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E2T1 > Endocrine Path 1: Pituitary > Flashcards

Endocrine Path 1: Pituitary Flashcards

1
Q

organs

A
  • pituitary gland
  • thyroid gland
  • parathyroid gland
  • pancreas
  • adrenal glands
  • pineal gland
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2
Q

posterior pit- consists of?

A

-modified glial cells (pituicytes) and axonal processes that extended from the hypothalamus thru the pit stalk to the posterior lobe (axon terminals)

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3
Q

what stim ADH secretion?

A
  • dec BP- baroRs(in cardiac atria and carotids)

- inc in plasma osmotic P- osmoRs

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4
Q

Anterior pituitary- cell types

A
  • somatotrophs- GH
  • mammosomatotroph- GH and prolactin
  • lactotroph- prolactin
  • corticotroph- ACTH and POMC, and MSH (melanocyte-stimulating H)
  • thyrotroph- TSH
  • gonadotroph- FSH and LH
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5
Q

somatotroph- secrete? adenoma subtypes? assoc syndrome?

A
  • GH
  • densely and sparsely granulated somatotroph adenoma
  • silent somatotroph adenoma
  • gigantism (children); acromegaly (adults)
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6
Q

mammosomatotroph- secrete? adenoma subtypes? assoc syndrome?

A
  • GH and PRL (prolactin)
  • mammosomatotroph adenomas
  • combined features of GH and prolactin excess
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7
Q

lactotroph- secrete? adenoma subtypes? assoc syndrome?

A
  • PRL
  • lactotroph adenoma
  • silent lactotroph adenoma
  • galactorrhea and amenorrhea, sexual dysfxn, infertility
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8
Q

corticotroph- secrete?

A
  • ACTH and POMC, and MSH (melanocyte-stim H)
  • densely and sparsely granulated corticotroph adenoma
  • silent corticotroph adenoma
  • Cushing syndrome, Nelson syndrome
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9
Q

thyrotroph- secrete?

A
  • TSH
  • thyrotroph adenoma
  • silent thyrotroph adenoma
  • hyperthyroidism
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10
Q

gonadotroph- secrete?

A
  • FSH and LH
  • gonadotroph adenoma
  • silent gonadotroph adenoma
  • hypogonadism, mass effects, hypopituitarism
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11
Q

posterior pituitary- 2 hormones

A
  • oxytocin- stim uterine contractions; stim smooth m around lactiferous ducts
  • ADH- conserve water
  • made in hypothalamus
  • stored in axon terminals
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12
Q

diseases of the pituitary

A
  • hyperpituitarism (too much H)

- hypopituitarism

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13
Q

local mass effect

A
  • 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
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14
Q

hyperpituitarism- caused by?

A
  • pituitary carcinoma
  • hypothalamic disorders
  • pituitary adenomas!!!
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15
Q

most common cause of hyperpituitarism

A

-adenoma (in anterior lobe of pituitary)

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16
Q

most common alterations in pituitary adenomas?

A

G-protein mutations!!

-Gsalpha activation is transient- due to intrinsic GTPase activity in the alpha-subunit

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17
Q

40% of somatotroph cell adenomas have what mutation?

A

-GNAS mutations that abrogate the GTPase activity of Gsalpha- leads to constitutive act of Gsalpha, persistent generation of cAMP, and unchecked cellular proliferation!!!

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18
Q

5% of pit adenomas arise form an inherited genetic defect- what genes?

A

-MEN1, CDKN1B, PRKAR1A, AIP

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19
Q

GNAS- most commonly assoc pit tumor?

A

-GH adenomas

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20
Q

PRKAR1A (Protein kinase A, reg subunit 1)- most commonly assoc pit tumor?

A

-GH and prolactin adenomas

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21
Q

Cyclin D1- most commonly assoc pit tumor?

A

aggressive adenomas

22
Q

HRAS- most commonly assoc pit tumor?

A

-pituitary carcinomas

23
Q

loss of fxn- MEN1- most commonly assoc pit tumor?

