Saline Suppression Test Interpreter
Saline Suppression Test Interpreter
Two litres of saline over four hours should switch aldosterone off. Whether it did depends on which threshold you read it against — and the recumbent and seated protocols have different cut-offs, derived from different studies, with the immunoassay figure higher than the mass spectrometry one. Set the protocol and the assay before reading the number.
Saline suppression test
Protocol + assay → thresholdPost-infusion aldosterone 7.0 ng/dL, seated protocol, HPLC-MS/MS
The protocol, and the threshold that belongs to it
Aldosterone, cortisol and potassium at 0 and 4 hours
Recumbent (Endocrine Society 2016): <5 ng/dL unlikely · 5–10 indeterminate · >10 likely
Seated, HPLC-MS/MS (Stowasser 2018): 162 pmol/L (5.8 ng/dL)
Seated, immunoassay (Thuzar 2020): 171 pmol/L, or 217 pmol/L for balanced performance
- recumbent
- one hour of recumbency before the infusion and recumbent throughout. The Endocrine Society’s 2016 protocol, and the source of the 5 and 10 ng/dL bands
- seated
- the infusion begins 30 minutes after the patient sits up, and they stay seated. Same saline, same four hours, different threshold — and, in a head-to-head comparison, markedly better sensitivity
- the cortisol
- measured at 0 and 4 hours for a reason. If cortisol rises during the infusion the patient was stressed, aldosterone was being driven by ACTH rather than by volume status, and the test cannot be interpreted
- potassium first
- hypokalaemia directly suppresses aldosterone secretion and can produce a falsely suppressed result in genuine primary aldosteronism. Correct it before the test, not after a negative one
- contraindications
- two litres of saline in four hours is a real volume load. The test is contraindicated in uncontrolled hypertension, heart failure, significant arrhythmia, renal impairment and severe hypokalaemia
Worked example
Post-infusion aldosterone 7.0 ng/dL, seated protocol, HPLC-MS/MS
7.0 × 27.744 = 194 pmol/L
The seated HPLC-MS/MS cut-off is 162 pmol/L (5.8 ng/dL), from Stowasser and colleagues, 100 patients, 87% sensitivity and 94% specificity
194 is above 162, so aldosterone did not suppress → consistent with primary aldosteronism
The same 7.0 ng/dL on the recumbent protocol would fall in the guideline's indeterminate band of 5 to 10 ng/dL and settle nothing
And on an immunoassay it would sit between Thuzar's two seated cut-offs of 171 and 217 pmol/L — positive on one, negative on the other. One number, three answers, which is the whole reason this page asks for the protocol and the platform
Published thresholds, with the protocol and assay each belongs to
| Protocol | Assay | Threshold | Performance | Source |
|---|---|---|---|---|
| Recumbent | Not specified | 10 ng/dL (277 pmol/L) likely | Not stated in the guideline | Endocrine Society clinical practice guideline, Funder 2016 |
| Seated | Not specified | >6 ng/dL (166 pmol/L), with 4-hour cortisol below baseline | Not stated in the guideline | Endocrine Society clinical practice guideline, Funder 2016 |
| Seated | HPLC-MS/MS | 162 pmol/L (5.8 ng/dL) | Sensitivity 87%, specificity 94%, AUROC 0.96 | Stowasser 2018, n=100 patients / 108 studies |
| Recumbent | HPLC-MS/MS | Same patients, for comparison | Sensitivity 38%, specificity 94%, AUROC 0.80 | Stowasser 2018 |
| Seated | Chemiluminescent immunoassay | 171 pmol/L | Sensitivity 95.4%, specificity 80.0% | Thuzar 2020, n=80 seated studies |
| Seated | Chemiluminescent immunoassay | 217 pmol/L | Sensitivity 86.2%, specificity 86.7% | Thuzar 2020 |
Before the test, and what invalidates it
| Requirement | Why |
|---|---|
| Correct hypokalaemia first | Potassium is a direct secretagogue for aldosterone, so hypokalaemia suppresses it and can produce a falsely negative confirmatory test in genuine primary aldosteronism |
| Withdraw mineralocorticoid receptor antagonists for 4–6 weeks | Spironolactone, eplerenone and amiloride act on the pathway being tested. Verapamil slow-release, doxazosin and hydralazine are the usual substitutes for blood pressure control |
| Measure cortisol at 0 and 4 hours | A rise means a stress response, with aldosterone driven by ACTH rather than volume. The test is then uninterpretable rather than negative |
| Start between 08:00 and 09:00 | Aldosterone has a diurnal rhythm and the published thresholds were derived on morning infusions |
| Screen out volume-load contraindications | Two litres in four hours: not for uncontrolled hypertension, heart failure, significant arrhythmia, renal impairment or severe hypokalaemia |
One infusion, several thresholds, and why the protocol comes first
A positive aldosterone-renin ratio is a screening result, not a diagnosis, and the saline suppression test is one of the four standard ways of confirming it. The logic is simple: two litres of isotonic saline over four hours expands the extracellular volume enough that a normal adrenal switches aldosterone off. If aldosterone stays up, its secretion is autonomous. What is not simple is the number you compare the four-hour value against, because it belongs jointly to the position the patient was in and the assay that measured the sample.
