Endocrine Path 1: Pituitary Flashcards
organs
- pituitary gland
- thyroid gland
- parathyroid gland
- pancreas
- adrenal glands
- pineal gland
posterior pit- consists of?
-modified glial cells (pituicytes) and axonal processes that extended from the hypothalamus thru the pit stalk to the posterior lobe (axon terminals)
what stim ADH secretion?
- dec BP- baroRs(in cardiac atria and carotids)
- inc in plasma osmotic P- osmoRs
Anterior pituitary- cell types
- somatotrophs- GH
- mammosomatotroph- GH and prolactin
- lactotroph- prolactin
- corticotroph- ACTH and POMC, and MSH (melanocyte-stimulating H)
- thyrotroph- TSH
- gonadotroph- FSH and LH
somatotroph- secrete? adenoma subtypes? assoc syndrome?
- GH
- densely and sparsely granulated somatotroph adenoma
- silent somatotroph adenoma
- gigantism (children); acromegaly (adults)
mammosomatotroph- secrete? adenoma subtypes? assoc syndrome?
- GH and PRL (prolactin)
- mammosomatotroph adenomas
- combined features of GH and prolactin excess
lactotroph- secrete? adenoma subtypes? assoc syndrome?
- PRL
- lactotroph adenoma
- silent lactotroph adenoma
- galactorrhea and amenorrhea, sexual dysfxn, infertility
corticotroph- secrete?
- ACTH and POMC, and MSH (melanocyte-stim H)
- densely and sparsely granulated corticotroph adenoma
- silent corticotroph adenoma
- Cushing syndrome, Nelson syndrome
thyrotroph- secrete?
- TSH
- thyrotroph adenoma
- silent thyrotroph adenoma
- hyperthyroidism
gonadotroph- secrete?
- FSH and LH
- gonadotroph adenoma
- silent gonadotroph adenoma
- hypogonadism, mass effects, hypopituitarism
posterior pituitary- 2 hormones
- oxytocin- stim uterine contractions; stim smooth m around lactiferous ducts
- ADH- conserve water
- made in hypothalamus
- stored in axon terminals
diseases of the pituitary
- hyperpituitarism (too much H)
- hypopituitarism
local mass effect
- radiographic abnormalities of sella turcica
- compression of optic n’s and chiasm- bitemporal hemianopsia (temporal visual fields)
- elevated intracranial P sx’s- HA, N/V
hyperpituitarism- caused by?
- pituitary carcinoma
- hypothalamic disorders
- pituitary adenomas!!!
most common cause of hyperpituitarism
-adenoma (in anterior lobe of pituitary)
most common alterations in pituitary adenomas?
G-protein mutations!!
-Gsalpha activation is transient- due to intrinsic GTPase activity in the alpha-subunit
40% of somatotroph cell adenomas have what mutation?
-GNAS mutations that abrogate the GTPase activity of Gsalpha- leads to constitutive act of Gsalpha, persistent generation of cAMP, and unchecked cellular proliferation!!!
5% of pit adenomas arise form an inherited genetic defect- what genes?
-MEN1, CDKN1B, PRKAR1A, AIP
GNAS- most commonly assoc pit tumor?
-GH adenomas
PRKAR1A (Protein kinase A, reg subunit 1)- most commonly assoc pit tumor?
-GH and prolactin adenomas
Cyclin D1- most commonly assoc pit tumor?
aggressive adenomas
HRAS- most commonly assoc pit tumor?
-pituitary carcinomas
loss of fxn- MEN1- most commonly assoc pit tumor?
-GH, prolactin, ACTH adenomas
loss of fxn- CDKN1B- most commonly assoc pit tumor?
loss of fxn- AIP (aryl hydrocarbon R interacting protein)- most commonly assoc pit tumor?
- ACTH adenomas
- GH adenomas (esp < 35 yo)
loss of fxn- RB- most commonly assoc pit tumor?
-aggressive adenomas
pituitary adenoma
- non-fxnal- if big can cause hypopituitarism
- functional
- ages 35-60
- microadenoma- <1 cm
- macroadenoma- >1 cm
- atypical adenoma- aggressively
typical pituitary adenoma- pathology- gross
- soft and well-circumscribed
- if small- confined to sella turcica
- invasive adenomas- erode sella turcica and anterior clinoid processes; macroadenomas are invasive more freq!
- larger ones- compress optic chiasm and cranial n’s
typical pituitary adenoma- pathology- histology
- UNIFORM, polyglonal cells in sheets/cords
- CT (reticulin) is sparse!!- soft, gelatinous consistency
- sparse mitotic activity
histology- pituitary adenoma vs normal nonneoplastic ant pit parenchyma
-monomorphism and the absence of significant reticulin!!!!
atypical adenomas- histology
- elevated mitotic activity
- nuclear p53 expression (TP53 mutations)
- behave aggressively
Lactotroph adenoma- what is it?
