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secondary hyperparathyroidism
Etiology:
- renal failure (hypocalcemia secondary to phosphorus retention)
- inadequate calcium intake
- steatorrhea
- vitamin D deficiency or resistance
Pathology:
- reduced number of nephrons in chronic renal failure leads to hyperphosphatemia
- increased secretion of FGF-23 from bone osteocytes & osteoblasts increases urinary phosphate secretion to maintain normal plasma phosphate levels
- FGF-23 also suppresses renal 25-hydroxyvitamin D(3) 1-alpha-hydroxylase reducing calcitriol
- reduced calcitriol results in diminished calcium absorption from the intestine & hypocalcemia
- hypocalcemia stimulates PTH release resulting in release of calcium & phosphate from bone to normalize plasma calcium
- PTH also increases excretion of phosphate by reducing resorption of phosphate from renal tubules
- as renal function declines, increases in plasma FGF-23 & plasma PTH cannot normalize plasma phosphate & hyperphosphatemia occurs
- elevated plasma phosphate further stimulates PTH release
- ectopic calcification of calcium phosphate may worsen hypocalcemia
Laboratory:
- serum parathyroid hormone; hyperparathyroidism
- serum 25-hydroxyvitamin D
- consider 1,25-dihydroxyvitamin D in serum in patients with severe renal impairment & normal 25-hydroxyvitamin D levels
- serum calcium: hypercalcemia
- serum phosphorus
Management:
- treat hyperphosphatemia in patients with chronic renal failure (1st line) [2]
- sevelamer rather than calcium carbonate [2]
- normalize serum calcium & serum phosphorus to eliminate stimulus for PTH secretion [1]
- correct vitamin D deficiency
- calcitriol for patients with severe chronic renal failure regardless of serum 25-hydroxyvitamin D*
* patients with severe chronic renal failure may be deficient in 25-hydroxyvitamin D-1-alpha hydroxylase
* calcitriol suppresses PTH production by the parathyroid gland [1]
* ref [1] does not consider measuring 1,25-dihydroxyvitamin D in serum
* ref [2] argues against use of calcitriol in the setting of hypocalcemia because it may increase serum phosphate
General
hyperparathyroidism
References
- Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 18.
American College of Physicians, Philadelphia 2012, 2015, 2018.
- NEJM Knowledge+ Nephrology/Urology