LM 19.1: Galactorrhea

Question 1

what is galactorrhea?

Answer 1

breast milk production outside the context of normal lactation

Question 2

what are the causes of galactorrhea?

Answer 2

1. physiologic and occur because of nipple stimulation (breast feeding)
2. elevated prolactin levels
3. pathologic manifestation of anterior pituitary tumor
4. side effects of durgs
5. occur in patients with CKD who can’t clear serum prolactin
6. hypothyroidism

Question 3

is galactorrhea associated with malignancy?

Answer 3

not associated with malignancy, but it must be distinguished from other types of breast secretions / pathology that may be associated with malignancy

Question 4

where is prolactin secreted from?

Answer 4

anterior pituitary gland

Question 5

what does prolactin do?

Answer 5

1. can stimulate milk production in females
2. can stimulate milk production in males with pituitary tumors or gynecomastia
3. inhibits the synthesis and release of GnRH

Question 6

can you have galactorrhea with normal prolactin levels?

Answer 6

yes!

Question 7

what is a pituitary adenoma?

Answer 7

a benign tumor of the pituitary gland

can cause hyperprolactinemia

can be “non-functional” or “functional”

Question 8

what are non-functional pituitary adenomas?

Answer 8

1. do not alter hormone levels
2. cause symptoms due to its size/mass
3. compress pituitary tissue and decrease pituitary function

Question 9

what are functional pituitary adenomas?

Answer 9

they DO alter hormone levels

may cause elevated prolactin and inhibit GnRH synthesis

Question 10

what happens when there is hyperprolactinemia in women?

Answer 10

hyperprolactinemia results in decreased production of GnRH

decreased GnRH leads to decreased production of FSH and LH

decreased FSH and LH can result in a lack of ovulation and amenorrhea

functional pituitary adenomas in females can result in amenorrhea since elevated prolactin levels inhibit GnRH synthesis, leading to decreased FSH and LH, thus inhibiting ovulation.

Question 11

how does galactorrhea effect males?

Answer 11

decreased GnRH synthesis inhibits spermatogenesis

men with galactorrhea often experience decreased libido

not common in males unless androgen levels are low and gynecomastia is presen

Question 12

how would a patient with galactorrhea present?

Answer 12

women present with galactorrhea more often than men

patients normally present with bilateral breast secretions

it is crucial to take a thorough patient history; ask about the patient’s breast discharge: –> unilateral/bilater, color, timing

Question 13

what questions should you ask during a history for a patient presenting with galactorrhea?

Answer 13

1. is the discharge unilateral or bilateral?
2. what color is the discharge?
3. does the discharge occur when the breasts are physically stimulated
4. has the patient has su ered a chest wall injury? (This can induce hyperprolactinemia and therefore galactorrhea.)
5. do females have menstrual cycle abnormalities or other signs of hypogonadism?
6. are females experiencing any hot ashes or vaginal dryness?
7. is the patient taking any medication/supplements?
8. does the patient have any signs of decreased energy, libido, headaches, or visual changes?

Question 14

how do pre-menopausal women with galactorrhea present?

Answer 14

low GnRH can lead to low FSH and LH

low FSH and LH can result in oligomenorrhea, amenorrhea, infertility and/or galactorrhea

Question 15

how do post-menopausal women with galactorrhea present?

Answer 15

are already in a hypogonadal state, so they do not notice changes such as amenorrhea, oligomenorrhea, or infertility

low estrogen state makes galactorrhea less likely to occur

Question 16

what is a common presentation of pituitary adenoma?

Answer 16

pituitary adenoma can exert a mass e ect if it is large enough

since the mass would be located in the sella turcica region, it can compress the optic chiasm

any patient with a large enough pituitary adenoma (whether they are pre-menopausal or post-menopausal) may present with headache and/or bitemporal hemianopsia due to mass e ect

Question 17

what is the most common cause of galactorrhea in men?

