Involvement of the cholinergic pathway in the pathogenesis of pituitary Cushing's syndrome

Transsphenoidal adenomectomy is currently the first choice for treatment of patients with pituitary ACTH-dependent Cushing's syndrome. However, pharma cotherapy is prescribed for some patients, e.g., unsuccessful surgery. We t reated a woman in whom pituitary Cushing's syndrome was improved while she was on antimuscarinic cholinergic agents, atropine sulphate and pirenzepine hydrochloride. The diminished effect of anticholinergics on ACTH and corti sol was incidentally identified in an inferior petrosal sinus sampling proc edure. A single intramuscular injection of atropine significantly decreased both ACTH (43.9 pg/ml to less than 12.0; normal, 12.0-40.0 pg/ml) and cort isol (29.9 mug/dl to 13.6; normal, 7.6-23.6 mug/dl). An MI-muscarinic recep tor specific antagonist, pirenzepine hydrochloride, also had a diminishing effect on these hormones and this inhibiting effect was partially blocked b y the simultaneous administration of an anticholinesterase agent, pyridosti gmine bromide. Chronic oral ingestion of these agents led to improvement in clinical symptoms, and urinary 17-hydroxycorticosteroid and 17-ketosteroid levels were at normal to upper-normal levels. This is the first documentat ion of involvement of the cholinergic system in the pathogenesis of pituita ry Cushing's syndrome.