Tumors of the Endocrine System Flashcards
<p>What are the 3 classifications for endocrine tumors?</p>
<p>Non-neoplastic hyperplasias</p>
<p>Benign adenomas</p>
<p>Malignant carcinomas</p>
<p>How does non-neoplastic hyperplasia occur?</p>
<p>As a consequence of aberrant secretion of trophic hormones resulting in growth and increased function</p>
<p>Is hyperplasia reversible? Why is this controversial?</p>
<p>Not always even though the inciting cause is removed. Can be confused or difficult to differentiate from tumors as they grow independent of trophic factors</p>
<p>What are the general clinical manifestations of neuroendocrine tumors?</p>
<p>Result of growth, expansion, and metastasis of the tumor, producing traditional sequelae due to compression of normal tissue (adenoma), invasion and destruction of regional or systemic normal tissue function (carcinoma), and secretion of hormones or hormone-like substances</p>
<p>What is considered to be the classic theory of carcinogenesis in thyroid tissue? What has emerged recently?</p>
<p>Accumulation of somatic mutations leading to dedifferentiation from mature to anaplastic cells.</p>
<p></p>
<p>The theory of epithelial to mesenchymal transition which suggests the potential for cancer stem cells</p>
<p>What growth factors are known to play a role in the pathogenesis of endocrine neoplasia?</p>
<p>epidermal growth factor, insulin-like growth factors, growth hormone</p>
<p></p>
<p>Any single growth factor, however, cannot cause malignant transformation of a cell</p>
<p>From what cell types can pituitary tumors arise from (5)?</p>
<ul> <li>corticotrophs</li> <li>somatotrophs</li> <li>thyrotrophs</li> <li>gonadotrophs</li> <li>lactotrophs</li></ul>
<p>What are the different types of pituitary tumors?<em>histologic types maybe?</em></p>
<p>Non invasive adenoma, invasive adenomas, adenocarcinomas (reserved for when mets are present)</p>
<p>Clinical size of pituitary tumors depend on what 2 big things?</p>
<p>Size and what they secrete</p>
<p>Which is the most clinically important pituitary tumor in the <strong>dog?</strong> What does it produce and with what clinical signs is it associated with?</p>
<p></p>
<p>Pituitary adenoma, corticotroph adenoma</p>
<p>Chronically excessive amounts of ACTH</p>
<p>Associated with clinical signs of hypercortisolism</p>
<p>Which is the most clinically important pituitary tumor in cats? With what clinical sings is it associated with?</p>
<p>GH-secreting somatotroph pituitary adenoma,occurs in the pars distalis</p>
<p>Causes acromegaly and insulin-resistant diabetes mellitus</p>
<p>When do non-functional pituitary tumors become clinically significant?</p>
<p>When they are large enough to cause neurologic signs - obtundation, stupor, behavioral changes, decreased apetite, etc</p>
<p>In a case series of 177 cases, what was the second most common type of brain tumor found and for what percentage did it account for?</p>
<p>Pituitary tumors</p>
<p>25%</p>
<p></p>
<p><em>Secondary intracranial neoplasia in the dog: 177 cases. JVIM, 2008.</em></p>
<p>What is another way pituitary tumors may present?</p>
<p>With loss of their function, resulting in hypothyroidism, hypocotisolism, gonadal atrophy, central diabetes insipidus</p>
<p>What is the most common cause of hypercortisolism in dogs? It accounts for \_\_\_% of cases.</p>
<p>Pituitary dependent Cushing's disease = pituitary corticotroph adenoma</p>
<p>85%</p>
<p>What is the endocrinologic pathogenesis of pituitary corticotroph tumors?</p>
