Most thyroid problems are caused by issues in other tissues or organ systems. Read this post to learn more about the hypothalamic-pituitary-thyroid axis and other factors that influence thyroid function.

Introduction

The thyroid gland is involved in secreting important hormones T3 (triiodothyronine) and T4 (thyroxine).

T3 contains three iodine atoms and is created from the breakdown of T4. The breakdown of T4 is encouraged by the Thyroid Stimulating Hormone (TSH).

T4 is synthesized from the amino acid tyrosine, found in thyroglobulin (a protein created in the thyroid). It contains four iodine atoms.

Lack of T3 early in human development causes stunted growth.

T3 is very important in increasing energy production.

Main Thyroid Hormone Functions

  • Breathing
  • Energy production
  • Heart rate
  • Cognitive function
  • Mood
  • Body weight
  • Muscle strength
  • Menstrual cycles
  • Body temperature
  • Cholesterol levels
  • Growth and development
  • Intestinal flow
  • Digestion

Hyperthyroid Symptoms

Hyperthyroid (too much T3 or T4) symptoms include:

  • Sweating or sensitivity to high temperatures
  • Hair loss
  • Faster heart rate
  • Diarrhea
  • Weight loss
  • Missed or light menstrual periods

Hypothyroid Symptoms

Low levels of T3 causes a slower heart rate, constipation, and potential weight gain.

Hypothyroidism (too little T3 or T4) symptoms include:

  • Trouble sleeping and waking up earlier than you want
  • Tiredness and fatigue
  • Difficulty concentrating
  • Impaired memory
  • Depression
  • Anxiety
  • Sensitivity to cold temperature
  • Frequent, heavy periods
  • Constipation
  • Elevated blood cholesterol
  • Slowed heart rate
  • Weight gain
  • Joint and muscle pain
  • Dry skin and hair

The Hypothalamus-Pituitary-Thyroid (HPT) Axis

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The hypothalamus, pituitary, and the thyroid gland (also called the hypothalamic/pituitary/thyroid or HPT axis) control thyroid hormone levels (R).

Thyrotropin-releasing hormone (TRH) made in the hypothalamus binds to the receptors in the pituitary, causing it to release the thyroid stimulating hormone (TSH), which then stimulates T4 production (R).

If there is too little of the thyroid hormones in the bloodstream, the hypothalamus signals the pituitary gland (via TRH) to produce TSH for the thyroid to release more T3 and T4.

Once there is enough of these hormones, the hypothalamus is signaled to stop the release of TRH and the cascade of actions to increase T3 and T4.

High free T4 and free T3 levels signal the pituitary to adjust TSH and TRH levels (R).

Low free T3 and free T4 increase TSH, so TSH is typically the only hormone measured in a blood test to screen for hypothyroidism.

Somatostatin and dopamine from the hypothalamus also reduce TSH levels, thus reducing thyroid hormones (R).

Iodine is required for the synthesis of thyroid hormones.

rT3 is the mirror image of T3. It binds to the thyroid receptor but does not activate the receptor. It competes with T3, and prevents T3 from binding to and activating the thyroid receptor.

Conversion of T4 to the more active T3

Both T3 and T4 are produced in the thyroid gland, although T3 is much more potent than T4.

In the blood, T4 levels are around 45 fold higher (90 nM) than T3 (2 nM) (R).

Most T3 is produced by removing an iodine from T4 in a process that requires selenium (R).

The total activity of T3 thyroid hormone in the body depends on the enzyme that converts T4 to T3, which is found outside of the thyroid. This includes (R):

  • Type 1 deiodinase, which generates T3 for circulation, is found in the liver and kidney.
  • Type 2 deiodinase converts T4 to T3 within the cells of the brain, pituitary, and brown fat tissue.
  • Type 3 deiodinase, found in the placenta, brain, and skin, leads to the generation of rT3

Carrier proteins bind to most thyroid hormones, leaving only a very small fraction available. These include thyroxine binding globulin (TBG), albumin, and thyroid binding prealbumin (R).

Thyroxine Binding Globulin is made by the liver (R).

