Pituitary and thyroid Flashcards
PIT-1
TF which regulates differentiation of
somatotrophs
mammosomatotrophs
lactotrophs
SF-1 and GATA-2
TFs which regulates differentiation of gonadotrophs
What is most common cause of hyperpituitarism of ant pit
pituitary adenoma
what is the peak incidence of pituitary adenomas
35-60
genetic abnormaliites of pituitary adenomas
GPCR mutations -> GNAS
GNAS
codes for Galpha subunit
these mutation are also present in corticotroph adenomas
morphology of pituitary adenoma
- well circumscribed and soft (d/t lack of reticulin)
- if breaks thru diaphgragma sella its invasive
- CELLULAR MONOMORPHISM AND LOSS OF RETICULIN distinguished from nonneoplastic surrounding cells
Mass Effect signs
- radiographic abnromaliites of sella turcia
- bitemporal hemianopsia
- elevated intracranial pressure
- acute hemorrhage into adenoma leading to pituitary apoplexy
lactotroph adenoma
prolactin secreting
most frequent type of fnx pituitary adenoma
sparsely granulated lactotroph adenomas
most common
chromophobic cells w/juxtanuclear PIT-1
densely granulated lactotroph adenomas
diffuse cytoplasmic PIT-1
other morphological features of lactotroph adenomas
psammoma bodies or calcification of entire tumor
symptoms of lactotroph adenoma
amenorrhea
galactorrhea
loss of libido and fertility
other causes of pathologic prolactinemia
truama to pituitary stalk DR2 antagonists any mass in suprasellar compartment renal failure hypothyroidism
Tx of prolactinemia
surgery
bromocriptine
somatotroph adenomas
GH secreting
2nd most common type of fnx pituitary adenoma
densely granulated somatotroph adenomas
monomorphic acidophillic cells
mammosomatotroph
bihormonal: GH and prolactin
usually dense granulated variant
acromegaly
bone density may increase in spine and hips
sausage fingers
other issues associated with GH excess
gonadal dysfunction DM mm weakness HTN arthritis CHF GI CA
Dx of somatotroph adenoma
elevated GH and IGF1
FAILURE OF GLUCOSE load to suppress GH
corticotroph adenomas
excess ACTH -> adrenal hypersection of cortisol -> cushings disease
corticotroph adenomas morphology
stain with PAS due to CHO in POMC
Nelson syndrome
large destructive adenomas develop post adrenal gland removal
do not present until mass effect bc cannot become symptomatic
pleurihormonal
very rare and usually aggressive
gonadotroph adenomas
secrete hormones inefficiently and variably
usually discovered d/t mass effect
FSH usually dominantly secreted hormone
usually express SF-1 and GATA-2
thyrotroph adenomas
rare
non-fnx pituitary adeomas
aka silent or null-cell
most common type of pituitary adenoma
pituitary carcinomas
rare
presence of craniospinal or systemic mets
most are functional: prolactin and ACTH most common
when does hypopituitarism become symptomatic
when 75% of parenchyma is lost
Where is the likely pathology in neurogenic DI
hypothalmus
what is the most common cause of neurogenic DI
trauma
Pituitary apoplexy
sudden hemorrhage into pituitary gland
sudden onset of HA and diploplia
CV collapse, loss of conciousness, sudden death
neurosurgical emergency
sheehan syndrome
aka postparum necrosis of ant pit
most common cause of ant pit necrosis
pit enlarges during preg without increased blood supply, if blood loss occurs during labor ant pit at risk
other causes of pit necrosis
DIC Sickle cell elevated intracranial pressure trumatic injury shock
Rathke cleft cyst
lined by ciliated cuboidal epi w/occaision goblet and ant pit cells
proteinacious fluid
empty sella syndrome
any condition or Tx that destryoys all or part of pit gland
radiation or surgery
hypothalamic lesion
DI
tumors
inflammatory disorder and infections (TB and sarcoidosis)
genetic defects (PIT-1)
Post pit syndromes
DI
SIADH
SIADH
most common cause is SSC of lung
can also be caused by drugs
hypothalamic suprasellar tumros
may induce hypo or hyper fnx of ant pit, DI, or combos
gliomas and craniopharyngiomas most common
craniopharyngiomas
arise from vestigial remnants of Rathke pouch biomodal: 5-15 and 65 HA and visual disturbances WNT and beta catenin mutationa excellent prognosis
