Background: Severe deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) triggers activation of mineralocorticoid receptor (MR) by cortisol and causing apparent mineralocorticoid excess (AME) syndrome characterized mostly by low-renin arterial hypertension and hypokalemia. In 2003, we studied a patient with AME (3 years-old) having two homozygous mutation, D223N (rs121917833) and a SNP C>T in intron 3 (rs376023420) (Carvajal et al. JCEM 2003).
Objective and hypothesis: To study the current clinical and biochemical status of the same AME patient including his mother and sister, and to evaluate serum cortisol/cortisone as a biomarker of partial 11βHSD2 deficiency.
Method: We have recently evaluated the AME index case (17 years old), his mother (33 years old) and sister (8 years old). In all of them, we measured serum potassium, aldosterone, plasma renin activity (PRA) and microalbuminuria. Serum cortisol and cortisone were measured by LC-MS/MS, and cortisol/cortisone ratio was calculated. Genetic analyses of HSD11B2 gene were performed by PCR-HRM and DNA-sequencing.
Results: The medical record of the AME index case indicated he was not under treatment. His clinical evaluation showed: hypertension (165/110 mmHg (>p99)), stunting (53 kg; 153 cm (−2.92DS); BMI: 22.6 Kg/m2 (p69), cardiac abnormalities (LVH), microalbuminuria (112 mg/24 h), severe hypokalemia (2.1 mEq/l), low aldosterone (1 ng/dl), suppressed PRA (<0.2 ng/ml*h) and a high cortisol/cortisone ratio (28.8 (Reference value (RV): 1.635.15)). Evaluation of his mother and sister indicated that both were normotensive and heterozygous for the same mutations, without biochemical abnormalities (normal aldosterone, PRA, potassium) but with high cortisol/cortisone ratios (13.1 (RV: 2.587.8) and 7.4 (RV: 1.635.15), respectively).
Conclusion: Serum cortisol/cortisone ratio could be a sensitive tool to identify subjects with severe or partial 11βHSD2 deficiency. Since partial 11βHSD2 deficiencies -identified by high serum cortisol/cortisone ratio- may have no evidence of low-renin hypertension, low aldosterone or hipokalemia, is highly necessary to identify other complementary biomarkers to evaluate the progression of this condition.
Funding information: Supported by FONDECYT 1130427, 1150437; FONDEF-IDEA CA12i10150, CORFO 13CTI-21526-P1 and the IMII P09/016-F (ICM) Chilean Grants.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology