Division of Nephrology and Hypertension University of Berne 3010 Berne, Switzerland
To the editor:
We acknowledge the remark by Quinkler et al. that measurements of urinary free (unconjugated) cortisol (UFF) and cortisone (UFE) and particularly of their ratio (UFF/UFE) most likely provide a more sensitive index of renal 11ß-hydroxysteroid dehydrogenase type 2(11ßHSD2) activity (1, 2), particularly when 11ßHSD activity in the liver or elsewhere may be abnormal.
For the diagnosis of markedly reduced 11ßHSD2 activity, as
seen in classic apparent mineralocorticoid excess (AME)
syndrome, measurements of tetrahydrometabolites of cortisol and
cortisone [(THF+5THF)/THE] in urine is established and well
accepted (3). Limitation of the value of the
THF+5
THF)/THE ratio for the in vivo assay of 11ßHSD2
activity has been acknowledged in details by us elsewhere
(3).
Experiments using inhibitors of 11ßHSD activity, such as
glycyrrhetinic acid or carbenoxolone, suggest that the UFF/UFE ratio is
more sensitive than the urinary (THF+5THF)/THE ratio in uncovering a
decreased activity of the 11ßHSD2 enzyme. This has been shown so far
only in a few studies with a very small number of subjects. Moreover,
data proving that blood pressure increases on inhibition of 11ßHSD2
activity with exogenous inhibitors when UFF/UFE is increased but
(THF+5
THF)/THE) is not are missing. In cross-sectional
studies, differences between the UFF/UFE and (THF+5
THF)/THE ratios
have been reported in obese humans only (4, 5) or when
comparing male with female subjects (6).
Thus, the reasons we measured only the urinary (THF+5THF)/THE ratios
in our subjects were mainly due to the following considerations: 1)
this measure of 11ßHSD2 activity has long been established and
correlates with blood pressure while the UFF/UFE is not yet widely
recognized; 2) all subjects were lean with a body mass index well below
30 kg/m2, and 3) all subjects were healthy male
volunteers.
Nevertheless, it is possible that our results would have been even more
significant (7), if we would have used the UFF/UFE ratio
instead of (THF+5THF)/THE. Thus, we might well have missed some
subjects with impaired 11ßHSD2 activity as assessed by UFF/UFE.
However, the question of the clinical significance of a more sensitive
test for altered 11ßHSD2 activity arises. As long as the sensitivity
and specificity of UFF/UFE vs. (THF+5
THF)/THE in
predicting changes not only in 11ßHSD2 activity but also in blood
pressure is not demonstrated in a prospective study with subjects
exposed to low- and high-salt diet and/or glycyrrhetinic acid or
carbenoxolone, the question of the most appropriate assay for in
vivo 11ßHSD2 activity remains open.
Received September 13, 2000.
References
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