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282 Cards in this Set
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what are the 2 basic types of hormonal activity?
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1. trigger biochemical signals upon interacting with cell surface r's: peptide moleculs like insulin and small molecules like Epi
2. cross the PM to interact with intracellular R's (lipid soluble hormones) |
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what are the 2 portions of pituitary and what are they derived from?
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anterior (adenohypophysis): 80% Rathke pouch derived
Posterior (neurohypophysis): 20% glial derived from diencephalon |
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how does the pituitary appear histologically?
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ant: darker, more glandular, abundant cyoplasm, multiple cell types
post: glial derived therefore looks like brain tissue |
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what do acidophils secrete? basophils? Chromophobes? majority of ant pituitary cells?
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acidophils: GH, PrL
Basophils, ACTH, TSH, GnRH, FSH, LH Chromophobes: few cytoplasmic granuls, dont take up much color majority in ant pituitary = acidophils |
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what are teh 5 basic cell types of Ant pituitary cells? how wll they stain?
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1. somatotrophs (acidophilc): GH
2. lactotrophs (acidophilic): PrL 3. corticotrophs (basophilic)ACTH, MSH, POMC 4. thyrotrophs (basophilic) TSH 5. gonadotrophs (basophilc) FSH, LH |
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what is an effective route for hypothalamic control of ant pituitary fxn?
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the portal venous system linking hypothal with ant lobe
provides venous drainage of hypothal which contains releasing and inhibiting factors |
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is there a portal venous system for post hypophysis?
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no b/c hormones are released by nerve terminals which begin in hypothal and extend to terminal in post hypophysis
*directly linked to brain |
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when do you have a normal enlargement of pituitary?
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pregnancy
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will hypertension affect ant or post pituitary more?
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ant pituitary b/c of portal venous system is a low pressure system
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what does the neurohypophysis contain?
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modified glial cells (pituicytes) and axonal processes extending from hypothalamic nuclei (paraventricular and supraoptic) to terminate as synaptic processes releaseing ADH/AVP and Oxytocin
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what is an effective route for hypothalamic control of ant pituitary fxn?
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the portal venous system linking hypothal with ant lobe
provides venous drainage of hypothal which contains releasing and inhibiting factors |
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is there a portal venous system for post hypophysis?
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no b/c hormones are released by nerve terminals which begin in hypothal and extend to terminal in post hypophysis
*directly linked to brain |
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when do you have a normal enlargement of pituitary?
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pregnancy
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will hypertension affect ant or post pituitary more?
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ant pituitary b/c of portal venous system is a low pressure system
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what does the neurohypophysis contain?
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modified glial cells (pituicytes) and axonal processes extending from hypothalamic nuclei (paraventricular and supraoptic) to terminate as synaptic processes releaseing ADH/AVP and Oxytocin
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what is the most common cause of pituitary hyperpituitarism?
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adenoma
then hyperplasia very rare: carcinoma |
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what is the most commn source of carcinona that causes hyperpituitarism?
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prodxn from another site
ex: small cell carcinoma |
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what causes hypopituitarism?
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destructive processes
crowding out normal portions of gland ischemia inflammation radiation surgery |
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waht are 2 diseases of post pituitary?
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diabetes insipidus
inapporpriate ADH secretion |
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are pituitary adenomas benign?
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yes but can produce problems from mass effect usually visual problems from presing on optic chiasm
or prodxn of hormones such as prolactin or ACTH |
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waht is the most common cause of hyperpituitarism?
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pituitary adenoma arising in ant lobe
can be fxnl or silent/nonfxnl (can't demonstrate hormone being produced) |
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how are pituitary adenomas classified? how detected?
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based on waht hormones produced (mostly PrL, GH, ACTH)
detected by immunochemical stains: not by H&E |
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25% of routine autopsies find what?
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microadenomas (1cm) in ant pituitary
rarely have a signif hormonal output |
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what usually cuases a pituitary adenoma?
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G protein mutation
40% somatotroph cell adenomas-GH NOT seen in thyrotroph, lactotroph, Gonadotroph cell adenomas 2. MEN 3. RAS and c-myc oncogenes |
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what happens when the G protein is mutated and leads to pituitary adenoma?
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no neg-feedback
protein mutation stopping feedback from occuring *40% of somatotrophs -GH |
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what is the most common type of pituitary adenoma? 2?
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most common: prolactin (lactotroph)
2nd: Somatotoroph adenoma and ACTH corticotroph adenoma |
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how can you tell if its a nonfxnl adenoma based on presence?
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larger at time of diagnosis than those that secrete hormone
*when it grows to this size it wont produce anything slow growing = benign |
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how will a pituitary adenoma appear histologically that differentiates it from normal ant pituitary?
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monomorphism, uniformity, absence of reticulin network, very vascular, soft/gelatinous b/c no network
normal: mixture of cells |
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fxn of pituitary adenomas is Dx how?
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immunohisto staining to see what cells are producing
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25-30% of all fxning pituitary adenomas are? most common in who? triad?
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prolactinoma
women triad: amenorrhea, galactorhea, infertility AMEN! the gal is infertile (no clinical symptoms in men) |
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what will you see when looking at serum prolactin in prolactinoma case
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normal: <20 excludes the diagnosis of fxning prolactinoma
elevated: no absolute level of PrL is diagnostic of pituitary tumor *in general: >1000 ng/mL occur with maroadenoma but you have to take into acct the normal inhibitory control of PrL (anything that blocks inhibitiry effect will increase PrL) |
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when will prolactin be elevated?
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prolactinoma
later stages of pregnancy renal failure and hypothyroidsim |
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what is the typical 1st Tx for prolactinoma?
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Bromocriptine, dopamine R agonst b/c can block release of PrL
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what is the 2nd most common fxning pituitary adenoma? what are the subtypes
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GH (somatotroph) adenomas
1. densely granulated (acidophilc) 2. sparsely granulated (chromophobe) * according to EM appearance |
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if somatotroph adenoma occurs before puberty called waht? after?
