ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P436 | DOI: 10.1530/endoabs.63.P436

Measuring steroids hormones by liquid chromatography-tandem mass spectrometry in 21-hydroxylase deficiency (21OHD) reveal large interindividual differences in hormone levels amongst patient with the same genetic mutation

Per Medbøe Thorsby1, Sandra R. Dahl1, Ingeborg Brønstad2,3, Kristian Løvås4,5 & Ingrid Nermoen6

1Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway; 2National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway; 3Department of Clinical Medicine, University of Bergen, Bergen, Norway; 4Department of Medicine, Haukeland University Hospital, Bergen, Norway; 5Clinical Science and K.G. Jebsen-Center for Autoimmune Diseases; University of Bergen, Bergen, Norway; 6Department of Endocrinology, Division of Medicin, Akershus University Hospital, Lørenskog, Norway.

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 (2–10% 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.

Table 1 Patient cases and LC-MS/MS hormone profile [nmol/l]; (H) above reference, (L) below reference
Mutation group and geno-type*Pheno-typeAge17-OHP21DF11DFDOC
NullSW313.4 (H)9 (H)00.18
NullSW36811 (H)268 (H)0.190.51(H)
BSV630.69 (H)00.08
BSV50196 (H)50 (H)1.80.21
Table 1 Continued
BFET AMedication
0 (L)0 (L)0.4 (L)0.411.8Dexamethasone 0.5 mg evening + fludrocortisone 0.1 mg morning
2116 (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)0.510.36Dexamethasone 0.5 mg evening
2.6162493.8 (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.

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