Abstract
Experimental evidence suggests a Central-nervous-system origin of Cushing's disease and a role for serotonin in the regulation of ACTH release. The efficacy of cyproheptadine therapy, therefore, was studied in three patients with such disease. Administration of 24 mg daily over a period of three to six months was associated with prompt and sustained clinical and laboratory remission. Lessening of the physical manifestations of hypercorticism occurred, together with marked improvement in muscular weakness. Urinary corticosteroid excretion and cortisol secretory rate returned to normal. The urinary corticosteroid response to dexamethasone (2 mg per day) became normal; a paradoxical increase followed 8 mg per day. Abnormal circadian periodicity of plasma cortisol concentrations persisted. Return of normal amounts of Stage III to IV sleep occurred in the one patient so studied, who previously had markedly decreased periods of these stages. Discontinuance of therapy in one patient was associated with return of laboratory evidence of hypercorticism. (N Engl J Med 293:893–896, 1975)
THE concept of central neurotransmitter regulation of different aspects of ACTH release (basal, circadian, stress induced and feedback) is generally accepted.
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Cholinergic, adrenergic and serotoninergic involvement has been demonstrated. Different neurotransmitters appear to be involved in the regulation of each of the above aspects of ACTH release. Cushing's disease is characterized by alterations in basal, circadian, stress-induced and feedback regulations of ACTH release. We have previously suggested
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that such abnormalities may be indicative of altered Central-nervous-system function, perhaps related to altered neurotransmitter concentrations or sensitivity. Previous attempts to ameliorate the clinical and laboratory manifestations of Cushing's disease by L-dopa,
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L-tryptophan . . .