  • 99.97% of T4 is bound, and 0.03% is free.
  • 99.7% of T3 is bound and 0.3% of T3 is free.

Factors That Reduce Thyroid Function

1) Altered Gut Bacteria

Used thyroid hormones are deactivated by the liver and then excreted into the gut as part of bile. In the stomach, the thyroid hormones are absorbed and reabsorbed, so digestive problems reduce the levels of thyroid hormone reabsorption (R).

Gut bacteria also influences thyroid hormone levels. In rats, gut bacteria converts the deactivated thyroid hormone back into T3, and causes recycling of the T3 that would be eliminated (R).

Treatment with antibiotic increased blood T4 and rT3, but did not affect T3 levels(R).

2) Higher Estrogen

High estrogen levels increase Thyroxine Binding Globulin (TBG), which binds to more T3 and T4. This reduces the levels of free T3 and T4, even though total T3 and T4 levels are high (R, R2).

However, cell-based studies have not found the effect of estrogen on TBG production, suggesting that estrogen may increase TBG in other ways.

In a cell-based study, thyroid hormone, cortisol, estrogen, and nicotinic acid had little effect on the production of TBG (R).

In female rats that are menopausal from having their ovaries removed, estrogen replacement therapy changes the thyroid gland structure and function, which leads to hyperthyroidism (R).

In transsexual humans that are treated with sex hormones, oral estrogen increases TBG, while transdermal (skin-applying) estrogen does not. Testosterone lowers TBG and increases T3/T4 ratio. Estrogen does not affect T3/T4 ratio (R).

3) Stress

Most studies show that stress causes a decrease in thyroid hormones, although some studies show opposite effects. Acute stressors reduce TSH levels and thereby decrease T4 levels (R, R2). This makes TSH levels a less accurate marker to screen for hypothyroidism in the presence of stress.

Stress decreasing thyroid hormones:

  • In mice, repeated foot-shock stress increased cortisol, while reducing T3 and T4 (R).
  • Inescapable tail shock stress reduced thyroid hormones in rodents (R, R2).
  • Restraint (immobilization) stress decreased blood T3, increased blood rT3, and reduced T4 to T3 conversion in the liver and kidney. Removing the adrenals or blocking cortisol completely prevents the changes in thyroid hormones in response to stress (R).

Stress hormones reducing thyroid hormones:

  • Chronic HPA axis activation inhibits TSH and T4 to T3 conversion (R).
  • Cortisol inhibits TRH and the conversion of T4 to T3 in non-thyroid tissues in rats(R, RR).
  • CRH and cortisol both reduce blood T3 and T4 concentrations (R).
  • Administration of dexamethasone (a synthetic cortisol) suppress TSH levels in rats, including in hypothyroid rats (R).

However, in other studies, immobilization stress in rodents either increased or decreased thyroid hormone levels, depending on context (R, R2, R3, R4).

  • In mice, noise stress increases TSH levels but did not alter T3 and T4 levels (R).
  • In cell-based studies, cortisol stimulated TRH production (R).

4) Inflammation

In rats, injection of LPS (a bacterial toxin) suppresses production of TRH, TSH, and T3 levels, while increasing CRH and cortisol levels. However, blocking the CRH and cortisol increase does not prevent the reduction in TRH and TSH levels due to LPS-induced inflammation (R).

Chronic inflammation in mice reduces TRH production in mice and rabbits (R, R2).

Injection of IL-1, TNF, and IFN-gamma either in the blood or the brain results in a fall of blood TSH levels in rats. This may be because TNF reduces TRH production in rat hypothalamus (R, R2, R3).

Proinflammatory cytokines inhibit T4 to T3 conversion in a cell-based study (R).

TNF-alpha inhibited TSH activation of human thyroid cells in a cell-based study (R).

Cancer patients treated with IL-2 are temporarily hypothyroid (R).

Blood IL-2 levels are increased in patients with primary hypothyroidism and in a cell-based study (R).

5) Low Leptin or Leptin Resistance

Overfeeding newborns during the breastfeeding period may lead to obesity, leptin resistance, and lower thyroid hormone during adulthood (R, R2 ).

