Deficiency in 11β-hydroxylase is the second most common cause of CAH [
4]. Mutation of
CYP11B1 gene causes decreased activity or inactivation of enzyme, which causes a decrease in conversion of 11-deoxycorticosterone to corticosterone and 11-deoxycortisol to cortisol [
5]. Reduced cortisol now increases ACTH secretion through feedback mechanism. There is overproduction of precursors proximal to the enzyme defect which serve as substrates for the accelerated androgen pathways, so that adrenal androgen secretion is increased [
2]. In such a case, development of the female external genitalia is affected
in utero by excess fetal adrenal androgens, resulting in genitalia which are ambiguous. Females are so severely virilized at birth that their external genitalia are male looking, with a penile urethra and fused labioscrotal folds [
2]. This leads to error in gender assignment after birth as in our case. Due to a delay in diagnosis in our patient, our patient was raised as a boy. Elevated metabolites with mineralocorticoid activity, such as deoxycorticosterone and its derivatives, cause hypertension in approximately two-thirds of patients [
2]. In our case, our patient has hypertension and development of hypertensive heart disease at diagnosis. Patients undergo rapid somatic growth with premature epiphyseal closure. Pelvic imaging revealed presence of Müllerian structures in our case. Unlike the external genitalia, gonads and internal structures (ovarian tubes, uterus, and cervix) that are derivatives of the Müllerian ducts are preserved since the substance that normally causes involution of these structures in men (Müllerian inhibiting factor) is not produced by the fetal ovary [
6]. Biochemical findings and an imaging report along with clinical features led to the diagnosis of 11β-hydroxylase deficiency. Due to financial constraints, we were unable to perform plasma levels of 11-deoxycortisol and renin which would have conclusively proven the diagnosis, but, as described earlier, clinical and available biochemical results supported the diagnosis of CAH due to 11β-hydroxylase deficiency. CAH caused by 11β-hydroxylase deficiency has several mutations that may affect heme binding sites. Mutations that altered the heme binding site, such as R374W and R448H/C, resulted in high Prader scores (4/5), severe hypertension, and profoundly advanced bone age [
7]. These all are present in our case.
If the diagnosis is late, it is a dilemma whether to change the gender. The decision depends on the age at diagnosis. To preserve fertility, female assignment is recommended by most authorities in all 46,XX cases of CAH [
8]. But in our case, the time at which the initial diagnosis was suspected was too late for his parents to accept a new gender. Further, the ethical aspect, regarding performance of elective genital surgeries is challenging. Elective genital surgeries should not be considered until the affected individual is old enough to possess the intellectual capacity to decide [
9]. Also, early castration requires post-pubertal hormone replacement therapy, which poses its own risks such as elevated rates of cardiovascular disease, cancers, or osteoporosis [
10]. In cases in which the patient is a minor, as in our case, every aspect such as the disadvantage of sex change to genotypic sex, fertility issues, sexual functioning, expensive surgeries, and features of gender dysphoria should be clearly explained to the legal guardians. There is consensus to rear child as male when the individual has XX genotype with CAH with extensively fused labia and a penile clitoris [
11]. The legal guardian of our patient decided to retain the male gender identity of our patient, which was assigned at birth. Medical management for us is challenging since the child has now developed true puberty. The World Professional Association for Transgender Health (WPATH) that publishes a Standards of Care (SOC) document states that adolescents applying for hormone treatment and surgery should satisfy two sets of criteria which are eligibility and readiness before proceeding [
12]. In our case, the child’s serum estrogen, LH, and FSH have started rising signifying that ovaries have started to function. So, the addition of GnRH analogues was considered. In general, transsexual adolescents (Tanner stage 2) are treated by suppressing puberty with GnRH analogues until they are 16-years old, after which cross-sex hormones may be given [
13]. So, our patient was prescribed leuprolide (GnRH analogue) to decrease LH and FSH, letrozole (aromatase inhibitor) to decrease estrogen level, and his dose of spironolactone was adjusted. The challenges we faced in the management of this patient were ethical issues pertaining to consent, expensive drugs, and timely follow-up.