> Table of Contents > Galactorrhea
Galactorrhea
Nicole Nelson, DO
David Bode, MD
image BASICS
DESCRIPTION
  • Milky nipple discharge not associated with gestation or present >1 year after weaning. Galactorrhea does not include serous, purulent, or bloody nipple discharge.
  • System(s) affected: endocrine/metabolic, nervous, reproductive
  • Synonym(s): disordered lactation; nipple discharge
Pregnancy Considerations
Most cases of galactorrhea during pregnancy are physiologic.
EPIDEMIOLOGY
  • Predominant age: 15 to 50 years (reproductive age)
  • Predominant sex: female > male (rare, e.g., in patients with multiple endocrine neoplasia type 1 [MEN1], the most common anterior pituitary tumors are prolactinomas)
Incidence
Common
Prevalence
6.8% of women referred to physicians with a breast complaint have nipple discharge.
ETIOLOGY AND PATHOPHYSIOLOGY
Disorders of lactation are associated with elevated prolactin levels, either from overproduction or loss of inhibitory regulation by dopamine.
  • Nipple stimulation
  • Pituitary gland overproduction
    • Prolactinoma
  • Loss of dopamine via hypothalamic dysregulation
    • Craniopharyngiomas
    • Meningiomas or other tumors
    • Sarcoid
    • Irradiation
    • Vascular insult
    • Stalk disruption
    • Traumatic injury
  • Medications that suppress dopamine (1):
    • Typical and atypical antipsychotics
    • SSRIs
    • Tricyclic antidepressants
    • Cimetidine
    • Ranitidine
    • Reserpine
    • &agr;-Methyldopa
    • Verapamil
    • Estrogens
    • Isoniazid
    • Opioids
    • Stimulants
    • Neuroleptics
    • Metoclopramide
    • Domperidone
    • Protease inhibitors
  • Chest wall injury
    • Zoster, surgical, or other trauma
  • Postoperative condition, especially oophorectomy
  • Renal failure
  • Other causes
    • Primary hypothyroidism
    • Cirrhosis
    • Cushing disease
    • Ectopic prolactin secretion
    • Renal failure
    • Sarcoid
    • Lupus
    • Multiple sclerosis
    • Polycystic ovary syndrome
  • Idiopathic
    • Normal prolactin levels
GENERAL PREVENTION
  • Frequent nipple stimulation can cause galactorrhea.
  • Avoid medications that can suppress dopamine.
COMMONLY ASSOCIATED CONDITIONS
See “Etiology and Pathophysiology.”
image DIAGNOSIS
  • Findings vary with causes
  • Look for signs/symptoms of associated conditions:
    • Adrenal insufficiency
    • Acromegaly
    • Hypothyroidism
    • Chest wall conditions
PHYSICAL EXAM
Breast examination should be performed with attention to the presence of spontaneous or induced nipple discharge.
DIFFERENTIAL DIAGNOSIS
  • Pregnancy-induced lactation or recent weaning
  • Nonmilky nipple discharge
    • Intraductal papilloma
    • Fibrocystic disease
  • Purulent breast discharge
    • Mastitis
    • Breast abscess
    • Impetigo
    • Eczema
  • Bloody breast discharge: Consider malignancy (Paget disease, breast cancer).
DIAGNOSTIC TESTS & INTERPRETATION
Perform formal visual field testing if pituitary adenoma suspected.
Initial Tests (lab, imaging)
  • Prolactin level, thyroid-stimulating hormone, pregnancy test, liver, and renal functions
  • Drugs that may alter lab results: medications that can cause hyperprolactinemia
  • Situations that may alter lab results:
    • Lab evaluation of prolactin may be falsely elevated by a recent breast examination.
    • Vigorous exercise
    • Sexual activity
    • High-carbohydrate diet
    • Consider repeating the test under different circumstances if the value is borderline (30 to 40) elevated.
  • Prolactin levels may fluctuate. Elevated prolactin levels should be confirmed with at least one additional level drawn in a fasting, nonexercised state, with no breast stimulation (2)[C].
  • Prolactin levels >250 ng/mL are highly suggestive of a pituitary adenoma (3)[C].
  • If a breast mass is palpated in the setting of nipple discharge, evaluation of that mass is indicated with mammogram and/or ultrasound.
  • Pituitary MRI with gadolinium enhancement if the serum prolactin level is significantly elevated (>200 ng/mL) or if a pituitary tumor is otherwise suspected.
Follow-Up Tests & Special Considerations
  • Consider evaluation of follicle-stimulating hormone and luteinizing hormone if amenorrheic.
  • Consider evaluation of growth hormone levels if acromegaly suspected.
  • Measure adrenal steroids if signs of Cushing disease present.
Diagnostic Procedures/Other
If diagnosis is in question, confirm by microscopic evaluation that nipple secretions are lipoid.
Test Interpretation
None, unless pituitary resection required
P.393

image TREATMENT
  • Avoid excess nipple stimulation.
  • Idiopathic galactorrhea (normal prolactin levels) does not require treatment.
  • Discontinue causative medications, if possible.
  • Treat to manage symptoms, reduce patient anxiety, and restore fertility.
  • Treat tumors >10 mm (even if asymptomatic) to reduce pituitary tumor size or prevent progression to avoid neurologic sequelae.
