In normal physiology the thyroid gland regulates metabolism by maintain balance with the brain via the hypothalamus, the pituitary glands and the adrenals. This is referred to as the HPA axis. The hypothalamus produces Thyroid Stimulating Hormone (TSH) which tells the pituitary gland to stimulate the thyroid gland to release Thyroid Stimulating Hormone (TRH).

The function of the thyroid gland is to take iodine, found in many foods, and convert it into the thyroid hormones Thyroxine (T4) and triiodthyronine (T3). T3 is derived from T4 and is four times more active than T4. Reverse T3 (RT3) is an anti-thyroid hormone that can block the receptors for T3, causing or worsening hypothyroid conditions. Like most hormone systems, the HPA axis is controlled by feedback mechanisms to maintain balance and respond to the changing needs for active thyroid hormone production.


Eighty metabolic genes responding to thyroid all need iron, which is lower when hepcidin from your liver is elevated in response to inflammation.  High inflammation also interrupts the conversion of inactive T4 to active T3 inside tissue cells of the body. The result is a cellular hypothyroidism, even in the presence of normal T4 and T3, and is known as Peripheral Tissue Hypothyroidism.

On a lab test you will see: TSH is normal, T4 is normal, T3 is low and RT3 is high, indicating that inflammation is a problem, possibly due to autoimmune disease. In these scenarios, the elevations in inflammatory cytokines are depressing thyroid receptor site responsiveness while the hormones create a normal appearance of thyroid markers (TSH, T4 and T3).

Many autoimmune patients will not notice any difference even when taking T4 thyroid hormone because of decreased receptor site sensitivity and decreased conversion of T4 to T3 (Kharrazian, 2009).  As you correct the underlying inflammation, these patients do better with glandular thyroid or bioidentical hormones which contain time released T3.

Figure 6.28 Normal thyroid physiology


Cellular thyroid transporters play an important role in determining thyroid activity. Thyroid hormone transporters in the body require ATP energy for active transport and are effected by energy levels. In mitochondria disease. Low ATP leads to low thyroid levels in the tissues which is not reflected in TSH levels.

Mitochondrial disease, toxins and infections can lead to low concentrations of T3 and T4 inside tissues cells and elevated concentrations in the blood, while the pituitary may remain unaffected.


The first step is to take your temperature, as temperature reflects metabolic energy state. The average optimal temperature of a healthy individual is 98.6.Thyroid controls the metabolic sate and a lower than optimal temperature is indicative of hypothyroidism. A wide variability of temperature reflects an unstable or fatigued adrenal system. Core temperatures vary with the weather, rising when the weather is warm and falling when cold. Adrenal support will require two weeks to a few months to stabilized, progressing slowly to optimal temperature with fluctuations from day to day. If progress is not seen in several months you must address toxicity or nutritional deficiencies.


In adrenal fatigue total cholesterol tends to run low to low-normal while HDL tends to run high-normal to high.  In hypothyroidism the opposite tends to occur. Anxiety is usually related to the adrenals while depression more often reflects low thyroid. Obsessive compulsive actions improve as adrenals improve. Poor digestive as a result of low gastric production of HCL may be seen as an aversion to meat, indigestion, reflux and gut dysbiosis. Himalayan sea salt with over 87 trace minerals supports blood pressure which is often low in adrenal fatigue.  B5 and vitamin C support adrenal repair. Botanicals such as maca root licorice and eleutherococcus are excellent choices as well.

Low thyroid function shows a different pattern with a stable but low temperature. Treatment with Liothyroine SR will cause temperature to rise slowly and plateaus at a level reflective of the dose of T3. If adrenals cannot handle the increased level of energy, the rise in temperature is followed by a drop in temperature. The biggest mistake in treating thyroid conditions is not to address the adrenal function first.

A comprehensive discussion encompassing adrenal fatigue and the thyroid by Bruce Rind, MD may be found at The Thyroid Scale Interpretation Matrix and Metabolic Scorecard give excellent detail on this topic and are found at www.drrind.come/therapies/thyroid-scale matrix. (Rind, 2009)


Low thyroid function can be the body’s way of protecting a weakened heart by slowing down metabolism. Low levels of thyroid hormone are often the result of adrenal imbalance, nutritional deficiency such as low iron, or inflammation, all of which lead to stress on the heart as well as to low thyroid.  Support the heart by addressing the underlying conditions before trying to increase thyroid metabolism. Support the adrenal glands when supplementing with thyroid hormone or the result will be adrenal fatigue, as the thyroid and adrenals work together


Cellular hypothyroidism, which again is left undiagnosed by standard blood tests, increases the risk of the associated fatigue and depression often seen with chronic pain. Chronic pain will significantly suppress D1 in the body and upregulate D2 in the pituitary, resulting in a reduction in tissue T3 without a change in TSH. Unfortunately, significant cellular hypothyroidism is not detected by serum TSH and T4 testing (Ji, Xu, & Gao, 2014).


