Author’s Response: In Vivo Measurements of Renal 11ß-Hydroxysteroid Dehydrogenase Type 2 Activity

P. Ferrari

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+5{alpha}THF)/THE] in urine is established and well accepted (3). Limitation of the value of the THF+5{alpha}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+5{alpha}THF)/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{alpha}THF)/THE) is not are missing. In cross-sectional studies, differences between the UFF/UFE and (THF+5{alpha}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+5{alpha}THF)/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+5{alpha}THF)/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{alpha}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

  1. Palermo M, Shackleton CH, Mantero F, Stewart PM. 1996 Urinary free cortisone and the assessment of 11ß-hydroxysteroid dehydrogenase activity in man. Clin Endocrinol (Oxf). 45:605–611.[Medline]
  2. Best R, Walker BR. 1997 Additional value of measurement of urinary cortisone and unconjugated cortisol metabolites in assessing the activity of 11ß-hydroxysteroid dehydrogenase in vivo. Clin Endocrinol (Oxf). 47:231–236.[Medline]
  3. Ferrari P, Krozowski Z. 2000 Role of the 11ß-hydroxysteroid dehydrogenase type 2 in blood pressure regulation. Kidney Int. 57:1374–1381.[CrossRef][Medline]
  4. Andrew R, Phillips DI, Walker BR. 1998 Obesity and gender influence cortisol secretion and metabolism in man. J Clin Endocrinol Metab. 83:1806–1809.[Abstract/Free Full Text]
  5. Stewart PM, Boulton A, Kumar S, Clark PM, Shackleton CH. 1999 Cortisol metabolism in human obesity: impaired cortisone->cortisol conversion in subjects with central adiposity, J Clin Endocrinol Metab. 84:1022–1027.[Abstract/Free Full Text]
  6. Finken MJ, Andrews RC, Andrew R, Walker BR. 1999 Cortisol metabolism in healthy young adults: sexual dimorphism in activities of A-ring reductases, but not 11ß-hydroxysteroid dehydrogenases. J Clin Endocrinol Metab. 84:3316-3321.[Abstract/Free Full Text]
  7. Lovati E, Ferrari P, Dick B, et. al. 1999 Molecular basis of human salt-sensitivity: the role of the 11ß-hydroxysteroid dehydrogenase type 2. J Clin Endocrinol Metab.84:3745–3749.




This Article
Full Text (PDF)
Submit a related Letter to the Editor
Purchase Article
View Shopping Cart
Alert me when this article is cited
Alert me when eLetters are posted
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in PubMed
Alert me to new issues of the journal
Download to citation manager
Request Copyright Permission
Google Scholar
Articles by Ferrari, P.
Articles citing this Article
PubMed
PubMed Citation
Articles by Ferrari, P.


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals