What are the common causes of hyperprolactinemia (elevated prolactin levels)?

Common Causes of Hyperprolactinemia

The most common causes of hyperprolactinemia include prolactinomas (pituitary tumors), medication effects, hypothyroidism, and idiopathic hyperprolactinemia. 1, 2

Etiologies of Hyperprolactinemia

Physiological Causes

• Pregnancy
• Lactation
• Stress
• Sleep
• Exercise

Pathological Causes

1. Pituitary Disorders (30-50% of cases)

• Prolactinomas (most common pathological cause)
  • Microprolactinomas (<10mm)
  • Macroprolactinomas (≥10mm)
• Other pituitary tumors causing stalk compression
• Empty sella syndrome

2. Medication-Induced (very common cause) 3, 4

• Antipsychotics
  • Typical antipsychotics (haloperidol, chlorpromazine)
  • Some atypical antipsychotics (risperidone, paliperidone)
• Antidepressants
  • SSRIs (sertraline, fluoxetine)
  • MAOIs
  • Some tricyclics
• Other medications
  • Antihypertensives (verapamil, methyldopa)
  • Prokinetics (metoclopramide, domperidone)
  • Opiates
  • Estrogens
  • Anti-androgens
  • H2-receptor antagonists (cimetidine)
  • Anticonvulsants

3. Hypothyroidism

• Primary hypothyroidism (TRH stimulates both TSH and prolactin)

4. Idiopathic Hyperprolactinemia (30-40% of cases) 5

• No identifiable cause despite thorough investigation

5. Other Causes

• Chronic renal failure
• Cirrhosis
• Chest wall lesions/trauma
• Hypothalamic disorders
• PCOS (occasionally)
• Seizures

Clinical Presentation

Hyperprolactinemia typically presents with:

• In women: Oligomenorrhea, amenorrhea, galactorrhea, infertility
• In men: Decreased libido, erectile dysfunction, infertility, gynecomastia
• Both sexes: Headaches, visual field defects (with large tumors), osteoporosis (long-term)

Diagnostic Approach

1. Confirm hyperprolactinemia

   • Normal ranges 1:
     • Non-pregnant females: 3.0-30.0 ng/mL
     • Pregnant females: 10.0-209.0 ng/mL
     • Postmenopausal females: 2.0-20.0 ng/mL

2. Exclude macroprolactinemia

   • Biologically inactive form that can cause falsely elevated levels 6

3. Identify cause:

   • Medication review (crucial first step)
   • Thyroid function tests (TSH, free T4)
   • Pregnancy test in women of reproductive age
   • MRI of pituitary if no obvious cause identified

Clinical Pearls and Pitfalls

• Degree of elevation can suggest etiology:

  • Mild elevation (20-50 ng/mL): Medications, stress, hypothyroidism
  • Moderate elevation (50-100 ng/mL): Medications, microprolactinomas
  • Marked elevation (>100 ng/mL): Macroprolactinomas

• Common pitfalls:

  • Failing to review all medications (including over-the-counter)
  • Not considering stress-induced temporary elevations
  • Missing macroprolactinemia (biologically inactive form)
  • Overlooking hypothyroidism as a reversible cause

• Important note: A prolactin level of 44 ng/mL (as mentioned in the question) typically suggests either medication effect, microprolactinoma, or hypothyroidism as the most likely causes.