possible that the action of 5?deiodinase is dependent on a certain threshhold amount of T3.] Some patients, perhaps most, needed to stay on the T3 treatment. Other physicians find that these patients then have high-normal, above-normal, or way-above-normal FT3 levels, and subnormal or low-normal FT4 levels (unpublished data). This would be in a conventionally-treated hypothyroid patient, in which the FT4 level may be in or above the normal range but the FT3 level is at or below the low end of its normal range. We say almost as unfortunate because, since T3 carries out 90% of the thyroid function (Chopra, 1991), having it at least adequate would appear to be more important than having T4 at an adequate serum level ~ if one has to choose between the two (which, of course, is not the case, if one thinks clearly about the matter).
The other physician promoting a controversial alternative approach to the management of T3-hypothyroidism is a chiropractor by the name of John R Lowe, of Texas. He has, particularly, found high doses of T3 very beneficial in cases of fibromyalgia (Lowe & Garrison, 1997). He has found that a substantial percentage of these cases is improved or put into remission by the correction of their low T3 serum level. He used T3-only preparations, similarly to Dennis Wilson, which produced analogous outcomes in the relative T3 and T4 serum hormone concentrations. His research-partner, Richard Garrison, is apparently currently engaged in a Veterans Administration-approved study on the effects of T3 in Gulf War Syndrome, a condition thought to be related to chronic fatigue syndrome and fibromyalgia (which are, themselves, often present in the same patients). He is using hyaluronic acid,
which has been found to be a marker for fibromyalgia (Yaron, 1997), as a gauge of the improvement, if any, brought about by T3 in Gulf War Syndrome.
A recent paper shows the superiority of T4+T3 over T4-only treatment of 33 hypothyroid patients in a double-blind crossover study (Bunevicius et al, 1999). The 4th author, Arthur Prange, is one of the several American psychiatrists who have published articles on the great benefit of T3 in refractorily depressed patients (Haggerty & Prange, 1990; Whybrow & Prange, 1981). It is likely that the benefit of the combination-approach in this paper would have been even greater if the FT3 and FT4 levels had both been optimized, rather than a fairly arbitrary amount of the previous T4 treatment simply being substituted by a functionally-equivalent amount of T3. However, this is a landmark paper that, together with those of Escobar-Morreale et al (1996), Chopra (1997), DeGroot (1999), and the present paper, as well as the popular book by one of us (Arem, 1999), will revolutionize the treatment of hypothyroidism, despite the cautionary editorial in the same issue of NEJM (Toft, 1999). Still further evidence of the shift toward including T3 in both the measuring and treating of the various forms of hypothyroidism is provided by yet another paper published during the closing stages of the writing of the present paper: The multi-center Italian Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism has just reported that both FT4 and FT3 serum levels are necessary for a more accurate disclosure of over- or under-treated patients. (Ferretti et al, 1999)
Some Modern Conventional Myths about Diagnosis and Treatment
In the authors opinion the current conventional approach is due to the following errors of thought: The first four concerns are widely-held myths that persist in the conventional medical community regarding the TSH and its role in the diagnosis and treatment of hypothyroidism:
(1) The first is that an elevated ultrasensitive_TSH level is almost-always required before a diagnosis of hypothyroidism can be made; and
(2) that TSHs over-suppression almost-always means hat excessive treatment is in place. Normally, the anterior pituitary will secrete enough TSH to maintain adequate thyroid hormone levels. When this fails to occur, either grade-1-primary or secondary hypothyroidism is considered to be present. There seem to be subtle, conventionally called subclinical, failures of the anterior pituitary to produce sufficient TSH in response to low thyroid hormone levels that cannot be explained solely by the traditional form of secondary hypothyroidism (secondary to a pituitary tumor or outright pituitary failure, as in Sheehans Syndrome: postpartum hemorrhage or infarction of the pituitary gland). This could also be due to a tertiary hypothyroidism (where the thyrotropin-releasing hormone ~ TRH ~ from the hypothalamus fails, for poorly-understood reasons, to stimulate the anterior pituitary to secrete adequate amounts of TSH), or to a TSH_specific hidden hypopituitarism.
