Parathyroid

Embryology

• The two pairs of parathyroid glands develop from the 3rd and 4th pharyngeal pouches in about week five of gestation
  • Superior parathyroid from dorsal 4th pouch
    • Attaches itself to the dorsal surface of the caudally-migrating thyroid (which has partly formed from the ventral fourth pouch)
    • More predictable anatomic location
  • Inferior parathyroid from the 3rd pouch, along with thymus
    • Inferior parathyroid from dorsal region
    • Thymus from ventral region
    • Both organs together begin migrating caudally in week six
    • The thymus eventually fuses with its counterpart from the other side
    • Leads to a more variable position for the inferior parathyroid, since it has further to travel

Gross anatomy

• Oval, spherical or bean-shaped
• Vary in colour from 'London tan' to reddish-brown
  • Colour affected by the amount of fat, so become more yellow/tan in older patients - fat makes up 60% of gland volume in old age
  • When bruised they can turn brown or purple
• On average 5x3x2mm in size and weight 35 to 40mg (average combined weight of the four glands is 120mg)
• Typically surrounded by adipose tissue anteriorly, laterally and posteriorly. The fat is softer, paler and straw-coloured
• Vascular pedicle is medial

Variation in position

• 84% have four glands, 13% have >4, and 3% have 3
• 70-80% of people have symmetrical gland position
• 16% of patients with primary HPT have ectopic glands
• Usually found within 5mm of the superior and inferior margins of the tubercle of Zuckerkandl along the posterior capsule of the lateral lobes of the thyroid gland
• Superior glands: (more stable position)
  • Most commonly on the posterior surface of the upper pole of the thyroid - normally close to superior thyroid lobe
  • Almost invariably posterolateral to RLN
  • 80% found in expected anatomic location (1cm superior to the junction of ITA and RLN at the level of the cricoid cartilage). The rest found in the pharyngeal and neurovascular derivatives of the fourth pharyngeal arch, from angle of mandible and carotid bifurcation through to thyroid gland.
  • Often found within the capsule of the thyroid gland
  • If unable to find, usually because of insufficient mobilisation and anteromedial rotation the thyroid lobe to access posterior location
  • Pathologically enlarged glands can migrate posteriorly and inferiorly with gravity along the trache-oeosophageal groove, para-oesophageal space, or retro-oesophageal space. Can even be rarely found within the carotid sheath or thyroid gland.
• Inferior glands: (more variable position)
  • 42% found 1cm inferior to junction of ITA and RLN, anterior and medial to RLN on the posterolateral aspect of the inferior pole of thyroid
  • Normally inferior and lateral to lower lobe of the thyroid
  • Generally anterior to RLN
  • Can be found anywhere from the angle of mandible/skull base to the pericardium - around the thyro-thymic ligament, within the thymus, or even deeper in the anterior mediastinum
    • Most commonly intra-thymic

Blood supply

• Inferior thyroid artery is the predominant blood supply for both the superior and inferior parathyroid glands in 80% of cases
• Can also receive blood from STA or from small arterial branches direct from the thyroid gland
• Usually seen as a small end-vessel entering the broader end of the parathyroid gland

Histology

• Connective tissue capsule, from which fibrous septae develop that support and separate clusters of parenchymal cells
• Normally 25-40% adipose cells; increases with age
• Cell types
  • Chief cells
    • Main cell type
    • Responsible for synthesis and secretion of PTH
  • Oxyphil cells
    • Unknown function
    • Proportion increases with age
    • Possibly related to success of technetium localisation
  • Clear cells
• Histological evaluation cannot distinguish between a parathyroid adenoma and parathyroid hyperplasia or normal parathyroid tissue

Physiology

Control of PTH secretion

• • Calcium binds to calcium-sensing receptors on the surface of the chief cells and inhibits PTH secretion and PTH gene expression
  • High calcium also enhances PTH degradation
  • Conversely, low calcium increases PTH secretion and expression
  • The active form of vitamin D can bind to receptors on chief cells and inhibit PTH gene expression and parathyroid cell proliferation

PTH function

• • Half-life of PTH is 3-5 minutes (range 1-21 minutes)
  • Kidney - acts on ascending limb of the loop of Henle and distal convoluted tubule of the kidneys to enhance calcium reabsorption, inhibit phosphate reabsorption, and increase phosphate excretion causing phosphaturia. Also stimulates conversion of vitamin D to active metabolite, which then increases intestinal absorption of dietary calcium in the small intestine. Effects take minutes to hours.
  • Bones - increases bone remodelling and release of calcium and phosphate from the skeleton. With chronically elevated PTH, the net effect bone resorption leading ot osteopaenia and osteoporosis. Effects take hours to days.