Pituitary Hormone Excess

Question 1

Effect of estrogen on prolactin

Answer 1

Estrogen also promotes prolactin release by reducing DA secretion, reducing sensitivity to DA, and increasing sensitivity to TRH

Question 2

What does somatostatin inhibit?

Answer 2

GH

Question 3

What does prolactin inhibit?

Answer 3

GnRH

Question 4

What stimulated prolactin?

Answer 4

TRH and estrogen

Question 5

7 physiologic causes of hyperprolacinemia

How high are levels?

Answer 5

Pregnancy, lactation, nipple stimulation, REM sleep, stress, sex, exercise
Usually less than 50 ng/mL

Question 6

3 pharmacologic causes of hyperprolactinemia

How high are levels?

Answer 6

DA receptor blocker, antidepressants, estrogen

Usually less than 100 ng/mL

Question 7

5 pathologic cause sof hyperprolactinemia

Answer 7

Prolactinoma, pituitary stalk disruption, primary hypothyroidism (high TRH), renal failure, intercostal nerve stimulation / chest wall injury

Question 8

Prolactin levels in micro / macro adenomas

Size

Answer 8

•Microadenomas (200 ng/mL

Question 9

Treating prolactinomas (5)

Answer 9

• DA agonist is 1st line – bromocriptine or cabergoline. 90% of tumors respond
• Surgery / radiation is reserved for refractory cases.
• Others
• Oral contraceptives replace back estrogen for women, and allow endometrial shedding via progestin. Does not treat the galactorrhea.
• Thyroid hormone if due to primary hypothyroidism

Question 10

What stimulates somatostatin release?

Answer 10

High GH and GHRH

Question 11

Effects of GH (6)

Answer 11

• Primary function in kids is linear growth. Kids / teens secrete more GH than adults.
• In all people, it increases protein synthesis, increases lipolysis, and decreases carb utilization. Prevents protein breakdown, which aids in growth. Creates insulin resistance.

Question 12

Effects of IGF1 (3)

Answer 12

IGF1 acts similarly to insulin: increases glucose uptake peripherally, decreases hepatic glucose output, and decreases lipolysis.

Question 13

3 counter regulatory functions of GH

Answer 13

Increases insulin resistance, decreases peripheral glucose utilization, and increases hepatic glucose output.

Question 14

4 physiologic causes of high GH

Answer 14

Stress, exercise, REM sleep, fasting

Question 15

4 pharmacologic causes of high GH

Answer 15

Insulin-induced hypoglycemia, Norepi, clonidine (alpha 2 agonist for HTN), estrogen

Question 16

6 pathologic causes of high GH

Answer 16

Pituitary adenoma (most common), ectopic GHRH tumor, anorexia, hepatic / renal failure, cachexia

Question 17

Glucose effects on GH

Answer 17

Hypoglycemia stimulates GH.

Hyperglycemia inhibits GH.

Question 18

Metabolic consequences of high GH (7)

Answer 18

HTN, diabetes, hypertriglyceridemia, hypercalciuria, heart disease, sleep apnea, colon polyps / cancer.

Question 19

Diagnosing GH excess

Answer 19

• Elevated IGF1 is best screening test
• Gold standard is glucose tolerance test. Normal response is suppression of GH to less than 1 ng/mL 1-2 hrs after ingesting 75g glucose. Pxs w/ excess fail to suppress GH.
• Next step is to localize the tumor w/ imaging.

Question 20

Treating GH excess: 3 main types

Answer 20

• 1st line therapy is transsphenoidal surgery (TSS).
• Drugs are for pxs w/ persistent GH after TSS.
• Somatostatin analogs – octreotide, lanreotide, pasireotide
• DA agonists – bromocriptine, cabergoline.
• GH receptor antagonists – Pegvisomant
• Radiation is reserved for pxs refractory to surgery and drugs.

Question 21

3 somatostatin analogs

Mechanism

Answer 21

• Octreotide, lanreotide, pasireotide

* Mechanism - Inhibit GH secretion, and thus decrease IGF1 levels

Question 22

Pegvisomant
Type of drug
Mechanism
Change in GH and IGF1 level

Answer 22

• GH receptor antagonist
• Mechanism - Competitive inhibition
• IGF1 production decreases
• GH levels may rise due to lack of negative feedback.