What Causes Hypothyroidism?
- Renee Grandi
- Apr 29
- 4 min read
(A Deep Biochemical Dive Into the Root Causes)
Hypothyroidism is not simply "bad luck" or "just ageing". It is a complex metabolic dysfunction caused by disruptions across immune regulation, nutrient metabolism, hormone balance, mitochondrial function, gut integrity, and environmental exposures.
To truly heal, you must understand the deeper WHY behind it and why a basic TSH test barely scratches the surface.
Let’s go through it systematically:
1. Autoimmune Thyroiditis (Hashimoto’s Disease)
✅ The science behind it:
Over 90% of adult-onset hypothyroidism is autoimmune.
Driven by loss of self-tolerance, the immune system mistakenly identifies thyroid enzymes (TPO and thyroglobulin) as foreign invaders.
✅ Biochemical why:
T-regulatory cells (Tregs) become suppressed, leading to immune hyperactivity.
Gut permeability (zonulin disruption) allows foreign antigens to cross into the bloodstream, leading to immune confusion (molecular mimicry).
✅ Common autoimmune triggers:
Epstein-Barr Virus (EBV) reactivation
Yersinia enterocolitica infection
Gut dysbiosis (loss of Lactobacillus spp. and Bifidobacteria)
Gluten sensitivity (gliadin cross-reactivity with thyroid tissue)
Vitamin D deficiency (lowers Treg formation)
✅ Testing markers:
TPOAb, TgAb, ANA, cytokine profiles (IL-6, IL-17A)
2. Nutrient Deficiencies in Hypothyroidism: The Unsung Drivers
✅ Essential nutrients + biochemical roles:
Nutrient | Role in Thyroid Biochemistry | Deficiency Effect |
Iodine | Forms backbone of T3 and T4 | Hormone deficiency |
Selenium | Converts T4 to T3 via deiodinase; reduces oxidative damage | Hashimoto’s risk, T3 underconversion |
Zinc | Needed for TSH binding, deiodinase activity | Poor T4 → T3 conversion |
Iron | Cofactor for TPO enzyme | Reduced hormone synthesis |
Vitamin D | Immune regulation (Treg activation) | Increased autoimmunity |
Magnesium | Energy for all thyroid enzyme activity (ATP cofactor) | Cellular sluggishness |
Vitamin A | Sensitises thyroid hormone receptors | Hormone resistance |
✅ Real world: If you are low in selenium and zinc, your T4 may look fine, but your T3 will be functionally low and your cells will feel "hypothyroid" even if TSH is “normal”.
3. Chronic Stress and HPA Axis Dysfunction
✅ The science behind it:
Chronic cortisol elevation suppresses hypothalamic thyrotropin-releasing hormone (TRH) production and pituitary thyrotropin (TSH) secretion.
Cortisol blocks peripheral T4 to T3 conversion and increases reverse T3 (rT3) (inactive hormone).
✅ Biochemical why:
Stress can steal from the pregnenolone pathway, a phenomenon known as "pregnenolone steal."
High cortisol levels trigger the NF-κb pathway, exacerbating systemic inflammation and impairing thyroid receptor sensitivity.
✅ Common clues:
Flattened cortisol curve
Elevated rT3, low free T3
Poor sleep, burnout, anxiety
4. Gut Dysbiosis, Intestinal Permeability, and the Thyroid
✅ The science behind it:
25% of T4 is converted to active T3 by gut bacteria.
Dysbiosis reduces conversion efficiency.
"Leaky gut" allows LPS (lipopolysaccharides) to enter circulation, driving autoimmunity.
✅ Biochemical why:
Zonulin overexpression opens gut tight junctions.
Microbial imbalance skews Th17 immune activation, leading to chronic inflammation.
