Endocrine Neoplasia Flashcards
If clinical signs are present with thyroid tumors, what are they?
dysphagia, voice change, laryngeal paralysis, Horner’s syndrome, dyspnea
What percentage of thyroid tumors in dogs are carcinomas/adenocarcinomas
90%
Potential complications of thyroid tumor removal in dogs?
hemorrhage, recurrent laryngeal nerve damage
Locations for ectopic thyroid carcinomas?
Base of tongue, hyoid apparatus, cranial mediastinum, right heart base
Prognosis for dogs with unilateral mobile thyroid carcinomas?
MST of 36 months; 70% 2 year survival rateR
Risk factors associated with hyperthyroidism in cats?
canned cat food, iodine content of cat food, indoor residence, use of litter, exposure to brominated flame retardants, flea control products
Clinical signs and PE findings hyperthyroidism in cats
Weight loss with polyphagia, hyperactivity, GI signs, PU/PD, palpable thyroid nodule, tachycardia, arrhythmia, heart murmur/gallop, poor hair coat
Potential side effects of methimazole
lethargy, anorexia, vomiting, facial excoriations, hepatotoxicity, bleeding diatheses, blood dyscrasias
Doses of I131 for feline hyperthyroidism
2 to 6 mCi
Outcome of I131 treatment for cats with hyperthyroidism?
95% of cats are euthyroid after one treatment
What is the difference between hypersomatotropism and acromegaly?
Hypersomatotropism - excess growth hormone
Acromegaly - clinical condition associated with excess GH
In a European study, what percentage of diabetic cats had elevated IGF-1 consistent with acromegaly?
18%
What is the prevalence of acromegaly in the average diabetic cat? In cats that are difficult to regulate?
Average - 10-15%
Difficult - 30%
Is there a sex predilection for acromegaly?
Males more common
What is one clinical finding that differs between poorly regulated diabetic cats and acromegalic cats?
Acromegalic cats gain weight vs poorly regulated diabetic cats lose weight
What test is performed in the US to test for acromegaly in cats?
Serum IGF-1 concentrations
What is the sensitivity and specificity of IGF-1 concentrations to test for acromegaly?
Sens - 84%
Spec - 92%
What is the recommended treatment of acromegaly in humans? In cats?
Humans - hypophysectomy (surgery)
Cats - Radiation therapy
What was the outcome of SRT administered in 3 or 4 doses to 53 acromegalic cats?
MST 1072 days (36 months)
What is a potential side effect to another endocrine system in acromegalic cats treated with SRT?
Hypothyroidism
What are the medical management options for acromegaly in cats?
Somatostatin analogs - octreotide, pasireotide ($$$)
Insulin management - 10 - 20 U or more per dose
What is the median survival time in general for cats with acromegaly without specific therapy?
MST 20.5 mos
What percentage of adrenal tumors are cortical? Medullary?
Cortical - 75%
Medullary - 23%
What percentage of adrenal tumors are carcinomas? Adenomas? Hyperplasia?
Carcinoma - 57%
Adenoma - 39%
Hyperplastic - 4%
What size cutoff is an adrenal tumor more likely to be a carcinoma in dogs?
> 2 cm
What percentage of adrenocortical carcinomas invade the phrenicoabdominal vein with extension into the renal v/ caudal vena cava?
20%
At time of diagnosis how many dogs with adrenocortical carcinoma have evidence of metastasis?
50%
What is the sensitivity of ACTH stim for adrenal dependent hyperadrenocorticism?
60%
What is the prognosis for dogs with ADH undergoing adrenalectomy after 4 weeks post op?
MST 3 yrs
What is the median survival time for dogs with adrenocorticocarcinoma undergoing adrenalectomy?
230 - 778 d (8 - 26 mos)
What is the median survival time for dogs with adrenal adenomas with surgery?
MST 688 days (23 mos)
With SRT, what is the median survival time of adrenocortical tumors with vascular invasion treated with external beam radiation?
1030 days (34 mos)
What is the mean survival time for dogs with functional adrenal tumors and no evidence of metastasis treated with mitotane?
16.4 mos
In a retrospective comparing mitotane to trilostane, what was the median survival time for each in the treatment of functional adrenal tumors?
Mitotane - 102 d (3 mos)
Trilostane - 353 d (~12 mos)
What is the survival time reported for functional adrenal tumors with metastatic disease treated with mitotane and trilostane?
Mitotane - 15.6 mos
Trilostane - 14 mos
What is Conn’s syndrome?
