Hypothalamic/Pituitary Hormones

Question 1

What is the MOA of somatotropin?

Answer 1

Somatropin is a direct agonist of the growth hormone receptor stimulating gene expression e.g. IGF1

Question 2

Somatotropin: indications?

Answer 2

HRT for children w GH deficiency
Other conditions of small stature
Prader-willi syndrome
Turner’s syndrome
Noonan’s syndrome
Chronic renal insufficiency
Idiopathic short stature

Question 3

Somatotropin: adverse effects?

Answer 3

Children:
Idiopathic intracranial HTN
Increased intraocular pressure
Development of insulin resistance

Adults:
Peripheral edema
Arthralgias
Carpal tunnel
Parathesis
Worsening glucose intolerance
Acute pancreatitis

Question 4

Somatotropin: contra-indications?

Answer 4

Contraindications:
Active malignancy
Uncontrolled diabetes
Proliferative retinopathy
Children with closed epiphyses
Prader-willi with severe obesity 
and/or respiratory obstruction

Question 5

Mescarmin: MOA?

Answer 5

Recombinant IGF1

Is a downstream effector of GH-bypasses GHR defects and/or anti-GH Abs

Activates the IGF1R

Question 6

Mescarmin: indications?

Answer 6

Children with impaired growth non-responsive to GH

e.g. mutations in GHR or downstream signaling pathway, neutralizing antibodies to GH, or IGF-1 gene defects (v. rare)

Question 7

Mescarmin: adverse effects?

Answer 7

Hypoglycemia

Intracranial hypertension

Question 8

Mescarmin: contraindications?

Answer 8

Active malignancy

Children with closed bone epiphyses

Question 9

Name two somatostatin analogues

Answer 9

Octreotide

Lanreotide

Question 10

Octreotide/Lanreotide: MOA?

Answer 10

Octreotide/Lanreotide are somatostatin receptors agonists

Stimulate pathways that inhibit production of GH

Question 11

Octreotide/lanreotide: indications?

Answer 11

GH excess
Gigantism
Acromegaly

Other clinical uses
Esophageal varices
Carcinoid syndrome
Gastrinoma
glucagonoma

Question 12

Octreotide/lanreotide: adverse effects?

Answer 12

Nausea/Diarrhea (~50%)
Gallstones (~25%)
Suppresses TSH (monitor for hypothyroidism
low risk- typically only transient effect)
Bradycardia & cardiac arrhythmias

Question 13

Pegvisomant: MOA?

Answer 13

Direct antagonist of the growth hormone receptor

Question 14

Pegvisomant: indications?

Answer 14

GH excess
Gigantism
Acromegaly

Question 15

Name two dopamine agonists

Answer 15

Cabergoline

Bromocriptine

Question 16

Bromocriptine/Cabergoline: MOA?

Answer 16

Direct agonists of D2 dopamine receptors

Question 17

Bromocriptine/Cabergoline: indications?

Answer 17

Hyperprolactinemia

Other uses;
At high doses- treatment of acromegaly/gigantism

Question 18

Bromocriptine/Cabergoline: adverse effects?

Answer 18

Nausea/headache
Orthostatic hypertension
Psychiatric symptoms

Question 19

Name 5 gonadotropin releasing hormone agonists

Answer 19

Leuprolide
Goserlin
Buserlin
Triptorelin
Naferelin

Question 20

What is the MOA of Leuprolide/Goserlin/Buserlin/Triptorelin/Naferelin?

Answer 20

Sustained activation of GnRH receptor inhibits

release of gonadotropins

Question 21

Leuprolide/Goserlin/Buserlin/Triptorelin/Naferelin: indications?

Answer 21

Controlled ovarian stimulation
Palliative therapy of hormone-dependent tumors
Suppression of inappropriate growth of hormone-dependent tissues e.g. endometriosis & fibroids
Treatment of precocious puberty
Suppression of endogenous puberty in gender dysmorphic adolescents

Question 22

GnRH agonists/antagonists contraindications?

