title: Furosemide stimulation of parathormone in humans: role of the calcium-sensing receptor and the renin-angiotensin system.
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.
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Muller
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Forni Ogna
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Maillard
authors.affiliation: Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Candice
authors.initials: C
authors.lastname: Stoudmann
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Carole
authors.initials: C
authors.lastname: Zweiacker
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Christiane
authors.initials: C
authors.lastname: Anex
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Wuerzner
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Burnier
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland. Olivier.Bonny@unil.ch.|Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland. Olivier.Bonny@unil.ch.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bonny
mesh_terms: D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood; D057966:Calcimimetic Agents / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D000069449:Cinacalcet / Q000494:pharmacology; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood*; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D012083:Renin / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D064466:Solute Carrier Family 12, Member 1 / Q000235:genetics / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D057966:Calcimimetic Agents; D004232:Diuretics; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; C578714:SLC12A1 protein, human; C578877:SLC12A2 protein, human; D064466:Solute Carrier Family 12, Member 1; D064506:Solute Carrier Family 12, Member 2; D000450:Aldosterone; D005665:Furosemide; D012083:Renin; D002118:Calcium; D000069449:Cinacalcet
keywords: Calcium-sensing receptor; Cinacalcet; Furosemide; Mineral metabolism; Renin-angiotensin-aldosterone system