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1
Question:

A 29-year-old woman comes to the office due to an intermittent nipple discharge for the past several weeks.  She has had no fever or breast pain.  The patient has never been pregnant despite having unprotected intercourse.  She experienced menarche at age 12.  Beginning a year ago, the patient's menses slowed to 2- to 3-month intervals and stopped completely 6 months ago.  She has no other medical conditions and takes no medications.  The patient's mother was diagnosed with metastatic breast cancer at age 60 and died recently.  BMI is 31 kg/m2.  On physical examination, white discharge is expressible from both nipples.  The remainder of the physical examination is within normal limits.  Urine β-hCG testing is negative.  Which of the following is the most likely diagnosis in this patient?

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Explanation:

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Prolactinoma

Clinical
features

  • Premenopausal women: oligomenorrhea/amenorrhea, infertility, galactorrhea, hot flashes, decreased bone density
  • Postmenopausal women: mass-effect symptoms (headache, visual field defects)
  • Men: infertility, decreased libido, impotence, gynecomastia

Laboratory/
imaging

  • Serum prolactin (often >200 ng/mL)
  • Tests to rule out renal insufficiency (creatinine) & hypothyroidism (TSH, thyroxine)
  • MRI of the head/pituitary

Treatment

  • Dopamine agonist (cabergoline)
  • Transsphenoidal surgery

Galactorrhea is the abnormal secretion of breast milk not associated with pregnancy or breastfeeding.  It is most commonly due to excess prolactin, which directly stimulates milk secretion in the breasts.  Hyperprolactinemia also causes amenorrhea in women due to the inhibitory effect of prolactin on hypothalamic GnRH secretion.

Lactotroph adenomas (prolactinomas) are the most common hormonally active pituitary tumors and can cause very high prolactin levels.  In addition, unlike most pituitary hormones, which are under positive regulation from the hypothalamus, prolactin is under negative regulation by hypothalamic dopaminergic neurons via the pituitary stalk, and any disruption of these pathways (eg, by a nonfunctioning pituitary adenoma) can cause moderate hyperprolactinemia.

In premenopausal women, such as this patient, prolactinomas typically present with galactorrhea and irregular menses.  However, in men and postmenopausal women, early symptoms (eg, decreased libido) are often mild and nonspecific, and presentation typically occurs at a later stage with headaches and bitemporal hemianopsia due to compression of the optic chiasm in the suprasellar region.  The diagnosis can be confirmed by MRI of the brain, and dopamine agonists (eg, bromocriptine, cabergoline) can be used to suppress prolactin secretion.

(Choice A)  Fibroadenomas are benign neoplasms of the breast that often occur in young women.  They present as a painless unilateral breast mass without nipple discharge.

(Choice B)  Fibrocystic changes of the breast, a normal variant in which breasts feel dense and lumpy, commonly presents with cyclic mastalgia.

(Choice C)  Galactocele, a mass filled with breast milk, can occur with hyperprolactinemia but is more often seen with normal lactation following pregnancy.

(Choices D, F, and G)  Inflammatory breast carcinoma presents with diffuse breast induration, erythema, and peau d'orange (orange peel) skin due to blockage of lymphatic drainage by cancerous invasion.  Lobular breast carcinoma typically presents as a painless breast mass.  Paget disease is a manifestation of ductal carcinoma characterized by crusty, scaly redness on the nipple and areola with oozing and bleeding.  Breast cancer may be associated with nipple discharge, but white galactorrhea is unusual, and menses are generally unaffected.

(Choice E)  Intraductal papilloma is a benign tumor within the mammary duct.  It is the most common cause of spontaneous nipple discharge, but the discharge is unilateral and typically bloody or serosanguineous.

Educational objective:
Prolactinomas are the most common hormonally active pituitary adenomas.  The excess prolactin produced by these tumors can cause galactorrhea and amenorrhea in premenopausal women.  With a large mass, visual changes and headaches may occur due to compression of the optic chiasm.