Answer 17

most likely to occur in men with hyperprolactinemia due to pituitary tumors and gynecomastia

if galactorrhea was triggered by hyperprolactinemia, they may also present with Erectile Dysfunction (ED) – if the hyperprolacinemia is treated, the ED can be reversed

hyperprolactinemia can cause decreased testosterone secretion and therefore, hypogonadotropic hypogonadism

males may initially present with decreased energy and decreased libido

over the long term, males with hyperprolactinemia may have decreased muscle mass, decreased body hair, osteoporosis, and infertility due to decreased FSH and LH

Question 18

how can we distinguish various types of breast discharge?

Answer 18

only approximately 5% of women with breast cancer present with breast discharge but if breast discharge is present, the type of discharge should be determined

galctorrhea is a benign condition, but other forms of breast discharge may suggest malignancy

galactorrhea can appear clear, milky, green, or black

galactorrhea normally causes bilateral secretions

ig the discharge contains fat, milk production (galactorrhea) is con rmed

if the discharge contains blood, consider other possibilities

Question 19

what are the red flags of breast discharge that suggest malignancy?

Answer 19

1. unilateral, occurs spontaneously, and is persistent
2. serous, serosanguinous, or bloody
3. present along with a breast lump/mass
4. present in elderly patients

symptoms that suggest benign galactorrhea: milky breast discharge, bilateral discharge, green breast discharge

Question 20

which medications can induce galactorrhea?

Answer 20

1. antipsychotic medications such as: Haloperidol, Loxitane, Mellaril, Moban, Navane, Prolixin, Risperidone, Stelazine, Thioxanthenes, Thorazine, Trilafon
2. anti-anxiety drugs including: Benzodiazepines, Buspirone
3. anti-depressant medications including: Monoamine Oxidase Inhibitors (MAOIs), Selective Serotonin Receptor Inhibitors (SSRIs), and Tricyclic Antidepressants
   Neurological medications including: Dihydroergotamine, Sumatriptan, Valproic Acid
4. gastrointestinal agents including: Histamine 2 blockers (Cimetidine, Famotidine, Ranitidine) and Metoclopramide
5. hormonal Preparations including: Danazol, estrogen, medroxyprogesterone acetate, oral contraceptives
6. controlled Substances/Illicit Drugs including: Amphetamines, cannabis, cocaine, opiates
7. Anti-hypertensive medications including: Atenolol, methyldopa, reserpine, verapamil Source: Smith, MA; Schrager, S.; Winkler Prins, V. Matus, C. Speer, L.
   Essentials of Family Medicine. 7th ed. Women’s Health. Wolfers Kluwer. 2018.

Question 21

what testing should be done for galactorrhea?

Answer 21

1. if a patient presents with galactorrhea and no breast mass, measure serum prolactin
2. normal prolactin: 5 to 20 ng/mL in women and 2 to 18 ng/mL in men
3. best to obtain the blood sample when the patient is fasting
4. strenuous exercise, sleep, and physical/emotional stress can raise serum prolactin levels

patients with elevated prolactin levels should undergo MRI of the hypothalamic/pituitary region with contract –> if a mass if found other hormone levels should be assessed

Question 22

what do you do if someone has serious, serosanguinous or bloody discharge?

Answer 22

other breast pathology may be present, including the possibility of breast malignancy

imaging should be performed:

1. ultrasound = Initial imaging modality of choice for women with a breast
   mass under age 30
2. mammography = Initial imaging modality of choice for women with a breast mass over age 30

Question 23

how do you treat galactorrhea due to hyperprolactinemia?

Answer 23

1. prevent neurological complications that could arise due to a pituitary adenoma
2. treat hypogonadism
3. alleviate bothersome symptoms of galactorrhea

Question 24

what is a pituitary macro adenoma vs. microadenoma?

Answer 24

macroadenomas
1. 1 cm or more in diameter

2. serum prolactin usually over 200 ng/mL

microadenomas
1. less than 1 cm in diameter

2. serum prolactin levels under 200 ng/mL

Question 25

what is the medical treatment of pituitary adenomas?

