Background: Prolactin is a peptide hormone that is produced and released from the anterior pituitary. The pituitary is an autonomous prolactin factory. The pituitary will produce increased amounts of prolactin automatically unless it is inhibited from doing so by dopamine, a hormone secreted by the adjacent hypothalamus; dopamine travels down the pituitary stalk to the pituitary gland.
As the name “prolactin” suggests, this hormone is secreted in increasing amounts during pregancy to prepare the breasts for lactation. Prolactin is also secreted episodically during nursing to maintain milk production. Men also produce prolactin, but usualy in smaller amounts than women.
Causes of hyperprolactinemia: Hyperprolactinemia refers to serum levels of prolactin that are above the normal range for sex. The most common cause of hyperprolactinemia is pregnancy. Other causes for hyperprolactinemia include a variety of medications, nipple stimulation, chest wall lesions, hypothyroidism, renal failure, liver disease, anterior pituitary adenomas (tumors), and anything that damages the hypothalamus or pituitary stalk (inflammation, other tumors, etc.).
Manifestations: Hyperprolactinemia can cause menstrual periods to become irregular or cease (amenorrhea). Women may also note abnormal breast milk secretion (galactorrhea). Hyperprolactinemia can interfere with fertility in both women and men. Hyperprolactinemia reduces the secretion of pituitary gonadotropins. In men, this results in diminished testosterone production, low libido, and erectile dysfunction.
Evaluation of Hyperprolactinemia: A careful medication and drug history must be obtained, since so many medications cause hyperprolactinemia. A serum beta-hCG is determined in women to screen for pregnancy. A chest exam is performed to look for surgical scars, nipple rings, or other causes of stimulation of the same chest nerves that are titillated by normal breast feeding. If autoimmune disease is a clinical consideration, a serum ANA is checked to screen for lupus erythematosis. If acromegaly is a consideration, testing for excessive growth hormone and IGF-I should be done , as described in the accompanying section on acromegaly. We always screen for hypothyroidism with a serum TSH and free thyroxine. Renal failure can cause hyperprolacttinemia (especially in patients with zinc deficiency), so a serum BUN is checked. We screen for liver disease with a serum bilirubin and AST. A neurologic exam is also performed.
Magnetic Resonance Imaging (MRI): If serum levels of prolactin are persistently elevated without ready explanation, we obtain an MRI of pituitary and hypothalamus. If no pituitary tumor is seen and there is no other obvious cause for hyperprolactinemia, we check for “big prolactin”, a variant larger prolactin molecule that some individuals produce genetically that is simply cleared from the circulation more slowly.
Patients with large (>1cm diameter) PRL-secreting pituitary tumors (macro-prolactinomas) can have very high serum prolactin levels, sometimes over 10,000 ng/mL. IRMA assays can seriously underestimate the serum prolactin level, due to the “high dose hook effect”: Extremely high concentrations of PRL (or other antigens) can overwhelming exceed the binding capacity of the tagged antibody, leaving huge amounts of unbound PRL to bind the surface-bound antibody and thereby inhibit the antibody-bound PRL from binding to the surface antibody. Therefore, all patients with large pituitary tumors should have serum PRL measured with serial dilutions.
Treatment: Many patients with hyperprolactinemia require no treatment. Women with very small PRL-secreting pituitary “microadenomas” may wish to receive an oral estrogen/progestin contraceptive in order to have regular light menses, avoid pregnancy, and maintain bone density. Pituitary “microprolactinomas” tend to be quite stable. Prolactin secretion can be suppressed with certain medications called “dopamine agonists”. These medications mimic hypothalamic dopamine that the hypothalamus naturally makes to suppress pituitary prolactin production. The best current dopamine agonist is cabergoline, which is given orally twice weekly. Cabergoline successfully suppresses prolactin production and shrinks pituitary adenomas, even larger “macroprolactinomas”. Although such larger tumors can look quite nasty on MRI scanning, most patients do quite well with cabergoline treatment alone. There is usually no need to biopsy, operate upon or radiate such pituitary tuumors that are responding to cabergoline therapy.