The subject of ultra-sensitive oestradiol assays crops up regularly
and illustrates an interesting 'dilemma' for manufacturers and users
of assays and their clients.
Without entering into a discussion about the need for oestradiol
measurements in all the clinical applications listed, if you ask
clinicians what they require of oestradiol assays they appear to
want four kinds (a) an ultra low level assay (say 5-100pmol/L) for
paediatric work, (b) a low level assay (say 50-250) for peri
menopausal / infertility work, (c) a normal range assay (say 100-
1000) and (d) a high-level assay (say 1000 - 10,000) for the
stimulation phase of assisted conception.
Immunoassay theorists and developers will tell you that a single
assay in 'competitive' limited reagent format cannot cover this
whole range with adequate imprecision. The assay has to be
optimised for part of the range and assay producers have usually
chosen to emphasise the normal to high levels. Most 'routine'
methods in use are not particularly 'sensitive' at low levels
(<150pmol/L), although people still use them and report results (at
least to UK NEQAS) well below their 'functional senstivity' (lowest
result with an imprecision <20% CV).
In an average UK NEQAS distribution of a male oestradiol sample
(ALTM = 133 pmol/L), one can see huge ranges of results (eg 11 -
203 pmol/L) for a well-known automated analyser and an absolute
range for all methods of 11 - 327 pmol/L). Most clinicalns and
many labs are unaware of this variability and uncertainty.
In the research field, laboratories have re-optimised traditional
extraction assays to achieve adequate imprecision at ultra low
levels (10 pmol/L).
Manufacturers shy away from producing more than one assay for
'marketing' reasons, even though the bulk of work that most
endocrinology sections see for oestradiol is < 400 pmol/L. One
manufacturer tried to sell a low level version of its RIA kit some
years ago, but this was not taken up in the UK. Of course there
would be practical issues for laboratories in 'guessing' from the
clincal details on the request as to whether a 'low-level' of 'high-
level' assay should be applied, but clinicians could be educated to
assist with this.
Most manufacturers of automated systems have been 'ear-bashed'
by yours truly about this over the years, but only one is known to
be actively considering the production of two separately optimised
In principle, if accurate and precise assays are required at ultra low
levels for clinical decision making and there is sufficient demand,
then laboratories must ask manufacturers to provide suitable
methods. If two or three separately optimised assays are required
for oestradiol, so be it. The marketing and sample sorting
difficulties will have to be overcome if patient benefit is at stake.
I surveyed participants some years ago as to whether an ultra-low
level oestradiol UK NEQAS would be helpful. I received only 10
expressions of interest, and half of these were non-UK. This
number is not really viable for EQA. Is there a feeling that more
laboratories want to measure ultra low levels now?
Best wishes to list members for the coming festivities!
Date sent: Thu, 16 Dec 1999 08:40:28 +0100
Subject: high sensitive estradiol
From: "Auch, Dieter" <[log in to unmask]>
To: "'Acb-Clin-Chem-Gen (E-Mail)" <[log in to unmask]>
Send reply to: "Auch, Dieter" <[log in to unmask]>
> Our endocrinologists request a reportable range of estradiol down to 10
> pmol/L (5pg/ml).
> Our present automated CLIA has a lower limit of 70pmol/L (20pg/ml). The
> reason given is (1.) diagnosis of pubertal development and (2.) (diagnosis
> or managment of) osteoporosis.
> Is someone measuring E2 down to 10pmol/l and can give some advice (on kit,
> manufacturer and extraction procedure, if necessary? Any help is welcome.
> Dieter Auch
> [log in to unmask]
> Dr. med. Dieter Auch
> Inst. f. Klin. Chemie und Pathobiochemie
> Gaffkystr. 11
> D-35392 Gießen
> Tel: +49 641 99 41552
> Fax: +49 641 99 41569
Jonathan Middle PhD
Organiser UK NEQAS for Steroid Hormones
Chairman UK NEQAS Executive
Deputy Director UK NEQAS (Birmingham)
UK NEQAS PO Box 3909 Birmingham B15 3NY
tel 0121 414 7300, fax 0121 414 1179
[log in to unmask] http://www.ukneqas.org.uk