<p>Chronic excessive production of ACTH, which subsequently stimulates both of the adrenal glands to produce cortisol.</p>
<p>There is loss of negative feedback inhibition at the level of the pituitary gland and the hypothalamus can no longer control the production of ACTH as it does not matter if it produces CRH or not, pituitary gland will do what it wants. <em>Feedback loops</em> <em>are not inhibited by the increased amount of cortisol.</em></p>
<p>What proteins and receptors are thought to be involved in pituitary corticotrophs?</p>
<p>leukemia inhibitory factor and its receptor are expressed but not mutated</p>
<p>Dopamine type 2 and somatostatin type 2 receptors are more prevalent in pituitary tumors when compared to normal pituitary tissues but expressed at low levels</p>
<p>What is the difference between a pituitary macroadenoma and a microadenoma?</p>
<p>This comes from human medicine</p>
<p>Micro <1cm in diameter</p>
<p>Macro >1cm in diameter</p>
<p>Controversial in human medicine</p>
<p>In a 2010 cross-sectional imaging study of 33 dogs with pituitary tumors, what percentage were found to be adenomas, invasive adenomas, and adenocarcinomas?</p>
<p>Adenomas - 61%</p>
<p>Invasive adenomas - 33%</p>
<p>Adenocarcinomas - 6%</p>
<p><em>Cross-sectional imaging characteristics of pituitary adenomas, invasive adenomas, and adenocarcinomas in dogs: 33 cases. JVIM, 2010.</em></p>
<p>What is the typical age, sex,and breed for dogs with PDH?</p>
<p>Older than 9 years</p>
<p>Females overrepresented</p>
<p>Dachshunds, terrier breeds, GSD, poodle breeds</p>
<p>What are the most common clinical signs of hypercortisolism?</p>
<p>PU, PD, polyphagia, abdominal enlargement, lethargy, panting, exercise intolerance, muscle weakness, alopecia, calcinosis cutis, thinning of the skin, reproductive abnormalities</p>
<p>Glucose intolerance and insulin resistance can develop in up to \_\_\_ of Cushing's cases.</p>
<p>10%</p>
<p>What are the 4 effects of glucocorticoids that are responsible for the changes seen in dogs with HC or Cushings?</p>
<p>Glucocorticoid effects:</p>
<ul> <li>Gluconeogenic effects</li> <li>Catabolic effects</li> <li>Immunosuppressive effects</li> <li>Antiinflammatory effects</li></ul>
<p>The catabolic effects of glucocorticoids result in what?</p>
<ul> <li>Thinning of the skin</li> <li>Poor wound healing</li> <li>Muscle wasting</li> <li>Decreased bone density</li></ul>
<p>The antiinflammatory and immunosuppressive properties of glucocorticoids are responsible for what?</p>
<p>Increased susceptibility to infection seen</p>
<p>What is the most common infection seen in dogs with HC?</p>
<p>UTI</p>
<p>In one study of dogs with HC, what percentage had UTIs?</p>
<p>46%</p>
<p>Hypertension and proteinuria are more serious disorders associated with canine HC. True or false?</p>
<p>True</p>
<p>Over 80% of dogs with Cushin's were reported to be hypertensive in one case series.</p>
<p>PTE although uncommon, can also be seen.</p>
<p>Over \_\_\_% of dogs with canine Cushing's were reported to be hypertensive in one case series.</p>
<p>80%</p>
<p>What are some labwork abnormalities seen in dogs with Cushing's disease?</p>
<p>CBC: Neutrophilia, monocytosis, lymphopenia, eosinopenia, thrombocytosis</p>
<p>Chemisty:elevated ALP, ALT, cholesterol</p>
<p>UA: isosthenuria or hyposthenuria</p>
<p>What are some screening tests used for suspicion offor Cushing's? How are their specificity and sensitivity?</p>
