Prolactinomas are monoclonal tumors that secrete prolactin.

• Men: Decreased facial and body hair, infertility, small testicles; may also have de creased libido, erectile dysfunction, and delayed puberty (caused by decreased testosterone as a result of inhibition of gonadotropin secretion).
• Women: Physical examination may be normal; history may reveal amenorrhea, galactorrhea (Fig. E1), oligomenorrhea, and anovulation.
• Both sexes: Visual field defects and headache may occur depending on size of tumor and its expansion.

Prolactin-secreting pituitary adenomas: Microadenomas (<10 mm diameter) or macroadenomas (>10 mm diameter). No risk factors have been identified for sporadic prolactinomas. Rarely prolactinomas can be part of multiple endocrine neoplasia (MEN) type 1 syndrome.

Secretion of prolactin is under tonic inhibitory control by hypothalamic dopamine. Hyperprolactinemia may be caused by the following:

• Drugs: Risperidone, phenothiazines, methyldopa, reserpine, monoamine oxidase inhibitors, androgens, progesterone, cimetidine, tricyclic antidepressants, haloperidol, meprobamate, chlordiazepoxide, estrogens, opioids, metoclopramide, verapamil, amoxapine, cocaine, oral contraceptives
• Hepatic cirrhosis, renal failure, primary hypothyroidism
• Ectopic prolactin-secreting tumors (hypernephroma, bronchogenic carcinoma)
• Infiltrating diseases of the pituitary (sarcoidosis, histiocytosis)
• Head trauma, chest wall injury, spinal cord injury
• Polycystic ovary disease, pregnancy, nipple stimulation
• Idiopathic hyperprolactinemia, stress, exercise

• The diagnosis of prolactinoma is established by demonstration of an elevated serum prolactin level (after exclusion of other causes of hyperprolactinemia) and radiographic evidence of a pituitary adenoma.
  1. Normal mean prolactin levels are 8 ng/ml in women and 5 ng/ml in men.
  2. Prolactin levels >100 ng/ml are suspicious for prolactinomas. Most macroprolactinomas raise prolactin levels >250 ng/ml, and levels >500 ng/ml are virtually diagnostic of macroprolactinomas.
  3. Prolactin levels can vary with time of day, stress, sleep cycle, and meals. More accurate measurements can be obtained 2 to 3 hr after awakening, preprandially, and when patient is not distressed.
  4. Serial measurements are recommended in patients with mild prolactin elevations.
• Thyroid-stimulating hormone (TSH), free T₄, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (ALT), alanine aminotransferase (AST) are useful tests. Pregnancy test in all women of childbearing age.
• All patients with prolactinomas should undergo visual field testing. Serial evaluation is recommended, particularly during pregnancy in patients with macroadenomas.

• MRI (Fig. E2) with gadolinium enhancement is the procedure of choice in the radiographic evaluation of pituitary disease.
• In absence of MRI, a radiographic diagnosis is best accomplished with a high-resolution computed tomography (CT) scanner and special coronal cuts through the pituitary region.

Pregnancy and breastfeeding should be avoided because they can encourage tumor growth. The management of patients with prolactinoma planning pregnancy is summarized in Table E1.

• Management of prolactinomas depends on their size and encroachment on the optic chiasm and other vital structures, the presence or absence of gonadal dysfunction, and the patient’s desires regarding fertility. Patients with microprolactinomas without symptoms of hypogonadism do not require treatment. Fig. 3 describes a management algorithm for prolactinomas. Women with hypogonadism related to a microadenoma who do not desire fertility can be treated with a combined oral contraceptive.
• Medical therapy is preferred when fertility is an important consideration. Prolactinomas are treated with the dopamine agonists (DA) bromocriptine and cabergoline.
  1. Bromocriptine: Initial dose is 0.625 mg at bedtime for the first wk. After 1 wk, add morning dose of 1.25 mg. Gradually increase dose by 1.25 mg/wk until dose of 5 to 10 mg/day is achieved. Bromocriptine decreases size of the tumor and generally lowers the prolactin level into the normal range when the initial serum prolactin is <500 ng/ml. Side effects of bromocriptine are nausea, constipation, dizziness, and nasal stuffiness. Bromocriptine appears to be safe during pregnancy.
  2. Cabergoline is a longer-acting dopamine agonist that is more expensive but may be more effective and better tolerated than bromocriptine; initial dose is 0.25 mg twice weekly.
  3. After therapy is initiated, MRI should be repeated in 1 yr for microprolactinomas if the prolactin level normalizes. For macroprolactinomas, MRI is repeated after 2 mo and every 6 to 12 mo until stable on serial studies.
• Transsphenoidal resection: Option in an infertile patient who cannot tolerate bromocriptine or cabergoline or when medical therapy is ineffective. The success rate depends on the location of the tumor (entirely intrasellar), experience of the neurosurgeon, and size of the tumor (<10 mm in diameter); the recurrence rate may reach 80% within 5 yr. Possible complications of transsphenoidal surgery vary with experience and skill of the neurosurgeon and tumor anatomy and include transient diabetes insipidus, hypopituitarism, cerebrospinal fluid rhinorrhea, and infections (meningitis, wound infection).
• Pituitary irradiation is useful as adjunctive therapy of macroadenomas (>10 mm in diameter) and in patients with persistent hypersecretion after surgery. Potential complications include cranial nerve damage, radionecrosis, and cognitive abnormalities.
• Stereotactic radiosurgery (gamma knife) has become popular as a modality in the treatment of prolactinomas. A high dose of ionizing radiation is delivered to the tumor through multiple ports. Its advantage is minimal irradiation to surrounding tissues. Proximity of the tumor to the optic chiasm limits this therapeutic modality.

Figure 3 Prolactinoma management.

After secondary causes of hyperprolactinemia have been excluded, subsequent management decisions are based on clinical imaging and biochemical criteria. MRI, Magnetic resonance imaging; PRL, prolactin.

From Melmed S et al: Williams textbook of endocrinology, ed 14, Philadelphia, 2020, Saunders.

• Patients on medical therapy require periodic measurement of prolactin levels. An attempt to reduce the dose of bromocriptine or cabergoline can be made after the prolactin level has been normal for 2 yr. An MRI scan of the pituitary should be obtained to rule out tumor enlargement within 6 mo of initiation of tapering regimen.
• Evaluation and monitoring of pituitary function are recommended after transsphenoidal surgery.

• Transsphenoidal surgery will result in a cure in nearly 50% to 75% of patients with microadenomas and 10% to 20% of patients with macroadenomas.
• Nearly 20% of microprolactinomas resolve during long-term dopamine agonist treatment.

• Patients must be monitored for several years after surgery because up to 50% of microadenomas and nearly 90% of macroadenomas can recur.
• Pituitary microadenomas are found in 10.9% of autopsies, and 44% of these microadenomas are prolactinomas.

Prolactinoma (Patient Information)

Pituitary Adenoma (Related Key Topic)