Adrenal Vein Sampling Interpreter

Adrenal Vein Sampling Interpreter

Adrenal vein sampling decides whether someone with primary aldosteronism gets an adrenalectomy or lifelong medical therapy, and it is misread often. This computes both indices side by side and applies them in the only order that works: selectivity first, because a failed cannulation makes the lateralisation index meaningless. Where the published thresholds disagree, the page prints the disagreement.

Selectivity first, then lateralisation

Two indices → unilateral or bilateral
Any consistent unit — ng/dL in North America, pmol/L in much of Europe. Both indices are ratios of ratios and therefore dimensionless, so the units cancel provided you use the SAME aldosterone unit for all three samples and the same cortisol unit for all three. The aldosterone converter converts if your three results are not already in one unit.
µg/dL or nmol/L, consistently across all three samples. Adrenal vein cortisol runs far above peripheral — that gradient is the whole basis of the selectivity index. The cortisol converter is next door.
The right adrenal vein is the short one that drains straight into the inferior vena cava, and it is the sample that most often fails selectivity. If this cortisol is close to the peripheral value, suspect that the catheter was in the cava.
From the infra-adrenal inferior vena cava or a peripheral vein, drawn at the same time as the adrenal samples. This is the denominator of both selectivity indices and of the contralateral suppression index, so an error here moves three of the five figures below.
This changes the selectivity threshold used below from 2 to 5, and it is the single input that most changes the interpretation. Cosyntropin raises adrenal vein cortisol several-fold, which makes selectivity far easier to demonstrate; the 2016 Endocrine Society guideline neither recommended nor opposed it, and practice still varies by centre.
12.00lateralisation indexExample

Cosyntropin-stimulated study. Left adrenal vein aldosterone 1,650 and cortisol 550; right adrenal vein aldosterone 220 and cortisol 880; IVC aldosterone 30 and cortisol 25.

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Two indices, in the order they have to be applied

1. Selectivity index, per side = adrenal vein cortisol ÷ IVC cortisol.
   Threshold — ≥2 unstimulated, ≥5 stimulated. If either side fails, stop.
2. Lateralisation index = (aldosterone ÷ cortisol)higher side ÷ (aldosterone ÷ cortisol)lower side.
   Threshold — ≥4 per the 2025 Endocrine Society guideline, stimulated or not. See the table for where this is disputed.
3. Contralateral suppression index = (aldosterone ÷ cortisol)lower side ÷ (aldosterone ÷ cortisol)IVC.
   Threshold — <1. A supporting criterion, not a deciding one.
why cortisol at all
because an adrenal vein sample is diluted to an unknown and variable degree by the blood already in the vessel. Cortisol is secreted by both adrenals at a rate far above the peripheral concentration, so the cortisol gradient measures how much adrenal blood is in the sample and dividing aldosterone by cortisol cancels the dilution out. Everything on this page rests on that one step, which is also why an unexpectedly low adrenal vein cortisol invalidates the ratio built from it
selectivity first, always
a diluted sample has its aldosterone-to-cortisol ratio pulled towards the peripheral value, which drags the lateralisation index towards 1 and towards a false report of bilateral disease. So a failed selectivity index does not make the lateralisation index less reliable — it makes it biased in a specific and clinically harmful direction, and the two cannot be reported together as though both were findings
the operative side
the side with the HIGHER aldosterone-to-cortisol ratio. Written out, the lateralisation index is the dominant side over the non-dominant side, so it is 1 or greater by construction and the scale on this page starts at 1. The side it names is not always the side with the nodule on CT, and above about age 35 the sampling is the better guide
units cancel
all three indices are ratios of ratios, so they are dimensionless and it does not matter whether the aldosterone is in ng/dL or pmol/L. What matters is consistency: the same aldosterone unit for all three samples and the same cortisol unit for all three. The two aldosterone-to-cortisol ratios shown above are NOT dimensionless and are printed in whatever units you entered, for checking rather than for comparison against a published figure
what this page does not compute
the aldosterone selectivity index, the simple aldosterone lateralisation index and the comparative aldosterone index, all of which appear in the literature with their own cut-offs and none of which is in the 2025 guideline’s table. Nor the relative aldosterone secretion index. Adding them would multiply the thresholds on the page without settling anything