<ul> <li>Urine cortisol:creatinine ratio <ul> <li>Very sensitive but not specific, should not be used in ill patients</li> </ul> </li> <li>Low-dose dexamethasone suppression test (LDDST) <ul> <li>Highly sensitive (less likely to give false negatives)</li> <li>Able to distinguish between PDH and ADH in some cases</li> </ul> </li> <li>ACTH stimulation test <ul> <li>Lower sensitivity and higher specificity than the LDDST</li> </ul> </li></ul>
<p>Which tests are considered differentiation tests for Cushing's disease?</p>
<ul> <li>HDDST</li> <li>Endogenous ACTH levels <ul> <li>Dogs with ADH, these should be low</li> <li>Dogs with PDH, theese should be high</li> </ul> </li> <li>Advancedimaging</li></ul>
<p></p>
<p>Approximately what percentage of dogs with HC have PDH?</p>
<p>80 to 85%</p>
<p>Neuro clinical signs is not common</p>
<p>In an 1996 study of 13 dogs that underwent MRI evaluation of the brain at the time of PDH diagnosis, how many dogs had a visible pituitary mass and how many had neurologic clinical signs from the disease? How many dogs had neuro signs at the 1 year follow up?</p>
<p>8</p>
<p>None</p>
<p>2</p>
<p>\_\_\_ to \_\_\_ % ofdogs with PDH have tumors that are not visible on MRI and \_\_\_ to \_\_\_ are at risk for the development of neurologic clinical signs. If clinical signs develop, they develop \_\_\_ to \_\_\_ months from the diagnosis.</p>
<p>40-50% - these are unlikely to develop neurologic clinical signs</p>
<p>15 to 25% of dogs with PDH are at risk for development of neurologic clinical signs due to the presence of an enlarging tumor</p>
<p>6 to 18 months</p>
<p>Canine hyperadrenocorticism (Cushing’s syndrome). Canine and feline endocrinology and reproduction, 2004.</p>
<p>Transphenoidal hypophysectomy has an overall success rate of \_\_\_.</p>
<p>65% - not done commonly, only in a place in Europe</p>
<p></p>
<p>Complications: central diabetes insipidus,</p>
<p>In a 1990 study of 6 dogs with functional pituitary macrotumors that were treated with 10 4Gy fractions (total of 40Gy), what was the MST? What happened with the neurologic clinical signs and ACTH levels?</p>
<p>MST 743</p>
<p>Neuro CS resolved in all dogs</p>
<p>ACTH levels remained high for at least 1 year after therapy</p>
<p>In one study, megavoltage irradiation on pituitary tumors in 24 dogs with neurologic CS, \_\_\_ dogs achieved a complete remission of the neurologic CS and \_\_\_ achieved a partial remission. What correlation between what 2 things was noted in this sutudy?</p>
<p></p>
<p>10 and 10</p>
<p>Tumor size and CS</p>
<p>Early treatment is better for these</p>
<p></p>
<p><em>Megavoltage irradiation of pituitary macrotumors in dogs with neurologic clinical sings. JAVMA, 1998.</em></p>
<p>In a 2007 study comparing the neurologic response and prognostic factors in dogs with pituitary masses treated with radiation therapy versus untreated dogs, the MST in the treated group was \_\_\_ dayscompared to \_\_\_ days in the untreated group. What were the 1, 2, and 3 year estimated survival rates for the trated vs the untreated group?</p>
<p>Treated group:</p>
<ul> <li>MST 1405 days</li> <li>1-yr survival rate 93%</li> <li>2-yr survival rate 87%</li> <li>3-yr survival rate 55%</li></ul>
<p>Untreated group:</p>
<ul> <li>MST 551 days</li> <li>1-yr survival rate 45%</li> <li>2-yr survival rate 32%</li> <li>3-yr survival rate 25%</li></ul>
<p>Treated dogs with smaller tumors lived longer than those with large, again suggesting that early treatment is better</p>
<p><em>Survival, neurologic response, and prognostic factors in dogs with pituitary masses treated with radiation therapy and untreated dogs. JVIM 2007.</em></p>
<p>What is the endocrinologic in dogs with PDH treated with RT?</p>
