Tumors of the Endocrine system -Part 2

Question 1

Carcinomas or adenocarcinomas were diagnosed in __% of thyroid tumors in dogs.

Carcinomas can be further divided into ____ and ____ with immunohistochemistry;

o ____ tumors are more common.

o It has been suggested that ____ carcinomas may have a less aggressive behavior, although this distinction rarely is used clinically.

Answer 1

90%

follicular, medullary carcinomas

follicular

medullary

Question 2

Potential causes of thyroid carcinoma in humans include exposure to what 4 things?

Answer 2

o radiation

o persistently elevated thyroid-stimulating hormone (TSH)

o dietary and genetic factors

Question 3

Thyroid carcinoma in dogs tends to metastasize to the___ and ___, but metastasis to _____ also has been reported.

Answer 3

draining LNs, lungs, abdominal organs

Question 4

The lymphatic drainage of the thyroid gland is to the ___ (cranial portion) and the ___ (caudal portion)

Answer 4

cranial deep cervical lymph node, caudal deep cervical lymph node

Question 5

One additional potential complication of total thyroidectomy is transient or permanent postoperative hypocalcemia.

o In one study of 15 dogs treated with total thyroidectomy because of bilateral disease, parathyroid tissue was preserved in two dogs, reimplanted in four dogs, and removed completely in nine dogs.

§ In that study postoperative hypocalcemia occurred in 11 dogs, with only seven dogs requiring long- term management of hypocalcemia.

o Another study reported the intentional preservation of at least one external parathyroid gland in six cases of total thyroidectomy for thyroid carcinoma. The blood supply was preserved in five dogs, and the parathyroid gland was reimplanted in one dog.

§ The MST was not reached, and the mean ST was 920 days, with no evidence of recurrence.223 Attempts should be made to preserve parathyroid tissue in cases of total thyroidectomy in dogs.

Question 6

Ectopic thyroid carcinoma has been reported in dogs at the ___, involving the ___, ___, and the ___.

o The treatment approach to these tumors is similar to that for eutopic thyroid carcinomas, with long-term survival reported with surgery alone or with radioactive iodine.

Answer 6

base of tongue, hyoid apparatus. cranial mediastinum, right heart base

Question 7

Invasive thyroid carcinomas generally are not amenable to surgery because of invasion of what 4 critical structures in the neck? s

Answer 7

trachea, esophagus, carotid artery, and recurrent laryngeal nerve

Question 8

RT

o Two reports exist on the use of external beam RT to treat thyroid carcinoma in dogs.

§ A hypofractionated protocol reported in 13 dogs resulted in an MST of 96 weeks.

o Interestingly, evidence of pulmonary metastasis at the time of diagnosis was not prognostic.229 Definitive fractionated RT was reported in eight dogs with invasive thyroid carcinoma, with a similar MST of 24.5 months.

o A more recent study reported an MST of only 170 days for 20 dogs treated with palliative radiation for advanced thyroid carcinoma.

§ In that study, achieving a partial or complete response was the only vari- able that was prognostic.231

§ Hypothyroidism has been reported as a consequence of RT for thyroid carcinoma,232 therefore monitoring of the patient’s thyroid status after RT or surgery is recommended.

Question 9

Radioactive iodine (131I) is not readily available for dogs because of the facilities required for isolation after high-dose 131I therapy.

o Two reports of 131I therapy for invasive thyroid carcinoma indi- cate relatively long STs.

§ One study reported 43 dogs treated with 131I, either as sole therapy or in combination with surgery. The first 24 dogs were treated with a dose that was calculated by means of scintigraphy, with a dose range of 555 to 1850 MBq; the remaining 19 dogs were treated with a dose of 1600 MBq with- out dose calculation or taking body weight into account.

§ The MSTs for 131I used alone and in combination with surgery were 30 months and 34 months, respectively, and no adverse events were noted.

§ A similar study reported 131I therapy as primary therapy in 39 dogs with nonresectable thyroid carcinoma.2

· The MSTs

o MET MST=366 DAYS

o NO METS= 839 DAYS

· Three dogs in this study developed fatal bone marrow suppression.

· The advantage of 131I is that metastatic lesions also can be treated with this therapy. RT should be considered in cases of invasive thyroid carcinoma because prolonged STs may be possible.

Question 10

The prognosis for dogs with unilateral mobile thyroid carci-noma is excellent with surgery alone, with a reported MST of ___ and a __% 2-year survival rate.

