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Table 26 2 Causes of hyperprolactinemia
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Physiologic Causes Exercise Idiopathic Macroprolactinemia ( big prolactin ) Pregnancy Puerperium Sleep (REM phase) Stress (trauma, surgery) Suckling Pharmacologic Causes Amoxapine Amphetamines Anesthetic agents Antipsychotics (conventional and atypical) Butyrophenones Cimetidine and ranitidine (not famotidine or nizatidine) Estrogens Hydroxyzine Methyldopa Metoclopramide Opioids Nicotine Phenothiazines Protease inhibitors Progestins Reserpine Risperidone Selective serotonin reuptake inhibitors Tricyclic antidepressants Verapamil Pathologic Causes Acromegaly Chronic chest wall stimulation (postthoracotomy, postmastectomy, herpes zoster, breast problems, chest acupuncture, nipple rings, etc) Cirrhosis Hypothalamic disease Hypothyroidism Multiple sclerosis Optic neuromyelitis Pituitary stalk section Prolactin-secreting tumors Pseudocyesis (false pregnancy) Renal failure (especially with zinc deficiency) Spinal cord lesions Systemic lupus erythematosus
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When hyperprolactinemia persists without obvious cause, MRI of the pituitary and hypothalamus is indicated Small prolactinomas may thus be demonstrated, but clear differentiation from normal variants is not always possible
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The causes of hyperprolactinemia are shown in Table 26 2 Chronic nipple stimulation, nipple piercing, augmentation or reduction mammoplasty, and mastectomy may stimulate PRL secretion The pituitary tumor of acromegaly can cosecrete GH and PRL Hyperprolactinemia may also be idiopathic Increased pituitary size is a normal variant in young women About 10% of hyperprolactinemic patients are found to be secreting macroprolactin, a relatively inactive big prolactin ; pituitary MRI is normal in 78% of cases The differential diagnosis for galactorrhea includes the small amount of breast milk that can be expressed from the nipple in many parous women that is not cause for concern Nipple stimulation from nipple rings, chest surgery, or acupuncture can cause galactorrhea; serum PRL levels may be normal or minimally elevated Some women can have galactorrhea with normal serum PRL levels and no discernible cause (idiopathic) Normal breast milk may be various colors besides white Bloody galactorrhea requires an evaluation for breast malignancy
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developing osteoporosis; such women require periodic bone densitometry Pituitary macroprolactinomas (> 10 mm in diameter) have a higher risk of progressive growth, particularly during treatment with estrogen or testosterone replacement therapy or during pregnancy Therefore, patients with macroprolactinomas should not be treated with sex hormone replacement therapy (HRT) unless they are in remission with dopamine agonist medication or surgery Pregnant women with macroprolactinomas should continue to receive treatment with dopamine agonists throughout the pregnancy to prevent tumor growth
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Medications known to increase PRL should be stopped if possible Hyperprolactinemia due to hypothyroidism is corrected by thyroxine Patients with hyperprolactinemia not induced by drugs, hypothyroidism, or pregnancy should be examined by pituitary MRI Women with microprolactinomas who have amenorrhea or are desirous of contraception may safely take oral contraceptives or estrogen replacement there is minimal risk of stimulating enlargement of the microadenoma Patients with infertility and hyperprolactinemia may be treated with a dopamine agonist in an effort to improve fertility Women who elect to receive no treatment have an increased risk of
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Dopamine agonists are the initial treatment of choice for patients with giant prolactinomas and those with hyperprolactinemia desiring restoration of normal sexual function and fertility Of the ergot-derived dopamine agonists, cabergoline is usually the best tolerated and is prescribed beginning with a dosage of 025 mg orally once weekly for 1 week, then 025 mg twice weekly for the next week, then 05 mg twice weekly Further dosage increases may be required monthly, based on serum PRL levels, up to a maximum of 15 mg twice weekly Higher doses of cabergoline, ( 2 mg daily, have been reported to cause mitral valve regurgitation Alternative drugs include bromocriptine (125 20 mg/d orally) Women who
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experience nausea with oral preparations may find relief with deep vaginal insertion of cabergoline or bromocriptine tablets; vaginal irritation sometimes occurs Quinagolide (Norprolac; not available in the United States) is a non-ergotderived dopamine agonist for patients intolerant or resistant to ergot-derived medications; the starting dosage is 0075 mg/d orally, increasing as needed and tolerated to a maximum of 06 mg/d Patients whose tumor is resistant to one dopamine agonist may be switched to another in an effort to induce a tolerable remission Dopamine agonists are given at bedtime to minimize side effects of fatigue, nausea, dizziness, and orthostatic hypotension These symptoms usually improve with dosage reduction and continued use Erythromelalgia is rare Dopamine agonists can cause a variety of psychiatric side effects that are not dose related and may take weeks to resolve once the dopamine agonist is discontinued Therefore, dopamine agonists should be used judiciously in psychiatric patients whose antipsychotic medications have caused hyperprolactinemia Cabergoline has caused cardiac valve insufficiency in patients with Parkinson s disease after prolonged administration at doses greater than 3 mg/d, but such doses are seldom used for suppression of pituitary prolactinomas With dopamine agonist treatment, 90% of patients with prolactinomas experience a fall in serum PRL to 10% or less of pretreatment levels; about 80% of treated patients achieve a normal serum PRL level Shrinkage of a pituitary adenoma occurs early, but the maximum effect may take up to a year Nearly half of prolactinomas even massive tumors shrink more than 50% Such shrinkage of giant prolactinomas can result in spinal fluid rhinorrhea Discontinuing therapy after months or years usually results in the reappearance of hyperprolactinemia and galactorrhea-amenorrhea, but some patients with microadenomas remain in remission Because dopamine agonists usually restore fertility promptly, many pregnancies have resulted; no teratogenicity has been noted with any of the dopamine agonists However, women with microadenomas may have treatment safely withdrawn during pregnancy Macroadenomas may enlarge significantly during pregnancy; if therapy is withdrawn, such patients must be monitored clinically with serum PRL determinations and with computer-assisted visual field perimetry Women with macroprolactinomas who have responded to dopamine agonists may safely receive oral contraceptive agents as long as they continue receiving therapy
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