Primary hyperaldosteronism in cats
Are dog cortitroph adenomas functional or non-functional?
functional - produce adrenocorticotrophic hormone (ACTH)
Are feline somatotroph adenomas functional or non-functional?
functional - produce growth hormone
What percent of dog and cat HAC is pituitary dependent?
80-85%
What part of the pituitary gland do ACTH secreting tumors typically arise?
70-80% arise from pars distalis
Remainder from pars intermedia
Do dogs with PDH commonly have tumors that can be seen with CT/MRI?
40-50% are not visible
(note: so only 15-25% are at risk for developing neuro signs due to an enlarging tumor)
Which cells in the adrenal gland make up pheochromocytomas?
Chromaffin cells
What percentage of pheochromocytoma cases have metastasized at the time of diagnosis?
40%
What percentage of pheochromocytomas have evidence of vascular invasion?
82%
What is the prognosis for pheochromocytomas after surgical resection?
MST 374 d (12.5 mos)
How does primary hyperparathyroidism cause hypercalcemia
PTH is released in excess
PTH causes directed affects through increased resorption of calcium from the bone ( increased bone turnover) and decreased calcium excretion ( increased reabsorption of ca and increased excretion of phosphorus) from the kidneys and increased production of Vitamin D
indirectly that vitamin D increases calcium absorption from the intestines
What treatment prior to surgery has been shown to significantly improve outcomes in dogs with pheochromocytomas?
Phenoxybenzamine
In which type of adrenal tumor is caval thrombus more common?
Pheochromocytoma
What is the perioperative mortality rate of adrenalectomy in dogs?
15-37%
For cats undergoing adrenalectomy, what is the median survival time?
12 to 43 months
MOA of Mitotane
Potent adrenocorticolytic agent that is cytotoxic to the adrenal cortex (particularly the zona fasciculata and zona reticularis)
In a series of 11 cats undergoing laparascopic adrenalectomy, what was the median survival time?
803 d (27 mos)
What percentage of dogs undergoing abdominal ultrasound are found to have incidental adrenal tumors?
4%
What was the MST for dogs with non-cortisol secreting adrenal tumors without surgical intervention?
17.8 mos
MOA of trilostane
synthetic corticosteroid analog that competitively inhibits 3-beta-hydroxysteroid dehydrogenase
This enzyme is essential for cortisol synethesis
What percentage of dogs undergoing CT scan had an incidentally identified adrenal mass?
9.3%
When should adrenalectomy be considered?
functional masses, >2.5 cm, locally invasive
MOA of pasireotide
Somatostatin receptor analog that binds to receptors SST1, SST2, SS, and SST5
whats the most common tumor type fo the parathyroid gland
adenoma > cystadenoma, carcinoma and hyperplasia
90% are single masses
MOA of Selegiline
Inhibits degradation of dopamine which may inhibit ACTH secretion from the intermediate lobe of the pituitary gland
what is the metastatic rate of parathyroid tumors
extremely rare
clinical signs of hypercalcemia
pu/pd weakness, lethargy decreased appetite weight loss muscle wasting vomiting and trembling
bloodwork findings in a patient with parathyroid tumors
hypercalcemia
hypophosphatemia
PTH can be high or withing the normal reference range - 73%
Dow et al (1990) treated 6 dogs with pituitary macrotumors with RT (40gy in 10 fractions) - what was the MST?
743 days
Kent et al (2007) - retrospective of RT for pituitary masses - MST for treated vs non-treated dogs?
