Cortisol secretory patterns in Cushing's disease and response to cyproheptadine treatment

To investigate whether cortisol secretory patterns are associated with a response to cyproheptadine treatment in Cushing's disease, we studied two patients with a hyperpulsatile pattern and one patient with a hypopulsatile pattern before and during chronic cyproheptadine therapy (24 mg daily). In the two patients with a hyperpulsatile cortisol secretory pattern, pituitary magnetic resonance imaging with gadolinium did not reveal a pituitary adenoma, whereas in the patient with a hypopulsatile cortisol secretory pattern, a microadenoma was identified. Plasma cortisol levels were measured every 30 min for 24 h. In the two patients with a hyperpulsatile cortisol secretory pattern, chronic treatment with cyproheptadine resulted in sustained clinical and biochemical improvement and normalization of the median of absolute and relative increments in cortisol spikes. In the patient with a hypopulsatile cortisol secretory pattern, only a reduction of cortisol spikes was noticed during treatment. These results suggest that patients with Cushing's disease who are characterized by a hyperpulsatile cortisol secretory pattern and in whom no pituitary lesion can be identified by magnetic resonance imaging, cyproheptadine treatment may be useful.