Thyroid gland and parathyroid glands

Thyroid gland

Overview

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.

Gross anatomy

Gross anatomy

Vasculature and innervation

Vessel Supplies
Arterial supply
  • Superior and anterior portions of the gland
  • Superior parathyroid glands
  • Posterior and inferior portions of the gland
  • Inferior parathyroid glands
  • Anterior surface and isthmus
Venous drainage

The inferior thyroid artery runs close to the recurrent laryngeal nerve and the superior thyroid artery close to the superior laryngeal nerve. Both nerves are at risk during thyroid surgery!

Microscopic anatomy

Lobules of thyroid gland

Cell type Characteristics Function

Thyroid epithelial cell (= follicular cells)

  • Appearance: basophilic cuboidal epithelium
  • Occurence: arranged in spherical follicles surrounding colloid
  • Surface receptor: TSH receptors

C cells (= parafollicular cells)

Function

The thyroid gland produces thyroid hormones, which stimulate metabolism and growth, as well as calcitonin, which decreases bone resorption and is involved in plasma calcium homeostasis.

Calcitonin

Thyroid hormones

Thyroid hormone synthesis

The thyroid hormones T3 (triiodothyronine) and T4 (thyroxine, tetraiodothyronine) are synthesized by thyrocytes in the thyroid follicles.

  1. Thyroglobulin, an iodine-free hormone precursor, is stored in the follicular lumen.
  2. Iodide is actively taken up by thyrocytes and transported into the follicular lumen.
  3. Here, thyroid peroxidase catalyzes the iodination of tyrosine residues of thyroglobulin, creating precursors monoiodotyrosine (MIT) and diiodotyrosine (DIT) and eventually the thyroid hormones.
  4. 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.
  5. T4 and T3 are then transported out of the thyrocyte into the blood.

Detailed steps of thyroid hormone synthesis

Steps Description Site

1. Synthesis of thyroglobulin (TG)

  1. Thyroglobulin (TG) is produced in the rough ER of the follicular cells.
  2. TG is packed in vesicles in the Golgi apparatus.
  3. TG is released into the follicular lumen via exocytosis.
Thyrocytefollicular lumen

2. Uptake of iodide

  1. Basolateral transport
    • Na+/I-symporter: Uptake of iodide by thyrocytes
  2. Apical transport
Blood vessel → thyrocytefollicular lumen

3. Iodination of thyroglobulin

  • Thyroid peroxidase (TPO)
    1. Oxidation of iodide (I- → I2)
    2. Organification of the generated I2 by covalently linking it with the tyrosine residues present in TG.
      • Generates single (TG + H2O2 + I2 = monoiodotyrosine, MIT) or double-iodinated species of tyrosine (TG-MIT + H2O2 + I2 = diiodotyrosine, DIT)
    3. Coupling reaction: conjugation of iodinated tyrosine residues
      1. Two DIT molecules form tetraiodothyronine (T4)
      2. One MIT and one DIT form triiodothyronine (T3)
  • NADPH-oxidase: apical enzyme that generates H2O2 for thyroid peroxidase
In follicular lumen

4. Storage

In follicular lumen

5. Release

  1. Reuptake of iodinated TG in thyrocytes via endocytosis
  2. Fusion of endocytosis vesicles with lysosome
  3. Proteolytic enzymes cleave TG to release T3, T4, DIT, and MIT
  4. T3 (∼ 20%) and T4 (∼ 80%) are released into the blood (via the MCT8 transporter)
  5. Deiodinase removes the iodine from the MIT and DIT
    • Iodine is then redistributed to the intracellular I- pool (iodine salvage).
Thyrocyte → fenestrated capillary network

Thyroxine hormone is produced from tyrosine and iodine.

TPO is stimulated by TSH and inhibited by propylthiouracil, methimazole, and excess iodine (Wolff-Chaikoff effect), resulting in high or low levels of thyroid hormones, respectively.

Transport and degradation

Thyroid hormones are lipophilic; 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.

Effect

In general, thyroid hormones increase the metabolic rate: oxygen and energy consumption as well as thermogenesis increase under their influence. See thyroid hormones in the general endocrinology learning card for more information regarding their functionality.

Target organ Effect
Heart
Lungs
Skeletal muscle
  • Increased development of type II muscle fibers (fast-twitch muscle fibers), which are capable of fast and powerful contractions
Metabolism
  • ↑ Basal metabolic rate due to ↑ expression of Na+/K+ ATPase in many tissues → ↑ oxygen consumption, ↑ body temperature, and ↑ RR
  • Anabolism of proteins (in high doses: catabolism of proteins)
  • Induces either lipolysis or liponeogenesis depending on metabolic status
  • Stimulation of carbohydrate metabolism (↑ glucose reabsorption, ↑ gluconeogenesis, ↑ glycogen synthesis, ↑ glucose oxidation)
Growth during childhood
Thermoregulation

Regulation

Like the adrenal steroid hormones, the thyroid hormones are under the control of the hypothalamic-pituitary axis (see “Feedback control mechanisms” in general endocrinology).

Thyroid-stimulating hormone (TSH) from the pituitary gland stimulates the basolateral uptake of iodine, as well as the biosynthesis and release of thyroid hormones.

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.

Embryology

During embryological thryroid migration, remnants of thyroid tissue can remain in the tongue (lingual thyroid) or along the migration path. Ectopic thyroid should always be considered when performing surgical procedures involving thyroid tissue.

Follicular cells arise mainly from the median thryoid anlage!
Parafollicular C cells arise mainly from the lateral thyroid anlagen!

Clinical significance

Parathyroid glands

Overview

  • Characteristics
    • There are four, oval-shaped endocrine glands embedded in the posterior surface of the thyroid gland
      • Two superior parathyroid glands: located near the superior pole of the thyroid gland at the junction of cricoid and thyroid cartilages.
      • Two inferior parathyroid glands: located in the area between the inferior poles of the thyroid lobes and the superior mediastinum.
  • Function: secretion of parathyroid hormone (PTH) in response to low calcium serum levels
  • Vasculature
    • Arterial supply: inferior thyroid arteries
    • Venous drainage: thyroid plexus of veins
    • Lymphatic drainage: deep cervical nodes, paratracheal nodes
  • Innervation: thyroid branches of the cervical ganglia

Microscopic anatomy

Function

Embryology

  • Superior parathyroid glands: derived from the fourth pharyngeal pouch
  • Inferior parathyroid gland: derived from the third pharyngeal pouch

DiGeorge syndrome 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.

Clinical significance

Surgery of the thyroid and parathyroid glands can result in destroyed or removed parathyroid glands due to their variable position. This may result in hypoparathyroidism and hypocalcemia.

last updated 11/24/2018
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