The thyroid gland is a butterfly-shaped endocrine gland located inferior to the larynx and anterior to the trachea. The thyroid gland develops from the fusion of the median thyroid anlage with the two lateral thyroid anlages, which are derived from the pharyngeal pouches. The thyroid gland is contained by the pretracheal fascia and internal capsule. It receives its arterial supply from the superior and inferior thyroid arteries and drains into the superior, middle, and inferior thyroid veins. The lymphatics drain into the paratracheal and deep cervical lymph nodes. It receives sympathetic innervation via the cervical ganglion and parasympathetic innervation via the vagus nerve. The thyroid gland secretes thyroid hormones, which regulate body metabolism and growth, and calcitonin, which lowers serum calcium and phosphate through inhibition of osteoclasts. Hormone synthesis occurs in the epithelial lining of the thyroid follicles. The epithelial lining consists of follicular (thyroid epithelial) cells, which synthesize thyroid hormone, and parafollicular (C) cells, which synthesize calcitonin.
The parathyroid glands are four, oval-shaped endocrine glands located on the posterior surface of the thyroid gland. They are derived from the third and fourth pharyngeal pouches. The parathyroid glands receive their arterial supply from the inferior thyroid arteries and drain into the thyroid venous plexus. The lymphatics drain into the paratracheal and deep cervical lymph nodes. The parathyroid glands are innervated by the thyroid branch of the cervical ganglia. The parathyroid chief cells secrete parathyroid hormone, which maintains serum calcium and phosphate homeostasis and, furthermore, antagonizes the effect of calcitonin by increasing serum calcium and decreasing serum phosphate. The recurrent laryngeal nerves, parathyroid glands, sympathetic trunks, and the nerves of the carotid sheath are at risk of injury during thyroid surgery.
- Characteristics: butterfly-shaped, unpaired endocrine gland composed of two lobes
- Located anteriorly in the lower part of the neck
- Extends from C5–T1
- Surrounded by pretracheal fascia (along with pharynx, trachea, esophagus)
- Relations of the thyroid gland
- Anteriorly: strap muscles (i.e., sternohyoid, sternothyroid, thyrohyoid, and omohyoid muscles)
- Medially: the trachea, esophagus, recurrent laryngeal nerve (RLN), and the external branch of the superior laryngeal nerve
- Posteriorly: the parathyroid glands cricoid cartilage, lower thyroid cartilage, and the carotid sheath with its contents (i.e., internal jugular vein, vagus nerve, and common carotid artery)
Damage to the recurrent laryngeal nerves, parathyroid glands, sympathetic trunks, and even the nerves of the carotid sheath is possible during thyroidectomy because of the thyroid's location in the anterior neck.
- The thyroid gland is made up of a left lobe and a right lobe connected by an isthmus.
- An ascending pyramidal lobe is present in ∼ 50% of the population.
- The thyroid gland is encapsulated by:
Vasculature and innervation
|Overview of arterial supply and venous drainage|
|Venous drainage|| |
- Paratracheal nodes
- Deep cervical nodes
Lobules of thyroid gland
- Main component: thyroid follicles
- Interfollicular spaces are filled by reticular connective tissue, fenestrated capillaries (facilitate the release of hormones into the blood), lymphatic vessels, adipocytes, and sympathetic nerves.
|Overview of thyroid cells|
Thyroid epithelial cell (follicular cells)
C cells (parafollicular cells)
Function: lowers calcium in serum (see “ ”)
- Bones: inhibits osteoclast activity
- Kidneys: increases excretion of calcium and phosphate
- Intestine: lowers calcium absorption
- The physiological role of calcitonin is low as bone and calcium metabolism are mainly regulated by the parathyroid hormone and vitamin D
- Released in response to increased serum calcium levels
- Clinical significance
Thyroid hormone synthesis
The thyroid hormones T3 (triiodothyronine) and T4 (thyroxine, tetraiodothyronine) are synthesized by thyrocytes in the thyroid follicles. 
- Thyroglobulin, an iodine-free hormone precursor, is stored in the .
- Iodide is actively taken up by thyrocytes and transported into the follicular lumen.
- Here, thyroid peroxidase catalyzes the iodination of tyrosine residues of thyroglobulin, creating precursors monoiodotyrosine (MIT) and diiodotyrosine (DIT) and eventually the thyroid hormones.
- To release T3 and T4, the iodinated thyroglobulin must be taken up again by thyrocytes, where it is broken down by lysosomes, thus releasing attached T4 and T3.
- T4 and T3 are then transported out of the thyrocyte into the blood.
- More T4 is produced than T3 but T3 is more potent than T4.
