Prolactin adenomas are pituitary adenomas that express and secrete prolactin (PRL) to varying degrees, are overwhelmingly benign, and are a common clinical occurrence and a challenge to treat. Depending on the size of the tumor, PRL adenomas are often divided into microadenomas (less than 10 mm in diameter) and macroadenomas (greater than 10 mm in diameter). more than 90% of PRL adenomas are small intra-saddle tumors that are rarely enlarged. Occasionally, these tumors are aggressive or locally invasive, causing compression of vital structures. Malignant PRL adenomas are very rare, difficult to treat, and disseminate metastases within and outside the central nervous system.
The mechanism of PRL adenoma development is unclear and may involve early genomic mutations leading to pituitary stem cell mutations. Various possible factors stimulate the propagation of mutant stem cells. Familial PRL adenoma patients have been reported suggesting that the genetic component helps to explain the pathogenesis.
Endocrine features PRL adenomas have PRL secretion by prolactin cells, a process enhanced by estrogen and inhibited by dopamine. PRL adenomas cause hyperprolactinemia, but hyperprolactinemia can also be caused by drugs and conditions that inhibit hypothalamic dopamine production, transport, and action at dopaminergic receptors. Therefore, hyperprolactinemia is not always predictive of concomitant PRL adenoma. Although estrogen stimulates PRL secretion, there is no evidence of an association between estrogen treatment and the formation of PRL adenomas. mixed GH and PRL adenomas usually produce acromegaly with hyperprolactinemia. PRL-secreting tumors also produce TSH or ACTH, but these tumors are uncommon. Occasionally, PRL adenomas may be a manifestation of the MEN1 phenotype; this is rare and should not be used as a basis for screening for MEN1 in every patient with a PRL adenoma, but rather a basal calcium measurement is recommended.
Clinical features PRL adenomas account for 40% of pituitary adenomas. The age range of the disease is wide, with reported patients ranging from 2 to 80 years. PRL adenomas are more common in women, with peak incidence in the reproductive years. There is no correlation between the use of oral contraceptives and the development of PRL adenomas, although the development of such tumors is often noted after discontinuation of oral contraceptives.
The clinical features of PRL adenoma derive mainly from hyperprolactinemia, which stimulates lactation and affects gonadal function secondary to PRL, and from the effect of PRL on gonadal activity. Hyperprolactinemia blocks the pulsatile secretion of gonadal releasing hormones, inhibits the release of LH and FSH, and directly impairs steroid production in the gonads. Altogether, these effects lead to various forms of primary (in children) and secondary amenorrhea.
Very large tumors compressing other pituitary cells or hypothalamic pituitary stalk cause hypopituitarism. Neurological manifestations are commonly seen in macroadenomas or giant adenomas because of their occupying effect and possible compression of the optic cross. Neurologic symptoms include headache, visual impairment (ranging from quadrant blindness to typical bilateral temporal hemianopia or blind spots). Extended PRL adenomas resulting in total blindness are an exception, but are seen in patients with stroke episodes of pituitary adenomas.