Parathyroid

Score of ≥3 indicates single gland disease

This passage outlines the complex feedback mechanisms between parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D), and fibroblast growth factor 23 (FGF23), all of which play a key role in calcium and phosphate homeostasis. Here's a breakdown of these interactions:

Key Hormonal Interactions:

1. Parathyroid Hormone (PTH):
   • Stimulates the production of 1,25(OH)2D in the kidney.
   • Increases blood calcium levels by:
     • Promoting bone resorption, releasing calcium.
     • Stimulating calcium reabsorption in the distal convoluted tubule of the kidney.
     • Indirectly increasing calcium absorption in the intestine through the stimulation of 1,25(OH)2D production.
   • Reduces blood phosphate levels by decreasing phosphate reabsorption in the proximal convoluted tubule.
   • Secretion is regulated by:
     • High calcium levels suppress PTH secretion.
     • Low calcium levels stimulate PTH secretion via the calcium-sensing receptor (CaSR).
     • High phosphate levels stimulate PTH secretion, while low phosphate levels suppress it.
2. 1,25-dihydroxyvitamin D (1,25(OH)2D):
   • Produced in the kidney under the stimulation of PTH.
   • Inhibits PTH secretion from the parathyroid gland (PTG).
   • Stimulates FGF23 production in bone, creating a feedback loop.
3. Fibroblast Growth Factor 23 (FGF23):
   • Inhibits 1,25(OH)2D production in the kidney.
   • Inhibits PTH secretion from the PTG.
   • Stimulated by PTH secretion from bone, forming a regulatory loop.

Feedback Loops:

• PTH and Calcium: PTH increases calcium levels, and elevated calcium levels in turn suppress further PTH secretion.
• PTH and Phosphate: PTH reduces phosphate levels, and high phosphate levels stimulate PTH secretion, although no specific phosphate receptor in the PTG has been identified.
• FGF23 and 1,25(OH)2D: FGF23 inhibits 1,25(OH)2D production, and 1,25(OH)2D stimulates FGF23 secretion from bone.

Key Functions of FGF23:

1. Reduces Phosphate Levels:
   • FGF23 reduces renal reabsorption of phosphate in the proximal convoluted tubule, similar to PTH.
   • Indirectly reduces phosphate by inhibiting the production of 1,25(OH)2D in the kidney.
   • Low phosphate levels inhibit FGF23 production, while high phosphate levels stimulate its production in bone. However, no specific phosphate receptor has been identified for this regulation.
2. Limited Effect on Calcium:
   • FGF23 does not have a direct action on serum calcium levels.

Role of 1,25-dihydroxyvitamin D (1,25(OH)2D):

1. Increases Both Calcium and Phosphate Levels:
   • Raises serum calcium and phosphate levels by enhancing intestinal absorption of these minerals.
   • At high levels, 1,25(OH)2D also stimulates bone resorption, releasing both calcium and phosphate.
   • It promotes calcium reabsorption in the distal convoluted tubule of the kidney.
2. Regulation by Calcium and Phosphate:
   • Elevated calcium and phosphate levels inhibit 1,25(OH)2D production in the kidney.
   • This inhibition occurs both directly and through their regulation of PTH and FGF23.

Feedback Mechanisms:

• FGF23 reduces phosphate levels by inhibiting both phosphate reabsorption in the kidney and 1,25(OH)2D production.
• 1,25(OH)2D increases both calcium and phosphate levels, primarily through the intestines.
• High calcium and phosphate levels suppress further 1,25(OH)2D production, thus forming a tightly regulated system to maintain mineral balance.

This summary highlights the regulatory roles of FGF23 and 1,25(OH)2D in maintaining phosphate and calcium balance through their respective actions in the kidney, bone, and intestines.