H-P pathophys 175

Question 1

Congenital hypothalamic diseases are often due to mutations in ____________.

Answer 1

Congenital hypothalamic diseases are often due to mutations in transcription factors necessary for hypothalamic/pituitary development.

Question 2

What do craniopharyngiomas arise from?

Answer 2

cysts from Rathke’s pouch

Question 3

Of the acquired causes of hypothalamic diseases, ________ often leads to mass effect and _________ often leads to stalk thickening.

Answer 3

Of the acquired causes of hypothalamic diseases, tumors often leads to mass effect and infiltrative disease often leads to stalk thickening.

Question 4

What are major causes of infiltrative hypothalamic disease?

Answer 4

• Langerhans cell histiocytosis
• Sarcoidosis
• Tuberculosis

Question 5

What are the major clinical manifestations of hypothalamic disorders?

Answer 5

• hypopituitarism
• hyperprolactinemia
• disordered vasopressin regulation
• disordered food intake or temperature regulation possible

Question 6

What is Kallmann’s syndrome?

Answer 6

forebrain defect resulting in anosmia and absent GnRH with hypogonadism

caused by muttation in anosmin gene that facilitates migration of olfactory and GnRH neurons to final location

Question 7

What is hypothalamic amenorrhea?

Answer 7

anovulation and/or hypogonadism in women due to severe illness, weight loss, psychological stress, excessive exercise

usually reversible

Question 8

What is precocious puberty?

Answer 8

a condition more common in girls than boys where puberty starts earlier than it is supposed to

caused by early gonadotropin secretion

can be “central” or “peripheral”

Question 9

What is the mechanism of hyperprolactinemia?

Answer 9

interference with hypothalamic tonic inhibition of PRL secretion by dopamine leads to excess PRL secretion

Question 10

Mutations in which two transcription factors may lead to congenital hypopituitarism?

Answer 10

PIT-1 and PROP-1

transcription factors that code for formation of parts of the anterior pituitary during embryogenesis

Question 11

What are major causes of acquired anterior pituitary hypofunction?

Answer 11

• tumors
• infarcts
• empty sella

Question 12

What is pituitary apoplexy? What are symptoms?

Answer 12

hemorrhagic infarct of existing tumor in the anterior pituitary

leads to headache, stiff neck, hypotension, and sudden onset hypopituitarism

Question 13

What is Sheehan syndrome? What are the symptoms?

Answer 13

postpartum pituitary infarction usually in setting of postpartum hemorrhage

acute: hypotension, failure to lactate
chronic: fatigue, failure to lactate, failure to menstruate

Question 14

What is the manifestation of growth hormone deficiency in adults? Children?

Answer 14

adults: subtle, variable, decreased muscle and bone mass, increased fat mass
children: “falling off the growth curve,” failure to grow normally

Question 15

How are growth hormone deficiencies diagnosed?

Answer 15

GH stimulation test

IGF-1 level is not a good measure

Question 16

What are the clinical manifestations of TSH deficiency? How is it diagnosed?

Answer 16

manifestation: secondary hypothyroidism
diagnosis: low thyroid hormones (T4, T3) and low to normal TSH

Question 17

What are the major clinical manifestations of adrenocorticotropic hormone (ACTH) deficiency?

Answer 17

secondary adrenal insufficiency

leads to hyponatremia (cortisol loss) but NOT hyperkalemia (aldosterone normal)

Question 18

Mutation in the gene for Pit-1 transcription factor can lead to congenital deficiencies of which anterior pituitary hormones?

Answer 18

GH, PRL, TSH

Question 19

Mutation in the gene for PROP-1 transcription factor can lead to congenital deficiencies of which anterior pituitary hormones?

Answer 19

GH, PRL, TSH, LH/FSH

Question 20

Tumors in what organs are associated with multiple endocrine neoplasia type 1?

Answer 20

pituitary, parathryoid, pancreas

Question 21

Familial isolated pituitary adenomas are frequently due to a mutation in __________ gene and are most commonly _____ or _____ producing.

Answer 21

Familial isolated pituitary adenomas are frequently due to a mutation in aryl hydrocarbone receptor interacting protein (AIP) gene and are most commonly GH or PRL producing.

Question 22

What gene is mutated in carney syndrome? What are the major manifestations?

Answer 22

mutation of type 1a subunit of protein kinase A

symptoms: pituitary adenoma (often GH), spotty skin pigmentation, myxomas, schwannomas, cortical disease causing Cushing’s syndrome

Question 23

How are pituitary tumors treated?

Answer 23

usually surgery (transsphenoidal or transcranial)

EXCEPT prolactinomas (treated with dopamine agonists)

Question 24

What are the major mass effect related symptoms of pituitary tumors?

Answer 24

optic chiasm compression (bitemporal hemianopsia)

cavernous sinus CN compression (III, IV, V1, VI)

hypothalamus (hypopituitarism, diabetes insipidus, hyperprolactinemia)

Question 25

What happens to prolactinomas during pregnancy?

Answer 25

dopamine agonist drugs are safe for pregnancy

hormones during pregnancy can stimulate tumors to grow more

Question 26

How is diabetes insipidus diagnosed?

Answer 26

osmotic stimulation (dehydration test)

measure urine and serum osmolalities

if positive, serum osmolality will go up but urine will not concentrate

Question 27

What are major etiologies of hyponatremia/hypoosmolality?

Answer 27

• volume depletion or other triggers of AVP release
• pituitary surgery
• SIADH
• ectopic cancer producing AVP

Question 28

Diabetes insipidius is usually acquired following __________ or ___________ and is treated with _____________.

Answer 28

Diabetes insipidius is usually acquired following surgery or head trauma and is treated with desmopressin.

Question 29

A 16 yo boy is brought in by his parents because he has not yet started puberty. On examination he is found to be prepubertal. On your examination of him, which of the following senses might be expected to be abnormal?

a) vision
b) hearing
c) smell
d) touch
e) pain

Answer 29

b) hearing

Kallmann’s syndrome –> failure of olfactory tracts and GnRH neurons to migrate to the final resting place in the brain

Question 30

A 27 yo woman who had been previously well has developed amenorrhea (loss of menses) and galactorrhea. Which one of the following hormones might you expect to be elevated?

a) growth hormone
b) vasopressin
c) prolactin
d) ACTH
e) leutinizing hormone

Answer 30

c) prolactin

• prolactinomas are most common hormone-secreting pituitary tumors*
• high PRL suppresses gonadotropin secretion –> amenorrhea, breast milk production*

Question 31

An 18 yo woman developed amenorrhea and galactorrhea one year ago. Several weeks ago she noticed the onset of polyuria and polydipsia. She has to get up 3-4 times per night to drink and urinate. In retrospect, she also feels more fatigued. She has seen her primary physician who noted that her blood glucose level was normal but her serum sodium was elevated at 152 mEq/L. Which of the following treatments would be expected to decrease her polyuria and polydipsia?

a) bromocriptine
b) octreotide
c) hydrocortisone
d) desmopressin
e) thyroxine

Answer 31

d) desmopressin

symptoms suggest diabetes insipidus with polyuria and polydipsia –> treat with desmopressin (synthetic analog of vasopressin)