Hyperprolactinemia13'1

• In women, the most common causes of pathologic hyperprolactinemia are prolactin-secreting pituitary microadenomas and idiopathic hyperprolactinemia (Table 24-3).

TABLE 24-3

MAJOR CAUSES OF HYPERPROLACTINEMIA

Pregnancy and lactation

Prolactin-secreting pituitary adenoma (prolactinoma)

Idiopathic hyperprolactinemia

Drugs (e.g., phenothiazines, atypical antipsychotic medications, metoclopramide, verapamil)

Interference with synthesis or transport of hypothalamic dopamine

Hypothalamic lesions

Nonsecretory pituitary macroadenomas

Primary hypothyroidism

Chronic renal failure

• In men, the most common cause is a prolactin-secreting macroadenoma.

• Hypothalamic or pituitary lesions that cause deficiency of other pituitary hormones often cause hyperprolactinemia.

• Medications are an important cause to consider in all patients.

DIAGNOSIS

Clinical Presentation

• In women, hyperprolactinemia causes amenorrhea or irregular menses and infertility. Only approximately half of these women have galactorrhea. Prolonged estrogen deficiency increases the risk of osteoporosis. Plasma prolactin should be measured in women with amenorrhea, whether or not galactorrhea is present. Mild elevations should be confirmed by repeat measurements.

• In men, hyperprolactinemia causes androgen deficiency and infertility but not gynecomastia; mass effects and hypopituitarism are common.

• The history should include medications and symptoms of pituitary mass effects or hypothyroidism.

Diagnostic Testing

Pituitary imaging should be performed in most cases because large nonfunctional pituitary or hypothalamic tumors may present with hyperprolactinemia. Testing for hypopituitarism is needed only in patients with a macroadenoma or hypothalamic lesion (see “Pituitary Adenomas and Hypopituitarism” section).

TREATMENT

• For microadenomas and idiopathic hyperprolactinemia, most patients are treated because of

infertility or to prevent estrogen deficiency and osteoporosis. Indications for treatment include adenoma gt;1 cm, bothersome symptomatic galactorrhea, or hypogonadism.

• Some women may be observed without therapy by periodic follow-up of prolactin levels and symptoms. In most patients, hyperprolactinemia does not worsen, and prolactin levels sometimes return to normal. Enlargement of microadenomas is rare.

• Dopamine agonists: cabergoline and bromocriptine suppress plasma prolactin and restore normal menses and fertility in most women.

î Initial dosages are bromocriptine, 1.25-2.50 mg PO at bedtime, or cabergoline, 0.25 mg twice a week.

î Plasma prolactin levels are initially obtained at 2- to 4-week intervals, and doses are adjusted to the lowest dose required to maintain prolactin in the normal range. In general, the maximally effective doses are bromocriptine 2.5 mg tid and cabergoline 1.5 mg twice a week.

î Side effects include nausea and orthostatic hypotension, which can be minimized by increasing the dose gradually and usually resolve with continued therapy. Side effects are less severe with cabergoline.

î Women should consider barrier contraception because fertility may be restored quickly.

î Women who want to become pregnant should be managed in consultation with an endocrinologist.

î Women who do not want to become pregnant should be followed with clinical evaluation and plasma prolactin levels every 6-12 months. Every few years, plasma prolactin may be measured after the dopamine agonist has been withdrawn for several weeks to determine whether the drug is still needed. Follow-up imaging studies are not warranted unless prolactin levels increase substantially.

• Prolactin-secreting macroadenomas should be treated with a dopamine agonist, which usually suppresses prolactin levels to normal, reduces tumor size, and improves or corrects abnormal visual fields in 90% of cases.

î If mass effects are present, the dose should be increased to maximally effective levels over a period of several weeks. Visual field tests, if initially abnormal, should be repeated 4-6 weeks after therapy is started.

î Pituitary imaging should be repeated 3-6 months after initiation of therapy. If tumor shrinkage and correction of visual abnormalities are satisfactory, therapy can be continued indefinitely, with periodic monitoring of plasma prolactin levels.

î The full effect on tumor size may take more than 6 months. Further pituitary imaging is probably not warranted unless prolactin levels rise despite therapy.

î Transsphenoidal surgery is indicated to relieve mass effects if the tumor does not shrink or if visual field abnormalities do not resolve quickly with dopamine agonist therapy. However, the likelihood of surgical cure of a prolactin-secreting macroadenoma is low, and most patients require further therapy with a dopamine agonist.

î Women with prolactin-secreting macroadenomas should not become pregnant unless the tumor has been resected surgically or has decreased markedly in size with dopamine agonist therapy because the risk of symptomatic enlargement during pregnancy is 15%-35%. Contraception is essential during dopamine agonist treatment for macroadenoma.