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before: gigantism b/c epiphyses haven't closed yet-get long arms and legs
after: acromegaly : enlarged features, won't get taller; develops slowly over time |
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major clinical characteristics of acromegaly? who is more affected?
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organomegaly, spade like hands, frontal bossing
thickened calvaria (hat wont fit) DM headaches and visual loss if tumor is large equal in men and women |
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when will prolactin be elevated?
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prolactinoma
later stages of pregnancy renal failure and hypothyroidsim |
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what is the typical 1st Tx for prolactinoma?
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Bromocriptine, dopamine R agonst b/c can block release of PrL
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what is the 2nd most common fxning pituitary adenoma? what are the subtypes
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GH (somatotroph) adenomas
1. densely granulated (acidophilc) 2. sparsely granulated (chromophobe) * according to EM appearance |
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if somatotroph adenoma occurs before puberty called waht? after?
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before: gigantism b/c epiphyses haven't closed yet-get long arms and legs
after: acromegaly : enlarged features, won't get taller; develops slowly over time |
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major clinical characteristics of acromegaly? who is more affected?
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organomegaly, spade like hands, frontal bossing
thickened calvaria (hat wont fit) DM headaches and visual loss if tumor is large equal in men and women |
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dx of acromegaly?
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elevated serum GH and IGF-1
when give glucose load: GH non suppression |
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most common cause of hypopituitarism is waht?
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iatrogenic: surgical procedure
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what do corticotroph adenomas look like
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microadenoma at time of Dx
basophilic (densely granulated) and occasionally chromophobic (sparsely granulated) |
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what does the excess ACTH prodxn by corticotroph adenoma lead to?
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hypercortisolism = Cushings Disesase
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how do you get Cushings Syndrome?
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when hypercorticolism is a result of any cause (disease is due to ACTH b/c of pituitary adenoma)
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what is Nelson syndrome?
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large adenoma after adrenalectomy
most common seen in breast cancer after you do the adrenalectomy the pituitary will keep telling the adrenal to produce cortisol--lose feedback loop |
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why are gonadotroph adenomas difficult to diagnose?
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bc they secrete hormones variabley and inefficiently
secretory products do not cause recognizable clinical syndromes *most common in middle age women and men and are clinically apparent b/c of mass effec (headache, visual disturbances) |
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are thyrotroph adenomas common? are primary carcinoma of pituitary common?
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rare.1% pituitary adenomas
carcinoma is quite RARE and is rarey fxnl only diagnossed by the presence of mets |
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how do you know that you have nonfxning pituitary adenoma?
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b/c 25% are silent you will know b/c of mass effect and disturbance of normal pituitary fxn
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what are some causes of Hypopitutarism?
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tumors and other mass lesions
pituitry surgery or radiation *ischemic necrosis of pituitary (Sheehan syndrome-post partum necrosis of pituitary) Empty sella turcica see in obese multips due to continual enlarging during each pregnancy |
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what is Sheenan syndrome?
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post partum necrosis of pituitary
most commonly seen after pregnancy b/c enlarges during preg thus more vulnerable to changes in BP hypertension can cause ischemia (good idea to send out questionaires to mothers after pregnancy to check on them..follo w up with those you don't hear from) |
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what is the cause of Diabetes Insipidus?
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too little ADH (without flavor vs mellitus = sweet)
Syndrome of Inappropriate ADH (SIADH)-too much ADH |
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what is the diff b/n neurogenic (central) vs nephrogenic diabetes insipidus?
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central: pos pituitary b/c of injury fails to secrete sufficient ADH
nephrogenic: kidney fails to respond to ADH **most common |
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what are the major clinical characteristics of Diabetes Insipidus?
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Polyuria: dilute urine
Polydypsia: thirst, dehydration Hypernatremia: routine screening test |
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what is SIADH?
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syndrome of hyponatremia and fluid overload due to inability to make dilute urine
*most common cause of hospital aquired hyponatremia |
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what is the most common cause of hospital hyponatremia?
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SIADH
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what are the 2 causes of SIADH?
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Abnormal regulation of Post Pituiatary secretion of ADH (high levels of ADH)
Ectopic secrtion of ADH by a malignant tumor with small cell carcioma as te most common cause |
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how will you know that someone has SIADH?
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hyponatremia found during routine testing
inparticular in geriatric pts transient overprodxn of ADH *hyponatremia occurs in 25% of hospitalized pts over age 65 |
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what are 2 Suprasellar tumors?
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Gliomas
Craniopharyngioma |
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what are Cranipharyngiomas derived from? who do they occur in?
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derived from vestigial remnants of Rathke's pouch therefore see squamous epi
occurs in hypothal region above sella turcica therefore can cause visual disturbances: bilateral hemianopsia Bimodal age distribution: Children 5-15 and adults 50up |
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cystic tumor lined with squamous epi?
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craniopharyngioma
derived from remnants of Rathke's pouch |
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is it difficult to palpate a normal thyroid?
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yes..its very small and smooth
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where is the most common site of disribution of heterotropic thyroid tissue?
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lingual
*thyroid tissue is found in a lot of different places. it begins at base of tongue then follows midline downward through thyroid bone. can stop anywhere along pathway |
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waht must you do when looking for thryoid and can't find it?
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do whole body scan to look for HETERTOPIC thyroid tissue
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what will a thryoglossal duct cyst look like?
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gelatinous contents
colloid like (normal thyroid will have colloid filled with stored TH) find remnants of thyroid tissue |
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what type of antibodies will you use when looking for autoimmune conditions in thryoid?
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anti-microsomal
antibody to calcitonin that identifies C cells (they will be present in thryoid interstitum b/n follicles and secrete calcitonin) |
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TSH R activates what when bound?
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G protein that cuaes incrase in cAMP
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what is a diffuse nontoxic (simple) goiter? cause?
