Galactorrhea is lactation in men or in women who are not breastfeeding. It is generally due to a prolactin-secreting pituitary adenoma.
Galactorrhea is generally due to a prolactin-secreting pituitary adenoma (prolactinoma). Most tumors in women are microadenomas (< 10 mm in diameter), but a small percentage are macroadenomas (> 10 mm) when diagnosed.
Hyperprolactinemia and galactorrhea also may be caused by ingestion of certain drugs, including phenothiazines, other antipsychotics, certain antihypertensives (especially α-methyldopa), and opioids. Primary hypothyroidism can cause hyperprolactinemia and galactorrhea, because increased levels of thyroid-releasing hormone increase secretion of prolactin as well as thyroid-stimulating hormone (TSH).
Symptoms: Abnormal lactation is not defined quantitatively; it is milk release that is inappropriate, persistent, or worrisome to the patient. The milk is white. Women with galactorrhea commonly also have amenorrhea or oligomenorrhea. Women with galactorrhea and amenorrhea may also have symptoms and signs of estrogen deficiency, including dyspareunia, due to inhibition of pulsatile luteinizing hormone and follicle-stimulating hormone release by high prolactin levels. However, estrogen production may be normal, and signs of androgen excess have been observed in some women with hyperprolactinemia…
Diagnosis: Prolactin levels | Thyroxine (T4) and TSH levels | CT or MRI
Diagnosis of galactorrhea due to a prolactin-secreting pituitary adenoma is based on elevated prolactin levels. In general, prolactin levels correlate with the size of a pituitary tumor and can be used to follow patients over time. Primary hypothyroidism is easily ruled out by absence of elevated TSH.
High-resolution CT or MRI is the method of choice in identifying microadenomas. Visual field examination is indicated in all patients with macroadenomas and in any patient who elects drug therapy or surveillance only.
Treatment:
Asymptomatic patients who have prolactin levels < 100 ng/mL and normal CT or MRI results or who have only microadenomas can probably be observed; serum prolactin often normalizes within years. Indications for treatment in women include the desire for pregnancy, amenorrhea or significant oligomenorrhea (because of the risk of osteoporosis), hirsutism, low libido, and troublesome galactorrhea. Indications in men include hypogonadism (because of the risk of osteoporosis), erectile dysfunction, low libido, and troublesome infertility.
The initial treatment is usually a dopamine agonist such as bromocriptine (1.25 to 5 mg po bid) or the longer-acting cabergoline (0.25 to 1.0 mg po once/wk or twice/wk). Cabergoline is the treatment of choice because it appears to be more easily tolerated and more potent than bromocriptine.
Patients with macroadenomas generally should be treated with dopamine agonists or surgically but only after thorough testing of pituitary function and evaluation for radiation therapy. Dopamine agonists are usually the initial treatment of choice and usually shrink the tumor.
CLINICAL VIGNETTES
A 32-year-old woman comes to the physician because of amenorrhea. She had menarche at age 13 and has had normal periods since then. However, her last menstrual period was 8 months ago. She also complains of an occasional milky nipple discharge. She has no medical problems and takes no medications. She is particularly concerned because she would like to become pregnant as soon as possible. Examination shows a whitish nipple discharge bilaterally, but the rest of the examination is unremarkable. Urine human chorionic gonadotropin (hCG) is negative. Thyroid stimulating hormone (TSH) is normal. Prolactin is elevated. Head MRI scan is unremarkable. Which of the following is the most appropriate pharmacotherapy?
A. Bromocriptine
B. Dicloxacillin
C. Magnesium sulfate
D. Oral contraceptive pill (OCP)
E. Thyroxine
The correct answer is A. Hyperprolactinemia is the cause in approximately 10 to 20% of cases of amenorrhea. It is known that elevated prolactin levels alter the hypothalamic-pituitary-ovarian axis such that ovulation is suppressed and menses do not occur. This patient has amenorrhea, galactorrhea (i.e., a milky discharge from the breasts), and an elevated prolactin level. All of these findings are consistent with hyperprolactinemia, likely coming from a pituitary microadenoma. The fact that no mass is seen on the head MRI is also consistent with a pituitary microadenoma, as small microadenomas may not be visualized. The treatment of choice for this patient is with bromocriptine. Bromocriptine is a dopamine agonist that has been shown to decrease prolactin levels and bring about a return of ovulation and menses. The re-establishment of ovulation is especially important for this patient who wishes to conceive.
Dicloxacillin (choice B) is often used to treat a breast infection, which can occur in a nursing mother. This patient, however, does not have findings consistent with breast infection. Rather, the nipple discharge is secondary to the patient’s elevated prolactin levels. Magnesium sulfate (choice C) is used in obstetrics to prevent seizures in patients with pre-eclampsia and to stop the uterus from contracting in patients with preterm labor. It is not indicated for the treatment of hyperprolactinemia. The oral contraceptive pill (choice D) would not be appropriate as this is a young woman who wishes to become pregnant. If she did not desire pregnancy, the oral contraceptive pill would be appropriate therapy. One of the major concerns in young women with microadenomas is that decreased levels of estrogen will lead to bone loss and the eventual development of osteoporosis. The oral contraceptive pill, by providing daily estrogen and progestin, will help to prevent bone loss. Thyroxine (choice E) is used in patients with hypothyroidism. This patient has a normal TSH and no evidence of hypothyroidism, and would, therefore, not need thyroxine.
A 45-year-old woman returns to her psychiatrist for her routine biweekly appointment two months after being hospitalized for an episode of major depressive disorder, recurrent, severe with psychotic features. During her hospitalization, she was started on two medications, an antidepressant and an antipsychotic, and she has continued these medications daily as an outpatient. At her appointment, she complains to her physician that she has missed her menstrual period for two months. She also complains of tenderness in her breasts, and an occasional small amount of milky discharge from her breasts onto her blouse. When questioned further, she also admits to low libido over the past month. Which of the following medications is most likely responsible for this constellation of symptoms?
A. Olanzapine
B. Paroxetine
C. Quetiapine
D. Risperidone
E. Sertraline
The correct answer is D. Although risperidone is an atypical antipsychotic, it is like conventional antipsychotics in its ability to cause significant elevations in plasma prolactin levels. In the tuberoinfundibular dopamine pathway, dopamine inhibits the release of prolactin from the anterior pituitary. Conventional antipsychotics and risperidone can cause hyperprolactinemia due to their dopamine antagonism in this pathway, releasing the tonic dopamine inhibition. Clinical manifestations of hyperprolactinemia may include galactorrhea, sexual dysfunction, menstrual irregularities including amenorrhea, infertility, and weight gain.
Olanzapine (choice A) is an atypical antipsychotic agent that causes minimal, if any, elevation in prolactin concentrations. It would be very unlikely that routine doses of olanzapine would cause symptoms of hyperprolactinemia. Paroxetine (choice B) is a selective serotonin reuptake inhibitor (SSRI) used in the treatment of depression and certain anxiety disorders. It would not induce hyperprolactinemia causing the above clinical manifestations. Quetiapine (choice C) is an atypical antipsychotic that causes minimal, if any, elevation in prolactin concentrations. Sertraline (choice E) is an SSRI and would not cause hyperprolactinemia.