Pituitary excess syndromes

Question 1

What hormones work on the hypothalamus by negative feedback regulation?

Answer 1

hormones from target glands, ex estrogen, testosterone, thyroxine, cortisol

Question 2

What hormones are “releasing” hypothalamic hormones?

Answer 2

TRH, GnRH, CRH, GHRH

Question 3

What hormones are “inhibiting” hypothalamic hormones

Answer 3

somatostatin, dopamine

Question 4

List the anterior pituitary hormones

Answer 4

ACTH, GH, PRL, FSH, LH, TSH

Question 5

List the posterior pituitary hormones

Answer 5

vasopressin/ ADH and oxytocin

Question 6

Describe in general the mechanisms of syndromes of excess pituitary hormones

Answer 6

• hypersecretion by pituitary
• ectopic secretion of pituitary hormones
• disruption of inhibitory signals (ex stalk effect)
• excess stimulatory signals for pituitary hormone release
• impaired renal clearance

Question 7

Prolactin is secreted in a ____ and ____ fashion, with highs around 5 am and lows around noon

Answer 7

bimodal, pulsatile

Question 8

Prolactin is under tonic _____ control

Answer 8

inhibitory control by dopamine

Question 9

How does dopamine inhibit prolactin secretion

Answer 9

• syntehsized in tuberoinfundibular neurons, transported into hypophyseal portal circulation
• reaches anterior pituitary, interacts with inhibitory G protein coupled receptors on lactotrophs

Question 10

What factors stimulate prolactin release?

Answer 10

• TRH- ex the cause of hyperprolactinemia in people with primary hypothyroidism
• estrogen: lowers lactotroph sensitivity to inhibition by dopamine, decreases dopamine secretion, increases sensitivity to TRH stimulation

Question 11

List physiologic effects of prolactin

Answer 11

• inhibits GnRH, thus leading to decreased LH/FSH and decreased gonadal function
• stimulates milk production

Question 12

List physiologic causes of hyperprolactinemia

Answer 12

pregnancy
lactation
nipple stimulation
stress
REM sleep
sex
exercise

Question 13

List pharmacologic causes of hyperprolactinemia

Answer 13

dopamine receptor antagonists
antidepressants
estrogen

Question 14

List pathologic causes of hyperprolactinemia

Answer 14

prolactinoma
pituitary stalk disruption- stalk effect
primary hypothyroidism
renal failure
intercostal nerve stimulation ex chest wall injury

Question 15

A prolactin level of greater than 200 is almost always indicative of a __________

Answer 15

prolactin secreting tumor

Question 16

List the major symptoms of hyperprolactinemia

Answer 16

• gonadal dysfunction: infertility, amenorrhea, decreased libido, ED, loss of body hair, reduced muscle mass, gynecomastia
• galactorrhea- most common in pre-menopausal women
• mass effect: headaches, visual changes

Question 17

Why are do men and post-menopausal women not usually experience galactorrhea in hyperprolactinemia?

Answer 17

need estrogen to sensitize breast tissue to the effects of prolactin

Question 18

Prolactinomas arise from monoclonal expansion of a single ________ after having undergone mutation

Answer 18

lactotroph

Question 19

Up to 10% of prolactinomas co-secrete GH because they are made up of lactotrophs and _______

Answer 19

somatotrophs

Question 20

What is first line treatment of prolactinomas?

Answer 20

dopamine agonists such as bromocriptine or cabergoline

Question 21

What are the side effects of dopamine agonist therapy?

Answer 21

NV, headache, congestion, orthostasis

Question 22

______ is reserved for patients with prolactinomas that are refractory to dopamine agonist treatment

Answer 22

surgery, radiation

Question 23

Describe the major physiological functions of growth hormone

Answer 23

• linear growth in children

- lipid, protein, carb metabolism in adults; protein sparing effects- increased protein synthesis and lipolysis

Question 24

Many GH effects are mediated by _____

Answer 24

IGF-1

Question 25

Contrast the effects of GH vs IGF-1 on carbohydrate metabolism

Answer 25

IGF-1 increases glucose uptake peripherally, decreases hepatic glucose output, and decreases lipolysis. GH increases insulin resistance, decreases peripheral glucose utilization, and increases hepatic glucose output.

Question 26

Both GH and GHRH stimulate _____ release

Answer 26

somatostatin

Question 27

List physiologic causes of GH excess

Answer 27

stress exercise REM sleep fasting

Question 28

List pharmacologic causes of GH excess

Answer 28

insulin induced hypoglycemia norepinephrine clonidine estrogen

Question 29

List pathologic causes of GH excess

Answer 29

``` pituitary adenomas ectopic GHRH secreting tumors anorexia nervosa hepatic/ renal failure cachexia ```

Question 30

Pituitary adenoma is the most common cause of ______ and _______

Answer 30

acromegaly, gigantism

Question 31

Describe the pattern of GH secretion in acromegaly

Answer 31

still episodic but increased number, duration, frequency, amplitude of spikes loss of response to hypoglycemia/ hyperglycemia

Question 32

List the clinical manifestations of GH excess

Answer 32

``` acral enlargement soft tissue overgrowth hyperhidrosis fatigue arthralgias weight gain paresthesias acanthosis nigricans HTN renal stones cardiomegaly impaired glucose tolerance ```

Question 33

_____ is a good screening test for GH excess because its levels are not affected by food intake or time of testing

Answer 33

IGF-1

Question 34

What treatments are used for GH secreting pituitary adenomas?

Answer 34

- trans-sphenoidal surgery - somatostatin analogue ex octreotide - dopamine agonists (generally less effective) - GH receptor antagonists- still high body level of GH but decrease in GH mediated actions