The syndrome of apparent
mineralocorticoid syndrome (
AME) results from defective
11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2). This
enzyme is co-expressed with the
mineralocorticoid receptor (MR) in the kidney and converts
cortisol to its inactive metabolite
cortisone. Its deficiency allows the unmetabolized
cortisol to bind to the MR inducing
sodium retention, suppression of PRA and
hypertension. Thus, the syndrome is a disorder of the kidney. We present here the first patient affected by
AME cured by
kidney transplantation. Formerly, she was considered to have a mild form of the syndrome (Type II), but progressively she developed
renal failure which required dialysis and subsequent
kidney transplantation. To test the ability of the transplanted kidney to normalise the patient's
cortisol metabolism, we gave, in two different experiments, 25 and 50 mg/day of
cortisone acetate or 15 and 30 mg/day of
cortisol after inhibition of the endogenous
cortisol by synthetic
glucocorticoid (
methylprednisolone and
dexamethasone). The
AME diagnostic urinary
steroid ratios tetrahydrocortisol+5alphatetrahydrocortisol/
tetrahydrocortisone and
cortisol/
cortisone were measured by gas chromatography/mass spectrometry.
Transplantation resulted in lowering blood pressure and in normalization of serum K and PRA. After administration of a physiological dose of
cortisol (15 mg/day), the urinary free
cortisol/
cortisone ratio was corrected (in contrast to the A-ring reduced metabolites ratio), confirming that the new kidney had functional
11beta-HSD2. This ratio was abnormally high when the supra-physiological dose of
cortisol 30 mg/day was given. After
cortisone administration, the tetrahydrocortisol+5alphatetrahydrocortisol/
tetrahydrocortisone ratio resulted normalised with both physiological and supra-physiological doses, confirming that the hepatic
reductase activity is not affected. As expected, the urinary free
cortisol/
cortisone ratio was normal with physiological, but increased after supra-physiological doses of
cortisone. The described case indicates a normalisation of
cortisol metabolism after
kidney transplantation in
AME patient and confirms the supposed pathophysiology of the syndrome. Moreover, it suggests a new therapeutic strategy in particularly vulnerable cohorts of patients inadequately responsive to
drug therapy or with
kidney failure.