[Variations in the concentration of the sex hormone binding globulin is a major factor causing a variation in total...

Measurement of total testosterone concentrations is the initial test for the diagnosis of androgen deficiency or excess in men. However, total testosterone concentrations may be affected by alterations in sex hormone binding globulin (SHBG) concentrations. Most circulating testosterone is bound to SHBG and to albumin and only 0.5-3% of circulating testosterone is unbound or free. The free fraction can be measured by equilibrium dialysis or calculated using published algorithms. The term bioavailable testosterone refers to unbound testosterone plus albumin-bound testosterone; this term reflects the view that, in addition to unbound testosterone, albumin-bound testosterone is readily dissociable and thus bioavailable. Bioavailable testosterone can be measured by precipitation methods or calculated from total testosterone, SHBG, albumin concentrations and their affinity constants. Free testosterone measurements by analog methods are frequently available, but these measurements are affected by alterations in SHBG and are inaccurate. We report the cases of a 42-year-old man with testosterone excess and a 29-year-old man with testosterone deficiency, in whom total testosterone concentrations were affected by SHBG alterations.