Differentiating Between CAH and PCOS Using Hormone Levels and LC-MS/MS

Abstract

Introduction: PCOS is one of the most common endocrine issues affecting women today, with almost 10% of women suffering from this condition. CAH is a rarer disease that affects both men and women at a rate of around 1:1000 people. The problem with these two disorders arises in the fact that variants of these conditions may have very similar clinical presentations. This makes a proper diagnosis and treatment protocol difficult. Both PCOS and CAH present with high androgens but differ in that the former usually presents with high cortisol/insulin resistance, and the latter with low cortisol and aldosterone. Another difficulty in diagnosis is due to CAH presenting itself in 4 variants; 21-hydroxylase deficiency, the most common with over 95% prevalence, 11-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase type 2 deficiency, and 17α-hydroxylase deficiency. We have developed and validated an LC-MS/MS assay using a first morning saliva that measures a full panel of steroids necessary to clearly differentiate PCOS from all 4 variants of CAH. This full spectrum of steroids includes precursors of the active steroids (pregnenolone sulfate, DHEA, androstenedione) as well as parent steroids (progesterone, testosterone, estradiol, cortisol, aldosterone) and their precursors (17-OH progesterone) and downstream metabolites (11-hydroxycortisol, corticosterone) that differentiate PCOS from CAH and define the 4 variants of CAH. Clinical Case: We will present several example case reports showing that PCOS presents with high androgens and normal to high cortisol and aldosterone, and in sharp contrast, classic CAH presents with high androgens and 17-hydroxy progesterone, but very low steroids distal to 21-hydroxylase deficiency (i.e low 11-deoxycortisol, cortisol, cortisone, corticosterone, and aldosterone). In contrast the more rare variant of 11-hydroxylase deficiency shows a typical pattern of low cortisol and cortisone and elevated 11-deoxycortisol. 3β-hydroxysteroid dehydrogenase type 2 deficiency is extremely rare to see in an adult as most babies born with this condition do not survive. 17α-hydroxylase deficiency is also very rare but shows elevated progesterone, 11-deoxycorticosterone, corticosterone, and aldosterone. For all these cases aldosterone can be tricky to interpret as there are multiple mechanisms at which aldosterone is produced and thus should not be used as a definitive marker for CAH.