morphology of craniopharyngiomas
most commonly cystic and mulitloculates
2 variants of craniopharyngiomas
adamantinomatous
papillary
adamantinomatous craniopharyngiomas
kids
calcification (psomma bodies)
cysts of machine oil fluid
papillary craniopharyngiomas
adults
calcifications and cysts rare
parafollicular cells
aka C cells
in thyroid
secrete calcitonin
3 most common causes of thyrotoxicosis
Diffuse hyperplasia associated with graves (85%)
hyperfunctional multinodular goiter
hyperfunctional thyroid adenoma
Thyrotoxicosis and BMR
increased
skin warm, soft, flushed
heat intolerance and sweating
weigh loss despite increased appetite
Thyrotoxicosis and heart
earliest and most consistent features elevated contractility and CO tachy, palps, cardiomegaly arrhythimia (a-fib) in older patients CHF
Thyrotoxic cardiomyopathy
left ventricular dysfunction -> decreased CO
Thyrotoxicosis and NS
tremor hyperactivity emotional lability anxiety inability to concentrate insomnia mm weakness and decreased mm mass
Thyrotoxicosis and eyes
wide staring gaze with lid lag
exopthalmus only in graves
Thyrotoxicosis and skeleton
over stimulation of bone resorption -> osteoporosis
Thyroid storm
abrupt onset of severe Thyrotoxicosis most common in graves febrile and tachy medical emergency b/c arrhythmias fatal predisposing factors: infection, surgery, stress, cessation of meds
apathetic hyperthyroidism
older adults and various co-morbidities blunt features of excess TH
Tx of Thyrotoxicosis
beta blockers thionamide iodine radioiodine ablation surgery
congenital hypothyroidism
worldwide d/t endemic iodine deficiency
autoimmune hypothyroidsim
most common in developed countries
almost all are hashimotos
Abs against thyroid
antimicrosomal
antithyroid peroxidase
antithyroglobulin
drugs which can induce hypothyroidsim
methimazole
PTU
lithium
p-aminosalcylic acid
myxedema
hypothyroidism in developing in older child or adult slowing of physical and mental activity listless, cold intolderant, overweight constipation, decreased sweating reduced CO -> SOB atherogenic profile deepening of voice, non pitting edema
histo of myxedema
glycosaminglycans and hyaluronic acid in skin
Dx of myxedema
TSH
hashimotos thyroiditis
women 45-65
CTLA4 and PTPN22 (regulate T cells)
progressive apoptosis or thyroid epi replaced by mononuclear cells and fibrosis
morphology of hashimotos
diffusely enlarged, with intact capsule and pall surface
extensive mononuclear infiltrates with germinal centers
Hurthle cells
fibrosis does NOT extend beyond capsule
hashitoxicosis
transient thyrotoxicosis d/t disruption of thyroid follicles and release of TH
hashimotos at risk for what CA
extranodal marginal zone B cell lymphomas in thyroid
subacute lymphocytic thyroiditis
postpartum thyroiditis is in this category
autoimmune (Abs)
lymphocytic infiltrates w/large germinal centers
unlike hasimotos NO fibrosis or Hurthle cells
granulomatous thyroiditis
aka dequervain thyroiditis 40-50 tirggered by viral infection, Hx of URI painful u/l or b/l enlarged firm thyroid with intact capsule that may adhere to surrounding structures multinucleated giant cells lasts 2-6 weeks elevated TH, decreased TSH radioactive I uptake diminished
graves
most common cause of endogenous hyperthyroidism
peak 20-40
graves triad
hyperthyroidism with diffuse enlargement of gland
exopthalamus
pretibial myexedema
Ab in graves
TSI- thyroid stimulating immunoglobulin
Pathogenesis of graves
linked to CTLA4 and PTPN22 and HLA-DR3
morphology of graves
-symmetrically enlarged with diffuse hypertrophy and hyperplasia of follicular epi cells
-soft meaty appearance resembling mm
small papillae project into lumen, but NO fibrovascular core
T cell and B cell infiltratates
germinal centers
colloid scalloped
Tx of graves
beta blockers thionamides PTU radioiodine ablation thyroidectomy
what is TH in most goiters
euthyroid
diffuse nontoxic/simple goiter
aka colloid goiter
2 categories:
endemic
sporadic
endemic diffuse nontoxic/simple goiter
10%+ of pop must be affected