- most common type of hyperfxning pit adenoma- 30% of cases
- secrete prolactin (even small tumors secrete enough to cause hyperprolactinemia)
Lactotroph adenoma- clinical course
- Amenorrhea, galactorrhea, loss of libido, infertility
- women 20-40- amenorrhea!! (causes 1/4 of cases of amenorrhea)
- men and postmenopausal women- subtle!- macroadenomas before detected clinically
Other causes of hyperprolactinemia
- physiologic/normal- pregnancy, nipple stim (suckling), stress
- lactotroph hyperplasia when there is loss of dopamine-mediated inhibition of prolactin:
- damage of dopaminergic neurons in hypothalamus
- damage of pit stalk (head trauma)
- drugs that block dopamine Rs on lactotroph cells
- mass in suprasellar compartment can interfere with inhibitory effect of hypothalamus on PRL secretion
- renal failure
- hypothyroidism
Lactotroph Adenoma- tx
- bromocriptine- dopamine R agonist that causes the lesions to diminish in size
- surgery
Somatotroph Adenomas- secretes? effects?
- second most common type of fxning pit adenoma!
- secrete GH!:
- stim hepatic secretion of IGF-1 (insulin-like GF)
- gigantism in children; acromegaly in adults
- need A LOT of GH to cause clinical signs!!- usually big when come to attention
Gigantism- clinical course
- children b/f the epiphyses have closed
- inc in body size with disproportionately long arms/legs
- some signs of acromegaly
Acromegaly- clinical course
- after closure of epiphyses
- growth- skin/soft tissues, viscera (thyroid, heart, liver, adrenals, bones of face, hands, feet
- jaw protrusion (prognathism), broadening of lower face
- enlarged hands, feet
- sausage-like fingers
- inc bone density in spine and hips
other findings seen with excess GH?
- gonadal dysfxn
- DM
- generalized m weakness
- HTN
- arthritis
- CHF
- risk of GI cancers
Somatotroph Adenomas- morphology
- classified into densely granulated and sparsely granulated subtypes
- densely granulated- strong cytoplasmic GH reactivity on immunohistochemistry
- sparsely granulated- focal, weak staining for GH
Somatotroph Adenomas- diagnosis
- elevated serum GH and IGF-1 levels
- failure to suppress GH production in response to an oral load of glucose- sensitive test for acromegaly!
Somatotroph Adenomas- tx
- surgery
- somatostatin analogs- inhibits pit GH secretion
- GH R antagonists
- tissue overgrowth gradually recedes, metabolic abnormalities improve
Mammosomatotroph Adenomas- secrete?
- GH and PRL
- signs, sx of both
- same tx
Corticotroph adenomas- secrete? morphology?
- ACTH-> adrenal hypersecretion of cortisol- hypercortisolism (Cushing syndrome)
- usually microadenomas
- often basophilic- densely granulated!
- occasionally chromophobic-sparsely granulated!
- PAS positive!!!- carbohydrate in POMC (ACTH precursor molecule)
Cushing syndrome- clinical course; vs Cushing Dz
- round face, hump, easy bruising, abd weight gain, stretch marks
- syndrome- hypercortisolism
- disease- when due to excessive prod of ACTH by pit!!
Nelson syndrome
- pt with preexisting corticotroph microadenoma
- occurs after surgical removal of the adrenal glands for tx of Cushing syndrome
- loss of inhibitory effect of adrenal corticosteroids- large destructive pit adenoma with mass effect!!
- hypercortisolism doesnt develop (no adrenal glands)
- hyperpigmentation (ACTH precursor molecule stim melanocytes)
Gonadotroph adenomas- secrete? clinical?
- FSH (predominantly) and LH); or nonfxning!
- difficult to recognize- secrete H’s inefficiently/variably- dont cause a recognizable clinical syndrome
- middle-aged men and women- mass effect
- impaired vision, HA, diplopia, pit aploplexy
- can get pit hormone deficiencies, most commonly LH!- dec energy and libido in men, amenorrhea in women
Thyrotroph adenomas
- produce TSH
- uncommon- 1% of all pit adneomas
- causes hyperthyroidism
plurihormonal adenomas
- elaborate more than 1 H (ex- mammosomatotroph adenoma)
- usually aggressive
Nonfunctioning pituitary adenomas
- 20-30% of all pit tumors
- sx’s of mass effect!!
- can compress the residual ant pituitary- hypopituitarism- slowly from enlargement, or abruptly from pituitary apoplexy (acute intratumoral hemorrhage)
Pituitary carcinoma
- rare, <1% of pit tumors
- defined my metastases (Craniospinal or systemic)!! (late in course)
- most are fxnal- PRL and ACTH most commonly
