Combined T4/T3 Therapy: Placebo or Tomato?

THE TSH TEST: HOW IT WORKS, AND HOW IT DOESN’T

The American Association of Clinical Endocrinologists states that laboratory evaluation is critical to establish the diagnosis and causes of hypothyroidism and the most valuable test they use is the ultra-sensitive TSH (thyroid stimulating hormone). The AACE believes the target TSH level should be between 0.3 and 3.0 mIU/mL. 6 The TSH is a negative feedback test, working similarly to the way that your thermostat works in your house. If your thermostat perceives a “cold house”, it will send more electricity to your boiler to produce more heat. When your body “needs” more thyroid hormone, the TSH will go up to stimulate more thyroid hormone production. Most commonly, an elevated TSH signifies hypothyroidism caused by the thyroid gland’s inability to produce enough thyroid hormone to suppress the TSH back into the normal range. (There are exceptions to this rule – such as a pituitary tumor producing too much TSH leading to a hyperthyroid state.) Conversely, a suppressed TSH usually signifies a hyperthyroid state that occurs when there is too much thyroid hormone in the body and the brain does not want to produce anymore. (Again, there are exceptions such as a patient having a malfunctioning pituitary gland that is unable to produce TSH despite the body’s need for more thyroid hormone.)

On occasion, some patients may have their TSH drawn even though they are not experiencing typical “thyroid symptoms”. If the TSH reports back high (such as 7.0), despite no overt symptoms, this person is termed to have “subclinical hypothyroidism”. There is controversy as to whether laboratory evidence of hypothyroidism, in the absence of overt symptoms, should be treated. ^7,8 Possible side effects of unnecessary treatment include progression to overt hyperthyroidism, cardiac effects and skeletal effects. Withholding thyroid hormone, however, could also lead to coronary heart disease and osteoporosis, and these medical conditions can be reversed by initiating thyroid hormone therapy. ^9,10

Another controversial situation is one in which a patient has a normal TSH, but many symptoms of hypothyroidism. Patients with “sublaboratory hypothyroidism” often present to physicians with a long checklist of symptoms and multiple articles (often printed out from the internet) desiring treatment with thyroid hormone. ¹¹ Despite their “normal” pre-treatment TSH test, some patients do indeed receive thyroid hormone therapy, and do “feel better” with this therapy. When therapy is withdrawn, symptoms regress and patients feel worse. Restarting therapy, despite suppressing their TSH, makes them feel better once again.¹² Lastly, despite a “suppressed TSH”, most of these patients do not experience untoward effects of subclinical hyperthyroidism when they are closely followed clinically (follow up physical exams), and with testing (EKG / Echocardiograms for possible heart disease and AXIAL DEXA Bone Density Scans for possible osteoporotic bone disease).¹³

There are many possible reasons for why patients may have resistance to thyroid hormone and exhibit symptoms despite having a normal TSH. Thyroid Peroxidase and Thyroglobulin Antibodies can interfere with the thyroid hormone function in the peripheral tissues while not affecting the suppressive effect of thyroid hormone on the TSH.¹⁴ The T3 receptor has 4 different gene variants with different types of receptors expressed in the brain than in the peripheral tissues.¹⁵ Lastly, there are some patients who have difficulty converting T4 to the active T3 hormone because of selenium deficiency or other conditions that interfere with human iodothyronine selenodeiodinases.¹⁶ In any of these cases, the TSH might appear normal despite clearly abnormal thyroid hormone function.

THE TOMATO EFFECT

I brought up the above discussion of the TSH test and the way it is used (and misued) to transition to a topic affectionately known as “The Tomato Effect.” According to folklore, newly settled Americans would not eat tomatoes because they belonged to the “nightshade family” of vegetables and were thought to be poisonous (as in “deadly nightshade”). They held onto this belief despite much evidence that they were safe to eat (tomato plants imported back to the old world where they were used quite extensively by the Italians (marinara sauce)). The belief system of the day did not match up with the facts available, and for quite some time, the facts were suppressed.