Treated (19 dogs) - 1405 days (47 mos, 4 yrs)
Non-treated (27 dogs) - 551 days (18 mos)
imaging for parathyroid tumors
ultrasound
scintigraphy has not been useful
how does hyper calcemia lead to an AKI
altered glomerular permeability
reduced renal blood flow
mineralization of the kidenys
when calcium x phosphorus product >70 the risk of mineralization is increased
methods for treatment of parathyroid tumors
surgery
ultrasound guided ablation (radiofrequency and ethanol have been reported)
how many parathyroid glands can safely be removed
3/4 without risk of hypoparathyroidism
preferred treatment for hypocalcemia
calcitriol - rapid onset and short half life
oral calcium is not sufficient
success of radiofrequency ablation
8/11 responded with one or two treatments
3/11 were unsuccessful
another paper showed persistent or recurrent disease in 31%
Ultrasound-guided ethanol ablation success
85% resolved hypercalcemia
when comparing surgery to RFA to US ethanol ablation - what is the success of hypercalcemic control
94% OF PARATHYROIDECTOMY
72% of ethanol ablation
90% RFA
what % of dogs experience recurrence after treatment of parathyroid tumor
10%
long term prognosis is very good
insulinoma hallmark on bloodwork
increased insulin levels and low glucose levels
feline insulinoma cells express what abnormal enzymes that contribute to increased glucose sensitivity and abnormal insulin secretion
glucokinase and hexokinase
hormones associated with insulinomas
insulin, glucagon, somatostatin, pancreatic polypeptide, GH, IGF1 and gastrin
what % of canine insulinomas are metastatic
50% - most commonly to liver and LN
pulmonary mets are rare
most are malignant
how does hormone expression differ in metastatic insulinoma lesions
higher expression of GH and IGF1 in mets
less somatostatin in met sites and therefor increase GH
highly metastatic insulinomas have been shown to have what gene expression profile
genes for acinar enzymes are down regulated
down regulates dna repair and cell cycle regulation pathways
tumor prognostic factors for insulinomas
tumor size, TNM stage, ki67, necrosis, nuclear atypia, stromal fibrosis
common breeds for insulinomas
labs, goldens, GSD, pointers, irish setter, boxers, mbd , westies
neuropathy and insulinoma
paraneoplastic peripheral neuropathy has been described in dogs with insulinoma. This is rare, although sub-clinical neuropathies may be present and undetected and dogs rarely have brain lesions
what is the success of ultrasonography of insulinomas
miss 50% of pancreatic masses
low sensitivity and specificity for the detection of metastatic lesions
what is the best imaging for pancreatic insulinomas
contrast US
CT - 3 phase
single photon emission ct (SPECT) with octreotide
(50% SN)
Somatostain receptor scintigraphy - indium IN111 pentetreotide
PET CT - only in people
treatment of insulinomas
surgery of mass and mets
streptozotocin
diet - frequent small meals high in fat protein complex carbs
prednisone- 0.25mg/kg bid
diazoxide
octreotide
palladia
streptozotocin toxicity
nephrotoxic - mitigated with fluid diuresis
vomiting during administration, diabetes mellitus, hypoglycemia, increase liver enzymes, mild hematologic changes
how does prednisone treat hypoglycemia
antagonizes insulin
gluconeogenic
glycolytic
how does diazoxide treat insulinomas and whats the RR
nondiuretic benzothiadiazine
suppresses insulin from beta cells
stimulates hepatic gluconeogenesis and glycogenolysis and inhibits cellular uptake of glucose
NOT CYTOTOXIC
does not inhibit insulin synthesis
70% RR
diazoxide SE
ptyalism, vomiting, anorexia, and diarrhea.
VERY EXPENSIVE
diazoxide dose
5mg/kg PO BID - increased up to 30 mg/kg daily
how does octreotide work and whats the RR
somatostatin receptor ligand
inhibits insulin secretion
RR 50%
octreotide dose
10-50 ug SQ 2-3 times daily
insulinoma prognosis with partial pancreatectomy
good short term
poor longterm
MSTs after partial pancreatectomy range from 12 to 14 months - newer study showed 26 month (785 d) survival
50% of dogs with mets are dead at 6 months
prognosis of insulinoma with medical management alone
196 day (6.5 months)
how does the use of medical therapy after surgery affect survival
subset of P MST 1316 d ( 44 mths)
use of post of medical treatment in another study inc survival to 452 d (15 mths)
insulinomas in cats st with surgery
1-32 mths
what is zollinger -ellison syndrome
non beta cell neuroendocrine tumor in the pancreas, hypergastrinemia, and GI ulceration
occurs with gastrinomas
gastrinoma location
pancreas one report of duodenum
gastrinoma metastasis
highly metastatic
liver, regional lymph nodes, spleen, peritoneum, small intestine, omentum, or mesentery identified in 85% of dogs and cats at the time of initial diagnosis
how to diagnose gastrinoma
cs or evidence of gi ulceration
CT
US - limited to find tumor
elevated serum gastrin
scintigraphy with radiolabeled pentetreotide
treatment of gastrinoma
surgery - even with mets surgical debulking
reduces the gastrin secretory capacity and enhances the efficacy of medical management
ppi and sucralfate
octreotide reported
survival of gastrinomas in dogs and cats
1-26 months
what skin condition do glucagonomas cause
crusting dermatologic condition termed necrolytic migratory erythema (NME)
signs of glucagonoma
skin lesions, hyperglycemia or overt diabetes mellitus, hypoaminoacidemia, and increased liver enzyme activity
