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
how is GH measured in the lab?
immunoassays
26
expcted final outcomes of GH
raises glucose and FFA aconcentrations
27
the actions of GH are mediated directly through these and indirectly through these
directly = GH receptors on many tissues indirectly = hpatic insulin growth factor release (IGF-1)
28
normal pattern of GH secretion from pituitary
- pulsatile release, with most release at night (very low during the day) - circadian rhythm - influenced by age, gender, and body composition
29
when should blood samples be collected if a physician wants to know if a patient is making enough GH?
repetitive sampling under standardized conditions
30
these stimuli stimulates release of GHRH from the hypothalamus
- exercise - stress - sleep - alpha 2 adrenergic activity - fasting (hypoglycemia) - increased amino acids - hormones - neurotransmitters
31
what inhibits GHRH ?
- cortisol - beta-adrenergic acitivty - hyperglycemia - obesity - FFA - hypothyroidism - aging - IGF-1
32
T or F. IGF-1 inhibits more release of GH by shutting down production at hypothalamus and pituitary
T
33
SRIF (somatostatin)
inhibitory to GH | - IGF-1 also stimulates this to stop release of GH
34
how is IGF-1 measured in the lab?
immunoassay
35
GH excess causes
pituitary tumors (adenoma) hypothalamic lesions GHRH-producing tumors
36
result of GH excess
soft tissue and bone overgrowth - gigantism in children - acromegaly in adults
37
characteristic physical features in kids with GH excess
- very tall | - large long-bones
38
characteristic physical features in adults with GH excess
- large/coarse facial features - large organs - skin changes - osteoarthritis - hypertension - insulin resistance
39
what is seen often in patients with GH excess?
DM, myopathy, CVD risk
40
testing for GH excess dynamic testing
- 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
testing for GH excess (3)
- 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
causes of GH defiicency or resistance
- pituitary or hypothalamic abnormalities (def) | - GH insensitivity (resistance)
43
characteristic features in children with GH deficiency or resistance
- low growth rate - short stature - central adiposity - susceptible to hypoglycemia
44
characteristic features in adults with GH deficiency or resistance
- decreased bone density - abnormal body composition - impared serum lipids - premature mortality
45
things that might contribute to the inability to produce GH
- GHRH receptor mutation - pituitary damage - GH gene mutation - GH antibodies - GH receptor mutation - target organ resistance - IGF-1 deficiency
46
testing for GH deficiency
- 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
treatment for patients with GH deficiency
- GH supplements like recombinant hGH (22kDa monomer) | - athletes misuse to increase lipolysis, lean muscle mass, VO2 max