- The half-life of T3 is about one day (∼ 20 hours) and the half-life of T4 is about one week (∼ 190 hours) .
|Detailed steps of thyroid hormone synthesis|
1. Synthesis of (TG)
2. Uptake of iodide
3. Iodination of thyroglobulin
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Transport and degradation
Thyroid hormones are lipophilic, but due to their charged amino acid derivatives, they cannot simply diffuse across the lipid bilayer. Instead, they cross the plasma membrane with the help of transporter proteins (). Also, most of the circulating thyroid hormones are inactive and bound to transport proteins. Only a very small fraction (∼ 0.3%) is unbound and biologically active.
Thyroxine-binding globulin (TBG)
- TBG binds most of the serum T3/T4.
- The bound fraction of T3/T4 is biologically inactive.
- Hyperestrogenemia (e.g., pregnancy, OCP use) → ↑ TBG synthesis → ↓ free T3/T4 in serum → ↑ thyroid hormone synthesis
- Hypoproteinemia (e.g., nephrotic syndrome, chronic liver disease) → ↓ TBG synthesis → ↑ free T3/T4 in serum → ↓ thyroid hormone synthesis
- Transport protein synthesized by the liver that carries thyroxine and the retinol-RBP complex
- Negative acute phase protein
- Decrease in transthyretin leads to the preservation of amino acids for positive acute phase reactants.
- Conditions that result in the accumulation of transthyretin include senile cardiac amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy.
- Thyroxine-binding globulin (TBG)
- Degradation (liver): after sulfation/glucuronidation (biotransformation), thyroid hormones are excreted via bile
|Overview of thyroid hormone effects|
|Nervous system|| |
|Reproductive system |
- Stimulant (e.g., stress, extreme cold) → release of thyrotropin-releasing hormone (TRH) → ↑ secretion of thyroid-stimulating hormone (TSH) by the pituitary gland → ↑ synthesis and release of T3 and T4 by the thyroid gland
- Negative feedback by ↑ free T3 or T4 → ↓ release of TRH and ↓ pituitary sensitivity to TRH → ↓ thyroid hormones synthesis
- TSH release can also be decreased by somatostatin, dopamine, and glucocorticoids (outside of the hypothalamic-pituitary axis).
- TSH stimulating antibodies in Graves disease result in the direct stimulation of the pituitary gland and TSH release. (See “ for more information.)
- TBG: See “Transport and degradation” section above.
- Wolff-Chaikoff effect: a transient decrease in the production of thyroid hormones following the ingestion of a large amount of iodine via thyroid peroxidase inhibition
TSH levels are very sensitive to thyroid hormone dysfunction. If thyroid hormone levels are very high, TSH can fall below detection limits and if they are very low, TSH increases markedly. Therefore, serum TSH is an important parameter for assessing thyroid function and is usually the first step in thyroid diagnostics.
The thyroid gland develops in the first trimester of pregnancy from the fusion of the median thyroid anlage with the two lateral thyroid anlages derived from the pharyngeal pouches. Both follicular cells and C cells arise from pharyngeal endoderm 
- Median thyroid anlage
- Lateral thyroid anlagen (ultimobranchial bodies)
- A thyroid gland precursor that originates from the floor of the primordial pharynx
- It is located initially at the middle of the floor of the pharynx, near the base of the tongue, i.e., foramen cecum (tongue).
- It descends the neck, forming the thyroglossal duct, to settle into its adult anatomical position.
The thyroglossal duct usually obliterates after the thyroid gland has descended.
- However, in about 50% of people, the distal portion of the duct remains as a clinically unremarkable pyramidal lobe of extra thyroid tissue
- Thyroglossal cyst: caused by a persistent thyroglossal duct (See “ ” for more details)
- Lingual thyroid: caused by failure in descent of the thyroid gland to its normal position during embryogenesis
- The foramen cecum of the tongue remains.
During embryological thyroid migration, remnants of thyroid tissue can remain in the tongue (lingual thyroid) or elsewhere along the migration path. Incidental removal of ectopic thyroid tissue may result in hypothyroidism if the ectopic tissue is the only functioning thyroid tissue in the body.
- (e.g., de Quervain)
- Drug-induced: ,
- (e.g., )
- There are four, oval-shaped endocrine glands embedded in the posterior surface of the thyroid gland
- Function: secretion of parathyroid hormone (PTH) in response to low calcium serum levels
- Innervation: thyroid branches of the cervical ganglia
- Adipocytes (∼ 50%)
- Parathyroid cells (parathyroid chief cells)
- Oxyphil cells: red/pink cytoplasm; function not clear
Function of PTH
- PTH increases serum calcium and decreases serum phosphate (see “Calcium homeostasis”).
- Superior parathyroid glands: derived from the fourth pharyngeal pouch
- Inferior parathyroid gland: derived from the third pharyngeal pouch
is a congenital T-cell immunodeficiency that is caused by microdeletion at chromosome 22 (22q11.2). The deletion leads to defective development of the third and fourth pharyngeal pouches, resulting in aplastic parathyroids and hypocalcemia due to PTH deficiency.