<p>Hard to predict, ACTH does not always normalize alhtough neuro CS do tend to resolve. IfACTH normalizes, it is in the minority and it is long after treatment was received.</p>
<p>Approximately what percentage of cats with HC are due to pituitary disease?</p>
<p>80 to 85%</p>
<p>Feline HC is often associated with what other endocrinologic condition?</p>
<p>Insulin-resistant diabetes</p>
<p>What are some clinical signs of cats with HC?</p>
<p>PU/PD, polyphagia, weight loss, pot-bellied appearance due to hepatomegaly, muscle weakness, thin fragile skin that tears and bruises easily, generalized muscle atrophy, unkempt haircoat, alopexia</p>
<p>What are treatment options for cats with PDH?</p>
<p>Surgical bilateral adrenalectomy was the treatment of choice for some time. Also reported hypophysectome and RT. Medical treatment with trilostane - could be use as sole treatment or in preparation for surgery or RT.</p>
<p></p>
<p>They are poor surgical candidates because of poor healing.</p>
<p>What is feline acromegaly?</p>
<p>A disease of older cats resulting from chronic excessive GH secretion, usually from a <strong>functional somatotroph adenoma</strong> of the pars distalis of the pituitary gland.</p>
<p></p>
<p>This is the most clinically significant pituitary tumor in cats</p>
<p>Is there a sex predisposition for pituitary somatotroph tumors in cats? What is the typical history in these cats?</p>
<p>Has been reported most commonly in male cats</p>
<p>History: Insulin-resistant diabetes mellitus, with affected cats requiring 10 to 20 units of insulin per dose or more, often with inadequate control of their diabetes.</p>
<p>Why does insulin resistance occur in cats with feline acromegaly due to a pituitary somatotroph tumor?</p>
<p>Due to a GH-induced post receptor defect in the action of insulin on target cells.</p>
<p>What are clincal signs seen in cats with feline acromegaly?</p>
<p><strong>Weight gain</strong>, as opposed to weight loss seen in cats with poorly regulated diabetes mellitus - this is highly suggestive of feline acromegaly.</p>
<p>Also, PU/PD, polyphagia, enlarged feet, broadening of the face, protrusion of the mandible, increased spacing between the teeth, abdominal enlargement, noisy or stertorous breathing, respiratory stridor, enlarged abdominal organs, cardiac murmurs, arrhythmias, gallop rhythm</p>
<p>What is the differnece in weight in cats with feline acromegaly vs PDH?</p>
<p>Feline acromegaly - FAT</p>
<p>PDH - SKINNY</p>
<p>How are neurologic clinical signs in cats with feline acromegaly?</p>
<p>Generally uncommon</p>
<p>Is there a reliable assay for dx feline acromegaly in USA?</p>
<p>Nope.</p>
<p>In Europe, however, there is an ovine GH assay validated for the diagnosis of feline acromegaly</p>
<p>Can there be an overalp in cats with diabetes and cats with acromegaly?</p>
<p>yes</p>
<p>Why are physical changes seen in cats with feline acromegaly?</p>
<p>Due to the anabolic effects of GH, which are mediated by peripherally synthesized IGF-1.</p>
<p></p>
<p>Where is IGF-1 produced? Which is more sensitive for dx acromegaly? GH or IGF-1?</p>
<p>Produced in the liver, levels of it increasesin the presence of chronically increased GH production. Because GH may be pulsatile, even in some acromegalics, and because it has a short half, life, IGF-1 is a more sensitive test for acromegaly because it may reflect GH over the preceding 24 hours.</p>
<p>What is the sensitivity and specificity of IGF-1? For what type of test is it used?</p>
<p>Sensitivity 84%</p>
<p>Specificity 92%</p>