The Endocrine Society’s 2016 guideline describes both positions and gives thresholds for each: recumbent throughout after an hour of lying down, with post-infusion aldosterone below 5 ng/dL making primary aldosteronism unlikely, above 10 ng/dL making it likely and the span between the two indeterminate; or seated throughout after half an hour sitting, with a figure of 6 ng/dL and the condition that cortisol at four hours is lower than at baseline. Those bands are what most laboratories still report against. Then Stowasser and colleagues did the experiment that matters, putting 100 patients through both protocols and comparing them against a confirmed diagnosis. The seated test reached 87% sensitivity at 94% specificity with a cut-off of 162 pmol/L by mass spectrometry. The recumbent test, in the same people, reached 38% sensitivity at the same specificity. Areas under the curve were 0.96 and 0.80. A recumbent saline suppression test that comes back suppressed misses well over half of the disease it is meant to exclude, and that is the single most useful thing to know about this investigation.
The assay adds a second layer. Thuzar and colleagues measured 80 seated studies by both chemiluminescent immunoassay and HPLC-MS/MS and found the immunoassay needed a higher cut-off: 171 pmol/L for maximum sensitivity, or 217 pmol/L for a more even trade-off, against 162 pmol/L by mass spectrometry. Their conclusion was that a higher diagnostic cut-off should be used when aldosterone is measured by immunoassay. Work elsewhere points the same way — a Korean group deriving an immunoassay-specific seated cut-off by radioimmunoassay arrived at 6.6 ng/dL, again above the mass-spectrometry figure — which is why this page will not read an immunoassay result against a mass-spectrometry threshold and asks which platform produced the number.
Three practical conditions decide whether any of this is interpretable. Potassium must be corrected before the test, because hypokalaemia directly suppresses aldosterone and will produce a falsely negative confirmatory test in a patient who genuinely has the disease. Mineralocorticoid receptor antagonists must be withdrawn for four to six weeks, with verapamil slow-release, doxazosin or hydralazine holding the blood pressure in the meantime. And cortisol must be measured at both ends of the infusion, because a rise means the patient mounted a stress response and the aldosterone was being driven by ACTH rather than by volume; that result is uninterpretable, not negative. Two litres of saline in four hours is also a genuine volume load, so the test is contraindicated in uncontrolled hypertension, heart failure, significant arrhythmia, renal impairment and severe hypokalaemia.
One final point about where this test sits. The thresholds on this page come from the 2016 guideline and from the two studies named above. A 2025 Endocrine Society guideline has since narrowed the indication considerably, suggesting aldosterone suppression testing where screening suggests an intermediate probability of lateralising disease and the patient wants to be considered for surgery — in other words, fewer confirmatory tests, done to answer a specific question. That is a change in when to do the test rather than in how to read it, and no threshold on this page is attributed to it.
Frequently asked questions
What aldosterone level confirms primary aldosteronism after saline infusion?
It depends on the protocol and the assay. Recumbent, the Endocrine Society guideline uses above 10 ng/dL (277 pmol/L) to confirm and below 5 ng/dL (139 pmol/L) to exclude. Seated, the published cut-offs are 162 pmol/L by HPLC-MS/MS and 171 or 217 pmol/L by immunoassay. Reading one against another’s threshold is the commonest error.
Is the seated or the recumbent saline suppression test better?
Seated, clearly, where it can be done. Stowasser and colleagues put 100 patients through both and found 87% sensitivity for the seated test against 38% for recumbent, at the same 94% specificity, with areas under the curve of 0.96 and 0.80. A suppressed recumbent result misses more than half the disease it is meant to exclude.
Why does the immunoassay need a different cut-off?
Because it does not measure the same way. Thuzar and colleagues compared chemiluminescent immunoassay with HPLC-MS/MS on 80 seated studies and found the immunoassay needed 171 pmol/L for maximum sensitivity or 217 pmol/L for balanced performance, against 162 pmol/L by mass spectrometry, and concluded that a higher cut-off should be used with immunoassay.
Why is cortisol measured during a saline suppression test?
To detect a stress response. If cortisol at four hours is higher than at baseline, aldosterone was being driven by ACTH rather than by volume status, and the test cannot be interpreted in either direction. The Endocrine Society’s seated criterion states the requirement explicitly.
Does hypokalaemia affect the test?
Yes, and in the direction that causes harm. Potassium is a direct stimulus to aldosterone secretion, so hypokalaemia suppresses it and can produce a falsely negative confirmatory test in a patient who genuinely has primary aldosteronism. Correct potassium before testing rather than around it.
Who should not have a saline suppression test?
Anyone in whom two litres of saline in four hours is unsafe: uncontrolled hypertension, heart failure, significant arrhythmia, renal impairment or severe hypokalaemia. A fludrocortisone suppression test or captopril challenge is the alternative where the volume load is contraindicated.
Related calculators
References
- Funder JW, Carey RM, Mantero F, et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889–1916. doi:10.1210/jc.2015-4061
- Stowasser M, Ahmed AH, Cowley D, Wolley M, Guo Z, McWhinney BC, Ungerer JP, Gordon RD. Comparison of Seated With Recumbent Saline Suppression Testing for the Diagnosis of Primary Aldosteronism. J Clin Endocrinol Metab. 2018;103(11):4113–4124. doi:10.1210/jc.2018-01394
- Thuzar M, Young K, Ahmed AH, et al. Diagnosis of Primary Aldosteronism by Seated Saline Suppression Test—Variability Between Immunoassay and HPLC-MS/MS. J Clin Endocrinol Metab. 2020;105(3):e477–e483. doi:10.1210/clinem/dgz150
- Adler GK, Stowasser M, Correa R, et al. Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2025;110(9):2453.
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.