Note: In patients with an extensive constellation of notable symptoms suggestive of hypothyroidism, or fluctuating symptoms of hypothyroidism, we suggest blood testing through your local GP for Hashimoto’s thyroiditis. This includes: 

 

• Thyroid Peroxidase Antibodies (TPOAb)

• Thyroglobulin Antibodies (TgAb)

 

This distinction is clinically important, as management differs between hypothyroidism and Hashimoto, whereby iodine is removed from treatment in cases of Hashimoto's until disease markers are rectified to avoid exacerbating autoimmune activity.

 

Hashimoto’s Thyroiditis Explained

 

Hashimoto’s thyroiditis is characterized by an immune-mediated attack on the thyroid gland. The condition involves the production of autoantibodies against thyroid peroxidase (TPO) and thyroglobulin, leading to progressive destruction of thyroid follicular cells and eventual fibrosis [13][14]

 

This immune process includes the infiltration of cells that release inflammatory cytokines. These immune assaults impair hormone synthesis and contribute to gland atrophy. The chronic nature of the autoimmune attack results in a gradual decline in thyroid hormone production and the development of overt hypothyroidism. Treating hypothyroidism is still applicable here, but with modifications to the approach. 

 

Iodine Deficiency

 

Iodine deficiency typically occurs due to insufficient dietary intake. One may notice that supplementation for iodine is actually potassium “iodide”. Iodide is the bioavailable form of the element iodine. 

 

Once absorbed, iodide is transported into thyroid follicular cells where the enzyme thyroid peroxidase (TPO) catalyzes its oxidation to elemental iodine. This iodine is then covalently attached to tyrosine residues on thyroglobulin, forming iodinated intermediates. These intermediates are subsequently coupled by TPO to produce the thyroid hormones triiodothyronine (T3) and thyroxine (T4). 

 

Without sufficient iodide, this entire hormone production cascade is impaired, resulting in reduced levels of T3 and T4 and a compensatory rise in thyroid-stimulating hormone (TSH) due to disrupted negative feedback [29].

 

Iron Deficiency

 

Iron deficiency frequently occurs due to poor dietary intake, chronic blood loss and malabsorption. It impairs thyroid function because iron is a vital cofactor for thyroid peroxidase (TPO), the enzyme responsible for iodination of tyrosine and coupling of iodotyrosines during hormone synthesis [10].

 

Without adequate iron, TPO activity diminishes, reducing the efficiency of thyroid hormone synthesis despite sufficient iodine availability. This bottleneck leads to lower circulating thyroid hormone levels and elevated TSH as the pituitary attempts to compensate.

 

A study in hypothyroid women with iron deficiency found that 150 mg/day elemental iron supplementation for 12 weeks significantly improved TPO activity and serum T3 and T4 levels [10].

 

Selenium Deficiency

 

Selenium deficiency interferes with thyroid hormone metabolism and redox balance. Selenium is required for the synthesis of iodothyronine deiodinases, which convert inactive T4 into active T3, and for glutathione peroxidases that protect thyroid cells from hydrogen peroxide-mediated oxidative damage during hormone synthesis [30].

 

When selenium is insufficient, the conversion of T4 to T3 is compromised, often resulting in elevated reverse T3 (rT3), which is biologically inactive. Additionally, impaired antioxidant defense mechanisms make thyroid cells more vulnerable to damage and underproduction.

 

Zinc Deficiency

 

Zinc plays a multifaceted role in thyroid hormone metabolism and receptor function. It is essential for the activity of deiodinase enzymes, which convert the inactive hormone thyroxine (T4) into the biologically active form triiodothyronine (T3). 

 

Additionally, zinc is important for the function of thyroid hormone receptors that bind to T3. Once activated, these receptors support metabolism, growth, and development. Without sufficient zinc, these receptors may not function optimally, leading to impaired cellular responses to T3.

 

Therefore zinc deficiency can reduce both the efficiency of T4 to T3 conversion and the sensitivity of tissues to T3, thereby contributing to symptoms of hypothyroidism even when circulating hormone levels appear normal [20].

 

In clinical research, supplementation with 30 – 50 mg/day elemental zinc for 3 months improved thyroid function in patients with low zinc status [20].

 

Chronic Stress

 

The hypothalamic-pituitary-thyroid (HPT) axis is a central regulatory system that maintains thyroid hormone homeostasis. It functions through a hormonal cascade where the hypothalamus secretes thyrotropin-releasing hormone (TRH), stimulating the pituitary gland to produce thyroid-stimulating hormone (TSH), which in turn signals the thyroid gland to release T3 and T4. Dysfunction at any point along this axis, particularly in the hypothalamus or pituitary, can result in hypothyroidism [1]

 

One of the key disruptors of this axis is chronic stress. Stress activates the hypothalamic pituitary adrenal (HPA) axis, elevating cortisol levels, which suppress the release of TRH and TSH. This reduces thyroid hormone production and leads to hypothyroid symptoms [31][42]. 

