What is hypothyroidism?

Hypothyroidism is a medical condition characterized by insufficient activity of the thyroid gland and other tissues involved in thyroid hormone signaling. 

Medical definitions related to hypothyroidism

Primary hypothyroidism:

  •  The thyroid gland is unable to produce sufficient thyroid hormones
  •  The most common form of hypothyroidism

Secondary hypothyroidism:

  • Thyroid hormone production is affected by dysfunction of the pituitary gland or hypothalamus
  • A relatively rare form of hypothyroidism

Hashimoto’s Disease (Hashimoto’s Thyroiditis)

  • An autoimmune disorder characterized by inflammation and damage to the thyroid gland 
  • Results in decreased production of thyroid hormones

Graves’ Disease

  • An autoimmune disorder characterized by the production of autoantibodies which stimulate the thyroid gland
  • Results in excess amounts of thyroid hormones


  • an abnormal enlargement of the thyroid gland, caused by iodine deficiency, inflammation, autoimmune disorder, or other factors

Key functions of thyroid hormone  (Shahid et al., 2024):

  • increases the basal metabolic rate, which influences the rate of energy use, body temperature, and rate at which food moves through the digestive tract
  • raises heart rate, stroke volume, cardiac output, and contractility
  • stimulates the respiratory function and leads to increased oxygenation
  • increases muscle and bone growth
  • promotes memory, speech, and sleep
  • regulates cholesterol synthesis (Mullur et al., 2014)
  • has roles in regulating other hormones, including leptin, insulin, growth hormone, and sex steroid hormones (Mullur et al., 2014)
  • has roles in fertility, ovulation, and menstruation
  • is critical for brain development in infants – promoting brain maturation by regulating axonal growth and the formation of the myelin sheath
  • stimulates bone growth in children

The thyroid system

The thyroid system refers to the network of organs, glands, hormones, and feedback mechanisms that regulate thyroid function and hormone production in the body.

Common symptoms of thyroid system under-functioning (Hypothyroidism, n.d.)(Hypothyroidism (Underactive Thyroid) – Symptoms and Causes, n.d.)

  • feeling tired and having low energy levels
  • sensitivity to cold
  • constipation
  • dry skin
  • weight gain
  • swelling or puffiness in the face
  • hoarse voice
  • coarse hair
  • muscle weakness
  • heavier or irregular menstrual cycles in women
  • feeling depressed or experiencing low mood
  • forgetfulness and difficulty with concentration or short-term memory

Key thyroid system components 

Hormones (Thyroid Hormone, n.d.):

  • Thyroxine (T4) – considered the inactive form of thyroid hormone. Once released into the bloodstream, T4 can be converted into the active form of thyroid hormone, T3, by various organs and tissues, including the liver, kidneys, and muscles [1] [8] .
  • Triiodothyronine (T3) –  the active form of thyroid hormone. Most of the T3 in the bloodstream comes from the conversion of T4 into T3 outside of the thyroid gland, particularly in the liver and kidneys [1] [8] [11] .
  • Thyroid-stimulating hormone (TSH) – produced by the pituitary gland and stimulates the thyroid gland to produce T4. TSH levels are regulated by a feedback loop involving the hypothalamus, pituitary gland, and thyroid gland. TSH is also known as thyrotropin.


  • Thyroid peroxidase (TPO) is an enzyme that attaches iodine molecules to tyrosine, and join the two of those tyrosines to form T4
  • Deiodinase enzymes (“de–iodine” enzymes) – activate and deactivate thyroid hormones in various tissues to maintain thyroid hormone balance (Sabatino et al., 2021)
  • Other molecules:
  • Thyroglobulin  a glycoprotein that serves as a framework for the synthesis of thyroid hormones T4 and T3, as well as storage of inactive forms of thyroid hormone and iodine
  • Transthyretin (TTR) – a protein in the blood that primarily functions as a transporter of thyroid hormones and retinol (vitamin A).

How the thyroid system works

The thyroid system involves a complex interplay between the hypothalamus, pituitary gland, thyroid gland, and various tissues and organs.

This is a simplified version of how the thyroid system works:

  1. The hypothalamus releases thyrotropin-releasing hormone (TRH).
  2. TRH stimulates cells in the pituitary gland to release thyroid-stimulating hormone (TSH).
  3. The pituitary gland produces and releases TSH.
  4. TSH stimulates the thyroid gland to produce and release thyroxine (T4) and also increase the number of iodine transporters in the thyroid.
  5. Thyroid cells produces and releases T4 into the bloodstream.
  6. The liver converts T4 to T3 (active form) and releases it into blood circulation.
  7. T3 is transported from the blood into cells.
  8. T3 binds to thyroid hormone receptors in the nucleus of cells, which activates DNA transcription and new protein synthesis.
  9. The new proteins facilitate actions throughout the body (See Key functions of  thyroid hormone above)

Key mechanisms of hypothyroidism

Hypothyroidism, or under-functioning of the hypothyroid system, is caused by one or more of the following mechanisms:

  • decreased production of T4
  • decreased conversion of T4 to T3
  • increased conversion of T4 to rT3
  • decreased function of cellular thyroid hormone receptors

All of these hypothyroid-causing mechanisms are influenced by nutrient depletions and other contributing factors presented on the hypothyroid webpages.

