Hormone Optimization Part II: Thyroid & Adrenal Health in Cellular Medicine

August 14, 2025

Introduction

Thyroid and adrenal hormones are central regulators of metabolism, energy production, stress response, and cellular maintenance. Thyroid hormones primarily control metabolic rate, influence mitochondrial activity, drive cellular energy production, and are essential for protein synthesis and tissue repair. Adrenal hormones, including cortisol and adrenaline, coordinate the body’s response to stress, regulate metabolism, blood pressure, and help manage immune and cardiovascular function.

Dysregulation of these hormones, whether from autoimmune disorders, chronic stress, or nutrient deficiencies, can impair mitochondrial efficiency, disrupt protein synthesis, and compromise redox balance in multiple tissues. For example, low thyroid hormone reduces antioxidant defenses and alters cellular metabolism, while chronic overstimulation of the adrenal glands by stress can lead to persistent oxidative stress and mitochondrial dysfunction.

This article explores the cellular physiology of the hypothalamic–pituitary–thyroid (HPT) axis and hypothalamic–pituitary–adrenal (HPA) axis; common dysfunctions; and evidence-based nutritional interventions.

Thyroid Physiology & Cellular Impact

  • The hypothalamic–pituitary–thyroid (HPT) axis regulates thyroid hormone synthesis and release. TRH (thyrotropin-releasing hormone) from the hypothalamus stimulates pituitary secretion of TSH (thyroid-stimulating hormone), which prompts the thyroid gland to release T4 and T3. In peripheral tissues, deiodinase enzymes (DIO1 and DIO2) convert T4 to the active T3 form. T3 binds nuclear receptors, modulating gene expression to influence:
    • Mitochondrial Biogenesis: T3 up-regulates PGC‑1α, promoting mitochondrial proliferation, oxidative phosphorylation (OXPHOS), and increased ATP generation.
    • Protein Synthesis: T3 enhances ribosomal activity and expression of TCA cycle enzymes, elevating metabolic turnover and cellular repair.
    • Thermogenesis & Lipid Metabolism: Thyroid hormones induce UCP1 expression in brown adipose tissue, increasing heat production and stimulate fatty acid oxidation in muscle.

When hypothyroidism occurs, basal metabolic rate declines, antioxidant defenses diminish, and mitochondrial function is impaired, raising oxidative stress and increasing vulnerability to metabolic and cardiovascular dysfunction.

Adrenal Physiology & Stress Response

  • The hypothalamic–pituitary–adrenal (HPA) axis governs adrenal hormone synthesis in response to stress. Corticotropin-releasing hormone (CRH) from the hypothalamus stimulates adrenocorticotropic hormone (ACTH) release from the pituitary, which drives production of cortisol and DHEA in the adrenal cortex. Cortisol is the primary glucocorticoid involved in:
    • Supporting Gluconeogenesis & Lipolysis: Cortisol increases hepatic gluconeogenesis and lipolysis in adipose tissue to maintain adequate blood glucose during stress and fasting.
    • Modulating Inflammation: It represses NF‑κB activity in immune cells, thereby reducing the production of pro-inflammatory cytokines and dampening immune responses.
    • Influencing Autophagy & Apoptosis: Cortisol and the broader cellular stress response regulate autophagy and apoptosis to maintain cellular homeostasis during various stressors.

Chronic elevation of cortisol, from persistent stress, leads to HPA axis dysregulation, insulin resistance, and mitochondrial dysfunction, which increase cardiometabolic and cognitive risks. Conversely, adrenal insufficiency impairs physiological stress adaptation and disrupts redox buffering in steroidogenic tissues, heightening vulnerability to oxidative damage

Common Dysfunctions

  1. Hashimoto’s Thyroiditis: Anti‑TPO antibodies target and damage thyroid cells, driving local inflammation that impairs deiodinase activity and causes mitochondrial dysfunction. This disrupts metabolic regulation, leading to slowed ATP production and increased oxidative stress in tissues
  2. Subclinical Hypothyroidism: Marked by elevated TSH and normal T3/T4, this condition slows mitochondrial gene transcription and may reduce mitochondrial gene expression, contributing to fatigue and adverse lipid profiles. While some studies note increased mitochondrial activity as a compensatory response, overall metabolic efficiency is diminished and dyslipidemia is common
  3. HPA Axis Dysregulation: Chronic psychological and physiological stress blunts normal cortisol rhythms, impairing the HPA axis. Reduced cortisol output fails to support PGC‑1α–mediated mitochondrial biogenesis and energy regulation, resulting in decreased resilience to stress and poorer mitochondrial functions.

