Serum prolactin (PRL) and thyroid-stimulating hormone (TSH) responses to the intravenous administration of domperidone or metoclopramide in normal subjects (left), patients with microprolactinomas (centre) and patients with macrolesions (either prolactin- or nonsecreting) (right). In normal subjects, hypothalamic dopamine exerts dominant inhibition on lactotroph prolactin secretion and has relatively little effect on thyrotroph secretion—typical dopamine antagonist responses are therefore characterized by a marked rise in prolactin and a relatively small TSH increment. In patients with microprolactinomas, hypothalamic dopamine output is increased in response to the significant hyperprolactinaemia. This has little effect on the prolactinoma which has a separate arterial blood supply, but exerts increased inhibitory tone on the normal thyrotrophs. Dopamine antagonist administration therefore has little effect on serum prolactin but causes release of thyrotroph inhibition, with an exaggerated rise in serum TSH. In patients with macrolesions, the increased hypothalamic dopamine output is prevented from reaching the normal lactotrophs and thyrotrophs; consequently, prolactin/TSH levels do not rise after dopamine antagonism.