Hyperprolactinaemia Flashcards
(36 cards)
1
Q
Clinical presentation pre vs post menopausal
A
Typical sx occur in premenopausal women and men, but not in postmenopausal women.
2
Q
Clinical presentation pre-menopausal women
A
Causes hypogonadism:
- infertility (48%)
- headache (39%)
- oligomenorrhoea or amenorrhoea (29%)
- galactorrhea less often (24%)
3
Q
Hyperprolactinaemia accounts for what proportion of cases of amenorrhoea (excluding pregnancy)
A
10-20%
4
Q
How does hyperprolactinaemia cause amenorrhoea
A
Inhibition of LH and FSH via inhibition of GnRH
5
Q
Degree of hyperprolactinaemia correlates with sx how?
A
- Prolactin >100ng/mL = overt hypogonadism -> subnormal oestradiol -> amenorrhoea, hot flashes, vaginal dryness
- Moderate, e.g. 50-100ng/mL = amenorrhoea or oligomenorrhoea
- Mild, e.g. 20-50ng/mL, may only cause insufficient progesterone secretion => short luteal phase (may cause infertility even when there is no abnormality of the menstrual cycle = about 20% of those evaluated for infertility)
6
Q
Hyperprolactinaemia and bone density
A
women with amenorrhoea secondary to hyperprolactinaemia have lower bone mineral density. Increases after restoration of menses but may not return to normal.
7
Q
Hyperprolactinaemia in post-menopausal women
A
- are already hypogonadal => sx are absent
- hyperprolactinaemia only recognized when lactotroph adenoma becomes large enough to cause headaches or impair vision, or may be found incidentally on imaging
8
Q
Hyperprolactinaemia in men
A
Also causes hypogonadotropic hypogonadism
- decreased libido, impotence, infertility (4% of men presenting for fertility work up), gynaecomastia, rarely galactorrhea.
- longer term: decreased muscle mass, body hair and osteoporosis
9
Q
Eval of hyperprolactinaemia - aims
A
- Most patients have a lactotroph adenoma => eval is aimed at exclusion of pharmacologic or extrapituitary causes, and neuroradiologic eval of the hypothalamic-pituitary region
10
Q
Hyperprolactinaemia - hx
A
- Pregnancy? (physiologic hyperprolactinaemia)
- Medications (oestrogens, neuroleptic drugs such as resperidone, metoclopramide, antidepressants, cimetidine, methyldopa, verapamil)
- Headache, visual sx, sx of hypothyroidism, hx of renal disease
11
Q
Hyperprolactinaemia - exam
A
Neurological exam with focus on vision field (bitemporal field loss = chiasmal syndrome)
Look for chest wall injury and signs of hypothyroidism or hypogonadism
12
Q
Hyperprolactinaemia - Ix
A
- prolactin
- eval for hypopituitarism
- primary hypothyroidism
- renal insufficiency (reduced clearance of prolactin)
- MRI of pituitary to look for a mass, unless taking a medication known to cause hyperprolactinaemia or marked renal impairment
13
Q
Hyperprolactinaemia indications for rx
A
- Existing or impending neurologic sx due to large size of lactotroph adenoma
- Hypogonadism or other sx such as galactorrhoea
- Infertility (even if mild hyperprolactinaemia and normal cycles may have subtle luteal phase dysfunction)
14
Q
1st line rx
A
Dopamine agonists
- cabergoline 1st line due to efficacy and favourable side-effect profile (less nauseating than Bromocriptine)
- for hyperprolactinaemia of any cause
- including prolactinomas of all sizes because the drug reduces serum prolactin concentrations and decreases the size of most lactotroph adenomas
15
Q
Causes of hyperprolactinaemia:
A
- Reduced dopamine inhibition of prolactin release:
- drugs such as risperidone, metoclopramide, verapamil
- hypothalamic tumour
- head trauma, cranial irradiation, surgery - Increased prolactin production:
- hypothyroidism
- lactotroph adenoma (mico/macro)
- stress
- depression
- PCOS - Reduced prolactin clearance:
- CKD
16
Q
Microadenoma Rx in women wishing to conceive:
A
- Cabergoline (better tolerated than bromocriptine)
- Evaluate for side effects and measure prolactin at 1 month
- If normalized, continue dose. Gonadal function will likely return over a few months.
- If prolactin slightly high but menstruation normalized, continue current dose
- If neither of the above, but no side effects, increase dose gradually
17
Q
Intolerance to dopamine agonists
A
- Can trial alternative (i.e. switch between bromocriptine and cabergoline)
- nausea can be avoided by vaginal administration
18
Q
If all dopamine agonists unsuccessful
A
- transsphenoidal surgery or ovulation induction with clomiphene can be considered for women wishing to become pregnant
- for women not wishing to become pregnant, oestradiol and progesterone replacement can be considered.
19
Q
Follow up after rx of microadenoma
A
- Once normal serum prolactin achieved, should be treated for at least 1 year
- After one year, if prolactin is normal, dose can be decreased
- If prolactin has been normal for two or more years and no adenoma is seen on MRI, discontinuation of the drug can be considered
- Serum prolactin measurements should be obtained at least every 12 months
- Dopamine agonists should be stopped in women who become pregnant
20
Q
Microadenoma - Rx
A
Cabergoline
- If vision was abnormal before therapy, should be reassessed within one month
- MRI should be repeated in 6-12 months to determine if size has decreased
- 6 monthly prolactin measurement if stable
21
Q
Macroadenoma - stopping therapy
A
- if prolactin concentration has been normal for at least 1 year and then adenoma has decreased markedly in size, dose can be decreased gradually
- Discontinuation can be considered if size 1-1.5cm (at initial presentation) and prolactin normal for more than 2 years and whose adenomas can no longer be seen on MRI for > 2 years.