✅ Associated gut conditions:
SIBO (small intestinal bacterial overgrowth)
Candida overgrowth
H. pylori infection (triggers molecular mimicry)
Chronic constipation (reduces enterohepatic recirculation of thyroid hormones)
5. Viral, Bacterial and Stealth Infections
✅ Key infections linked with hypothyroidism:
Pathogen | Mechanism |
Epstein-Barr Virus (EBV) | Molecular mimicry, direct thyroid invasion |
Cytomegalovirus (CMV) | Immune suppression and gland inflammation |
Helicobacter pylori | Cross-reactivity with thyroid tissues |
Borrelia (Lyme disease) | Chronic immune activation |
Mycoplasma | Persistent immune irritation |
✅ Biochemical why:
Chronic infections trigger cytokine storms (IL-1β, TNF-α), leading to thyroid tissue damage.
Reactivation of latent viruses under chronic stress suppresses thyroid function.
6. Environmental Toxins and Xenoestrogens
✅ The science behind it: Xenoestrogens (chemical oestrogens) and environmental pollutants directly disrupt thyroid function at multiple levels:
Toxin | Impact |
BPA (plastics) | Blocks thyroid receptor binding |
Perchlorates (water contaminants) | Block iodine uptake into thyroid cells |
Pesticides (glyphosate) | Gut dysbiosis, immune disruption |
Flame retardants (PBDEs) | Alter thyroid hormone transport proteins |
✅ Biochemical why:
Xenoestrogens bind to oestrogen receptors → increased TBG → less free T3/T4.
Direct oxidative damage to thyroid gland mitochondria.
7. Hormonal Imbalances (Oestrogen Dominance, Progesterone Deficiency)
✅ Specific hormone imbalances that impact the thyroid:
Elevated oestrogen increases thyroid-binding globulin (TBG), which reduces the free, active thyroid hormone.
Progesterone deficiency reduces T4→T3 peripheral conversion.
✅ Biochemical why:
Imbalanced hormone ratios increase susceptibility to autoimmunity through Th2 skewing.
Poor hormonal communication between the ovary-adrenal-thyroid axis.
✅ Common signs:
PMS, heavy periods and breast tenderness
Mid-cycle spotting, irregular cycles
8. Poor Liver Function
✅ Scientific fact:
60% of T4 → T3 conversion occurs in the liver.
✅ Why:
Liver dysfunction impairs the deiodinase enzymes (types D1 and D2).
Oestrogen clearance impairment raises TBG.
✅ Markers:
Elevated ALT, GGT
Symptoms of sluggish liver (bloating, poor skin, hormonal imbalance)
9. Blood Sugar Dysregulation and Insulin Resistance
✅ The science behind it:
Insulin resistance reduces thyroid receptor sensitivity.
Chronic blood sugar instability stresses the adrenal-thyroid axis.
✅ Biochemical why:
High insulin levels drive systemic inflammation, as evidenced by a rise in CRP.
Impaired glucose regulation starves mitochondria, reducing thyroid hormone action at the cellular level.
10. Genetic Factors
✅ Polymorphisms involved:
MTHFR mutations: Impaired methylation, poor detoxification, and higher homocysteine (which can damage thyroid tissue).
DIO2 gene variants: Impaired T4 → T3 conversion.
✅ Biochemical why:
Reduced glutathione synthesis, mediated by MTHFR, increases oxidative stress within the thyroid gland.
Poor T3 generation despite normal T4 and TSH levels.
Conclusion: Hypothyroidism Is Never Just About the Thyroid
It is about the entire system: immunity, gut, nutrients, hormones, mitochondria, and environment.
If you have been told "your thyroid is just slow" or only tested for TSH, you have not been given the whole picture.
Feeling Overwhelmed? You Are Not Alone.
Investigating the root causes of hypothyroidism requires a comprehensive assessment, including thyroid panels, nutrient levels, immune profiles, gut health mapping, hormonal analysis, and toxin evaluations.
🌿 At Women's Integrative Health Clinic, I specialise in uncovering YOUR unique thyroid story.
🌿 You deserve an individualised investigation, not just another prescription.
🔗 Book your Root Cause Thyroid Consultation today and take the first empowered step toward true healing.
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