 

An 8-week study using 600 mg/day on the stress inhibiting herb Ashwagandha root extract in stressed hypothyroid individuals showed normalization of TSH and significant increases in T3 and T4 levels [31].

 

Heavy Metal Toxicity

 

Mercury

 

Mercury is a well-documented endocrine disruptor with a strong affinity for the thyroid and pituitary glands. It accumulates in these tissues and interferes with thyroid hormone production by occupying iodine-binding sites on thyroglobulin, thereby blocking thyroid hormone synthesis. 

 

Mercury also impairs hormone action by altering receptor interactions, and it is known to induce thyroid inflammation and hypothyroidism. Case reports have linked topical mercury-containing creams and high fish mercury exposure with reduced free T4 levels and overt thyroid dysfunction. [28].

 

Lead 

 

Lead exposure has been shown to alter thyroid function by interfering with the hypothalamic pituitary thyroid (HPT) axis. Lead accumulates in the pituitary gland and may reduce the secretion of TSH, which indirectly suppresses thyroid hormone production. 

 

Additionally, lead may directly impact the thyroid gland and inhibit peripheral conversion of T4 to T3, the active hormone. Epidemiological studies cited in your materials demonstrate lower T3 levels and elevated TSH levels in populations exposed to lead through contaminated water and industrial waste [23][28].

 

Cadmium 

 

Cadmium, commonly released from industrial pollution and cigarette smoke, accumulates in various tissues including the thyroid gland. It induces oxidative stress and impairs the biosynthesis of thyroid hormones. 

 

Cadmium exposure has also been associated with inflammatory changes in thyroid tissue and altered feedback regulation within the HPT axis. Animal models and human studies show decreased T4 levels and elevated TSH with cadmium exposure, indicating hypothyroidism [28].

 

Arsenic 

 

Arsenic interferes with thyroid hormone homeostasis through several mechanisms. It competes with iodine uptake in the thyroid gland, impairs the synthesis of T3 and T4, and influences gene expression of thyroid hormone receptors. 

 

Chronic arsenic exposure is associated with increased TSH levels and decreased free T4. It is often found in contaminated groundwater in various regions, and studies have linked long-term exposure to hypothyroidism [14].

 

Smoking

 

Cigarette smoke contains thiocyanate, a substance that competitively inhibits the sodium-iodide symporter, thus reducing iodide uptake by the thyroid. Additionally, smoking introduces reactive compounds that can interfere with thyroid hormone metabolism [9]. These mechanisms can exacerbate pre-existing thyroid dysfunction or hasten the progression to hypothyroidism.

 

In one study smokers with overt hypothyroidism had significantly higher clinical symptom scores and TSH levels than non-smokers, even when T3 levels were similar [9].

 

General Environmental Pollutants (PCBs, Dioxins, BPA)

 

Persistent organic pollutants such as polychlorinated biphenyls (PCBs), dioxins, and bisphenol A (BPA) mimic or interfere with thyroid hormones. PCBs and dioxins can induce hepatic enzymes that increase the degradation of thyroid hormones, thereby lowering their serum levels. BPA competes with thyroid hormone receptors and affects gene transcription in a hormone-disruptive manner. These compounds can also impair TSH regulation and influence fetal neurodevelopment by disrupting maternal thyroid function during pregnancy. Populations exposed to high levels of these chemicals, especially via industrial contamination or plastic consumption, show elevated rates of thyroid dysfunction [1][12][23].

 

Pesticides and Herbicides

 

Numerous pesticides and herbicides, particularly organochlorines and glyphosate-containing compounds, act as endocrine-disrupting chemicals (EDCs). These chemicals interfere with the synthesis, release, transport, metabolism, and elimination of thyroid hormones. Some pesticides have structural similarity to thyroid hormones and bind to thyroid receptors, disrupting their function. Others inhibit iodide uptake or thyroid peroxidase (TPO), enzymes essential for thyroid hormone synthesis. Exposure to these agents has been associated with increased incidence of hypothyroidism, particularly among agricultural workers and populations with chronic low-dose exposure [12][16].

 

Post-Surgical or Radioiodine Therapy

 

Thyroidectomy or radioiodine (RAI) ablation is often performed for hyperthyroidism or thyroid nodules. These procedures can lead to complete or partial loss of thyroid function depending on the extent of tissue removal [8].

 

As a result, the body loses its endogenous capacity to produce T3 and T4, necessitating lifelong thyroid hormone support and potential replacement.

 

Hyperestrogenism

 

Hyperestrogenism refers to elevated levels of estrogen, particularly estradiol. This can significantly impact thyroid function through multiple mechanisms. 

