Thyroid Anatomy and Physiology


Thyroid Anatomy

  1. Embryology
    • thyroid originates from the base of the tongue (foramen cecum)
    • descends along the thyroglossal tract anterior to the hyoid bone and larynx
    • descending thyroid is joined laterally by parafollicular cells from the neural crest - these cells secrete calcitonin

    1. Lingual Thyroid
      • thyroid develops but fails to descend
      • usually presents as a posterior tongue mass
      • may represent the patient’s only functioning thyroid tissue
      • diagnosis made by thyroid scan
      • treatment consists of thyroid suppression with thyroxine
      • malignancy is rare

    2. Thyroglossal Duct Cyst
      • arises from persistence of a portion of the thyroglossal tract (duct)
      • usually presents as a midline neck mass in childhood or adolescence
      • diagnosis can be made by asking the patient to protrude his tongue - a thyroglossal cyst should move upward
      • treatment is surgical excision and should include the entire thyroglossal duct remnant as well as the central portion of the hyoid bone (Sistrunk procedure)
      • ~ 1% of thyroglossal duct cysts contain thyroid cancer

      Thyroglossal Duct Cyst
    3. Lateral Aberrant Thyroid
      • now felt to represent a well-differentiated thyroid cancer that has metastasized to a cervical lymph node
      • the primary tumor is usually found in the ipsilateral thyroid lobe

  2. Surgical Anatomy
    1. Strap Muscles
      • cover the thyroid anteriorly
      • innervated by the ansa cervicalis
      • sternothyroid muscle lies deep to the sternohyoid muscle

      Thyroid Strap Muscles
    2. Blood Supply and Lymphatic Drainage
      1. Arterial Supply
        • paired superior thyroid arteries arising as the first branch of the external carotid
        • paired inferior thyroid arteries arising from the thyrocervical trunk of the subclavian arteries
        • occasionally the thyroid ima is present, arising from the aortic arch or innominate artery

        Thyroid Arterial Blood Supply
      2. Venous Drainage
        • superior thyroid veins → internal jugular vein
        • middle thyroid veins → internal jugular vein
        • inferior thyroid veins → brachiocephalic vein

        Thyroid Venous Drainage
      3. Lymphatic Drainage
        • categorized according to superior, inferior, and lateral drainage patterns
        • superior aspect of the isthmus and median aspects of the lateral lobes drain upward into the prelaryngeal (delphian) nodes
        • inferior lymph vessels follow the inferior thyroid veins to drain into the pretracheal and innominate nodes
        • lateral lobes drain into the internal jugular nodes

        Thyroid Lymphatic Drainage
    3. Parathyroid Glands
      • usually closely related to the thyroid and are covered by the thyroid sheath
      • upper glands are more posterior, and may descend into the posterior mediastinum
      • lower glands are more variable in position but are usually anterior to the recurrent laryngeal nerves, and may descent into the thyrothymic tract or thymus gland
      • blood supply of all glands comes from the inferior thyroid artery

    4. Laryngeal Nerves

      5. Recurrent Laryngeal Nerve - Lateral
      1. Recurrent Laryngeal Nerve
        • branch of the vagus nerve
        • innervates all the muscles of the larynx except the cricothyroid
        • unilateral injury leads to vocal cord paralysis and hoarseness, as well as ineffective cough and aspiration
        • bilateral injury leads to complete loss of voice and airway obstruction
        • on the right, the recurrent nerve loops under the subclavian artery
        • on the left, the recurrent nerve arises at the level of the aortic arch and loops beneath the ligamentum arteriosum
        • usually ascends upwards in the tracheoesophageal groove
        • may run behind the inferior thyroid artery, between its branches, or in front of it
        • in ~ 1% of cases, the right nerve is nonrecurrent and enters the larynx directly

      2. Superior Laryngeal Nerve
        • also arises from the vagus nerve
        • at the level of the hyoid bone, it splits into internal (sensory) and external (motor) branches
        • external branch travels with the superior thyroid artery and innervates the cricothyroid muscle
        • cricothyroid muscle alters vocal cord tension and affects the pitch of the voice
        • injury to the superior laryngeal nerve results in a loss of timbre and volume in the voice, making singing and shouting difficult
        • to avoid injury, the superior pole thyroid vessels should be ligated and divided low on the thyroid gland

Thyroid Physiology

  1. Thyroid Follicle
    • functional unit of the thyroid gland
    • sphere of cuboidal epithelium containing a central core of colloid
    • contains a rich capillary network

  2. Iodine Metabolism
    • formation of thyroid hormone is dependent on the availability of exogenous iodine
    • average daily iodine requirement is 0.1 mg and is found mainly in fish, milk, and eggs
    • in the U.S., iodine is routinely added to bread and salt
    • iodine is rapidly reduced to iodide in the stomach and jejunum
    • under the influence of thyroid stimulating hormone (TSH), iodide is actively transported into the thyroid follicular cells