  • If microadenoma, watchful waiting can be appropriate because 95% do not enlarge.
MEDICATION
  • Dopamine agonists work to reduce prolactin levels and shrink tumor size. Therapy is suppressive, not curative (4)[C].
  • Treatment is discontinued when tumor size has reduced or regressed completely or after pregnancy has been achieved.
  • Cabergoline (Dostinex)
    • Start at 0.25 mg PO twice weekly and increase by 0.25 mg monthly until prolactin levels normalize. Usual dose ranges from 0.25 to 1 mg PO once or twice weekly.
    • More effective and better tolerated than bromocriptine (5)[A]
    • Convenient dosing
  • Although cabergoline has been associated with valvular heart disease in patients treated for Parkinson disease, the lower doses used in treatment of prolactinomas have not been adequately studied (6)[C].
  • Bromocriptine
    • Start at 1.25 mg/day PO with food and increase weekly by 1.25 mg/day until therapeutic response achieved (usually 2.5 to 15 mg/day, divided once daily/TID).
    • More expensive and more frequent dosing; however, most providers have experience with this effective drug.
    • Long-term treatment can cause woody fibrosis of the pituitary gland.
  • Contraindications are similar for all and include the following:
    • Uncontrolled hypertension
    • Sensitivity to ergot alkaloids
  • Precautions
    • Nausea, vomiting, and drowsiness are common.
    • Orthostasis, light-headedness, or syncope
    • Hypertension, seizures, acute psychosis, and digital vasospasm are rare.
  • Significant possible interactions
    • Phenothiazines, butyrophenones; other drugs listed under “Etiology and Pathophysiology”
SURGERY/OTHER PROCEDURES
  • Surgery
    • Macroadenomas need surgery if (a) medical management does not halt growth, (b) neurologic symptoms persist, (c) size >10 mm, or (d) patient cannot tolerate medications. Also considered in young patients with microadenomas to avoid long-term medical therapy.
    • Transsphenoidal pituitary resection
    • 50% recurrence after surgery
  • Radiotherapy
    • Radiation is an alternative tumor therapy for macroprolactinomas not responsive to other modes of treatment:
      • 20-30% success rate
      • 50% risk of panhypopituitarism after radiation
      • Risk of optic nerve damage, hypopituitarism, neurologic dysfunction, and increased risk for stroke and secondary brain tumors
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • Outpatient care unless pituitary resection required
  • Bromocriptine patients need adequate hydration
  • Dopamine agonist therapy should be discontinued in pregnancy.
Patient Monitoring
  • Varies with cause
  • Check prolactin levels every 6 weeks until normalized, then every 6 to 12 months.
  • Monitor visual fields and/or MRI at least yearly until stable.
DIET
No restrictions
PATIENT EDUCATION
  • Warn about symptoms of mass enlargement in pituitary.
  • Discuss treatment rationale, risks of treating, and expectant management.
  • Patient education material available from American Family Physician: www.aafp.org/afp/20040801/553ph.html
PROGNOSIS
  • Depends on underlying cause
  • Symptoms can recur after discontinuation of a dopamine agonist.
  • Surgery can have 50% recurrence.
  • Prolactinomas <10 mm can resolve spontaneously.
REFERENCES
1. Molitch ME. Drugs and prolactin. Pituitary. 2008;11(2):209-218.
2. Huang W, Molitch ME. Evaluation and management of galactorrhea. Am Fam Physician. 2012;85(11):1073-1080.
3. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273-288.
4. Majumdar A, Mangal NS. Hyperprolactinemia. J Hum Reprod Sci. 2013;6(3):168-175.
5. Wang AT, Mullan RJ, Lane MA, et al. Treatment of hyperprolactinemia: a systematic review and meta-analysis. Syst Rev. 2012;1:33.
6. Córdoba-Soriano JG, Lamas-Oliveira C, Hidalgo-Olivares VM, et al. Valvular heart disease in hyperprolactinemic patients treated with low doses of cabergoline. Rev Esp Cardiol. 2013;66(5):410-412.
Additional Reading
&NA;
  • Mancini T, Casanueva FF, Giustina A. Hyperprolactinemia and prolactinomas. Endocrinol Metab Clin North Am. 2008;37(1):67-99.
  • Patel BK, Falcon S, Drukteinis J. Management of nipple discharge and the associated imaging findings. Am J Med. 2015;128(4): 353-360.
See Also
&NA;
Hyperprolactinemia
Codes
&NA;
ICD10
  • N64.3 Galactorrhea not associated with childbirth
  • N64.52 Nipple discharge
Clinical Pearls
&NA;
  • Galactorrhea is a common disorder, affecting up to 50% of reproductive-age women.
  • Common causes include idiopathic, from excess nipple stimulation, dopamine-suppressing medications, or pituitary prolactinoma
  • Most cases may be adequately evaluated by thyroid-stimulating hormone, prolactin, and human chorionic gonadotropin measurement, with additional testing as suggested by the presence of other symptoms or signs.
  • Lab evaluation of prolactin may be falsely elevated due to recent sexual activity, breast examination, exercise, or a high-carbohydrate diet. Repeat any borderline elevation before continuing evaluation or initiating treatment.
  • Evaluate prolactin >200 ng/mL (or suspicion of pituitary macroadenoma) with a gadolinium-enhanced MRI.