Answer 22

Pregnancy

Question 23

Name three GnRH antagonists

Answer 23

Ganirelix
Cetrorelix
Degarelix

Question 24

Ganirelix, Cetrorelix, Degarelix: MOA?

Answer 24

Antagonize GnRH receptor –> reduce gonadotropin release

Question 25

Ganirelix/Cetrerelix: indication?

Answer 25

Control ovarian stimulation

Question 26

Degarelix: indication?

Answer 26

Advanced prostate cancer

Question 27

GnRH antagonists/agonists: adverse effects?

Answer 27

``` Side effects associated with gonadal hormone deprivation e.g. hot flashes Decreased bone density Vaginal dryness/atrophy Erectile dysfunction ```

Question 28

Name the exogenous FSH/LH

Answer 28

hMG

Question 29

Name the exogenous FSH

Answer 29

Urofollitropin

Question 30

Name the recombinant FSH

Answer 30

Follitropan alpha/beta

Question 31

What is the MOA of FSH and hMG in females?

Answer 31

FSH and hMG stimulates follicular development

Question 32

What is the MOA of HCG in females?

Answer 32

HCG triggers ovulation via the LH receptor

Question 33

What is the MOA of HCG in males?

Answer 33

HCG stimulates endogenous testosterone production in males via stimulation of the LH receptor

Question 34

What are the indications of exogenous gonadotropins?

Answer 34

Infertility treatment in anovulatory women Ovarian hyperstimulation Male infertility in hypogonadotopic hypogonadism

Question 35

What are side effects of exogenous HCG in men?

Answer 35

Gynecomastia

Question 36

What are the side effects of exogenous FSH and HCG in women?

Answer 36

Multiple pregnancies | Ovarian hyperstimulation

Question 37

What is the MOA of oxytocin?

Answer 37

Acts through cognate GPCR expressed on uterine SMC and breast

Question 38

What are the indications for oxytocin?

Answer 38

Induction of labor | Treatment of uterine atony (failure of uterus to contract following delivery)

Question 39

What are the adverse effects of oxytocin at low vs. very high levels

Answer 39

Low; excessive stimulation of uterine contractions --> fetal distress, placental abruption or uterine rupture High: off-target activation of vasopressin receptors leading to excessive fluid retention

Question 40

What is synthetic vasopressin called?

Answer 40

Desmopressin

Question 41

What is the MOA of desmopressin?

Answer 41

Selectively activates V2 vasopressin receptors in the kidney to promote water reabsorption Activates V2 receptors on endothelial cells to release vWF Long acting!

Question 42

Desmopressin: indications?

Answer 42

Central diabetes insipidus Nocturnal enuresis Minor bleeding in minor hemophilia and von willebrand's disease

Question 43

Desmopressin: adverse effects?

Answer 43

Headache, hyponatremia Acute thrombotic events- very rare

Question 44

Vasopressin: MOA

Answer 44

Direct full agonist of both V1 and V2 receptors

Question 45

What is the only indication of vasopressin?

Answer 45

Second line agent used in treatment of vasodilatory shock refractory to epinephrine

Question 46

What are the adverse effects of vasopressin

Answer 46

Hyponatremia, cardiac arrhythmia, low cardiac output, atrial fibrillation

Question 47

Name two vasopressin antagonists

Answer 47

Tolvaptan, Conivaptan

Question 48

Conivaptan: MOA

Answer 48

V1 and V2 antagonist- promotes increased water excretion and raises serum Na+

Question 49

Tolvaptan: MOA

Answer 49

Selectively antagonizes V2 receptors

Question 50

What is the indication for conivaptan and tolvaptan?

Answer 50

Hypervolemic hyponatremia- due to SIADH

Question 51

Which -vaptan is associated with liver hepatotoxicity?

Answer 51

Tolvaptan