Macroprolactin PEG Recovery Calculator

Macroprolactin PEG Recovery Calculator

Work out the post-PEG prolactin recovery and read it against the 60% scheme — then read the part underneath, because the laboratories that established that scheme have since argued for reporting the post-PEG prolactin against its own interval instead.

Macroprolactin PEG recovery

Post-PEG ÷ pre-PEG × 100
The original result that triggered the screen. Any unit — mIU/L, µg/L or ng/mL — as long as the post-PEG value below is in the SAME unit. The ratio cancels the unit out.
The prolactin measured in the supernatant after polyethylene glycol precipitation, in the same unit as the value above.
Serum is mixed with an equal volume of 25% PEG, so the supernatant is a 1:2 dilution and the result must be doubled before it is compared with the original. Most laboratories do this before reporting. Getting it wrong is the commonest way this calculation lands out by exactly a factor of two — if you are unsure, ask, do not assume.
30.0% recoveryExample

Total prolactin 1,200 mIU/L, dilution-corrected post-PEG prolactin 360 mIU/L

Formula

Recovery (%) = post-PEG prolactin ÷ pre-PEG prolactin × 100
Raw supernatant × 2 = dilution-corrected post-PEG prolactin
< 40% macroprolactin predominant · 40–60% indeterminate · > 60% monomeric
the ratio
unit-free. As long as both prolactin values are in the same unit — mIU/L, µg/L or ng/mL — the unit cancels and the percentage is the same
× 2
serum is mixed with an equal volume of 25% (w/v) PEG 6000, vortexed, left to stand about thirty minutes and spun, so the supernatant is a 1:2 dilution of the original. The result must be doubled before it is compared with the pre-PEG value. Most laboratories report the corrected figure; if yours reports the raw supernatant, say so above
< 40%
macroprolactin predominant. Not a universal cut-off: one widely used method paper sets the bands at < 40%, 40–65% and > 65% instead, and the choice moves how many patients are labelled
what PEG actually does
precipitates immunoglobulins, and with them the IgG-bound prolactin that makes up macroprolactin. It also takes down a little monomeric prolactin, which is exactly why a post-PEG result has to be read against a PEG-treated reference interval rather than the ordinary one
the better report
the post-PEG monomeric prolactin itself, against a method-specific PEG-treated interval. A recovery percentage misleads when macroprolactin and a genuinely raised monomeric prolactin are present together — the percentage can be low while the monomeric concentration is still above the interval

Worked example

Total prolactin 1,200 mIU/L, dilution-corrected post-PEG prolactin 360 mIU/L
360 ÷ 1200 = 0.30
0.30 × 100 = 30.0% recovery
Below 40% → macroprolactin predominant
Cross-check the absolute value: 360 mIU/L sits inside the Abbott Architect post-PEG female interval of 39–422 mIU/L, so the monomeric prolactin is not raised either and the two readings agree
If the laboratory had reported the raw supernatant as 180 mIU/L, doubling it gives the same 360 and the same 30.0%

Reading the recovery

RecoveryReadingWhat it meansNext step
< 40%Macroprolactin predominantMost of the measured prolactin is IgG-bound and biologically inertIn an asymptomatic patient, no imaging and no dopamine agonist. Still check the absolute post-PEG value against the PEG-treated interval
40 – 60%IndeterminateDifferent laboratories classify this band differently; the percentage alone cannot decideRead the absolute post-PEG prolactin against a PEG-treated interval. Gel filtration chromatography if the answer changes management
> 60%Monomeric prolactinThe raised total prolactin is real and biologically activeFull hyperprolactinaemia work-up: repeat sample, drug review, pregnancy, thyroid and renal function, then imaging
These boundaries are laboratory conventions, not a guideline. One widely used method paper uses 40% / 40–65% / > 65%, and Šostarić showed that moving the single cut-off from 40% to 60% raises the proportion labelled macroprolactinaemic from 3.3% to 8.8%.

The two ways a PEG screen gets reported

ApproachWhat appears on the reportStrengthWeakness
Percentage recoveryA recovery figure and a bandSimple, needs no extra reference data, and is what most laboratories still issueBreaks down when macroprolactin and genuine hyperprolactinaemia coexist: the recovery can be low while the monomeric prolactin is still above the interval
Post-PEG monomeric prolactinA prolactin concentration with its own PEG-treated reference intervalAnswers the question that actually matters — whether the bioactive prolactin is raisedRequires the laboratory to have established a PEG-treated interval on its own assay, which not all have
Both Šostarić 2019 and Whitehead 2015 conclude that the post-PEG concentration with a method-specific interval is the better report. The percentage remains on most reports, which is why this calculator exists.

Post-PEG reference intervals, Abbott Architect

Total prolactin (mIU/L)Post-PEG monomeric prolactin (mIU/L)
Male58 – 41932 – 309
Female63 – 56139 – 422
From Whitehead 2015, for the current-generation Abbott Architect assay. These are assay-specific and are printed here as an illustration of what a PEG-treated interval looks like — they are not transferable to another platform. Use the interval your own laboratory established.

