Anatomy and Physiology of the Thyroid Gland
The thyroid gland is located anterior to the trachea, below the thyroid cartilage, approximately one centimeter below the Adam's apple. This position makes it accessible for palpation, which is important for internists, surgeons, and oncologists when assessing size, consistency, and the presence of nodules.
The gland consists of follicles. In the center of the follicle is a colloid containing thyroglobulin, which binds T3 and T4 hormones. The periphery of the follicle is lined with thyrocytes, which capture iodine, store T3 and T4 in the colloid, and release them into the blood.
The thyroid gland synthesizes three hormones:
- T3 (triiodothyronine) — actively affects tissue metabolism
- T4 (thyroxine) — less active, but converted into T3 in peripheral tissues with the help of deiodinases
- Calcitonin — participates in calcium metabolism, serves as a marker for medullary thyroid cancer
It is also worth mentioning procalcitonin — synthesized in adipose tissue cells, it is a marker of bacterial inflammation and is used in the diagnosis and prognosis of sepsis.
Biosynthesis of Thyroid Hormones
For hormone synthesis, the thyrocyte requires amino acids and iodine. Amino acids form thyroglobulin, which enters the colloid, where tyrosine is attached to it—the basis for future T3 and T4. Iodine enters the cell via the sodium-iodide symporter.
In the colloid, with the help of the enzyme thyroperoxidase, iodine is attached to tyrosine: one atom yields monoiodotyrosine, two atoms yield diiodotyrosine. The combination of monoiodotyrosine and diiodotyrosine forms T3 (three iodine atoms), while the combination of two diiodotyrosine molecules forms T4 (four iodine atoms).
Thyroglobulin returns to the cell, where T3 and T4 are cleaved from it and enter the bloodstream. Unreacted mono- and diiodotyrosine return iodine back to the cell's reserve for reuse.
The entire process is regulated by the hormone TSH (thyroid-stimulating hormone), which binds to the TSH receptor and controls thyroperoxidase activity, thyroglobulin endocytosis, and iodine transport. There are three levels of regulation: hypothalamus (thyrotropin-releasing hormone) → anterior pituitary (TSH) → thyroid gland (T3, T4), with negative feedback from T3/T4 on the hypothalamus and pituitary gland.
Mechanisms of Disorders: Thyrotoxicosis and Hypothyroidism
At the biochemical level, antibodies to various components of the system may appear:
- TSH receptor antibodies — can be stimulating (causing Graves' disease), blocking, or neutral; used in the diagnosis of thyrotoxicosis
- thyroglobulin antibodies
- anti-TPO (thyroperoxidase) antibodies — the main marker in the diagnosis of hypothyroidism
Excess iodine temporarily inhibits thyroperoxidase (the Wolff-Chaikoff effect), after which the gland begins synthesizing hormones even more actively. This effect is used to protect the thyroid gland from radioactive iodine during radiation exposure.
It is important to distinguish between the concepts: thyrotoxicosis — the increased effect of T3 and T4 hormones on body tissues (which may be caused by hyperfunction of the gland or its destruction), whereas hyperthyroidism is a specific case of thyrotoxicosis associated specifically with excessive hormone production by the gland itself. Based on the level of the lesion, primary, secondary (pituitary), and tertiary (hypothalamic) forms of hypothyroidism and hyperthyroidism are distinguished.
Clinical Manifestations of Hypothyroidism and Hyperthyroidism
Symptoms develop slowly over weeks and months. Acute onset of weakness is not typical for thyroid pathology.
- Metabolism: in hypothyroidism — decreased cold tolerance, weight gain, decreased appetite; in hyperthyroidism — heat intolerance, weight loss, increased appetite
- Cognitive sphere: fatigue or irritability in both conditions
- Heart: decreased function in hypothyroidism, increased in hyperthyroidism
- Skin: cold and dry in hypothyroidism, warm and moist in hyperthyroidism
- Gastrointestinal tract: constipation in hypothyroidism, frequent stools in hyperthyroidism
- Muscles: cramps and pain, myopathy and weakness occur in both conditions
- Edema due to fluid accumulation in glycosaminoglycans can occur in both conditions
Most symptoms are nonspecific. Relatively specific signs include exophthalmos (in thyrotoxicosis) and pretibial myxedema on the anterior surface of the shin.
