Drugs Hypothalamic/Pituitary/etc

Question 1

What is IGF-2 used for?

Answer 1

gestational growth (note that GH is only present after birth)

Question 2

What are some drug analogs of GH?

Answer 2

Somatropin (brand names Serstim, Genotropin, Humatrope, Nutropin, and Saizen)

Question 3

What are some drug analogs of IGF-1 (aka somatomedin C)?

Answer 3

Mecasermin (Increlex)

NOTE: IGF-1 is made mostly in the liver.

This drug is not to be confused with mecasermin rinfabate (trade name Iplex), which is a combination of recombinant human IGF-1 (rhIGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3). IGFBP-3 serves to prolong the action of IGF-1 in the human body.

Question 4

What is a GH antagonist?

Answer 4

Pegvisomant (Somavert)

Question 5

What are some somatostatin (somatotroph antagonist) analogs?

Answer 5

Octreotide (Sandostatin)

Lanreotide (Somatuline LA)- better choice because its longer-acting BUT costs way more

Question 6

What are some dopamine agonists (aka prolactin antagonists)?

Answer 6

Cabergoline (dostinex)- higher affinity for D2 receptors, longer half-life

bromocriptine (Parlodel)- not well tolerated but FDA approved

Question 7

How is GH released?

Answer 7

GH is released in a pulsatile manner, thus, measuring GH levels is meaningless. Note that hypoglycemia is one factor that stimulates GH release while hyperglycemia would inhibit it

GH represents almost 50% of all anterior hormones released

Question 8

What are the actions of GH again?

Answer 8

The main effects of GH are either through direct action of via action of IGF-1 and consist of increased protein synthesis and linear growth, as well as increased lipolysis

NOTE: GH opposes the effects of insulin, and thus hypoglycemia is a symptom of children with deficient GH

Question 9

T or F. A child deficient of GH during gestation will be small for its gestational age

Answer 9

F. GH is not needed for prenatal growth

Question 10

Would a GH deficient adult be skinny or fat?

Answer 10

Fat because of GH’s actions of mediating lipolysis

Question 11

What is Sermorelin acetate?

Answer 11

GHRH analog that has been discontinued

Question 12

How should GH deficiency in childhood be treated?

Answer 12

hGH therapy in children is most effective in the first 2 yrs of life and therapy should continue until growth stops.

Question 13

What are the AEs of hGH therapy in children?

Answer 13

Few AEs but some children develop ntracrnail HTN, papilledema, visual changes, HA, and N/V

Question 14

What malignancy has been associated with hGH use in children?

Answer 14

Leukemia (thus hGH should NOT be used within 1-2 yrs following treatment of pediatric leukemia tumors)

Question 15

AEs of hGH in adults?

Answer 15

This leads to wanted effects such as increased muscle mass and bone and decreased fat, but may lead to peripheral edema, carpal tunnel syndrome, myalgias, and arthralgias

Question 16

How is IGF-1 deficiency (or a lack of GH receptor) treated?

Answer 16

This is a rare disorder that is treated with Mecasermin (Increlex), hIGF-1 only or Mecasermin rinfabate (iPlex), a complex of hIGF-1 and hIGFBP-3 (necessary to produce a longer half-life because children with severe IGF-1 deficiency usually have IGFBP deficiency also)

The benefit of iPlex is that there is not the hypoglycemia associated with Increlex but it is more expensive.

Question 17

How is GH excess treated?

Answer 17

Somatostatin analogs are the best treatment when pitutiary surgery is impossible and the most widely used is octreotide (Sandostatin) given as 3 daily injections or a long-acting slow release form called Sandostatin-LAR which is injected once every 4 weeks

NOTE: Lanreotide (somatuline LA) is now available in the US

Question 18

AEs of somatostatin analogs?

Answer 18

Mostly Gi disturbances including diarrhea, nausea, and abdominal pain

Question 19

What is the effect of Pegvisomant?

Answer 19

It is a GH receptor antagonist that decreases IGF-1 used for tx of acromegaly

NOTE: PEG is covelantly bound to decrease renal clearnace and extend half-life

Question 20

When do prolactin levels rise in a person?

Answer 20

Prolactin rises during pregnancy, remains elevated until birth, and falls thereafter unless the mother breast-feeds.

Question 21

What commonly causes hyperprolactinemia and how would it present?

Answer 21

Hyperprolactinemia is most often caused by pituitary adenomas or inhibition of dopamine. This may present as galactorrhea, amenorrhea, and infertility in women and loss of libido, impotence, and infertility in men

Question 22

How is hyperprolactinemia treated?

Answer 22

Usually treated by surgery, radiation, or the use of dopamine-receptor agonists (Cabergoline or bromocriptine) that suppress prolactin production through D2 receptors

Question 23

What are some thyrotropin-releasing hormone analogs and their functions?

Answer 23

• Protirelin (stimulates TSH release from the pituitary to test thyroid function not Tx)
• Thyrotropin alpha hTRH (Thyrogen) (used is diagnostics for thyroglobulin levels)

Question 24

What are the thyroid hormone analogs?

Answer 24

Levothyroxine (L-T4) (Synthroid, Levoxyl, Levothroid)

Liothyronine sodium (L-T3) (Cytomel tablets, Triostat injectables)

Liotrix (mixture of L-T4 and L-T3) (Thyrolar)

Question 25

What are some antithyroid synthesis drugs?

Answer 25

Propylthiouracil (PTU)

Methimazole (Tapazole)

Carbimazole (Neo-mercazole)

Question 26

How does iodine deficiency change the ratio of T4:T3 produced in the thyroid gland?

