Transport Link Disorders
The first barrier on the hormone's path to tissues is the plasma protein system. The essence of the disorder lies in an excessive increase or decrease in the binding of the hormone to blood transport proteins.
The pathogenetic outcome is always a change in the level of the free (active) hormone, since the bound form serves merely as a reserve. The clinical presentation directly depends on this fraction:
- Decrease in the free fraction leads to symptoms of hypofunction.
- Increase in the free fraction causes signs of hyperfunction.
Insulin, cortisol, and iodine-containing thyroid hormones (T3 and T4) are the most dependent on plasma carriers.
Counter-Hormonal Link of Pathogenesis
This stage is characterized by the inactivation of the hormone even before it manages to bind to the target cell receptor. Suppression mechanisms include:
- Formation of anti-hormone antibodies. Immunoglobulins bind to protein hormones (e.g., ACTH, growth hormone, insulin), sharply reducing their free fraction in body fluids.
- Hyperactivity of degrading enzymes. For epinephrine, this is the excessive action of monoamine oxidase (MAO) and catechol-O-methyltransferase. For insulin, it is the excessive activity of insulinase, glutathione reductase, or glutathione transferase.
- Alteration of molecule conformation. The hormone structure can be deformed under the influence of severe tissue acidosis, free radicals, toxins, or heavy metal salts.
- Action of antagonist hormones. High concentrations of counter-regulatory hormones (cortisol, glucagon, catecholamines, GH, and thyroid hormones) physiologically prevent the realization of insulin effects.
Receptor (Reactive) Link
If the hormone successfully reaches the target cell, a failure may occur at the level of membrane receptors. This block includes several fundamentally different types of breakdowns:
- Quantitative changes: inadequate decrease or increase in the number of receptors on the membrane.
- Affinity alterations: imbalance between high-affinity and low-affinity receptors, which distorts the strength of the response.
- Antireceptor antibodies: autoantibodies physically block receptors (commonly seen with TSH and insulin receptors), preventing the hormone from binding.
- Blockade by non-hormonal ligands: foreign substances structurally similar to a hormone fragment occupy the receptor. This is characteristic of thyroid hormones, insulin, and insulin-like growth factors (IGFs).
- Cross-effects: the hormone erroneously binds to "foreign" receptors. A classic example is the activation of prolactin receptors by an excess of growth hormone (GH), clinically manifesting as galactorrhea.
Metabolic (Post-Receptor) Link
The final stage of postglandular pathologies is associated with disturbances in intracellular metabolism after successful contact of the hormone with the receptor, as well as disorders of systemic hormone utilization.
- Decreased hormone clearance rate: In severe hepatocyte pathology, the liver loses its ability to effectively inactivate insulin and steroids. As a result, active substances accumulate in the blood, forming the clinical picture of hyperinsulinism or hypercortisolism.
- Peripheral metabolism disorders: Excessive peripheral deiodination of thyroxine (T4) leads to the excessive formation of the more active form, which manifests as a hyperthyroid state.