Prolactinomas and hyperprolactinaemia (including macroprolactinaemia)
Authors: Bevan John S. 
Published: July 2011

Prolactin promotes milk production in mammals. It was characterized as a hormone distinct from growth hormone, which also has lactogenic activity, as recently as 1971. In humans, the predominant prolactin species is a 23 kDa, 199 amino acid polypeptide synthesized and secreted by lactotroph cells in the anterior pituitary gland. Prolactin is produced also by other tissues including decidua, breast, T lymphocytes, and several regions of the brain, where its functions are largely unknown and its gene regulation different from that of the pituitary gene. Pituitary prolactin production is under tonic inhibitory control by hypothalamic dopamine, such that pituitary stalk interruption produces hyperprolactinaemia. The neuropeptides thyrotrophin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP) exert less important stimulatory effects on pituitary prolactin release (1).

Following the discovery of prolactin as a separate hormone it became apparent that many apparently functionless ‘chromophobe’ pituitary adenomas were prolactinomas. Indeed, prolactinoma is the commonest type of functioning pituitary tumour diagnosed in humans. There is a marked female preponderance and prolactinoma is relatively rare in men. Several studies have revealed small prolactinomas in approximately 5% of autopsy pituitaries, most of which are undiagnosed during life. From a clinical standpoint, prolactinomas are divided arbitrarily into microprolactinomas (≤10 mm in diameter) and macroprolactinomas (>10 mm). This is a useful distinction which predicts tumour behaviour and indicates appropriate management strategies. Generally, microprolactinomas run a benign course. Some regress spontaneously, most stay unchanged over many years, and very few expand to cause local pressure effects. In contrast, macroprolactinomas may present with pressure symptoms, often increase in size if untreated and rarely disappear. Some clinicians find an intermediate category of meso-prolactinoma useful (10–20 mm in diameter), since this tumour group may have a more favourable treatment outcome than for larger macroprolactinomas.

Prolactinomas are usually sporadic tumours. Molecular genetics has shown nearly all to be monoclonal, suggesting that an intrinsic pituitary defect is likely to be responsible for pituitary tumorigenesis (see Chapter 2.3.2). Occasionally, prolactinoma may be part of a multiple endocrine neoplasia syndrome type I, but this occurs too infrequently to justify screening in every patient with a prolactinoma. Mixed growth hormone and prolactin-secreting tumours are well recognized and give rise to acromegaly in association with hyperprolactinaemia. Most contain separate growth hormone and prolactin-secreting cells whereas a minority secrete growth hormone and prolactin from a single population of cells, the mammosomatotroph adenomas. Prolactin-secreting adenomas may produce other hormones such as thyroid-stimulating hormone (TSH) or adrenocorticotropic hormone (ACTH), but such tumours are uncommon. Malignant prolactinomas are also very rare. A few cases have been described which have proved resistant to aggressive treatment with surgery, radiotherapy, and dopamine agonists. In a small proportion, extracranial metastases in liver, lungs, bone, and lymph nodes have been documented. The alkylating agent temozolomide is effective against some aggressive prolactinomas (2).