Targeted Nutritional & Lifestyle Strategies

  • Micronutrients for Thyroid Support
    • Iodine: Recommended daily intake for adults is 150µg; levels above 1,100µg may risk thyroid dysfunction
    • Selenium: 55µg/day is sufficient for thyroid health, but some protocols use 200µg/day for lowering thyroid antibodies in Hashimoto’s and improving thyroid hormone conversion; higher doses should be monitored
    • Zinc: 25–30mg/day supports thyroid hormone synthesis and conversion, upper end is commonly used in deficiency or Hashimoto’s
    • Iron: If ferritin < 50ng/mL, iron supplementation improves energy and normalizes metabolic function
  • Adrenal Cofactors:
    • Vitamin C: 500mg twice daily (1g total) aids adrenal steroidogenesis and stress resilience, with increased requirements in chronic stress
    • Magnesium: 250–500mg at bedtime supports relaxation, sleep quality, and stress buffering
    • Pantothenic Acid (B5): 300mg/day may enhance adrenal hormone production and stress adaptation
    • Adaptogens: Ashwagandha (300–600mg/day) and rhodiola (200–400mg/day) have evidence for stress reduction and HPA axis normalization
  • Circadian Alignment:
    • Morning light exposure and time‑restricted feeding (e.g. see [Intermittent Fasting & Calorie Restriction: Cellular Pathways to Longevity]) reinforce diurnal hormone rhythms, benefiting both HPT and HPA axis activity
  • Stress Management:
    • Daily meditation/breath-work and yoga reliably improve vagal tone, restore cortisol rhythms, and support overall HPA axis stability.

*All supplementation should be tailored based on individual lab results and under clinical supervision, especially for micronutrients with narrow safety margins like selenium and iron

Precision Peptide & Hormonal Therapies

  • Thyroid and Pineal Peptides: Specific low-molecular-weight peptides (derived from thyroid and pineal glands) have shown promise in improving thyroid function, lowering antibody levels, and enhancing tissue repair. Typical regimens involve short courses (e.g., 4–8weeks) under medical supervision
  • DHEA-S Supplementation: 10–25mg daily can restore adrenal androgen levels, support stress resiliency, and improve redox enzyme activity, especially in cases of adrenal exhaustion or underproduction

Practical Protocol & Monitoring

  1. Baseline Testing:
    • Assess: TSH, Free T4, Free T3, reverse T3, anti-TPO, anti-Tg, thyroid-associated antibodies (TAA), thyroid-stimulating immunoglobulin (TSI), morning serum cortisol, DHEA-S, salivary cortisol, ferritin, zinc, vitamin D, and hs-CRP
      • TAA refers to a broad panel of thyroid autoantibodies and helps screen for autoimmune thyroid diseases (such as Hashimoto’s or Graves’ disease).
      • TSI is the key marker for Graves’ disease and can distinguish autoimmune hyperthyroidism from other causes. Including TAA and TSI improves assessment of both hypothyroid and hyperthyroid autoimmune conditions.
  2. Phase 1 (Weeks 1–4):
    • Focus: Micronutrient repletion (iodine, selenium, zinc, iron, vitamin D) plus adaptogens (ashwagandha, rhodiola) and lifestyle alignment (morning light, time-restricted eating, stress reduction practices).
      • Nutrient repletion lays the foundation for healthy thyroid and adrenal function; adaptogens help manage stress and support HPA axis normalization.
  3. Phase 2 (Weeks 5–8):
    • Add: Peptide and hormonal interventions (e.g., DHEA-S 10–25mg daily for adrenal support, thyroid and pineal peptides if indicated); continue cofactors and adaptogens
      • Direct use of peptides and hormonal therapies should be done only under medical supervision
  4. Monitoring:
    • Repeat labs at Week 4 and Week 8 for TSH, Free T4/T3, cortisol, DHEA-S, ferritin, zinc, vitamin D, hs-CRP, and now TAA/TSI if autoimmune thyroid disease is suspected or being managed.
    • Track symptoms weekly (energy, mood, sleep, blood pressure) to ensure efficacy and safety.
    • Including TAA and TSI enhances diagnostic accuracy, helps tailor treatment for autoimmune thyroid disorders, and ensures ongoing monitoring for both hypothyroidism and hyperthyroidism.

Conclusion & Call to Action

Balancing your thyroid and adrenal hormones is the cornerstone of unlocking cellular energy, sharpening mental clarity, and building unshakable resilience to stress. By combining precision nutrition, strategic lifestyle alignment, and evidence-driven hormonal support, you can awaken your body’s innate ability to restore balance and thrive. This is about more than just hormone levels, it’s about reclaiming your vitality from the inside out.

Ready to harness your full potential? Book a consultation with Dr. Seeds and begin your personalized path to optimal thyroid and adrenal health.