LECTURE - Prolactin & GH Testing Flashcards

1
Q

target tissue of prolactin

A

mammary glands

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2
Q

major stimulus for PRL pathway

A

suckling

- also estrogen and stress (severe illness and traumatic experience)

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3
Q

_______ is inhibitory to the release of prolactin

A

dopamine (brake that is always ON; unless there is a strong positive stimulus)
= if prolactin is released = brake is released

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4
Q

made by lactotroph cells in the anterior pituitary

A

prolactin

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5
Q

several forms of prolactin in circulation

A
  • little = monomer (23 kDa)
  • big = dimeric
  • big-big (macro) = polymeric and/or attach immunoglobulin
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6
Q

functions of prolactin

A
  • pregnancy and lactation (breast milk production and secretion)
  • uterine smooth muscle contraction
  • reproduction (Sex hormone synthesis and fertility)
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7
Q

diagnosis of hyperprolactinemia

A
  • increased prolactin conctn detected in serum: immunoassay methods
  • screen hyperprolactinemic samples for macroprolactin
  • magnetic resonance imaging (MRI) scan for tumors
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8
Q

prolactin is a _________ hormone

A

peptide

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9
Q

T or F. Prolactin is under negative regulation by the hypothalamus!

A

T

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10
Q

this can be a source of falsely elevated serum prolactin

A

macroprolactin (clumped molecules)

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11
Q

target tissue of growth hormones

A

entire body

from somatotroph

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12
Q

these are produced and secreted by somatotrophic cells of the anterior pituitary gland

A

GH

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13
Q

major functions of GH

A
  • tissue and bone growth
  • response to stress
  • modulates fat/carbohydrate/protein metabolism and body composition
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14
Q

made primarily by liver in response to GH

A

insulin-like growth factor (IGF-1)

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15
Q

IGF-1

A
  • mediates indirect growth and fat metabolism effects of GH
  • protein binding increases half-life in circulation
  • fairly steady conctn throughout the day (good marker of GH status)
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16
Q

lactotrophs

A

in anterior pituitary = PRL

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17
Q

hyperprolactinemia causes

A
  • physiological = pregnancy, breast feeding, stress, etc.
  • pituitary tumour = increase PRL is a marker for adenoma
  • damage to hypothalamic pituitary dopamine path (brake not working)
  • primary hypothyroidism (increased TRH) = spillage; pituitary works overtime and thus PRL increases as well
  • macroprolactin
  • medications, renal failure, liver disease
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18
Q

T or F. macroprolactin is not related to a clinical condition

A

T!

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19
Q

clinical presentation of hyperprolactinemia

A
  • galactorrhea
  • hypogonadism + infertility
  • low sex drive
  • headaches and visual probs
  • females = menstrual dysfunction, vaginal dryness
  • males = ED, decreased body hair and muscle mass, delayed puberty
20
Q

what is macroprolactin?

A
  • multimeric PRL complex
  • delayed clearance = increased levels = more likely to clump
  • less/minimal biological activity than monomeric PRL
  • detected variably by many PRL immunoassays
  • seen in 10-45% of hyperprolactinemia cases
  • may lead to delayed diagnosis or misdiagnosis
21
Q

how to identify macroprolactin

A
  • gel filtration (size exclusion) chromatography
  • polyethylene glycol (PEG) precipitation **
  • obtain results from more than 1 immunoassay

PEG clears most of macroprl - re-run test - see if PRL still elevated = then true elevation

22
Q

what effects do dopamine-receptor antagonists have on the H-P axis?

A

increase proalctin secretion

23
Q

GH distribution

A
  • found as monomer, homodimer, heterodimer, or multimer form
  • distribution = 50% free and 50% bound to Gh-binding poteins
  • short half-life in circulation (about 20 mins)
24
Q

lipogenesis and lipolysis, AA uptake, glucose protein synthesis effects on GH

A

lipogenesis = negative stimulus on GH

lipolysis, AA uptake, glucose protein synthesis = positive stimulus

25
Q

how is GH measured in the lab?

