Postoperative Copeptin Concentration Predicts Diabetes Insipidus After Pituitary Surgery.
BACKGROUND
Copeptin is a stable surrogate marker of vasopressin release; the peptides are stoichiometrically secreted from the neurohypophysis due to elevated plasma osmolality or nonosmotic stress. We hypothesized that following stress from pituitary surgery, patients with neurohypophyseal damage and eventual diabetes insipidus (DI) would not exhibit the expected pronounced copeptin elevation.


OBJECTIVE
The objective was to evaluate copeptin's accuracy to predict DI following pituitary surgery.


METHODS
This was a prospective multicenter observational cohort study.


METHODS
Three Swiss or Canadian referral centers were used.


METHODS
Consecutive pituitary surgery patients were included.


METHODS
Copeptin was measured postoperatively daily until discharge. Logistic regression models and diagnostic performance measures were calculated to assess relationships of postoperative copeptin levels and DI.


RESULTS
Of 205 patients, 50 (24.4%) developed postoperative DI. Post-surgically, median [25th-75th percentile] copeptin levels were significantly lower in patients developing DI vs those not showing this complication: 2.9 [1.9-7.9] pmol/L vs 10.8 [5.2-30.4] pmol/L; P < .001. Logistic regression analysis revealed strong association between postoperative copeptin concentrations and DI even after considering known predisposing factors for DI: adjusted odds ratio (95% confidence interval) 1.41 (1.16-1.73). DI was seen in 22/27 patients with copeptin <2.5 pmol/L (positive predictive value, 81%; specificity, 97%), but only 1/40 with copeptin >30 pmol/L (negative predictive value, 95%; sensitivity, 94%) on postoperative day 1.


CONCLUSIONS
Lack of standardized DI diagnostic criteria; postoperative blood samples for copeptin obtained during everyday care vs at fixed time points.


CONCLUSIONS
In patients undergoing pituitary procedures, low copeptin levels despite surgical stress reflect postoperative DI, whereas high levels virtually exclude it. Copeptin therefore may become a novel tool for early goal-directed management of postoperative DI.
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Bettina
B
Winzeler
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Christian
C
Zweifel
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Nicole
N
Nigro
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Birsen
B
Arici
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Martina
M
Bally
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Philipp
P
Schuetz
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Claudine Angela
CA
Blum
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Christopher
C
Kelly
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Sven
S
Berkmann
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Andreas
A
Huber
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Fred
F
Gentili
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Gelareh
G
Zadeh
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Hans
H
Landolt
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Luigi
L
Mariani
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Beat
B
Müller
Departments of Endocrinology, Diabetology and Metabolism (B.W., N.N., B.A., C.A.B., M.C.-C.), and Neurosurgery (C.Z., C.K., L.M.), University Hospital of Basel, 4031 Basel, Switzerland; Department of Neurosurgery (S.B., H.L.), Medical University Clinic (M.B., P.S., A.H., B.M.), Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland; and Division of Neurosurgery (C.Z., F.G., G.Z.), Toronto Western Hospital, University Health Network and University of Toronto, Toronto, M5T 2S8 Canada.
Mirjam
M
Christ-Crain
D000328:Adult; D000368:Aged; D020790:Diabetes Insipidus, Neurogenic / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000601:surgery*; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000601:surgery*; D011183:Postoperative Complications / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D011184:Postoperative Period; D011379:Prognosis; D016896:Treatment Outcome; D014883:Water-Electrolyte Imbalance / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology
D006020:Glycopeptides; C048197:copeptins