Decreased production of T4 due to:

  • decreased TSH levels
  • low iodine intake
  • inhibition of iodine and tyrosine uptake and utilization by other substances (competitive inhibition)
  • low levels of nutrients needed for T4 production – for example iodine,  tyrosine, selenium, iron, and vitamin A
  • oxidative stress (Ruggeri et al., 2020)
  • autoimmune destruction of thyroid cells

Decreased conversion of T4 to T3 due to:

  • Stress via increased cortisol (Heyma & Larkins, 1982)
  • Medications such as beta-blockers, corticosteroids, and some antidepressants can inhibit T4 to T3 conversion. [REF]
  • Nutrient deficiencies including selenium, zinc, and iron (Krishnamurthy et al., 2021)
  • Inflammation (De Luca et al., 2021) (Köhrle & Frädrich, 2022)
  • Oxidative stress
  • Low calorie diets (Fontana et al., 2006)
  • BPA (da Silva et al., 2019)
  • Hypoxia (low cellular oxygen) (Köhrle & Frädrich, 2022)
  • Endocrine disrupting chemicals (Köhrle & Frädrich, 2022)
  • Estrogen

Increased conversion of T4 to reverseT3 due to:

  • stress hormones (cortisol)
  • low nutrients required by enzymes as cofactors
  • environmental toxins (Köhrle & Frädrich, 2022)
  • inflammation (Köhrle & Frädrich, 2022)
  • oxidative stress [REF]?

Decreased function of cellular thyroid hormone receptors due to:

  • environmental toxins (Babić Leko et al., 2021)
  • BPA (da Silva et al., 2019) (Babić Leko et al., 2021)
  • inflammation [REF]
  • oxidative stress [REF]
  • genetics (Ortiga-Carvalho et al., 2014)

Medical standard of care

The medical standard of care for hypothyroidism primarily involves hormone replacement therapy to normalize thyroid hormone levels and alleviate symptoms.

The main hormones used are:

  • Levothyroxine (T4) –  a synthetic form of thyroxine (T4), which helps restore normal levels of T4 and T3 in the body.
  • Liothyronine (T3) – synthetic triiodothyronine (T3), used when patients do not adequately respond to levothyroxine alone.

Why consider an orthomolecular approach?

Hypothyroidism has numerous biological causes and contributors that have been identified through nutritional research and clinical practice. Each individual may experience hypothyroid symptoms for different reasons.

An orthomolecular approach:

  • identifies the drivers and causes of anxiety and focuses on understanding them
  • works WITH the body to restore balance and normal function, and considers the person with the condition vs. just the condition
  • addresses nutrient depletions that promote hypothyroidism whereas medications do not
  • can be done SAFELY in conjunction with most medical interventions

Atul Khullar, M. D. (2012). The Role of Melatonin in the Circadian Rhythm Sleep-Wake Cycle. 29. https://www.psychiatrictimes.com/view/role-melatonin-circadian-rhythm-sleep-wake-cycle    

Barnett, K. J. (2008). The effects of a poor night sleep on mood, cognitive, autonomic and electrophysiological measures. Journal of Integrative Neuroscience, 07(03), 405–420. https://doi.org/10.1142/S0219635208001903  

Bonnet, M. H. (n.d.). Caffeine Use as a Model of Acute and Chronic Insomnia. 11. 

Buysse, D. J., Angst, J., Gamma, A., Ajdacic, V., Eich, D., & Rössler, W. (2008). Prevalence, course, and comorbidity of insomnia and depression in young adults. Sleep, 31(4), 473–480. https://doi.org/10.1093/sleep/31.4.473 

Chapman, J. L., Comas, M., Hoyos, C. M., Bartlett, D. J., Grunstein, R. R., & Gordon, C. J. (2018). Is Metabolic Rate Increased in Insomnia Disorder? A Systematic Review. Frontiers in Endocrinology, 9, 374. https://doi.org/10.3389/fendo.2018.00374 

Sakami, S., Ishikawa, T., Kawakami, N., Haratani, T., Fukui, A., Kobayashi, F., Fujita, O., Araki, S., & Kawamura, N. (2002). Coemergence of Insomnia and a Shift in the Th1/Th2 Balance toward Th2 Dominance. Neuroimmunomodulation, 10(6), 337–343. https://doi.org/10.1159/000071474 

Schutte-Rodin, S., Broch, L., Buysse, D., Dorsey, C., & Sateia, M. (2008). Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults. Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine, 4(5), 487–504. 

Taylor, D. J., Mallory, L. J., Lichstein, K. L., Durrence, H. H., Riedel, B. W., & Bush, A. J. (2007). Comorbidity of chronic insomnia with medical problems. Sleep, 30(2), 213–218. https://doi.org/10.1093/sleep/30.2.2138. Van Cauter, E., & Knutson, K. L. (2008). Sleep and the epidemic of obesity in children and adults. European Journal of Endocrinology, 159 Suppl 1(S1), S59-66. https://doi.org/10.1530/EJE-08-0298 

Van Cauter, E., & Knutson, K. L. (2008). Sleep and the epidemic of obesity in children and adults. European Journal of Endocrinology, 159 Suppl 1(S1), S59-66. https://doi.org/10.1530/EJE-08-0298 

What Is Sleep Pressure and How to Get Enough of It. (2022, July 14). HealthNews. https://healthnews.com/sleep/sleep-science/what-is-sleep-pressure-and-how-to-get-enough-of-it/ 

What’s the Difference Between Dopamine and Serotonin? (2020, July 16). Healthline. https://www.healthline.com/health/dopamine-vs-serotonin