Worked example

Cosyntropin-stimulated study. Left adrenal vein aldosterone 1,650 and cortisol 550; right adrenal vein aldosterone 220 and cortisol 880; IVC aldosterone 30 and cortisol 25.
Step 1, selectivity. Left 550 ÷ 25 = 22.0; right 880 ÷ 25 = 35.2. The stimulated threshold is 5, so both sides pass comfortably and the study may be interpreted
Step 2, the ratios. Left 1,650 ÷ 550 = 3.00; right 220 ÷ 880 = 0.25; IVC 30 ÷ 25 = 1.20
Step 3, lateralisation. Dominant over non-dominant = 3.00 ÷ 0.25 = 12.00, well above the threshold of 4. The left is the dominant side, so the left adrenal is the operative one
Step 4, the supporting criterion. Contralateral suppression index = 0.25 ÷ 1.20 = 0.21, which is below 1 — the right adrenal has been suppressed, exactly as autonomous left-sided secretion should do. The two criteria agree
Verdict. Unilateral primary aldosteronism, left-sided; a candidate for laparoscopic left adrenalectomy if fit for surgery and willing
Now change one number. Had the right adrenal vein cortisol been 100 rather than 880, its selectivity index would have been 4.0 — below the stimulated threshold of 5 — and the lateralisation index would have read 3.00 ÷ 2.20 = 1.36, which looks like clear bilateral disease. That is the failure mode this page is ordered around: the same patient, a mis-sited catheter on one side, and an answer that would have cost them a curative operation

The published thresholds, and where they disagree

Index2025 Endocrine Society guidelineRossi 2025 reviewNaruse 2021 review
Selectivity, unstimulated>1.4 to 3 (printed as a range)≥2.02 recommended; ~60% of 24 centres used 2, range 1.1 to 3.0
Selectivity, cosyntropin-stimulated>5≥3.0 to ≥4.05 recommended; ~60% of 24 centres used 3 to 5
Lateralisation, unstimulated≥4No single figure nominated>2, as a complementary criterion
Lateralisation, cosyntropin-stimulated≥4No single figure nominated>4 — "the most widely accepted criterion"
Contralateral suppression<1<0.96 to ≤1.00<1 with ACTH, used in combination with the lateralisation index
Three authorities, read in full rather than summarised, and they agree on only one line: the stimulated lateralisation threshold of 4. The unstimulated lateralisation row is the consequential disagreement — a patient with an unstimulated index of 3 is unilateral under one criterion and bilateral under another, and that decides whether they are offered surgery. This page reports that band as disputed rather than picking a side. The selectivity rows disagree too, which is why the threshold actually applied is printed above the result.

How the two indices combine

SelectivityLateralisationWhat it means
Either side failsAny valueUninterpretable. Repeat the study. Dilution biases the lateralisation index towards bilateral, so a failed study read as successful risks denying a curative operation
Both sides passAt or above thresholdUnilateral primary aldosteronism. Adrenalectomy of the higher-ratio side, if the patient is fit and willing
Both sides passBelow thresholdBilateral aldosterone excess. Mineralocorticoid receptor antagonist. Unilateral surgery would not cure it
Both sides passIn the disputed 2-to-4 band, unstimulatedIndeterminate. Report the numbers, weigh the contralateral suppression index, the potassium, the age and the imaging, and consider a stimulated study
The first row is the one this page exists for. It is the only row in which the lateralisation index should not be quoted at all.

