Hyperprolactinemia

Background

• Hyperprolactinemia is a common condition in which the serum level of the pituitary hormone prolactin is higher than normal, which is due to excess synthesis and secretion, or decreased hepatic or renal clearance.
• Elevated prolactin may be physiologic, for example during pregnancy and lactation.
• Pathologic hyperprolactinemia is often due to medication, pituitary tumors (especially prolactin-secreting micro- or macroprolactinomas), pituitary stalk damage or underlying disorders (such as primary hypothyroidism or renal failure).

Evaluation

• Suspect hyperprolactinemia in:
  • children and adolescents with menstrual problems, galactorrhea, and/or delayed puberty
  • premenopausal women with amenorrhea and/or galactorrhea or infertility
  • men with erectile dysfunction and/or gynecomastia or infertility
• Measure serum prolactin in the fasting state to confirm the diagnosis of hyperprolactinemia (Strong recommendation).
  • Prolactin < 25 mcg/L usually rules out hyperprolactinemia.
  • Prolactin > 250 mcg/L usually indicates a prolactinoma.
• If asymptomatic hyperprolactinemia, consider assessing for macroprolactin (Weak recommendation).
• If drug-induced hyperprolactinemia is suspected, consider discontinuing medication for 3 days and retesting serum prolactin (Weak recommendation). Caution should be used in changing medications in patients with severe psychiatric disease.
• If hyperprolactinemia persists, perform further testing to determine underlying cause (Strong recommendation):
  • pregnancy test
  • thyroid, liver, and renal function tests
  • pituitary imaging to detect pituitary or hypothalamic mass (gadolinium-enhanced magnetic resonance imaging preferred to computed tomography)
  • genetic testing if syndrome associated with hyperprolactinemia suspected (This is quite rare and multiple endocrine neoplasia type 1 [MEN-1] would be the most common genetic disorder associated with hyperprolactinemia).
• In patients with prolactinomas, consider screening for:
  • hypopituitarism, especially if tumor ≥ 10 mm; tests may include:
    • free thyroxine (T4)
    • morning cortisol
    • morning testosterone levels (men)
    • thyroid stimulating hormone
    • luteinizing hormone and follicle-stimulating hormone
    • insulin-like growth factor 1 (IGF-1)
  • hormone hypersecretion, especially if symptoms of growth hormone or cortisol excess; tests may include:
    • IGF-1
    • dexamethasone suppression, late-night salivary cortisol, or 24-hour urine free cortisol tests
• Additional blood testing may be performed using serial dilutions of serum to eliminate potential hook effect if prolactin level lower than expected in presence of very large tumor (Strong recommendation).
• If patient presents with visual symptoms or if imaging reveals adenoma abutting or impinging the optic apparatus (optic nerves, optic chiasm, or optic tracts), consider referral for neuro-ophthalmological evaluation.

Management

• Consider not treating patients with asymptomatic medication-induced hyperprolactinemia or stable, asymptomatic microprolactinoma, particularly in eugonadal men or premenopausal women who are not seeking fertility or in postmenopausal women (Weak recommendation).
• For symptomatic medication-induced hyperprolactinemia, consider, in preferential order, drug discontinuation, drug substitution, or dopamine agonist therapy, if not contraindicated due to psychiatric disease (Weak recommendation).
• For patients with symptomatic prolactinoma, dopamine agonists, specifically cabergoline, are first-line treatment (Strong recommendation).
  • During pregnancy, discontinue dopamine agonists in most women (Strong recommendation).
  • Consider tapered discontinuation of dopamine agonist therapy after ≥ 2 years if serum prolactin is no longer elevated and no visible tumor remnant on magnetic resonance imaging (Weak recommendation).
• For patients with hypogonadism, consider hormone replacement therapy (Weak recommendation)
  • Estrogen or testosterone therapy should be considered for long-term hypogonadism related to drug-induced hyperprolactinemia if the medication cannot be discontinued (Weak recommendation).
  • In women with amenorrhea caused by microadenoma, consider oral contraceptive as an alternative to a dopamine agonist, unless fertility is desired. (Weak recommendation).
• For aggressive or malignant prolactinoma, consider temozolomide (Weak recommendation).
• For prolactinomas unresponsive to medication, consider surgery (Weak recommendation) or radiation therapy (Weak recommendation).