Sexual Development Disorder in CAH

Both pictures adapted from Langman's Medical Embryology by T.W Sadler

Sex is determined by chromosome, in which the Y chromosome contained the gene SRY that at first induce the development of testes at the gonadal ridge. The medulla develop, cortex regress and a layer of tunica albuginea forms. In the absence of SRY, the medulla regress, cortex develop to surround clusters of primordial germ cell and form ovary.

In male, testis have Sertoli cell and Leydig cell. Sertoli secrete anti-Mullerian hormone which suppressed Mullerian duct(or paramesonephronic duct that will develop into uterine tube, uterus, upper portion of vagina) while testosterone secreted by Leydig cells will stimulate wolffian duct (mesonephric duct) to form efferent ductules, epididymis, vas deferens and seminal vesicles while dihydrotestosterone(converted from testosterone by 5-alpha reductase enzyme) will stimulate growth of penis, scrotum and prostate. 

*5-alpha reductase enzyme is also produced by ovary

In female pseudohermaphroditism which commonly caused by congenital adrenal hyperplasia (adrenogenital syndrome), 21-hydroxylation is inhibited, such that ACTH level increase in response to defective cortisol production, which leads to excessive production of androgens. Patients have a46, XX chromosome complement, chromatin-positive nuclei and ovaries but excessive production of androgens masculinizes the external genitalis, frequently, there is clitoral hypertrophy and partial fusion of labia majora, giving the appearance of a scrotum and a small persistent urogenital sinus. 

Referring back to the mindmap above, female patient who experiences virilization in CAH will have uterine tube, uterus and upper portion of vagina as the Mullerian duct is not suppressed. Instead the external genitalia is stimulated by excessive testosterone and dihydrotestosterone to form ambiguous genitalia.

According to Paediatric Protocols for Malaysian Hospital 3rd ed, DSD is a neonatal emergency

History, Physical examination and Criteria that important to be noted in this topic are highlighted.

(From Speiser and White; Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency; 

Endocrine Reviews 21(3): 245-291; 2000)