Approach to nipple discharge: Clinical sciences

Nipple discharge is the expression of fluid from the breast, and can be caused by both physiologic and pathologic conditions, ranging from normal lactation to cancer. Because nipple discharge can have so many different causes - some more worrisome than others - it’s crucial to perform a detailed diagnostic workup to differentiate between them.

When assessing a patient with nipple discharge, the first step is to obtain a focused history and physical exam. When taking history, you want to find out if the discharge is one sided or bilateral; if it’s spontaneous or has any provoking factors; if it’s associated with other symptoms; and what the discharge fluid looks like.

On physical exam, first look for lumps, asymmetries, or changes to the breast skin or nipple and areola, as well as regional lymph nodes.

Then, try to elicit nipple discharge by carefully applying manual pressure in a clockwise fashion around the areola. If you are unable to elicit any nipple discharge, apply a warm compress to the breast and wait a few minutes before trying again. Make sure to apply pressure at the base of the areola and not the nipple itself. It can also be helpful to palpate from the periphery of the areola toward the nipple. Finally, make sure to note the quality of any expressed discharge.

Let’s start with physiologic nipple discharge. Patients typically report bilateral nipple discharge associated with breast or nipple stimulation. On physical exam you’ll find bilateral, multiductal nipple discharge that is white, clear, or milky. If this is the case, consider physiologic discharge, and order labs including hCG, prolactin, CBC, CMP, and TSH to help you find the cause. Also, don’t forget to check if the patients’ screening mammograms are up-to-date according to their age.

Alright, our first cause of physiologic nipple discharge is pregnancy or lactation. This is common among patients who are or were pregnant, recently gave birth, or breastfed within the past year.

On physical exam, you might see a gravid uterus if they’re currently pregnant, and bilaterally engorged breasts. Typically, labs reveal a positive hCG if the patient is currently pregnant, or hyperprolactinemia if they’re breastfeeding. With any of these findings, you can make your diagnosis of nipple discharge due to pregnancy or lactation. The leakage in this case is breast milk, which is normal.

Okay, let’s move on to non-pregnancy related breast milk production, or galactorrhea.

The most common cause is a pituitary adenoma, more specifically a prolactinoma. On history, patients might report recent new onset of vision changes or headaches; in addition to symptoms of hypogonadism, such as oligomenorrhea or hot flashes in biological females, and sexual dysfunction or gynecomastia in biological males.

The physical exam usually reveals visual field defects, while labs show hyperprolactinemia.

If you see these findings, consider a pituitary adenoma, and obtain an MRI of the brain to look for a mass in the sella turcica. If you see one, that confirms your diagnosis of a pituitary adenoma.

Alright, our next cause is primary hypothyroidism. These patients typically report fatigue, cold intolerance, weight gain, and constipation. On physical exam you might notice dry skin, bradycardia, or even a goiter. Lab would reveal elevated TSH and hyperprolactinemia, but a normal CBC, CMP, and a negative hCG. At this point, you should consider hypothyroidism.

Then, obtain additional labs, such as a free T4 level, and a brain MRI to rule out a pituitary mass. If the free T4 is low, and the MRI doesn’t show any mass, you can diagnose your patient with primary hypothyroidism. Remember, in primary hypothyroidism, thyrotropin releasing hormone is increased, which stimulates prolactin release causing galactorrhea.

Okay, moving onto chronic kidney disease. History in this case is going to be a bit more vague. Patients might report hypertension and peripheral edema, which you can also notice on the physical exam. Labs will show hyperprolactinemia, as well as an elevated creatinine and BUN, sometimes hypercalcemia, and even anemia. Typically, TSH is normal, while hCG is negative. With these findings, think about chronic kidney disease.

Next, order a urinalysis with microscopy, a renal ultrasound, and a brain MRI. Urinalysis with microscopy might reveal proteinuria, microhematuria or casts; while renal ultrasound might show renal atrophy and maybe even renal cysts. On brain MRI, there’s no evidence of a mass. These findings should confirm your diagnosis of chronic kidney disease. In this case, the kidneys lose their ability to filtrate adequately, so prolactin can accumulate causing galactorrhea.

Alright, let’s talk about our last cause of galactorrhea! Once you have ruled out the previous causes, consider medication-induced galactorrhea, which can be caused by antipsychotics, tricyclic antidepressants, SSRIs, metoclopramide, oral contraceptives, or methyldopa.

Now, history might reveal the onset of nipple discharge while taking these medications. The physical exam is usually unremarkable, while labs only show hyperprolactinemia. In this case, consider galactorrhea as a medication side effect, and try switching to a different medication, or cessation if appropriate. If there’s resolution of symptoms, great! In some cases, you may also consider obtaining a brain MRI to rule out a pituitary tumor. As long as the MRI is negative, and galactorrhea stops upon medication discontinuation, you can diagnose it as a medication side effect.

Okay, now that we’ve gone over the physiologic causes of nipple discharge, let’s go all the way back.