Pharm - Hypothalamic & Pituitary

Question 1

How do the connections between the hypothalamus and the anterior and posterior pituitary differ?

Answer 1

The hypothalamus communicates with the anterior pituitary via vascular supply, whereas it communicates with the posterior pituitary via axonal projections

Question 2

Describe how the control and action of prolactin is different than the other Hypothalamic/Pituitary hormones

Answer 2

Prolactin does not have a corresponding releasing hormone from the hypothalamus like the other hormones does. Prolactin acts directly on target tissues instead of stimulating hormone release from a peripheral gland.

Question 3

What are the 5 endocrine axes?

Answer 3

HPL: growth hormone
HPT: thyroid stimulating hormone
HPA: ACTH
HPG: LH and FSH
Prolactin

Question 4

Which hormones act through a JAK/STAT pathway?

Answer 4

Prolactin and Growth hormone

Question 5

Describe the feedback that tightly regulates most hypothalamic/pituitary hormones

Answer 5

End products cause negative feedback through long, short, and ultrashort loops. This feedback shuts down the axes in order to maintain stable levels of hormones.

Question 6

How does GH affect muscle and fat?

Answer 6

GH is anabolic on muscles and catabolic on fat

Question 7

What hypothalamic hormones regulate GH?

Answer 7

GHRH causes GH release and somatostatin inhibits GH release

Question 8

What is the effect of GH in childhood?

Answer 8

Linear growth, growth of long bones, cartilage, muscle, and organ systems

Question 9

What are the effects of GH in adulthood?

Answer 9

Protein synthesis, bone density
Lipolysis
Glucose release, reduced insulin sensitivity

Question 10

What enzyme mediates most of the effects of GH?

Answer 10

IGF-1

Question 11

Characteristics of child with GH deficiency

Answer 11

Short stature, adiposity, hypoglycemia (due to hyperinsulinemia)

Question 12

Characteristics of adult with GH deficiency

Answer 12

Increased adiposity, decreased muscle mass
Decreased bone mass
Cardiac muscle atrophy, atherogenic lipid profile
Overall malaise

Question 13

What is Sermorelin?

Answer 13

Synthetic GHRH

Used when pituitary has normal function, defect in GHRH/hypothalamus

Question 14

What are Somatropin and Somatrem?

Answer 14

Synthetic GH

Works as long as IGF-1 function is intact

Question 15

What is Mecasermin?

Answer 15

Synthetic IGF-1

Used when defect is in GH receptor or there are antibodies against GH

Question 16

How does the structure of Somatropin and Somatrem differ from GH?

Answer 16

Somatropin is identical to GH

Somatrem has an extra methionine at the N-terminus

Question 17

What pediatric conditions are treated with recombinant human growth hormone (Somatropin/Somatrem)?

Answer 17

GH deficiency
Chronic renal failure
Prader-Willi
Turner syndrome
Idiopathic short stature

Question 18

What adult conditions are treated with recombinant human growth hormone (Somatropin/Somatrem)?

Answer 18

GH deficiency
AIDS associated wasting
Short bowel syndrome

Question 19

What side effects are associated with recombinant human growth hormone (Somatropin/Somatrem)?

Answer 19

Neoplasms: Leukemia, melanocytic lesions
Hypothyroidism
Insulin resistance
Arthralgias
Induces CYP450 enzymes

Question 20

What are the contraindications for recombinant human growth hormone (Somatropin/Somatrem)?

Answer 20

Pediatric patients with closed epiphyses
Active underlying intracranial lesion
Active malignancy
Proliferative diabetic retinopathy

Question 21

What conditions are associated with GH excess?

Answer 21

In children: Gigantism (excessive long bone growth)

In adults: Acromegaly (growth of cartilagenous and deep organs)

Question 22

What diseases are patients with acromegaly at high risk for?

Answer 22

CV disease
GI disease
GI cancers
Reproductive disorders

Question 23

What are the treatment options for pituitary adenoma?

Answer 23

Surgical removal

Medical management with somatostatin analogues, GH receptor antagonists or dopamine agonists

Question 24

What drugs are somatostatin analogues?

Answer 24

Octreotide
Lanreotide
*These drugs inhibit GH secretion from the pituitary

Question 25

What is the GH receptor antagonist?

Answer 25

Pegvisomant

Question 26

What dopamine receptor agnonist is used for acromegaly treatment?

Answer 26

Bromocriptine

Question 27

What conditions are treated with somatostatin analogues (Octreotide/Lanreotide)?

Answer 27

Pituitary adenoma/Acromegaly Carcinoid crisis Secretory diarrhea due to VIPoma Control acute GI bleed (varices)

Question 28

What are the side effects of somatostatin analogues (Octreotide/Lanreotide)?

Answer 28

Nausea, vomiting, cramps, GI discomfort Sinus bradycardia, conduction abnormalities Hypoglycemia Gallstones

Question 29

What drug-drug interactions occur with octreotide?

Answer 29

Octreotide decreases cyclosporin levels and increases bromocriptine levels

Question 30

Describe the mechanism of action of Pegvisomant

Answer 30

Binds to GH receptors and prevents the dimerization the initiates the signaling cascade and thus blocking the action of GH

Question 31

What is the indication for Pegvisomant?