(3) The third TSH-myth is that, just because the new ultrasenstive TSH test is a very sensitive and accurate test for measuring the TSH level, this suggests to imply that TSH is always or usually the correct yardstick by which to measure the function of the thyroid hormones, T4 and T3. There is an unconscious, unintentional sleight of hand occurring here. The assumption is that, if TSH is low-normal, adequate amounts of T4 are being converted to T3 in the pituitary receptors; and that, if TSH is below normal, excessive amounts of T3 are being formed from T4 in those receptor cells. There does not appear to be any evidence that the pituitary gland ~ or any organ or tissue, for that matter ~ can convert T4 to T3 at any greater rate than that which is reflected in the serum FT3 level. Anyone who routinely measures the serum FT3 evel will observe that the serum FT3 level is often low, even when the TSH level is low-normal or below normal ~ even in the absence of identifiable pituitary or hypothalamic disease. Some of these cases are so-called euthyroid sick/ non-thyroidal illness syndrome cases, some are subtle secondary or tertiary hypothyroid cases without known disease involvement of either the pituitary or the hypothalamus. And some are any combination of these two forms of hypothyroidism, or of non-thyroidal-illness hypothyroidism, or of grade-3 primary hypothyroidism.
The TSH is an indirect gauge of T4 and T3 activity and depends on its own integrity-of-function and not only on the relative heights of the two thyroid hormones. Most realize this truth when there is known hypopituitarism or hypothalamic malfunction, but we dont recognize it is also true in subtle/ occult pituitary and ypothalamic failure, and in the hypothyroidism that is now increasingly recognized as a frequent accompaniment of non-thyroidal illness or the euthyroid sick syndrome (Palazzo & Suter, 1990; Chopra, 1997; DeGroot, 1999). It is incorrect to state that the FT4 and FT3 levels are inconsequential: High or high_normal levels would indicate that the high or high-normal TSH is not even due to hypothyroidism but is due to lab error, stress or a spurious high TSH, or some other condition. This is another example of why it is always necessary to measure FT4 and FT3. A TSH level can be FT4 and FT3 are not elevated, but, in our opinion, FT4 and FT3 can never be dispensed with.
(4) The normal range of TSH is approx. 0.5_4.2 mIU: Where is the evidence for this range? Many patients with TSHs of 1.0_4.5 (and lowish-normal FT4 and FT3 levels) have classic hypothyroid symptomsand they virtually always respond with dramatic resolutions of these symptoms and a quantum leap in their sense of well-being, mood, energy, bowel_function, memory, etc. (unpublished data). Sometimes, patients with these mild degrees of thyroid hypofunction can be taken off the thyroid treatment after 3-12 months without relapsing. Perhaps the treatment, which causes a period of rest for the gland and which is known to reduce the auto-immune antibodies (Trbojevic et al, 1986), enables the gland to recover, at least temporarily.
(5) It is not necessary to measure the FT3 level because FT4 usually converts adequately to FT3?: The other myths involve the FT4 and FT3 serum levels and the inappropriateness of T3 in the treatment of hypothyroidism. This is simply not true. FT4 often _ more often than not, in hypothyroid patients doesnt convert sufficiently to FT3 (Joffe et al, 1985; Cooke et al, 1992; Gelenberg, 1992; Dommisse, 1993; Whybrow, 1994), nor in laboratory rats (Escobar-Morreale et al, 1996). Routine measurement of FT3 whenever screening for, or monitoring treatment of, hypothyroidism will quickly confirm this.
