Peripheral Parathyroid Hormone Metabolism

Intact PTH 1-84 is rapidly cleared from the human circulation and has a half-life of only a few minutes.19114 This degradation ensures that activation of the PTH receptor can be closely regulated by parathyroid cell secretion of PTH. Moreover, there is no evidence for dynamic regulation of peripheral PTH metabolism. PTH clearance mainly depends on high-capacity uptake of Kupffer cells in the liver and on glomerular filtration. A small amount of PTH, however, appears in the urine because of tubular reabsorption and proteolysis. Circulating PTH is molecularly heterogeneous and contains various carboxyterminal peptide sequences arising by cleavage, mainly at residues 33 to 43. Although only 15% of intact PTH 1-84 is metabolized to such circulating fragments, they make up at least half, and sometimes substantially more, of the immunoreactive PTH in the circulation.115116 This discrepancy is due to the release of such fragments from the parathyroid gland, sequestration from Kupffer cells, and slower clearance from the circulation than for intact hormone. The metabolism of these fragments depends only on intact renal function; consequently, the fragments are accumulated to a considerable degree in renal insufficiency. In contrast, very few aminoterminal PTH fragments exist in the circulation of euparathyroid individuals, although these fragments may become appreciable in primary and secondary HPT.

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