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form of goiter that involves the entire thyroid gland and is NOT fxnl
cause: iodine def pts usually euthryoid b/c gland can respond by increasing in size |
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what does toxic goiter mean?
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a fxnl state of producing excessive thryoid hormone autonomously
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what is thyroiditis?
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inflamm of thyroid which can be caused by diverse group of disorders
mainly: autoimmne |
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how will multinodular goiters look?
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varied
normaly euthryoid recurrent issues of hyperplasia and involution in a diffuse goiter *very irregular histologically: follicles are very enlarged, with flattened epi** |
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worldwide, what is the most common disease of the thyroid? in who?
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multinodular goiter
Tx thyroid replacement: turn off TSH in US: in young adult women |
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what is thyrotoxicosis?
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hypermetabolic state caused by elevated circulating levels of free T4 and free T3
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what is hyperthyroidism?
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synonomous with thyrotoxicosis, but is best though of as representing hyperfxn of the thyroid 2nd to a primary thyroid disorder such as Graves**
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what is subclinical hyperthyroidism?
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asymptomatic pt with low measured sensitive TSH and a normal T4 and T3
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what is thyroid storm?
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abrupt onsent
severe thyrotoxicosis |
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what are the major clinical characteristics of thyrotoxicosis?
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Increased BMR therfore see cardiac symptoms, wt loss
in 50% of older pts: Tachycardia, Fatigue, Weight loss ten times more common in women |
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who does thyrotoxicosis appar in mostly?
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ten times more common in women
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what are the 4 basic causes of thyrotoxicosis?
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primary: overactivity of thyroid gland *most common
secondary: excessive TSH tertiary: hypothal disorder Exogenous: taking thyroid hormones therefore you aren't hyperthyroid b/c gland isnt overacting |
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if someone has thyrotoxicosis b/c they are taking exogenous thryoid H are they hyperthyroid?
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NO! b/c gland isn't overacting.. they are just taking too much meds
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what is the cause of transient thyrotoxicosis?
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thyroiditis
see on thyroid scan: won't light up b/c due to inflamation gland is destroyed..not overacting |
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Graves is what type of thyrotoxicosis?
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primary
cause of 85% of primary=diffuse hyperplasia (Graves) |
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name 4 causes of primary hyperthyroidsm and what is the most common/
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Graves Disease (diffuse hyperplasia-85%)
toxic multinodular goiter toxic adenoma/carcinoma drug induced goiter |
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what is the differene b/c iatrogenic and factitious thyrotoxicosis that are the causes of exogenous hyperthyroidism?
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iatrogenic: excessive admin thyroxine by doctor
factitious : result of pt self administering excessive doses of thyroxine for weight loss etc. |
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who does hyperthyroidism occur in?
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40-60
more females caucasians and asians (lower in blacks) more often hyperovert vs subclinical overt: TSH <0.01 subclinical: TSH 0.01-.3 |
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what was initially desribed as long activity thyroid stimulator (LATS)
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the cause of Graves
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clinical triad of Graves?
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hyperthyroidism b/c gland overacting
infiltrative opthalmopathy-exophthalmos localized infiltrative dermopathy-Pretibial myxedema |
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who does Graves occur in? are there genetics involved?
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20-40
females impt genetic compoent |
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why is Graves referred to as an episodic disease?
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symptsoms of thyrotoxicosis w/o an elevated fT4--a clinical condition termed T3 Thyrotoxicosis
(normal T4 look at T3 b/c more hormonally active) |
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what is the diff in goiter in Graves and multinodlar?
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graves is smooth
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what are the Igs involved in causing Graves?
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IgG antibody of Thryotropin Receptor Antibodies (TRA) called TSI
binds to and triggers normal TSH R |
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how will Graves appear histolgically?
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hyperplastic infoldings with follicles line with tall columnar epi
"scalloped" thick epi lining Very active looking (normal is flat) clear vacules in colloid |
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vast majority of thyroidits is caused by ?
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autoimmune disorder
unless infectious thyroiditis which is caused by Pneumocystis carnii in immuno pts |
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Hashimotos full name?
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Hashimoto thyroiditis
most common cuase of hypothyroidis in US |
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who does Hashimoto occur in?
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women
after age 45 |
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wht causes subacute Granulomatous Thyroiditis (DeQuervain)? who does it occur in?
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viral infxn from prevoius RT infxn
women 30-50 |
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symptoms of subacute granulomatous thyroiditis (DeQuervain)?
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**painful goiter
resolvs after 2-6 wks symptoms of hyperthyroidism recovery is viturally always complete** and the disorder does not progress to throiditis and hypothyroidsm |
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does DeQuervain progress to become thyroiditis?
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no>>resolves in 2-6 weeks
recovery is virtually always complete |
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what is the silent autoimmune disease that may be exacerbated in the postpartum period so young women exhibit symptoms or signs of hyperthyroidism?
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Subacute Lymphocytic (painless) thryoiditis
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how do you differentiate subacute lymphocytic throidits from DeQuervai?
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only a minority of individuals may progress to hypothyroidism
whereas in DeQearvain no one progresses DeQuervain: painful* Subacute : painless |
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what is subacute lymphocytic thyroiditis? who do you see it in?
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silent autoimmune disease
exaccerbated in the postpartum period young adult women have signs and symptoms of hyPERthyroidsim minority progress to hyPOthryoidism |
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what is the rare varient of Subacute Lympocytic (painless) thryoidits that involves complete replacement of the thyroid gland by fibrous tissue?
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rare variant called Reidel Struma or Thryoiditis
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what is myxedema?
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exaggerated clinical features of hypothyroid disease characterized by slowing of physical and mental activity
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what is cretinism?
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hypothyroidism developing in infancy/early childhood
severe retardation short stature protruding tongue |
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what are 2 impt causes of Primary Hypothyroidism?
