Exam 2: Growth Hormone Flashcards
Where is GH produced/released?
GH produced/released from anterior pituitary
What stimulates the release of GH from the anterior pituitary? And where does it come from?
GHRH (growth hormone releasing hormone) released from the hypothalamus
What inhibits the release of GH?
Somatostatin
What target organs does GH act on?
Many but liver, muscle, fat, bone, etc
When GH stimulates the liver what does the liver then release?
IGF-1 (which then goes to act on muscle, fat, bone, etc)
GH is made from what type of hormone-producing cells?
Somatotrophs (which are the most abundant type)
What do malignant somatotrophs often produce?
GH and prolactin (often due to pituitary adenoma)
Why would malignant somatotrophs produce both GH and prolactin when prolactin is produced by lactotrophs?
GH, prolactin, and human chorionic lactotrophs are considered of the same family
GH can act on prolactin receptors as GH and prolactin share 40% of amino acid sequence homology
While a pituitary adenoma can increase release of GH and prolactin, why does it decrease release of TSH, ACTH, and gonadotropins (FSH and LH)?
A pituitary adenoma can compress the infundibulum (thus hypophyseal vein) decreasing hypothalamic hormonal stimulation of anterior pituitary hormone release (TSH, ACTH, and gonadotropins)
If the infundibulum is compressed, why would prolactin release be increased?
Prolactin release is suppressed by dopamine from the hypothalamus so if the infundibulum is compressed there is less dopamine getting to anterior pituitary so less inhibition of prolactin, thus more prolactin release
Pathway of GH from start to finish?
Arcuate nucleus of hypothalamus releases GHRH into hypophyseal portal system
Then GHRH transported to somatotrophs in anterior pituitary which then releases GH to secondary capillary plexus
Then GH travels to target organs of the body
Somatostatin inhibits the release of GH. Where is somatostatin released from in the hypothalamus?
periventricular nucleus
So GHRH is released from what? And somatostatin is released from what?
hypothalamus- arcuate nucleus
hypothalamus- periventricular nucleus
GH and IGF-1 have positive feedback on what?
periventricular nucleus of hypothalamus so release somatostatin to inhibit GH release from anterior pituitary
GH and IGF-1 have neg feedback on what?
arcuate nucleus of hypothalamus so inhibit release of GHRH thus inhibit GH release from anterior pituitary also neg feedback directly on anterior pituitary (see image)
What is the result of GH deficiency in childhood?
dwarfism
Causes of GH deficiency in childhood?
congenital functional defect or structural damage of hypothalamus or pituitary
What causes GH deficiency in adulthood?
acquired, not by genetic reasons
tumors destroying/compressing infundibulum
pituitary structural damage of pituitary or hypothalamus
What is the purpose of GH in childhood?
linear growth (soft tissue, visceral organ, muscle, bone) in growing ages
What is the purpose of GH in adulthood?
maintain lean body mass in adulthood
While GH is very important in childhood growth, what is important in fetal growth?
IGF-1 (late fetal growth: triggered by insulin not GH) and IGF-2 (early fetal growth)
so GH deficient infants have normal birth lengths
How does GH achieve its goals of growth and maintenance of lean body mass?
cell proliferation and energy metabolism
GH predisposes cell metabolism to enhance lean body mass production by what three ways?
utilize fat as the main energy source
maximize protein deposition for lean body mass
earmark glucose for the use by the brain
(this is why GH receptors are in almost all tissues)
What organs/tissues contain the most GH receptors?
liver and cartilage
The action of GH on fat (utilization of fat as the main energy source so lipolysis and fatty acid release) is antagonistic to what?
insulin
What would you expect in your GH deficient patient in regards to fat?
elevated plasma LDL
elevated plasma triglyceride
premature atherosclerosis, thus elevated cardiovascular morbidity
mild obesity (increased fat mass)
What would you expect least in your GH deficient patient in regards to fat?
decreased plasma HDL because GH does not down regulate this
The action of GH maximizing protein deposition for lean body mass is synergistic to the action of what?
insulin
What would you expect in your GH deficient patient in regards to protein?
GH should strengthen muscles so:
reduced skeletal muscle cross sectional area
muscle weakness
decreased plasma urea levels
decreased myocardial contractility
decreased exercise performances
decreased left ventricle mass index and internal diameter
What would you expect least in your GH deficient patient in regards to protein?
