Hyperprolactinemia

INTRODUCTION ˇ@

Background: Hyperprolactinemia is a condition of elevated serum prolactin. Prolactin is a 198 amino acid protein (23-kD) produced in the lactotroph cells of the anterior pituitary gland. Its primary function is to enhance breast development during pregnancy and to induce lactation. However, prolactin also binds to specific receptors in the gonads, lymphoid cells, and liver. Secretion is pulsatile; it increases with sleep, stress, pregnancy, and chest wall stimulation or trauma, and therefore must be drawn after fasting. Normal fasting values generally are less than 30 ng/mL depending on the individual laboratory.

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Pathophysiology: The primary action of prolactin is to stimulate breast epithelial cell proliferation and induce milk production. Estrogen stimulates the proliferation of pituitary lactotroph cells, resulting in an increased quantity of these cells in premenopausal women, especially during pregnancy. However, lactation is inhibited by the high levels of estrogen and progesterone during pregnancy. The rapid decline of estrogen and progesterone in the postpartum period allows lactation to occur. During lactation and breastfeeding, ovulation may be suppressed due to the suppression of gonadotropins by prolactin.

Dopamine has the dominant influence over prolactin secretion. Secretion of prolactin is under tonic inhibitory control by dopamine, which acts via D2-type receptors located on lactotrophs. Prolactin production can be stimulated by the hypothalamic peptides, thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP). Thus, primary hypothyroidism (a high TRH state) can cause hyperprolactinemia. VIP increases prolactin in response to suckling, probably because of its action on receptors that increase adenosine 3?5?cyclic phosphate (cAMP).

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CLINICAL ˇ@

History:

Physical: Physical findings most commonly encountered in patients with hyperprolactinemia are galactorrhea and, occasionally, visual-field defects. Typically, the diagnosis is made via the aid of laboratory studies.

Causes: The diagnosis of hyperprolactinemia should be included in the differential for female patients presenting with oligomenorrhea, amenorrhea, galactorrhea, or infertility or for male patients presenting with sexual dysfunction. The condition is discovered in the course of evaluating the patient’s problem. Once discovered, hyperprolactinemia has a broad differential that includes many normal physiologic conditions.

DIFFERENTIALS ˇ@

Acromegaly
Acute Renal Failure
Erectile Dysfunction
Herpes Zoster
Hypothyroidism
Pituitary Macroadenomas
Pituitary Microadenomas
Prolactinoma

Other Problems to be Considered:

Alcoholic cirrhosis
Pregnancy
Postparturition
Nipple stimulation
Nonfasting specimen
Drug effect
Postictal state
Chest wall trauma
Chest wall tumors

WORKUP ˇ@

Lab Studies:
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Imaging Studies:
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Other Tests:
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TREATMENT ˇ@

Medical Care: Direct treatment is geared toward resolving hyperprolactinemic symptoms or reducing tumor size. Patients on medications causing hyperprolactinemia should have them withdrawn if possible. Patients with hypothyroidism should be given thyroid hormone replacement therapy.

Surgical Care: General indications for pituitary surgery include patient drug intolerance, tumors resistant to medical therapy, patients who have persistent visual-field defects in spite of medical treatment, and patients with large cystic or hemorrhagic tumors.

Consultations: Physicians who are comfortable with the initial evaluation of a patient (without evidence of tumor mass effect) can easily initiate therapy and provide follow-up. However, given the time constraints of modern ambulatory medicine, consultation with an endocrinologist often is necessary.

MEDICATION ˇ@

The goal of pharmacotherapy is to reduce morbidity and prevent complications.
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Drug Category: Dopamine agonists -- These agents directly stimulate postsynaptic dopamine receptors. Dopaminergic neurons in tuberoinfundibular processes modulate the secretion of prolactin from the anterior pituitary by secreting a prolactin inhibitory factor, believed to be dopamine.

Drug Name
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Bromocriptine (Parlodel) -- Semisynthetic ergot alkaloid derivative; strong dopamine D2-receptor agonist; partial dopamine D1-receptor agonist. Inhibits prolactin secretion with no effect on other pituitary hormones. May be given with food to minimize possibility of GI irritation.
Adult Dose 1.25-2.5 mg PO initially; increase gradually every few days to approximately 5-10 mg daily in divided doses.
Pediatric Dose Not recommended
Contraindications Documented hypersensitivity; ischemic heart disease, uncontrolled hypertension, peripheral vascular disorders; breastfeeding
Interactions Toxicity may increase with ergot alkaloids; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine may decrease effects
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Caution in renal or hepatic disease; generally stopped during pregnancy but can be restarted if symptoms recur; perform regular visual-field testing during pregnancy to monitor for tumor growth; should be given hs to minimize postural hypotension or nausea
Drug Name
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Cabergoline (Dostinex) -- Semisynthetic ergot alkaloid derivative; strong dopamine D2-receptor agonist with low affinity for D1 receptors.
Adult Dose 0.25-1 mg twice/wk; start with a low dose and increase q4wk based on prolactin levels
Pediatric Dose Not recommended
Contraindications Documented hypersensitivity; ischemic heart disease, uncontrolled hypertension, peripheral vascular disorders; breastfeeding
Interactions Toxicity may increase with ergot alkaloids; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine may decrease effects
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Caution in renal or hepatic disease; generally stopped during pregnancy but can be restarted if symptoms recur; perform regular visual-field testing during pregnancy to monitor for tumor growth; can be given hs to minimize postural hypotension or nausea
FOLLOW-UP ˇ@

Further Outpatient Care:
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Complications:
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Patient Education:
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MISCELLANEOUS ˇ@

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BIBLIOGRAPHY ˇ@

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