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Title: Congenital deficiency of 11beta-hydroxysteroid dehydrogenase (apparent mineralocorticoid excess syndrome): diagnostic value of urinary free cortisol and cortisone.
Author: Palermo M, Delitala G, Mantero F, Stewart PM, Shackleton CH.
Journal: J Endocrinol Invest; 2001 Jan; 24(1):17-23. PubMed ID: 11227727.
Abstract:
The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension. This disorder results from an inability of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD) to inactivate cortisol to cortisone. The diagnosis of AME is usually based on an elevated ratio of cortisol to cortisone reduced metabolites in the urine [tetrahydrocortisol plus allotetrahydrocortisol to tetrahydrocortisone (THF+alloTHF/THE)]. The principal site of "A" ring reduction is the liver, but AME arises from mutation in the gene encoding 11beta-OHSD2 in the kidney. We used a gas chromatographic/mass spectrometric method to measure the urinary free cortisol (UFF) and free cortisone (UFE) in 24 patients affected by the two variants of AME [19 with the classical form (type I) and 5 with the mild form called AME type II] in order to provide a more reproducible in vivo measure of the renal enzymatic activity. Type I patients were divided into two groups: children under 12 and adults. UFF levels (microg/24 h) did not differ between under-12 controls and AME type I children (mean+/-SD, 9+/-4 and 15+/-12, respectively), but was significantly higher in affected adults compared to controls: (62+/-32 vs 29+/-8, p<0.01). No differences were found between adult controls and AME type II patients (29+/-8 and 37.0+/-14, respectively). UFE was undetectable in 63% of AME type I and significantly lower in AME type II (p<0.05). As a consequence UFF/UFE ratio was significantly higher in AME type I patients both in children and adults compared to controls (AME children: 5.1+/-2.6; normal children: 0.43+/-0.2, p<0.01; AME type I adults: 17.7+/-19.6; normal adults: 0.54+/-0.3 p<0.01). For AME type II, where UFE was detectable in every case, the UFF/UFE ratio was significantly higher than adult controls (2.75+/-1.5 vs 0.54+/-0.3, p<0.01). In conclusion, our study indicates that UFE and UFF/UFE ratio are sensitive markers of 11beta-OHSD2, directly reflecting the activity of the renal isozyme and readily identifying patients with AME. The presence of an altered UFF/UFE ratio in both types of AME, although with different degree of severity, calls for re-evaluation and the classification of AME as a single disorder.

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