Snapshot An 8-month-old female presents with ambigous genitalia. Her urinary ketosteroids and 17-OH progesterone are twice the normal level. Additionally, testosterone levels are four times normal and urinary 17-hydroxycorticosteroids are decreased. Her brother had a similar disorder. Introduction A condition characterized by ambiguous genitalia in female Also known as congenital adrenal hyperplasia An enzymatic deficiency in cortisol and aldosterone synthesis leads to a decrease in downstream cortisol and an increase in upstream androgens Causes male sexual characteristics to appear either early or inappropriately Epidemiology 1:15,000 children born with disorder can affect both males and females There is a non-classical from of this condition that may present in adolesence or adulthood with signs of hypertestosteronism Most commonly females present with hirsuitism Presentation Symptoms in females abnormal mestruation cycles deep voice excessive hair growth ambiguous genitalia (more male than female in most cases) loss of vigor loss of appetite in males no phenotypic problems at birth may enter puberty early, sometimes at 2-3 years of age deep voice early, excessive hair growth early development of male secondary sexual characteristics including enlarged penis small testes muscular development Physical exam in females usually normal reproductive organs (i.e. uterus, ovaries, fallopian tubes) hirsuit (male distribution) signs of hypoglycemia renal dysfunction secondary to hypocortisolism and hypoaldosteronism salt loss volume depletion in males, as above in both above average growth as child final height usually smaller than normal adult adrenal crisis may develop in some newborns due to salt loss and can result in dehydration electrolyte changes cardiac arrhythmia vomiting Evaluation Labs decreased cortisol and aldosterone increased 17-OH progesterone increased serum DHEA sulfate increased 17-ketosteroids Urinary 17-hydroxycorticosteroids normal or decreased in contrast to 11-Hydroxylase Deficiency Chemistry electrolyte abnormalities may be evident at infancy EKG may show cardiac arrhythimia(s) secondary to renal dysfunction XR may demonstrate "older bone age" than true age Genetic testing may diagnose or confirm suspected diagnosis may determine genotypic gender of child to guide treatment Differential 11-Hydroxylase deficiency, 17-hydroxylase deficiency Treatment Medical management control cortisol levels goal is to achieve normal cortisol levels dexamethasone, fludrocortisone, or hydrocortisone may be indicated determine gender checking karyotype can accomplish this task Surgical management gender assignment surgery based on karyotypic findings females usually undergo surgery 1-3 months of age to remove male anatomy Prognosis, Prevention, and Complications Prognosis good to very good in most individuals if untreated, adrenal crisis can lead to death within 1-6 weeks males usually have normal fertility; females may be abnormal fertility Prevention genetic counseling may help parents with family history of disorder there is no preventive measure available at this time Complications shortened adult height, ambiguous genitalia, hypertension, hypglycemia, smaller vaginal introitus, death via adrenal crisis if untreated, steroid side effects, patients medicated for life, male testicular tumors