Thyroid

• Thyroglossal duct development


  1. Develops from the median bud of the pharynx

  2. Foramen caecum at the junction of the anterior two-thirds and posterior one-third of the tongue is the vestigial remnant of the duct

  3. Initially hollow structure migrates caudally and passes in close continuity with, and sometimes through, the developing hyoid cartilage

  
• Parathyroid gland development


  1. Develop from the third and fourth pharyngeal pouches

  2. The thymus also develops from the third pouch

  3. As it descends, the thymus takes the associated parathyroid gland with it, which explains why the inferior parathyroid, which arises from the third pharyngeal pouch, normally lies inferior to the superior gland

  4. However, the inferior parathyroid may be found anywhere along this line of descent
• Parafollicular cells (C cells)


  From the neural crest reach the thyroid via the ultimobranchial body

  
• Normal thyroid gland


  • Weighs 20–25 g
  • Functioning unit is the lobule supplied by a single arteriole and consists of 24–40 follicles lined with cuboidal epithelium

  
• Follicle


  Contains colloid in which thyroglobulin is stored
• Arterial supply


  • Rich, and extensive anastomoses occur between the main thyroid arteries and branches of the tracheal and oesophageal arteries

  
• Lymphatic network


  • Extensive within and around the gland
  • Some lymph channels pass directly to the deep cervical nodes
  • Subcapsular plexus drains principally to the central compartment juxtathyroid – 'Delphian' and paratracheal nodes and nodes on the superior and inferior thyroid veins (level VI)
  • From there to the deep cervical (levels II, III, IV and V) and mediastinal groups of nodes (level VII)
• Recurrent laryngeal nerve (RLN)

  • Branch of the vagus, recurs round the arch of the aorta on the left and the subclavian artery on the right
  • On the left the nerve has more distance in which to reach the tracheoesophageal groove and therefore runs in a medial plane
  • On the right, there is less distance and the nerve runs more obliquely to reach the tracheoesophageal groove
  • Approximately 2% of nerves on the right are non-recurrent and will enter the larynx from above
  • The nerve runs posterior to the thyroid and enters the larynx at the cricothyroid joint
  • This entry point is at the level of Berry's ligament, a condensation of pretracheal fascia that binds the thyroid to the trachea, where the nerve is at most risk of injury during surgery
  • The nerve can be located in the tracheosophageal groove where it forms one side of Beahrs' triangle (the other two sides are the carotid artery and the inferior thyroid artery) or at the cricothyroid joint
  • The nerve will normally be found as the thyroid lobe is mobilised laterally, lying under the most posterolateral portion of the gland called the tubercle of Zuckerkandl

  
• Thyroid hormone synthesis


  1. Trapping of inorganic iodide from the blood

  2. Oxidation of iodide to iodine

  3. Binding of iodine with tyrosine to form iodotyrosine

  4. Coupling of monoiodotyrosines and di-iodotyrosines to form T3 and T4

  
• Thyroid hormone release


  1. When hormones are required, the complex is resorbed into the cell and thyroglobulin is broken down

  2. T3 and T4 are liberated and enter the blood, where they are bound to serum proteins: albumin, thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA)

  3. The small amount of hormone that remains free in the serum is biologically active

  
• T3


  • The more important physiological hormone, also produced in the periphery by conversion from T4
  • Quick acting (within a few hours)
• T4


  Acts more slowly (4–14 days)
• Calcitonin


  Produced by the parafollicular C cells of the thyroid, which are of neuroendocrine origin and arrive in the thyroid via the ultimobranchial body

  
• Pituitary-thyroid axis


  1. Synthesis and release of thyroid hormones from the thyroid is controlled by thyroid-stimulating hormone (TSH) from the anterior pituitary

  2. Secretion of TSH depends upon the level of circulating thyroid hormones and is modified in a negative feedback manner

  3. In hyperthyroidism TSH production is suppressed, whereas in hypothyroidism it is stimulated

  4. Regulation of TSH secretion also results from the action of thyrotrophin releasing hormone (TRH) produced in the hypothalamus

  
• Thyroid-stimulating antibodies


  • A family of IgG immunoglobulins that bind with TSH receptor sites (TRAbs) and activate TSH receptors on the follicular cell membrane
  • They have a more protracted action than TSH (16–24 versus 1.5–3 hours) and are responsible for virtually all cases of thyrotoxicosis not due to autonomous toxic nodules
  • Serum concentrations are very low but their measurement is not essential to make the diagnosis
• Serum TSH


  • Can be measured accurately down to very low serum concentrations with an immunochemiluminometric assay
  • Interpretation of deranged TSH levels depends on knowledge of the T3 and T4 values
• Thyroid functional states


  • Euthyroid: Normal TSH, T4 and T3
  • Thyrotoxic: Undetectable TSH, High T4 and T3
  • Myxoedema: High TSH, Low T4 and T3
  • Suppressive T4 therapy: Undetectable TSH, High T4, Often normal T3
  • T3 toxicity: Low/undetectable TSH, Normal T4, High T3

  
• Thyroid autoantibodies


  • Serum levels of antibodies against thyroid peroxidase (TPO Ab) and thyroglobulin are useful in determining the cause of thyroid dysfunction and swellings
  • Autoimmune thyroiditis may be: thyrotoxic, thyroid failure or euthyroid goitre
  • Levels above 25 units/mL for TPO antibody and titres of greater than 1:100 for anti-thyroglobulin are considered significant
  • Antithyroglobulin antibody and serum thyroglobulin, are used for follow-up of thyroid cancers
  • TSH receptor antibodies (TSH-Rab or TRAB) are often present in Graves' disease

