Differential Diagnosis

Prolactin is a hormone produced by the lactotroph cells of the anterior pituitary gland (adenohypophysis). Secretion of this hormone is regulated by dopamine, which has an inhibitory effect. Dopamine is released from the hypothalamus, and, in its absence, prolactin secretion increases. Hyperprolactinemia refers to the persistent elevation of serum levels of this hormone. Radioimmunoassays for the detection of prolactin are specific with little cross-reactivity with other hormones. Normal values for men are less than 15 ng/ml, and normal values for women are slightly elevated at 20 ng/ml or less.

Symptoms of hyperprolactinemia include infertility, oligomenorrhea, amenorrhea, and galactorrhea in women. Whereas in men, a decrease in libido or erectile dysfunction are the common manifestations.

There are many potential causes for hyperprolactinemia which include pregnancy, breast-feeding, prolactinomas, hypothyroidism, infiltrative disorders of the hypothalamus and pituitary (sarcoidosis, hemochromatosis, eosinophilic granuloma, tuberculosis, etc.), chronic renal failure, cirrhosis, compressive lesions of the pituitary stalk, stimulation of the intercostal nerve (chest wall burns, trauma or herpes zoster), or idiopathic hyperprolactinemia. Multiple medications serve to increase serum prolactin levels. These medications include: methyldopa, phenothiazine derivatives, metoclopramide, estrogens, narcotics, reserpine, tricyclic antidepressants, risperdal, and cimetidine.

Once the diagnosis of hyperprolactinemia has been established in the absence of medications known to increase serum levels, tests to exclude secondary causes such as hypothyroidism, chronic renal failure, pregnancy, and hepatic cirrhosis should be obtained. If such a workup is unrewarding, an MRI scan of the pituitary gland is the next diagnostic maneuver. Possible pathologic changes that cause hyperprolactinemia and may be detected by MRI scanning include prolactinomas, compressive stalk lesions, and infiltrative disorders. MRI scanning may be inadequate at detecting prolactinomas less than 3 mm in diameter. Therefore, if the above serologic and radiologic workup is unrewarding, the disorder is considered idiopathic hyperprolactinemia; however, a prolactinoma less than 3 mm is still a potential etiology. One important note is that when hyperprolactinemia is secondary to hypothyroidism, the pituitary may have the same changes on MRI as if a prolactinoma were present; therefore, it is important to either rule out or treat concomitant hypothyroidism before obtaining an MRI scan.

The therapy for hyperprolactinemia is variable and depends on the underlying etiology. Secondary elevations of prolactin usually resolve with correction of the primary pathology. Hyperprolactinemia secondary to chronic renal failure will not resolve with dialysis therapy, but the abnormality will resolve after renal transplantation. There are two types of prolactin-secreting adenomas with regards to therapy. Those tumors that are less than 10 mm in diameter are termed microadenomas whereas macroadenomas are greater than 10 mm in diameter. A prolactin-secreting microadenoma usually does not enlarge; therefore, therapy is not indicated unless amenorrhea is present (this indicates an estrogen deficient state and the patient is therefore at risk for osteoporosis) or if the other symptoms of hyperprolactinemia (galactorrhea, decreased libido, or impotence) are viewed as bothersome by the patient. If therapy for a microadenoma is deemed unnecessary, the patient should undergo annual physical examination, serial prolactin measurements and serial MRI scans until it has been determined that the tumor is stable and is not exhibiting a tendency toward enlarging. Symptomatic microadenomas may be treated with the same medications to treat macroadenomas. All prolactin-secreting macroadenomas require therapy in order to prevent continuous enlargement with resultant mass effect. Pharmacological therapy for macroadenomas includes either bromocriptine mesylate (Parlodel), pergolide mesylate (Permax) or cabergoline. When patients fail or are not candidates for pharmacologic intervention, transsphenoidal surgical removal of the prolactinoma or radiation therapy may be considered.