Effects of Bromocriptine and Cyproheptadine on Basal and Corticotropin-Releasing Factor (CRF)-Induced ACTH Release in a Patient with Nelson's Syndrome

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The effects of bromocriptine, a dopamine agonist, and cyproheptadine, a serotonin antagonist, on basal and corticotropin-releasing factor (CRF)-stimulated ACTH release were investigated in a 40-year-old female patient with Nelson's syndrome.
Oral administration of either bromocriptine (2.5mg) or cyproheptadine (8mg) caused a marked drop in plasma ACTH levels. Intravenous administration of synthetic ovine (o) CRF (50μg) produced an exaggerated response of plasma ACTH. Short-term (3-week) treatment with either bromocriptine (7.5mg/day) or cyproheptadine (12 mg/day) resulted in a marked suppression of basal ACTH release. Furthermore, a blunted response of plasma ACTH to oCRF was observed after short-treatment with either drug. However, after a longer period of treatment with cyproheptadine (18-week), plasma ACTH levels rose again and hyperresponsiveness to oCRF was restored to the pretreatment levels.
These data indicate that synthetic oCRF is a potent secretagogue for ACTH release in a patient with Nelson's syndrome. It is suggested that bromocriptine and cyproheptadine are effective drugs in reducing basal and CRF-stimulated ACTH release, possibly acting at the pituitary level in this case. However, the apparent refractoriness after chronic treatment with cyproheptadine may limit its therapeutic use in the present case.