Disorders of Testosterone Synthesis

Disorders of testosterone synthesis are rare causes of 46XY DSD. Testosterone is the main driver of male sexual differentiation. Absence of testosterone due to defects in synthesis affects the formation of both external and internal genitalia in the fetus and development of secondary sexual characteristics later. Since there is a common metabolic pathway for synthesis of glucocorticoids, mineralocorticoids, and testosterone, most of these disorders are associated with deficiency of glucocorticoids and mineralocorticoids. This could lead to life-threatening complications like hypotension and salt wasting at birth. Majority of the children with these disorders have rudimentary external and internal genitalia and behave as females. These children may only be diagnosed at puberty due to amenorrhea. Due to absolute deficiency of testosterone, male pattern brain imprinting and virilization potential are minimal. Feminizing genitoplasty and estrogen supplementation can help them function as a sexually active female despite infertility. These children may also need to be supplemented with glucocorticoids and mineralocorticoids to prevent life-threatening symptoms due to hypertension and salt wasting. Diagnosis is reached by low level of testosterone, not increasing in response to gonadotropin levels along with higher level of the precursor substrates which differ according to the level of the block. Genetic testing for these disorders is confirmatory but difficult due to incomplete characterization of all genes involved, high costs, and limited availability.