A copeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis.
Hyponatremia, the most frequent electrolyte disorder, is caused predominantly by the syndrome of inappropriate antidiuresis (SIAD). A comprehensive characterization of SIAD subtypes, defined by type of osmotic dysregulation, is lacking, but may aid in predicting therapeutic success. Here, we analyzed serial measurements of serum osmolality and serum sodium, plasma arginine vasopressin (AVP), and plasma copeptin concentrations from 50 patients with hyponatremia who underwent hypertonic saline infusion. A close correlation between copeptin concentrations and serum osmolality existed in 68 healthy controls, with a mean osmotic threshold±SD of 282±4 mOsM/kg H2O. Furthermore, saline-induced changes in copeptin concentrations correlated with changes in AVP concentrations in controls and patients. With use of copeptin concentration as a surrogate measure of AVP concentration, patients with SIAD could be grouped according to osmoregulatory defect: Ten percent of patients had grossly elevated copeptin concentrations independent of serum osmolality (type A); 14% had copeptin concentrations that increased linearly with rising serum osmolality but had abnormally low osmotic thresholds (type B); 44% had normal copeptin concentrations independent of osmolality (type C), and 12% had suppressed copeptin concentrations independent of osmolality (type D). A novel SIAD subtype discovered in 20% of patients was characterized by a linear decrease in copeptin concentrations with increasing serum osmolality (type E or "barostat reset"). In conclusion, a partial or complete loss of AVP osmoregulation occurs in patients with SIAD. Although the mechanisms underlying osmoregulatory defects in individual patients are presumably diverse, we hypothesize that treatment responses and patient outcomes will vary according to SIAD subtype.
Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Leipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany;
Wiebke Kristin
WK
Fenske
Division of Endocrinology, University Hospitals, Basel, Switzerland;
Mirjam
M
Christ-Crain
Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany;
Anna
A
Hörning
Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany;
Jessica
J
Simet
Pediatric Endocrinology, University Children's Hospital Basel, University Basel, Basel, Switzerland;
Gabor
G
Szinnai
Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany; Department of Internal Medicine IV, Ludwig-Maximilians-Universität, Munich, Germany;
Martin
M
Fassnacht
University Clinic for Internal Medicine, Kantonsspital Baselland-Bruderholz, Bruderholz, Switzerland; and.
Jonas
J
Rutishauser
Department of Physiology and Medicine, Hôpital du Sacré-Coeur, Université de Montréal, Montréal, Canada.
Daniel G
DG
Bichet
Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany;
Stefan
S
Störk
Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; wiebkekristin.fenske@medizin.uni-leipzig.de allolio_b@ukw.de.
Bruno
B
Allolio
D000328:Adult; D000368:Aged; D001127:Arginine Vasopressin / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D064368:Healthy Volunteers; D006801:Humans; D007177:Inappropriate ADH Syndrome / Q000097:blood / Q000145:classification*; D008297:Male; D008875:Middle Aged; D064587:Osmoregulation; D012462:Saline Solution, Hypertonic; D017422:Sequence Analysis, DNA; D055815:Young Adult
D006020:Glycopeptides; D012462:Saline Solution, Hypertonic; C048197:copeptins; D001127:Arginine Vasopressin