Lactation, Galactorrhoea, Prolactinomas Flashcards

1
Q

Breast Development in Puberty

  • both … and … stimulate the development
  • Effects of … hormone via …-1
    • develop … buds
    • develop …
A
  • oestrogen, progesterone stimulate the development
  • Effects of Growth hormone via IGF-1
    • develop alveolar buds
    • develop lobules
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2
Q

Breast Development in Pregnancy

  • both … and … stimulate the development
  • Also produced from the placenta in 1st trimester of pregnancy as well as pro…
  • There is …. development
    • increased … and lobules
  • differentiated … unitis (acini)
  • … accumulates
A
  • both oestrogen and progesterone stimulate the development
  • Also HCG produced from the placenta in 1st trimester of pregnancy as well as prolactin
  • There is alveolar development
    • increased ducts and lobules
  • differentiated secretory unitis (acini)
  • colostrum accumulates
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3
Q

Milk Production is known as what?

A

Lactogenesis

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4
Q

Milk production - lactogenesis

  1. Secretory initiation
  • … hormone helps regulate
  • occurs during …
  • colostrum
  1. Secretory activation
  • decreased … and … levels
  • increased levels of … (also cortisol, insulin)
  • copius milk production after delivery (usually … days post-partum)
A

Milk production - lactogenesis

  1. Secretory initiation
  • Progesterone hormone helps regulate
  • occurs during pregnancy
  • colostrum
  1. Secretory activation
  • decreased progesterone and oestrogen levels
  • increased levels of prolactin (also cortisol, insulin)
  • copius milk production after delivery (usually 2-3 days post-partum)
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5
Q

Milk Composition (interest only - not for reproduction)

  • sugar
    • lactose and oligosaccharides
  • milk facts
    • triglycerides, cholesterol, phospholipids, steroid hormones
  • proteins
    • casseins, 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)
A
  • sugar
    • lactose and oligosaccharides
  • milk facts
    • triglycerides, cholesterol, phospholipids, steroid hormones
  • proteins
    • casseins, 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)
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6
Q
  • What feedback mechanism is lactation?
  • What is it triggered by?
A
  • positive feedback loop mechanism
  • triggered by the regular removal of milk and nipple stimulation
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7
Q

What 2 hormones regulate lactation?

A
  • prolactin (anterior pituitary)
  • oxytocin (posterior pituitary)
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8
Q
  • Where is prolactin released from?
  • What inhibits it’s release? (1)
  • What stimulates it’s release? (3)
A
  • Released from anterior pituitary
  • release inhibited by dopamine
  • release stimulated by 5HT(Serotonin), TRH, oxytocin
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9
Q

What is this diagram representing?

A

Prolactin secretion/inhibition

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10
Q

What does this graph represent an increase of?

A

prolactin in pregnancy

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11
Q

What does this graph represent?

A

Prolactin levels and suckling

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12
Q

What happens to prolactin levels? (1) pregancy, 2) post-partum, 3) baby developing - breastfeeding established)

A
  • increasing during pregnancy
  • high post-partum (increased by suckling)
  • levels relatively low once breast-feeding is established (80 days postpartum)
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13
Q
  • Lactational amenorrhoea refers to what?
  • Contraceptive efficacy depends on what?
A
  • The time period when a women is breast-feeding and her periods do not resume
  • contraceptive efficancy depends on the frequency and duration of breast feeding
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14
Q
  • Increased prolactin levels have a supressive effect on all levels of what axis?
  • What hormone levels decrease? (4)
A
  • gonodal axis
  • decreased LH and FSH productiona and pulsatility, decrease oestrogen and testosterone
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15
Q

Oxytocin is a … amino acid peptide

A
  • Oxytocin is a nine amino acid peptide
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16
Q

Oxytocin is synthesised in hypothalamic … neurons which reside in the ….

  • S… nucleus
  • P… nucleus
A

Oxytocin is synthesised in hypothalamic magnicellular neurons which reside in the ….

  • supraoptic nucleus
  • paraventricular nucleus
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17
Q

After oxytocin is synthesised, neurosecretory granules are released into the capillary system of the … …

This is where oxytocin is released from

A

posterior pituitary - where the distal axons of hypothalamic magnocellular neurons reside

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18
Q

Regulation of oxytocin production

  • Afferent signal from receptors in the nipple when the infant … ascend to …
    • uterine myometrial … at birth
    • … … activation in breast - ‘myoepithelial contraction’
    • … let-down

role in … behaviour?

