Growth hormone

Question 1

metabolic function of GH

Answer 1

promotes lipolysis and is counter-regulatory for hypoglycemia

Question 2

mechanism of action

Answer 2

cytokine receptor activates JAK-STAT pathway

Question 3

Laron’s dwarfism

Answer 3

inactivating mutation in GHR; treatment with IGF-1

Question 4

direct actions of GH

Answer 4

opposes insulin, synergizes with cortisol

Question 5

indirect actions of GH

Answer 5

dependent on IGF-1; IGF-1 has spillover with insulin and will activate insulin receptors (countering the effects of GH) at high enough levels

Question 6

hypothal

Answer 6

positive: GHRH
negative: somatostatin

Question 7

ant. pit.

Answer 7

40% of the cells here are somatotropes

release is pulsatile (more release during sleep)

Question 8

feedback reg.

Answer 8

IGF-1 receptors at pituitary and hypothalamus

Question 9

physiological stimulants of GH release

Answer 9

alpha-adrenergics; protein rich meal, hypoglycemia, stress, exercise, sleep

Question 10

physiological inhibitors of GH

Answer 10

glucose, fatty acids and beta-adrenergics

Question 11

acquired GH deficiency

Answer 11

traumatic brain injury, infection, iatrogenic (most common, esp. following resection)

Question 12

genetic GH deficiency

Answer 12

defects in HESX1, PIT1, PROP1

Question 13

clinical manifestations children (deficiency)

Answer 13

impaired growth; measured as >2 SD below normal, delayed bone age; hypoglycemia

Question 14

clinical manifestations in adults (deficiency)

Answer 14

insidious, increased bone mass and adiposity

Question 15

diagnosis of GH deficiency

Answer 15

based on provocative testing

arginine (protein load), clonidine (alpha agonist), insulin (induces hypoglycemia)

Question 16

clinical manifestations children (excess)

Answer 16

gigantism, glucose intolerance

Question 17

clinical manifestations adults (excess)

Answer 17

acromegally, arthralgias, glucose intolerance, hypertension

Question 18

diagnosis of GH excess

Answer 18

elevated IGF-1, oral glucose tolerance test (failure to respond is indicative of GH adenoma), MRI for adenoma,

Question 19

treatment for GH excess

Answer 19

transphenoidal surgery, or radiation + medical therapy if surgery is not successful

Question 20

somatropin indications

Answer 20

GH deficiency

stature conditions: (Turner syndrome, chronic renal disease)

Question 21

somatropin contraindication

Answer 21

any active malignancy

critically ill patients

Question 22

somatropin dosage

Answer 22

SQ injection @ bedtime; considerably higher dose than normal

Question 23

adverse effects somatropin children

Answer 23

headache, increased ICP, SCFE (all generally rare)

Question 24

adverse effects somatropin adults

Answer 24

edema, arthralgias, carpal tunnel syndrome (adjust levels to keep them healthy)

Question 25

Mecasermin definition

Answer 25

IGF-1 recomb. SQ BID

Question 26

Mecasermin indications

Answer 26

Laron's, STAT5b mutations, autoimmunity vs. GH

Question 27

Mecasermin contraindications

Answer 27

active neoplasia, hypoglycemia

Question 28

Mecasermin adverse effects

Answer 28

local hypoglycemia and lipohypertrophy at injection site; rarely SCFE and ICP

Question 29

Mecasermin eval. of response to therapy

Answer 29

must monitor growth effect (IGF-1 levels not useful)

Question 30

octreotide definition and structure

Answer 30

somatostatin analog for the suppression of GH release; 8 AA ring peptide with longer half life than somatostatin

Question 31

octreotide dosage

Answer 31

not PO, every four weeks

Question 32

octreotide indications

Answer 32

acromegally, portal HTN, hyperinsulinism (SST receptors @ beta cell block release)

Question 33

octreotide adverse effect

Answer 33

gallstones/sludge, n/v, injection site discomfort

Question 34

octreotide eval to therapy

Answer 34

symptom reduction, IGF-1 normalizing, GH levels should improve

Question 35

Pegvisomant definition

Answer 35

PEGylated GH, occupies receptors, longer half-life and decreased antigenicity

Question 36

Pegvisomant dosage

Answer 36

SQ

Question 37

Pegvisomant indications

Answer 37

acromegally not surgically responsive

Question 38

Pegvisomant adverse effects

Answer 38

hepatitis - monitor ALT, AST | tumor growth - loss of negative feedback

Question 39

Pegvisomant eval

Answer 39

serum IGF-1 levels should be eval'ed

Question 40

Dopamine agonists role in acromegally and names

Answer 40

paradoxical inhibition of GH by blocking co-secreting (somato/lactotrophic) adenomas; D2 receptors agonists - bromocriptine and cabergoline