Answer 26

It changes from 4:1 to 1:3

Question 27

Adequate amounts of thyroid hormone are essential for normal fetal brain development. How does the baby get thyroid early in pregnancy?

Answer 27

The fetus relies on thyroid from maternal circulation in the first trimester

Question 28

How are thyroid hormones cycled through the body?

Answer 28

T3 and T4 are both metabolized in the liver through glucuronide conjugation and sulfate conjugation pathways that allow excretion of these hormones through the bile. Once in the GI, these hormones are subject to enterohepatic cycling because glucuronidases secreted by microorganisms in the lower intestine hydrolyze the glucuronide conjugates and release the free hormones to be reabsorbed.

Question 29

T or F. Thyroxine binding globulin binds T3 more tightly than T4

Answer 29

F. It binds T4 more tightly than T3 and in a 1:1 fashion

Question 30

What are some other carriers of thyroid hormones?

Answer 30

Transthyretin (TTR) binds 2:1 and also transports T4 in CSF

Albumin binds both T4 and T3

Question 31

When the pituitary reacts to levels of thyroid hormones in the blood, what is it reacting to?

Answer 31

Only the amount of ‘free’ or unbound hormone

Question 32

How does thyroid hormone act on target tissue?

Answer 32

They (both T4 and T3) bind to nuclear receptors on target tissues, specifically TRa1 receptor proteins, as well as TRB1 and TRB2, that bind to specific DNA sequences called thyroid hormone response elements to increase or decrease DNA transcription (note that while T4 binds to these receptors, only T3 can stimulate transcription).

T3 also binds avidly to mitochondrial membranes and activates the mitochondrial adenine nucleotide transporter

Question 33

What are the cardiac effects of thyroid hormone?

Answer 33

The CV effects of thyroid can be thought of as a response to increased peripheral oxygen consumption and are designed to get more blood to the periphery. This occurs via increasing HR (tachycardia), stroke volume, inducing cardiac hypertrophy, decreasing peripheral vascular resistance, and increased pulse pressure

This about how hyperthyroidism and hypothyroidism might present on a cardiac exam then

Question 34

What is Grave’s disease? Tx?

Answer 34

Condition where autoantibodies directed against TSH receptors on the thyroid gland stimulate increased hormone production and usually requires surgery, radiaoctive iodine, and drugs to treat

Question 35

One drug included for the treated of hyperthyroidism is PTU. How does it work?

Answer 35

Propylthiouracil binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines found in thyroglobulin.

PTU also acts by inhibiting the enzyme 5’-deiodinase, which converts T4 to T3 in the periphery

Question 36

Another drug for hyperthyroidism is methimazole. How does it work?

Answer 36

Methimazole binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine.

NOTE: Carbimazole is a pro-drug for methimazole

Question 37

Which is more potent, PTU or methimazole?

Answer 37

Methimazole is 10x more potent

Question 38

AEs of PTU?

Answer 38

The most common side effects are related to the skin, and include rash, itching, hives, abnormal hair loss, and skin pigmentation.

• agranulocytosis or thrombocytopenia (common in the first 3 months of treatment)
• fulminant liver failure (may occur at any point in treatment)

Question 39

Which hyperthyroid drug is preferred in pregnancy?

Answer 39

Propylthiouracil is classified as Drug Class D in pregnancy. Class D signifies there is positive evidence of human fetal risk. Maternal benefit may outweigh fetal risk in life-threatening situations. PTU is preferred over methimazole (which is also a class D) only in the first trimester of pregnancy and in woman who may become pregnant because of the increased risk of teratogenicity of methimazole during critical organogenesis. In the second and third trimester, this risk is diminished and methimazole is preferred to avoid the risk of liver complications from PTU in the mother

Question 40

What happens if PTU crosses the placenta?

Answer 40

The primary effect on the fetus from transplacental passage of PTU is the production of a mild hypothyroidism when the drug is used close to term. This usually resolves within a few days without treatment. The hypothyroid state may be observed as a goiter in the newborn, and is the result of increased levels of fetal pituitary thyrotropin. The incidence of fetal goiter after PTU treatment in reported cases is approximately 12%

Question 41

How is Propranolol used to treat hyperthyroidism? When is it preferred?

Answer 41

Prevents conversion of T4 to T3 and is preferred in some patients such as Graves disease and thyroid storm patients because T3 has potent effects on the heart

Question 42

What are some possible AEs of Iodinated contrast media (which are approved for improved contrast CT scans, cardiac caths, etc.)?

Answer 42

Can cause incident hyperthyrodisim in euthyroid pts. OR thyroid storm in hyperthyroid pts.

Question 43

How does large amounts of iodine affect the thyroid gland?

Answer 43

It inhibits all aspects of iodine metabolism by the thyroid gland, thus blocking release of thyroid hormone

Question 44

What are some of the treatment uses of iodine?

Answer 44

Can be used to treat thyroid storm in some patients and helps to decrease size, vascularity, and fragility of a hyperplastic gland. Thus, iodine is not designed to be a long-term treatment option but is a valuable adjuvant therapy, especially for pre-operative treatment.

Question 45

T or F. Iodine should not be used prior to radioactive iodide treatment

Answer 45

T.

Question 46

How is radioactive (Na131I) iodine used?

Answer 46

PO drug that concentrates in the thyroid gland, where B-radiation will destroy all or part of the parenchymal cells in several weeks causing hypothyroidism, but not surrounding thyroid tissue.

NOTE: There is no evidence of radiation-induced dmaage of other tissues

Question 47

What patients can use radioactive iodine?

Answer 47

Adults 35+, but not in women of child-bearing age