A
  • Afferent signal from receptors in the nipple when the infant suckles ascend to hypothalamus
    • uterine myometrial contraction at birth
    • smooth muscle activation in breast - myoepithelial contraction
    • milk let-down

role in maternal behaviour?

19
Q

Evolutionary perspective of lactation

  • Mammals lactate
    • … strategy involves producing a nutritious secretion from an exocrine gland & encouraging offspring to consume it
    • continued nurturing of offspring … birth with benefits including enhanced … development
  • Strategies for success:
    • milk …
    • complementary changes in the mother’s … - metabolic and psycho-social/ behavioural
    • same …
A
  • Mammals lactate
    • 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
  • Strategies for success:
    • milk production
    • complementary changes in the mother’s brain - metabolic and psycho-social/ behavioural
    • same hormones
20
Q

Discovering pregnancy

  • humans - take a …
  • other mammals - brain responds to … changes associated with ovulation, mating, implantation and pregnancy - via … & placental …
A
  • humans - pregnancy test
  • other mammals - brain responds to hormonal changes associated with ovulation, mating, implantation and pregnancy - via prolactin & placental lactogens
21
Q

What is hyperprolactinaemia?

A

The presence of abnormally high levels of prolactin in the blood (unrelated to pregancy and breastfeeding)

22
Q

Presentation of Hyperprolactinaemia - Women

  • What is the typical triad?
A
  • oligo / amenorrhoea leading to an increased risk of osteoporosis
  • galactorrhoea
  • subfertility

They may not have all of these - may present after stopping contraceptive pill - coincidental

23
Q

Presentation of Hyperprolactinaemia - Men

  • low testosterone levels may cause 2 things, what are they?
  • is presentation earlier or later than women?
  • what other 3 symptoms present?
  • What is a rare presentation?
A
  • low testosterone levels may cause erectile dysfunction or loss of libido
  • presentation is later than women
  • visual symptoms, headaches, hypopituitarism
  • rare - galactorrhoea/gynaecomastia
24
Q

Causes of Hyperprolactinaemia

  • physiological causes include … and …
  • what disease can cause it?
  • drugs
  • stress
  • other causes include P.., renal .., or hypo….
A
  • physiological causes include pregnancy and lactation
  • what disease can cause it - hypothalamic-pituitary disease (non-functioning adenoma, micro/macroprolactinoma)
  • drugs
  • stress
  • other causes include PCOS, renal failure / cirrhosis or hypothyroidism (increased TRH)
25
Q

Drugs that increase prolactin

  • Drugs used for n… and
  • Anti… and Anti…
A
  • Drugs used for nausea and vertigo (phenothiazines, metoclopramide, domperidone)
  • Antipsychotics and Antidepressants
  • also others
26
Q

nausea and vertigo drugs (phenothiazines, metoclopramide, domperidone) and antidepressants/antipsychotics can increase what?

A

prolactin

27
Q
A
28
Q

Mechanisms of drugs that increase prolactin

  • inhibiton of secretion/action of … (… antagonists or receptor blockers)
  • stimulation of … … pathways (… re-uptake inhibitors)
A
  • inhibiton of secretion/action of dopamine - DA antagonists or DA receptor blockers
  • stimulation of central serotonin (5HT) pathways - 5HT re-uptake inhibitors
29
Q

Investigations in hyperprolactinaemia

  • … test
  • Renal … (including ..&.. and c….)
  • Liver function tests
  • .. function
  • … - repeat
  • Hormones - … and …
  • In men, test … levels
  • after this - imaging - … of pituitary (micro if what size? macro if what size?)
  • If they have a … - test visual fields and rest of anterior pituitary function tests
A
  • pregnancy test
  • Renal function (including U&E & Creatinine)
  • Liver function tests
  • .. function
  • … - repeat
  • Hormones - … and …
  • In men, test … levels
  • MRI of pituitary (micro if what size - <1cm macro if what size > 1cm)
  • Macroadenoma - visual fields, rest of anterior pituitary function tests
30
Q

Aims of treatment - prolactinoma

  • restore …
  • stop … - also stop stimulation of …
  • restore regular … - women / … mostly in men (can use exogenous oestrogen and testosterone - needed for protection of …)
  • shrink the … (if macro) to help recover function of … and restore their …
A
  • restore fertility
  • stop galactorrhoea - stop nipple stimulation
  • restore regular menstrual periods, libido - men mainly (Can use exogenous oestrogen/testosterone - both are needed for bone protection)
  • shrink the tumour if macro - restore vision and recover function of anterior pituitary
31
Q

