Retinoic acid
The retinoic acid receptor is a type II nuclear receptor involved with transcriptional regulation. In a murine corticotrope tumor cell line, retinoic acid has been shown to reduce ACTH secretion and pro-opiomelanocortin (POMC) synthesis. Further, there is evidence that, with prolonged treatment, retinoic acid induces increased caspase-3 activity and cell death in ACTH-secreting cells. It has also demonstrated inhibition of corticosterone production and cell proliferation in adrenal cortex cells [69]. Retinoic acid had demonstrated reduced ACTH secretion and prevented tumor growth in mice with implanted with tumoral corticotropes [70]. In a 6-month study in dogs with spontaneous corticotrope tumors, retinoic acid reduced cortisol excess and improved associated symptoms [71].
A recent small study showed a marked reduction in UFC levels in 5/7 patients (22–73 % of baseline values), and UFC normalization in three patients. There was no apparent pattern of decrease in plasma cortisol. Plasma ACTH decreased in the first month of treatment and then returned to pretreatment levels in responsive patients. Blood pressure, glycemia, and signs of hypercortisolism improved on treatment. Patients reported only mild adverse effects (e.g., xerophthalmia and arthralgias) [59].