Answer 25

1. dopamine agonists

medication class used to treat pituitary adenomas and hyperprolactinemia.

2. cabergoline

1st choice dopamine agonist for most patients with hyperprolactinemia –> efficacious and less side effects than bromocriptine but increased risk of valvular heart disease at high doses

3. bromocriptine

2nd choice dopamine agonist for patients with hyperprolactinemia

more likely to cause nausea than Cabergoline

Question 26

if women with a lactotroph adenoma desire pregnancy but their prolactin levels do not reach normal levels, how do you induce ovulation?

Answer 26

dopamine agonist therapy like Clomiphene Citrate or Gonadotropin

Question 27

what are the surgical managements of pituitary adenomas?

Answer 27

transphenoidal surgery could be performed to treat a macro adenoma

but this is reserved only for when:
1. prolactinoma does not decrease in size after medical treatment

2. symptoms do not improve after several months of high-dose medical therapy
3. a woman has a lactotroph adenoma larger than 3 cm in diameter and desires pregnancy

Question 28

how can radiation be used to treat pituitary adenoma?

Answer 28

radiation may be used after surgery in an attempt to prevent tumor recurrence

Question 29

what are the complications associated with radiation treatment for pituitary adenomas?

Answer 29

1. nerve damage
2. nausea
3. hair loss
4. 50% chance anterior pituitary hormone secretion will be lost within 10 years of radiation

Question 30

what is the general class of medication used to treat pituitary adenoma or hyperprolactinemia?

Answer 30

dopamine agonists

Question 31

1st line medication used to treat pituitary adenoma or hyperprolactinemia

Answer 31

cabergoline

Question 32

2nd line medication used to treat pituitary adenoma or hyperprolactinemia

Answer 32

bromocriptine

Question 33

how do you treat galatorrhea that doesn’t have hyperprolactinemia?

Answer 33

it doesn’t require treatment

however, if symptoms are bothersome it can be treated with a dopamine agonists like cabergoline

Question 34

A 28 year-old female visits her primary care doctor. Her blood pressure is 115/70, HR is 70, and her BMI is 21.2. She has no previous substantial medical history and denies taking any medications, supplements, alcohol, or illicit drugs. Over the past few months, her menstrual cycles have been irregular. She has also experienced bilateral discharge from her breasts that has soaked through her bra. A breast examination is performed. There are no palpable masses, but white discharge emerges from both nipples on examination. If her beta human chorionic gonadotropin test is negative and her prolactin levels are at 227ng/mL, which test would be most appropriate to order next?

Answer 34

MRI of the pituitary/hypothalamic region with contract

she has menstrual irregularities, bilateral galactorrhea, and an elevated prolactin level of 227ng/mL – she most likely has a pituitary adenoma in the sella turica region

MRI of the hypothalamaus/pituitary with contrast would provide the best chance of discerning a pituitary adenoma.

mammography is not be necessary because she is 28 years old (it should not be performed in women under 30) and because her clinical presentation and lab results do not suggest the possibility of malignancy or other breast mass

no need to perform a bilateral biopsy for galactorrhea induced by hyperprolactinemia

Question 35

A 32 year old woman presents to her primary care physician because she has had bilateral nipple discharge over the past couple of months. The discharge appears white and milky. Her periods used to occur regularly, but have been “more sporadic” over the past few months. She denies any vision changes, headaches, hirsutism, acne, weight gain, or male pattern baldness. Her current medications include insulin, risperidone, and a combined calcium and vitamin D supplement. what is the most likely cause of her bilateral nipple discharge?

Answer 35

risperidone

risperidone is an anti-psychotic medication that has been commonly associated with increased prolactin levels, galactorrhea, and also irregular periods

PCOS can cause menstrual cycle irregularities, this patient denies hirsutism, acne, weight gain, or male pattern baldness