Thyroid Problems

Thyroid Gland:  an endocrine gland located in the anterior neck which consists of two lobes connected by an isthmus. The thyroid tissue within the gland is comprised of spherical structures called " thyroid follicles". "Follicular cells will form the borders of the follicles and a substance called "colloid" is located within the follicles. The follicular cells contain TSH-receptors, which when stimulated will synthesize thyroid hormones (T3 and T4). The thyroid will produce 80% T4 and 20% of T3. Most of the T3 originates from the conversion of T4 to T3 in peripheral tissues in a process called deiodination. 

Thyroid Stimulating Hormone (TSH): a hormone released from the anterior pituitary lobe in response to TRH (Thyrotropin Releasing Hormone, which is synthesized and released by the hypothalamus. TSH will stimulate the thyroid cells to synthesize T3 (triiodothyronine) and T4 (thyroxin). TSH is the one of the routine labs I will draw on your first visit, and this hormone is by far the most important one, as it is the most sensitive and specific marker of thyroid function. One important caveat is that TSH will spike in the AM, we call this the "TSH-circadian spike", so if your labs are drawn in the AM, and the TSH is high, I will likely redraw them after 12:00 noon, before initiating any treatment. Oftentimes, the TSH level will be significantly lower in the afternoon and I don't want to start any medicines that are not absolutely necessary. 

Thyroxin (T4): a thyroid hormone released from they thyroid gland in response to TSH. Free T4 is the active form of T4 that enters into cells all over the body to regulate your metabolism. Metabolism is measured in calories. Free T4 is one of the routine labs I will draw on your first visit. The half-life of T4 is long, about 4-6 days and for this reason, it is a relatively good marker of your thyroid function. 

Triiodothyronine (T3): a thyroid hormone released from they thyroid gland in response to TSH. Free T3 is the active form of T3 that enters into cells all over the body to regulate your metabolism. I will also draw a total T3 as well as a free T3 during your first visit. However, it is important to remember the T3s are not as important markers of thyroid function, as compared to TSH and Free T4, namely because the half-lives are so much shorter (between 6 hrs to one day), so levels of this hormone will be wax and wane much more rapidly as compared to levels of TSH and T4. 

Primary HYPOthyroidism: this diagnosis is made when the patient has HIGH blood levels of Thyroid Stimulating Hormone (TSH) and LOW or LOW-normal levels Free T4.

Subclinical HYPOthyroidism:  this diagnosis is made when the patient has HIGH or HIGH-normal levels of TSH with normal levels of Free T4. 

Central (Secondary) HYPOthyroidism:  this diagnosis is made when the patient has LOW or LOW-normal levels of T3 and T4 and the TSH level is not appropriately elevated..

Autoimmune Thyroiditis: a condition in which a person's body makes antibodies against proteins that are part of the person's own thyroid tissue; these are called "auto-antibodies". 

Hashimoto's Thyroiditis: a condition were there is inflammation within the thyroid tissue due to auto-antibodies, most often anti-thyroid peroxidase antibodies (anti-TPO Abs) or anti-thyroglobulin antibodies (anti-TG Abs). The inflammation is caused by lymphocytes infiltrating the thyroid tissue, which will eventually cause the thyroid cells to die causing HYPOthyroidism. We don't know why this happens, but most likely there is a combination of environmental factors and a genetic predisposition. 

HYPERthyroidism: this diagnosis is made when the patient has LOW blood levels of Thyroid Stimulating Hormone (TSH) and HIGH or HIGH-normal levels Free T4. 

Graves' Disease: an autoimmune thyroiditis and the most common cause of  HYPERthyroidism. The pt will make Thyroid Stimulating Immunoglobulins (TSIs) also called TSH-receptors antibodies. These autoantibodies will bind to the TSH-receptor sites located on the follicular cells within the thyroid gland and over stimulate the production of T3 and T4.  

Thyroid Function Tests (TFTs): laboratory tests that are done to diagnose thyroid conditions. The most common tests I will ask for are: TSH, FT4, T3 (total and Free), anti-TPO antibodies, anti-TG antibodies, and/or Thyroid Stimulating Immunoglobulins (TSIs).

Thyroid-Binding Globulins: proteins that bind T4 and T3 to transport the hormones through the blood. More than 99.95 % of T4 and 99.5 % of T3 are tightly bound to proteins in the blood, a very small percentage of these hormones are "Free"; only free hormones are metabolically active. 

Thyroglobulin: is a protein found inside the lumen of the thyroid follicles (circular structures within the thyroid tissue). Follicular cells form the borders of the follicles and contain receptors for TSH. When the TSH-receptors are stimulated by TSH (or at times by TSIs), thyroid hormones (T3 and T4 )will be synthesized within the follicles and then released into the blood stream. The thyroglobulin protein serves a a substrate for the synthesis of T3 and T4. 

Thyroid Stimulating Immunoglobulins (TSIs): antibodies made to the TSH-receptors located on the follicular cells within thyroid tissue. TSI's are  also called "TSH-receptor antibodies". They are the most common auto-antibodies found in Graves' Disease. The overstimulation of the TSH-receptors and subsequent over-production of thyroid hormones is the underlying cause of Graves' Disease. 

Anti-thyroid peroxidase antibodies (anti-TPO Ab): antibodies made against thyroid peroxidase, which is an enzyme that catalyzes the synthesis of the thyroid hormones which takes place within the thyroid tissue. 

Anti-Thyroglobulin antibodies (anti-TG Ab): antibodies are made against the person's own thyroglobulin protein. Anti-TG Abs are found in about 70% of the time in Hashimoto's thyroiditis, 60% of idiopathic thyroiditis, 30% of Graves' disease, and about 3% of thyroid cancers. 

