Prolactinoma is a usually benign tumor of the pituitary gland that results in hyperprolactinemia.
Prolactinomas induce galactorrhoea, amenorrhoea and infertility in women, and hypogonadism, sexual dysfunction, impotence, infertility and, more rarely, gynecomastia in men.
Medical treatment consists of dopamine agonists such as cabergoline, bromocriptine, pergolide and quinagolide .
Frequency of prolactinoma in Belgium is 1/1,600, with similar results across other European countries (UK, Switzerland, and Malta). A female preponderance is observed, particularly among premenopausal women. Prolactinoma accounts for 66% of clinically relevant pituitary adenomas.
Disease onset is usually in the second to fourth decades of life with galactorrhea, amenorrhea and infertility presenting in women and impotence, decreased libido and infertility in men. Prolactinoma can also cause mass effects (visual field defects, headaches) or psychiatric manifestations (anxiety, depression). Prolactinoma may be associated with multiple endocrine neoplasia type 1 (MEN1) and familial isolated pituitary adenoma (FIPA) (see these terms).
Prolactinoma is a prolactin-secreting pituitary adenoma. The mechanism that leads to this benign growth of prolactin secreting cells is still unknown. Hyperprolactinemia inhibits secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus, which results in decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and finally in decreased estrogen (females) and testosterone (males) levels. Prolactin itself stimulates lactation from breast tissues. Prolactinomas represent about 50% of adenomas in FIPA, but only a small number of FIPA and young sporadic patients have inactivating mutations of the AIP gene (11q13.3). Almost all AIP mutation-related prolactinomas are macroadenomas with male predominance and young age at diagnosis. Prolactinoma can also occur in MEN1, due to inactivating mutations in MEN1 (11q13).
Diagnosis includes laboratory testing showing hyperprolactinemia and decreased estrogen levels. Pituitary adenomas may be visualized by contrast-enhanced pituitary magnetic resonance imaging (MRI). Tumors are classified according to their size: microadenomas (≤10 mm), macroadenomas (>10 mm), or giant adenomas (>40 mm). Females with prolactinomas usually have microadenomas, while macroadenomas are more frequent in male patients.
Causes of hyperprolactinemia without pituitary adenoma include: pregnancy, lactation, exercise, stress and polycystic ovary syndrome. Pituitary lesions that do not produce prolactin can also cause hyperprolactinemia by pituitary stalk impingement (stalk effect).
Most prolactinomas occur sporadically but up to 5% are familial (FIPA and MEN1).
Initial therapy is a dopamine agonist (bromocriptine and cabergoline) for normalizing hyperprolactinemia and decreasing tumor size. Doses should be titrated upwards gradually according to hormonal response and tolerability. For dopamine analog-resistant patients, changing to another dopamine agonist, increasing the dose of the drug, or neurosurgery may be proposed. Patients receiving high doses of dopamine agonists should be monitored with echocardiography to identify cardiac valve dysfunction. Radiotherapy is recommended in cases where both dopamine agonists and surgery have failed. Temozolomide may be useful for aggressive, invasive tumors (e.g. carcinomas) that are refractory to other therapies.
Prolactinoma is usually readily controlled with dopamine agonists that improve symptoms/ signs and shrink and/or control the pituitary tumor mass. Patients with MEN1 and those harboring mutations in AIP have a poorer response to therapy.