Why selectivity comes first, and why this page prints a disagreement

Primary aldosteronism is the commonest curable cause of secondary hypertension, and it comes in two forms that look identical in the clinic and require opposite treatment. Unilateral disease — usually an aldosterone-producing adenoma — is cured, or substantially improved, by removing one adrenal gland. Bilateral adrenal hyperplasia is not, and is managed for life with a mineralocorticoid receptor antagonist. Computed tomography cannot reliably tell them apart: non-functioning adrenal nodules are common with age, small adenomas are missed, and the visible lesion is sometimes on the wrong side. Adrenal vein sampling is the test that settles it, and the 2025 Endocrine Society guideline recommends it before surgery is offered. The diagnostic step that comes before all of this — establishing that the patient has primary aldosteronism at all — is on the aldosterone-to-renin ratio calculator.

The procedure’s difficulty is anatomical. The left adrenal vein drains into the left renal vein and gives a reasonable target. The right adrenal vein is short, enters the inferior vena cava directly at an oblique angle, and is the reason the published success rates for the procedure vary so widely between centres. If the catheter is not actually in the adrenal vein, the sample is inferior vena cava blood, or a mixture, and the selectivity index is the only thing that reveals it.

That is why the order on this page is not negotiable. Both indices divide aldosterone by cortisol, which is what cancels out the unknown dilution in an adrenal vein sample — cortisol is secreted by both glands at concentrations far above peripheral, so the cortisol gradient measures how much adrenal blood the sample contains. When a sample is diluted, its aldosterone-to-cortisol ratio moves towards the peripheral ratio. Both ratios moving towards a common value drives the lateralisation index towards 1, and therefore towards a report of bilateral disease. So the bias from a failed cannulation is not random: it runs in one direction, and the direction it runs is towards denying a patient with a unilateral adenoma an operation that would have cured them. A lateralisation index computed on a non-selective sample is not a weak result. It is a misleading one, and this page refuses to display it as a finding.

The second thing this page does is print a disagreement instead of hiding one. Reading the three authorities in full rather than in summary, they differ on four of the five thresholds in the table above, and one of those differences changes management. The 2025 Endocrine Society guideline gives a single lateralisation cut-off of 4, for stimulated and unstimulated sampling alike. Naruse and colleagues state that a lateralisation index above 2 without ACTH stimulation can be used complementarily, alongside contralateral suppression, to support a unilateral diagnosis. Rossi and colleagues, reviewing the field, decline to nominate a single number and observe instead that there is wide variability in the cut-offs centres use and that the right value depends partly on assay imprecision. An unstimulated lateralisation index of 3 is therefore a unilateral result at one centre and a bilateral result at another. Choosing one of those silently would make this page look more decisive and would misrepresent the evidence, so the middle band says so and lists what narrows the question: the contralateral suppression index, the potassium, the age, the imaging, and whether a stimulated study is available, since the stimulated threshold of 4 is the one figure nobody disputes.

On cosyntropin itself, the honest position is that practice varies and the evidence is not settled. Stimulation raises adrenal vein cortisol several-fold and makes selectivity much easier to demonstrate, which is a real advantage when cannulation is the limiting step. Against that, it raises the selectivity threshold you have to clear and there is published concern that stimulated sampling under-identifies surgically curable disease relative to basal sampling, presumably because ACTH recruits aldosterone secretion from the suppressed gland as well. The 2016 Endocrine Society guideline neither recommended nor opposed it. This page applies the threshold appropriate to whichever was used and says which one it applied. Related pages: the short Synacthen test interpreter for the other use of cosyntropin, the aldosterone converter and the cortisol converter for units, and the potassium converter for the potassium that usually prompted the investigation.

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Frequently asked questions

What is the selectivity index in adrenal vein sampling?

The adrenal vein cortisol divided by the inferior vena cava or peripheral cortisol, calculated separately for each side. It asks a purely technical question: was the catheter actually in the adrenal vein? Cortisol is secreted by both adrenals at concentrations far above peripheral, so a large gradient confirms the sample is adrenal blood and a small one means it is mostly caval blood. The 2025 Endocrine Society guideline gives the unstimulated cut-off as a range of greater than 1.4 to 3 and the cosyntropin-stimulated cut-off as greater than 5; Rossi and colleagues give at least 2.0 unstimulated and 3.0 to 4.0 stimulated. This page applies 2 and 5 and prints which one it used.

What is the lateralisation index, and what is the cut-off?

