Detectable Serum Pro-opiomelanocortin-Derived Peptides in Bromocriptine-Sensitive Cushing Disease:

We report a rare case of Cushing disease in whom plasma adrenocorticotropic hormone (ACTH) has been continuously suppressed with a low daily dose of bromocriptine for over 4 years. A 78-year-old woman presenting with hypercortisolism (65.0 mu g/dL at 8:00 AM) with an exceedingly high concentration of plasma ACTH (840 pg/mL at 8:00 Ann) developed the abrupt onset of sepsis. She recovered from multiple organ failure after intensive therapy. Subsequent studies demonstrated that plasma ACTH showed no response to high-dose dexamethasone (8 mg) and no circadian rhythm. A corticotropin-releasing hormone stimulation test revealed a significant increase in plasma ACTH (from 79 pg/mL to 140 pg/mL), and based on cavernous sinus sampling, we concluded that the source of elevated ACTH test levels was not ectopic, but pituitary, although no visible pituitary lesion had been observed. After oral administration of 2.5 mg bromocriptine, plasma ACTH showed a 63% reduction after 4 hours (from 270 pg/mL to 100 pg/mL). Clinical remission has continued for 4 years with daily administration of 3.75 mg bromocriptine and 360 mg trilostane. The examination of pro-opiomelanocortin (POMC)-derived peptides such as alpha-MSH and beta-endorphin suggested POMC processing in the pituitary intermediate lobe, which is not usually well defined in adult humans. Interestingly, only a few samples taken before the administration of bromocriptine contained detectable alpha-MSH. Bromocriptine is effective for a certain type of Cushing disease, and in such cases, it is thought to contribute to the normalization of POMC processing in addition to the suppression of ACTH secretion.