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Galactorrhea
is lactation in men or in women who are not breastfeeding. It is
generally due to a prolactin-secreting pituitary adenoma. Diagnosis
is by measurement of prolactin levels and imaging tests. Treatment
involves tumor inhibition with dopamine agonist drugs
and sometimes removal or destruction of the adenoma.
Etiology
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. The frequency of microadenomas is much lower in men, perhaps because of later recognition.
Hyperprolactinemia and galactorrhea also may be caused by ingestion of certain drugs, including phenothiazines, 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). It is unclear why hyperprolactinemia is associated with hypogonadotropism and hypogonadism. Causes of hyperprolactinemia are listed in
Table 3: Pituitary Disorders: Causes of Hyperprolactinemia .
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Table 3
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Causes of Hyperprolactinemia
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Cause
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Example
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Physiologic
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Nipple stimulation in women
Pregnancy
Postpartum period
Stress
Food ingestion
Sexual intercourse in some women
Sleep
Hypoglycemia
Early infancy (up to 3 mo)
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Hypothalamic disorders
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Hypothalamic tumors
Nontumerous hypothalamic infiltration: Sarcoidosis, TB, Langerhans' cell histiocytosis (Hand-Schüller-Chrisitan disease)
Postencephalitis
Idiopathic galactorrhea (presumed abnormality in dopamine secretion)
Head trauma
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Pituitary disorders
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Prolactin-secreting pituitary tumors
Tumors causing pituitary stalk compression
Surgical pituitary stalk section and other stalk lesions
Empty sella syndrome
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Other endocrine disorders
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Acromegaly
Cushing's disease
Primary hypothyroidism
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Disorders of other systems
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Chronic renal failure
Liver disease
Ectopic production of prolactin: Bronchogenic carcinoma (not squamous cell; mostly small cell undifferentiated)
Hypernephroma
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Chest wall lesions
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Surgical scars
Trauma
Tumors
Herpes zoster
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Pharmacologic
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Antihypertensive drugs: Resperine, α- methyldopa , labetalol , atenolol , verapamil , clonidine
H2-antagonists, eg, ranitidine
Oral contraceptives and estrogens
Opioids
Psychoactive drugs: eg, phenothiazines, tricyclic and some other antidepressants, butyrphenones ( haloperidol ), benzamides ( metoclopramide , sulpiride)
Thyrotropin-releasing hormone
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Data from Rebar RW: ''Practical evaluation of hormonal status,'' in Reproductive Endocrinology: Physiology, Pathophysiology and Clinical Management, edited by SSC Yen and RB Jaffe. Philadelphia, WB Saunders Company, 1978, p 493
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Symptoms and Signs
Abnormal lactation is not defined quantitatively; it is milk release that is inappropriate, persistent, or worrisome to the patient. Spontaneous lactation is more unusual than milk released in response to manual expression. 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. Hyperprolactinemia may occur with other menstrual cycle disturbances besides amenorrhea, including infrequent ovulation and corpus luteum dysfunction.
Men with prolactin-secreting pituitary tumors typically have headaches or visual difficulties. About 2⁄3 of affected men have loss of libido and erectile dysfunction.
Diagnosis
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. Serum gonadotropin and estradiol levels are either low or in the normal range in women with hyperprolactinemia. 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
The treatment of microprolactinomas is controversial. Asymptomatic patients with prolactin levels < 100 ng/mL and with normal CT or MRI scans or those who have only microadenomas can probably be observed; serum prolactin often normalizes within years. Patients with hyperprolactinemia should be monitored with quarterly prolactin levels and undergo sellar CT or MRI annually for at least an additional 2 yr. The frequency of sellar imaging can then be reduced if prolactin levels do not increase. 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 or twice/wk). Cabergoline is the treatment of choice because it appears to be more easily tolerated and more potent than bromocriptine . Women trying to become pregnant should switch to bromocriptine at least 1 mo before planned conception and stop bromocriptine use at the time of a positive pregnancy test; long-term safety data are better established for bromocriptine than for cabergoline . Exogenous estrogen can be given to women with a microadenoma who are clinically hypoestrogenic or have low estradiol levels. Exogenous estrogen is unlikely to cause tumor expansion.
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. If prolactin levels fall and symptoms and signs of compression by the tumor abate, no other therapy may be necessary. Surgery or radiation therapy may be easier to perform or yield better results after tumor shrinkage induced by a dopamine agonist. Although dopamine agonist treatment usually needs to be continued long-term, prolactin-secreting tumors sometimes remit, either spontaneously or perhaps aided by the drug therapy. Sometimes, therefore, dopamine agonists can be stopped without a recurrence of the tumor or a rise in prolactin levels; remission is more likely with microadenomas than macroadenomas. Remission is also more likely after pregnancy.
Radiation therapy should be used only in patients with progressive disease who do not respond to other forms of therapy. With irradiation, hypopituitarism often develops several years after therapy. Monitoring endocrine function and sellar imaging are indicated yearly for life.
Last full review/revision February 2007 by Ian M. Chapman, MBBS, PhD
Content last modified February 2007
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