Growth Hormone - Trachte

Question 1

What type of hormone is growth hormone?

Answer 1

Sommatotropic

Question 2

What type of hormone is prolactin?

Answer 2

Mammotropic

Question 3

What kind of receptor does Growth hormone act on?

Answer 3

Cytokine receptor (with tyrosine kinase) that activates JAK/STAT secondary messenger signal transduction pathway

(Hormone binding causes dimerization and internalization of complex)

Question 4

What is stimulatory for GH release?

Answer 4

Hypothalamus => Growth Hormone Releasing Hormone (GHRH)

Question 5

What are the target cells for Growth Hormone?

Answer 5

Several receptor isoforms of GHR expressed in nearly all cells

Liver produces Insulin-like growth factor-1 (IGF-1 = somatomedin)

IGF-1 has impressive similarity to insulin in structure

GH and IGF-1 are final hormones mediating GH Axis effects

Question 6

What are the direct effects of Growth Hormone?

Hint: 6 things

Answer 6

Na retention

Decreased insulin sensitivity

Lipolysis

Protein synthesis

Epiphysial growth

IGF-1 production by the liver

Question 7

What are the indirect effects of Growth Hormone via IGF-1?

Hint: 4 things

Answer 7

Insulin-like activity

Anti-lipolytic activity

Protein synthesis

Epiphysial growth

***IGF-1 > GH stimulates chondrogenesis (growth) at epiphyseal growth plates in children.

Question 8

What additional effects does Growth Hormone have on protein metabolism?

Answer 8

Increases amino acid uptake and protein synthesis

Retention of nitrogen, phosphorous and potassium

Abuse by athletes to increase muscle mass and athletic performance

Proposed for elderly to increase muscle mass

Question 9

What additional effects does Growth Hormone have on mineral metabolism?

Answer 9

Increases mineral density in bones after longitudinal growth ceases and epiphyses have closed.

Question 10

What additional effects does Growth Hormone have on carbohydrate metabolism?

Answer 10

Carbohydrate utilization is uniformly decreased

Hyperglycemia- diabetogenic

• reduces tissue uptake of glucose
• increases liver production of glucose
• secondary insulin release

Question 11

What additional effects does Growth Hormone have on fat metabolism?

Answer 11

increased mobilization of fats for energy

Question 12

When (day/night) does Growth Hormone typically get released?

Answer 12

Primarily at night.

Question 13

What if you have no production of Growth Hormone?

Answer 13

No production of IGF-1

No inhibition of GHRH

Question 14

What is the control pathway for Growth Hormone?

Answer 14

GHRH (hypothalamus) => increase GH production in pituitary

Somatostatin (hypothalamus) => decrease growth hormone production in anterior pituitary

GH => negative feedback on GHRH / increase IGF-1 production in liver

IGF-1 => negative feed back on GH and GHRH

Question 15

What conditions occur due to a severe GH deficiency in children?

Answer 15

Proportional dwarfism

Laron syndrome (insensitive to GH => resistant to cancer and diabetes)

Turner’s syndrome (XO or XX with missing parts of one chroms.)

Question 16

What conditions occur with GH deficiency in adults?

Answer 16

generalized obesity

reduced muscle mass

asthenia (reduced energy, weakness)

reduced cardiac output

Question 17

Why is it not useful to assess for GH deficiency by testing random serum samples for hyposecretion?

Answer 17

due to pulsatile pattern of GH release

Question 18

How does the Insulin Tolerance Test assess for GH deficiency?

Answer 18

Administration of insulin to induce hypoglycemia which should stimulate the adrenal glands to secrete cortisol and the pituitary gland to secrete growth hormone.

Failure to respond to insulin may suggest the need for glucocorticoid and growth hormone replacement.

Question 19

What is the drug used as a GHRH analog for the arginine co-stimulation test?

Answer 19

SERMORELIN is a GHRH1-29 analog

Question 20

How does the Arginine/GHRH protocol to induce GH response?