Increased pulmonary capacity
The action of GH on glucose metabolism is antagonistic to what?
insulin
So GH and insulin counteract each other in regards to glucose metabolism so what happens when there is a pathologic excessive chronic GH release?
action of insulin to decrease plasma glucose is overpowered by GH’s action to increase plasma glucose…thus you get insulin resistance so diabetogenesis
Should you treat diabetic patient with GH?
No, they are already hyperglycemic and the action of GH is to increase plasma glucose
At what time of day could hyperglycemia of DM patients be super severe?
morning following nocturnal GH release
Is the release of GH constant or pulsatile? And when is it at its greatest?
Pulsatile
Throughout the night
What would you expect in your GH deficient patient in regards to glucose metabolism?
decreased fasting glucose levels
decreased insulin secretion
increased hepatic glucose production
How does GH achieve its goals of growth through IGF-1?
GH stimulated release of IGF-1 from liver increases cell proliferation via a insulin-like metabolic action (but this is insufficient to override GH’s direct effect on glucose and fat) and proliferative action on body organs such as muscle, bone, soft tissue, visceral organs (so synergistic action with GH in amino acid metabolism to build muscles)
Action of GH and IGF-1 action in regards to fat and glucose metabolism is antagonistic or synergistic?
Antagonistic (IGF-1 action is insufficient to override GH’s direct effect on glucose and fat)
Action of GH and IGF-1 action in regards to protein/amino acid metabolism is antagonistic or synergistic?
Synergistic
Want a nice visual of GH action?
See image
What measurements are used to dx GH disturbances?
glucose and insulin
List four main actions of GH?
increase plasma fatty acid for energy source
decrease plasma amino acids by increasing uptake into tissues to build muscle
increase plasma glucose for the brain
promote body growth and repair
Things that would increase GH secretion?
See image
Things that would decrease GH secretion?
See image
What are some clinical signs of GH deficiency?
fatigue
weakness
decreased energy level
mild obesity
decreased muscle mass
high LDL levels
decreased cardiac function
decreased insulin sensitivity
etc
How could you test if your patient is GH deficient?
Insulin challenge:
Inject insulin into pt
Injecting insulin into healthy pt would inc GH
Injecting insulin into GH deficient pt would not change anything/no inc in GH
Insulin challenge to test for GH deficiency is contraindicated in what patients?
ischemic heart disease
epilepsy
elderly patients
Define acromegaly in regards to GH release?
excessive and sustained GH release even during the day (normally just elevated at night)
What are the three main causes of excess GH?
pituitary adenoma
extra pituitary tumor (pancreatic islet cell tumor, lymphoma, iatrogenic)
excess GHRH (pancreatic islet tumor, bronchial carcinoid, small lung cancer, adrenal adenoma)
Excess GH in kids results in?
Gigantism
Excess GH in adults results in?
Acromegaly
What are the facial features of acromegaly?
increase frontal bossing (enlargement of sinuses)
increase in base of nose
thickening of nano-labial sulcus and lips
parotid hypertrophy
loss of oval facial features
worsening of prognathism (the positional relationship of the mandible or maxilla to the skeletal base where either of the jaws protrudes beyond a predetermined imaginary line in the coronal plane of the skull)
wide tooth spacing
What are more features of acromegaly?
hypertrophy of soft tissue (thickened tongue and skin, increased skin-folds, enlarged visceral organs particularly the liver and spleen)
HTN if CO is decreased due to cardiomegaly
enlargement of hands and feet
oily skin texture
peripheral neuropathy and pain by connective tissues compressing nerves (i.e. carpal syndrome)
insulin resistance
degenerative joints
deepening voice and sleep apnea (due to soft tissue growth in pharynx)
malignant polyps and colon cancer
What is the mortality of patients with acromegaly?
2-3x increase in mortality
If the cause of acromegaly is enlarged anterior pituitary, what other features can you see?
headache
peripheral vision loss
double vision
other anterior pituitary deficits that can cause: impotence, fatigue, amenorrhea, and galactorrhea
How is acromegaly dx?
measure IGF-1
if elevated, then do glucose intolerance test and GH measure
if this shows inadequate GH suppression, then do pituitary MRI
MRI may show pituitary mass (dx: GH secreting adenoma)
but if not, do chest abdominal CT and GHRH measure (dx: extra pituitary acromegaly)
What is the initial test you would order if you suspect acromegaly?
IGF-1 level
