Differentiating 11β-hydroxylase deficiency from primary glucocorticoid resistance syndrome in male precocity: real challenge in low-income countries

Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency (11-BHD) and primary glucocorticoid resistance syndrome (PGRS) are two relatively uncommon causes of gonadotropin-releasing hormone-independent isosexual male precocity; PGRS, however, is considerably rarer than 11-BHD. Other than serum and urinary cortisol, which are elevated in PGRS and low/low-normal in 11-BHD, both of these conditions are indistinguishable by clinical, biochemical or radiological parameters. In 11-BHD, oxidation of 11-deoxycortisol (11-DOC) to cortisol is impaired, resulting in accumulation of 11-DOC and other cortisol precursors. 11-DOC shares structural homology with cortisol, and falsely elevated serum cortisol values are observed in older generation immunoassays (Siemens ADVIA Centaur) due to antibody cross-reactivity. 11-BHD, thus, may be misdiagnosed as PGRS. Structure-based cortisol assays are not widely available in low-income countries. Hence, immunoassays using highly specific antibodies against cortisol are required to ensure assay selectivity. Newer generation analysers probably are effective alternatives to liquid chromatography-tandem mass spectrometry in conditions associated with 11β-hydroxylase defect.