Answer 31

Treatment refractory acromegaly

Question 32

What are the side effects of Pegvisomant?

Answer 32

Increases pituitary adenoma size | Increases liver enzymes

Question 33

What are the two gonadotropins?

Answer 33

``` Leutinizing hormone (LH) Follicle stimulating hormone (FSH) ```

Question 34

In women, what is the main function of LH and FSH?

Answer 34

LH stimulates thecal cells to produce androgens. FSH stimulates granulosa cells to convert the androgens to estrogens.

Question 35

What are the pharmacological gonadotropins?

Answer 35

Human menopausal gonadotropin/menotropin Human chorionic gonadotropin Urofollitropin Follitropin

Question 36

What analog of GnRH is used pharmacologically?

Answer 36

Gonadorelin

Question 37

How is the gonadal axis inhibited?

Answer 37

Long acting GnRH analogues | GnRH antagonists

Question 38

What are the long acting GnRH analogues?

Answer 38

Goserelin, Histrelin, Leuprolide, Nafarelin, and Triptorelin

Question 39

What are the GnRH receptor antagonists?

Answer 39

Ganirelix Centrorelix Abarelix

Question 40

What are the indications for the Gonadotropins?

Answer 40

Ovulation induction for hypogonadotropic hypogonadism, PCOS, obesity Ovarian hyperstimulation for IVF

Question 41

What is ovarian hyperstimulation syndrome?

Answer 41

Ovarian enlargement, ascites, hydrothorax, hypovolemia and potential shock due to treatment with gonadotropins

Question 42

What are the side effects of gonadotropin therapy?

Answer 42

``` Ovarian hyperstimulation syndrome Multiple pregnancies Gynecomastia in men Ovarian cancer Ovarian cysts and hypertrophy ```

Question 43

What are contraindications of gonadotropin therapy?

Answer 43

``` Endocrine disorders Primary gonadal failure Pituitary or sex hormone dependent tumors Ovarian cyst Pregnancy ```

Question 44

What are the indications of gonadorelin?

Answer 44

Diagnosis of hypogonadism Stimulate ovulation Infertility in men (Hypogonadotropic hypogonadism)

Question 45

What are the side effects of gonadorelin?

Answer 45

Anaphylaxis with multiple administrations Lightheadedness & flushing Hypersensitivity dermatitis

Question 46

How do long acting GnRH analogs inhibit the gonadal axis?

Answer 46

Nonpulsatile GnRH inhibits the release of LH and FSH by desensitizing the GnRH receptors in the pituitary

Question 47

Indication for sustained GnRH analogs

Answer 47

IVF: keep LH surge low to provide multiple mature oocytes Endometriosis and uterine fibroids Prostate cancer adjuvant Central precocious puberty

Question 48

Side effects of sustained GnRH analog treatment

Answer 48

Hotflashes, sweats, headache Osteoporosis Urogenital atrophy

Question 49

Contraindications of sustained GnRH analog treatment

Answer 49

Pregnancy/Breast feeding | Hypersensitivity

Question 50

What is the biphasic effect of GnRH analog treatment?

Answer 50

First there is a flare of increased FSH and LH due to agonist effect, this is followed by a long lasting suppression of the entire axis.

Question 51

What is one advantage of GnRH receptor antagonists compared with the sustained GnRH analog therapy?

Answer 51

Antagonists do not have the flare effect that is associated with the long acting GnRH analogues.

Question 52

What are the indications for GnRH receptor antagonists?

Answer 52

Ganirelix and Cetrorelix are used for IVF controlled ovarian stimulation Abarelix is used for metastatic prostate cancer

Question 53

What are the side effects of GnRH receptor antagonists?

Answer 53

Ovarian hyperstimulation QT prolongation (Abarelix) Ectopic pregnancy, thrombotic disorder, spontaneous abortion (Ganirelix) Anaphylaxis (Cetrorelix)

Question 54

What are the contraindications for GnRH receptor antagonists?

Answer 54

Pregnancy, lactation, ovarian cysts (not from PCOS) Primary ovarian failure Thyroid/adrenal dysfunction Vaginal bleeding of unknown etiology

Question 55

What controls prolactin release?

Answer 55

Dopamine tonically inhibits prolactin release Prolactin release is increased by TRH *There is no negative feedback regulation*

Question 56

What is the physiologic role of prolactin?

Answer 56

Mammary gland development and milk biosynthesis | Inhibits GnRH release (suppresses ovulation during lactation)

Question 57

Presentation of hyperprolactinemia

Answer 57

Amenorrhea, galactorrhea and infertility in women | Loss of libido and infertility in men

Question 58

What drugs are used to treat hyperprolactinemia?

Answer 58

Dopamine agonists: Bromocriptine, Cabergoline, Pergolide

Question 59

How is prolactin deficiency treated?

Answer 59

No currently available treatments

Question 60

Side effects of dopamine agonists

Answer 60

Orthostatic hypotension Cerebrovascular accident, seizure, MI (bromocriptine) Arrhythmia, MI, heart failure (Pergolide) Pulmonary fibrosis and pleural effusion (Cabergolide)