(6) It is not a good idea to treat with a combination of T4 and T3 because the FT3 level is so unstable and inconsistent that one cannot obtain useful information from measuring it, potentially leaving the patient open to the wrong dosage of (usually too much) T3?: All that is required to invalidate this objection is to always prescribe any T3-containing preparation twice_daily. Taking these split doses after breakfast and dinner assists in stabilizing the FT3 level by slowing its absorption _ and therefore extending its duration of action. There seems to be no appreciable fluctuation of the FT3 level when this simple dosing regimen is implemented.
(7) The euthyroid sick/ non-thyroidal illness syndrome should never be treated with any thyroid hormone because it never involves malfunction of the thyroid hormones, causing any symptoms: Again, this is not accurate. Chopra (1997) expands on this. Palazzo and Suters letter suggested that at least some euthyroid sick patients, even acutely-ill ones in an intensive care unit, do not have adequate thyroid function. They believe the patients would probably benefit from increasing their thyroid hormone levels, especially T3 (1990). Finally, Leslie deGroot has also joined the questioning of the prevailing dogma on this issue (1999).
(8) T4 is the only hormone that should be used in treatment; one should never prescribe more than one thyroid hormone: Why not? If that is the only way to optimize both the FT4 and FT3 serum levels and that is usually the case what is wrong with treating with two thyroid hormones? The gland itself secretes both. The fact that it usually requires the prescribing of both hormones to optimize the serum levels of T3 and T4, certainly gives one pause about the adequacy of the treatment of most patients in the US (and in countries where no form of T3 is even available, such as Australia, Israel and Spain).
(9) Keeping both the FT4 and FT3 levels at the high ends of their normal ranges will cause osteoporosis: This concern was merited 30-50 years ago, when much-higher doses of thyroid hormone were used in the treatment of most cases of hypothyroidism. One of us (JVD) has not observed this complication in over eleven years of this more-aggressive treatment (unpublished data). In fact, his treatment_optimized hypothyroid osteoporotic patients bone density scans not only dont deteriorate from one year to the next but almost-invariably improve, without the use of overtreatment of hypothyroidism, it has to be more substantial than is currently thought. Concurrent correction of other factors, such as deficiencies of vitamins, minerals, other hormones, and amino-acids, seems to maintain and extend bone density, even in the presence of optimal or aggressive treatment of hypothyroidism.
If thyroidologists, endocrinologists and other physicians were to incorporate these principles, millions of patients would improve their diminished quality of life that they are currently leading. Many of the hyperlipidemias, myocardial infarctions, affective disorders, dementias, obesities, hypertension, chronic fatigue, impotence, peripheral neuropathy, hair-loss, some psychoses, immune suppression, and chronic constipation could easily be ameliorated.
Although this is not a report of any actual findings on his part, it is fair to say that JVD has observed clinical improvement in hundreds of patients whose thyroid status was previously regarded as normal, based on the older tests or on a single TSH level, or a combination of these two assessments, when I has boosted patients free-T3 levels (and sometimes the FT4 level as well). This new approach always utilizes the FT3 and FT4, as well as the ultrasensitive TSH serum level. The TSH is given a new reference-range of 0.1-1.0 mU/L. Readings above the high end of this range are only valid as indicators of hypothyroidism if the FT4 and FT3 levels are not above the lower-one-third of their normal ranges. Understandably, the suppression of a TSH that was not elevated without treatment is not going to be in the low end of its normal range on optimal FT4 and FT3 levels but will be well below that level, possibly even as low as 0.01.
There are a significant number of patients who have a TSH level below 1.0 but their FT3 (and possibly the FT4 as well) will be below normal. These are cases of secondary/ pituitary or tertiary/ hypothalamic central or of euthyroid sick/ non-thyroidal illness syndrome. These individuals should receive supplemental thyroid hormone therapy, especially if they have a serious condition, like depression or dementia, that is dependent on good thyroid hormone function for its reversal. There are far too many of these vulnerable patients to ever believe that a TSH, alone, is an adequate screening tool.