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Postablative: surgery, radioiodine thereapy
Autoimmune hypothyroidism: Hashimoto |
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what is the diff b/n primary, secondary, and tertiary hypothyroidism?
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primary: disorder of thryoid
secondary: inadequate TSH as a result of pituitary disease tertiary: inadequate TRH b/c of hypothalamic disorder |
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what does subclinical hypothyroidism mean?
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midly elevated TSH values
normal free T4 no or few clinical symptoms |
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what are some symptoms seen with hypothyroidism?
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coarse, brittle hair,
myxedema peripheral edema cold intelerance |
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what is Hashimotos also called?
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Chronic Lymphocytic Thryoiditis
affects older females: 40-60 pt initially hyperthryoid by progresses to hypothyroid |
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what Ab are preesnt in Hashimoto?
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anti-microsomal or anti-thryoid peroxidase antibodies (anti TPO)
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Grossly, Hashimoto thryoidits resembles what?
histologically? |
lymph node b/c much of tissue is lymphoid
small thryoid gland: atrophy Histo: deeply eosinophilc, well formed germinal centers, *pink Hurthle cells |
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what are 2 ways to test for thyroid disease
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sTSH (sensitive Thryoid Stimulating Hormone) to evaluate pituitary thryoid axis
FT4 (free T4): meausre free T4 to eliminate the influence of changes in levels binding protein *want to elimnate the influence of binding proteins |
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what do you use FT4 to test and not T3?
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even though FT3 is the hormone that is most fxnl, FT3 is in equilibruim with muh more abundant FT4
therefore, measure FT4 since it is easier to measure and more reliable |
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what is Hashimotos also called?
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Chronic Lymphocytic Thryoiditis
affects older females: 40-60 pt initially hyperthryoid by progresses to hypothyroid |
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what Ab are preesnt in Hashimoto?
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anti-microsomal or anti-thryoid peroxidase antibodies (anti TPO)
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Grossly, Hashimoto thryoidits resembles what?
histologically? |
lymph node b/c much of tissue is lymphoid
small thryoid gland: atrophy Histo: deeply eosinophilc, well formed germinal centers, *pink Hurthle cells |
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what are 2 ways to test for thyroid disease
|
sTSH (sensitive Thryoid Stimulating Hormone) to evaluate pituitary thryoid axis
FT4 (free T4): meausre free T4 to eliminate the influence of changes in levels binding protein *want to elimnate the influence of binding proteins |
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what do you use FT4 to test and not T3?
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even though FT3 is the hormone that is most fxnl, FT3 is in equilibruim with muh more abundant FT4
therefore, measure FT4 since it is easier to measure and more reliable |
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what tests do you perform ot test for thyroid disease: autoimmune status?
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preffered test: Antithryoid Perioxidase Antibody (Anti TPO Ab)
suspeced Graves: TRA including TSI |
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what does it mean when the sTSH is elevated?
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need more T4/3
hypothyroid |
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what does it mean when sTSH is within reference range?
decreased? |
w/n ref range: euthryoid
decresaed: too much T4/3 hyperthryoid |
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what doe it mean when Ft4 is high? low?
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high: hyperthyroid
low: hypothyroid |
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what is the difference in sTSH levels in subclinical hypothyroidism vs clincal?
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clinical "overt": elevated sTSH, decreased FT$
subclinical: mildly elevated sTSH, w/n reference range FT$ |
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what do you do after you tested and found that High TSH and Low FT4?
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confirmatory testing : Anti TPO Ab
if positive = Hashimoto negative: non autoimmune, think post surgical ablation |
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what do you do after you tested and found High TSH and normal FT4?
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confirmatory teesting: Anti TPO Ab
if positive: retest TSH every 3-6mo and moniter for s/s of hypothyroidsm if negative: repeat TSH in 1 year |
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what do you do after you tested and found Low sTSH and High FT4?
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hyperthyroidism: need to obtain Thryrotropin R Ab and Anti TPO Ab
if + TRA w or w/o anti TPO= Graves if - TRA w/ + anti TPO= thryoiditis |
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what do you do after you tested and found low sTSH but normal FT4?
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obtain FT3
if normal: sublinical hyperthyroidsim, repeat TSH in 1 yr if high: hyperthryoidism T3 thryotoicosis, obtain TRA |
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Graves disease typically has undetectable ?
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TSH
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if Low TSH, High FT4, order what?
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TPO-Ab
TSI, TGI, LATS (TRA) |
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if low TSH, normal FT4, order what?
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free T3
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what is a solitary nodule? who is it more common in?
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palpably discrete mass w/n otherwise normal thryoid gland
4 times more commen in WOMEN non-neoplastic disorders acct for 90% of solitary nodules *assure pts clinicaly NOT significant |
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90% of solitary nodules consist of what?
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non neoplastic disorders:
nodular hyperplasia colloid cysts foci of thryoidits *assure pts clinically non significant |
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what percent of thryoid nodules are neoplastic ?
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10%
benign neoplasms outnumber malignant 10:1 |
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what percent of solitry nodules are carcinoma?
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less than 1%
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what are the risk factors for solitary nodule containing carcinoma?
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solitary nodule vs multiple
nodules in younger pts nodules in males history of radiation to neck *non fxning nodules are more likely to contain carcinoma but still very small percentage |
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are fxning or non fxning throid nodules more likely to contain carcinoma?
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only less than 1% of nodules contain carcinoma
nonfxnl : more likely, but sill small chance fxning: almost always bening |
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why do radionuclide thryoid scan? ultrasound? Fine needle aspiration biopsy?
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scan: fxnl test and anatomic , Ab aren't always reliable
ultrasound: see if cystic FNAB: excellent test, reduce # nodules that need be removed |
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if there is no pathology in thryoid, after you administer RaI, what will the scan show?
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shows uptake ony in thryoid tissue
calculate % uptake, if overactive 50-75% taken up |
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what does a cold thryoid scan mean?
