Pituitary Pathophys Flashcards
pituitary gland location and nearby nerves
in sella turcica of sphenoid bone
suspended from hypothalamus by pituitary stalk
nearby:
- optic chiasm, superiorly
- cavernous sinus
- CN 3, 4, 6 (all involved in eye movement)
- opthalmic and maxillary branches of CN 5
- internal carotid artery, laterally
clinical implications w/ pituitary tumor or bleed:
- bitemporal hemianopsia (vision loss)
- cranial nerve palsies, especially involving extraocular movement
- transsphenoidal surgery to avoid ICA
origin/makeup of anterior vs posterior pituitary
anterior pituitary
- adenohypophysis
- non-neuronal tissue
- formed from Rathkes pouch (ectodermal evagination of oropharynx)
- 5 subtypes of secretory cells:
- corticotropes (ACTH)
- gonadotropes (LH and FSH)
- somatotropes (GH)
- thyrotropes (TSH)
- lactotropes (prolactin)
posterior pituitary
- neurohypophysis
- nervous origin
- axons of hypothalamic and paraventricular origin
corticotroph axis
- ht: CRH, corticotropin-releasing hormone
- ap: ACTH, adrenocorticotropic hormone
- medulla of adrenal gland: cortisol
somatotroph axis
- ht: GHRH, growth hormone releasing hormone
- ap: GH, growth hormone
- liver (mainly): IGF-1
gonadotroph axis
- ht: GnRH, gonadotropin-releasing hormone
- ap: FSH and LH, follicular stimulating and luetenizing hormones
3f. ovaries: estradiOL, indirectly stimulates progesterone
3m. testes: testosterone
thyrotroph axis
- ht: TRH, thyrotropin releasing hormone
- ap: TSH, thyroid stimulating hormone
- thyroid: T3/T4
lactotroph axis
- ht: dopamine
- DOWNREGULATES ap: prolactin
when ht signalling is interrupted, all ap hormones except prolactin go down, prolactin goes up
cortisol stimuli
- circadian (morning, just before waking)
- inflammation
- hemorrhage
- hypoglycemia, fasting
- etc
cortisol suppression
- circadian (night)
- exogenous glucocorticoids, e.g. therapeutics
- pathophys e.g. primary adrenal insufficiency
LH and FSH stimuli
- pulsatile GnRH (continuous results in suppression)
LH and FSH suppression
- continuous GnRH (pulsatile stimulates)
- pathophys e.g. secondary hypogonadism
- negative feedback from estradiol or testosterone
GH suppression
- hypothalamic somatostatin
- IGF-1 negative feedback
- circadian (daytime)
GH stimuli
- pulsatile, circadian (night/sleep)
- GHRH
GH/IGF-1 functions
lipolysis –> FFA
amino acid uptake, protein synth –> muscle and soft tissue mass
growth plate chondrocytes –> skeletal linear growth
insulin antagonism –> hyperglycemia
prolactin stimuli
- estrogen
- sucking
- ht TRH
pathophys/hyperprolactinemia:
- prolactinoma
- hypophyseal stalk compression, lesion (interruption of ht dopamine)
- dopamine inhibitors
- enhanced TRH, e.g. primary hypOthyroid
- breast stimulation, e.g. chest wall injury
- reduced clearance (hepatic, renal insufficiency)
prolactin suppression
ht dopamine
arginine vasopressin (AVP)
- aka ADH
- posterior pituitary
- osmoreceptors in ht trigger in supraoptic and paraventricular nuclei (SON and PVN)
stimuli
- most sensitive: increased plasma osmolality
- also: RAAS system following 10-20% change in plasma volume or bp
suppressors
- baroreceptors in heart and lung (i.e. high bp shuts down production)
central diabetes insipidus etiology
- too little AVP (ADH)
caused by any of:
- lesion must destroy both PVN and SON (large lesion, they are far apart)
- lesion interrupting communication b/w PVN/SON and pp (i.e. directly above diaphragm sella/pituitary stalk)
- AVP gene mutations (autosomal recessive)
- pregnancy d/t placental vasopressinASE
central DI tx
- drink lots of water (but usually not sufficient in itself as demand could be upward of 18-20 L intake per day in absence of any AVP to concentrate urine)
- DDAVP (desmopressin) replacement therapy
SIADH etiology, labs
- too much ADH
caused by any of:
- ectopic production e.g. cancer
- drugs, esp psychotropes
- disruption of baroreceptor pathway (thorax or brain)
labs:
- concentrated urine: low volume, high Osm
- hyponatremia d/t continued water consumption despite decreased output
- potential volume overload
tx chronic vs acute hyponatremia
acute: treat fast
chronic: treat slow d/t risk of osmotic demyelination syndrome
only ____ hormones can be made ectopically (e.g. in tumors)
peptide
steroid hormones require too much machinery
basis for oral administration of sex steroid administration to lower sex steroids
tonic low-level GnRH (versus pulsatile GnRH) inhibits FSH/LH
Laron syndrome
GH insensitivity
high GH, low IGF-1
sx:
- short stature
- truncal obesity
- hypogonadism
- prominent forehead
- depressed nasal bridge
- underdeveloped mandible
- reduced susceptibility to cancer (tumors rely on IGF-1)
tx:
- IGF-1 injections help
pseudohypOparathyroidism
PTH resistance
high PTH
low Ca++
high PO4-
most common subtype: Albright’s hereditary osteodystrophy
- includes resistance to other hormones
McCune albright syndrome
Gs protein subunit activation
enhanced sensitivity to many hormones
mosaic pattern
sx:
- cafe au lait pigmentation d/t mosaic hypersensitivity to MSH
- fibrous dysplasia (fibrous, weak, uneven bone growth) d/t FGF hypersensitivity
- precocious puberty, F>M d/t GnRH production and ovarian cysts (F) or autonomous testosterone production (M)
- in males, macroorchidism (large testes) and/or testicular lesions
- hypophosphatemia
- other peptide hormone hypersensitivities may also occur, e.g. hyperthyroidism, growth hormone excess, neonatal Cushing’s syndrome (ACTH)
tx:
- hormone antagonists
- (including puberty blockers)
acidophils
pink-staining cells of anterior pituitary
somatotrophs: GH
mammotrophs/lactotrophs: prolactin
basophils (pituitary)
dark staining cells of anterior pituitary
thyrotrophs: TSH
gonadotrophs: FSH and LH
corticotrophins: ACTH
chromophobes
non-staining cells of anterior pituitary
degranulated/dying cells
stem cells
posterior pituitary histology
mostly storage cells
storage only, ADH and oxytocin
monotonous appearance on AP histology
indicates an adenoma (overgrowth of one cell type)
H&E (acidophilic/basophilic), IHC, clinical picture can identify hormone
prolactinoma
eosinophilic monotonous AP adenoma
most common pituitary adenoma
hypogondadism
amenorrhea
galactorrhea
