SM146/147 Hypothalamus Pathophys

Question 1

Congenital hypothalamic malformation: genes, associated defects?

Answer 1

HESX2, LHX2, LHX4, SOX2, SOX3

Absent septum pellucidum, corpos callosum agenesis, optic nerve dysplasia

Question 2

Infiltrative hypothalamic disease types?

Answer 2

Langerhans cell histiocytosis: most common, interstitial lung disease, lytic bone lesions, decreased DLCO

Sarcoidosis: lung, non-caseating granulomas

TB

Question 3

Manifestations of hypothalamic disease?

Answer 3

Hypopituitarism (if transcription facto defect, more likely to be global hypopituitarism)

Disorders of vasopressin regulation

Hyperprolactinemia (stalk disfunction)

Question 4

Hypogonadotropic hypogonadism (two types)

Answer 4

Kallmann’s syndrome: absent GnRH causes hypogonadism. Mutation in anosmin, gene that facilitates migration of olfactory and GnRH neurons (also see anosmia)

Hypothalamic amenorrhea: an ovulation and/or hypogonadism during severe illness, weight loss, stress, associated with anorexia

Question 5

Mutations that can cause anterior pituitary hypofunction?

Answer 5

PIT-1 and PROP-1 (transcription factors)

Transcription factors cause multiple deficiencies, hormone and hormone receptor genes cause single deficiencies

Question 6

Craniopharyngioma

Answer 6

Benign childhood tumor (most common supratentorial tumor), derived from Rathke’s pouch, calcifications, cholesterol crystals

Question 7

Septo-optic dysplasia

Answer 7

Congenital: hypopituitarism, absent septum pellucidum, agenesis of corpus callosum, optic nerve dysplasia

Implicated genes: HESX1, SOX2, SOX2, OTX2

Question 8

Precocious puberty

Answer 8

More common in girls, about 1/3 have CNS disease, mechanism unknown

Question 9

Hyperprolactinemia

Answer 9

Caused prolactin-secreting tumors (most common) or by interference with hypothalamic tonic inhibition of PRL secretion by dopamine or by dopamine antagonists

Causes reproductive/sexual dysfunction

Question 10

Mass effects of seller lesions

Answer 10

Headache, visual defects, nerve palsies, hypopituitarism, DI

Question 11

Pituitary apoplexy

Answer 11

Hemorrhagic infarction of a preexisting tumor. Signs: headache, stiff neck, hypotension, hypopituitarism

Question 12

Sheehan’s syndrome

Answer 12

Postpartum pituitary infarction secondary to occlusive vasospasm caused by hypotension. Acute: hypotension, failure to lactate. Chronic: fatigue, failure to lactate, amenorrhea.

Question 13

Empty sella syndrome

Answer 13

Congenital or acquired (from chronic high intracranial pressure). 1/3 have hypopituitarism

Question 14

Hypoprolactinemia

Answer 14

Postpartum failure to lactate

Rare, need to destroy a lot of the pituitary (very common cell)

Question 15

Still need to finish these

Answer 15

Still need to finish these