Hyperprolactinemia

Description

Hyperprolactinemia is an abnormal elevation in the serum prolactin (PRL) level from either physiologic or pathologic influences of the lactotroph cells of the pituitary gland.

Epidemiology

Prevalence

• Predominant age: reproductive age
• Predominant sex: female (70%) > male (30%)
• More readily detected in females because a slight elevation in PRL causes changes in menstruation and galactorrhea; men present with headache, visual disturbances, and erectile dysfunction (1)
• Adenomas in men are typically larger because of delayed onset of symptoms (1).

Etiology and Pathophysiology

• PRL, which is produced by lactotrophs in the anterior pituitary, is regulated by:
  • Inhibitory factors, primarily dopamine, are produced in the hypothalamus and delivered via the hypothalamic-pituitary vessels in the pituitary stalk.
  • Stimulatory factors, primarily thyrotropin-releasing hormone (TRH)
• Causes of hyperprolactinemia include the following:
  • Physiologic
    • Pregnancy due to increased estrogen
    • Breastfeeding or nipple stimulation
    • Stress, including postoperative state
    • Medications: Concentrations are typically in the 25 to 100 ng/mL range (2)[A].
      • Dopamine (D₂) blockers: prochlorperazine, metoclopramide
      • Dopamine depleters: α-methyldopa, reserpine
      • Antidepressants: tricyclic antidepressants (TCAs); paroxetine (an SSRI) causes transient hyperprolactinemia—usually resolves in 7 to 10 days
      • Gastric motility drugs: metoclopramide and domperidone
      • Verapamil (but no other calcium channel blockers; thought to decrease the hypothalamic synthesis of dopamine)
      • Older antipsychotics (category is the most common cause of medication induced): haloperidol, fluphenazine, risperidone (level of elevation with risperidone greater than with other antipsychotics)
      • Newer antipsychotics (asenapine, iloperidone, lurasidone) may cause elevation but less than the older antipsychotics (1).
  • Pathologic
    • Hypothyroidism (due to elevated TRH)
    • Chest wall conditions such as herpes zoster, trauma, or postthoracotomy
    • PRL-secreting adenoma in the anterior pituitary (microadenoma: <1 cm; macroadenoma: >1 cm)
    • Pituitary stalk compression/disruption:
      • Craniopharyngioma, Rathke cleft cyst
      • Meningioma, astrocytoma
      • Metastases
      • Head trauma
      • Infiltrative/inflammatory disorders
    • Diminished PRL clearance (chronic renal failure, cirrhosis, cocaine)
  • Idiopathic hyperprolactinemia—a substantial number of cases where the serum levels are between 20 and 100 ng/mL the cause cannot be found (3)[A]

Genetics
Unknown

Risk Factors

See causes in “Etiology and Pathophysiology” section.

General Prevention

Avoid offending medications.

Commonly Associated Conditions

• Infertility
• Osteoporosis
• Amenorrhea
• Gynecomastia