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 don't 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 TSH's of 1.0_4.5 (and lowish-normal FT4 and FT3 levels) have classic hypothyroid symptoms _and they virtually always respond with dramatic resolutions of thesesymptoms 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 (unpublished data).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 _ doesn't 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 Suter's 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 don't 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.
Sensitive Diagnosis
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 FT4as 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.
Optimal Treatment
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 patient's thyroid hormone function and the patient's 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 foremost 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.
Monitoring Treatment
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 TSH 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.