Parathyroid Glands

The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. The glands secrete parathyroid hormone, which plays a key role in regulating calcium levels.

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Development

The parathyroid glands are derived from pharyngeal pouches, which originate in the mesoderm.

  • The parathyroid glands develop by the 7th week of gestation.
  • The 3rd pharyngeal pouch gives rise to inferior parathyroid glands.
  • The 4th pharyngeal pouch gives rise to superior parathyroid glands.

Gross Anatomy and Neurovasculature

Gross anatomy

Structure:

  • Total of 4 parathyroid glands
  • Left and right superior parathyroid glands
  • Left and right inferior parathyroid glands

Relations: posterior aspect of the lateral lobes of the thyroid gland

Parathyroid glands anatomy

Posterior view of the thyroid gland showcasing the parathyroid glands

Image by Lecturio.

Neurovasculature

  • Arterial supply: inferior thyroid arteries
  • Venous drainage: parathyroid veins → thyroid plexus of veins
  • Innervation: thyroid branches of the cervical ganglia
Arterial supply of parathyroid glands

Arterial supply of parathyroid glands

Image by Lecturio.

Microscopic Anatomy and Function

Microscopic anatomy

  • Chief cells (principal cells): 
    • Polygonal cells with round nuclei
    • Appear purple due to the granules within the cytoplasm
  • Oxyphil cells: 
    • Large cells with abundant cytoplasm
    • Pinker cytoplasm than chief cells
Parathyroid oxyphil and chief cells

High magnification micrograph with hematoxylin and eosin (H&E) stain:
The small, dark cells are chief cells, which are responsible for secreting parathyroid hormone (PTH). The cells with the orange-/pink-stained cytoplasm are oxyphil cells.

Image: “Parathyroid oxyphil and chief cells – annotated” by Mikael Häggström. License: CC0 1.0

Function

Effects of the parathyroid glands are exerted through chief cells, which produce and secrete parathyroid hormone (PTH):

  • Regulate calcium levels in the blood
  • Calcium-sensing receptors (CaSRs) within chief cells monitor calcium blood levels and moderate PTH secretion.
  • ↓ Blood calcium levels → ↑ secretion of PTH → ↑ serum calcium
  • PTH effects: 
    • Stimulation of calcium reabsorption and phosphate excretion in the distal tubule of the kidney
    • Increases renal activation of vitamin D:
      • Calcitriol (1,25-dihydroxyvitamin D) is the active form.
      • Increases intestinal reabsorption of calcium
    • Stimulation of calcium and phosphate release from the bones through osteoclast activation
  • PTH secretion regulation: 
    • Stimulated by decreases in serum calcium, low levels of calcitriol, hyperphosphatemia, and mild hypomagnesemia
    • Inhibited by high levels of serum calcium
Diagram showcasing the role of PTH in the regulation of calcium levels

Diagram showcasing the role of parathyroid hormone (PTH) in the regulation of calcium levels

Image by Lecturio.

Clinical Relevance

  • Hyperparathyroidism: demonstrated by pathologically elevated PTH levels. Depending on the pathogenesis, the presentation may be primary, secondary, or tertiary hyperparathyroidism. The most frequent cause is adenomas of the parathyroid gland, which can be localized utilizing a Tc-99m sestamibi scan with SPECT imaging for 3D localization. Hyperfunctioning adenomas are typically removed with surgery.
  • Hypoparathyroidism: Parathyroid hormone deficiency results in low serum calcium levels and elevated phosphate levels. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery (e.g., thyroidectomy). Treatment is calcium replacement therapy with frequent lab monitoring to ensure appropriate physiological levels.
  • Parathyroid carcinoma: accounts for approximately 1% of all cases of hyperparathyroidism (hypersecretion of PTH accounts for approximately 90% of cancers). Neck ultrasound and/or Tc-99m sestamibi scans are utilized for enlarged gland detection but lack the sensitivity or specificity to differentiate between benign and malignant etiologies of hyperparathyroidism. Fine-needle aspiration biopsy is not recommended due to the difficult task of differentiating benign and malignant cells on cytopathology and the high risk of seeding the parathyroid soft tissues. Both diagnosis and treatment are achieved with surgical resection.

References

  1. Wei, C.H., Harari, A. (2012). Parathyroid carcinoma: update and guidelines for management. Curr Treat Options Oncol. 13(1), 11–23. https://pubmed.ncbi.nlm.nih.gov/22327883/
  2. Fuleihan, G.E., Silverberg, S.J. (2020). Primary hyperparathyroidism: Diagnosis, differential diagnosis, and evaluation. UpToDate. Retrieved February 6, 2021, from https://www.uptodate.com/contents/primary-hyperparathyroidism-diagnosis-differential-diagnosis-and-evaluation
  3. Silverberg, S.J., Fuleihan, G.E. (2019). Primary hyperparathyroidism: Management. UpToDate. Retrieved February 6, 2021, from https://www.uptodate.com/contents/primary-hyperparathyroidism-management

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