What the percentage does and does not settle

Between ten and twenty-five per cent of hyperprolactinaemia is macroprolactinaemia: prolactin bound to IgG in a complex large enough to be trapped in the circulation, where it is measured enthusiastically by immunoassays and does almost nothing biologically. Patients with it are often asymptomatic, and the cost of missing it is a pituitary MRI and a dopamine agonist given for a laboratory artefact. Polyethylene glycol precipitation is the screen: serum is mixed with an equal volume of 25% PEG 6000, which drags the immunoglobulins and everything bound to them out of solution, and the prolactin remaining in the supernatant is measured and compared with the original.

The arithmetic is trivial and the trap is in the dilution. Mixing one volume of serum with one volume of PEG halves everything, so the supernatant result has to be doubled before it is divided by the pre-PEG value. Most laboratories apply that correction before reporting; some do not. A recovery calculated from an uncorrected supernatant comes out at exactly half the true figure, which turns a genuine 70% into an apparent 35% and converts a real prolactinoma into a reassuring artefact. That is why this page asks rather than assumes.

The conventional reading is that under 40% recovery indicates macroprolactin, over 60% indicates monomeric prolactin, and the band between is indeterminate. Those boundaries are laboratory convention rather than guideline, and they move: one widely used method paper puts the upper edge at 65%, and Šostarić showed that shifting a single cut-off from 40% to 60% takes the proportion of patients labelled macroprolactinaemic from 3.3% to 8.8%. A recovery of 45% therefore means different things in different hospitals, and no amount of decimal places fixes that.

There is a deeper problem with the percentage, and the laboratories that use it most have said so. A ratio cannot distinguish a patient whose prolactin is all macroprolactin from one who has macroprolactin and a prolactinoma at the same time — in the second, the recovery is low and the monomeric prolactin is still frankly raised. Both Šostarić and Whitehead conclude that the right report is the post-PEG monomeric prolactin itself, read against a PEG-treated reference interval established on that laboratory’s own assay, because PEG removes a little monomeric prolactin too and the ordinary interval does not apply to a PEG-treated sample. Where your laboratory publishes such an interval, use it in preference to the percentage; where it does not, use the percentage but always look at the absolute post-PEG number as well. One further point on who to test: Fahie-Wilson and Smith argue for PEG on every sample above the manufacturer’s upper reference limit, because screening only above 700 mU/L misses more than half of macroprolactinaemia and screening above 1000 mU/L misses 85% of it.

Frequently asked questions

How is macroprolactin PEG recovery calculated?

Divide the post-PEG prolactin by the pre-PEG prolactin and multiply by 100, with both values in the same unit. If the laboratory reported the raw supernatant rather than a dilution-corrected result, double it first — serum is mixed 1:1 with PEG, so the supernatant is a 1:2 dilution.

What recovery indicates macroprolactinaemia?

Conventionally under 40%, with over 60% indicating monomeric prolactin and 40 to 60% indeterminate. These are laboratory conventions rather than a guideline: some laboratories put the upper edge at 65%, and shifting the lower cut-off from 40% to 60% roughly doubles the proportion of patients labelled.

Should I use the recovery percentage or the post-PEG prolactin?

The post-PEG prolactin against your laboratory’s PEG-treated reference interval, where one exists. A percentage cannot separate a patient whose prolactin is all macroprolactin from one who has macroprolactin and a prolactinoma together — in that case the recovery is low but the monomeric prolactin is still raised.

Why does the post-PEG result need its own reference interval?

Because PEG precipitates a small amount of monomeric prolactin along with the immunoglobulins, so a PEG-treated sample reads slightly lower than an untreated one. The ordinary prolactin interval does not apply, and the PEG-treated interval is specific to the assay and the precipitation protocol.

Does macroprolactinaemia need rechecking?

Rarely. It is stable over time in most people, so a patient already characterised does not need the PEG screen repeated at every visit. Recheck if the clinical picture changes — new galactorrhoea, new menstrual disturbance or a visual field defect — because macroprolactin and a genuine prolactinoma can coexist.

Related calculators

References

  1. Whitehead SJ, Cornes MP, Ford C, Gama R. Reference ranges for serum total and monomeric prolactin for the current generation Abbott Architect assay. Ann Clin Biochem. 2015;52(1):61–66.
  2. Šostarić M, Bokulić A, Marijančević D, Zec I. Optimizing laboratory defined macroprolactin algorithm. Biochem Med (Zagreb). 2019;29(2):020706.
  3. Fahie-Wilson M, Smith T. Reflex and reflective testing for macroprolactinaemia in cases of hyperprolactinaemia. Ann Clin Biochem. 2021;58(3):257–258.

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.