Pituitary Hormone Excess Flashcards
Effect of estrogen on prolactin
Estrogen also promotes prolactin release by reducing DA secretion, reducing sensitivity to DA, and increasing sensitivity to TRH
What does somatostatin inhibit?
GH
What does prolactin inhibit?
GnRH
What stimulated prolactin?
TRH and estrogen
7 physiologic causes of hyperprolacinemia
How high are levels?
Pregnancy, lactation, nipple stimulation, REM sleep, stress, sex, exercise
Usually less than 50 ng/mL
3 pharmacologic causes of hyperprolactinemia
How high are levels?
DA receptor blocker, antidepressants, estrogen
Usually less than 100 ng/mL
5 pathologic cause sof hyperprolactinemia
Prolactinoma, pituitary stalk disruption, primary hypothyroidism (high TRH), renal failure, intercostal nerve stimulation / chest wall injury
Prolactin levels in micro / macro adenomas
Size
•Microadenomas (200 ng/mL
Treating prolactinomas (5)
- 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
What stimulates somatostatin release?
High GH and GHRH
Effects of GH (6)
- 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.
Effects of IGF1 (3)
IGF1 acts similarly to insulin: increases glucose uptake peripherally, decreases hepatic glucose output, and decreases lipolysis.
3 counter regulatory functions of GH
Increases insulin resistance, decreases peripheral glucose utilization, and increases hepatic glucose output.
4 physiologic causes of high GH
Stress, exercise, REM sleep, fasting
4 pharmacologic causes of high GH
Insulin-induced hypoglycemia, Norepi, clonidine (alpha 2 agonist for HTN), estrogen
6 pathologic causes of high GH
Pituitary adenoma (most common), ectopic GHRH tumor, anorexia, hepatic / renal failure, cachexia
Glucose effects on GH
Hypoglycemia stimulates GH.
Hyperglycemia inhibits GH.
Metabolic consequences of high GH (7)
HTN, diabetes, hypertriglyceridemia, hypercalciuria, heart disease, sleep apnea, colon polyps / cancer.
Diagnosing GH excess
- 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.
Treating GH excess: 3 main types
- 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.
3 somatostatin analogs
Mechanism
- Octreotide, lanreotide, pasireotide
* Mechanism - Inhibit GH secretion, and thus decrease IGF1 levels
Pegvisomant
Type of drug
Mechanism
Change in GH and IGF1 level
- GH receptor antagonist
- Mechanism - Competitive inhibition
- IGF1 production decreases
- GH levels may rise due to lack of negative feedback.