Acute or chronic dieting can result in a significant decrease in intracellular and circulating T3 levels by up to 50% (Araujo, Andrade, da Silva, Ferreira, & Carvalho, 2009), significantly reducing the basal metabolic rate (number of calories burned per day) by 15–40% (Wadden, Mason, Foster, Stunkard, & Prange, 1990).

Chronic dieting often results in low thyroid levels and metabolism which may not return to normal levels; the body stays in starvation mode for years with significantly reduced metabolism despite the resumption of normal food intake, making it very difficult to lose or maintain lost weight. Individuals with a history of intense dieting have dramatic reductions in T4 to T3 conversion with an intracellular deficiency of T3. Standard testing fails to detect the resulting dramatic reduction in tissue levels of T3.


    A ferritin blood test measures the amount of ferritin in the blood. Ferritin is a protein that binds to iron, and most of the iron stored in the body is bound to ferritin.

Iron deficiency is shown to significantly reduce T4 to T3 conversion, increase reverse T3 levels, and block the thermogenic (metabolism boosting) properties of thyroid hormone (Smith, Johnson, & Lukaski, 1993).


Traditional thyroid screening involves testing blood levels of circulating thyroid hormones. Thyroid hormone transport across cellular membranes is called autocrine or intracellular signaling. This form of hormone communication plays an important role in intracellular thyroid hormone levels and is proving to have considerable clinical significance.

Increases in rT3 levels are mainly a result of reduced transport of T4 into the cell and not due to increased T4 to rT3 conversion by D3 deiodinase enzyme.

High reverse T3 is a condition reflecting either an inhibition of reverse T3 uptake into the cell and/or there is increased T4 to reverse T3 formation (Hennemann, Vos, de Jong, Krenning, & Docter, 1993).

Due to rT3 and T4 transporters being equally energy dependent, a high serum rT3 has been shown to be a marker for reduced uptake of T4 into the cell (Hennemann et al., 1993). Reverse T3 is a reliable marker for identifying reduced cellular T4 and T3 levels that would not normally be detected by TSH or serum T4 and T3 tests (Hinz et al., 2015).

When this occurs, T4-only replacement is not advised. While a high rT3 can occasionally be associated with hyperthyroidism, as the body tries to reduce cellular thyroid levels. More often, identifying symptoms and using the free T3/rT3 ratio, which correlates with intracellular thyroid levels leads to a better analysis of the problem (van den Beld et al., 2005). A physician should test for indications of mitochondrial disease an analysis of imbalances of thyroid hormones,  as low ATP production would affect active transport of these hormones

Symptoms to look for when diagnosing hypothyroidism include fatigue, weight gain, depression, cold extremities, muscle aches, headaches, decreased libido, weakness, cold intolerance, water retention and PMS. It is best to use a combination of both clinical and laboratory assessments to determine the likely overall thyroid status.

A free T3/reverse T3 ratio of less than 0.2 being a marker for tissue hypothyroidism (when the free T3 is expressed in pg/mL (2.3–4.2 pg/mL) and the reverse T3 is expressed in ng/dL (8–25 ng/dL), (van den Beld, Visser, Feelders, Grobbee, & Lamberts, 2005).


A therapeutic trial of straight time released Liothyronine (SRT3) or Nature-Throid (T4/T3 combination therapy) can then be instigated in the presence of an elevated TSH.

In 2009, the 11th European Congress of Endocrinology released research showing that T3 supplementation can be significantly beneficial (Batterham, Le Roux, et al., 2003) in the presence of high or high-normal reverse T3 levels (Gomberg-Maitland & Frishman, 1998) compared to standard T4. Sustained release T3 is available from compounding pharmacies such as Liothyronine SR. When combined with supplemental ATP to drive transporter uptake by the cells, sustained release T3 can be extremely beneficial. Following up with immune system support and detoxification can further restore proper thyroid hormone balance.