Health care providers often face patients complaining of symptoms that appear to be related to hypothyroidism. These symptoms can include fatigue, weight gain, hair loss, cold intolerance, constipation, decreased concentration, depression, dry skin, infertility, hyperlipidemia, irregular or heavy menses, memory impairment and muscle aches [Source: Milner]. In some patients with these symptoms, TSH and T4 levels can be within normal limits, which could lead health care providers to rule out low thyroid function. However, thyroid metabolism is complex, and each step can be influenced by nutrition, prescription medications and lifestyle factors. Considering these influences can help practitioners in their understanding of how patients can suffer from symptoms of hypothyroidism even when their blood levels appear normal.

The thyroid hormone process begins when the pituitary gland in the brain produces thyroid-stimulating hormone (TSH). TSH then acts upon the thyroid gland to produce thyroid hormones. The two main thyroid hormones produced are thyroxine (T4) and triiodothyronine (T3). Although the thyroid gland produces more T4 (80 percent) compared with T3 (20 percent), T3 is 300 percent more active than T4 and is the thyroid hormone responsible for increasing metabolism. In fact, much of the T4 is converted into the more active T3 inside the cells of the body. Once the brain senses the thyroid gland has produced enough thyroid hormone, it will decrease TSH production. Through this negative feedback loop, the production of the thyroid hormones is slowed [Source: Brownstein].

Problems may arise when outside factors act upon the thyroid metabolism cycle which can lead to disruptions in TSH levels, decreased production of T4, incomplete conversion of T4 to T3 or imbalance in the ratio of T3 to reverse T3. High levels of cortisol caused by stress, for example, can suppress the production of TSH, leading to symptoms of hypothyroidism due to low hormone production. The thyroid gland could also appear to be functioning normally if TSH is the only blood level tested and it is being artificially suppressed by high cortisol levels [Source: Paoletti].

The production of T4 might also be disrupted. T4 is produced by the thyroid gland and is comprised of iodine and the amino acid tyrosine. If there is a lack of sufficient quantity of tyrosine or iodine, the production of T4 can be compromised [Source: Paoletti].

Incomplete conversion of T4 to T3 can also lead to low thyroid symptoms. T4 receptors in the body have not yet been identified; therefore, T4 needs to be converted in the peripheral tissue to the more active thyroid hormone T3 in order to relieve low thyroid symptoms. T4 is converted into T3 by removing an iodine from the T4 molecule at the 5’ position [Source: Paoletti]. Factors such as nutritional deficiencies and medications can inhibit this conversion. Nutritional deficiencies such as iodine, iron, selenium, zinc, vitamin A, riboflavin, pyridoxine and B12, along with the use of certain medications including beta blockers, birth control pills, estrogen, iodinated contrast agents, lithium, phenytoin and theophylline can inhibit the conversion of T4 into T3. Other factors that can cause this inhibition include aging, alcohol, alpha-lipoic acid, diabetes, fluoride, lead, mercury, pesticides, radiation, stress and surgery [Source: Brownstein].

Problems can arise if T4 is converted preferentially to reverse T3. Reverse T3 can bind to the T3 receptor, but it only has 1 percent of the activity of T3. T4 is normally converted into equal amounts of T3 and reverse T3. However, if there is a preferential conversion of T4 to reverse T3, the reverse T3 can act as an antagonist to T3 at the receptor level. This scenario leads to symptoms of low thyroid since reverse T3 can be considered inactive. Factors that may lead to a preferential conversion to reverse T3 include high cortisol, glucocorticoids, stress, excess estrogen and nutritional deficiencies such as selenium, iodine, zinc and iron [Source: Paoletti].

Symptoms of low thyroid can also be caused by factors not related to thyroid metabolism. Factors such as thyroid receptor numbers and their ability to function properly can play an important role in thyroid function. Cortisol levels need to be within normal range (morning saliva level of 3.7 to 9.5 ng/mL) and vitamin D levels need to be between 50 to 70 ng/mL for thyroid receptors to respond properly. Iron also plays an important role in thyroid hormone synthesis. Thyroid peroxidase activity depends on iron; therefore, iron deficiency could lead to hypothyroidism. Ferritin levels may need to be in the range of 90-110 to achieve proper thyroid function [Source: Paoletti].

This view inside thyroid metabolism helps to illustrate the many factors besides TSH and T4 levels that may be necessary in evaluating thyroid function. Evaluating TSH, free T4, free T3, reverse T3, thyroid antibodies, cortisol, vitamin D, ferritin, medication use and nutritional habits all can help health care providers determine the cause of a patient’s thyroid symptoms, and an appropriate care plan can be developed. Nutritional deficiencies can be corrected, lifestyle habits can be addressed and medication dosages can be adjusted based on a detailed patient history and evaluation of the lab values mentioned previously. If thyroid replacement is necessary, health care providers can utilize a commercially available thyroid medication, or they can contact a compounding pharmacist to prepare customized therapy with specific amounts of T4 and T3 based on that particular patient’s needs.