Thyroid Gland

The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck, spanning the regions between the C5 and T1 vertebrae and encircling the anterolateral trachea. The left and right lobes of the thyroid gland are connected by a central isthmus. Important processes in metabolism, growth, cardiac function, and calcium homeostasis are regulated by the thyroid hormones (thyroxine and triiodothyronine) and calcitonin.

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Development

Embryologic origins

  • Originates from the thyroid diverticulum
  • Develops during the 3rd to 4th gestational week
  • Develops from endoderm that lines the pharyngeal arches
  • Composed of:
    • 1 medial thyroid anlage 
    • 2 lateral thyroid anlagen

Medial thyroid anlage

  • Single midline structure
  • Makes up the follicular cells in the thyroid gland
  • Arises from the endoderm between the 1st and 2nd pharyngeal pouches at a point later known as the foramen cecum
  • Endoderm enlarges and forms the thyroid diverticulum.
  • Thyroid diverticulum migrates downward, deep into the neck, forming the thyroglossal duct.
  • Bifurcates to form the right and left lobes
  • Fuses with the lateral thyroid anlagen, forming the thyroid gland
  • Thyroglossal duct:
    • Typically obliterated and reabsorbed
    • May result in a pyramidal thyroid lobe extending up the neck
    • Fluid-filled thyroglossal duct cysts may form if the duct fails to fully regress.
Development of the thyroid diverticulum

Thyroid diverticulum formation and migration

Image by Lecturio.

Lateral thyroid anlage

  • Paired lateral structures
  • Ultimately forms the C cells of the thyroid gland
  • Also called ultimobranchial bodies
  • Arises from the endoderm 4th pharyngeal arch
  • Tissue is incorporated into the thyroid gland when medial and lateral anlagen fuse.
Thyroid gland development and migration of C cells from the ultimobranchial bodies

Thyroid gland development and migration of C cells from the ultimobranchial bodies

Image by Lecturio.

Gross Anatomy

Characteristics

  • Brown-reddish in color
  • H- or butterfly-shaped structure
  • Nodular
  • Approximate size:
    • Dimensions: approximately 4.5 cm x 1.5 cm x 1 cm 
    • Weight: approximately 10–20 grams 
  • Regions:
    • Right and left lobes
    • Isthmus: connects the right and left lobes
    • Pyramidal lobe: variable, often absent, extends from the isthmus toward the hyoid bone
  • Surrounded by the pretracheal fascia:
    • With the esophagus, trachea, and pharynx
    • Attached firmly to the laryngoskeleton 
  • 2 parathyroid glands are associated with the posterior aspect of each lobe (4 parathyroid glands in total).
(A) Anterior and (B) posterior views of the thyroid gland

Anterior (left) and posterior (right) views of the thyroid gland

Image by Lecturio.

Location

  • Anteriorly between the C5 and T1 vertebrae
  • Immediately inferior to the larynx
  • Encircles the anterolateral trachea
Thyroid in relation to trachea

The thyroid gland and its location in relation to the trachea

Image by Lecturio.

Borders, attachments, and associated anatomy

  • Superior to the isthmus: cricoid cartilage
  • Anterior:
    • Sternocleidomastoid muscles
    • Strap muscles:
      • Omohyoid
      • Sternohyoid
      • Sternothyroid
  • Posterior:
    • Parathyroid glands
    • Posteromedial:
      • Trachea
      • Esophagus
    • Posteroinferior to the left lobe: thoracic duct
  • Lateral: carotid sheath
  • Ligament attachments:
    • Anterior suspensory ligament: attaches the medial superior aspect of the thyroid to the cricoid cartilage and thyroid cartilage
    • Posterior suspensory ligament (Berry ligament): attaches the posteromedial thyroid to the cricoid cartilage, 1st and 2nd tracheal rings
  • Nearby nerves (can be injured during thyroidectomy):
    • Superior laryngeal nerve:
      • Innervates the cricothyroid muscles of the larynx
      • Travels with the superior thyroid artery until approximately 1 cm from the gland
    • Recurrent laryngeal nerve:
      • Innervates all intrinsic muscles of the larynx except the cricothyroid muscle
      • Located in the tracheoesophageal groove

Cross-section of the neck displaying the lobules and isthmus of the thyroid gland

Cross-section of the neck displaying the lobules and isthmus of the thyroid gland

Image by Lecturio.

Microscopic Anatomy and Function

Thyroid follicles

Thyroid follicles are the structural and functional units of the thyroid glands. Thyroid follicles are composed of a simple epithelial layer that encloses a colloid-filled cavity.

  • Follicular epithelial cells:
    • Presence of receptors for thyroid-stimulating hormone (TSH)
    • Production of thyroid hormones:
      • Triiodothyronine (T3)
      • Thyroxine (T4)
    • Production of colloid
  • Colloid:
    • Produced by the follicular epithelial cells
    • Contains iodo-thyroglobulin, the precursor of thyroid globulin
    • Stains pink on H&E stains
  • Functions of thyroid hormones:
    • To promote tissue oxygen consumption
    • To increase catecholamine production
    • To promote:
      • Cellular catabolic pathways
      • Heat production
      • Energy availability: glycolysis, glycogenolysis, fatty acid oxidation, Krebs cycle, and protein synthesis
    • To inhibit glycogen synthesis, gluconeogenesis, and fat deposition
    • To help regulate long bone growth and neural maturation
Histologic structure of the thyroid gland

Histologic structure of the thyroid gland

Image by Lecturio.

