Background: We have previously shown that LC-MS/MS analyses of steroid hormones are superior to immunoassays monitoring 21OHD, due to better specificity and the possibility to multiplexing several steroid hormones in the same assay. This may lead to better understanding of the individual steroid hormone profile in patients with CAH. Here we present four patients cases with the same genotype in the CYP21A2 gene, and evaluate their steroid profile by LC-MS/MS analyses.
Method: Four female patients from a cohort of 104 Norwegian patients diagnosed with CAH between 1972 and 1999 were selected. Mutations in the CYP21A2 gene were identified by direct DNA sequencing and deletions were determined by real time PCR. CYP21A2 mutations were divided into two groups according to their enzyme activity; group Null (no enzyme activity), two patients, group B (210% enzyme activity), two patients. Serum concentrations of testosterone, androstenedione, 17 - hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, deoxycorticosterone (DOC), corticosterone, cortisone and cortisol were determined by an in-house LC-MS/MS method developed at the Hormone Laboratory in Oslo.
Results: The results are presented in table 1 and shows large interindividual differences in steroid profiles amongst patients with the same genotype/phenotype.
|Mutation group and geno-type*||Pheno-type||Age||17-OHP||21DF||11DF||DOC|
|Null||SW||31||3.4 (H)||9 (H)||0||0.18|
|Null||SW||36||811 (H)||268 (H)||0.19||0.51(H)|
|B||SV||50||196 (H)||50 (H)||1.8||0.21|
|0 (L)||0 (L)||0.4 (L)||0.41||1.8||Dexamethasone 0.5 mg evening + fludrocortisone 0.1 mg morning|
|21||16 (L)||3.5 (L)||3.7 (H)||29 (H)||Prednisolone 5 mg + fludrocortisone 0.05 mg morning|
|0.1 (L)||0 (L)||0.2 (L)||0.51||0.36||Dexamethasone 0.5 mg evening|
|2.6||162||49||3.8 (H)||27 (H)||no|
|*First row: reference values. Genotype Null = no enzyme activity, B= severe enzyme failure, SW= salt wasting, SV= simple virilizing,, F (female), 17OHP (17- hydroxyprogesterone), 21DF (21-deoxycortisol), 11DF (11-deoxycortisol), DOC (Deoxycorticosterone), B (corticosterone), F (cortisol), E (cortisone), T (testosterone), A (androstenedione)|
Conclusion: Using LC-MS/MS steroid homone multiplexing in patients with 21OHD reveal large interadindividual steroid profiles within the same genotype. On may speculate that these differences may have clinical implications and may lead to better individualize treatment.
18 - 21 May 2019
European Society of Endocrinology