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BASICS

Description

  • Elevated serum prolactin (PRL) due to physiologic or pathologic lactotroph activity.
  • PRL regulated primarily by dopamine inhibition and TRH stimulation.

Epidemiology

  • Predominantly affects reproductive-age females (70% female, 30% male).
  • Males typically present later with larger adenomas.

ETIOLOGY AND PATHOPHYSIOLOGY

  • PRL produced by anterior pituitary lactotrophs.
  • Inhibitory control mainly via hypothalamic dopamine delivered through pituitary stalk.
  • Stimulatory control via thyrotropin-releasing hormone (TRH).

Causes

Physiologic

  • Pregnancy (↑ estrogen)
  • Breastfeeding/nipple stimulation
  • Stress/postoperative state

Medications (Prolactin levels typically 25-100 ng/mL)

  • Dopamine D2 blockers: prochlorperazine, metoclopramide
  • Dopamine depleters: α-methyldopa, reserpine
  • Antidepressants (TCAs, paroxetine)
  • Gastric motility agents: metoclopramide, domperidone
  • Verapamil (specific calcium channel blocker)
  • Older antipsychotics (haloperidol, risperidone, fluphenazine)
  • Newer antipsychotics (asenapine, iloperidone, lurasidone; less effect)

Pathologic

  • Hypothyroidism (↑ TRH)
  • Chest wall lesions (herpes zoster, trauma)
  • Pituitary prolactinomas (microadenoma <1 cm; macroadenoma >1 cm)
  • Pituitary stalk compression (craniopharyngioma, Rathke cleft cyst)
  • Tumors (meningioma, astrocytoma, metastases)
  • Head trauma, infiltrative or inflammatory diseases
  • Reduced PRL clearance (renal failure, cirrhosis, cocaine use)
  • Idiopathic hyperprolactinemia (20-100 ng/mL with no cause found)

Genetics

  • Unknown.

RISK FACTORS

  • Medications causing dopamine blockade or depletion.
  • Hypothyroidism.
  • Pituitary tumors or stalk lesions.
  • Chest wall trauma or infections.
  • Renal or hepatic impairment.

COMMONLY ASSOCIATED CONDITIONS

  • Infertility
  • Osteoporosis
  • Amenorrhea
  • Gynecomastia

DIAGNOSIS

History

  • Women: galactorrhea, amenorrhea, oligomenorrhea, infertility.
  • Men: decreased libido, erectile dysfunction, headaches, visual changes.
  • Signs of pituitary mass effect: headache, visual field defects (bitemporal hemianopia).
  • Symptoms of hypothyroidism, Cushing disease, acromegaly, MEN-1 syndrome.

Physical Exam

  • Visual field testing for bitemporal hemianopia.
  • Cranial nerve exam.
  • Chest wall inspection for lesions.
  • Signs of hypothyroidism.

Differential Diagnosis

  • Macroprolactinemia (immunoassay artifact; biologically inactive; no treatment needed).

Diagnostic Tests

  • Serum prolactin (fasting morning sample preferred):
  • Normal <25 µg/L
  • Postmenopausal <30 µg/L

  • 250 µg/L suggests prolactinoma.

  • Pregnancy test.
  • Thyroid-stimulating hormone (TSH).
  • LH/FSH in amenorrhea.
  • Pituitary MRI (best imaging).
  • Visual field testing if adenoma suspected.
  • CT if MRI contraindicated.

TREATMENT

General Measures

  • Discontinue offending drugs.
  • Treat underlying causes.
  • Observation in mild/asymptomatic cases.

Medication

First Line

  • Dopamine agonists:
  • Cabergoline (preferred): 0.25 mg twice weekly or 0.5 mg weekly.
    • More effective, better tolerated than bromocriptine.
    • Improves prolactin levels, symptoms, body mass index, lipid profile, insulin sensitivity.
  • Bromocriptine: 1.25 mg at bedtime initially, then BID; often preferred in infertility.
  • Adverse effects: nausea, headache, dizziness, fatigue, postural hypotension.
  • Contraindications: uncontrolled hypertension, cardiac valvular disease, fibrotic disorders.

Second Line

  • Pergolide no longer used.

Additional Therapies

  • Radiotherapy for refractory cases with low complication rates.

Surgery

  • Indicated for:
  • Medication intolerance/resistance.
  • Headache or visual field loss.
  • CSF leak from tumor apoplexy.
  • Cranial nerve deficits.
  • Risks: recurrence (up to 40%), CSF leak, meningitis, pituitary insufficiency, transient diabetes insipidus.

ONGOING CARE

  • Monitor prolactin levels monthly initially; titrate medication dose accordingly.
  • After 2 years of treatment with tumor control and normalized prolactin, medication taper and discontinuation may be considered with close follow-up.
  • Annual visual field testing and MRI as clinically indicated.

PREGNANCY CONSIDERATIONS

  • Discontinue dopamine agonists when pregnancy confirmed unless neurologic symptoms.
  • Microprolactinoma: monitor with monthly pregnancy tests; bromocriptine may be used.
  • Macroprolactinoma: individualized plan including pre-pregnancy surgery or bromocriptine continuation.
  • Monitor visual fields each trimester.

PATIENT EDUCATION

  • Risks of untreated hyperprolactinemia: headache, visual loss, osteoporosis, infertility.
  • Medication side effects and adherence importance.
  • Impact of antipsychotics on prolactin levels.

PROGNOSIS

  • 5-10% of microadenomas may progress.
  • Low recurrence after treatment but requires monitoring.

COMPLICATIONS

  • Visual field loss from tumor mass effect.
  • Cardiac valvular abnormalities with high-dose cabergoline (recommend cardiac ultrasound every 2 years).

REFERENCES

  1. Somerall WE Jr, Somerall DW. Hyperprolactinemia: the ABCs of diagnosis and management. Women's Healthcare. 2020;8(6):6-12.
  2. Casanueva FF, et al. Guidelines of the Pituitary Society for prolactinomas. Clin Endocrinol (Oxf). 2006;65(2):265-273.
  3. Inder WJ, Castle D. Antipsychotic-induced hyperprolactinemia. Aust N Z J Psychiatry. 2011;45(10):830-837.
  4. Hoffman AR, Melmed S, Schlechte J. Patient guide to hyperprolactinemia. J Clin Endocrinol Metab. 2011;96(2):35A-36A.
  5. Wang AT, et al. Treatment of hyperprolactinemia: systematic review. Syst Rev. 2012;1:33.
  6. Bloomgarden E, Molitch ME. Surgical treatment of prolactinomas: cons. Endocrine. 2014;47(3):730-733.
  7. Inancli SS, et al. Effect of cabergoline on insulin sensitivity and inflammation in prolactinoma patients. Endocrine. 2013;44(1):193-199.

Clinical Pearls

  • Serum prolactin >250 µg/L strongly suggests prolactinoma; MRI imaging indicated.
  • Macroprolactin may cause elevated prolactin without symptoms; test for macroprolactin if asymptomatic.
  • Discontinuation of dopamine-blocking medications may normalize prolactin.
  • Cabergoline preferred due to better efficacy and tolerability.
  • Hyperprolactinemia inhibits GnRH, LH, and FSH secretion, causing hypogonadism and sexual dysfunction.