Setting: office
CC: “I’m making breast milk, but I’m not pregnant.”
HPI: A 34-year-old woman comes to office with abnormal milk production from her breasts for the last few weeks. She did three home pregnancy tests and all are negative. She has been unsuccessfully trying to get pregnant for 2 years. Her menstrual periods are irregular.
PMHX:
Depression
Medications:
Fluoxetine
PE:
Normal except galactorrhea
Initial Orders:
Urine beta-human chorionic gonadotropin (HCG)
Prolactin level
The patient’s repeat urine beta-HCG level is normal. Bring the patient back in a few days to discuss the results of the prolactin level. Of all the endocrinopathies, prolactin is unique in that so many medications and mechanical problems like nipple stimulation can cause hyperprolactinemia and galactorrhea (Figure 3-7).
Figure 3-7. Physiologic effects of prolactin. Prolactin plays an important role in the normal development of mammary tissue and in milk production. Prolactin release is predominantly under negative control by hypothalamic dopamine. Suckling stimulates the release of prolactin. Prolactin inhibits its own release by stimulating dopamine release from the hypothalamus. (Reproduced with permission from Molina PE. Endocrine Physiology, 3rd ed. New York: McGraw-Hill; 2010.)
Which of the following is not clearly associated with hyperprolactinemia?
a. Antipsychotic medications
b. Tricyclic antidepressants
c. SSRIs
d. Cimetidine
e. Verapamil
f. Opiates
Answer c. SSRIs
SSRIs are just not clearly associated with increased prolactin levels.
• Dopamine inhibits prolactin release.
• Antipsychotics decrease dopamine levels.
The patient returns and her prolactin level is elevated.
Which of the following endocrinopathies is associated with high prolactin level?
a. Estrogen deficiency
b. Addison disease
c. Cushing syndrome or hypercortisolism
d. Hypothyroidism
e. GH deficiency
Answer d. Hypothyroidism
It is reasonable to exclude hypothyroidism in any person with hyperprolactinemia. Increased estrogen directly stimulates the pituitary to release prolactin. This is the mechanism in pregnancy of how breast glands normally grow. The placenta makes estrogen. Estrogen makes prolactin. Prolactin makes the breast glands grow.
What is the mechanism of high prolactin level in hypothyroidism?
a. T4 normally suppresses prolactin release.
b. TRH level is increased.
c. Hypothyroidism decreases dopamine release.
d. TSH stimulates prolactin.
Answer b. TRH level is increased.
TRH stimulates prolactin release. This is usually only at pathologically increased levels of TRH such as found in hypothyroidism. Low T4 level removes feedback inhibition on TRH. Very high TRH level stimulates prolactin.
Opiate substance abusers have erectile dysfunction.
Opiates increase prolactin level.
Because of the high prolactin level and the absence of identifiable causes of hyperprolactinemia, you send the patient for an MRI of the head.
What functional biological test is there of prolactin?
a. Metoclopramide stimulation test
b. Dopamine suppression test
c. Estrogen stimulation test
d. Naloxone stimulation test
e. None
Answer e. None
High Prolactin + Exclude Correctable Causes = Brain MRI
An MRI is done. The patient returns for the results and is told she has a 5-mm lesion in the pituitary gland.
What is the next best step?
a. Refer to neurosurgery
b. Radiation treatment
c. Octreotide
d. Cabergoline
e. Pergolide
Answer d. Cabergoline
Cabergoline is an oral dopamine receptor antagonist that causes less nausea and vomiting than bromocriptine. This is clearly the first line of therapy for all microadenoma. Surgery is done if the lesion is larger than 3 cm or the dopamine agonist has failed. Radiation is a third or fourth attempt at treatment. Octreotide is a somatostatin analogue. There is no significant efficacy with a somatostatin analogue. Prolactinomas are managed exactly opposite to acromegaly. Surgery is the first-line treatment in acromegaly.
Cabergoline is an ergot derivative.
Transsphenoidal surgery is performed. Prednisone, T4, and sex hormones replacement therapy is started. Follow up with the patient until the program ends the case.