In five studies including both overt and subclinical CS (Beuschlein et al., 2014; Di Dalmazi et al., 2014b; Goh et al., 2014; Nakajima et al., 2014; Sato et al., 2014), PRKACA mutations are significantly associated with overt CS and higher serum cortisol level after 1 mg of dexamethasone, increased urinary free cortisol and midnight cortisol levels compared to patients without mutations (Beuschlein et al., 2014). Here, PRKACA is linked to Cowden syndrome 1.