The next issue is: With what substance to treat these patients? The approach we are advocating, which has been used very successfully since 1988 in one thousand patients (unpublished data), is the one which has the goal of optimizing the free (unbound-to-protein) serum levels of both the T3 and T4 thyroid hormones. One uses whatever combination of both hormones (or, occasionally, T4-only) it takes for the treatment to produce this result.
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 could not produce abundant T3 from their gland (which produces some T3 directly), and from the conversion of T4 to T3 peripherally, when they have a high TSH level (which drives the T4-to-T3 conversion), then they will not convert enough T3 from T4-only after the TSH level drops, on treatment. 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. Unfortunately, clinical experience shows this is not true for the majority of patients.
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. A certain minority of hypothyroid patients do convert enough T4 to T3 at a sufficient rate for T4 treatment to be adequate as a source of T3. However, the majority of patients require some combination of both exogenous T3 and T4. Improving the FT3 level to an optimal level improves the patients thyroid hormone function and the patients health and performance. It also dispells the myth of extrathyroidal causes of low thyroid hormone levels not being an appropriate focus of concern for the physician.
Optimizing both the FT3 and FT4 levels usually requires either a combined T4/T3 preparation, or separate T4 and T3 preparations, or a combination of a T4 and a T4/T3 combination-preparation to be prescribed. Desiccated whole hog-thyroid (e.g., Armour Thyroid) is a good, relatively-inexpensive starting-point for the fixed-combination T4/T3 treatment. Since it contains T3, it should always be prescribed after breakfast and supper daily, to reduce the rapidity of onset and prolong the duration of its action. The major shift here for most physicians is to recognize that dessicated thyroid hormone should be used twice daily and not just once a day. If dessicated thyroid alone does not optimize both hormones free-levels, additional T4-only or (much less often) T3-only treatment can be added in order to achieve this goal. Alternatively, an estimated amount of T4 can be prescribed daily, and an estimated amount of T3 can be prescribed separately after breakfast and supper daily.
Once on hormone replacement its normal range. Then thyroid function will have been optimized by the TSH yardstick, if FT4 and FT3 remain suboptimal; it then remains to be optimized by the yardstick of the accurate measures of the 2 thyroid hormones, the FT4 and FT3 levels, if there remains a discrepancy between these 2 yardsticks.
The TSH, FT3 and FT4 serum levels are then repeated in one month to 8 weeks, depending on whether T4-only or some combination of both T4 and T3 are being used in the treatment, and the doses of T4 and/ or T4/T3 and/ or T3 are then adjusted. If T4-only is used as the treatment, the FT4 and FT3 levels ~ and, when indicated, the SH level ~ should only be obtained after 6-8 weeks of continuous treatment, because the much-longer half-life of T4 necessitates a longer period before its ~ and that of the T3 hormone into which it is converted ~ steady state is reached.
In order to optimize the hormone replacement in an otherwise-healthy young or middle-aged patient, the FT3 and FT4 should be in the upper one-third or near the upper end of the laboratory normal reference range. Lower levels (in the middle one-third of the ranges) should be utilized in cardiac-arrhythmic and/or elderly or frail patients. Once stabilized, the levels need only be checked annually or semi-annually, unless clinical indicators demand earlier re-testing.
A small number of large, overweight, thyroid_resistant usually-women may need up to 6_8 grains of Armour Thyroid (or the equivalent of thyroxine, counting 0.1mg of T4 as 1 grain; or in a combination of the two) per day. They must represent some form of thyroid resistance syndrome (Refetoff, 1991).
Patients who are already on once-daily Armour Thyroid should be advised to split their doses immediately and take half of their daily intake after breakfast and half after dinner. Since the only change will be in the FT3 level, which has a short half_life, the serum FT3 level can be measured 48_72 hrs after the splitting of the doses, if the patient has been on the same daily intake of the combined T4/T3 treatment for 5 weeks before the splitting of the doses.