This patient has clinical features consistent with 17-alpha hydroxylase deficiency, a form of congenital adrenal hyperplasia (CAH). 17-alpha hydroxylase deficiency leads to increased aldosterone, causing hypokalemia.
CAH is classified based on the enzymatic defect present, most commonly 21-hydroxylase deficiency followed by 11-beta-hydroxylase deficiency, and then 17-alpha-hydroxylase deficiency. These different defects create different phenotypes in male and female patients with CAH and can be distinguished both clinically and by laboratory studies. 17-alpha hydroxylase deficiency leads to decreased production of cortisol and sex hormones, routing production instead towards mineralocorticoids. This leads to hypertension and hypokalemia. In females, it causes absence of secondary sex characteristics with normal internal sex organs.
Master-Hunter and Heiman review the evaluation and treatment of amenorrhea. An important juncture in the evaluation of a young woman with primary amenorrhea includes identifying the presence or absence of secondary sex characteristics, which indicates whether or not sex hormones are present. If absent, the next step is measuring LH and FSH levels, whereas if secondary sex characteristics are present, the next step is an ultrasound of the uterus.
Coulm et al. evaluate a screening program for 21-hydroxylase deficiency, the most common type of CAH. Specifically, they took blood samples from newborns and used measured 17-hydroxyprogesterone concentrations using an immunoassay. Importantly, they found their screening program to be highly sensitive to diagnose this condition (>90%) but was also associated with a low positive predictive value (2.3%), especially in pre-term infants.
Illustration A shows a schematic for steroid synthesis, useful for recalling the CAH phenotypes. In 17-alpha hydroxylase deficiency, one is unable to synthesize cortisol and sex hormones, routing production towards mineralocorticoids. In 21-hydroxylase and 11-beta-hydroxylase deficiency, cortisol and mineralocorticoids are suppressed while sex hormones are produced.
Answer 1: Aromatase deficiency is not associated with 17-alpha-hydroxylase deficiency.
Answer 3: Decreased levels of sex hormones are seen in 17-alpha-hydroxylase deficiency.
Answer 4: This patient is expected to have a normal female XX karyotype.
Answer 5: This patient would be expected to have low cortisol activity due to the enzyme deficiency.
Master-Hunter T, Heiman DL. Amenorrhea: evaluation and treatment. Am Fam Physician. 2006 Apr 15;73(8):1374-82.
PMID:16669559 (Link to Abstract)
Coulm B et al. "Efficiency of neonatal screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency in children born in mainland France between 1996 and 2003." Archives of pediatrics & adolescent medicine 166.2 (2012): 113-120.
PMID:22312171 (Link to Abstract)