Figure 2 illustrates the pathophysiology of 3βHSD2D. HSD3B2 catalyzes reactions responsible for synthesis of a 3-keto-Δ4 A-ring, which is an essential part of endogenous mineralocorticoids, glucocorticoids, progestins, and androgens [3, 12, 24]. As a result, 3βHSD2D impairs the synthesis of progesterone, the precursor hormone of aldosterone, 17OHP, the precursor for cortisol, androstenedione, testosterone, and estrogen in the adrenal glands and gonads [13, 24]. Reduced levels of cortisol decrease the negative feedback on the pituitary gland causing excess ACTH production. Subsequently, ACTH drives the accumulation of β-hydroxy-Δ5-steroids pregnenolone, 17-hydroxypregnenolone, and DHEA, and their sulfates [25]. These precursor steroids cannot compensate for the cortisol and aldosterone deficiencies resulting in electrolyte disturbances and SW in most patients [12].
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In addition, testosterone replacement therapy might be considered for male patients with testosterone responsive microphallus to augment penile growth [33]. Hormonal replacement therapy should be combined with regular clinical and biochemical evaluation of these patients [15]. Surgical intervention might be indicated in some circumstances including undescended testis [63], hypospadias repair [20], and severe genital virilization [136,137,138].
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