The thyroid gland is a butterfly-shaped endocrine organ located in the anterior neck, just inferior to the larynx, spanning the C5 to T1 vertebral levels. It consists of two lateral lobes connected by a thin bridge called the isthmus , which lies over the trachea.
Structure and Histology
The thyroid is composed of multiple spherical follicles , the functional units of the gland. Each follicle is lined by follicular cells (thyrocytes) and filled with a protein-rich colloid containing thyroglobulin , a precursor to thyroid hormones. Scattered between follicles are parafollicular cells (C cells) that secrete calcitonin , a hormone involved in calcium homeostasis
Hormones of the Thyroid Gland
The thyroid gland produces three main hormones:
- Thyroxine (T4) – the primary hormone secreted, biologically less active
- Triiodothyronine (T3) – the active form, mostly produced by peripheral conversion of T4
- Calcitonin – a peptide hormone involved in calcium regulation, secreted by C cells
Biosynthesis of Thyroid Hormones
The synthesis of T3 and T4 involves several tightly regulated steps
- Iodide uptake – Follicular cells actively transport iodide from the blood via the sodium-iodide symporter.
- Iodide oxidation and organification – Iodide is oxidized by thyroid peroxidase (TPO) and binds to tyrosine residues on thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT) .
- Coupling reaction – TPO mediates the coupling of MIT and DIT to form T3 (MIT + DIT) and T4 (DIT + DIT).
- Storage – The iodinated thyroglobulin is stored in the colloid within follicles.
- Release – Upon stimulation, colloid is endocytosed, and T3 and T4 are cleaved and released into the bloodstream.
Regulation: Hypothalamic-Pituitary-Thyroid Axis
Thyroid function is regulated by the hypothalamic-pituitary-thyroid (HPT) axis
- The hypothalamus secretes thyrotropin-releasing hormone (TRH) .
- TRH stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH) .
- TSH binds to receptors on thyroid follicular cells, stimulating hormone synthesis and release.
This axis operates via negative feedback . Elevated levels of circulating free T3 and T4 inhibit TRH and TSH production, while low hormone levels stimulate them.
Actions of Thyroid Hormones
Thyroid hormones have widespread systemic effects , primarily by binding to nuclear receptors that regulate gene transcription
- Basal Metabolic Rate (BMR) – Increase oxygen consumption and heat production in most tissues.
- Cardiovascular system – Increase heart rate, cardiac output, and myocardial contractility.
- Growth and development – Essential for normal growth in children and fetal brain development.
- Metabolism – Enhance glucose absorption, lipid mobilization, and protein turnover.
- Neuromuscular system – Promote synaptic development and reflexes.
Peripheral Conversion of T4 to T3
Only about 20 percent of T3 is secreted directly from the thyroid gland. The rest is formed peripherally by deiodinases :
- Type I and II deiodinases convert T4 to active T3.
- Type III deiodinase converts T4 to reverse T3 (rT3) , an inactive form.
This peripheral conversion allows fine-tuned control of thyroid hormone activity in different tissues
Calcitonin and Calcium Homeostasis
Although not involved in metabolism, calcitonin helps regulate blood calcium by:
- Inhibiting osteoclastic bone resorption
- Promoting calcium deposition in bones
- Decreasing calcium reabsorption in the kidneys
Its role is relatively minor compared to parathyroid hormone (PTH) and vitamin D
High-Yield Notes
- Primary hormone secreted : T4 (inactive), converted to T3 (active) in tissues.
- TSH stimulates : Iodide uptake, hormone synthesis, and thyroid growth.
- Main hormone regulator : Hypothalamus-pituitary-thyroid axis.
- Function : Controls metabolic rate, thermogenesis, cardiovascular output, and CNS development.
- Disorders : Graves disease (hyperthyroidism), Hashimoto’s thyroiditis (hypothyroidism), thyroid storm (life-threatening thyrotoxicosis).