Iodine: Iodine is obtained only by diet. It can be found in iodized salt (not sea salt), seafood, seaweed, kelp, dairy products and some vegetables. The easiest way to ensure you have adequate iodine intake is by just using iodized salt. 

I do not recommend any iodine drops or supplements. Supplements, in general, are not regulated, and it has been demonstrated numerous times that ingredients do not accurately reflect what the bottles claim the do. I have personally seen iodine 8x the upper limit in a pt who was taking iodine drops recommended by a holistic practitioner. Too much iodine puts the pt at risk of "Iodine-Induced Thyroiditis", which can be life-threatening in some individuals. 

- This is an image of what thyroid gland tissue looks like under a microscope. 

- Notice the thyroid follicles, which are circular structures. 

- Follicular cells form the borders form the follicles. The follicular cells have TSH receptors on them. 

- When the TSH receptors are filled, the synthesis of T4 and T3 ensues. 

- Thyroglobulin forms the colloid (the pink substance within the follicles), which is the site of thyroid hormone synthesis.

Pathology: 

The image to the Left is a surgical specimen from a patient with Hashimoto's thyroiditis. Some areas show normal-appearing follicles with minimal lymphocytic infiltrates, while other areas have complete destruction of follicles with dense lymphocytic infiltrates, in which the lymphocytes form germinal centers. 

Ref: image is from From Up-To-Date. 

You may be hearing about a rT3 test. Many providers feel this is helpful to demonstrated that you are "not converting an adequate amount of T3 to T4. 

My personal opinion is that testing for rT3 and treating for abnormal rT3 levels can cause more harm than benefit for my pts. Here is my thinking: 

• To the best of my knowledge, research has been done for many years and results have remained somewhat contradictory, which overall makes the studies less convincing. 
• rT3 has a half-life that is very short (~ 3 hrs) and this hormone is released in response to a rise in cortisol. 
• Cortisol rising and falling is a normal healthy response to day-to-day stressors. Thus, rT3 levels will rise and fall throughout the day in a normal healthy individual. Albeit, one would be expected to have higher levels of rT3 when stressors are high and/or one's response to environmental stressors is sub-optimal. 
• As mentioned above (Anatomy & Physiology section). The thyroid gland will make much more T4 than T3, and the T4 is converted to T3 in the liver, kidney, brain and skeletal muscle. 
• Assessment of this "conversion of T4 to T3" is  most done by calculating a "total T3:rT3 ratio", with an optimal ratio being 10:1. 
• Thus, when rT3 rises, this indicates a decrease in the conversion of T4 to T3. Remember it is only "free T3" that is active in our cells. 

How is High rT3 is Treated? 

Generally, two treatments are recommended: 

1. Decrease stress, which I recommend to ALL of my pts, regardless of their rT3 levels. Read about CBT on my "Therapist" webpage. 
2. Replace T3 hormone via pharmacotherapy, eg: liothyronine/cytomel. 

Additional Important Information: 

• Research is robust in demonstrating that it is much easier to optimize thyroid function (measured by TSH levels) using T4 replacement (eg: levothyroxine/synthroid) as compared to replacing T3 (eg: liothyronine/cytomel). 
• T3 has a much shorter half-life (=5-6 hrs) as compared to T4 (=5-6 days). Therefore it is much more difficult to keep the TSH at optimal levels, which is between 1.0 and 2.5 to optimize fertility. 
• Thus, I typically prefer to manage thyroid dysfunction using only T4 replacement. 
• Additionally, patients are at a much higher risk of lowering their TSH (below 1.0) when using cytomel. 
• A TSH lower than 1.0 can predispose the patient to HYPERthyroidism, which can in turn increase her risk of developing early osteopenia and osteoporosis (read more about this below). 
• However, If my patients demonstrate an adequate knowledge of what I teach them, and they would still like me to check their rT3 and try replacing their T3 using cytomel, I will be happy to work with you. 
• I would monitor your thyroid function tests every 12 weeks and adjust your medications accordingly. 

•  High levels of T3 and T4 (with low levels of TSH) will stimulate the osteoclasts to breakdown the bone, ie: increase bone resorption.
• This will result in an a decreased density of cortical bone and reduced volume of trabecular bone. 
• Thus, the patient with HYPERthyroidism is at an increased risk of developing osteopenia and/or osteoporosis earlier in life.

There have been many  studies published indicating there may be a benefit in treating anti-thyroid antibodies such as those seen in Hashimoto's Thyroiditis (anti-TPO and anti-TG), see "Important Definitions" above. 

However, from what I have seen the studies have remained contradictory. We know it is true that the presence of anti-thyroid antibodies (when greater than 50) indicates the pt's immune system is recognizing something in the normal healthy thyroid tissue as "abnormal" and is mounting an immune response to attack the normal protein. Therefore, it is likely that over time, the pt will eventually develop HYPOthyroidism. 

The theory presented is that LDN (low dose naltrexone at 4-4.5 mg daily) will decrease the anti-thyroid antibodies and prolong the time the patient has before she becomes hypothyroid. 

However, I am not sure sure there a way to design a quality, evidenced based study to evaluate the effect of LDN on thyroid antibodies, because we also know for sure that these antibodies will naturally wax and wane over time without any treatment. In other words, we cannot prove the LDN is lowering the antibodies, because they will often lower completely on their own. 

That being said, I do believe LDN may have a positive effect in mitigating  inflammation which is found in many disease conditions, including but not limited to Endometriosis and Infertility Below I have posted some studies were LDN has been used to treat inflammatory conditions, such as Rheumatoid Arthritis and Crohn's Disease, as well as a study looking at LDN use in cancer patients.