<p>Screening test</p>
<p><i>One study reported no differnce in IGF-1 in well controlled diabetics, poorly controlled diabetics, and healthy cats. In cats with acromegaly, it is usually at least twice the upper reference range value. There is a test for IGF-1 in USA.</i></p>
<p>Which imaging modality is more sensitive in cats with acromegaly?</p>
<p>MRI</p>
<p>Can be normal on imaging</p>
<p>What is the most widely reported treatment modality for cats with feline acromegaly secondary to a pituitary tumor?</p>
<p>ConventionalRT</p>
<p>CSU - SRT</p>
<p>Some owners can just do insulin - dose used should be the one that controls the diabetes. Ranges usually in between 10 to 20 per dose.</p>
<p>What drugs are used in humns with acromegaly? MOA?</p>
<p>Somatostatin analogs, dopamine agonists, GH-receptor antagonists</p>
<p>MOA:</p>
<p>Somatostatin analogs - bind to GH receptors suppressing GH release from the pituitary - response assessed by measurement of IGF-1, GH, tumor size</p>
<p>Octreotide - one study show it did not work, another study suppressed GH for 120 post injection - using short acting</p>
<p>What is the short term and long term prongosis for cats with acromegaly? What do they usually succumb to? What is the MST in once case series?</p>
<p>Short term - fair to good</p>
<p>Long term prognosis - poor</p>
<p>Cardiac or renal faolure, neurologic disease, complications od poorly regulated diabetes</p>
<p>MST 20.5 months</p>
<p>What is the overall prevalence of adrenal tumors in dogsand cats? From whatzone do they most commonly arise? In on study going over 191 canine cases that underwent surgery, what % were cortical and what % were medullary? What % of the cortical were further classidied as carcinomas, adenomas, and hyperplasia?</p>
<p>0.17-0.76% of dogs (1-2% of all canine tumors)</p>
<p>0.03% of cats (0.2% of all feline tumors)</p>
<p>cortical more common than medullary;</p>
<p>In one study of 191 dog cases:</p>
<p>-80% were cortical: 50% carcinomas, 43% adenomas, 6% hyperplasia</p>
<p>-17% were medullary:</p>
<p></p>
<p>Probably underdiagnosed</p>
<p>When the data from several cases evaluating the outcome of adrenal surgery in 191 dogsis combined, excuding the large restrospective study at UC Davis, what % arised from the medulla and cortex? What % of the cortical tumors were carcinomas, adenomas, or hyperplasia?</p>
<p>-80% were cortical: 50% carcinomas, 43% adenomas, 6% hyperplasia</p>
<p>-17% were medullary</p>
<p>In one very large retrospective study performed over a 20-year period at UC davis of patients with adrenal tumors what % of tumors in both dogs and catswere cortical, medullary (pheochromocytoma), and metastatic? What was the most common metastatic neoplasm in both spp?</p>
<p>Dogs:</p>
<ul> <li>41% cortical (78% adenomas, 21% carcinomas)</li> <li>32% medullary/pheochromocytoma</li> <li>27% medullary</li></ul>
<p>Cats:</p>
<ul> <li>30% adrenocortical</li> <li>10% medullary/pheochromocytoma</li> <li>60% metastatic</li></ul>
<p>Lymphoma!!!</p>
<p><em>Metastatic tumors to the adrenal glands in domestic animals. Vet Pathol, 2005. </em>All metastatic melanomas were found at the medulla.</p>
<p>How sensitive and specific has ultrasound beenreported to be for the detection ofinvasion of adrenal tumors into the caudal vena cava? What about contrast enhanced CT?</p>
<p>US:</p>
<ul> <li>Sensitivity 80-100%</li> <li>Specificity 90%</li></ul>
<p>Contrast enhanced CT:</p>
<ul> <li>Sensitivity 92%</li> <li>Specificity 100%</li></ul>
