Galactorrhea

para>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
- Î±-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."

DIAGNOSIS

Findings vary with causes
Look for signs/symptoms of associated conditions:
- Adrenal insufficiency
- Acromegaly
- Hypothyroidism
- Chest wall conditions

HISTORY

Usually bilateral milky nipple discharge; may be spontaneous or induced by stimulation
Determine possibility of pregnancy or recent discontinuation of lactation
Signs of hypogonadism from hyperprolactinemia
- Oligomenorrhea, amenorrhea
- Inadequate luteal phase, anovulation, infertility
- Decreased libido (especially in affected males)
Mass effects from pituitary enlargement
- Headache, cranial neuropathies
- Bitemporal hemianopsia, amaurosis, scotomata

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

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

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.

COMPLICATIONS

If enlarging pituitary adenoma, risk of permanent visual field loss
Panhypopituitarism can complicate radiation or surgical therapy.
Osteoporosis if amenorrhea persists without estrogen replacement.

REFERENCES

11 Molitch ME. Drugs and prolactin. Pituitary. 2008;11(2):209-218.22 Huang W, Molitch ME. Evaluation and management of galactorrhea. Am Fam Physician. 2012;85(11):1073-1080.33 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):273-288.44 Majumdar A, Mangal NS. Hyperprolactinemia. J Hum Reprod Sci. 2013;6(3):168-175.55 Wang AT, Mullan RJ, Lane MA, et al. Treatment of hyperprolactinemia: a systematic review and meta-analysis. Syst Rev. 2012;1:33.66 C ³rdoba-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

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.

CODES

ICD10

N64.3 Galactorrhea not associated with childbirth
N64.52 Nipple discharge

ICD9

611.6 Galactorrhea not associated with childbirth
611.79 Other signs and symptoms in breast

SNOMED

78622004 Galactorrhea not associated with childbirth (disorder)
54302000 Discharge from nipple (disorder)
198115002 Galactorrhea due to non-obstetric cause (disorder)

CLINICAL PEARLS

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.

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