Growth Hormone

Question 1

growth hormone - feedback loop

Answer 1

1. growth hormone releasing hormone (GHRH) released from hypothalamus
2. GHRH stimulates anterior pituitary to release growth hormone (GH)
3. GH travels in bloodstream and acts at target tissues (adipose, liver, stomach)
4. IGF-1 (from liver) and free fatty acids (from adipose) provide negative feedback to prevent more release of GH

Question 2

growth hormone (GH) - overview

Answer 2

*aka somatotropin
*secreted by somatoproph cells in the anterior pituitary gland
*pulsatile release, short half-life

Question 3

growth hormone (GH) - functions

Answer 3

1. raises blood glucose:
   -increase lipolysis during times of fasting (facilitates breakdown of lipids over protein for energy)
   -increases gluconeogenesis
   -increases insulin resistance
2. stimulates IGF-1 release from the liver

Question 4

IGF-1 - overview

Answer 4

*released from the liver in response to growth hormone
*aka insulin-like growth factor (IGF-1) and somatomedin C
*long half-life

Question 5

IGF-1 - functions

Answer 5

*functions as the primary growth factor, causes increase in protein synthesis and growth of muscle, bone, soft tissue
*some homology with insulin, can bind to insulin receptors; functions to lower blood glucose:
-decreases lipolysis
-increases glycogen stores in liver and muscle
-increases insulin sensitivity

Question 6

growth hormone (GH) release - over a day

Answer 6

*pulsatile, large peak within minutes of entering slow-wave sleep
*falls to undetectable levels for ~50% of day

Question 7

growth hormone (GH) release - over the lifetime

Answer 7

*pulsatile release begins in early puberty
*pulse amplitude decreases after puberty, with aging

Question 8

growth hormone (GH) regulation - STIMULATION of GH release

Answer 8

*fasting/hypoglycemia
*ghrelin
*stress/exercise

Question 9

growth hormone (GH) regulation - INHIBITION of GH release

Answer 9

*glucose
*IGF-1 (feedback loop)
*obesity

Question 10

IGF-1 signaling pathway

Answer 10

*tyrosine kinase receptor (MAP kinase pathway)

Question 11

growth hormone signaling pathway

Answer 11

*non-tyrosine kinase receptor (JAK/STAT pathway)

Question 12

growth hormone deficiencies - features

Answer 12

*can present in childhood or adulthood
*can be congenital (idiopathic, mutations, structural brain malformations) or acquired (pituitary adenomas, other tumors, cranial radiation therapy, etc)
*can be isolated, or occur with other pituitary hormone deficits
*can be transient or permanent

Question 13

growth hormone deficiencies in children

Answer 13

*most commonly presents as decreased growth velocity in early childhood, or lack of growth spurt during puberty → short stature
*other sx: increased fat mass/truncal obesity; short, round face, other abnormal facies; decreased bone age (particularly during adolescence)

Question 14

growth hormone deficiencies in adults

Answer 14

non-specific signs and symptoms:
*fatigue, low mood, poor concentration, decreased physical capacity
*central and general obesity, decreased lean body mass, decreased bone density
*hyperlipidemia, glucose intolerance

Question 15

growth hormone deficiency - diagnosis

Answer 15

1. start with measurement of IGF-1
2. if IGF-1 is low in a pt with high suspicion of GH deficiency, this is highly suggestive
   *provocative/dynamic testing is the gold standard:
   -insulin tolerance test
   -synthetic GHRH

Question 16

treatment of growth hormone deficiencies in children

Answer 16

*treat with recombinant human GH until early adulthood until they reach their expected height
*then, stop tx and assess to see if GH deficiency persists
*decide whether to restart/continue into adulthood

Question 17

treatment of growth hormone deficiencies in adults

Answer 17

*consider treating with recombinant human growth hormone (once daily or once weekly injection)

Question 18

acromegaly - overview

Answer 18

*excess growth hormone in adults
*typically caused by a growth hormone secreting pituitary adenoma
*when it occurs prior to growth plate closure → pituitary gigantism

Question 19

acromegaly - appearance

Answer 19

*coarse, prominent facial features:
-widened nose
-thickened lips & tongue
-elongated jaw → prognathism, TMJ issues, dental spacing
-frontal bossing (large forehead) - enlargement of supraorbital ridges
*increased lean muscle mass, but muscles are weaker
*skin tags
*enlarged hands & feet: doughy, fat sausage hands/fingers, feet wider

Question 20

acromegaly - manifestations & associated conditions

Answer 20

*arthropathy
*obstructive sleep apnea (OSA)
*carpal tunnel syndrome
*hyperhidrosis, oily skin
*HTN, DM2
*colon polyps/cancer
*organ enlargements, esp heart → acromegalic cardiomyopathy (leading cause of death)

Question 21

acromegaly - diagnosis

Answer 21

1. start by measuring serum IGF-1 levels
2. if elevated, perform confirmatory testing with oral glucose tolerance test (OGTT):
   -hyperglycemia should suppress GH in a normal person
   -if GH does not suppress, that suggests autonomous secretion from an adenoma

Question 22

acromegaly - treatment

Answer 22

*first line = surgery
*second line = medical therapy:
-somatostatin analogues (octreotide, lanreotide)
-GH antagonists