Parathyroid Hormone (PTH)

1. Overview

Parathyroid Hormone (PTH) is a peptide hormone secreted by the parathyroid glands that plays a key role in regulating calcium and phosphate homeostasis. PTH increases blood calcium levels by acting on bones, kidneys, and indirectly on the intestines. It functions as part of a tightly regulated feedback loop that maintains serum calcium within a narrow physiological range, critical for nerve conduction, muscle contraction, and various enzymatic processes.

2. Location

PTH is secreted by the chief cells of the parathyroid glands, which are typically four small glands located on the posterior surface of the thyroid gland in the neck. These glands monitor circulating calcium levels and respond quickly to hypocalcemia (low blood calcium) by increasing PTH secretion.

3. Structure

Parathyroid hormone is an 84-amino-acid polypeptide with a molecular weight of approximately 9.4 kDa. The first 34 amino acids (N-terminal portion) are biologically active and essential for receptor binding and function. PTH is synthesized as a larger preprohormone (preproPTH), which is processed into proPTH and then cleaved into the mature active hormone before secretion.

4. Function

PTH increases blood calcium concentration through coordinated effects on three major target organs:

• Bone: Stimulates osteoclast-mediated bone resorption, releasing calcium and phosphate into the bloodstream.

• Kidneys:

  • Increases calcium reabsorption in the distal convoluted tubules, reducing urinary calcium loss.

  • Decreases phosphate reabsorption in the proximal tubules, leading to increased phosphate excretion (phosphaturia).

  • Activates renal 1α-hydroxylase to convert 25(OH)D into active 1,25(OH)2D (calcitriol), enhancing intestinal calcium absorption.

• Intestines (indirectly): Through calcitriol, PTH promotes increased dietary calcium and phosphate absorption.

5. Physiological role(s)

PTH maintains calcium balance and contributes to broader metabolic regulation:

• Calcium homeostasis: Essential for maintaining serum calcium levels within normal limits (8.5–10.5 mg/dL).

• Phosphate regulation: Prevents hyperphosphatemia by promoting renal phosphate excretion.

• Bone remodeling: Facilitates continuous turnover of bone tissue to maintain skeletal integrity; intermittent exposure promotes bone formation (basis for therapeutic use in osteoporosis).

• Vitamin D activation: Enhances synthesis of calcitriol, which supports both calcium and phosphate absorption from the intestine.

6. Clinical Significance

Abnormal PTH levels can lead to significant disturbances in calcium and bone metabolism:

• Primary Hyperparathyroidism:

  • Caused by a parathyroid adenoma, hyperplasia, or rarely carcinoma.

  • Characterized by elevated PTH and hypercalcemia with symptoms such as kidney stones, bone pain, fatigue, abdominal pain, and depression ("stones, bones, groans, and psychiatric overtones").

  • Treatment is usually surgical removal of the overactive gland(s).

• Secondary Hyperparathyroidism:

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

  • PTH levels are elevated, but serum calcium may be low or normal.

  • Treatment includes phosphate binders, vitamin D analogs, and dialysis management.

• Tertiary Hyperparathyroidism:

  • Develops when long-standing secondary hyperparathyroidism leads to autonomous PTH secretion.

  • Common in post-transplant patients with chronic kidney disease.

• Hypoparathyroidism:

  • Caused by surgical removal of parathyroid glands, autoimmune destruction, or genetic mutations.

  • Results in low PTH, hypocalcemia, hyperphosphatemia, and symptoms such as tetany, muscle cramps, and seizures.

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

• Pseudohypoparathyroidism:

  • A rare inherited condition where tissues are resistant to PTH, despite high circulating levels.

  • Presents with hypocalcemia, hyperphosphatemia, and characteristic physical features in some subtypes (Albright hereditary osteodystrophy).

• Osteoporosis therapy:

  • Intermittent administration of recombinant PTH analogs (e.g., teriparatide) stimulates bone formation and is used to treat severe osteoporosis.