Hyperprolactinemia & Prolactinomas

What is prolactin

hormone that stimulates breast tissue to produce milk

define Hyperprolactinemia

persistent serum prolactin elevation

•Prolactin (PRL) \> 30 ng/mL
•Normal range 15-25 ng/mL

What affect does dopamine have on the release of prolactin

Dopamine inhibits prolactin production

What inhibits prolactin production

dopamine

What can cause elevations in prolactin to 30-100 ng/mL

•pregnancy
•medications (may increase to 150)
•stress, hypothyroidism, kidney or liver failure, "stalk effect"

What can cause elevations in prolactin to \>200-250 ng/mL

prolactinoma

What can cause elevations in prolactin to 500 ng/mL

macroprolactinoma

what is a prolactinoma

Benign prolactin-secreting pituitary tumors

What is the size of a microadenoma

•

What is the size of a macroadenoma

≥10mm, and they often continue to grow

What types of drugs increase prolactin by a primary mechanism?

Dopamine antagonists
- Antipsychotics (Typical, atypical, phenothiazines)
- Metoclopramide

What types of drug classes increase prolactin by a secondary mechanism?

•SSRIs, MAOIs, TCAs
•Estrogen, progesterone
•Verapamil, methyldopa, GnRH analogs, opioid

How do SSRIs, MAOIs, and TCAs increase prolactin

•Increase serotonin - secondary control of prolactin secretion (stimulator)

How do Estrogen and progesterone increase prolactin

•Secondary control of prolactin secretion (stimulators)

What are the indirect effects of hyperprolactinemia

GnRH inhibition leads to FSH/LH inhibition leading to Estrogen/ testosterone inhibition

What are the direct effects of hyperprolactinemia

Galactorrhea

What are the structural effects of a prolactinoma

•Headache, loss of vision
•Inability to secrete other anterior pituitary hormones

What symptoms of a prolactinoma do patients who are assigned female at birth normally present with

1) Indirect effects - Estrogen deficiency
•Commonly have menstrual abnormalities
•Infertility
•Decreased libido
•Osteoporosis

2)Direct effects
•Galactorrhea (inconsistent symptom)

3)Structural effects
•May have headache or loss of vision
•females are more likely to have microadenomas (because they normally present sooner)

What symptoms of a prolactinoma do patients who are assigned male at birth normally present with

1) Indirect effects - Testosterone deficiency
•Erectile dysfunction (years prior to diagnosis)
•Decreased libido
•Loss of body hair
•Osteoporosis

2) Direct effects
•Galactorrhea (Inconsistent symptom)
•Higher prolactin on presentation

3)Structural effects
•Commonly have headaches or loss of vision
•Males are more likely to have macroadenoma because they normally present later

How do you diagnose hyperprolactinemia/ a prolactinoma?

•Signs & symptoms + elevated prolactin level (May repeat level to rule out transient causes of prolactin elevation)
•Imaging (MRI, CT with contrast) (Size classification)
•Measure other anterior pituitary hormones for deficiencies

What are the goals of treatment when treating hyperprolactinemia/prolactinoma

•Identify and correct underlying causes
•Normalize serum prolactin
•Alleviate symptoms

What is the preferred form of treatment for hyperprolactinemia/prolactinoma

Pharmacologic Therapy

When do you use pituitary surgery in treatment of a prolactinoma

Reserved for prolactinomas resistant to DAs

When do you use radiotherapy in treatment of a prolactinoma

Reserved for prolactinomas resistant to DAs, surgery

What drug class is used to treat a prolactinoma/hyperprolactinemia

dopamine receptor (D2) agonist

What drug is preferred red when treating prolactinoma/hyperprolactinemia

Cabergoline

What drug is preferred red when treating prolactinoma/hyperprolactinemia in pregnancy

Bromocriptine

Cabergoline brand

Dostinex

Bromocriptine brand

Parlodel

Cabergoline drug class

•long-acting, dopamine receptor (D2) agonist

Cabergoline dosing for prolactinoma/hyperprolactinemia

•Initiate: 0.25mg twice weekly
•Usual dosing: up to 1 mg twice weekly

(available as 0.5mg tablets)

Bromocriptine dosing for prolactinoma/hyperprolactinemia

•Initiate: 1.25 - 2.5 mg daily, divided as 1-3 administrations daily
•Usual dosing: 2.5 - 15 mg daily, divided

(Available as 2.5mg divided tablets and 5mg capsules and vaginal preparations)

Dopamine agonist therapy side effects

•Nausea, vomiting, diarrhea, headache, dizziness, hypotension (Occur at initiation/ dose titration and usually subside)
•Cardiac valvopathy

Dopamine agonist therapy counseling points

•Recommend to take 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)

Dopamine agonist therapy metabolism

•Majority hepatic metabolism
•CYP3A4 interactions

What is the recommended treatment strategy for a pregnant patient with prolactinoma/hyperprolactinemia

discontinue dopamine agonist therapy as soon as patient discovers they are pregnant

If prolactinoma requires treatment during pregnancy, bromocriptine is preferred.

Describe the monitoring for patients being treated for prolactinoma/hyperprolactinemia

Symptom reduction
•menstrual cycles, sexual function, headache, visual disturbances

Prolactin levels
•3-4 weeks after initiation/ dosage adjustment
•Every 6-12 months with established therapy

Imaging
•may be repeated every 6-12 months

May consider tapering/discontinuation of DA therapy after 2-3 years of normalized prolactin, continued monitoring

Patients with a prolactinoma assigned female at birth are most likely to present with...?

menstral changes

Patients with a prolactinoma assigned male at birth are more likely to present with...?

vision loss
headache
ED

A long-term effect of the suppression of FSH/LH by prolactin is...?

Osteoporosis/decreased BMD