<p>What % of functional cortisol-secreting tumors of the adrenal cortex are responsible for canine and feline cases of naturally occuring HC?</p>
<p>15 to 20%</p>
<p>Dogs with PDH accounts for 80 to 85% of cases</p>
<p>A review of <strong>functional</strong>adrenal tumors in dogs suggested that approximately \_\_\_% of them were \_\_\_.</p>
<p>60% carcinomas</p>
<p>Approximately what % of adrenocortical carcinomas invade the phrenicoabdominal vein? Extension into what veins can be seen?</p>
<p>20%</p>
<p>Renal vein and caudal vena cava</p>
<p>Metastasis in dogs with adrenocortical carcinomas has been identified in approximately \_\_\_% of cases. Where do they most commonly metastasize to?</p>
<p>50%</p>
<p>Liver and lungs</p>
<p>In an 1986 study evaluating the results of surgical treatment for hyperadrenocorticism caused by adrenal gland neoplasia in 25 dogs, the perioperative mortality was \_\_\_%. In more recent case series, the perioperative mortality ranges from \_\_\_ to \_\_\_ %.</p>
<p>60%</p>
<p>19 to 28%</p>
<p>MSTs reported for dogs undergoing adrenalectomy for both carcinomas and adenomas is?</p>
<p>MST carcinoma 230-778 days</p>
<p>MST adenoma</p>
<p>687.5 days</p>
<p>Using mitotane as a cytotoxic agent for dogs that cannot undergo surgery for the treatment of ADH reports a MST in 32dogs of \_\_\_ months.</p>
<p>A recent study comparing mitotane vs trilostane for dogs with adrenal tumors reported a MST of \_\_\_ days and \_\_\_ days. This study confimred that the survival time is negatively affected by the presence of what?</p>
<p>16.4 months</p>
<p>Uses higher doses than that used in PDH</p>
<p>Mitotane MST: 102 days</p>
<p>Trilostane MST : 353 days</p>
<p>Metastatic disease</p>
<p>Recent study:JVIM 2011</p>
<p>What is the most common adrenocortical disorder in cats? What are the most common tumors associated with this?</p>
<p>What are some key features if this condition in cats?</p>
<p>Hyperaldosteronism</p>
<p>Aldosterone secreting arenocortical tumors; adenoma or carcinoma</p>
<p>Hypokalemia, hypertension (w or w/o ocular changes), concurrent renal disease</p>
<p>What cells in the adrenal medulla form part of the sympathetic system? These neoplastic cells give rise to what tumors? Predominantly, what do they secrete?</p>
<p>Chromaffin cells</p>
<p>Pheochromocytoma</p>
<p>Catecholamines</p>
<p>How common are pheochromocytomas in dogs and cats?</p>
<p>Uncommon in dogs, rare in cats</p>
<p>Pheochromocytomas are considered to be a \_\_\_\_ tumor. Metastasis from them is seen in \_\_\_ of cases. What are common metastatic sites? Vacular invasion has been reported in as many as \_\_\_% of cases.</p>
<p>Malignant tumors</p>
<p>40% met rate</p>
<p>Liver, spleen, lungs, regional LN, bone, and CNS</p>
<p>82% have vascular invasion</p>
<p></p>
<p>How is catecholamine release? What are some CS and PE findingsassociated with them?</p>
<p>Episodic - CS may be intermittent</p>
<p>Weakness, episodic collaps, panting, anxiety, restlessness, excercise intolerance, decreased eppetite, weight loss, PU/PD, hypertension, panting, tachypnea, tachycardia, cardiac arrhythmias, weakness, pallor</p>
<p>What IHC marker can distinguish pheochromocytoma from adrenocortical tumors?</p>
<p>Chromogranin A</p>
<p>What can be measuredin urine and plasma ofdogs with pheos?</p>
<p>Urinary catecholamine and metanephrine to creatinine ratios</p>
<p>{lasma free metanephrine and normetanephrines</p>
<p>What is the tx of choice for pheos? What are life threatening complications of this type of treatment?</p>
<p>Surgery</p>
<p>Intraoperative hypertension, hypotension, cardiac arrhythmias, hemorrhage</p>