Hyperprolactinemia

Hyperprolactinemia, which refers to the increased production of prolactin by the anterior pituitary, occurs physiologically during pregnancy, lactation, and periods of stress. Pathological hyperprolactinemia is most often the result of pituitary adenomas and less commonly due to primary hypothyroidism and/or dopamine antagonists (e.g., metoclopramide, haloperidol). Women with pathological hyperprolactinemia present with galactorrhea, loss of libido, infertility, menstrual dysfunction, and/or osteoporosis. Men generally present with loss of libido, erectile dysfunction, and/or gynecomastia. The diagnosis is confirmed by repeated measurement of early morning prolactin levels. After ruling out hypothyroidism, a cranial MRI should be performed to detect pituitary adenomas. Management consists of dopamine agonists (e.g., bromocriptine, cabergoline) and treating the underlying cause.

• Sex: ♀ > ♂
• Prevalence
  • ∼ 0.4% of the general population
  • Hyperprolactinemia is the most common form of hyperpituitarism.

Epidemiological data refers to the US, unless otherwise specified.

• Prolactin-secreting pituitary adenomas (prolactinomas)
• Damage to the hypothalamus and/or infundibular stalk ^[1]
• Severe primary hypothyroidism: ↓ T₃/T₄ → ↑ TRH → ↑ prolactin ^[2]
• Drugs
  • Dopamine antagonists:
    • Antiemetics: metoclopramide, domperidone
    • Antipsychotics (e.g., haloperidol, risperidone)
  • Certain tricyclic antidepressants: e.g., clomipramine
  • Catecholamine depletors: e.g., reserpine
  • Dopamine synthesis inhibitors: α-methyldopa
  • Oral contraceptive pills ^[3]
  • Verapamil
  • Opiate analgesics
  • Histamine H2-receptor antagonists (cimetidine, ranitidine)
• Certain types of focal epilepsy: directly after temporal lobe seizures, due to proximity to the hypothalamus. ^[4][5][6]
• Chronic renal failure
• Stimulation of the reflex suckling arc in the chest wall (e.g., following chest wall surgery, post-herpes zoster)
• Physiological causes: stress, pregnancy, lactation, nipple stimulation, crying baby, sexual orgasm, sleep, exercise

Hypothalamic dopamine inhibits prolactin, whereas thyrotropin-releasing hormone (TRH) stimulates prolactin release.

Pituitary adenomas are the most common cause (∼ 50%) of pathological hyperprolactinemia.

• ↑ Prolactin → galactorrhea
• ↑ Prolactin → suppression of GnRH → ↓ LH, ↓ FSH → ↓ estrogen, ↓ testosterone → hypogonadotropic hypogonadism
• For more details, see “Hypothalamus and pituitary gland.”

Patients with hyperprolactinemia due to a pituitary adenoma may also present with bitemporal hemianopsia and headache (see “Clinical features” in “Pituitary adenomas”)

• Laboratory tests
  • Basal prolactin level ; ^[8]
    • Prolactinoma is the most likely cause if the prolactin blood level is permanently > 200 ng/mL.
    • Hypothyroidism and drug-induced hyperprolactinemia (with the exception of risperidone) usually result in mild elevations of prolactin (< 100 ng/mL).
  • Prolactin stimulation test : a prolactinoma is the most likely diagnosis if the prolactin blood level does not increase ^[9]
  • TSH, T₄ levels: to exclude primary hypothyroidism
  • In premenopausal women: pregnancy test
• Cranial contrast MRI: to rule out pituitary adenomas (see “Diagnostics” in “Pituitary adenomas”)

• Dopamine agonists (treatment of choice): bromocriptine, cabergoline, quinagolide
• Treat the underlying cause
  • Transsphenoidal resection of the pituitary adenoma (see “Therapy” in “Pituitary adenomas”)
  • Discontinue or lower the dose of the offending drug
  • Treatment of primary hypothyroidism
  • Renal transplant for patients with CRF