Copeptin Interpreter
Copeptin Interpreter
Copeptin is reported in one unit, so there is nothing to convert. The mistake worth guarding against is reading a baseline value against a stimulated cut-off — the two differ by a factor of seven, and 3 pmol/L means nothing at rest and diagnoses AVP deficiency after hypertonic saline. This page asks which test the sample came from before it applies a threshold to it.
Copeptin
Test context + value → interpretationCopeptin 3.1 pmol/L, drawn at a plasma sodium of 151 mmol/L at the top of a 3% saline infusion
Four thresholds, and the sample each one belongs to
Hypertonic saline, sodium ≥ 150 mmol/L: ≤ 4.9 pmol/L → AVP deficiency
Arginine at 60 min: < 3.0 → AVP deficiency · > 5.2 → primary polydipsia · 3.0–5.2 grey zone
Baseline 2.9 pmol/L: a boundary, not a decision
- 21.4 pmol/L
- baseline, without prior thirsting. 100% sensitivity and specificity for nephrogenic diabetes insipidus in Timper's 55-patient series, in which 10 patients had it. This is the one question a single unstimulated copeptin answers on its own
- 4.9 pmol/L
- at the top of a 3% saline infusion. 96.5% accuracy in Fenske's prospective study, against 76.6% for the water deprivation test in the same patients. Values at or below the threshold indicate AVP deficiency; above it, primary polydipsia
- 3.8 pmol/L at 60 minutes
- arginine 0.5 g/kg to a maximum of 40 g, in 500 mL of 0.9% saline over 30 minutes, with copeptin sampled 60 minutes after the infusion STARTS — half an hour after it finishes, not immediately after. 93% accuracy in the derivation study and 74.4% in the head-to-head trial, which is why this page treats 3.0 to 5.2 pmol/L as a grey zone
- 2.9 pmol/L
- quoted for a baseline sample with 82% sensitivity and 78% specificity in the 2026 JALM review. The figure could not be traced to a primary report and the sensitivity is given elsewhere as 72%, so this page reports which side of it a value falls and calls both sides not diagnostic
- why there is no unit converter here
- copeptin is measured against an assay calibrator and the 39-residue glycopeptide is variably glycosylated, so the measurand has no single molar mass. Every platform reports pmol/L and there is nothing to convert it to
Worked example
Copeptin 3.1 pmol/L, drawn at a plasma sodium of 151 mmol/L at the top of a 3% saline infusion
3.1 pmol/L is well below 21.4, so this is not AVP resistance
The sodium reached 151 mmol/L, above the 150 mmol/L target Fenske used and above the 149 mmol/L figure the 2025 approach paper gives — so the stimulated threshold is defined for this sample
3.1 ≤ 4.9 → AVP deficiency, with a diagnostic accuracy of 96.5% at this threshold
Now change one field and nothing else. The same 3.1 pmol/L entered as a BASELINE sample returns "not diagnostic" — because at rest a copeptin of 3.1 is entirely compatible with primary polydipsia, and treating it as deficiency would mean desmopressin for someone who is simply drinking too much
Change it again to an arginine sample and it returns AVP deficiency, but from the 3.0 pmol/L high-specificity boundary rather than from 3.8 — a value of 3.5 would come back indeterminate
The published thresholds and what each one is actually for
| Sample | Threshold | Reading | Performance | Source |
|---|---|---|---|---|
| Baseline, no thirsting | > 21.4 pmol/L | AVP resistance (nephrogenic DI) | 100% sensitivity and specificity | Timper, JCEM 2015 |
| Baseline, no thirsting | ≈ 2.9 pmol/L | Not diagnostic either way | 82% / 78% as published; 72% sensitivity elsewhere | JALM 2026 review, primary untraced |
| 3% saline to sodium ≥ 150 mmol/L | ≤ 4.9 pmol/L | AVP deficiency | 96.5% accuracy (92.1–98.6) | Fenske, NEJM 2018 |
| Arginine 0.5 g/kg over 30 min, sample at 60 min | ≤ 3.8 pmol/L | AVP deficiency | 93% accuracy on derivation; 74.4% head to head | Winzeler, Lancet 2019; Refardt, NEJM 2023 |
| Arginine, same sample | 5.2 pmol/L | Deficiency or polydipsia respectively | Specificity > 90%; resolves over half of cases | Newell-Price, JCEM 2025 |
| Water deprivation test, for comparison | — | Indirect, measures the kidney not the hormone | 70–77% accuracy | Fenske 2018; Newell-Price 2025 |
Choosing between the two stimulation tests
| Hypertonic saline | Arginine | |
|---|---|---|
| Stimulus | 3% saline until plasma sodium ≥ 150 mmol/L | Arginine 0.5 g/kg (max 40 g) in 500 mL of 0.9% saline over 30 min |
| Diagnostic sample | At the target sodium | 60 minutes after the infusion starts |
| Accuracy, derivation study | 96.5% | 93% |
| Accuracy, head-to-head trial in 158 patients | 95.6% | 74.4% |
| Monitoring required | Sodium every 30 minutes, clinician present throughout | None beyond routine observation |
| Patient preference | 28% | 72% |
| Main hazard | Overshooting the sodium; nausea and vomiting raise copeptin independently | Nausea; a result in the 3.0–5.2 pmol/L overlap that cannot be acted on |
Why the test context matters more than the number
Copeptin is the 39-residue C-terminal glycopeptide of pro-vasopressin. It is cleaved from the same precursor as arginine vasopressin and released with it in equimolar amounts, so it reports vasopressin secretion without any of vasopressin's pre-analytical problems: it is stable at room temperature for days, needs no chilled centrifuge, circulates at concentrations an automated immunoassay handles comfortably, and can be reported the same day. It is not an approximation of vasopressin secretion. It is a stoichiometric marker of it, and that is why it has displaced both the vasopressin assay and, for this indication, the water deprivation test.