  3. Synthesis of Thyroid Hormone
    • inside the follicular cell, iodide diffuses through the cytoplasm to the apical membrane, where it is oxidized by peroxidase back to iodine
    • iodine then binds to tyrosine residues on the thyroglobulin molecule to form monoiodotyrosine (MIT) and diiodotyrosine (DIT)
    • 2 molecules of DIT combine to form thyroxine (T4); MIT and DIT combine to form T3 or reverse T3 (rT3)
    • coupling steps are catalyzed by peroxidase
    • TSH positively regulates the iodination and coupling process
    • antithyroid drugs (propylthiouracil, methimazole) are competitive inhibitors of peroxidase
    • in high doses, iodide blocks iodide uptake by the thyroid as well as hormone synthesis

  4. Storage and Secretion of Thyroid Hormone
    • T4 and T3 are bound to thyroglobulin and stored in the colloid of the thyroid follicles
    • thyroglobulin is a glycoprotein that is virtually the sole constituent of follicular colloid
    • in response to TSH, the follicular cell reabsorbs thyroglobulin by endocytosis
    • thyroglobulin then fuses with lysosomes containing hydroxylases
    • hydrolysis results in release of T4, T3, rT3, MIT, and DIT
    • MIT and DIT undergo deiodinatination in the thyroid cell and the iodide is reused in the cell
    • T4, T3, and rT3 are released into the circulation

  5. Metabolism of Thyroid Hormone
    • T4 is the major thyroid hormone released
    • 80% of circulating T4 undergoes peripheral conversion in the kidney and liver to T3 and rT3
    • T3 is 10 times as biologically active as T4
    • rT3 is biologically inactive
    • 99.98% of thyroid hormone is reversibly bound to 3 plasma proteins: thyroid-binding globulin (TBG), thyroid-binding prealbumin (TBPA), and albumin
    • TBG may be increased as a result of the estrogen effects of pregnancy or oral contraceptives
    • increased TBG results in a higher circulating amount of T4 because of increased serum binding capacity, but the active free T4 levels remain unchanged

  6. Molecular Basis of Thyroid Hormone Action
    • unbound thyroid hormones are transported across cell membranes by diffusion
    • at the cellular level, T3 is the active hormone
    • T3 binds to specific receptors located in the cell nucleus
    • T3/T3 receptor complex then binds to regulatory regions of genes and modifies their transcription

  7. Regulation of Thyroid Activity
    1. TSH
      • principal agent that modulates thyroid function and thyroid cell growth
      • produced by the anterior pituitary
      • stimulates iodide uptake, iodination of thyroglobulin, and promotes release of T3 and T4 from thyroglobulin
      • stimulates gene transcription and synthesis of thyroglobulin and thyroid peroxidase
      • secretion is inhibited by high levels of thyroid hormone

    2. TRH
      • thyrotropin releasing hormone is produced in the hypothalamus
      • secreted into the hypophyseal portal system and is transported to the anterior pituitary
      • stimulates TSH secretion

  8. Physiologic Actions of Thyroid Hormone
    • regulates heat production by increasing oxygen consumption and elevating the basal metabolic rate
    • essential for normal growth and development
    • affects protein, lipid, and carbohydrate metabolism
    • increases GI motility
    • increases the sensitivity of the sympathetic nervous system to the effects of catecholamines

Thyroid Function Tests

  1. TSH
    • single most valuable test
    • may detect hypothyroidism (↑ TSH) or hyperthyroidism (↓ TSH) before it is clinically apparent

  2. Total T4
    • measures thyroid production
    • will be elevated in hyperthyroidism and decreased in hypothyroidism
    • measures free and bound hormone levels, which can be affected by the availability of thyroid-binding proteins

  3. Free T4, T3
    • measures biologically active thyroid hormone

  4. Thyroid Antibodies
    • produced in autoimmune thyroid disorders such as Hashimoto’s thyroiditis and Graves’ Disease
    • may allow earlier detection of Graves’ disease and more accurate monitoring of the effects of antithyroid medications

  5. Serum Thyroglobulin
    • most useful for monitoring thyroid cancer patients for recurrence after total thyroidectomy and RAI ablation

  6. Calcitonin
    • can be used as a screening test in MEN2 kindreds or in any patient in whom medullary carcinoma of the thyroid is suspected

Thyroid Imaging

  1. Radioactive Iodine Scan
    • directly evaluates thyroid gland function
    • much less widely used now because of accurate measurements of TSH, T4, T3, and improved thyroid ultrasound
    • used primarily to distinguish between causes of hyperthyroidism – solitary nodule vs diffuse goiter
    • also used to detect thyroid cancer metastases after remnant thyroid radioactive ablation

  2. Ultrasound
    • should be considered as an extension of the physical exam
    • valuable in evaluating thyroid nodules: size, cystic vs solid, characteristics concerning for malignancy (borders, presence of calcifications, vascularity)

    1. FNA
      • key diagnostic modality in the workup of thyroid nodules
      • size of the nodule and ultrasound characteristics are used to determine which nodules to biopsy
      • ultrasound-guided biopsy yields more diagnostic specimens than freehand biopsies
      • FNA analyzes cellular features, but not tissue architecture
      • FNA is extremely accurate in diagnosing papillary thyroid cancer
      • FNA cannot diagnose follicular cancer, since this requires demonstration of capsular or vascular invasion
      • FNA has a false-negative rate between 1% - 6%







References

  1. Sabiston, 20th ed., pgs 881 – 889
  2. Schwartz, 10th ed., pgs 1521 - 1530
  3. O’Leary, pgs 312 – 317
  4. Simmons and Steed, pgs 288 - 291