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area where there is no uptake of RaI
therefore nonfxning. consider carcinoma |
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what does a warm thryoid scan mean? hot?
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warm: fxning nodule but remainder gland fine
hot: fxning nodule and pts remaining thryoid is turned off (can't see it) |
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when do you perform FNAB?
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when solid nodule
isolate fluid |
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what is another term of adenoma and what do they both mean? are they fxning or non fxning usually?
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uninodular (one mass)
always in regard to single thryoid nodule or mass usually non fxnl and non toxic** |
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how do follicular adenomas appear?
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defined external rim of fibrous tissue called a capsule
*white capsule looks very round with slimy center that cloesly resemebles normal tissue |
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waht does toxic mean?
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indicates that the ademona is producing thryoid hormone independent of the regulation of TSH
TSH R is usually mutated to some extent leading to an overprodxn of cAMP |
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what makes up 1.5% of human cancers in US?
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carcinoma of thryoid
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waht is the survival for carcinoma of thyroid?
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indolent, well differentiated neoplasm with 20 yr survival (GOOD surival) w/ the exception of anaplastic carcinoma
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waht are the 4 types of carcinoma of thyroid in order of most occuring?
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1. papillary (75-85%) *rarely long term effects
2. Follicular carcinoma (10-15%) 3. Medullary carcinoma (5%) 4. Anaplastic (<10%) |
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|
what are the risk factors for carcinoma of thyroid?
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Ionizing radiation
after exosure nodules develop at 2% annual rate reaching peak in 15-25 yrs |
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waht is the most common type of carcinoma of thryoid and what does it look like?
|
papillary
formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epi cells *comonly multifocal "carcinomas" b/n 1-3cm below 1 cm = microcarcinomas |
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how does papillary carcioma present clinically
|
presents with spread already to LN
more common in younger pts (90%) at presentation 1/3 of pts have clinically eveident enlarged LN** nodal involvement is seen in 35-50% 90% confined to neck |
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is the survival rate for ppillary carcinoma good?
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yes. hardly ever kils you
5 yr 105% or 100% 10 yr 105% *the cancer population had a better survival than the control or index population b/c they get their other health problems picked up earlier |
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what am i describing?: larger mass that is cystic and contains papillary excresences
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papillary carcinoma of thryoid
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what has Orphan Annie cells?
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papillary carinoma of thryoid: looks like eye w/o pupil
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if a neoplasm is lacking pappillations but behaves like a papillary carcinoma, waht do you need to confirm papillary carinoma?
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Orphan Annie Eye nuclie: washed out, look empty
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what are the 3 clues for Papillary carcinoma?
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psammoma bodies: concentric area of calcification
Orphan Annie nuclei papillations |
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what are psammoma bodies and where are they normally seen?
|
can be present in normal tissues
concentric areas of calcification if you see them then consider papillary carcinoma |
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what do you need to make sure that what looks like a "follicular variant' of pap carcinoma is actually that?
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b/c follicular variant has worse prognosis
papillary carcinoma: better prognosis ( it will have follicles but nuclear changs of papillary carcinoma |
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the Dx of papillary carcinoma is rendered on prescence of what ? irrespective of the presence or absence of papillae?
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nuclear features: Orpan Annie
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How do you differentiate follicular carcinma from follicular adenoma?
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adenoma: capsule
carcinoma: blood vssl invasion |
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who is follicular carcinoma more common in and when does it occur?
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women
6th decade |
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waht are the genetic/familal associations with follicular carcinoma?
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increased freq w/ I deficiency/endemic goiter
radiation exposure TSG may be involved |
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how does follicular carcinoma spread?
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spread more hematogenously unlike pap carcinoma (LN spread)
LN involvement: less than 10% Distant Mets: 15% overall *also good surival |
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what has there been a decline in prevalence and Dx criteria of follicular carcinoma?
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true decreasing incidence of unequivocal follicular carcinoma
*increased recognition of follicular variant of papillary thryoid cancer -relutance of pathologits to base Dx on thryoid follicles in capsule (15% of normal thryoid glands have thryoid follicles in the capsule) |
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waht are the 2 settings of medullary carcinoma of thyroid?
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familial (MEN syndrome) 20%
sporatic 80% |
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how do you differentiate b/n familal and sporatic medullary carinomas of thyroid?
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familal: BILATERAL, associated with other benign or malignant tumors, more comon in CHILDREN and earlier onset with mean 35yrs
sporatic: UNILATERAL, 40-60 |
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how are medullary carinomas of thyroid id histologicaly? what do they all produce?
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presence of amyloid**
produce calcitonin |
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is the survival rate medullary better or worse than papillary or follicualr?
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worse
10 yr 65% |
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what will you see in scan of medullary carinoma? ultrasound? FNA?
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scan: see cold nodule
ultrasound: solid not cystic FNA : show amyloid |
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medullary carcioma of thyroid derive from what?
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C cells therefore secrete calcitonin and will see neurosecretory granules full of calcitonin
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what is anaplastic carcinoma of thyroid and who does it appear in?
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Rapidly progressive
lethal rare older individuals (65) who have history of long standing goiter (50%), prior papillary thryoid carinoma (20%), concurrent papillary carcioma (20%) |
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what is the surivial rate for anaplastic carcinoma of thyroid?
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bad> 6 months from Dx
no good therapy |
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how does anaplastic carcioma appear histologically?
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bizarre
undiff apperance no resemblance to thryoid areas of necrosis |
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what is the clue to locating the parathyroid glands?
|
arterial supply
keep in mind that 10% have only 2 or 3 parathyroid glands |
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what is the best measure of normal parathyroid?
|
weight
avg: 30mg each |
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how does size help you in determing neoplasia of parathyroid?
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4 big glands = Hyperplasia
1 big gland + 3 avg= adenoma |
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PTH affects waht 3 organs?
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bone: osteoclast simulation
kidney: Increase Ca resorption GI: increase Ca resorption |
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mxn of action of PTH?
