From the Guidelines
Parathyroid hormone (PTH) plays a crucial role in regulating calcium homeostasis through its actions on bone, kidneys, and the gastrointestinal system, with its effects on these organs ultimately maintaining serum calcium within narrow physiological limits. In bone, PTH has dual effects: acute exposure stimulates osteoclast activity, increasing bone resorption and calcium release, while chronic intermittent exposure promotes bone formation via osteoblast activation 1. The kidneys are another key target, where PTH increases calcium reabsorption in the distal tubules and inhibits phosphate reabsorption in the proximal tubules, effectively raising serum calcium and lowering phosphate levels 1. Furthermore, PTH enhances the production of 1,25-dihydroxyvitamin D (calcitriol) by activating 1α-hydroxylase in the kidneys, which in turn increases intestinal absorption of calcium 1.
The pathophysiology of PTH action is complex and involves the interplay of several hormones, including 1,25-dihydroxyvitamin D and fibroblast growth factor 23 (FGF23), to maintain normal serum concentrations of phosphate and calcium 1. FGF23, secreted by osteocytes and osteoblasts, is involved in calcium and phosphate homeostasis and is released in response to high concentrations of phosphate, PTH, and 1,25-dihydroxyvitamin D 1. In the gastrointestinal system, PTH acts indirectly through increased calcitriol production, enhancing calcium absorption in the small intestine 1.
Key aspects of PTH's role in mineral homeostasis include:
- Regulation of calcium levels through actions on bone, kidneys, and the gastrointestinal system
- Interplay with other hormones like 1,25-dihydroxyvitamin D and FGF23 to maintain phosphate and calcium balance
- Dual effects on bone, with acute exposure increasing bone resorption and chronic exposure promoting bone formation
- Enhancement of calcitriol production, which increases intestinal calcium absorption
Disruptions in PTH secretion or action can lead to disorders such as hyperparathyroidism or hypoparathyroidism, highlighting the hormone's critical role in maintaining mineral homeostasis 1. Understanding the pathophysiology of PTH action is essential for managing these disorders and preventing associated morbidity and mortality.
From the Research
Pathophysiology of PTH Action
- PTH increases the release of serum calcium through osteoclasts, leading to bone resorption 2
- PTH stimulates osteoblasts, leading to an increase in RANKL expression and differentiation of osteoclasts 2
- In the kidneys, PTH increases calcium reabsorption and decreases phosphate reabsorption 2, 3, 4
- PTH stimulates 1alpha-hydroxylase to synthesize active vitamin D in the kidneys 2
Effects on Bone
- PTH leads to bone resorption, primarily affecting cortical bone, but also trabecular bone 2, 5
- PTH has anabolic actions on bone, particularly in trabecular and cortical bone, making it useful for osteoporosis treatment 5, 6
- Bone turnover is reflected by a balance of circulating full-length PTH and amino-terminally truncated C-PTH fragments 6
Effects on Kidneys and GI System
- PTH enhances calcium reabsorption and inhibits phosphate reabsorption in the kidneys 3, 4
- PTH increases the synthesis of 1,25-dihydroxyvitamin D, leading to increased gastrointestinal absorption of calcium 4
- PTH has a role in regulating extracellular calcium and phosphate levels, making it essential for maintaining mineral homeostasis 4
Clinical Implications
- Primary hyperparathyroidism (PHPT) is characterized by skeletal or renal complications, and can lead to bony demineralization, nephrolithiasis, and hypercalcemic crisis 2, 3
- PHPT may also be associated with mental disturbances, neuromuscular disease, hypertension, and glucose intolerance 3
- Accurate assessment of parathyroid hormone is essential for diagnosing parathyroid disease, and various therapeutic options are available for treatment 4