Nelson's syndrome: complete remission with cabergoline but not with bromocriptine or cyproheptadine treatment

A woman affected by Cushing's disease underwent bilateral adrenalectomy followed by radiotherapy of the hypothalamic-pituitary area when she was 18 years old. Thereafter, she used hydrocortisone acetate replacement therapy (35.5 mg divided into two daily doses). At the age of 26 years, the patient exhibited the clinical signs of the Nelson's syndrome, i.e. skin and gingival hyperpigmentation accompanied by amenorrhea, and elevated ACTH plasma levels (2,850 pg/ml, normal range 15-80 pg/ml). The magnetic resonance imaging (MRI) analysis of the sellar region evidenced a pituitary macroadenoma, measuring 14 x 13 mm. The patient was initially treated with cyproheptadine hydrochloride (12 mg/day) for 18 months. There was a partial improvement of the symptoms, with a reduction of the ACTH plasma levels to 112 pg/ml, but without any modification of the tumor mass. Due to sleepiness and weight gain, the cyproheptadine treatment was interrupted and substituted by a cabergoline (0.5 mg twice a week) therapy. Soon after cabergoline was applied an improvement of the clinical symptoms and signs was observed such as a regression of the tumor mass and the normalization of the ACTH plasma titers (38 pg/ml). Later, cabergoline was substituted by bromocriptine (7.5 mg/day) and the plasma levels of ACTH increased again (247 pg/ml), and headache and cutaneous hyperpigmentation were recorded. When cabergoline was reintroduced there was a clinical improvement and normalization of ACTH plasma levels (64 pg/ml). The MRI analysis of the sella region demonstrated a complete remission of the pituitary adenoma. The results obtained show for the first time that a long-term treatment with cabergoline also brings about a complete remission of Nelson's syndrome in the presence of a pituitary macroadenoma.