Endocrine (GH Lecture)

Question 1

List at least 5 conditions that stimulate GHRH bioactivity?

Answer 1

Hypoglycemia, Arginine, Ghrelin hormone, Dopamine, Serotonin.

Question 2

What role does Somatostatin have in the GH scheme? Describe it’s clinical relevance.

Answer 2

Somatostatin (released from somatotropes) inhibits GH secretion. It can be used as a supplement against excessive GH secretion such as can be observed in acromegaly or gigantism.

Question 3

Name 3 examples of binding proteins produced by the liver. What is the main role of these binding proteins?

Answer 3

GHBP, IGFBP and Albumin. They help related hormones last much longer in circulation. This is done by increasing half life and lowering renal clearance.

Question 4

What are the functions of GH on lipolysis, proteolysis and glycolysis for metabolism? What metabolic byproducts do they make?

Answer 4

GH promotes lipolysis to form triglycerides, FFAs, and glycerol. It inhibits protein breakdown that would usually form amino acids and urea. It inhibits glycogen breakdown.

Question 5

What condition is excess GH secretion associated with? Why?

Answer 5

Insulin resistance since the hormone interferes with glucose uptake by the liver and muscle. This upsets the balance of maintaining blood sugar levels if high GH levels are prolonged.

Question 6

What does GH and IGF-1 do to the metabolism of glycogen?

Answer 6

GH + IGF-1 shifts metabolism AWAY from glycogenolysis and towards production FFAs and glycerol.

Question 7

What effect does GH and IGF-1 have on bone growth and remodeling? Mention the specific cells affected.

Answer 7

The duo stimulates growth of long bones via longitudinal growth at chondrocytes and deposition of calcium at osteoblasts.

Question 8

Describe how GH expression is involved in growth of long bones.

Answer 8

GH-R expression helps with the growth plates (ephiphysis) and longitudinal growth of long bones. Once they fuse, the adolescent stops growing.

Question 9

How does GH change after 20 years of age?

Answer 9

GH declines by 14% per decade after 20 years of age. At age 80+, the person experiences “somatopause” in which GH levels are 60% lower than early adulthood.

Question 10

What signs and symptoms can accompany GH excess?

Answer 10

Resistant Hypertension, Insulin Resistance, Excessive bone deposition, muscle weakness, water retention, sexual dysfunction

Question 11

List 3 phenotypes that can present clincally after several years of excess GH.

Answer 11

Frontal bossing, cranial ridging above the eyebrows, wider hands, feet, nose, mandibular overgrowth can be used to diagnose acromegaly after 9 years for the signs to manifest.

Question 12

What effects does GH and IGF-1 have on chondrocytes and osteoblasts, respectively, in regards to bone growth?

Answer 12

Chondrocytes experience longitudinal growth and osteoblasts help deposit minerals into bone when expressing IGF1.

Question 13

Can GH stop or reverse the musculoskeletal effects of aging, especially at somatopause?

Answer 13

No. There is a narrow window of growth where these anabolic hormones have an actual effect on the developing body. But as the window closes later in life, there is less benefit.

Question 14

What lab values, signs and symptoms might a physician expect for a patient with high GH secretion? (Name at least 5).

Answer 14

High levels of vLDL, triglycerides, cholesterol, calcium and glucose in serum. Truncal fat distribution, high blood pressure, water retention, possible pituitary adenoma (CT scan)

Question 15

How does acromegaly differ from gigantism?

Answer 15

Acromegaly shows up after an epiphyseal closure in adults. It can be presented as frontal bossing, cranial ridging, widening of hands, feet or nose as well as a mandibular overgrowth. This differs from gigantism which can be manifested earlier in children. This pathology features a large stature, longer bones and cardiac defects.

Question 16

Explain the effects that acromegaly has on the cardiovascular system.

Answer 16

Acromegalic cardiomyopathy can result from biventricular hypertrophy. This reduces heart compliance and cardiac output as the heart needs more O2 than usual due to the excess growth.

Question 17

Why is it not a good idea for someone to supplement with exogenous growth hormone?

Answer 17

Although this can incease lean body mass (most of it will be water weight), this can develop hypertension, Na+ retention and unfavorable vascular remodeling.

Question 18

Explain the pathogenesis of resistant HTN in acromegaly that resulted from high levels of GH.

Answer 18

Increased Lean body mass (LBM) and aldosterone INCREASES the effective circulating volume that in turn inhibits RAS system.

Question 19

What are 3 clinical tests that can be run to determine GH excess?

Answer 19

1. Somatostatin - inhibits GH secretion. Measure baseline, apply the inhibitor and take new measurements. If nothing changes, it might be an adenoma.
2. Oral Glucose Tolerance Test (OGGT) - a spike in blood sugar should effectively reduce GH secretion
3. Lipid panel - can determine high triglycerides, FFAs, cholesterol and vLDL levels associated with GH.

Question 20

Describe how bromocriptine works to lower GH secretion.

Answer 20

Bromocriptine is a dopamine receptor agonist that blocks prolactin (PRL) secretion. Since GH and PRL are coupled, this treatment would also reduce growth hormone levels.

Question 21

Under physiologic conditions, dopamine _________ GH secretion. When treating a pathophysiologic conditon, dopamine receptor agonists _________ secretion.

Answer 21

Stimulates;

Block

Question 22

What is Laron’s Syndrome and what can be expected in blood results? Describe 2 ways to test for it.

Answer 22

Laron’s Syndrome is a type of prepubertal GH deficiency marked by a short stature and tissue resistance to GH. Blood labs would show elevated GH levels and low IGF-1. This can be tested by fasting or use of an insulin supplement to raise the low blood sugar.

Question 23

List 3 methods that can be done to a patient stimulate GH secretion.

Answer 23

The following would stimulate GHRH up-regulates GH secretion

1. Arginine supplement
2. Exercise
3. Insulin infusion

Question 24

List at least 5 drawbacks of exogenous GH/IGF-1 that athletically-competitive adults can experience.

Answer 24

Biventricular hypertrophy, acromegaly, fluid overload (resistant HTN), unfavorable remodeling, infertility or kidney disease in the long run.