H-P pathophys 175 Flashcards
Congenital hypothalamic diseases are often due to mutations in ____________.
Congenital hypothalamic diseases are often due to mutations in transcription factors necessary for hypothalamic/pituitary development.
What do craniopharyngiomas arise from?
cysts from Rathke’s pouch
Of the acquired causes of hypothalamic diseases, ________ often leads to mass effect and _________ often leads to stalk thickening.
Of the acquired causes of hypothalamic diseases, tumors often leads to mass effect and infiltrative disease often leads to stalk thickening.
What are major causes of infiltrative hypothalamic disease?
- Langerhans cell histiocytosis
- Sarcoidosis
- Tuberculosis
What are the major clinical manifestations of hypothalamic disorders?
- hypopituitarism
- hyperprolactinemia
- disordered vasopressin regulation
- disordered food intake or temperature regulation possible
What is Kallmann’s syndrome?
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
What is hypothalamic amenorrhea?
anovulation and/or hypogonadism in women due to severe illness, weight loss, psychological stress, excessive exercise
usually reversible
What is precocious puberty?
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”
What is the mechanism of hyperprolactinemia?
interference with hypothalamic tonic inhibition of PRL secretion by dopamine leads to excess PRL secretion
Mutations in which two transcription factors may lead to congenital hypopituitarism?
PIT-1 and PROP-1
transcription factors that code for formation of parts of the anterior pituitary during embryogenesis
What are major causes of acquired anterior pituitary hypofunction?
- tumors
- infarcts
- empty sella
What is pituitary apoplexy? What are symptoms?
hemorrhagic infarct of existing tumor in the anterior pituitary
leads to headache, stiff neck, hypotension, and sudden onset hypopituitarism
What is Sheehan syndrome? What are the symptoms?
postpartum pituitary infarction usually in setting of postpartum hemorrhage
acute: hypotension, failure to lactate
chronic: fatigue, failure to lactate, failure to menstruate
What is the manifestation of growth hormone deficiency in adults? Children?
adults: subtle, variable, decreased muscle and bone mass, increased fat mass
children: “falling off the growth curve,” failure to grow normally
How are growth hormone deficiencies diagnosed?
GH stimulation test
IGF-1 level is not a good measure
What are the clinical manifestations of TSH deficiency? How is it diagnosed?
manifestation: secondary hypothyroidism
diagnosis: low thyroid hormones (T4, T3) and low to normal TSH
What are the major clinical manifestations of adrenocorticotropic hormone (ACTH) deficiency?
secondary adrenal insufficiency
leads to hyponatremia (cortisol loss) but NOT hyperkalemia (aldosterone normal)
Mutation in the gene for Pit-1 transcription factor can lead to congenital deficiencies of which anterior pituitary hormones?
GH, PRL, TSH
Mutation in the gene for PROP-1 transcription factor can lead to congenital deficiencies of which anterior pituitary hormones?
GH, PRL, TSH, LH/FSH
Tumors in what organs are associated with multiple endocrine neoplasia type 1?
pituitary, parathryoid, pancreas
Familial isolated pituitary adenomas are frequently due to a mutation in __________ gene and are most commonly _____ or _____ producing.
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.
What gene is mutated in carney syndrome? What are the major manifestations?
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
How are pituitary tumors treated?
usually surgery (transsphenoidal or transcranial)
EXCEPT prolactinomas (treated with dopamine agonists)
What are the major mass effect related symptoms of pituitary tumors?
optic chiasm compression (bitemporal hemianopsia)
cavernous sinus CN compression (III, IV, V1, VI)
hypothalamus (hypopituitarism, diabetes insipidus, hyperprolactinemia)
What happens to prolactinomas during pregnancy?
dopamine agonist drugs are safe for pregnancy
hormones during pregnancy can stimulate tumors to grow more
How is diabetes insipidus diagnosed?
osmotic stimulation (dehydration test)
measure urine and serum osmolalities
if positive, serum osmolality will go up but urine will not concentrate
What are major etiologies of hyponatremia/hypoosmolality?
- volume depletion or other triggers of AVP release
- pituitary surgery
- SIADH
- ectopic cancer producing AVP
Diabetes insipidius is usually acquired following __________ or ___________ and is treated with _____________.
Diabetes insipidius is usually acquired following surgery or head trauma and is treated with desmopressin.
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
b) hearing
Kallmann’s syndrome –> failure of olfactory tracts and GnRH neurons to migrate to the final resting place in the brain
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
c) prolactin
- prolactinomas are most common hormone-secreting pituitary tumors*
- high PRL suppresses gonadotropin secretion –> amenorrhea, breast milk production*
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
d) desmopressin
symptoms suggest diabetes insipidus with polyuria and polydipsia –> treat with desmopressin (synthetic analog of vasopressin)