Answer 20

Procedure:

1. Baseline growth hormone and somatomedin-C (IGF1)levels.
2. Inject 0.5 g/kg Arginine over 30 minutes intravenously.
3. Inject 1 mcg GHRH over 1 minute intravenously.
4. Serum growth hormone levels at 15, 30, 45, 60 minutes

Interpretation:
A growth hormone level greater than 8 ng/ml is a normal response.
A growth hormone level less than 8 ng/ml is an abnormal response suggesting growth hormone deficiency.

Question 21

What is the recombinant human growth hormone used to treat GH deficiencies?

Answer 21

Somatropin

Question 22

What is the goal in therapeutic treatment of GH hyposecretion syndromes like hypopituitarism, idiopathic short stature, Turner Syndrome growth deficiency, SHOX mutations, or trauma in children?

Answer 22

promote growth by:

give GH to maintain IGF-I levels in the mid-normal range for age- and gender-matched controls

Question 23

What is an early sign of hypopituitarism?

Answer 23

hypoglycemia is an early sign

=> due to unopposed action of insulin

Question 24

What things do you monitor in patients at 1- to 2-month intervals during recombinant human GH (rhGH) dose titration and semiannually to annually thereafter?

Answer 24

IGF-I levels

children: growth
adults: lipid profile, fasting glucose, bone density

Question 25

What are the potential negative side effects or rhGH therapy?

Answer 25

Antibodies to GH in 30% (usually of little consequence) Scoliosis during rapid growth Diabetogenic => Can see an impaired glucose tolerance test, ketosis/severe acidosis in diabetics (may require an increase in insulin) Cortisol or hypothyroidism may inhibit growth following GH therapy

Question 26

Recombinant human IGF for IGF deficiencies not responsive to GH is used to treat which syndrome?

Answer 26

***Laron-type dwarfism*** - Autosomal recessive - GH receptor variant which has weak binding to GH - Result is also low IGF-1 levels - Present at birth

Question 27

What are the two rhIGF treatments?

Answer 27

1. Mecasermin (Increlex) = rh IGF-1 2. Mecasermin rinfabate (Iplex) = contains a complex of recombinant human rhIGF-1 plus rh-insulin-like growth factor binding protein-3 (IGFBP3 = IGF carrier protein and hence modulates IGF effects)

Question 28

What are the potential adverse side effects of rhIGF treatments?

Answer 28

Hypoglycemia (administer immediately before or after a meal) Liver effects: Increases cytochrome p450 - reduces the duration of drugs metabolized by that system - steroids, anticonvulsants

Question 29

What usually causes GH Hypersecretion?

Answer 29

Usually pituitary tumor (adenoma) of the somatotropes

Question 30

Hypersecretion of GH results in gigantism and/or acromegaly is determined by what?

Answer 30

determined by timing of epiphyseal plates closure in children => gigantism (before growth plates close) in adults => acromegaly (after growth plates close)

Question 31

What is different about the GH levels in acromegaly compared to normal GH levels?

Answer 31

GH levels in acromegaly do not show circadian rhythm or peaks and nadirs ***but are within normal range*** (This makes it difficult to identify GH secretory excess)

Question 32

What receptors are targeted in potential medical treatments for hypersecretion of Growth Hormone or pituitary tumors?

Answer 32

Somatostatin (SSTRs analogs) and Dopamine (D2 agonists)

Question 33

What are the symptoms of acromegaly?

Answer 33

Lengthened jaw Coarsened features Growth in hands and feet Stubby fingers

Question 34

How do you diagnose GH hypersecretion?

Answer 34

1. An elevated IGF-1 is the first indication 2. Confirmed by an elevated GH level 2hr after glucose administration (usually suppresses GH) - drinking 75 to 100 grams of glucose solution lowers blood GH levels to less than 1 (ng/ml) in normal individuals.

Question 35

What drug is a GH Receptor Antagonist that is an alternative and newer treatment for hypersecretion of GH?

Answer 35

Pegvisomant

Question 36

What is the MOA of Bromocriptine?

Answer 36

dopamine agonist

Question 37

What is the MOA of Octreotide?

Answer 37

long-acting somatostatin analog