Thyroid hormone replacement is not as simple and straightforward as many practitioners believe. Thyroid hormone effect is derived from the effects of both tetra-iodothyronine, the pro-hormone or T4, and triiodothyronine, the actual thyroid hormone or T3. The latter should not be confused with the T3 uptake measurement which measures thyroid hormone binding capacity and can be used to indirectly estimate the amount of free thyroid hormone available. The T3 uptake is referred to as the T3u and the free thyroid hormone index as the FTI. Complicating things further, there are various tests which directly estimate the free thyroxine and the free triiodothyronine. All of these tests are subject to interference by outside factors such as medications, disease states, or even normal physiology such as pregnancy.
When the physician receives a laboratory report, the report slip will have stated normal ranges for each of the analytes. This is the subject of confusion since when a patient is on thyroid hormone replacement therapy, the stated normal ranges are altered somewhat. Specifically, the serum thyroxine or serum T4 tends to be higher with adequate replacement by administered thyroxine, particularly when the assay is done early in the day after morning administration of the dose of L-thyroxine. Thus, a total normal thyroxine might be stated to be less than 11 or 11.5 ugm% whereas in a patient on maintenance hormone, a normal value might be as high as 14 or 15 ugm%. When thyroxine binding capacity is elevated in pregnancy or by the use of birth control medications the total thyroxine may appear to be elevated at a time when the free thyroxine index or the free T4 is normal.

Quite commonly, physicians will reduce thyroid hormone dosage to reduce the serum thyroxine levels to within the stated range on the thyroid function test slip. This may result in symptomatic hypothyroidism. Typically, the actual hormone is not measured as frequently as the total thyroxine or the free thyroxine index although both the serum level of tetraiodothyronine (prohormone) and the triiodothyronine (actual hormone) contribute to the sum of thyroid hormone effect. The T3 is approximately 3 to 4 times as potent as the T4 for most metabolic effects. With thyroid injury by disease or treatment, there is a shift to T3 production with less relative T4 production. Conversely, various disease states may alter the peripheral deiodination of T4 to form T3 in peripheral tissues, decreasing the totality of thyroid hormone effect. These variations in the ratios of T3 to T4 are sufficiently frequent and of a magnitude that we prefer to measure both in evaluating thyroid function. The thyroid stimulating hormone measurement is also of fundamental importance since it reflects the sufficiency of central nervous supply of thyroid hormone. A normal range TSH indicates that the hypothalamus senses a normal range of thyroid hormone and is stimulating the thyroid to continue making and releasing thyroid hormone at the same rate. An elevated TSH signals central nervous system insufficiency of thyroid hormone, while a reduced TSH indicates that the central nervous system senses either increased amounts of thyroid hormone or exactly the amount that turns off this signaling mechanism.

Within the range of normal for thyroid hormone, there is a rather wide degree of variation from individual to individual. Significant numbers of people are relatively hypo-metabolic and therefore sub-clinically hypothyroid in the lower normal ranges of thyroid hormone levels. Among more active normals, we expect to find thyroid hormone levels tending toward the upper normal ranges. It is our belief that it is good and acceptable medical practice, when a person has a symptom complex suggestive of thyroid hypofunction but is shown to have lower normal ranges of thyroid hormone, to do a clinical trial on thyroid hormone maintenance therapy sufficient to increase these lower normal thyroid hormone values to upper normal values should be considered. If there is a sustained favorable response without any evidence of clinical hyperthyroidism, long term replacement therapy may be justified. Certainly, thyroid hormone therapy at high doses is never justified just to achieve weight loss, as has been the practice in some weight loss clinics.

We observe subclinical hypothyroidism with surprising frequency among patients with clinical depression, especially those who have shown less than satisfactory response to antidepressive therapy, and are always willing to very carefully evaluate people with depression for the presence of any hypothyroidism. There is considerable psychiatric literature about the psychotropic effects of thyroid hormone and some psychiatrists employ thyroid hormone, particularly Cytomel or triiodothyronine, for its psychotropic effect in depression.

The long term effects of excess thyroid hormone which are recognized include depletion of bone mineral, some minor electrocardiographic changes the significance of which is uncertain, and in older patients the occurrence of atrial fibrillation (a disordered heart rhythm.) Bone mineral measurement can be used to detect developing bone disease in people who are on long term thyroid maintenance therapy, particularly those who require higher dose replacement or maintenance such as individuals with thyroid cancer or thyroid eye disease. We are careful to assure adequate calcium and vitamin D availability in these patients, and during their later years, we advocate sex hormone replacement therapy as well. Ordinarily, with these provisions, we do not observe osteoporosis developing in patients on long term high dose thyroid hormone therapy. Although the thyroid hormone related osteodystrophy would be expected to affect the long bones of the extremities preferentially, we prefer to monitor the lumbar spine as the measurement of choice in following these patients.

During thyroxine replacement therapy, it is important that some monitoring be performed, probably at no less than two year intervals in adults, and more frequent intervals as appropriate in children. During pregnancy and menopause, we prefer to monitor more frequently, re-evaluating thyroid hormone values and clinical status at three month intervals during pregnancy and with increased frequency during lactation. Typically, thyroid hormone requirement is increased somewhat during pregnancy and lactation.

Some comments might be helpful about actual use of thyroid hormone. Patients should be aware that it is heat intolerant and therefore should not be left in an automobile subject to heating by the sun. The medication is also best stored in a dry environment and only a limited number of tablets should be kept out in a bottle used in high humidity. There seems to be little or no difference in bioavailability among the name brands, but there is significant bioavailability variation among the generics, and, since prescription of thyroid hormone in a generic form does not assure that you will have a refill with the same generic, we prefer to restrict our prescriptions to name brands. Patients should be cautioned to avoid taking thyroid hormone with iron supplements since this will restrict absorption. Several other medications may interfere with thyroid hormone absorption or with bioavailability.

Some comments might be in order about the efficacy of "natural" or dessicated thyroid hormone vs. synthetic thyroid hormone or L-thyroxine. Dessicated thyroid hormone is a mix of T3 and T4 which gives sorne short-acting T3 effect immediately after ingestion, presumably in the early part of the day, while T4 provides a more continuous availability of thyroid hormone since the T4 is converted to T3 in the body at whatever rate the body requires. We prefer the synthetic and have seldom used desiccated thyroid except at patient insistence in the last 38 years.

When in doubt about your thyroid hormone therapy, never fail to ask, as you can see from the foregoing, thyroid replacement therapy is not a completely simple and straightforward medical task. It requires careful, periodic review and attention.
Ref: Marin Endocrine Associates Medical Group, Inc.