A

-GH, prolactin, ACTH adenomas

24
Q

loss of fxn- CDKN1B- most commonly assoc pit tumor?

loss of fxn- AIP (aryl hydrocarbon R interacting protein)- most commonly assoc pit tumor?

A
  • ACTH adenomas

- GH adenomas (esp < 35 yo)

25
Q

loss of fxn- RB- most commonly assoc pit tumor?

A

-aggressive adenomas

26
Q

pituitary adenoma

A
  • non-fxnal- if big can cause hypopituitarism
  • functional
  • ages 35-60
  • microadenoma- <1 cm
  • macroadenoma- >1 cm
  • atypical adenoma- aggressively
27
Q

typical pituitary adenoma- pathology- gross

A
  • 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
28
Q

typical pituitary adenoma- pathology- histology

A
  • UNIFORM, polyglonal cells in sheets/cords
  • CT (reticulin) is sparse!!- soft, gelatinous consistency
  • sparse mitotic activity
29
Q

histology- pituitary adenoma vs normal nonneoplastic ant pit parenchyma

A

-monomorphism and the absence of significant reticulin!!!!

30
Q

atypical adenomas- histology

A
  • elevated mitotic activity
  • nuclear p53 expression (TP53 mutations)
  • behave aggressively
31
Q

Lactotroph adenoma- what is it?

A
  • most common type of hyperfxning pit adenoma- 30% of cases

- secrete prolactin (even small tumors secrete enough to cause hyperprolactinemia)

32
Q

Lactotroph adenoma- clinical course

A
  • 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
33
Q

Other causes of hyperprolactinemia

A
  • 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
34
Q

Lactotroph Adenoma- tx

A
  • bromocriptine- dopamine R agonist that causes the lesions to diminish in size
  • surgery
35
Q

Somatotroph Adenomas- secretes? effects?

A
  • 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
36
Q

Gigantism- clinical course

A
  • children b/f the epiphyses have closed
  • inc in body size with disproportionately long arms/legs
  • some signs of acromegaly
37
Q

Acromegaly- clinical course

A
  • 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
38
Q

other findings seen with excess GH?

A
  • gonadal dysfxn
  • DM
  • generalized m weakness
  • HTN
  • arthritis
  • CHF
  • risk of GI cancers
39
Q

Somatotroph Adenomas- morphology

A
  • classified into densely granulated and sparsely granulated subtypes
  • densely granulated- strong cytoplasmic GH reactivity on immunohistochemistry
  • sparsely granulated- focal, weak staining for GH
40
Q

Somatotroph Adenomas- diagnosis

A
  • elevated serum GH and IGF-1 levels

- failure to suppress GH production in response to an oral load of glucose- sensitive test for acromegaly!

41
Q

Somatotroph Adenomas- tx

A
  • surgery
  • somatostatin analogs- inhibits pit GH secretion
  • GH R antagonists
  • tissue overgrowth gradually recedes, metabolic abnormalities improve
42
Q

Mammosomatotroph Adenomas- secrete?

A
  • GH and PRL
  • signs, sx of both
  • same tx
43
Q

Corticotroph adenomas- secrete? morphology?

A
  • 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)
44
Q

Cushing syndrome- clinical course; vs Cushing Dz

A
  • round face, hump, easy bruising, abd weight gain, stretch marks
  • syndrome- hypercortisolism
  • disease- when due to excessive prod of ACTH by pit!!
45
Q

Nelson syndrome

A
  • 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)
46
Q

Gonadotroph adenomas- secrete? clinical?

A
  • 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
47
Q

Thyrotroph adenomas

A
  • produce TSH
  • uncommon- 1% of all pit adneomas
  • causes hyperthyroidism
48
Q

plurihormonal adenomas

A
  • elaborate more than 1 H (ex- mammosomatotroph adenoma)

- usually aggressive

49
Q

Nonfunctioning pituitary adenomas

A
  • 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)
50
Q

Pituitary carcinoma

A
  • rare, <1% of pit tumors
  • defined my metastases (Craniospinal or systemic)!! (late in course)
  • most are fxnal- PRL and ACTH most commonly

E2T1 (6 decks)

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