What causes a prolactinoma?
Although research continues to unravel the mysteries of disordered cell growth, the cause of pituitary tumors remains unknown. Most pituitary tumors are sporadic--they are not genetically passed from parents to offspring. Prolactin secretion in the pituitary is normally suppressed by the brain chemical, dopamine. Drugs that block the effects of dopamine at the pituitary or deplete dopamine stores in the brain may cause the pituitary to secrete prolactin. These drugs include the major
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tranquilizers trifluoperazine (Stelazine) and haloperidol (Haldol); metoclopramide (Reglan), used to treat gastroesophageal reflux and the nausea caused by certain cancer drugs; and less often, alpha methyldopa and reserpine, used to control hypertension. Other tumors arising in or near the pituitary--such as those that cause acromegaly or Cushing's syndrome--may block the flow of dopamine from the brain to the prolactin-secreting cells. Increased prolactin levels are often seen in people with hypothyroidism, and doctors routinely test people with hyperprolactinemia for hypothyroidism. Breast stimulation also can cause a modest increase in the amount of prolactin in the blood.
The secretion and release of prolactin are mediated by dopamine, and any process that disrupts dopamine secretion or interferes with the delivery of dopamine to the portal vessels may cause hyperprolactinemia. Normal prolactin levels in women and men are below 25 µg per liter and 20 µg per liter, respectively. There is a 10-fold increase in prolactin during pregnancy, and levels rise after exercise, meals, and stimulation of the chest wall. Physical and psychological stress increases the secretion of prolactin, but the level rarely exceeds 40 µg per liter. Breast examination is infrequently associated with elevation of the prolactin level.
Metoclopramide, phenothiazines, and butyrophenones antagonize lactotroph dopamine receptors, leading to prolactin levels that exceed 100 µg per liter. Risperidone causes a similar elevation, and monoamine oxidase inhibitors and tricyclic antidepressants raise prolactin levels through effects on the delivery of dopamine to the portal vessels. Serotonin-reuptake inhibitors may cause hyperprolactinemia, but the prolactin levels rarely exceed the normal range. Nearly 10 percent of patients taking verapamil have elevated prolactin levels, but other calcium-channel blockers are not associated with hyperprolactinemia. Less commonly used antihypertensive agents that are associated with hyperprolactinemia include reserpine and methyldopa. Prolactin levels may also be mildly elevated after the administration of estrogen.18 The magnitude of medication-induced elevations in the prolactin level is variable, and the level returns to normal within days after the cessation of therapy. In general, medication-induced hyperprolactinemia is associated with levels of prolactin in the range of 25 to 100 µg per liter.
Craniopharyngioma, acromegaly, granulomatous infiltration of the hypothalamus, severe head trauma, and large nonfunctioning pituitary tumors may also lead to hyperprolactinemia. In patients with acromegaly, prolactin may be secreted along with growth hormone. The development of large nonfunctioning pituitary tumors can compress the pituitary stalk and lead to prolactin levels in the range of 25 to 200 µg per liter, with increases to levels of less than 100 µg per liter in most cases. In some patients with primary hypothyroidism, mild hyperprolactinemia develops owing to the increased synthesis of thyrotropin-releasing hormone. Prolactin levels are elevated in patients with chronic renal failure because of decreased clearance of the hormone.
When no cause of hyperprolactinemia can be identified, the diagnosis is idiopathic hyperprolactinemia. A prolactinoma may be present but may be too small to be detected radiographically. In one third of patients with idiopathic hyperprolactinemia, the level of prolactin later returns to the normal range, and in nearly half, it remains unchanged. In one study, only 10 percent of patients with idiopathic hyperprolactinemia had radiographic evidence of a pituitary tumor during a follow-up period of six years. |
