Why does the thyroid gland secrete thyroid hormones (T4 and T3) and calcitonin?

Why the Thyroid Gland Secretes Hormones

The thyroid gland secretes thyroid hormones (T4 and T3) to regulate metabolism, growth, and development throughout the body, and calcitonin to participate in calcium homeostasis. 1

Primary Functions of Thyroid Hormone Secretion

Metabolic Regulation

• The thyroid produces predominantly T4 (thyroxine), which serves as a prohormone that is converted peripherally to the biologically active T3 (triiodothyronine) in target tissues. 2
• T3 exerts the majority of thyroid hormone action through ligand-dependent modulation of T3 receptors in nuclei, mitochondria, and other subcellular compartments, thereby controlling metabolic rate throughout the body. 3
• Both hyperthyroidism and hypothyroidism significantly impact metabolism, with hyperthyroidism increasing metabolic rate and hypothyroidism decreasing it. 1

Developmental Functions

• Thyroid hormone is critically important for development of various tissues, particularly the brain, and for regulation of metabolic processes throughout life. 4
• The biological activity requires transport of iodothyronines across cell membranes via specific transporters (such as OATP1C1 and MCT8) to reach intracellular receptors and deiodinases. 4

Regulation of Thyroid Hormone Production

TSH-Mediated Control

• TSH from the pituitary gland is the primary regulator of thyroid hormone production, controlling multiple aspects of synthesis including stimulation of iodide uptake, activation of thyroid peroxidase enzyme, regulation of oxidation and organification of iodide, control of secretion of T4 and T3 into circulation, and influence on post-translational modifications of thyroglobulin. 1
• Thyroid hormone biosynthesis is under tonic control of TSH, which maintains appropriate hormone levels through negative feedback mechanisms. 2

Biosynthetic Process

• Iodide is avidly taken up through the sodium/iodide symporter (NIS) at the basolateral membrane of thyrocytes. 2
• Thyroid hormone biosynthesis depends on the interaction of iodide, thyroglobulin (TG), hydrogen peroxide (H₂O₂), and thyroid peroxidase (TPO) at the apical plasma membrane of thyrocytes. 2
• The iodination of tyrosyl residues of thyroglobulin precedes thyroid hormone biosynthesis within the unique structures called thyroid follicles. 2

Calcitonin Secretion

Source and Function

• Calcitonin is synthesized by parafollicular C-cells that are interspersed between the follicles and the dense network of blood capillaries in the thyroid gland. 5
• Medullary thyroid cancer arises from these calcitonin-producing C cells, and malignant transformed C cells produce and secrete large amounts of calcitonin, making elevated serum calcitonin a marker of medullary thyroid cancer presence. 6
• Calcitonin participates in calcium homeostasis, with direct effects on bone metabolism (calcitonin at 100 mU/ml can inhibit bone resorption stimulated by other factors). 7

Peripheral Conversion and Activation

T4 to T3 Conversion

• The liver is the primary site where T4 is converted to T3 through type 1 deiodinase (DIO1), a selenoenzyme that produces the majority of peripheral T3. 8
• This peripheral conversion is essential for normal thyroid hormone action since T3 is the major active form of thyroid hormone. 8
• The conversion process is ATP-dependent and requires selenium as a cofactor for the deiodinase enzymes. 8

Nutritional Requirements

• Adequate iodine intake is essential for proper thyroid hormone synthesis, with daily requirements of 150 μg/day in adults. 1
• Iron is essential for thyroid peroxidase (TPO) activity, and iron deficiency impairs thyroid hormone synthesis by reducing TPO activity and affects tissue conversion of T4 to T3. 1
• Selenium is required for the deiodination of T4 to T3 via the selenoenzyme Type 1 5'-deiodinase. 1

Clinical Pitfalls

• Overtreatment with levothyroxine can lead to iatrogenic hyperthyroidism, increasing risk for osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy. 1
• TSH levels alone are not a sensitive indicator of iodine status, as concentrations are usually maintained within normal range despite frank iodine deficiency. 1
• Iron deficiency can impair thyroid metabolism and affect the conversion process, leading to relative T3 deficiency despite normal T4 levels. 8