The aldosterone-to-cortisol ratio of the higher side divided by that of the lower side. Because it is defined that way it is always 1 or more, and the side with the higher ratio is the operative one. The 2025 Endocrine Society guideline gives a cut-off of 4 or above, for unstimulated and stimulated sampling alike. For stimulated sampling that figure is undisputed. For unstimulated sampling it is not: Naruse and colleagues describe an index above 2 as usable complementarily, and Rossi and colleagues nominate no single figure, so a patient with an unstimulated index between 2 and 4 is classified differently depending on the centre.

Why must the selectivity index be checked before the lateralisation index?

Because a failed cannulation biases the lateralisation index in one particular and harmful direction. A diluted adrenal vein sample has its aldosterone-to-cortisol ratio pulled towards the peripheral value; when that happens on one or both sides the two ratios converge, the lateralisation index falls towards 1, and the study reads as bilateral disease. A patient with a unilateral aldosterone-producing adenoma can therefore be told they need lifelong medical therapy on the strength of a technically failed study, which is the commonest serious misreading of this test. A non-selective study has no lateralisation result to report.

What is the contralateral suppression index and how much weight does it carry?

The aldosterone-to-cortisol ratio of the non-dominant adrenal vein divided by the same ratio in the inferior vena cava or a peripheral vein. Below 1 means the non-dominant gland has been switched off, which is what autonomous secretion from the other side should cause, and the 2025 Endocrine Society guideline gives less than 1 as the criterion. Rossi and colleagues give a range of below 0.96 to at or below 1.00. It is a supporting criterion rather than a deciding one: all three sources use it alongside the lateralisation index, not in place of it. Where the two disagree, the study is best reported as discordant with both numbers given.

Does cosyntropin stimulation change the thresholds?

Yes, for selectivity, and that is the main reason it is asked here. Cosyntropin raises adrenal vein cortisol several-fold, so the selectivity threshold rises from 2 to 5. The lateralisation threshold of 4 is given by the 2025 Endocrine Society guideline for both stimulated and unstimulated studies. Whether to stimulate at all remains unsettled: it makes cannulation much easier to confirm, but a retrospective cohort has argued that stimulated sampling under-identifies surgically curable primary aldosteronism compared with basal sampling, and the 2016 Endocrine Society guideline neither recommended nor opposed it.

What happens if only one adrenal vein was successfully cannulated?

The lateralisation index cannot be calculated, and this page will not report one. The failure is usually on the right, because that vein is short and enters the cava directly. Options are to repeat the study — ideally with intraprocedural cortisol measurement so cannulation is confirmed before the catheter is withdrawn, and possibly with cosyntropin to widen the selectivity gradient — or, where that is not feasible, to fall back on imaging, age and the confirmatory biochemistry. Some centres use a left-adrenal-vein-to-peripheral ratio to predict lateralisation when the right vein is unavailable, but that is a substitute model and not the lateralisation index.

Do the units of aldosterone and cortisol matter?

Not for the indices, provided you are consistent. All three indices are ratios of ratios, so they are dimensionless and ng/dL, pmol/L, µg/dL and nmol/L all give the same answer as long as the same aldosterone unit is used for all three samples and the same cortisol unit for all three. Mixing units between samples is the one thing that breaks them. The two aldosterone-to-cortisol ratios shown alongside the result are not dimensionless and are printed in whatever units you entered, for arithmetic checking rather than comparison with a published figure.