Prolactinoma management ‘medical’

  • … drugs - such as cabergoline, bromocriptine
  • preserve … function
  • side-effects -which are rare: … reactions (pulmonary, pericardial, retroperitoneal), … disturbances
A
  • dopaminergic drugs - such as cabergoline, bromocriptine
  • preserve pituitary function
  • side-effects -which are rare: fibrotic reactions (pulmonary, pericardial, retroperitoneal), psychiatric disturbances
32
Q

Microprolactinoma management

  • can take … if fertility not required
  • can discontinue treatment in …
  • may … post-partum
  • can trial withdrawal of treatment after approximately … years - may not recur
A
  • can take oral contraceptive if fertility not required
  • can discontinue treatment in pregnancy
  • may involute post-partum
  • can trial withdrawal of treatment after approximately 2 years - may not recur
33
Q

What is idiopathic hyperprolactinaemia?

A

assumed to be microprolactinoma too small to be detected radiologically

34
Q

Non-functioning pituitary adenoma - can cause high …

  • compression of the pituitary … - leading to d… hyperprolactinaemia, may also occur with masses
  • may need surgery and … - space-occupying effects, risk loss of …
  • prolactin will decrease with what drugs?
  • do we need to monitor it? if so, how?
A
  • compression of the pituitary stalk - leading to disconnection hyperprolactinaemia - may also occur with hypothalamic masses
  • may need surgery and radiotherapy - space occupying effects - risk loss of pituitary function
  • prolactin will decrease with what drugs - dopaminergic drugs
  • do we need to monitor it - yes - MRI scan and visual fields
35
Q

Case study : 63 year old women, abnormal CT head scan

What prolactinoma does she have?

A

Macroprolactinoma - visual field affected greatly - compression on optic chiasm

36
Q

Case study : 63 year old women, abnormal CT head scan

  • Is she hypothyroid, euthyroid, hyperthyroid?
  • TSH is normal - what does this tell us? (diagnosis?)
  • LH and FSH, what do these tell us?
A
  • Free T4 is low - hypothyroid (level is 7.1)
  • TSH normal - tells us that the patient does not have primary hypothyroidism - if it was, TSH would be very high - therefore pituitary problem (secondary hypothyroidism)
  • LH and FH low - usually high due to ovarian failure - not high = pituitary problem
37
Q

What are abnormal cortisol levels a sign of? (In which axis is there a problem)?

A

problem with hypothalamic pituitary adrenal axis

38
Q

What would have happened to prolactin levels between these MRI scans?

A

decreased

39
Q
  • Are her prolactin levels elevated?
  • TSH normal? FT4 normal?
  • LH and FSH ?
  • Testo - ? SHBG - ?
  • - taking oral contraceptive pill….
  • What is her diagnosis?
A
  • prolactin - Yes - upper limit of normal is around 500
  • TSH and FT4 normal
  • LH and FSH - suppressed
  • Testo - normal SHBG - very high
  • as she is taking pill - LH and FSH is low - not pituitary failure - oestrogen treatment suppresses these hormones
40
Q

If fertility isnt relevant after diagnosis of a microprolactinoma, can the pill be continued?

A

yes - avoid nipple stimulation, but may require cabergoline to conceive - also discontinue if fall pregnant

41
Q

Beth - 8 months of secondary amenorrhoea

  • negative pregancy tests
  • no regular medication
  • no PM Hx/ Family Hx of note
  • would like children but not yet
  • What is her possible diagnosis?
A
  • prolactin moderately elevated (upper limit 500)
  • LH and FSH normal
  • TSH normal FT4 normal
  • scan shows non-functioning pituitary adenoma - stalk compressing optic chiasm - increases the prolactin level - not a macro, cells not making prolactin - it is non functioning - just being compressed
42
Q

non-functioning pituitary adenoma - what treatment?

A
  • transphenoidal hypophysectomy - risk to vision with further growth
  • there is a risk to pituitary function - including future fertility prospects - would be amendable to treatment
43
Q

​Carol - 48

  • Galactorrhoea
  • regular 4-week menstrual cycle
  • long Hx of depression and anxiety, meds include risperidone, trazodone, duloxetine (antipsychotic and antidepressant)
  • is her prolactin raised? LH/FSH? TSH? FT4?
  • whats the diagnosis?
A
  • prolactin sustained and elevated
  • FSH and LH - levels normal for her age
  • TSH and FT4 - normal
  • pituitary - normal structure
  • result = medication-induced hyperprolactinaemia