Hyperprolactinaemia

Question 1

What are the causes of hyperprolactinaemia?

Answer 1

Physiologic:

• Breastfeeding
• Pregnancy
• Stress

Lactotroph adenomas of pituitary:

• Macroadenoma
• Microadenoma

Decreased dopaminergic inhibition of PRL secretion:

• Drugs/dopamine antagonists: haloperidol, respiradone, metoclopramide, domperidone, methyldopa
• Injury to dopamingeric neurons of hypothalamus and pituitary: hypothalamic tumours, sarcoidosis, head injury or surgery, other pituitary adenomas.

Decreased renal clearance of PRL: chronic kidney disease

Question 2

Describe the pathophysiology of how hyperprolactinaemia causes infertility:

Answer 2

Excess PRL causes negative feedback inhibition of GnRH secretion from hypothalamus and thus decreased FSH and LH secretion.

Mild: insufficiency progesterone and shortened luteal phase.
Moderate: oligo- or amenorrhoea.
Severe: overt hypo-gonadism and hypo-estrogenism (hot flushes, vaginal dryness, amenorrhoea)

Question 3

What is the possible clinical presentations of hyperprolactinaemia?

Answer 3

• Oligo- and amenorrhoea.
• Galactorrhoea
• Infertility
• May have: headache, visual disturbance, loss of bitemporal visual fields

Question 4

You suspect a premenopausal woman has hyperprolactinaemia.

Outline the investigations you would order in your work-up:

Answer 4

• Pregnancy test to exclude pregnancy.
• Prolactin level: >30 ng/mL abnormal.
• TSH level: to exclude hypothyroidism.
• Renal function tests: to exclude CKD.
• MRI head to look for pituitary tumour.
• If pituitary tumour, assess for other pituitary hormones: IGF-1, ACTH, FSH and LH.

Question 5

Outline the first-line treatment option for hyperprolactinaemia including:

• Mechanism of action
• Drug names / doses
• Side-effects
• Follow-up plan

Answer 5

First-line tx: dopamine agonist

Mechanism of action: dopamine binds lactotroph receptors in anterior pituitary, and decreases PRL secretion and decreases lactotroph adenoma size.

Drug names/doses:

• Cabergoline 0.25 mg twice WEEKLY or 0.5 mg once weekly. Less nausea.
• Bromocriptine

Side-effects:

• Nausea
• Postural hypotension
• Mental fogginess

Follow-up:

• Review and check PRL level after 1 month: same dose if normal PRL level or have ovulated.
• Check PRL level every 12 months.
• DA should continue for 1 year.
• If after 2 years PRL remains normal or no adenoma on MRI can consider stopping DA.

Question 6

How would you manage a woman with hyperprolactinaemia wanting to become pregnant?

Answer 6

• Fertility: transphenoid surgery to remove adenoma or ovulation induction with clomiphene or gonadotrophin therapy.
• Stop dopamine agonist when she becomes pregnant; limited safety data but no known adverse effects.

Question 7

What is pituitary apoplexy?
What symptoms are associated with it?
What complications arise from it

Answer 7

Sudden haemorrhage into the pituitary.

Associated with severe headache, diplopia.

Complications: hypopituitarism and hypotensive crises secondary to ACTH and cortisol deficiency.