Updated 2018-07-20
L-T3 medication without L-T4 has been used for decades in psychiatry in the management of certain types of depression, even in patients who are not hypothyroid.[184]
Animal experimentation in the 1980s demonstrated T3 was more efficient at crossing the blood-brain barrier than T4.[185]
More recently, animal experiments showed promise in the treatment of Multiple Sclerosis because it corrected pathological alterations in the deiodinases and thyroid hormone receptors in spinal cord. [186]
Although its role in psychiatry is debated, use of T3 and research on T3 therapy has continued, [187, 188, 189] and there are guidelines for its safe use in psychiatry.
In the literature, T3 has been used effectively in patients with normal thyroid glands to speed the course of recovery after non-thyroidal illness or Low-T3 syndrome.[152, 190, 191, 153, 192 ]
L-T3 has also been commonly used in the treatment of myxedema coma (coma resulting from severe hypothyroidism), although its use occurred largely before the 2000s, when medicine started to favor treatment with L-T4. [193] This shift away from L-T3 in myxedema coma was not only due to the rise of L-T4 therapy but also due to reports of patient deaths that resulted from poorly-regulated L-T3 treatment that was overdosing patients, resulting in 2x the normal level of T3 in serum. [194] The combination of both L-T3 and L-T4 has been used recently for myxedema coma, with good results.[195]
Low-dose T3 monotherapy
Low-dose T3 monotherapy can be virtually equivalent to combination therapy, at least from the perspective of the human body, in patients who have a functioning thyroid gland that produces T4. If L-T3 is not taken in doses large enough to fully suppress the patient’s TSH, the natural thyroidal stimulation and secretion of T4 will continue.
T3 therapy often achieves sufficient T3 thyroid levels by means of shifting the T3:T4 ratio in the favor of T3, which is the converse of the low ratio that T4 monotherapy achieves in all patients to varying degrees (see our section on the T3:T4 ratio).
Because T3 is the active hormone, as T3 is increased, T4 levels in serum may fall without symptoms of hypothyroidism, as long as T3 levels are sufficient to compensate. The shift to a higher T3:T4 ratio is biologically necessary from a purely mathematical perspective given that T3 is a deiodinated version of T4. To the degree one reduces Free T4 in circulation, one decreases the amount of T4 that is destined to convert to T3 after entering cells and tissues. In order to compensate for the loss of that T4-soon-to-be-T3, one must add T3 to the circulation to avoid a net T3 deficit.
Full replacement L-T3
One rare modality, long-term L-T3 monotherapy for hypothyroidism taken at suppressive replacement doses averaging 50-80 mcg / day, has been in use since liothyronine was first manufactured in the 1950s. [23] More recently, an international community of T3-only patients and their doctors have been supported in this therapy by Paul Robinson’s handbooks. [196 197]
High-dose L-T3 monotherapy is unusual because the human body is clearly designed to convert a stable, steady supply of T3 largely converted from T4 hormone. It is puzzling that the human body could develop an aversion to one of its hormones when delivered orally. However, L-T3 monotherapy has been a last resort in some patients. Some patients may discover only at the point of long-term L-T4 therapy that they have genetic limitations that hinder their conversion of exogenous T4 hormone to T3, and perhaps hormone transport as well. Over the decades, case reports have told of patients with existing cardiac disorders and hypothyroidism, for whom even small doses of T4 appear to trigger distressing symptoms such as angina or chest pain. [164, 198] In recovery from myxedema coma or severe hypothyroidism, sometimes the body rejects L-T4 therapy: one report described some patients’ health worsening on L-T4 within 3 weeks resulting in bradycardia and the need for mechanical ventilation. [199] The causes are varied and often difficult to explain since the cases are not frequent enough to do large scale studies.
In such rare and unfortunate cases, full L-T3 replacement therapy can be a viable alternative to increasing illness or chronic hypothyroidism.
In his 2004 response to an article in the British Medical Journal, Dr. Skinner, a specialist focusing on thyroid treatment, reported having had over fifty patients with “refractory hypothyroidism”: “Hypothyroid patients who do not respond to thyroid treatment comprise two groups — namely patients who show no improvement but become clinically thyrotoxic, and patients who show no improvement nor adverse effect.” [200] Dr. Skinner approached the question of risk from an ethical perspective:
“many patients unequivocally state that they would rather run the gauntlet of putative and unproven pathological sequelae than continue a wretched hypothyroid existence. This raises an ethical question on the degree of self-determination or self selection of medical care which is desirable, acceptable or indeed is a patient’s right in a society based on consensual rather than dictatorial principles.” [200]
Humans have lost limbs, certain organs, and have suffered severe brain injury, and they have survived with the aid of customized health care. Likewise, a patient’s response to exogenous T4 hormone may be severely limited or irreversibly damaged and they may need an individualized approach.
Many medical interventions are extremely unnatural yet can be extremely functional, like pacemakers implanted in the heart. Full replacement T3-only patients’ lives are long-term successful experiments that point to the adaptability of the human body.
On full replacement T3, the TSH is suppressed and T4 is not present in serum. Yet the patient continues to thrive based on physiologically appropriate doses of T3. This appears to prove that if necessary, L-T3 hormone may perform all the physiological functions that are normally only accomplished by TSH, T4, and a functional thyroid gland. Science has yet to discover a thyroid hormone receptor that does not have a strong affinity for T3.
However, due to the dependence on T3 alone, the peaks and troughs of serum T3 are much more noticeable to patients on full replacement doses. Multi-dosing is usually necessary, although there are reports of some patients being fine with a single dose per day. [23] Compounded slow release T3 formulations may assist some patients, while others favor the standard fast-release Liothyronine because of the patient’s ability to synchronize multiple daily doses with the natural circadian rhythm of cortisol. [197]
In conclusion, There is a wide range of human response to exogenous T4 and T3 thyroid hormone, and sometimes a “monotherapy” is a suitable approach. For those who depend on thyroid medication for the rest of their lives, multiple modalities of thyroid hormone therapy need to be available, not just the standard L-T4 monotherapy; each patient may need a unique approach to achieve an “optimal” T3 and T4 level and ratio and relief from a state of chronic hypothyroidism. [60, 61, 54]
Next page: Dose and therapy adjustments
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