17-Hydroxyprogesterone Response to Standard Dose Synacthene Stımulation Test in CYP21A2 Heterozygous Carriers and Non-Carriers in Symptomatic and Asymptomatic Groups: Meta-Analyses

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Objective Standard dose synacthene stimulation test (SDSST) is a gold standard screening test for evaluating adrenal gland functions. Despite the presence of the studies to determine heterozygosity of CYP21A2 by the SDSST, the reliability of the test is still controversial. Therefore, the meta-analyses were performed to determine the differences of the 17-hydroxyprogesterone(17-OHP) response to the standard dose(0.25mg) synacthene stimulation in the diagnosis of CYP21A2 heterozygous individuals with or without a clinical sign of androgen excess disorders. Methods PubMed and MEDLINE databases were searched. A total of 1215 subjects (heterozygous carriers n:669, mutation-free controls n:546) were included in the meta-analyses. Results Basal 17-OHP median-mean levels were determined to be 4.156(3.05-10.5)-5.241(2.59)nmol/L and 3.90(2.20-9.74)-4.67(2.62)nmol/L in symptomatic heterozygous carriers and symptomatic mutation-free controls, respectively. Stimulated 17-OHP median-mean levels were determined to be 17.29(14.22-37.2)-19.51(7.63)nmol/L and 9.27(7.32-15.9)-10.77(3.48)nmol/L in symptomatic heterozygous carriers and symptomatic mutation-free controls, respectively. Basal 17-OHP median-mean levels were determined to be 3.21(2.64-4.78)-3.33(±0.84)nmol/L and 3.12(1.82-3.6)-2.83(0.71)nmol/L in asymptomatic heterozygous carriers and asymptomatic mutation-free healthy controls, respectively. Stimulated 17-OHP median-mean levels were found to be 14.16(12.73-16.37)-14.16(1.37) nmol/L and 6.26(4.9-8.23)-6.48(1.2)nmol/L in asymptomatic heterozygous carriers and asymptomatic mutation-free healthy controls, respectively. The cut-off levels for stimulated 17-OHP were 10.48nmol/L and 13.48nmol/L for asymptomatic heterozygous and symptomatic heterozygous, respectively. Conclusion The meta-analyses support the idea that stimulated 17-OHP level has potential to use to determine CYP21A2 carriers. Besides, considering differences of the basal and stimulated 17-OHP levels in symptomatic heterozygous individuals than those who were asymptomatic heterozygous could increase the accuracy of the test.