Causes of Hypothyroidism
The development of the syndrome is caused by multiple factors that can act at various levels of the neuroendocrine axis or within target cells.
Key mechanisms and causes:
- At the pituitary and hypothalamic levels: Thyroid-stimulating hormone (TSH) deficiency in hypopituitarism or thyrotropin-releasing hormone (TRH) deficiency/defect.
- At the thyroid gland level (primary hypothyroidism):
- Autoimmune destruction (Hashimoto's disease) by antithyroid antibodies.
- Iatrogenic factors: surgical removal of part of the gland, radioactive iodine therapy, overdose of antithyroid medications.
- Dietary causes: iodine deficiency in the diet.
- Genetic abnormalities: mutations in genes (TITF1, TITF2, FOXE1, PAX8) leading to impaired gland development or defects in thyrocyte enzymes.
- Peripheral factors: hormone inactivation in the bloodstream, decreased sensitivity of cell receptors to triiodothyronine ($T_3$) and thyroxine ($T_4$), as well as conversion impairment (when $T_4$ is converted into inactive reverse $T_3$).
Additionally, triggering factors can include trauma, surgery, stress, infections, and intoxications.
Chronic Autoimmune Thyroiditis
Hashimoto's disease is the most common clinical form of hypothyroidism. The pathology has a hereditary basis and is most frequently diagnosed in girls over 6 years of age and adolescents.
Mechanism of development:
- Inherited defect in T-suppressor function.
- Disinhibition and stimulation of T-helper cells.
- T-helpers trigger the synthesis of autoantibodies (against thyroglobulin, colloid, and the microsomal fraction).
- Antibodies damage the thyroid tissue, leading to primary hypothyroidism.
- Due to the drop in $T_3$ and $T_4$ levels, TSH secretion increases compensatorily via a negative feedback loop.
- Constant stimulation by high TSH levels provokes gland growth, resulting in goiter formation.
Congenital and Endemic Cretinism
Severe forms of hypothyroidism developing in early childhood lead to cretinism.
- Sporadic (congenital) cretinism: Caused by genetic or intrauterine factors: absence or underdevelopment of the thyroid gland, mutations in TRH or TSH genes, congenital defects in $T_3$ and $T_4$ synthesis enzymes, target cell hyperreactivity to hormones, or severe maternal hyperthyroidism during gestation.
- Endemic cretinism: Associated with living in specific biogeochemical provinces. The main cause is iodine deficiency in water and soil (characteristic of mountainous regions like the Alps, Himalayas, Caucasus, as well as certain plains). An additional factor is the environmental excess of antithyroid substances (derivatives of thiouracil, thiourea, thiocyanates, rhodanides) that block hormone synthesis.
Clinical and Laboratory Manifestations
Thyroid hormone deficiency leads to widespread systemic disorders.
Changes in organs and systems:
- Nervous system: Hypothyroid encephalopathy develops. Characterized by reduced intellect, drowsiness, lethargy, depressive states, hyporeflexia, paresthesias, and cerebellar ataxia. Sympathoadrenal system tone is reduced.
- Cardiovascular system: Bradycardia, cardiomegaly, cardialgia, heart failure, slowed blood flow, and microcirculatory disturbances.
Laboratory picture:
- Decreased serum levels of total $T_4$ and $T_3$.
- Decreased radioactive iodine uptake by thyroid tissue.
- Anemia and hypercholesterolemia.
- TSH levels depend on the level of the lesion: in primary hypothyroidism, it is elevated; in secondary (central), it is decreased. In cases of thyrocyte resistance to TSH, levels are normal or slightly elevated.