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

Abstract

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.