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Prolactin (PRL) was characterized as a hormone distinct from growth hormone, which also has lactogenic activity, as recently as 1971. In humans, the predominant PRL species is a 23 kDa, 199-amino-acid, polypeptide synthesized and secreted by lactotroph cells in the anterior pituitary gland. Pituitary PRL production is under tonic inhibitory control by hypothalamic dopamine, such that pituitary stalk interruption produces hyperprolactinemia. The neu-ropeptides thyrotropin-releasing hormone (TRH) and vasoactive intestinal pep-tide (VIP) exert less important stimulatory effects on pituitary PRL release (1). Prolactin is essential for postpartum milk production and lactation. During pregnancy, increasing estrogen production stimulates the pituitary lactotrophs and causes increased PRL secretion. However, high estrogen levels inhibit PRL stimulation of the breasts, and, as a result, lactation does not occur until the estrogen levels decline postpartum.

Prolactinomas are the most common hormonally active pituitary tumors. There is a marked female preponderance, and prolactinoma is relatively rare in men. Several studies have revealed small prolactinomas in approx 5% of autopsy pituitaries, most of which are undiagnosed during life. From a clinical stand-

From: Management of Pituitary Tumors: The Clinician's Practical Guide, Second Edition Edited by: M. P. Powell, S. L. Lightman, and E. R. Laws, Jr. © Humana Press Inc., Totowa, NJ

point, prolactinomas may be divided arbitrarily into m/croprolactinomas (<10-mm diameter) and macroprolactinomas (>10-mm diameter). This is a useful distinction that predicts tumor behavior and indicates appropriate management strategies. Generally, microprolactinomas run a benign course. Some regress spontaneously, most stay unchanged for many years, and few expand to cause local pressure effects. Pooled data from seven studies, including 139 patients with untreated microprolactinomas, show documented tumor expansion in only 9 patients (7%) (2). In contrast, macroprolactinomas may present with pressure symptoms, often increase in size if untreated, and rarely disappear.

Prolactinomas are usually sporadic tumors. Molecular genetics have shown nearly all to be monoclonal, suggesting that an intrinsic pituitary defect is likely to be responsible for pituitary tumorigenesis. Occasionally, prolactinoma may be part of a multiple endocrine neoplasia syndrome (MEN-1), but this occurs too infrequently to justify MEN-1 screening in every patient with a prolactinoma. Mixed growth hormone (GH)- and PRL-secreting tumors are well recognized and give rise to acromegaly in association with hyperprolactinemia. Malignant prolactinomas are rare. A few cases have been described that have proved resistant to aggressive treatment with surgery, radiotherapy, dopamine agonists, and, occasionally, chemotherapy. In a small proportion, extracranial metastases in liver, lungs, bone, and lymph nodes have been documented.

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