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acts on surface R
activates G protein increases cAMP |
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what is the most common cause of hypercalcemia overall?
|
primary hyperparathyroidism
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what is the most common cause of symptomatic hypercalcemia?
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malignancy
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what accts for nearly 90% of cases of hypercalcemia?
|
primary hypercalcemia and malignancy
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primary hyperparathyroidism is known as the disease of?
|
bones, stones, groans, and moans if symptomatic
refers to non-specific bone pain, increased association iwth kidney stones, gallstones, peptic ulcer disease, and physiatric symptoms |
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casues of primary hyperparathyroidism?
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parathryoid adenoma (80%)
parathyroid hyperplasia (10-15) parathyroid carcinoma (<5% rare) |
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waht is the most common cardinal feature of hyperparathyroidism?
|
most common presentation: kidney stones
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waht will you see in Xrays of primary hyperparathryoidism pts?
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bone changes, lytic lesions present bc PTH in small bones of hand
"bubble like areas" |
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what is osteitis fibrosa cystica? where most commone? waht called if generalized?
|
LOCALIZED brown tumor associated with hyperparathryoidism
b/c vascular nature ..white osteoid removed b/c bone being resorbed *jaw is common location if generalized (multpile areas) called von Recklinghausen disease of Bone |
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who is primary hyperparathyroidism more prevalent in?
|
postmenopausal women
more females then men age 40-65 |
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what are the associated disesaes of hyperparathyroidism?
|
DM type 2: prrimarily in female DM2 pateints
Thryoid disease |
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which parathryoid glands are parathyroid ademonas more common in? what are the sizes of the adenomas?
|
superior paratthyroid glands
vary greatly in size normal: 30mg adenoma: 300 mg - 3,000 mg tan in apperance |
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how do you differentiate b/n parathyroid adenoma and parathyroid hyperplasia?
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on sestamibi scans there is incresaed uptake in only one of the parathyroid glands in adenoma (usually always solitary lesion) but if hyperplasia, see more than one gland having incresaed uptake
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histologically, how do you know if parathyroid has an adenoma?
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see NO fat..normal parathyroid has dispersed fat
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what cells are present in uniformity in histological section of parathyroid adenoma?
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chief cells
very uniform |
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what is the most common cause of hyperparathyroidism
|
parathryoid adenoma
2nd = hyperplasia 3rd = carcinoma |
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if parathyroid hyperplasia, what do you remove after ID the glands?
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remove 3 1/2 glands to avoid hypercalcemia
don't remove all of them |
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if there is fat present in histological section of parathyroid what does this indicate?
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normal or hyperplasia b/c just expansion of normal gland as opposed to pushing of neoplasm (adenoma = no fat)
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how do you Dx parathyroid carcinoma?
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not by gross apperaance
need to look for invasion: vascular and perinerual |
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secondary hyperparathyroidism is usually caused by? major clinical characteristics?
|
renal failure: serum calcium decreased as a result of renal failure and phosphate metabolism then decreased Ca stimulates PTH secretion
Fatigue, bone pain and fractures, nausea, musclar weakeness |
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what percent of patients with Creatine clearance <40 have histological eveidence of hyperparathyroid bone disease?
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75%
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waht is the most common cause of HYPOparathyroidism?
|
surgical removal-iatrogenic therefore routinely look if pt had thryoid surgery to look at Ca levels
post-op calcium level monitering |
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what does a adrenal cortex look like grossly?
|
yellow b/c of cholesterol
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|
how is the size of fetal adrenal gland in comparison to newborn?
|
large in comparison to size of baby
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|
what enzyme is involved in the prodxn of aldosteron and cortisol?
|
cyt P450 (21 hydroxylase)
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what is the last enzyme inolved in the prodxn of estradiol?
|
cyt P450 aromatase which is import in breast cancer Rx
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|
what do aromatase inhibitors do
|
decrease estrogen in breast cancer pts who are ER+
most common: Arimodex |
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|
what is the paraganglion system?
|
demonstrates sites of paraganglion cell nests in which neoplasms may form
Branchiomeric Intravagal Aorticosympathetic |
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|
what is another name for Hypercorticolism and what is the primary cause?
|
Cushing Syndrome
result of administration of EXOgenous glucocorticoids |
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|
what are the 3 sources of ENDOgenous Cushing Syndrome?
|
1. Primary hypothalamic pituitary disesae (Cushings Disease increased ACTH-70-80%)
2. Hypersecretion by adrenal neoplasm/hyperplasia (10-20%)-adenoma, nodular hyperplasia, carcinoma 3. Secretion of ACTH by nonpituitary neoplasm esp small cell carcinoma (10%) |
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what is the most common ENDOgenous cause of hypercorticolsm?
|
ENDO= Cushings Disease
EXO: Cushings Syndrome |
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|
what is the apearance of adrenals in Cushing Syndrome?
|
Adrenal atrophy b/c excess cortisol due to EXOgenous glucocroticoids
as opposed to Disiease: hyperplasia of andrenals |
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|
what are the top features associated with cushings syndrome?
|
central obesity (85-90%)
moon facies (85%) weakness and fatigability (85%) |
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|
what 3 things characterized primary hyperaldosteronism?
|
hypertension
decresed plasma renin activity hypokalemia or low serum potassium: get muscle weakness, parestesias, intermittent paralysis |
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|
what are the top 2 causes of Primary Hyperaldosteronism?
|
Conn syndrome: benign aldosterone-producing adenoma (APA) -70-80%
Idiopathic hyperaldosteronism (IHA) or primary adrenocortical Hyperplasia- 15-20% |
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|
what are the 3 clinical settings in which we see primary acute adrenocortical insufficiency?