A

immunoassays

26
Q

expcted final outcomes of GH

A

raises glucose and FFA aconcentrations

27
Q

the actions of GH are mediated directly through these and indirectly through these

A

directly = GH receptors on many tissues

indirectly = hpatic insulin growth factor release (IGF-1)

28
Q

normal pattern of GH secretion from pituitary

A
  • pulsatile release, with most release at night (very low during the day)
  • circadian rhythm
  • influenced by age, gender, and body composition
29
Q

when should blood samples be collected if a physician wants to know if a patient is making enough GH?

A

repetitive sampling under standardized conditions

30
Q

these stimuli stimulates release of GHRH from the hypothalamus

A
  • exercise
  • stress
  • sleep
  • alpha 2 adrenergic activity
  • fasting (hypoglycemia)
  • increased amino acids
  • hormones
  • neurotransmitters
31
Q

what inhibits GHRH ?

A
  • cortisol
  • beta-adrenergic acitivty
  • hyperglycemia
  • obesity
  • FFA
  • hypothyroidism
  • aging
  • IGF-1
32
Q

T or F. IGF-1 inhibits more release of GH by shutting down production at hypothalamus and pituitary

A

T

33
Q

SRIF (somatostatin)

A

inhibitory to GH

- IGF-1 also stimulates this to stop release of GH

34
Q

how is IGF-1 measured in the lab?

A

immunoassay

35
Q

GH excess causes

A

pituitary tumors (adenoma)
hypothalamic lesions
GHRH-producing tumors

36
Q

result of GH excess

A

soft tissue and bone overgrowth

  • gigantism in children
  • acromegaly in adults
37
Q

characteristic physical features in kids with GH excess

A
  • very tall

- large long-bones

38
Q

characteristic physical features in adults with GH excess

A
  • large/coarse facial features
  • large organs
  • skin changes
  • osteoarthritis
  • hypertension
  • insulin resistance
39
Q

what is seen often in patients with GH excess?

A

DM, myopathy, CVD risk

40
Q

testing for GH excess dynamic testing

A
  • dynamic = induce hyperglycemia - see how the system will respond
    > should be an inhibitory response (hyperglycemia) = should shut off somatostatin
  • if GH excess in the pituitary = hormone release remains sustained = overproduction not responsive to regular inhibition; inhibiting factors not working = typically due to tumor
41
Q

testing for GH excess (3)

A
  • measure serum IGF-1 (screen)
  • glucose supppresssion test
    > give oral glucose load
    > meausre serum GH 2 hrs psot-load
  • normally this would make GH undetectable
  • magnetic resonance imaging = see if it’s a tumor
42
Q

causes of GH defiicency or resistance

A
  • pituitary or hypothalamic abnormalities (def)

- GH insensitivity (resistance)

43
Q

characteristic features in children with GH deficiency or resistance

A
  • low growth rate
  • short stature
  • central adiposity
  • susceptible to hypoglycemia
44
Q

characteristic features in adults with GH deficiency or resistance

A
  • decreased bone density
  • abnormal body composition
  • impared serum lipids
  • premature mortality
45
Q

things that might contribute to the inability to produce GH

A
  • GHRH receptor mutation
  • pituitary damage
  • GH gene mutation
  • GH antibodies
  • GH receptor mutation
  • target organ resistance
  • IGF-1 deficiency
46
Q

testing for GH deficiency

A
  • IGF-1 levels; a screen
  • exercise stimulation test = 20 mins of exercise should cause GH elevation
  • insulin tolerance test = give IV insulin; measure GH = DANGEROUS
47
Q

treatment for patients with GH deficiency

A
  • GH supplements like recombinant hGH (22kDa monomer)

- athletes misuse to increase lipolysis, lean muscle mass, VO2 max