Endo 1-14 Acromegaly And Hyperprolactinemia

Front 1

Physical appearance of acromegaly

Back 1

coarse facies, large tongue, doughy hands (wide), small and soft testes, sweaty

expansion of frontal sinuses and elongation of mandible

spaces btwn teeth

thick finger pads

Front 2

Acromegaly cause

Back 2

Excessive GH secretion that is also not properly regulated (autonomous)

Front 3

Dx of acromegaly

Back 3

Oral glucose load doesn't suppress GH levels, as it normally should.

IGF1 will be grossly elevated as well.

Front 4

Things associated with acromegaly

Back 4

HTN and Type II Diabetes

Front 5

Secretion of GH

Back 5

pulsatile and the levels vary.

Front 6

Molecular cause of acromegaly

Back 6

Somatic mutation in the cell that gives origin to the tumor and makes GH (in the anterior pituitary)

Mutation often in G subunit of signaling of GHRH receptor. Gain of function. Adenylate cyclase engaged even without its ligand.

cAMP levels are very very high.

Front 7

Therapeutic options for acromegaly

Back 7

Transnasal adenectomy (standard) or subfrontal craniotomy (for very large tumors that may have invaded laterally)

Radiation

Medical - DA agonists (bromocryptine or cabergoline) or long-acting somatostatin analog (octreotide)

*somatostatin inhibits GH secretion

Front 8

When to use DA agonist vs. somatostatin analog to tx acromegaly?

Back 8

If cell giving rise to tumor was the progenitor that can give rise to both prolactin and GH secreting cell.

(embryological subtypes are present in the adult)

Front 9

Half life of somatostatin

Back 9

short - susceptible to peptidases.

Front 10

Can acromegaly features reverse?

Back 10

yes

Front 11

Secondary deficiencies

Back 11

means that the target gland is fine, but the hypothalamus/pituitary is busted.

Front 12

Clinical manifestations of hyperprolactinemia - female

Back 12

galactorrhoea, menstrual irreg, infertility

Front 13

Clinical manifestations of hyperprolactinemia - male

Back 13

galactorrhoea, visual field abnormalities, HA, impotence, EOM paralysis, ant pit malfunction

Front 14

DDx of hyperprolactinemia

Back 14

Hypothalamic disease - tumor (craniopharyngioma, met) or infiltrative (sarcoidosis, histiocytosis)

Pituitary disease - prolactinoma, acromegaly, TSH-oma, stalk section/compression (messes with dopamine)

Hypothyroidism (primary)

Chronic renal failure

Neurally-medicated (chest wall lesion or breast stimulation)

Drugs - antipsychotics, antidepressants, opiates, DA antagonists

Front 15

Effect of prolactin on gonadal function

Back 15

inhibits it, so LH and FSH are commonly low in a prolactinoma.

Front 16

Reasons to tx prolactinoma

Back 16

can get infertility/hypogonadism, osteoporosis (lack of sex steroids), mass effect of large tumors (visual issues)

Front 17

Tx options for prolactinoma

Back 17

Surgical (will have high recurrence rate) - transnasal

medical - long acting DA agonists - THIS IS THE PREFERRED TX - reduce prolactin secretion and size

Radiation - for large tumors not responded to meds and can be surgically treated.

Front 18

Bromocriptine and cabergoline during pregnancy?

Back 18

NO!

Front 19

Txpn factors in development of cells in pituitary (slide 28)

Back 19

Homeobox txpn factors.

Prop1 - without it, all cells secrete ACTH initially, but then structural issues make ACTH secretion go down too.

PIT1 - if deficient, children have secondary hypothyroidism, GH def, prolactin def. FSH, LH and ACTH are fine though.

Front 20

Most common cause of neonatal hypopituitarism

Back 20

Mutation of homeobox genes to cause familial combined pituitary hormone deficiency.

Front 21

For a pt with amenorrhea-galactorrhea, you must rule out...

Back 21

HYPOTHYROIDISM!!!

Front 22

Development of anterior pituitary

Back 22

invagination of oral ectoderm (Rathke's pouch)

Front 23

Cushing's disease vs. syndrome

Back 23

Disease - only hypercortisolism from excess pituitary ACTH production.

Syndrome - Any form of hypercortisolism (incl. Cushing's disease)

Front 24

Causes of pituitary hyperfunction

Back 24

Pituitary adenoma
Ectopic prod of hypothal releasing hormones by malignant tumors
Hyperprolactinemia only from compression of stalk, damage to hypothal, admin of DA antags.

Front 25

Causes of pituitary hypofunction

Back 25

Inactivating mutations in txpn factors (e.g. Pit-1)
Nonfunc. pituitary tumors (craniopharyngioma-from Rathke's pouch or cysts)
Tumors from adjacent tissues
Ischemia
Radiation
Infiltration
Mets
Hemochromatosis
Lymphocytic hypophysitis
Compression by carotid artery aneurysm.
C

Front 26

Testing thyroid axis

Back 26

TSH levels

in secondary disease, approp increase in TSH in response to a low free T4 fails to occur.

Front 27

Testing gonadal axis

Back 27

Clinical history, exam, LH and FSH levels.

Front 28

GH axis

Back 28

Hypofunction - GH secretion provoked by arginine+GHRH

Hyperfunction - GH levels suppressed after glucose load. Raised IGF1 levels.

Front 29

Testing prolactin axis

Back 29

Hypofunction - stimulating with anti-dopaminergics or TRH (TRH at high levels can induce prolactin production)

Hyperfunction - Static levels are elevated

Front 30

Adrenals

Back 30

Hypofunction - Cortisol should rise after ACTH injection. To tell if primary or secondary, approp raised ACTH levels with low cortisol will indicate primary.
(does that make sense?)

Hyperfunction - Supp of cortisol after glucocorticoid injection, 24 hour urine, failure of levels to fall in evening...

Front 31

GH stimulates...

Back 31

IGF1

Front 32

One other sx of acromegaly

Back 32

cardiomegaly

Front 33

Prolactin levels over ___ indicate prolactinoma?

Back 33

200 ng/mL

Front 34

Prolactin effects on gonadal axis

Back 34

suppresses GnRH release and inhibits responsiveness of LH/FSH producing cells to stimulationg by GnRH