Prolactinomas

prolactin

hormone that stimulates breast tissue to produce milk

hyperprolactinemia levels

prolactin >30ng/mL

normal range: 15-25

Level of Prolactin Elevation (ng/mL)

30-100

- pregnancy

- medications

- stress, hypothyroidism, kidney or liver failure

200-250

- prolactinoma

500

- macroprolactinoma

Prolactinomas

- benign prolactin-secreting pituitary tumors

Size classification

- Microadenoma --> <10mm

- macroadenoma : >10mm, often continue to grow

Medication Induced prolactinomas (dopamine antagonists)

- antipsychotics

- phenothiazines

- metoclopramide

- domperidone

Medication Induced (prolactin stimulators)

- SSRIs

- TCAs

- 5-HT1 RA

- estrogen/progestin

- opioids

- benzos

- H2-RA

- GnRH analogs

- MOAI

•Antipsychotics

- inhibit primary control of prolactin secretion (dopamine)

•SSRIs, MAOIs, TCAs

- increase serotonin, which is secondary control of prolactin secretion

•Estrogen, progesterone

secondary control of prolactin secretion

Drug Induced Treatment

- discontinue offending agent and initiate appropriate therapeutic alternative

- aripiprazole can be considered in antipsychotic-induced hyperprolactinemia

aripiprazole role in treatment

- partial D2 agonist activity

- can be considered as add-on therapy if pt is responding well to the initial antipsychotic

- may discontinue offending antipsychotic and trial aripiprazole if patient was not responding well to initial treatment

Presentation - Assigned Female at Birth

estrogen deficiency

- menstrual abnormalities

- infertility

- decreased libido

- osteoporosis

galactorrhea

structural effects

-headache or loss of vision

- microadenomas

Presentation - Assigned Male at Birth

testosterone deficiency

- ED

- decreased libido

- loss of body hair

- osteoporosis

galactorrhea

- higher prolactin on presentation

structural effects

- headache or loss of vision

- microadenoma

Goals of Therapy

- correct underlying causes

-normalize serum prolactin levels

- alleviate symptoms

Treatment

- pharmacologic therapy

- pituitary surgery

- radiotherapy

•Pharmacologic Therapy

- DA are first line

-cabergoline preferred over bromocriptine

- higher efficacy in normalizing levels and tumor shrinkage

•Pituitary Surgery

•Transsphenoidal surgery

•Reserved for prolactinomas resistant to DAs

radiotherapy

•Stereotactic radiation (Gamma Knife) or external beam radiation

•Reserved for prolactinomas resistant to DAs, surgery

Cabergoline (Dostinex) dosing

initiate

0.25mg PO TIW

titrate

- increase total weekly dose by 0.5mg Q4w

usual dosing

up to 1mg TIW (max)

Cabergoline (Dostinex) clinical pearls

•Higher affinity for D2 receptor vs. bromocriptine

•More efficacious in reducing tumor size and normalizing prolactin levels

•Better GI tolerance

Bromocriptine (Parlodel) dosing

•Available as 2.5 mg divided tablets and 5 mg capsules

oVaginal preparations

Initiate: 1.25 - 2.5 mg daily (with food)

Titration: ↑ dose as tolerated every 2-7 days

Usual dosing: 2.5 - 15 mg daily, divided as 1-3 administrations daily

bromocriptine clinical pearls

•Many patients who do not respond to bromocriptine will respond to cabergoline

•More data on safety in pregnancy compared to cabergoline à preferred in pregnancy

Dopamine agonist therapy ADE

- nausea, vomiting, diarrhea, headache, dizziness, hypotension

- occurs at initiation and usually subsides

- tk with food

- may initiate at bedtime

Dopamine agonist therapy contraindications

•Uncontrolled HTN

•History of cardiac valve disorder

•History of pulmonary or pericardial fibrotic disorders

•Breastfeeding (interfere with lactation)

Pregnancy recommendations

- D/C D2 therapy as soon as they discover theyre pregnant

- risk of fetal harm

if treatment is required, use bromocriptine

After Pregnancy

•Breastfeeding increases serum prolactin

•Treatment is typically withheld until breastfeeding is complete

•If visual field impairment develops, restart treatment

•Will have to stop breastfeeding

measure prolactin 3 months after delivery or cessation of breastfeeding

Monitoring

- symptom reduction

- prolactin levels 3-4 weeks after initiation and dose adjustment

- imaging may be repeated q6-12months

- may consider tapering/ D/C after 2-3 years of normalized prolactin

•Consider discontinuation of DA therapy if:

•Received at least 2 years of treatment

and

•Serum prolactin levels normalized

and

•Absence of visible tumor on imaging