Lactation and Prolactinomas

Question 1

Go over the key phases of breast development

Answer 1

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

Question 2

What is the stimulatory process of lactogenesis?

Answer 2

• 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

Question 3

What is the composition of Milk?

Answer 3

• 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)

Question 4

Give an overview of the controls of lactation

Answer 4

• 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

Question 5

What is the action of Prolactin?

Answer 5

• 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

Question 6

What is the effect of lactation?

Answer 6

• 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

Question 7

What is Oxytocin and what is its action?

• synthesis also

Answer 7

• 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?

Question 8

How does pregnancy cause adaptation in the maternal brain?

Answer 8

• placental lactogen acts on the maternal brain
• maternal prolactin from the pituitary feedback to the maternal brain

Question 9

What is Hyperprolactinaemia and what are its presentations?

in women

Answer 9

• High serum prolactin
• oligo / amenorrhoea
  
  • increased­ risk of osteoporosis
• galactorrhoea
• subfertility
• May not have all these symptoms
• May present after stopping contraceptive pill
  
  • coincidental

Question 10

What are the presentations Hyperprolactinaemia in men?

Answer 10

• Erectile dysfunction
  
  • decreased libido
• visual symptoms
• headaches
• hypopituitarism
• Present later
• Galactorrhoea/gynaecomastia RARE

Question 11

What are causes of Hyperprolactinaemia?

Answer 11

• Physiological
  
  • Pregnancy
  • Lactation
• Hypothalamic-pituitary disease
  
  • Micro / macroPRLoma
  • Non-functioning adenoma
• Drugs
• Stress
• Other
  
  • Polycystic ovarian syndrome
  • Hypothyroidism (­TRH)
  • Renal failure, cirrhosis

Question 12

What are the controls of Prolactin?

Answer 12

• 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

Question 13

What drugs and mechanisms increase Prolactin?

Answer 13

• 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

Question 14

What investigation should be carried out if hyperprolactinaemia is suspected?

Answer 14

• 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

Question 15

What are the aims of treatment for hyperprolactinaemia?

Answer 15

• 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

Question 16

What is the management for PRLoma?

Answer 16

• ‘MEDICAL’ line of action
• Dopaminergic drugs
  
  • Cabergoline
  • (Bromocriptine)
• these Preserve pituitary function with some Side-effects
  
  • RARE: Fibrotic reactions, Pulmonary, pericardial, retroperitoneal, Psychiatric disturbances
• for MicroPRLomas
  
  • can take COCP/HRT if fertility isn’t needed
    
    • treatment can be discontinued in pregnancy
    • may reoccur post-partum- can trial withdrawal of treatment after approx 2 yrs

Question 17

What is the effect of a Non-Functioning Pituitary Adenoma (NFA)

• what management should be carried out?

Answer 17

• Compression of the pituitary stalk
  
  • ‘Disconnection hyperPRLaemia’
  • May also occur with hypothalamic masses
• May need surgery & radiotherapy
  
  • space-occupying effects
  • risk loss of pituitary function
• [prolactin] will decrease with dopaminergic drugs
  
  • Need to monitor MRI scan & visual fields