Causes and Diagnostics of Primary Hypothyroidism
Main causes of primary hypothyroidism:
- Hashimoto's autoimmune thyroiditis — painless, with anti-TPO antibodies, the most frequent cause
- subacute thyroiditis — develops after an infection, initially increases T3/T4 levels due to destruction, then decreases glandular function
- lymphocytic thyroiditis — painless course, difficult to diagnose
- granulomatous thyroiditis — accompanied by neck pain
- iatrogenic causes — intake of amiodarone and other drugs
- iodine deficiency — leads to a compensatory enlargement of the gland (goiter) due to elevated TSH levels
- Riedel's thyroiditis — a rare form
- thyroid dysplasia — a congenital condition
Hypothyroidism is 3 times more common in women than in men.
The diagnostic algorithm begins with measuring TSH as the most sensitive marker:
- normal TSH — thyroid pathology is unlikely (reference values up to 2.5 as normal for everyone is an erroneous practice)
- elevated TSH with low T4 — primary hypothyroidism
- elevated TSH with normal T4 — subclinical hypothyroidism
- low TSH with low T4 — secondary or tertiary hypothyroidism, requires pituitary investigation
Due to the physiological variability of TSH (diurnal fluctuations, effect of physical exertion), the test is recommended to be repeated at an interval of at least a month.
Treatment of Primary Hypothyroidism and Emergency Conditions
The mainstay of treatment is lifelong replacement therapy with levothyroxine at a dose of 0.9 to 1.8 mcg/kg, taking into account age, comorbidities, and cardiac risk. In patients over 50 years old and with high cardiac risk, therapy is started at a low dose (about 25 mcg) to avoid myocardial strain and exacerbation of angina.
TSH monitoring is performed no more than once every 6 weeks, since the half-life of levothyroxine is about a week, and time is required to reach a steady-state concentration. The drug is taken one hour before meals, separately from calcium preparations, iron supplements, and proton pump inhibitors, which reduce its absorption. The effectiveness of therapy is also affected by Helicobacter pylori infection, autoimmune gastritis, celiac disease, and poor treatment adherence.
Subclinical hypothyroidism (elevated TSH with normal T4) is a condition with ambiguous management. With a TSH of less than 10 and normal T4, active treatment is not indicated; with a TSH above 10, a course of levothyroxine is possible, and therapy is also discussed when planning pregnancy or in the presence of high cardiovascular risk.
Myxedema coma — a rare emergency condition with three-digit TSH values, developing against the background of long-standing hypothyroidism under the influence of triggering factors (trauma, infection, drugs including lithium). It manifests as altered consciousness ranging to coma and myxedema. Diagnosis includes assessment of TSH, T3, T4, cortisol, and blood glucose. Treatment requires emergency intravenous administration of levothyroxine and liothyronine combined with intravenous hydrocortisone to prevent adrenal insufficiency, which is difficult to rule out at the initial stage.
Key points
- The thyroid gland synthesizes T3, T4, and calcitonin; regulation is carried out by the hypothalamus-pituitary-thyroid axis via TSH.
- Thyrotoxicosis is the increased effect of thyroid hormones on tissues, and hyperthyroidism is its specific case resulting from glandular hyperfunction.
- Symptoms of hypo- and hyperthyroidism develop slowly and are mostly nonspecific, with the exception of exophthalmos and pretibial edema.
- Diagnostics begins with TSH, followed by T4 evaluation to determine the level and severity of the disorder.
- The main cause of primary hypothyroidism is Hashimoto's autoimmune thyroiditis with anti-TPO antibodies.
- Levothyroxine is the drug of choice for lifelong replacement therapy; the dose is selected individually with TSH monitoring every 6 weeks.
- Subclinical hypothyroidism requires treatment primarily when TSH is above 10 or in the presence of additional risk factors.
- Myxedema coma is a rare, life-threatening condition requiring emergency hormone therapy and glucocorticoids