C cells

Also known as clear, light, or parafollicular cells.

  • Pale-staining cells
  • Have calcium-sensing receptors
  • Secrete calcitonin
  • Function of calcitonin: ↓ serum calcium levels
    • Inhibits osteoclast activity and bone resorption
    • Inhibits parathyroid hormone and vitamin D
Non-neoplastic thyroid epithelium

Non-neoplastic thyroid epithelium

Image: “Non-neoplastic thyroid epithelium” by Department of Immunoendocrinology, Chair of Endocrinology, Medical University of Lodz, Lodz, Poland. License: CC BY 4.0

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Neurovasculature

Blood supply

Multiple anastomoses are present, both ipsilaterally and contralaterally.

  • Superior thyroid artery:
    • Supplies the upper part of the thyroid
    • Originates as the 1st branch from the external carotid artery
    • Penetrates the thyroid gland on its anterior side
  • Inferior thyroid artery:
    • Supplies the lower half of the thyroid
    • Originates from the thyrocervical trunk (a branch off the subclavian artery)
    • Penetrates the thyroid gland on its posterior side
  • Thyroid ima artery:
    • Supplies the isthmus and the lower part of the thyroid
    • Variable origins; may be from the brachiocephalic trunk, right common carotid, subclavian, or others

Blood drainage

  • Superior and middle thyroid veins → internal jugular vein
  • Inferior thyroid veins → brachiocephalic vein
Blood supply of the thyroid

Blood supply to the thyroid gland

Image by BioDigital, edited by Lecturio

Lymphatic drainage

The thyroid gland drains into multiple different lymph nodes including:

  • Periglandular nodes
  • Prelaryngeal, pretracheal, and paratracheal nodes along the recurrent laryngeal nerve
  • Mediastinal nodes

Innervation

The thyroid gland is primarily innervated by the ANS.

  • Sympathetic innervation:
    • Superior, middle, and inferior cervical sympathetic ganglia
    • Activation may precipitate hyperthyroidism.
  • Parasympathetic innervation:
    • Fibers from the vagus nerve
    • Activation may precipitate hypothyroidism.
Innervation of the thyroid

Innervation of the thyroid gland

Image by BioDigital, edited by Lecturio

Clinical Relevance

High levels of thyroid hormone

  • Hyperthyroidism: an excess of triiodothyronine (T3) and thyroxine (T4). Clinical features of hyperthyroidism are mostly due to the body’s increased metabolic rate. Common findings include tachycardia, difficulty sleeping, and weight loss. Hyperthyroidism is diagnosed by determining TSH and free T4 and T3 levels. Typically, TSH levels will be low due to feedback inhibition on the pituitary gland resulting from elevated T4 and T3 levels.
  • Graves’ disease: the most common cause of hyperthyroidism. Graves’ disease is an autoimmune disorder characterized by a type II hypersensitivity reaction, in which antibodies stimulate the thyroid gland by binding to the TSH receptors.

Deficiency of thyroid hormone

  • Hypothyroidism: a deficiency of T3 and T4. Clinical features of hypothyroidism are primarily due to the accumulation of matrix substances and a decreased metabolic rate. Common symptoms include dry skin, fatigue, weight gain, and constipation.
  • Hashimoto thyroiditis: the most common cause of hypothyroidism in iodine-sufficient regions. Hashimoto thyroiditis is an autoimmune disorder that leads to goiter due to destruction of the thyroid gland.

Inflammatory disorders

  • Thyroiditis: inflammation of the thyroid gland. Thyroiditis can be due to many different causes, including autoimmune inflammation (most common), bacterial or viral infection, or a drug-induced reaction. Thyroiditis can lead to both hyperthyroidism and hypothyroidism. Initial inflammation of the thyroid gland can lead to a release of preformed thyroid hormone and cause subsequent hyperthyroidism. Once the preformed thyroid hormone is consumed, the individual may present with signs of hypothyroidism.
  • Goiter and thyroid nodules: a swollen thyroid gland due to hypo- or hypersecretion of thyroid hormones or inflammation is called goiter. Goiter and thyroid nodules can present singly (solitary nodular goiter) or as multiple nodules in different parts of the gland (multinodular goiter).

Neoplasms

Thyroid cancer: an uncommon cancer that can be managed well if detected early. Thyroid cancer arises from either the follicular or parafollicular cells within the thyroid gland. There are several subtypes of thyroid cancer depending on the cell of origin and the mutations that occur: mutated follicular cells can lead to papillary, follicular, and anaplastic carcinomas, whereas calcitonin-producing C cell mutations can result in medullary carcinomas.

References

  1. Dorion, D. (2017). Thyroid anatomy. In Medscape. Retrieved August 8, 2021, from https://emedicine.medscape.com/article/845125-overview 
  2. Lyden, M.L., Wang, T.S., and Sosa, J.A. (2021). Surgical anatomy of the thyroid gland. In UpToDate. Retrieved August 12, 2021, from https://www.uptodate.com/contents/surgical-anatomy-of-the-thyroid-gland

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