- If initial adenoma >2cm, discontinuation should probably not be considered as the hyperprolactinaemia will probably recur and the adenoma may increase in size
22
Q
Inadequate response/drug intolerance
A
- Trial alternative dopamine agonist
- Transsphenoidal surgery
—> f a significant amount of adenoma tissue remains after surgery, radiation therapy should be administered
23
Q
Role of transsphenoidal surgery
A
- when dopamine agonist rx unsuccessful in lowering the serum prolactin or size of the adenoma, and sx or signs persist after several months of rx at high doses
- or, a woman that has a giant lactotroph adenoma (e.g. >3cm) and wishes to become pregnant even if the adenoma responds to a dopamine agonist.
—> rationale is that if the patient becomes pregnant and discontinues the agonist, the adenoma may increase to a clinically important size before delivery
24
Q
Limitations of transsphenoidal surgery
A
- not all adenoma tissue is excised in many patients, esp those with macroadenomas
- the adenoma and hyperprolactinaemia may recur within several years after surgery
25
complications of radiation (if required as adjunct to surgery for giant lactotroph adenoma)
nausea
lassitude
loss of taste and smell
loss of scalp hair
possible damage to the optic nerve and neurologic dysfunction
50% chance of loss of anterior pituitary hormone secretion during subsequent 10 years
26
Patient counselling before pregnancy
- Discuss options for lowering serum prolactin to normal to restore ovulation
- Counsel re potential risks of treatment during pregnancy to her and the fetus
--> Maternal risk of adenoma growth: depends on size of the adenoma before pregnancy.
---> high levels of oestradiol in pregnancy increase the size of the pituitary by double by the 3rd trimester (in normal pregnancy). Similarly, higher levels of oestradiol in pregnancy may increase the size of the lactotroph adenoma -> may lead to neurological sx and most importantly visual impairment
---> for microadenomas (<10mm diameter) the risk of growth is very low
---> significantly higher for macroadenomas (> 20%)
- Fetal risk of dopamine agonist exposure
---> typically discontinued once pregnancy is confirmed, however by this time pregnancy has usually progressed at least 2 weeks => fetus is exposed.
---> Available evidence suggests that the fetus is not at risk of harm from this exposure (no increase risk of miscarriage or malformations)
27
Counselling before pregnancy in the case of macroadenoma
- higher risk of clinically important enlargement during pregnancy
- once adenoma size has decreased dramatically and is well within the confines of the sella and ovulation has been restored, pregnancy can be attempted
28
when should transsphenoidal surgery be used before an attempted pregnancy?
- If the adenoma elevates the optic chiasm and does not shrink substantially in response to a dopamine agonist --> recommend surgery to reduce size and reduce risk of symptomatic expansion occurring in pregnancy
- if the macroadenoma is unresponsive to a dopamine agonist, even if not elevating the optic chiasm, because the agonist is unlikely to be effective if the adenoma enlarges during pregnancy
- If the macroadenoma is elevating the optic chiasm and causing marked visual impairment
- If the macroadenoma is responsive to dopamine agonist, but in a prior pregnancy became so large that it caused marked visual impairment
29
Carbergoline dose
- Now used as first line as more likely to be tolerated and more effective
- Starting dose = 0.25mg twice/week
- Nocte to reduce the small chance of nausea and orthostatic hypotension
- Increase if the serum prolactin concentration does not normalize after 1-2 months
30
During pregnancy
- Sx:
---> see at routine intervals (3 /12 for microadenomas, may need more frequent for larger macroadenomas) and ask about HA and change in vision + assess visual fields
- Serum prolactin:
---> normal for levels to increase to as high as 400ng/mL => often not useful to measure this
- Pituitary MRI:
---> not required routinely, but if a patient develops severe headaches or visual field abnormalities, pituitary MRI without contrast should be performed to assess adenoma size
31
Rx of enlarging adenoma in pregnancy
If enlarged to a degree to account for HA and/or visual field defect, pt should be treated with a dopamine agonist throughout the remainder of the pregnancy.
---> see at least once/month to reevaluate sx and visual fields
---> if unsuccessful after several weeks and vision is compromised, consider transsphenoidal surgery in the second trimester.
---> In the 3rd trimester, surgery should be deferred until after delivery, if possible
32
Pituitary apoplexy
= Sudden haemorrhage into the pituitary
- Rare event
- Potential serious neuro and endocrine consequences
- Can occur in pts with micro or macroadenomas, during any trimester
- Most dramatic presentation = sudden onset excruciating headache, diplopia due to pressure on the oculomotor nerves, and hypopituitarism
- All pituitary hormonal deficiencies can occur, but the sudden onset of ACTH and therefore cortisol deficiency is the most serious as it can cause life-threatening hypotension
---> Rx high dose hydrocortisone
33
Breastfeeding and dopamine agonists
- Breastfeeding increases serum prolactin concentrations but does not appear to increase the risk of adenoma growth
- Dopamine agonist therapy, which lowers serum prolactin and inhibits lactation, should be witheld until breastfeeding is complete.
- Breastfeeding is contraindicated in women who have visual field impairment because they should be rx with dopamine agonist
34
Normalization of prolactin after pregnancy
- Serum prolactin should be measured 3/12 after delivery in women who do not breastfeed or 3/12 after cessation of breastfeeding
- Recurrence after pregnancy is more likely with macroadenomoas, but both may regress.
35
What % of microadenomas will regress after pregnancy and breastfeeding
>40%
36
