Hyper Prolactin A Emi A
Hyper Prolactin A Emi A
PHYSIOLOGY
Single chain polypeptide
Secreted by lactotrophs of anterior pituitary
Regulated by dopamine (Prolactin inhibitory factor)
Released by hypothalamic stalk
Effects on
Reproduction
Lactation
Metabolism
TYPES
Monomeric 80-90%
Most potent biological form
Dimeric 8-20%
Polymeric 1-5%
Macroprolactin
Antigen-antibody complex of monomeric prolactin and IgG
Biologically inactive
Immunoreactive
Causes 10% of cases of hyperprolactinaemia
Asymptomatic
No associated pituitary pathology
Sriskanthan Srisanjeevan
De Soysa Hospital for Women
HYPERPROLACTINAEMIA
Direct inhibitory effect on hypothalamus
Inhibits LH pulsatility
Anovulation
infertility
Compromise follicular development
Reduce corpus luteal sensitivity to LH
Reduction in progesterone
Significantly high levels of prolactin in antral follicular fluid
Marked reduction in FSH/oestradiol in antral follicular fluid
Severely deficient granulosa cells
Marked reduction in intra-ovarian activity
Directly suppresses progesterone and 17β-oestradiol secretion by ovary
Routine prolactin levels should only be offered to women with
Ovulatory disorders
Galactorrhoea
Pituitary tumours
Galactorrhoea
50% of women with hyperprolactinaemia have galactorrhoea
50% of women with galactorrhoea have hyperprolactinaemia
Sriskanthan Srisanjeevan
De Soysa Hospital for Women
INFERTILITY
Suppression of LH secretion
Reduced frequency/amplitude of pulsatile secretion
Inhibition of ovulation
Manifests as oligomenorrhoea/amenorrhoea
PCOS
Higher prevalence of hyperprolactinaemia and high levels of LH
Chronically opposed oestrogen
Stimulates lactotrophs
Increased secretion of LH
Reduced dopamine production from hypothalamus
Corrected by
Dopamine agonists
Restore ovulation in 90%
Result in pregnancy in 80%
10% of infertile ovulatory women have hyperprolactinaemia
Progesterone levels are lower
ASSESSMENT
Medication history
Clinical evaluation
To exclude physiological/secondary causes of hyperprolactinaemia
Symptoms
Subfertility
Amenorrhoea
Galactorrhoea
Frontal headache
Visual field defects Discriminatory during pregnancy
Diabetes insipidus
Repeat testing for confirmation of raised levels
Assessment for macroprolactin
Watch for “hook” effect
Prolactin measured in undiluted/diluted serum
Important to differentiate between adenoma/disconnection hyperprolactinaemia
Facilitate planning for appropriate therapy
TSH levels
Low TSH levels in hyperprolactinaemia
Direct stimulation of lactotrophs by TRH
Visual field testing
Sriskanthan Srisanjeevan
De Soysa Hospital for Women
Check for symptoms of mass expansion
Pituitary imaging
Magnetic resonance imaging
Investigation of choice for assessing for pituitary adenomas
PROLACTINOMA
Commonest pituitary tumours encountered in pregnancy
Rarely cause problems
Types
<10mm Micro prolactinoma
>10mm Macro prolactinoma
MANAGEMENT
Aims
Treat effects of hyperprolactinaemia
Anovulation
Infertility
Reduced bone mineral density
Galactorrhoea
Treat mass effects of prolactinoma
Headaches
Cranial nerve defects
Hypopituitarism
Visual field defects
Due to pressure on optic chiasma
Options
Medical
Surgical
Radiotherapy
MEDICAL THERAPY
Dopamine agonists
1st line for both micro/macro prolactinomas
Sriskanthan Srisanjeevan
De Soysa Hospital for Women
Nausea (causation by ergot
profile than
Vomiting feature via 5-HT
bromocriptine
Postural hypotension receptor)
6 monthly
Follow-up - -
echocardiography
Compliance Greater compliance
No increase in adverse Limited safety data
Pregnancy Safe
outcomes No teratogenic effects
Breastfeeding Safe Safe
SURGERY
Indications
Failure of medical therapy
Expanding prolactinomas with progressive neurological/ophthalmological defects not
responding to medical therapy
Pituitary apoplexy
Life threatening condition
Due to infarction/haemorrhage into prolactinoma
Results in
Sudden visual disturbance
Severe headache
Vascular collapse
Altered consciousness
Approach
Trans-sphenoidal
Craniotomy
Rarely performed
Reserved for tumours inaccessible via trans-sphenoidal route
Successful in controlling
75% of micro prolactinomas
35% of macro prolactinomas
RADIOTHERAPY
Restricted to those resistant to medical and surgical therapy
Adverse effects
Hypopituitarism (70%)
Radiation necrosis of adjacent brain tissue (<1%)
Cranial neuropathy (1%)
Damage to optic apparatus
PREGNANCY
Treatment depends on
Size of prolactinoma
Clinical presentation
Medical treatment preferred to surgical where possible
Control with medical therapy possible in
Sriskanthan Srisanjeevan
De Soysa Hospital for Women
Micro prolactinomas
Macro prolactinomas with no supracellar extension
Serum prolactin
Unreliable
Checked 2 months after cessation of breastfeeding
First line
Bromocriptine
MRI
If symptoms of mass expansion present
Visual field defects
Microadenoma Macroadenoma
Size <10mm >10mm
Clinically significant High (30-25%)
Low (2-3%)
enlargement during pregnancy Highest in 3rd trimester
Failure with dopamine agonists
Treatment Medical therapy
Require surgical decompression
Medical therapy Stopped in early pregnancy Throughout pregnancy
Following surgery
Foetal risks Minimum 1.5x risk of foetal loss in 1st trimester
5x risk of foetal loss in 2nd trimester
POSTPARTUM
Persistent milk secretion even after cessation of breastfeeding
May have to continue dopamine agonist therapy
40% of women will achieve remission
Rate of remission
46% for micro prolactinomas
26% for macro prolactinomas
Sriskanthan Srisanjeevan
De Soysa Hospital for Women