Parathyroid Glands

1. Overview

The parathyroid glands are small endocrine glands responsible for regulating calcium and phosphate balance in the body through the secretion of parathyroid hormone (PTH). PTH plays a vital role in maintaining calcium homeostasis by increasing blood calcium levels when they fall below normal. Although closely associated with the thyroid gland anatomically, the parathyroid glands function independently and serve a distinct physiological role.

2. Location

There are typically four parathyroid glands, located on the posterior surface of the thyroid gland—two superior and two inferior. However, the number and location can vary; some individuals may have more than four glands, and ectopic glands may be found in the thymus or along the esophagus. Each gland is about the size of a grain of rice (approximately 3–8 mm in diameter).

3. Structure

Each parathyroid gland is enclosed in a thin connective tissue capsule and composed of two main cell types:

• Chief cells: The predominant cell type responsible for synthesizing and secreting parathyroid hormone (PTH).

• Oxyphil cells: Larger cells with abundant mitochondria; their function is less understood but may increase with age and contribute to PTH secretion under certain conditions.

The glands are richly vascularized to ensure rapid hormone release in response to changing serum calcium levels.

4. Function

The primary function of the parathyroid glands is the secretion of parathyroid hormone (PTH), which increases serum calcium through multiple mechanisms:

• Bone: Stimulates osteoclast activity to resorb bone and release calcium into the bloodstream.

• Kidneys:

  • Enhances calcium reabsorption in the distal tubules.

  • Decreases phosphate reabsorption, leading to increased phosphate excretion.

  • Stimulates the activation of vitamin D (calcitriol) by increasing renal 1α-hydroxylase activity.

• Intestines: Indirectly increases calcium and phosphate absorption through calcitriol (active vitamin D).

5. Physiological role(s)

The parathyroid glands are essential for maintaining calcium and phosphate balance, which are critical for many bodily functions:

• Calcium homeostasis: Maintains extracellular calcium within a narrow range, crucial for neuromuscular function, blood clotting, and enzyme activity.

• Bone remodeling: Regulates bone turnover by balancing bone resorption and formation.

• Vitamin D metabolism: Supports the activation of vitamin D, which enhances dietary calcium absorption.

• Phosphate regulation: Reduces phosphate reabsorption in the kidneys to maintain appropriate serum phosphate levels.

6. Clinical Significance

Disorders of the parathyroid glands can lead to significant disturbances in calcium and bone metabolism:

• Primary hyperparathyroidism:

  • Most commonly caused by a parathyroid adenoma.

  • Leads to excess PTH secretion, resulting in hypercalcemia, kidney stones, bone pain, osteoporosis, and abdominal discomfort ("bones, stones, groans, and psychiatric overtones").

  • Treatment may include surgical removal of the affected gland(s).

• Secondary hyperparathyroidism:

  • Occurs as a compensatory response to chronic hypocalcemia, often due to chronic kidney disease or vitamin D deficiency.

  • Characterized by elevated PTH with low or normal calcium levels.

• Tertiary hyperparathyroidism:

  • Persistent hyperparathyroidism after long-standing secondary hyperparathyroidism, often seen in renal failure patients post-transplant.

  • Results in autonomous PTH secretion and hypercalcemia.

• Hypoparathyroidism:

  • Usually due to surgical removal or autoimmune destruction of the parathyroid glands.

  • Leads to hypocalcemia, causing tetany, muscle cramps, paresthesias, and seizures.

  • Treatment includes calcium and active vitamin D (calcitriol) supplementation.

• Pseudohypoparathyroidism:

  • A rare genetic disorder where tissues are resistant to PTH, despite normal or elevated levels.

  • Manifests with features of hypocalcemia and hyperphosphatemia.