Calcium-mediated parathyroid hormone suppression to assess progression of secondary hyperparathyroidism during treatment among incident dialysis patients

J Clin Endocrinol Metab. 2013 Feb;98(2):618-25. doi: 10.1210/jc.2012-3246. Epub 2013 Jan 30.

Abstract

Context: Parathyroid gland function is affected adversely by tissue hyperplasia and gland enlargement in hyperparathyroidism.

Objective: We examined the effects of 2 treatment strategies on the progression of secondary hyperparathyroidism using measurements of the nonsuppressible component of calcium-regulated PTH secretion as an index of parathyroid mass.

Design, subjects, and intervention: In this randomized, open-label study, subjects managed with hemodialysis for >3 but <12 months before entering the trial (mean, 7.2 months) who had baseline plasma PTH levels >300 pg/mL received cinacalcet and low-dose vitamin D sterols (Cin-D, n = 153) or larger, varying doses of calcitriol, or other vitamin D analogs (Flex-D, n = 151). Study drug doses were adjusted periodically based on PTH and serum total calcium determinations.

Main outcome measures: The exploratory endpoint was calcium-regulated PTH release, assessed using a standardized PTH suppression test before and after 52 weeks of treatment and 4 weeks after withdrawing treatment. PTH and serum total calcium were measured before hemodialysis using high-calcium (3.5 mEq/L or 1.75 mmol/L) dialysate and after 150 and 180 minutes.

Results: Mean (95% confidence interval) nonsuppressible calcium-regulated PTH release at baseline did not differ between Cin-D, 33.4% (25.9%, 40.9%), and Flex-D, 28.1% (23.2%, 32.9%). Corresponding values after 52 weeks of treatment were 34.3% (29.7%, 38.9%) and 42.0% (32.7%, 51.3%), not significant, and did not change measurably in either group when reevaluated 4 weeks after treatments were withdrawn.

Conclusion: Disease progression over 12 months was not documented using a PTH suppression test in this population. Calcium-mediated PTH suppression was maintained fully, however, in Cin-D despite reductions in serum total calcium concentration, whereas values did not increase in Flex-D despite substantial increases in serum calcium.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Calcitriol / pharmacology
  • Calcitriol / therapeutic use*
  • Cinacalcet
  • Disease Progression
  • Female
  • Humans
  • Hyperparathyroidism, Secondary / blood
  • Hyperparathyroidism, Secondary / drug therapy*
  • Hyperparathyroidism, Secondary / physiopathology
  • Male
  • Middle Aged
  • Naphthalenes / pharmacology
  • Naphthalenes / therapeutic use*
  • Parathyroid Glands / physiopathology
  • Parathyroid Hormone / metabolism*
  • Renal Dialysis
  • Treatment Outcome

Substances

  • Naphthalenes
  • Parathyroid Hormone
  • Calcitriol
  • Cinacalcet