Pflügers Archiv - European Journal of Physiology

, Volume 467, Issue 12, pp 2413–2421 | Cite as

Furosemide stimulation of parathormone in humans: role of the calcium-sensing receptor and the renin-angiotensin system

  • Marie-Eve Muller
  • Valentina Forni Ogna
  • Marc Maillard
  • Candice Stoudmann
  • Carole Zweiacker
  • Christiane Anex
  • Grégoire Wuerzner
  • Michel Burnier
  • Olivier Bonny
Integrative physiology

Abstract

Interactions between sodium and calcium regulating systems are poorly characterized but clinically important. Parathyroid hormone (PTH) levels are increased shortly after furosemide treatment by an unknown mechanism, and this effect is blunted by the previous administration of a calcimimetic in animal studies. Here, we explored further the possible underlying mechanisms of this observation in a randomized crossover placebo-controlled study performed in 18 human males. Volunteers took either cinacalcet (60 mg) or placebo and received a 20 mg furosemide injection 3 h later. Plasma samples were collected at 15-min intervals and analyzed for intact PTH, calcium, sodium, potassium, magnesium, phosphate, plasma renin activity (PRA), and aldosterone up to 6 h after furosemide injection. Urinary electrolyte excretion was also monitored. Subjects under placebo presented a sharp increase in PTH levels after furosemide injection. In the presence of cinacalcet, PTH levels were suppressed and marginal increase of PTH was observed. No significant changes in electrolytes and urinary excretion were identified that could explain the furosemide-induced increase in PTH levels. PRA and aldosterone were stimulated by furosemide injection but were not affected by previous cinacalcet ingestion. Expression of NKCC1, but not NKCC2, was found in parathyroid tissue. In conclusion, our results indicate that furosemide acutely stimulates PTH secretion in the absence of any detectable electrolyte changes in healthy adults. A possible direct effect of furosemide on parathyroid gland needs further studies.

Keywords

Mineral metabolism Calcium-sensing receptor Renin-angiotensin-aldosterone system Cinacalcet Furosemide 

Supplementary material

424_2015_1714_MOESM1_ESM.pdf (25 kb)
Supplemental Figure S1Area under the curve (AUC) of plasma PTH in the different subgroups over time (H0 to H6). A significant difference is noted between the AUC of plasma PTH in furosemide injected subjects on placebo as compared to other subgroups. The significantly higher value indicates that stimulation of PTH secretion under furosemide does not occur under cinacalcet. * denotes p < 0.05 compared to P/F+. (PDF 24 kb)
424_2015_1714_MOESM2_ESM.pdf (59 kb)
Supplemental Figure S2Plasma sodium (panel A) and potassium (panel B) over time. Values of plasma sodium and potassium remain stable in all subgroups during the whole investigation day, which denies a role of these electrolytes in plasma PTH secretion. Furosemide was injected at time 0. Values are means ± SEM. (PDF 59 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Marie-Eve Muller
    • 1
  • Valentina Forni Ogna
    • 1
  • Marc Maillard
    • 1
  • Candice Stoudmann
    • 2
  • Carole Zweiacker
    • 1
  • Christiane Anex
    • 1
  • Grégoire Wuerzner
    • 1
  • Michel Burnier
    • 1
  • Olivier Bonny
    • 1
    • 2
  1. 1.Service of Nephrology and Hypertension, Department of MedicineLausanne University HospitalLausanneSwitzerland
  2. 2.Department of Pharmacology and ToxicologyUniversity of LausanneLausanneSwitzerland

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