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 the target cells themselves.
Main mechanisms and causes:
- At the pituitary and hypothalamic levels: thyroid-stimulating hormone (TSH) deficiency in hypopituitarism or thyrotropin-releasing hormone 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 drugs.
- Dietary causes: lack of iodine in the diet.
- Genetic abnormalities: gene mutations (TITF1, TITF2, FOXE1, PAX8) leading to impaired gland development or enzyme defects in thyrocytes.
- Peripheral factors: hormone inactivation in the bloodstream, decreased sensitivity of cell receptors to triiodothyronine ($T_3$) and thyroxine ($T_4$), as well as conversion failures (when inactive reverse $T_3$ is formed from $T_4$).
In addition, 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.
Pathism / Mechanism of development:
- Inherited defect in T-suppressor function.
- Disinhibition and stimulation of T-helper cells.
- T-helper cells 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 feedback mechanism.
- Constant stimulation by high TSH levels provokes gland growth, leading to goiter formation.
Congenital and endemic cretinism
Severe forms of hypothyroidism developing at an early age lead to cretinism.
- Sporadic (congenital) cretinism. Caused by genetic or intrauterine factors: absence or underdevelopment of the thyroid gland, mutations in thyrotropin-releasing hormone 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 certain biogeochemical provinces. The main cause is iodine deficiency in water and soil (characteristic of mountainous regions: Alps, Himalayas, Caucasus, as well as some plains). An additional factor is the excess of antithyroid substances in the environment (thiouracil derivatives, 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. Characteristic features include intellectual decline, drowsiness, lethargy, depressive states, hyporeflexia, paresthesias, and cerebellar ataxia. The tone of the sympathoadrenal system decreases.
- Cardiovascular system: bradycardia, cardiomegaly, cardialgia, heart failure, slowed blood flow, and microcirculatory disturbances.
Laboratory findings:
- Decreased serum levels of total $T_4$ and $T_3$.
- Decreased radioactive iodine uptake by the thyroid tissue.
- Anemia and hypercholesterolemia.
- The TSH level depends on the level of the lesion: it is elevated in primary hypothyroidism and decreased in secondary (central) hypothyroidism. In cases of thyrocyte resistance to TSH, it is normal or slightly elevated.
Briefly: answers to topical questions
Which ECG changes are most characteristic of hypothyroidism?
According to sources, low-amplitude QRS complexes are directly confirmed for hypothyroidism on ECG.
- Low-amplitude QRS complex — hypothyroidism is listed as a possible cause of such an ECG finding.
- Low-voltage ECG — diagnosed if the amplitude of the QRS complex does not exceed 5 mm in any of the leads.
How does the blood lipid profile change in hypothyroidism?
Hypothyroidism leads to pronounced secondary hyperlipidemia caused by impaired lipid catabolism. Lipid profile abnormalities become a key risk factor for atherosclerosis.
- Dyslipoproteinemia — development of Fredrickson types II and IV against the background of elevated LDL levels.
- Hypercholesterolemia — persistent elevation of cholesterol levels, which serves as a permanent metabolic marker of this pathology.
Which clinical manifestations of hypothyroidism are characteristic of the digestive system?
Regarding the digestive system and oral cavity in hypothyroidism, sources indicate constipation and tongue swelling.
- Macroglossia — characteristic swelling and enlargement of the tongue; dental impressions are noted along the lateral edges of the tongue.
- Constipation — listed among the gastrointestinal manifestations of hypothyroidism; a tendency towards constipation is described in congenital hypothyroidism.
- Prolonged neonatal jaundice — an early manifestation of congenital hypothyroidism involving the gastrointestinal and hepatobiliary systems.
Class and exam questions
Which laboratory parameter changes first in hypothyroidism?
Serum TSH level. Its change is the earliest and most sensitive sign of the disease.
Why does goiter develop in Hashimoto's disease?
Due to autoimmune destruction of the thyroid tissue, thyroid hormone levels drop. In response, the pituitary gland produces high amounts of TSH, which chronically stimulates the thyroid gland, causing its hypertrophy (goiter).
What is the difference between primary and secondary hypothyroidism based on laboratory tests?
In primary hypothyroidism, the thyroid gland itself is affected, so the TSH level is compensatorily elevated. In secondary hypothyroidism, the pituitary gland or hypothalamus is affected, so the TSH level is decreased.
What else to study on this topic
- Pathogenesis of lipid metabolism disorders in hypothyroidism (hypercholesterolemia)
- Mechanisms of hypothyroid encephalopathy development at the cellular level
- Hematological changes: types of anemia in thyroid hormone deficiency
- Pathogenetic features of thyroid hormone resistance syndrome
Master the entire topic in the "Pathophysiology" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Hypothyroidism" and another 4,913 pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 139 video lessons on the subject
Other topics in "Chapter 27. Typical Forms of Endocrine System Pathology"
Free video lessons: pathophysiologyShort lessons with lecture notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.