mountainous areas
can be d/t goitrogens
sporadic
less frequent the endemic
mostly idiopathic
goiterogens
cabbage, cauliflower, brussel sprouts, turnips cassava root (thiocyanate)
phases of goiter
hyperplastic: symmetrically enlarged
colloid involution: when I is again available
multinodular goiter
virtually all long standing simole goiters progress to multinodular
produce most extreme thyroid enlargements
polyclonal and monoclonal nodules
can be complicated by follicular rupture, hemorrhages, cysts scarring, calcification
multinodular goiter morphology
pressure on midline structures
intrathroacic/plunging goiter: grows behind sternum
brown gelantinous colloid
mass effects of multinodular goiter
airway obstruction
dysphagia
compression of large vessels
SVC syndrome
plummer syndrome
less common presentation of goiter
hyperthyroidism (toxic)
exopthalmus and dermopathy of graves absent
determining malignancy in thyroid
- solitary nodules more likely to be neoplastic
- nodules in young more likely to be neoplastic
- noduels in males more likely to be neoplastic
- Hx of radiation more likely malignant
- fnx noduels more likely benign
thyroid adenomas
from follicualr epi
usually not forerunners to carcinomas
most are non functional
common mutations in thyroid adenomas
gain of fnx in TSHR or GRAS
these are RARE in follicular carcinomas
rare mutatuion in thyroid adenomas
RAD or pIK3CA mutation
PAX8-PPARG fusion
these ARE shared with follicualr carcinomas
morphology of thyroid adenomas
solitary spherical, encapsulated lesion
areas of hemorrhage, fibrosis, cystic changes common
HALLMARK is well formed capsule
integrity of capsule is only way to determine if it is truly benign
Dx of thyroid adenomas
surgical removal for capsule integrity determination
prognosis of thyroid adenomas
excellent
do not recur
thyroid carcinomas
uncommon
in kids M=F
types: papillary, follicular, anaplastic, medullary
which thyroid carcinomas arise from follicular epi
papillary
follicular
anaplastic
mutation in TK -> RAS -> MAPK pathway
papillary carcinomas
most common 85%
25-50
usually have radiation Hx
mutations in papillary carcinomas
gain of fnx in RET, NTRK1, or BRAF
RET mutations
part of MAP kinase pathway
RET/PTC fusion
more common in radiation
NOT seen in follicular adenomas or carcinomas
BRAF
in MAP pathwya
adverse prognosis
NOT seen in follicular adenomas or carcinomas
morphology of papillary carcinomas
GRAY WHITE
areas of fibrosis and cysts
papillae have fibrovascular stalk
nuclei of OPTICAL CLEARING (ground glass or orphan Annie nuclei)
psudoinclusions in nuclei of invading cytoplasm
psammoma bodies in papillay (never seen in follicular or medullary CA)
LYMPH invasion, but NOT blood
METS to cervical nodes
Dx of papillary carcinomas
on cellular findings alone
excellent prognosis
follicular carcinomas
more common in areas with I deficiency
40-60
mutation in follicular carcinoma
- RAS or PI3K/AKT TK pathway
- loss of fnx in PTEN
- PAX8-PPARG fusion
morphology of follicular carcinoma
usually well circumscribed but may rupture capsule gray-tan-pink central fibrosis and calcification hurthle cells NO psammoma bodies Dx with capsular invasion
spread of follicular carcinoma
lymph rarely involved, but common thru blood with mets to bone, liver, and lungs
Tx of follicular carcinoma
total thyroidectomy
radioactive iodine ablation
TH to suppress TSH
anaplastic carcinomas
aggressive 100% mortality
65
25% previous Hx of thyroid CA
25% concurrent CA in adjacent cells
anaplastic carcinomas mutations
TP53
beta catenin
anaplastic carcinomas morphology
lots of cell types (giant, spindle, mised, foci of papillary or follicular differentiation)
medullary carcinoma
neuroendocrine neoplasm derived from parafollicular C cells
secrete calcitonin
can also secrete serotonin, ACTH, VIP
familial causes of medullary carcinoma
MEN-2
germline RET mutations (not translocations)
morphology of medullary carcinoma
sporadic solitary, familial mulitple necrosis and hemorrhage AMYLOID CALCITONIN adjacent C cell hyperplasia -> MEN2