 

One of the primary ways is the stimulation of thyroid binding globulin (TBG). TBG is the main protein that binds and transports thyroid hormones in the bloodstream. When excessive estradiol increases TBG levels, a larger proportion of thyroid hormones become bound, when bound they are functionally unavailable, and can not exert their actions on the tissues. This often results in symptoms that mimic hypothyroidism, even when thyroid hormone levels are normal [1]. 

 

Additionally estradiol has been shown to reduce iodine uptake by the thyroid. Since iodine is essential for thyroid hormone synthesis, this suppression can impair the gland’s ability to produce adequate amounts of T3 and T4 [1].

 

There is also emerging evidence suggesting that estradiol may interfere with deiodinase activity, the enzymes responsible for converting T4 into the more active T3. This disruption further reduces the availability of active thyroid hormone at the cellular level [1].

 

Serotonin Deficiency 

 

Serotonin plays a key role in influencing the activity between the brain and the thyroid, known as  the hypothalamic-pituitary-thyroid (HPT) axis. Serotonin acts by stimulating the release of thyrotropin-releasing hormone (TRH) from the hypothalamus. This stimulation initiates the cascade that leads to the secretion of thyroid-stimulating hormone (TSH), and ultimately the production of thyroid hormones T3 and T4 by the thyroid gland. 

 

When serotonin levels are low the activation of TRH neurons diminishes, resulting in suppressed TSH secretion and reduced thyroid hormone synthesis, leading to hypothyroidism, even when the thyroid gland itself is structurally normal [1][43]. 

 

The association between serotonin deficiency and thyroid dysfunction is supported by studies showing that restoration of serotonergic tone, for example through SSRI antidepressants can normalize TSH and thyroid hormone levels in affected individuals. The relationship is also bidirectional with studies demonstrating thyroid medication, such as levothyroxine therapy can significantly improve depressive symptoms. In fact, levothyroxine is often used as an adjunctive treatment alongside antidepressants, showing faster and more effective improvement in mood symptoms compared to antidepressants alone [43].

 

Inflammation 

 

During systemic infection, trauma, or inflammatory states, the body mounts a "cytokine storm", where a surge of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) occur. 

 

In particular, cytokine IL-6 has been shown to  inhibit the expression and release of thyrotropin releasing hormone (TRH) and thyroid-stimulating hormone (TSH). This subsequently blunts the downstream synthesis of T3 and T4 by the thyroid gland. It has also been demonstrated that elevated IL6 even in the presence of low thyroid hormone levels, keeps TSH levels suppressed, thereby disrupting normal regulating mechanisms [44]

 

Elevated IL-6 has been linked to conditions including:
 

 

• Rheumatoid arthritis

• Systemic lupus erythematosus

• Ankylosing spondylitis

• Psoriasis

• Crohn's disease

• Impaired Glucose Tolerance

• Excess abdominal weight

• Low-grade anemia

• Chronic Stress

• Depression 

• Among many other disorders and diseases

​

Excessive Soy Consumption or Supplementation

 

Soybeans contain isoflavones such as genistein and daidzein, which are considered mild goitrogens. These compounds act by inhibiting TPO activity and impairing thyroid hormone biosynthesis. In individuals with compromised iodine intake, soy may contribute to elevated TSH levels and hypothyroid symptoms, but it is dose dependent [12][14][36].

 

An overview on several studies relating to the intake of soy isoflavones per day and the impact on thyroid function demonstrated the following:

 

< 25 mg per day

No Effect on Thyroid Function

 

40 – 80 mg per day 

May produce a very mild or negligible effect on thyroid function. 

 

> 100 mg per day

Studies have observed a modest increase in TSH levels, particularly in longer intake periods. This effect appears to be more pronounced in individuals with pre-existing thyroid vulnerabilities. While thyroid hormone levels T4 and T3 typically remain unchanged, the rise in TSH suggests a subtle interference with thyroid function or hormone sensitivity.

 

150 – 200 mg per day

Evidence of a more significant physiological response in susceptible individuals. A minority of participants with mild hypothyroidism progressed to overt hypothyroidism during long-term intake at this level. While this is not common in the general population, it highlights a potential risk when such high doses are consumed regularly, especially through supplementation rather than food.

 

[53] 

 

Soy Intake vs Soy Isoflavones content in mg

 

• 100g, Tempeh -  40 mg 

• 100g, Soy Beans - 40 mg

• 100g, Tofu -  25 mg 

• ½ cup Soy Milk  5 mg 

 

Cassava 

 

Cassava (also known as manioc) is a starchy root vegetable that is a staple food in many tropical and subtropical regions. Cassava contains high amounts of Thiocyanates and Thiocyanates interfere with iodine transport into the thyroid gland and this disruption leads to decreased synthesis of thyroid hormones, particularly in iodine-deficient individuals. Epidemiological data have shown higher rates of thyroid dysfunction among populations with cassava-based diets [24][36].