Congenital deficiency of 11β-hydroxysteroid dehydrogenase (apparent mineralocorticoid excess syndrome): Diagnostic value of urinary free cortisol and cortisone
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The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension. This disorder results from an inability of the enzyme 11β-hydroxysteroid dehydrogenase (11β-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 11β-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 (μg/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 11β-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.
Key-wordsApparent mineralocorticoid syndrome hypertension cortisol cortisone gas-chromatography/mass spectrometry
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