Lacatation and prolactinomas Flashcards
What are the evolutionary benefits of mammals lactating
- Reproductive strategy involves producing a nutritious secretion from an exocrine gland & encouraging offspring to consume it
- Continued nurturing of offspring after birth with benefits including enhanced brain development
- Complementary changed in the mothers brain (metabolic, psycho-social/behavioural)
In other mammals how is oxytocin important?
Brain responds to hormonal changes associated with ovulation, mating, implantation & pregnancy
via prolactin & placental lactogens
What are the aims of treatment for hyperprolactinaemia?
- Restore fertility
- Stop galactorrhoea
- Also stop nipple stimulation / ‘checking’ (oxytocin)
- Restore regular menstrual periods / libido
- Oestrogen / testosteone needed for bone protection
(Can use exogenous oestrogen / testosterone (contraceptive pill / HRT / testosterone)) - Shrink tumour (macroadenoma)
- Recovery of anterior pituitary function
- Restore vision
What changes occur in breast development in puberty?
Oestrogen and progesterone
GH (via IGF-1) increase alverolar buds and lobules
What changes occur in breast development in pregnancy?
Oestrogen and progesterone
hCG, Prolactin
Alveolar develpment involved increase in ducts and lobules; differentiated secretory units and colostrum accumulates
Consider lactogenesis
When and how is secretion initiated?
When and how is secretion activated?
Progesterone causes intiation during pregnancy. Colostrum formation
Decrease in progesterone and oestrogen. Increase in prolactin (cortisol, insulin)
Milk production 2-3 days post partum.
State the components of breast milk and give an example
Sugar (oligosaccharides, lactose)
Fat (TG, cholesterol, phospholipid, steroid hormone)
Protein (Caseins, lactalbumin,secretory IgA, lysozyme)
Minerals (Na, K, Ca, Mg, Cl, Phosphate)
Growth factors
Cellular components (especially in colostrum) - Macrophages, lymphocytes, neutrophils, epithelial cells, membrane fragments
Galactopoiesis relies on…
It results in…
Positive feedback loops
Nipple stimulation
Prolactin (from adenohypophysis)
Oxytocin (from neurohypophysis)
regular removal of milk
Where is prolactin produced?
Which factors inhibit and stimulate its release?
What hormone is it similar to?
What receptor is it similar to?
Lactotrophe cells in adenohypophysis.
Serotonin, TRH and oxytocin cause release.
Dopamine inhibits release
Similar to GH
Receptor similar to GH (Tyrosine phosphorylation, JAK-STAT signalling)
What is lactational amenorrhoea and how does it come about?
A state of reduced fertility such that it actually acts as an efficient contraception.It depends on frequency and duration of breast feeding
Increased prolactin leads to
- Reduces GnRH –> Reduced LH and FSH, pulsatility –> oestrogen/progesterone
Describe oxytocin
Include:
- Synthesis
- Secretion
- Function
It is a nonpeptide synthesised in the supraoptic and paraventricular nucleus of the hypothalamus.
It is secreted from the neurohypophysis in response to nipple stimulation (e.g. infant suckling)
Stimulates
- uterine myometrial contraction at birth
- smooth muscle activation in breast (myoepithelial contraction)
- milk let-down
May play a role in maternal behaviour
How do mammals know when theyre pregnant?
Humans - pregnancy tests
Other mammals - brain responds to hormonal changes associated with ovulation, mating, implantation and pregnancy via prolactin and placental lactogens
How does the maternal brain adapt to pregnancy?
And the rest of the body?
- Adult neurogenesis
- Reduced anxiety
- Suppressed stress responses
- Increased appetite and fat deposition
- Breast development
- Altered glucose metabolism
- Placenta development
How does hyperprolactinaemia present in women?
- Oligo/amenorrhoea (increased risk of osteoporosis)
- Galactorrhoea
- Subfertility
- Asymptomatic
- Contraceptive pill may hide symptoms
How does hyperprolactinaemia present in men?
- Erectile dysfunction
- Decreased libido
- Visual symptoms
- Headaches
- Hypopituitarism
- Galactorrhoea/gynaecomastia (RARE)
LATE PRESENTATION
What are the causes of hyperprolactinaemia?
- Physiological (pregnancy, lactation)
- Hypothalamic disease (micro/macroPRLoma, non-functional adenoma)
- Drugs
- Stress
- PCOS
- Hypothyroidism (High TRH)
- Renal failure, cirrhosis
Whta drugs increase [Prolactin]?
MOA?
- Antidepressants and antipsychotics
- Drugs used for nausea and vertigo (Phenothiazines, metoclopramide, domperidone)
MOA
- Inhibiton of secretion/action of dopamine
- Stimulaiton of central serotonin pathways (SSRIs)
What investigations would you in suspected hyperprolactinaemia?
How would you differentiate betweena micro and macro PRLoma?
Diagnosis of a macroadenoma?
- Pregnancy test
- Renal function (U&E
- Liver function tests
- Thyroid function
- Repeat prolactin
- LH/FSH
- Testosterone (men)
Micro <1cm
- Visual fields
- Anterior pituitary function tests
How would you ‘medically’ manage a PRLoma?
Side effects:
- Dopaminergic drugs (Cabergoline, Bromocriptine)
- Preserve pituitary function
(RARE)
- Fibrotic reactions (pulonary, pericardial, retroperitoneal)
- Psychiatric distrubances
How does managenement of a microPRLoma differe from idiopathic hyperPRLaemia?
Micro-
- Can take COCP/HRT if fertility is not required
- Discontinue treatment in pregnancy
Idiopathic hyperPRLaemia is assumed to be a microPRLoma too small for radiological detection.
How would you manage a non-functioning pituitary adenoma?
- Compression of pituitary stalk
- Surgery and radiotherapy (to relieve space-occupying effects, risk of pituitary function) e.g. transphenoidal hypophysectomy
- [Prolactin] will decrease with dopaminergic drugs (monitor using MRI and visual field tests)
What can you advise patients presenting with galactorrhoea?
Avoid nipple stimulation
