Interpretation of Results for
Thyrotropin In Serum
To the Editor:
For many years, Welicome Diagnostics (Beckenham,
Kent, BR3 3BS,
U.K.), which is a division of the Wellcome Foundation,
has operated an unmunoassay
quality-assessment
program for the benefit of laboratories
that do hormonal and other immunoassays. Although
this scheme is U.K.
based, its participants
are located
worldwide.
More than 1000 laboratories now subscribe to the scheme, of
which about 130 are in the U.K. However, most do not perform all assays
and so the number of returns
for each
analysis is significantly
less. The program
consists of two six-month cycles!
annum
of lyophilized
serum specimens, which are reconstituted
and assayed every two weeks. In recent cycles, participants
have been invited to
give a diagnosis associated with their
result; for example, they would be
asked to state whether they regarded
their cortisol result to be low, normal,
or above normal.
For thyrotropin
assay, participants
state whether they consider their restilts are compatible with primary hypothyroid, euthyroid,
or primary hyperthyroid
status.
We examined the summary data (see
Table 1) for the last full cycle, and
noted that about 10% of the laboratories misdiagnose
results
that are
clearly
in the primary
hypothyroid
range.
Such misdiagnosis
could be a
result of laboratory imprecision,
inaccuracy, or use of an inappropriate reference interval. We have tried to establish whether these data are methodrelated, but this information
is not
easily retrievable
from the program.
However, if any of these reasons were
responsible, the incidence of misdiagnosis would be greater when the alllaboratory mean value was equivocal.
This is not the case, because the rate of
misdiagnosis
is greatest when the alllaboratory
mean is unequivocally
in
the primary hypothyroid range.
We can only conclude, therefore,
that this results from a misunderstanding of the clinical significance
of
thyrotropin measurement.
This in turn
gives rise to considerable concern when
it is realized that 10% of participating
laboratories are making this mistake
(we do not know whether it is the same
10% each time), and we wonder whether this is extended to the interpretation
of patients’ results.
In the light of these observations, it
behooves all clinical chemists to consider their own interpretation of resuits for thyrotropin,
whether or not
their laboratory subscribes to the Wellcome Quality Assessment
Programme.
A. P. Roelli
H. G. J. Worth
Clin. Chem. Dept.
King’s Mill Hospital
Sutton-in-A shfield
Nottinghamshire,
NG1 7 4JL, U.K.
Correlations between Abnormalities
in Chromium and Glucose
Metabolism in a Group of Diabetics
To the Editor:
We have previously reported (1) that
the chromium
(Cr) concentration
in
randomly chosen plasma samples is
lower in diabetics than in controls. We
Table 1. Clinical Assessment of Results for Thyrotropin from a Complete
Cycle of the Weilcome Quality Assessment Programme
MI-laboratory
mean result for thyrotropln,
mull-mt. unlts/L
1.61
1.45
15.13
2.10
1.59
15.23
1.48
2.11
15.27
1.63
2.11
1.45
Numbsr of laboratorIes makIng each InterpretatIon
Primary
Primary
hypothyroidIsm
3
8
522
26
4
487
9
6
507
Euthyroldlsm
hyperthyroldlsm
523
595
3
4
7
53
534
575
12
561
586
14
4
7
543
8
3
3
572
583
540
2.04
496
13
46.83
These data are reproduced by the kindpermission of WeilcomeDiagnostics.
4
3
6
5
5
5
0
42
therefore performed a six-month longitudinal study on diabetics (Type 1, n =
11; Type 2, n = 5) attending an outpatient clinic. At each visit, blood and
urine were taken for estimation
of Cr,
glucose, and creatinine.
Each patient
provided one 24-h urine specimen during this period. Results were compared
with those for a control group of 11
healthy volunteers.
For chromium
analysis we used an
electrothermal
atomic absorption technique (2). Glucose was measured by
the “Glu-cinet” method (Technicon no.
ID/SM 4/001 F83) and creatinine by a
modified Jaffe method, in a Technicon
RA 1000 analyzer.
