Cytokines and the Hypothalamus-Pituitary-Thyroid Axis

IL-1 beta, IL-6, and TNF-alpha have been shown to down-regulate the HPT axis causing:

  • a reduced production of TSH (thyroid stimulating hormone)
  • an inhibition of 5’-deiodinase (hepatic converter of T4 to T3)
  • a reduction in thyroid hormone uptake
  • a reduction of thyroidal release of T4 & T3 in response to TSH
  • altered glycosylation of TSH
  • a suppressed hypothalamic TRH (thyroid releasing hormone) release

The TSH range used in the standard healthcare system is so extremely broad that these patterns are typically not considered in the clinical work-up of the patient.

  • Patients with imbalanced cytokine expression suffer from thyroid symptoms and experience receptor site resistance despite having a TSH that falls within the wide reference range.
  • TSH alone dose NOT accurately assess thyroid function.
  • In functional evaluations of TSH the low value is 1.8 verses the 0.5 value.
  • A value lower than 1.8 with thyroid symptoms suggests the possibility of TH1 cytokine up-regulation causing an imbalance of the thyroid-pituitary-thyroid axis feedback loop.

Cytokines and Peripheral Thyroid Hormone Conversion

  • Both TH-1 and TH-2 cytokines – IL-6, TNF-alpha, INF-gamma, and IL-1 beta – have demonstrated the ability to down-regulate thyroid conversion potentials of T3.
  • T3 levels have very litle influence on TSH negative feedback loop
  • When T3 levels decline from cytokine 5’deiodinase mechanism, the TSH level will typically not be elevated.
  • If TSH is the only marker being evaluated, T3 imbalances will be overlooked.


Lipopolysaccharides (LPS) & Thyroid Metabolism

  • Adjuvants such as LPS found in the gastrointestinal tract has the potential to influence the thyroid at all levels
    • Diminishing the expression of the thyroid hormone receptor
    • Increasing inactive T3 levels
    • Decreasing TSH concentration
    • Promotion of autoimmune thyroid disorders
  • The connections with euthyroid clinical inflammation, GI disorders, and immune activity should not be overlooked in a clinical setting.

Cytokines & Thyroid Receptor Site Expression

  • Proinflammatory cytokines have been associated with non-thyroid illness in view if their capability to
    • Decrease D1 and thyroid hormone receptor (TR) beta-1 mRNA expression
    • Lead to on inflammatory pathways nuclear-factory-kappa-B (NF-KB) and activator protein 1
  • Both of the above scenario’s lead to suppression of receptor responsiveness.
  • Clinically, this patient may have normal thyroid-marker levels but still present with hypothyroid symptoms.
  • If the concept of cytokines suppressing thyroid receptor site responsiveness is NOT clinically addressed the patient ends up without proper management.

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