Hyperprolactinemia 

Hyperprolactinemia is a condition of elevated serum prolactin. Prolactin is a 198-amino acid protein (23-kD) produced in the lactotroph cells of the anterior pituitary gland. Its primary function is to enhance breast development during pregnancy and to induce lactation. However, prolactin also binds to specific receptors in the gonads, lymphoid cells, and liver.^[1] Secretion is pulsatile; it increases with sleep, stress, pregnancy, and chest wall stimulation or trauma, and therefore must be drawn after fasting. Normal fasting values are generally less than 25-30 ng/mL, depending on the individual laboratory but can also vary for numerous reasons. Normal levels are also generally higher in women.

Nonpuerperal hyperprolactinemia is a state wherein pituitary lactotroph adenomas produce prolactin. These lactotroph adenomas, called "prolactinomas," ­account for approximately 40% of all pituitary tumors. However, hyperprolactinemia can also result from a pharmacologic cause or some other pathologic problem of the hypothalamic-pituitary dopaminergic pathways. Idiopathic hyperprolactinemia may be identified though a diagnosis of exclusion.^[2]

The primary action of prolactin is to stimulate breast epithelial cell proliferation thereby inducing and maintaining milk production. Estrogen stimulates the proliferation of pituitary lactotroph cells, resulting in an increased quantity of these cells in premenopausal women, especially during pregnancy. However, lactation is inhibited by the high levels of estrogen and progesterone during pregnancy. The rapid decline of estrogen and progesterone in the postpartum period allows lactation to commence. During lactation and breastfeeding, ovulation may be suppressed due to the suppression of gonadotropins by prolactin but may return before menstruation resumes. Therefore, this cannot be considered a reliable form of birth control.

Dopamine has the dominant influence over prolactin secretion. Secretion of prolactin is under tonic inhibitory control by dopamine, which acts via D2-type receptors located on lactotrophs. Prolactin production can be stimulated by the hypothalamic peptides, thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP), along with epidermal growth factor and dopamine receptor agonists. Thus, primary hypothyroidism (a high TRH state) can cause hyperprolactinemia. VIP increases prolactin in response to suckling, probably because of its action on receptors that increase adenosine 3',5'-cyclic phosphate (cAMP).

Frequency

United States

This condition occurs in less than 1% of the general population and in 10-40% of patients presenting with secondary amenorrhea. Approximately 75% of patients presenting with galactorrhea and amenorrhea have hyperprolactinemia. Of these patients, approximately 30% have prolactin-secreting tumors.

Mortality/Morbidity

Mortality is unlikely; however, in cases where the condition is due to a large prolactin-secreting tumor,^[3] local mass effect can lead to significant morbidity.

The condition causes systemic complaints that often resolve when the prolactin level returns to normal or once the tumor shrinks.

Rare cases of metastatic malignant prolactinoma have been described; however, less than 50 have been reported.

A study by Berinder et al found that overall cancer risk was increased in patients with hyperprolactinemia. However, no increased risk of breast cancer was found in women, and the risk of prostate cancer in men was reduced.^[4]

Bone resorption can be due to sex steroid attenuation mediated by the hyperprolactinemic state. A 25% decrease in spinal bone density can be seen in women with hyperprolactinemia and may be irreversible even with normalization of prolactin levels.^[2]

Sex

Clinical presentation in women is more obvious and occurs earlier than in men. They typically present with oligomenorrhea, amenorrhea, galactorrhea, or infertility. Galactorrhea is less common in postmenopausal women due to lack of estrogen. If a pituitary tumor is present, it is a microadenoma (< 10 mm) approximately 90% of the time.

Prolactinoma is less common in men than in women, typically presenting as an incidental finding on a brain CT scan or MRI, or with symptoms of tumor mass effect. This is most evident as a complaint of visual disturbances or headache. By the time of diagnosis in men, approximately 60% have macroprolactinomas.