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Clinical · Bloodwork · continued

Reference intervals: how they are constructed and why one in twenty flags posts 31–60

This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.

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KLindqvistTL4 Moderator3 Jan 2026#31

Whatever the answer on reference intervals turns out to be, the method for getting there is the same: state the assumption, do the arithmetic in public, invite the correction.

15 likes 7mo
KL
k.laurentTL25 Jan 2026#32

One caution on reference intervals: everything above assumes the underlying documentation is what it claims to be. That assumption is doing real work and is rarely stated.

31 likes 7mo
SK
s.karlsen_rphTL3Pharmacist8 Jan 2026 · edited#33

Post #30 is right about the mechanism and I think understates the practical bit.

Glycaemic markers integrate over different periods. A point glucose and a longer-term marker disagreeing is not a contradiction; it is two different questions.

The number is defensible. The precision I gave it is not.

1 like 7mo
OV
o.vukovicTL210 Jan 2026#34
LJankowiak, post #13: An update on my earlier reference intervals post: the pattern held for another six weeks and then stopped, which I did not predict and cannot explain. Go to post

Coming back to post #32, because the follow-up matters more than the original answer.

Comparing results across laboratories is harder than it looks because reference intervals and methods differ. The same sample can produce different numbers and different flags.

6 likes in reply to #13 7mo
KR
k.roosTL212 Jan 2026#35
new_here_2026, post #21: Repeat before acting is standard practice for an isolated abnormal result on most analytes, and it is standard for a reason. It cost nothing to check and would have cost something not to. Go to post

Taking post #34 at face value and following it one step further.

Reference intervals was covered in the wiki last year and the page has a review date on it, which is a better starting point than my memory of a thread.

22 likes in reply to #21 6mo
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k.salinasTL214 Jan 2026#36

Noted, and thank you for writing it out rather than summarising it.

0 likes 6mo
DF
d.fontaineTL217 Jan 2026#37

The number people quote for reference intervals is a central estimate presented without its interval, and the interval is wide enough that the estimate is nearly uninformative on its own.

3 likes 6mo
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i.bakkenTL219 Jan 2026#38

I read post #37 twice before replying, because I had assumed the opposite.

Time of day: some biomarkers vary across the day. Cortisol in the morning differs from cortisol in the evening. Comparing results from different times of day is comparing things that are not the same.

I am confident about the direction and much less about the magnitude.

10 likes 6mo
MM
m.malinowskiTL221 Jan 2026#39
k.roos, post #35: Taking post #34 at face value and following it one step further. Reference intervals was covered in the wiki last year and the page has a review date on it, which is a better starting point than my memory of a thread. Go to post

General information rather than advice about anyone's care. A single value outside a reference interval, on a single draw, in an otherwise unremarkable panel, is usually uninformative.

The disagreement above is smaller than it looks once the terms are fixed.

6 likes in reply to #35 6mo
PS
p.silvaTL223 Jan 2026#40

Post #37 put the caveat in the right place and I want to underline it.

I would be cautious about generalising from the reference intervals example above. It is a good example. It is one example.

16 likes 6mo
FP
f.petrovTL225 Jan 2026#41
c.rasmussen, post #20: Time of day: some biomarkers vary across the day. Cortisol in the morning differs from cortisol in the evening. Comparing results from different times of day is comparing things that are not the same. A modest claim, modestly supported. Go to post

Bringing the actual numbers with intervals to an appointment is far more useful than describing them, and clinicians here consistently say so.

One case, stated as one case.

23 likes in reply to #20 6mo
AS
a.stephanopoulosTL3Regular28 Jan 2026#42
n.bridgewater, post #11: This follows post #8 rather than contradicting it. Liver enzymes: elevation does not specify cause. ALT and AST can rise from many things. Bilirubin helps narrow down the cause. Multiple markers together are more informative than one alone. Adding a source would improve this post and I do not have one to hand. Go to post

The most useful thing this subcategory does is help people tell an interesting result from an uninteresting one before booking an appointment about it.

11 likes in reply to #11 6mo
PF
p.friskTL230 Jan 2026#43

Two claims get bundled together under reference intervals and they need separating. The descriptive one — this is what was observed — is usually well supported. The causal one — this is why — usually is not.

Almost every disagreement in threads like this one dissolves once you say which of the two you are making.

3 likes 6mo
VM
v.milanoviTL3Regular1 Feb 2026#44

Picking up post #41: that is the part I would want checked first.

On reference intervals, the part that usually goes wrong is that the question is asked as though it has one answer. It has a range, and the width of the range is the interesting bit.

If you can post the two or three numbers you are working from, several people here will check the arithmetic rather than argue about the conclusion.

0 likes 6mo
HF
h.fonsecaTL23 Feb 2026#45

I had read the opposite somewhere and cannot now find where, which tells me something.

