Sandbox:Mehrian

The hallmarks of 17OHD, first described in 1966 [3], include hypertension and hypokalemia due to the accumulation of cortisol precursors with mineralocorticoid activity upstream of the block, plus sexual infantilism due to inability to synthesize androgens and estrogens. Unlike most other forms of CAH, mineralocorticoid excess and high corticosterone production [9] mitigate the clinical consequences of cortisol deficiency, and symptomatic adrenal insufficiency is rare [4,10-16]. CYP17A1 metabolizes pregnenolone, progesterone, and their 17-hydroxy derivatives early in the steroidogenic cascades (figure 2) [11]. Consequently, 17OHD eliminates the synthesis of most steroids and limits steroidogenesis to progesterone, 11-deoxycoricosterone (DOC), corticosterone, and 18-oxygenated derivatives (table 1) [12,13]. DOC binds with high affinity to the mineralocorticoid receptor and is not a substrate for 11-beta hydroxysteroid dehydrogenase type 2. DOC excess causes volume expansion, hypertension, and kaluresis despite suppressed renin and aldosterone production. The lack of 17,20-lyase activity precludes conversion of 21-carbon steroids to 19-carbon androgen precursors in both 17OHD and ILD (figure 2). In ILD, 17-hydroxyation is largely preserved, and DOC does not accumulate, hence hypertension and hypokalemia are not found. Low 19-carbon steroid production, however, causes variable degrees of genital ambiguity in affected 46,XY males with a tendency for gynecomastia during puberty, as occurs in many states of low testosterone synthesis. Affected girls develop only sparse pubic hair and can have dysmenorrhea [14]. Clinical presentation — The classic presentation of severe 17OHD in phenotypic females (who can have 46,XX or 46,XY karyotypes) includes [3,9,10]: ● Hypertension ● Primary amenorrhea ● Absence of secondary sexual characteristics ● Minimal body hair