Results are expressed as mean ± SD.
In a preliminary
report (3) we
showed that, for the whole group
(Types 1 and 2), plasma Cr was 5.9 ±
3.5 nmol/L, which was significantly
(P <0.001) lower than in the control
group (9.2 ± 3.6 nmoLfL); however, 24h Cr excretion was 2.7 ± 1.3 imol per
mole of creatinine, which was three
times larger (P <0.001) than in the
control group (0.95 ± 0.42 zmol per
mole of creatinine).
Together, these findings imply a primary renal lesion, leading to an increase in Cr excretion. This must (at
steady state) be compensated by an
equivalent threefold increase in absorption of Cr from the gut, as found
previously by use of radiotracer methods (4). This increased absorption is
nevertheless unable to restore plasma
Cr to normal.
In our 11 Type 1 diabetic patients,
24-h Cr excretion was correlated with
24-h glucose excretion (r = 0.65; P
<0.05). This suggests that either poor
control exacerbates the renal lesion or,
when this lesion is worse, good control
is more difficult. Chromium excretion
also correlates with duration of disease
(r = 0.62; P <0.05), suggesting that the
renal defect gets worse with time.
However, all individual
values for
plasma Cr concentration (six values for
each patient, measured
during
six
months) correlate with individual values for plasma glucose (r = 0.27; P
<0.05). We have shown (5) that, in
healthy individuals, an oral 75-g glucose load decreases plasma Cr. This is
not accounted
for by increased renal
loss and presumably involves Cr uptake by “stores” (perhaps cells). Therefore, in the present group of patients, it
may be that temporary
insulin lack
(evidenced by high plasma glucose) is
associated
with a relative shift of Cr
out of stores into plasma. Thus small,
short-term variations in plasma Cr
may be ascribable to internal shifts,
even when mean plasma Cr is de-
CLINICAL CHEMISTRY, Vol. 34, No. 7, 1988
1525
creased because of increased renal loss
of Cr.
We conclude that the abnormalities
in the metabolism of Cr and glucose in
diabetics seem to be related. However,
it is not yet clear (a) whether Cr depletion has a causative
role in the pathogenesis of diabetes
mellitus,
as has
been shown in patients receiving longterm total parenteral nutrition (6), and
(b) whether renal Cr loss develops as a
consequence of early diabetic nephropathy.
References
1. Morris BW, Kemp GJ, Hardisty CA.
Plasma chromium and chromium excretion
in diabetics
[Letter].
Clin Chem
1985;31:334-5.
1526
2. Morris
BW, Kemp GJ. Chromium
in
plasma and urine measured by electrothermal atomic absorption spectroscopy [Letter]. Clin Chem 1985;31:171-2.
3. Morris BW, Kemp GJ, Hardisty CA.
Alterations in plasma and urine chromium
in diabetes mellitus [Abstract]. J Endocrinol 1986;108:298.
4. Doisy RJ, Streeton DHP, Souma ML, et
al. Metabolism of 51chromium in human
subjects, normal, elderly, and diabetic subjects. In: Mertz M, Cornatzer WE, eds. New
trace elements in nutrition. New York:
Marcel Dekker, 1971:155-68.
5. Morris BW, Grifliths H, Kemp GJ. Effect
of glucose loading on concentrations of chromium in plasma and urine in healthy
adults. Clin Chem 1988;34:1114-6.
6. Jeejeebhoy KN, Chu RC, Marliss EB, et
al. Chromium
deficiency,
glucose intoler-
CLINICALCHEMISTRY, Vol. 34, No. 7, 1988
ance and neuropathy reversed by chromium
supplementation in a patient receiving
long-term total parenteral nutrition. Am J
Clin Nutr 1977;30:531-8.
Brian W. Morris
Huw Griffiths
Graham
J. Kemp1
Dept. of Clin. Chem.
Northern General Hospital
Herries Road
Sheffield S5 7A U, U.K.
1 Present
address: Dept. of Human Metab. and Clin. Biochem., Med. School, Royal
Hallamshire Hosp., Sheffield, U.K.