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References

  1. Adler GK, Stowasser M, Correa RR, Khan N, Kline G, McGowan MJ, Mulatero P, Murad MH, Touyz RM, Vaidya A, Williams TA, Yang J, Young WF, Zennaro MC, Brito JP. Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2025;110(9):2453–2495. doi:10.1210/clinem/dgaf284. Table 9 gives the selectivity index as "[cortisol]AV/[cortisol]IVC" with an unstimulated cut-off of ">1.4 to 3" and cosyntropin-stimulated ">5"; the lateralisation index as "([aldosterone]/[cortisol])highAV/([aldosterone]/[cortisol])lowAV" with a cut-off of "≥4" unstimulated or stimulated; and the contralateral suppression index as "([aldosterone]/[cortisol])lowAV/([aldosterone]/[cortisol])IVC" with a cut-off of "<1". This guideline supersedes Funder 2016, which carried no numeric AVS criteria.
  2. Rossi GP, Battistel M, Seccia TM, Rossi FB, Rossitto G. Subtyping of Primary Aldosteronism by Adrenal Venous Sampling. Endocr Rev. 2025;46(4):501–517. doi:10.1210/endrev/bnaf007. Selectivity index ≥2.0 unstimulated and ≥3.0 to ≥4.0 cosyntropin-stimulated; contralateral suppression <0.96 to ≤1.00; no single lateralisation cut-off nominated. States that "there is a wide variability in the SI cutoff values used among centers" and that cut-offs "also depend on … accuracy (within-assay coefficient of variation)".
  3. Naruse M, Tanabe A, Yamamoto K, Rakugi H, Kometani M, Yoneda T, Kobayashi H, Abe M, Ohno Y, Inagaki N, Izawa S, Sone M. Adrenal Venous Sampling for Subtype Diagnosis of Primary Hyperaldosteronism. Endocrinol Metab (Seoul). 2021;36(5):965–973. doi:10.3803/EnM.2021.1192. Verbatim: "A questionnaire study on AVS conducted in 24 centers worldwide revealed that approximately 60% of the centers used a SI cutoff of 2 without ACTH stimulation and of 3 to 5 with ACTH stimulation, although the cutoff values varied among the centers"; "A LI >4 with ACTH stimulation is the most widely accepted criterion for unilateral diagnosis"; "a LI >2 without ACTH stimulation and a CLR <1 with ACTH stimulation can be utilized complementarily to enforce the accuracy of unilateral diagnosis"; and a selectivity index "≥1.4 without ACTH stimulation was recently demonstrated to correspond to that based on a SI ≥5 with ACTH stimulation".
  4. Rossi GP, Auchus RJ, Brown M, Lenders JWM, Naruse M, Plouin PF, Satoh F, Young WF. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension. 2014;63(1):151–160. doi:10.1161/HYPERTENSIONAHA.113.02097. Cited as the consensus document. Its full text could not be retrieved when this page was written, so no threshold on this page is attributed to it; the figures above come from the three sources that were read in full.
  5. Rossi GP, Barisa M, Allolio B, Auchus RJ, Amar L, Cohen D, et al. The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism. J Clin Endocrinol Metab. 2012;97(5):1606–1614. doi:10.1210/jc.2011-2830. The 24-centre survey quoted above; cosyntropin stimulation was used in 11 of the centres, 13 of 20 used sequential catheterisation and 7 bilaterally simultaneous catheterisation.
  6. 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. Recommendation 3.2 recommends AVS by an experienced radiologist to distinguish unilateral from bilateral disease, and notes that patients under 35 with spontaneous hypokalaemia, marked aldosterone excess and a unilateral cortical adenoma on CT may not need it. It sets out no numeric interpretation criteria.
  7. Wannachalee T, Zhao L, Nanba K, et al. Adrenocorticotropic Hormone-Stimulated Adrenal Venous Sampling Underestimates Surgically Curable Primary Aldosteronism: A Retrospective Cohort Study and Review of Contemporary Studies. Hypertension. 2021;78(5):1503–1512. doi:10.1161/HYPERTENSIONAHA.121.17248
  8. Rossitto G, Battistel M, Barbiero G, Bisogni V, Maiolino G, Diego M, Seccia TM, Rossi GP. The subtyping of primary aldosteronism by adrenal vein sampling: sequential blood sampling causes factitious lateralization. J Hypertens. 2018;36(2):335–343. doi:10.1097/HJH.0000000000001564. In 138 patients, simultaneous bilateral sampling at 15 minutes identified aldosterone-producing adenoma more accurately than simulated sequential sampling (P=0.001); sequential sampling produced artificial between-side gradients.

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.