DIAGNOSIS AND DRUG-THERAPY OF PROLACTINOMA

A prolactin-secreting pituitary tumour is the most frequent cause of h yperprolactinaemia that commonly occurs in clinical practice. Prolacti nomas occur more frequently in women than in men and may differ in siz e, invasive growth and secretory activity, At presentation, macroadeno mas are more frequently diagnosed in men. Specific immunohistochemical stains are necessary to prove the presence of prolactin in the tumour cells. The main investigations in the diagnosis of a prolactin-secret ing adenoma are hormonal and radiological. As prolactin is a pulsatile hormone, it is a general rule to obtain several blood samples by taki ng a single sample on 3 separate days or 3 sequential samples (every 3 0 minutes) in restful conditions. Prolactin levels of 100 to 200 mu g/ L are commonly considered diagnostic for the presence of a prolactinom a; however, prolactinoma cannot be excluded in the presence of lower l evels, and prolactin levels >100 mu g/L are present in some patients w ith idiopathic hyperprolactinaemia. Several dynamic function tests hav e been proposed to differentiate idiopathic from tumorous hyperprolact inaemia, Although they could be used for group discrimination, these t ests cannot be used for individual patients, To differentiate between a prolactinoma and a pseudoprolactinoma, thyrotrophin response to a do pamine receptor antagonist may be used, as only prolactinomas may have an increased response. A short course of dopaminergic drugs may also be of some help, as in macroprolactinomas only a shrinkage may be obse rved. After hyperprolactinaemia is confirmed, imaging with computerise d tomography (CT) and magnetic resonance imaging (MRI) are necessary t o define the presence of a lesion compatible with a pituitary tumour. There is now a general agreement that medical therapy is of first choi ce in patients with prolactinomas. Bromocriptine, the most common drug used in this condition, is a semisynthetic ergot alkaloid that direct ly stimulates specific pituitary cell membrane dopamine D-2 receptors and inhibits prolactin synthesis and secretion. In most patients, a re duction or normalisation of prolactin levels is usually observed, toge ther with the disappearance or improvement of clinical symptoms. The s ensitivity to bromocriptine is variable and patients may need differen t doses of the drug. Bromocriptine is also able to shrink the tumour i n most patients; however, a few reports of disease progression during therapy have been described. The need for close follow-up, including p rolactin levels and CT or MRI studies, is therefore emphasised. Bromoc riptine is conventionally given in 2 or 3 daily doses; however, a sing le evening dose has been shown to be equally effective. Bromocriptine is usually well tolerated by the majority of patients; some adverse ef fects (nausea, vomiting, postural hypotension) may be initially presen t, but they usually wear off in time. To prevent such adverse effects it is advisable to start treatment with a low dose during the evening meal and gradually increase the dose over days or weeks. A few patient s are unable to tolerate oral bromocriptine, so different formulations of bromocriptine or alternative dopamine agonist drugs (lisuride, ter guride, metergoline, dihydroergocryptine, quinagolide, cabergoline, pe rgolide) have been proposed. Of particular clinical relevance because of their good tolerability and sustained activity are cabergoline and quinagolide. Particular attention should be paid to pregnancy in prola ctinoma patients, as tumour enlargement has been reported. As the risk for this occurrence is low in patients with microprolactinoma, there is a general agreement that the drug can be stopped once pregnancy is diagnosed. In patients with macroprolactinoma the risk of tumour enlar gement is higher. Therefore, primary therapy with bromocriptine until the tumour has shrank is suggested before pregnancy is attempted. Brom ocriptine should be stopped as soon as pregnancy is confirmed, but rei nstated in case of neurological complication during pregnancy.