  
• Essential thyroid investigations


  • Serum: TSH (T3 and T4 if abnormal); thyroid autoantibodies
  • FNAC of palpable discrete swellings; ultrasound guidance may reduce the 'Thy1' rate

  
• Optional thyroid investigations


  • Corrected serum calcium
  • Serum calcitonin (carcinoembryonic antigen may be used as an alternative screening test for medullary cancer)
  • Imaging: chest radiograph and thoracic inlet if tracheal deviation/retrosternal goitre; ultrasound, CT and MRI scan for known cancer, some reoperations and some retrosternal goitres; isotope scan if discrete swelling and toxicity coexist

  
• Ultrasound


  • Assessment of the gland and the regional lymphatics
  • Thyroid nodules: Number, size, shape, margins, vascularity and specific features such as the presence of microcalcifications can be used to predict the risk of malignancy within a specific nodule
  • Regional lymphatics, assessed for the presence of metastatic deposits
  • Ultrasound guided fine needle aspiration (FNA) can be performed more accurately than free-hand techniques allow

  
• CT


  • Assess metastatic disease
  • Retrosternal extension, which can often be predicted on plain chest x-ray
  • Contrast enhanced CT is useful for determining the extent of airway invasion and MRI is superior at determining the presence of prevertebral fascia invasion

  
• PET scans


  • Considered in the setting of recurrent thyroid cancer, particularly useful when the disease does not concentrate iodine, at which point fluorodeoxyglucose (FDG) uptake increases and lesions become positive on PET scans

  
• Isotope scanning


  • The uptake by the thyroid of a low dose of either radiolabelled iodine (123I) or the cheaper technetium (99mTc) will demonstrate the distribution of activity in the whole gland
  • Routine isotope scanning is unnecessary and inappropriate for distinguishing benign from malignant lesions because the majority (80%) of 'cold' swellings are benign and some (5%) functioning or 'warm' swellings will be malignant
  • Its principal value is in the toxic patient with a nodule or nodularity of the thyroid
  • Whole-body scanning is used to demonstrate metastases

  
• Fine-needle aspiration cytology (FNAC)


  • The investigation of choice in discrete thyroid swellings
  • Use ultrasound to guide the needle to achieve more accurate sampling and reduce the rate of unsatisfactory aspirates

  
• Classification of fine-needle aspiration cytology reports

  • Thy1 - Non-diagnostic
  • Thy1c - Non-diagnostic cystic
  • Thy2 - Non-neoplastic
  • Thy3 - Follicular
  • Thy4 - Suspicious of malignancy
  • Thy5 - Malignant
• Goitre


  Generalized enlargement of the thyroid gland

  
• Isolated (or solitary) swelling

  A discrete swelling (nodule) in one lobe with no palpable abnormality elsewhere
• Dominant swelling


  Discrete swellings with evidence of abnormality elsewhere in the gland
• Classification of thyroid swellings

  • Simple goiter (euthyroid): Diffuse hyperplastic (Physiological, Pubertal, Pregnancy), Multinodular goiter
  • Toxic: Diffuse (Graves' disease), Multinodular, Toxic adenoma
  • Neoplastic: Benign, Malignant
  • Inflammatory: Autoimmune (Chronic lymphocytic thyroiditis and Hashimoto's disease), Granulomatous (De Quervain's thyroiditis), Fibrosing

  
• Thy4


  Suspicious of malignancy
• Isolated (or solitary) swelling


  Discrete swelling (nodule) in one lobe with no palpable abnormality elsewhere
• Classification of thyroid swellings

  • Simple goiter (euthyroid)
  • Toxic
  • Neoplastic
  • Inflammatory

  
• Simple goitre


  • Diffuse hyperplastic
  • Multinodular goiter
• Toxic


  • Diffuse (Graves' disease)
  • Multinodular
  • Toxic adenoma
• Neoplastic


  • Benign
  • Malignant
• Inflammatory


  • Autoimmune: Chronic lymphocytic thyroiditis and Hashimoto's disease
  • Granulomatous: De Quervain's thyroiditis
  • Fibrosing: Riedel's thyroiditis
  • Infective: Acute (bacterial thyroiditis, viral thyroiditis, 'subacute thyroiditis')
  • Chronic (tuberculous, syphilitic)
  • Other: Amyloid
• Aetiology of simple goitre

  • Inappropriate secretion from a microadenoma in the anterior pituitary
  • Chronically low level of circulating thyroid hormones

  
• Iodine deficiency


  • The daily requirement of iodine is about 0.1–0.15mg
  • Endemic areas are in the mountainous ranges, such as the Rocky Mountains, the Alps, the Andes and the Himalayas and in the UK areas of Derbyshire and Yorkshire
  • Endemic goitre is also found in lowland areas where the soil lacks iodide or the water supply comes from far away mountain ranges
  • Calcium is also goitrogenic and goitre is common in low-iodine areas on chalk or limestone, for example Derbyshire and Southern Ireland
  • Failure of intestinal absorption may produce iodine deficiency
• Dyshormonogenesis


  • Enzyme deficiencies of varying severity may be responsible for many sporadic goitres
  • There is often a family history, suggesting a genetic defect
  • Environmental factors may compensate in areas of high iodine intake