L32- Hypothalamic and Pituitary Hormones (GH)

Question 1

GH:

• most important during (1) age
• directly activates (2) signalling via cell surface receptors
• majority of effects are mediated by (3)

Answer 1

(somatotropin)
1- childhood, adolescence

2- JAK/STAT

3- IGF-1 (insulin like growth factor 1)

Question 2

list the many physiological effects of somatotropin:

• (1) MSK changes
• (2) renal changes
• stimulation of (3) cell development
• antagonizes action of (4)
• develops and increases functions of (5)

Answer 2

1- stimulates longitudinal bone growth inc bone mineral density, inc muscle mass

2- inc GFR

3- preadipocytes –> adipocytes

4- anti-insulin actions (dec glucose utilization, inc lipolysis)

5- immune system

Question 3

GH deficiency:

• (1) causes
• (2) seen in children
• (3) is main blood feature seen in all

Answer 3

1- genetic or damage to pituitary / hypothalamus

2- short stature, adiposity

3- hypoglycemia (unopposed insulin actions)

Question 4

GH deficiency: criteria for Dx

Answer 4

-growth rate <4cm per year
AND
-absence of serum GH response to two GH secretagogues

Question 5

(1) = recombinant GH

(2) = GH analog

Answer 5

1- somatotropin

2- somatrem

Question 6

Somatrem = (1)
Somatotropin = (2)

Answer 6

1- GH analog

2- recombinant GH

Question 7

describe administration of GH (pharmacokinetics)

Answer 7

• active blood levels persist for ~36 hrs

- give SQ x3-7 per wk

Question 8

recombinant GH AEs in children

Answer 8

(somatotropin)
Generally well-tolerated
-scoliosis (rapid growth)
-hypothyroidism

• intracranial HTN is rare
• otitis media, high risk in Turner Pts
• pancreatitis, gynecomastia, nevus growth
• diabetic syndrome with chronic use

Question 9

recombinant GH AEs for adults

Answer 9

• peripheral edema, myalgia, arthralgia (hands/wrists)
• carpal tunnel syndrome

-proliferative retinopathy (rare)

Question 10

recombinant GH contraindications

Answer 10

• cytochrome P450 inducer

- Pts with known malignancy

Question 11

Mecasermin = (1):

-(2) uses / indications, caused by (3)

Answer 11

1- IGF-1 analog (recombinant human IGF-1 and recombinant human IGF-binding protein-3)

2- IGF-1 deficiency (rare)

3- mutations in genes for GH receptor and development of neutralizing Igs to GH

Question 12

Mecasemin = (1): (2) AEs

Answer 12

1- IGF-1 analog (recombinant human IGF-1 and recombinant human IGF-binding protein-3)

2- hypoglycemia (usually eat w/in 20 mins of taking med, before or after)
Rare: intracranial HTN, asymptomatic elevation of liver enxymes

Question 13

GH secreting tumors are more common in (adults/children). If small in size, (2) is the treatment. If too large, (3) is generally the treatment.

Answer 13

1- adults- acromegaly (children gigantism)

2- GH receptor antagonists, somatostatin analogs, dopamine receptor agonists

3- surgery, radiation

Question 14

GH receptor antagonist = _______ (include indication)

Answer 14

Pegvisomant- for small GH producing tumors (adenomas)

Question 15

Somatostatin analog = (1):

• (2) actions
• (3) main indication

Answer 15

1- Octreotide

2- inhibits release of GH, TSH, glucagon, insulin, gastrin

3- small GH producing tumors (adenomas)

Question 16

name the drugs used to treat GH secreting tumors:

• (1) somatostatin analog
• (2) dopamine agonists
• (3) GH receptor antagonists

Answer 16

1- octreotide

2- bromocriptine, cabergoline

3- pegvisomant

Question 17

Octreotide:

• (1) analog with (2) better than (1)
• (3) is special formulation with (4) advantage

Answer 17

1- somatostatin analog

2- 45x more potent at reducing GH, 2x more potent at reducing insulin; 1/2 life ~80min vs 30min

3- octreotide acetate
4- long-acting suspension, given at 4 week intervals

Question 18

Octreotide clinical applications

Answer 18

(somatostatin analog)
-reduces Sxs from hormone secreting tumors: acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, nesidioblastosis, watery diarrhea, hypokalemia, achlorhydria syndrome, diabetic diarrhea

• localizing neuroendocrine tumors
• acute control of bleeding from esophageal varices

Question 19

Octreotide AEs

Answer 19

(somatostatin analog)

• n/v/d (steatorrhea), abdominal cramps, flatulence, constipation
• biliary sludge / gallstones (20-30% Pts after 6 mo. use)
• sinus bradycardia (25%, conduction disturbances (10%)
• vitB12 deficiency with long-term use
• pain at injection site is common

Question 20

_____ is main pharmalogical feature of PRL producing adenomas

Answer 20

they retain inhibition by dopamine

Question 21

list the main dopamine agonists; include route of administration, 1/2 life

Answer 21

oral or vaginal inserts

• bromocriptine- ~7hr 1/2 life
• cabergoline- ~65hr 1/2 life

Question 22

describe the uses of bromocriptine / cabergoline

Answer 22

(dopamine agonists)
Hyperprolactinemia: restores ovulation in 70% women with microadenoma, only 30% with macroadenoma

Acromegaly- alone or in addition to surgery, radiation, octreotide therapy

Question 23

Bromocriptine, Cabergoline AEs

Answer 23

(dopamine agonists)

• nausea (more bromo-)
• HAs, lightheadedness, orthostatic hypotension, fatigue

-occasionally psychiatric manifestations

• high doses = cold-induced peripheral digital vasospasm
• chronic high dose = pulmonary infiltrates