Lactation and Prolactinomas Flashcards
1
Q
Go over the key phases of breast development
A
Puberty
- oestrogen and progesterone are active
- GH (via IGF-I) act to increase
- increase alveolar buds
- increase no. of lobules
Pregnancy
- Oestrogen and progesterone are the main hormones
- hCG and prolactin are also active
- increase alveolar development
- increasing number of ducts and lobules
- differentiated secretory units (acini) form
- colostrum accumulates
2
Q
What is the stimulatory process of lactogenesis?
A
- Secretory initiation
- increased progesterone
- occurs during pregnancy
- presence of colostrum
- Secretory activation
- decrease in progesterone/ oestrogen
- increase in prolactin (and cortisol, insulin)
- after parturition copious milk production
- usually 2-3 days post-partum
3
Q
What is the composition of Milk?
A
- Sugar
- Lactose & oligosaccharides
- Milk fats
- triglycerides, cholesterol, phospholipids, steroid hormones
- Proteins
- Caseins, lactalbumin, lactoferrin, secretory IgA, lysozyme
- Minerals
- Na, K, Cl, Ca, Mg, Phosphate
- Growth factors
- Cellular components (esp in colostrum)
- Macrophages, lymphocytes, neutrophils, epithelial cells
- Phospholipids (membrane fragments)
4
Q
Give an overview of the controls of lactation
A
- positive feedback loop mechanism initiated by nipple stimulation
- Prolactin from the anterior pituitary and
- Oxytocin from the posterior pituitary stimulate this process
- there is regular removal of milk
5
Q
What is the action of Prolactin?
A
- produced in lactotroph cells in the anterior pituitary
- similar to GH with a similar receptor to GH
- results in tyrosine phosphorylation
- stimulants JAK-STAT signalling
- Release stimulated by
- 5-HT (serotonin)
- TRH (thyrotropin-releasing hormone),
- Oxytocin
- Release inhibited by
- DA
- both stimulation and inhibition is from the hypothalamus acting on the pituitary gland
6
Q
What is the effect of lactation?
A
- Lactational amenorrhoea
- frequency and duration of breastfeeding dictates the efficacy of the contraceptive efficacy
- this is because increased serum prolactin leads to
- decreased GnRH (gonadtrophin-releasing hormone)
- decreased LH and FSH, decreased pulsatility (no menstrual cycle)
- decreased oestrogen/ testosterone
7
Q
What is Oxytocin and what is its action?
- synthesis also
A
- a nonapeptide synthesised in hypothalamic magnicellular neurons
- Supraoptic nucleus
- Paraventricular nucleus
- released into the posterior pituitary via distal axon terminals of the hypothalamic magnocellular neurons
- Neurosecretory granules released into the capillary system of the posterior pituitary
- afferent signals ascend from nipple receptors to the hypothalamus when the infant suckles
- Oxytocin causes
- increased uterine myometrial contraction at birth
- increased smooth muscle activation in breast
- increased mil let-down
- ?potential role in maternal behavior?
8
Q
How does pregnancy cause adaptation in the maternal brain?
A
- placental lactogen acts on the maternal brain
- maternal prolactin from the pituitary feedback to the maternal brain
9
Q
What is Hyperprolactinaemia and what are its presentations?
in women
A
- High serum prolactin
- oligo / amenorrhoea
- increased risk of osteoporosis
- galactorrhoea
- subfertility
- May not have all these symptoms
- May present after stopping contraceptive pill
- coincidental
10
Q
What are the presentations Hyperprolactinaemia in men?
A
- Erectile dysfunction
- decreased libido
- visual symptoms
- headaches
- hypopituitarism
- Present later
- Galactorrhoea/gynaecomastia RARE
11
Q
What are causes of Hyperprolactinaemia?
A
- Physiological
- Pregnancy
- Lactation
- Hypothalamic-pituitary disease
- Micro / macroPRLoma
- Non-functioning adenoma
- Drugs
- Stress
- Other
- Polycystic ovarian syndrome
- Hypothyroidism (TRH)
- Renal failure, cirrhosis
12
Q
What are the controls of Prolactin?
A
- Release stimulated by
- 5-HT - serotonin
- TRH - Thyrotrophin releasing hormone
- Oxytocin
- Release inhibited by
- DA
stimulated and inhibited by hormones released from the hypothalamus exerting an effect on the pituitary gland
13
Q
What drugs and mechanisms increase Prolactin?
A
- Antidepressants and antipsychotics
- Anti-nausea and vertigo drugs
- Phenothiazines
- Metoclopramide
- Domperidone
- Mechanism of action
- Inhibition of secretion/ action of DA
- DA antagonist or Da receptor blockers
- stimulation of central 5HT pathways
- 5HT re-uptake inhibitors
- Inhibition of secretion/ action of DA
14
Q
What investigation should be carried out if hyperprolactinaemia is suspected?
A
- Pregnancy test
- Renal function
- U&E, creatinine
- Liver function tests
- Thyroid function
- Prolactin (repeat)
- LH, FSH
- Testosterone (men)
- MRI pituitary
- Micro < 1 cm diameter
- Macro > 1 cm diameter
- Macroadenoma
- Visual fields
- Rest of anterior pituitary function tests
15
Q
What are the aims of treatment for hyperprolactinaemia?
A
- 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