High leptin levels in newborn rats lead to high leptin, leptin resistance, and hypothyroidism in the hypothalamus at 30 days of age and at adulthood. In these animals, acute cold at 30 days old normalizes leptin levels and restores the leptin sensitivity in the hypothalamus. In addition, cold exposure further increased thyroid hormones (R).

Fasting reduces leptin and therefore reduces TRH, TSH production, T3, T4, and liver enzymes that convert T4 to T3 (R).

In addition, leptin-resistant humans have low T4 and normal TSH (R).

A leptin analog increased FT3 and FT4 in leptin-deficient children, and the reverse decreased T3 and T4 levels in people on a low-calorie diet (R, R2).

However, leptin administration does not reverse changes in thyroid hormone levels in acute fasting (R).

6) Environmental Toxins

Environmental toxins like polychlorinated biphenyls PCBs, polybrominated diphenyl ethers (PBDE), and other hormone disruptors, interfere with thyroid function (R, R2).

7) Fluoride

Fluoride at one point was a drug given to people who were hyperthyroid.

In zebrafish, mice, and rats, fluoride causes thyroid dysfunction, which could be ameliorated by taurine and calcium (R, R2, R3).

In a study of Indian school children, there were significant differences in TSH and thyroid hormone levels between two groups of students that are exposed to different levels of fluoride (R).

Nutrient Deficiencies That Can Cause Low Thyroid Hormones

1) Iodine

Iodine is required for the production of thyroid hormones.

However, getting more than 400mcg is problematic for many and some would argue even that’s way too much.

Excess iodine increases Th1 and Th17 immune responses (R).

Excess iodine increases IL-17, IL-23, IL-6 and TGF-b and it decreases Tregs.

What this means is that it increases inflammation, especially the Th17 immune system.

High iodine intakes are associated with a higher likelihood of autoimmune thyroid disease (R).

My recommendation is to experiment restricting or taking 400mcg. Do what works for you.

2) Selenium

Selenium is needed to convert T4 to T3 (R).

Selenium protects against autoimmune thyroid conditions (R).

Too much Selenium (300mcg) lowered T3 in men in one study, but a larger study couldn’t replicate the results (RR2).

Selenium also increases chromium excretion, so make sure to take chromium as well. I recommend 150-250mcg of chromium from all sources daily (RDA is 55mcg).

3) Iron

Iron is needed for thyroid peroxidase function, which is important in the synthesis of thyroid hormone (R).

I like to get ferritin over 70 and recheck.

4) Copper

Higher blood copper levels were associated with free and total T4 in males and both total T4 and T3 in females (R).

Higher levels of zinc were associated with lower free and total T4 in males (RR2).

5) Vitamin A

Vitamin A receptors bind to thyroid hormone receptors.

In obese women, vitamin A increased T3 and lowered TSH (R).

Hormones That Reduce Thyroid Hormones

Orexin, Ghrelin, and Neuropeptide Y

  • Orexin-A inhibits TRH, but causes no change in thyroid hormone levels (R).
  • NPY inhibits TRH (R).
  • In rats, ghrelin reduces thyroid hormones (R, R2). Ghrelin increases CRH from the hypothalamus (R). In rats, simultaneous injection of ghrelin and estradiol decreased the inhibitory effect of ghrelin on thyroid hormone concentration (R).

Ways to Optimize Thyroid Functions

In most cases, hypothyroidism and thyroid diseases result from dysfunctions in other systems. Nattha’s experience: When I work with my clients, I have better outcomes by working on #1 – #9 first:

  1. Maintain Circadian Rhythm and Leptin Sensitivity
  2. Correct Nutritional Deficiencies
  3. Correct Intestinal Gut Bacteria Imbalance and Gut Infections
  4. Reduce Inflammation
  5. Reduce Stress
  6.  Reduce Environmental Toxins

Cold Exposure

Cold exposure increases TRH (RR2R3R4).

Forskolin

Forskolin increases TSH, T3, and T4 (R).

LLLT

LLLT is also incredible at stimulating the thyroid and reducing local inflammation. Indeed, clinical trials have shown benefit for autoimmune thyroiditis (R).

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The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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