|
1. crisis in pts with chronic insuffiency precipitated by stress (Addisons)
2. too rapid withdrawal from exogenous corticosteroids (don't get Rx refilled) 3. massive adrenal hemorrhage (Waterhouse Friderichsen Sydrome) also metastatic carcinoma related to lung cancer b/c adrenal is common site mets |
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|
what is Waterhouse Friderichsen and what is it characterized by/
|
uncommon
overwhelming bacterial infxn, septicemia, usually Neisseria meningiditis rapidly progressive hypotension leading to shock DIC rapidly developing adrenocortical insuffiencency |
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|
what bacterial infxn commonly causes Waterhouse Friderichsen?
|
Neisseria meningiditis
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|
what are the 4 disorders that account for 90% of Addison Disease?
|
Autoimmune adrenalitis (60-70)
AIDs Tb (now rare) Metastatic cancer (rare) |
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|
do we see hyperpigmentation in Addison?
|
yes bc decreased cortisol stimulating increase in ACTH and increase in MSH
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|
the most common site for adrenal mets is ?
|
lung
|
|
|
what is the cause of secondary adrenal insufficiency
|
disorder of hypothal or pituitary which reduces the output of ACTH
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do we see hyperpig with secondary adrenal insufficiency? what is a constant finding with secondary insufficiency?
|
NO b/c melanotrophic levels are low
moderate to marked redxn in adrenal size |
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|
characteristics of adrenocorticol adenomas
|
benign neoplasm
if fxnl is autonomous (hypercorticolism hyperaldosteronism) do not exceed 5 cm yellow spherical mass sharply Incidentalamos avg 2.5cm |
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what is an Incidentalomas?
|
small enlargement not clinically significant unless producing hormone
|
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|
what is an incidentaloma?
|
incidentaloma is a tumor (-oma) found by coincidence (incidental) without clinical symptoms and suspicion. It is a common problem: up to 7% of all patients over 60 may harbor a benign growth, often of the adrenal gland, which is detected when diagnostic imaging is used for the analysis of unrelated symptoms. With the increase of "whole-body CT scanning" as part of health screening programs, the chance of finding incidentalomas is expected to increase
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waht is the avg size of aldosterone producing adenoma? rare cortisol producing adenoma? which is more common?
|
aldosterone: <2.0cm
cortisol: 4-5cm aldosterone producing are 10-20 times more common |
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|
are adrenocoricoal carcinomas common? age? survival?
|
very rare: 0.05% and 0.2%
large when discovered any age, including childhood poor prognosis, 2 yrs survival |
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|
the best indicators of malignancy are?
|
invasion and mets
|
|
|
what are more common than primary adrenal carcinoma?
|
metastatic carcinom to adrenals most commonly from lung cancer
|
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|
what is the major symptom of Pheochromocytoma? what is the Pluin triad?
|
Hypertension (surgically correctable)
Triad: Headache, sweating, palpitation associated w/ sudden release of cats |
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|
lab findings of pheochromocytoma?
|
increased urinary free cats and metabolites (VMA, metanephrines)
|
|
|
what are the rule of 10's associated with Pheochromocytomas?
|
10% familial
10% extra-adrenal (paragangliomas) 10% of nonfamilal are bilateral 10% biologically malignant 10% childhood |
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|
10% of pheochromocytomas occur where?
|
in the aortosympathetic system
|
|
|
grossly how do pheochromocytomas appear?
|
gray-tan compared with the yellow cortex stretched around them of cortex
soft, hemorrhagic |
|
|
how do pheochromocytomas appear histologicaly? cells involved?
|
nests of cells (zellballen) with abundant cytoplasm
bizarre cells that are benign EM: membrane bound secretory granules with cats |
|
|
what occur at a younger age, arise in multiple organs either syndronously or metachronously, and are usually preceded by an asymptomatic stage of endocrine hyperplasia?
|
MEN syndromes
|
|
|
carcinoma of what is associated with MEN-1 and what is teh other name for this syndroem?
|
Wermer syndrome
carcinoma of pancreatic islets |
|
|
carcinoma of what is associated with MEN-2a and what is the other name for this syndrome?
|
Sipple
medullary carcinoma of thyroid |
|
|
carcinoma of what is associated with MEN-2b/3?
|
medullary carcinoma of thyroid
|
|
|
what do the cells of pancreas make? in what percentages?
|
beta (68%)-insulin
alpha (20%)-glucagon delta (10%)-somatostatin |
|
|
how do pancreatic beta cells apear on EM? alph?
|
membrane bound granules with often rectangular core and distinct halo
alpha: dense, round center |
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|
the most impt stimulus that triggers insulin syn and release is?
|
glucose
|
|
|
principal fxn of insulin?
|
to increase the rate of glucose transport into certain cells f the body: strated muscle cells and adipose
|
|
|
what is the anabolic effect of insulin?
|
increase syn and reduce degradation of glycogen, lipids, and proteins thereby reducing circulating glucose level
|
|
|
what are the most numerous cell type affected by insulin?
|
hepatocytes
|
|
|
what happens to glucose in beta cell?
|
enters via GLUT-2 (insulin independent)
undergoes oxidative metabolism to yeild ATP ATP inhibits influx of K which leads to membrane depol influx of Ca release of stored insulin from beta cells |
|
|
insulin effects on liver?
|
decrease gluconeo
increase glycogen syn increase lipogen |
|
|
insulin effects on striated m?
|
increase glucose uptake
incresae glycogen syn increase protein syn |
|
|
in what age group are we seeing an increase in prevalace of Dx diabetes?
|
every age group (mostly related to DM2)
most marked in older age groups (65-74) |
|
|
what are the main cuases of DM1 and 2? how common are each?
|
1: absolute def of insulin caused by autoimmune destrxn of beta cells (5-10%)
2: combo of peripheral resistance to insulin and inadequate secretory response by the pancreatic beta cells (90%) |
|
|
what is MODY?
|
primary defect in beta cell fxn w/o beta cell destrxn (2-5% of DM)
|
|
|
what is gestational diabetes
|
any degree of glucose intolrance w/ onset or first recognition during pregnancy (4%)
chance of potential devlopment of overt diabetes |
|
|
DM symtpoms?