17 likes 6mo
ID
integrator_draftTL3Regular5 Feb 2026#46
r.jhannsdttir, post #7: Filing a mild objection to the consensus on reference intervals. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. Go to post

A trend needs at least three points to be a trend. Two points are a line and a line through noise is still a line.

The short answer was in the first line; everything after is the working.

7 likes in reply to #7 6mo
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s.solbergTL27 Feb 2026 · edited#47

Speaking only to reference intervals as I have actually seen it, rather than as it is usually described: the effect is real, it is smaller than the thread suggests, and the variance between people is larger than the effect.

1 like 6mo
VK
v.klausenTL3Regular9 Feb 2026#48

Reference intervals: constructed to contain the central 95% of a reference population, which means one in twenty healthy people falls outside one by definition. Add biological variation and analytical imprecision and the base rate of a meaningless flag is substantial.

0 likes 6mo
JP
j.palaciosTL211 Feb 2026#49
LJankowiak, post #13: An update on my earlier reference intervals post: the pattern held for another six weeks and then stopped, which I did not predict and cannot explain. Go to post

Everything in post #46 holds. The case it does not cover is the one I have.

Reference intervals would be much easier to settle if anyone reported the denominator. Almost nobody reports the denominator.

11 likes in reply to #13 5mo
IL
integrator_logTL3Regular14 Feb 2026#50

Narrowing post #49, because the general version has more than one answer.

Repeat before acting is standard practice for an isolated abnormal result on most analytes, and it is standard for a reason.

The variance between people here is larger than the effect being discussed.

3 likes 5mo
EN
e.nilsenTL216 Feb 2026#51
AL
aliquot_lineTL3Regular18 Feb 2026#52

Two people in this thread mean different things by reference intervals and are disagreeing about the definition while believing they are disagreeing about the facts. Worth pausing to define it.

0 likes 5mo
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a.teixeiraTL220 Feb 2026#53
aliquot_line, post #52: Two people in this thread mean different things by reference intervals and are disagreeing about the definition while believing they are disagreeing about the facts. Worth pausing to define it. Go to post

Thank you for taking the time. That was more work than a reply usually is.

4 likes in reply to #52 5mo
KB
k.brandl_deTL3Translator · DE22 Feb 2026#54
a.norgaard, post #12: Worth separating two things that post #10 runs together. What I would tell a new member reading about reference intervals for the first time: the confident posts are not the reliable ones, and the reliable ones are longer. Go to post

Post #50 describes the usual case. This is about the unusual one.

Glycaemic markers integrate over different periods. A point glucose and a longer-term marker disagreeing is not a contradiction; it is two different questions.

Written quickly, so the reasoning may be tighter than the wording.

12 likes in reply to #12 5mo
CH
c.haddadTL224 Feb 2026#55

Biological variation: the person-to-person variation in a biomarker for a healthy person is larger than most people realize. Comparing your result to the reference interval is one thing; comparing your result today to your result from months ago is more sensitive to change.

I have written this out at length because the short version keeps being misread.

25 likes 5mo
RF
resistance_firstTL2Regular26 Feb 2026#56

I had written a reply contradicting post #54 and deleted it. Here is what survived.

Lipid panel interpretation: total, LDL, HDL, triglycerides all on one panel. Reading them together is more informative than reading one value in isolation. An elevated triglyceride with low HDL is different from triglyceride elevation alone.

Not a conclusion. A place to stand while looking for one.

0 likes 5mo
AK
a.kirchnerTL228 Feb 2026 · edited#57

Picking up post #56: that is the part I would want checked first.

Reference intervals is well covered in the tag pages, and the older discussions are better than the recent ones because they were argued out properly. Worth twenty minutes before adding to this one.

1 like 5mo
LI
l.ibarraTL2Regular2 Mar 2026#58
e.lokken, post #19: The most useful thing anyone has posted about reference intervals in this category was a table of what had been measured and by whom. That is what I would want again. Go to post

The reason reference intervals keeps being re-asked is that the answer is conditional and people quote it without the condition. It is not that the answer is unknown.

7 likes in reply to #19 5mo
SP
s.perrinTL24 Mar 2026#59
i.bakken, post #38: I read post #37 twice before replying, because I had assumed the opposite. Time of day: some biomarkers vary across the day. Cortisol in the morning differs from cortisol in the evening. Comparing results from different times of day is comparing things that are not the same. I am confident about the direction and much less about the… Go to post

Post #56 is right about the mechanism and I think understates the practical bit.

Glycaemic markers integrate over different periods. A point glucose and a longer-term marker disagreeing is not a contradiction; it is two different questions.

The part I am sure of is shorter than the part I have written.

18 likes in reply to #38 5mo
SS
s.stavrianosTL2Member6 Mar 2026#60

Clear enough that I do not think I have a follow-up, which is unusual.

0 likes 5mo