What it has not displaced is the need to know which test produced the sample. Copeptin secretion is driven by plasma osmolality, so the interpretation of any value depends on the osmotic stimulus present when the blood was taken. At rest, a healthy person, a person with primary polydipsia and a person with partial AVP deficiency all sit in a narrow band of low single figures, and the distributions overlap so heavily that a baseline sample can only answer one question reliably — whether the copeptin is high, above 21.4 pmol/L, which identifies AVP resistance and needs no further testing. Everything else requires the pituitary to be provoked and the response measured.
The two provocations in use are not equivalent. Hypertonic saline raises the plasma sodium to at least 150 mmol/L and asks the osmoreceptors a direct question; copeptin at or below 4.9 pmol/L at that point means AVP deficiency, with 96.5% accuracy in the prospective study that established it. Arginine stimulates copeptin release by a route that is not osmotic, needs no sodium monitoring, and is markedly more comfortable, which is why nearly three-quarters of patients offered both preferred it. It is also less accurate: the derivation study reported 93%, and the head-to-head trial reported 74.4% against 95.6% for saline. The reconciliation is that arginine performs well at the extremes and badly in the middle, so this page reports 3.0 to 5.2 pmol/L as a grey zone rather than applying the 3.8 pmol/L cut-off across it.
One protocol detail is worth stating on its own, because a widely read 2026 review gets it wrong. The arginine infusion runs over 30 minutes, but the diagnostic sample is drawn at 60 minutes from the START of the infusion — a full half-hour after it finishes — because that is where the derivation study found optimal accuracy and where every protocol since has put it. Sampling immediately after the infusion catches a rising curve half an hour early, reads low, and misclassifies primary polydipsia as AVP deficiency. The consequence of that particular error is desmopressin given to someone who is already drinking too much, which is a recipe for hyponatraemia.
Frequently asked questions
What is a normal copeptin level?
There is no single normal value, because copeptin is interpreted against the osmotic stimulus present when the sample was taken. At baseline, healthy adults sit in the low single figures in pmol/L and overlap substantially with both primary polydipsia and partial AVP deficiency. The only baseline value that decides anything on its own is one above 21.4 pmol/L, which identifies AVP resistance.
Why can a copeptin of 3 pmol/L mean two opposite things?
Because the thresholds belong to different tests. After a 3% saline infusion has raised the plasma sodium to 150 mmol/L, a copeptin of 3 pmol/L is a failure to respond and diagnoses AVP deficiency. At rest, with no stimulus at all, the same 3 pmol/L is what a well-hydrated person with primary polydipsia would be expected to have. The number is identical; the question asked of it is not.
When is the sample taken in the arginine test?
Sixty minutes after the infusion starts. Arginine 0.5 g/kg, to a maximum of 40 g, is given in 500 mL of 0.9% saline over 30 minutes, and the diagnostic sample is drawn half an hour after that infusion ends. A 2026 review states that copeptin is sampled immediately after the infusion completes, which is not what the derivation study did and would read the response too early.
Is arginine as good as hypertonic saline?
No, although it is much more comfortable. The derivation study reported 93% accuracy for arginine, but a head-to-head comparison in 158 patients found 74.4% for arginine against 95.6% for hypertonic saline. Arginine is reliable at the extremes — below 3.0 or above 5.2 pmol/L, where specificity exceeds 90% — and unreliable in between, where hypertonic saline is needed.
Does copeptin need any special handling?
No, and that is the point of it. Unlike arginine vasopressin, which must be chilled, centrifuged cold and frozen within the hour and is largely platelet-bound, copeptin is stable at room temperature for days and is measured on a routine automated platform. It is released in equimolar amounts with vasopressin from the same precursor.
Why is copeptin not converted to ng/L or pmol per anything else?
Because the assay is calibrated against a variably glycosylated peptide, so the measurand has no single molar mass and a mass unit cannot be derived. Every platform in routine use reports pmol/L, which is why this page is an interpreter and not a unit converter.
Related calculators
References
- Timper K, Fenske W, Kühn F, et al. Diagnostic accuracy of copeptin in the differential diagnosis of the polyuria-polydipsia syndrome: a prospective multicenter study. J Clin Endocrinol Metab. 2015;100(6):2268–2274.
- Fenske W, Refardt J, Chifu I, et al. A copeptin-based approach in the diagnosis of diabetes insipidus. N Engl J Med. 2018;379(5):428–439.
- Winzeler B, Cesana-Nigro N, Refardt J, et al. Arginine-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a prospective diagnostic study. Lancet. 2019;394(10198):587–595.
- Refardt J, Atila C, Chifu I, et al. Arginine or hypertonic saline-stimulated copeptin to diagnose AVP deficiency. N Engl J Med. 2023;389(20):1877–1887.
- Newell-Price J, Drummond JB, Gurnell M, et al. Approach to the patient with suspected hypotonic polyuria. J Clin Endocrinol Metab. 2025;110(2):e506–e514.
- Khattri Bhandari S, Fan S-L. Copeptin as a marker for vasopressin dysregulation and diagnosis. J Appl Lab Med. 2026;11(1):143–154. — source of the 2.9 pmol/L figure and of the arginine sampling time this page corrects.
- Christ-Crain M, Gaisl O. Approach to the patient: "utility of the copeptin assay". J Clin Endocrinol Metab. 2022;107(6):1727–1738.
Medical Disclaimer: The tools and content provided here are for educational and reference purposes only. They are not intended to substitute for professional medical advice, diagnosis, or treatment. Clinical decisions should always be based on the comprehensive assessment of a qualified healthcare professional.