|
polyuria
polydipsia unexplaed wt loss PLUS (any 1 below): RANDOM glucose >200mg/dl (11.1mmol/L) OR FASTING plasma glucose >126 (7.0mmol/L) repeated on a DIFFERENT day OR Oral glucose tolerance test 2hr plasma glucose >200 (11.1mmol/L) |
|
|
what is the initial (diagnostic test for DM? confirmatory? Monitering?
|
diagnostic: fasting plasma glucose
confirmatory: repeat fasting plasma or serum glucose susequent day (min 8-12 hrs fasting) Monitering: HbA1c following initial Dx and 4x/yr until well controlled |
|
|
what is the best way for monitering DM over long period of time? what do you do when the pt is well controlled?
|
GlycoHb HbA1c
if pt is well controlled (levels <6.5%) only 2x/year is sufficient Self monitering Commercial Reagent Test Strip or Urine "dipstick" |
|
|
if you have renal glycosuria, should you use a urine dipstick to moniter your glucose?
|
No..only if hve nl renal fxn
|
|
|
what are the levels for Provisional Dx of diabetes? Impaired fasting glucose? Normal? what happens if levels are 126 or greater?
|
Provisional: 126mg/dL or greater
Impaired fasting: 110-125mg/dL Normal: below 110mg/dL repeat fasting glucose subsequent day and if value is 126 or greater = second value confirms Dx |
|
|
when is the most common time to present clinically?
|
around age 20
|
|
|
what is the histological hallmark of DM1? DM2?
|
DM1:lymphocytic infiltrate destroying beta cells
amyloid deposition for DM2 |
|
|
insulitis think? amyloid/pink hyalinization think?
|
insulitis: DM1
amyloid: DM2 |
|
|
incidence changes in DM1?
|
increasing incidence in young children
more than doubled in N European and N Amn countries |
|
|
90-95% of Caucasians with DM1 have waht HLA types?
|
HLA-DR3, DR4 or both while 90% DM1 cases sporadic with no clustering in families
*signif genetic component but vast majority = sporatic |
|
|
DM2 is a combo of what?
|
combo of resistance to insulin action and an inadequate compensatory insulin secretory response
|
|
|
are genetics more impt in dM1 or 2?
|
2
|
|
|
what is the inheritance of MODY and how does it present?
|
AD with high penetrance
early onset-before age 25 absence of obesity lack of islet cell autoAb and insulin resistance syndrome |
|
|
when/how does gestational diabetes present and how will you determine its existence?
|
normal pregnancy creates a condition of impaired target organ response to insulin or "insulin resitance" like DM2
begins in 2nd trimester post partum: insulin responsiveness returns to normal Test: 50g Oral glucose challenge test 24-28 weeks as a screening test if 2 hour values are >140 the test is + |
|
|
postive oral glucose challenge on pregnant patients should be followed by what?
|
diagnostic 3 hr oral glucose tolerance test
|
|
|
what is maternally associated with gestational diabetes? fetal?
|
maternal: more likely to develop hypertension and preeclampsia
fetal: fetal macrosomia (large baby) |
|
|
what are the long term complications of DM?
|
macrovascular disease:atherosclerotic changes, limb gangrene
microvascular disease: capillary BM thick and more permeable, neuropathy, retinopathy, blindness |
|
|
what is the leading cause of blindness in DM
|
microvascular disease: retinopathy
all related to underlying metabolic changes: HYPERGLYCEMIA |
|
|
what is the #1 cause of death in long term diabetics?
|
MI
|
|
|
what is a Kimmelstein-Wilson lesion?
|
associated with diabetic nephropathy
nodular glomerulosclerosis, prolif of mesangium |
|
|
severe renal hyaline arteriosclerosis is a complication of ?
|
DM
|
|
|
what is the EM hallmark of microvascular disease associated with DM?
|
thickened glomerular BM
|
|
|
is Ketaocidosis in DM1 or 2?
|
common type 1 that leads to a diabetic coma (look drunk, smell ketones which smell like alcohol)
|
|
|
what are 3 common Pancreatic ENDOcrine neoplasms?
|
1. insulinoma (hyperinsulinism)
2. gastrinoma (Zollinger Ellison syndrome) 3. MEN syndrome |
|
|
what is another name for pancreatic endocrine tumor?
|
islet cell tumor with monotonous neoplastic cells
*all fxnl and non fxnl are called islet cell carcinoma b/c likelihood of mets cannot be predicted from tumor microscopic appearance..malignant behavior is based on criteria of demonstrated mets |
|
|
when should you consider an islet cell tumor malignant?
|
all FXNL islet cell tumors should be considered potentially malignant b/c all have been assoiciated with metastatic disease
*fxnl pancreatic endocrine neoplasmas are named with an -oma on the end |
|
|
what is the best predictor of metastatic disese in islet cell carcinoma?
|
the polypeptide agent secreted by the tumor b/c isulinomas are the most common but only 10% malignant
|
|
|
which islet cell carcinomas have the hightest percent malignanc?
|
somatostatinoma 90
VIPoma 80 gastrinoma (MEN1) 75 |
|
|
what are the most common pancreatic endocrine neoplasms?
|
insulinoma
90% benign 80% have some degree of incresed secretion of insulin |
|
|
what is the clinical triad associated with insulinomas?
|
attackes of hypoglycemia
CNS symptoms: confusion, stupor attacks precipitated by fasting or exercise and relieved by administering glucose |
|
|
what is another name for gastrinoma? where are they found? what percent malignant?
|
Zollinger Ellison sydrome
arise in duodenom, pacreas, or near pancreas >50% malignant 95% have some degree of incresed secrtion of gastrin |
|
|
what is the clinical presentation (2) of gastrinomas?
|
peptic ulcer disease-may be severe
diarrhea |