Answer 10

36 months, 70%

Question 11

Factors associated with metastatic disease in dogs with thyroid tumors?

Factors associated with reduced disease free survival?

Answer 11

Tumor diameter, tumor volume, bilateral

gross and histologic evidence of vascular invasion

Question 12

When should chemotherapy be utilized for dogs with thyroid tumors?

Most common chemo?

Answer 12

large tumors with evidence of vascular invasion or metastasis

Carboplatin

No definitive evidence exists that chemotherapy improves STs in dogs with thyroid carcinoma.

o One study showed no benefit to the addition of chemotherapy for dogs that had been treated surgically for thyroid carcinoma.

o A recent study showed that dogs with thyroid carcinoma treated with isotretinoin 9-cis postoperatively had an increased survival rate compared to dogs treated with surgery alone or surgery with adjuvant doxorubi-

o Palladia

§ The response to toceranib has been reported in dogs with metastatic thyroid carcinoma in a phase I study of this therapy for solid tumors in dogs.

§ A clinical benefit was noted in 12 of 15 dogs with thyroid carcinoma, with four dogs having a partial response and eight dogs having stable disease.

Question 13

_____ is the most common endocrine disorder in cats

Answer 13

Hyperthyroidism (thyrotoxicosis)

Question 14

Feline hyperthyroidism is most often caused by a primary thyroid abnormality that results in the production and secretion of?

Both thyroid lobes are affected in ____% of cases

____ are the least common cause of hyperthyroidism, occurring in only ___ % of thyrotoxic

o however, one group recently proposed that the prevalence of malignant disease increases with disease duration.

Answer 14

thyroxine (T4) and triiodothyronine (T3)

70-90%

Malignant carcinomas, 1-3%

Question 15

Metastatic rate for feline thyroid carcinomas?

Common location?

Answer 15

70%

Regional LNs and lungs

Question 16

How do you diagnose feline hyperthyroidism?

Answer 16

Serum total T4 concentration is highly sensitive and spe- cific for the diagnosis

Question 17

Approximately__% of hyperthyroid cats have a total serum T4 concentration within the reference range

____ should never be used as a screening test for hyperthyroidism

Answer 17

10%

free T4

Question 18

4 treatment options for feline hyperthyroidism?

Answer 18

anti-thyroid drugs, dietary management, surgical thyroidectomy, and radioactive iodine therapy.

Question 19

____ resulting from transient or permanent ____ is the most commonly reported postoperative complication, with rates ranging from ___%.

Answer 19

Hypocalcemia, hypoparathyroidism, 6% to 15

Question 20

Cats with ectopic hyperplastic thyroid tissue also are at risk for postoperative recurrence of hyperthyroidism. ______ is recommended for patients with thyroid carcinoma or ectopic hyperplastic thyroid tissue.

• Radioactive iodine, or 131I therapy, generally is regarded as the treatment of choice for cats with hyperthyroidism, particularly those with bilateral thyroid hyperplasia, ectopic thyroid tis- sue, or thyroid carcinoma.a 131I has a half-life of 8 days and emits both beta and gamma radiation. Beta particles, which account for 80% of the tissue damage, travel a maximum of 2 mm in tissue and have an average path length of 400 μm. They therefore cause local destruction while sparing adjacent hypoplastic thyroid tissue, parathyroid glands, and other cervical structures.

Answer 20

Radioactive iodine therapy

Question 21

Parathyroid tumors arise from the ___ cells and autonomously secrete ____, leading to ____ as a result of primary hyperparathyroidism.

Answer 21

Chief, parathyroid hormone (PTH), hypercalcemia

Question 22

Parathyroid Tumors

Hypercalcemia is the result of direct effects of PTH on ____ and indirect effects on the____, mediated by_____.

Answer 22

bone and the kidneys, intestine, Vitamin D

Question 23

Approximately __% of dogs and cats with primary hyperparathyroidism have a single parathyroid mass

Answer 23

90%

Adenomas are most commonly diagnosed; cystadenoma, carcinoma, and hyperplasia are diagnosed less fre- quently; and metastatic disease is extremely rare

Question 24

A breed predisposition for parathyroid has been reported in ____ dogs, in which the disease appears to follow an

_____ mode of inheritance, although the affected gene has not yet been identified in this breed.

Answer 24

keeshond, autosomal dominant

Question 25

It is important to note that PTH frequently is within the reference range in patients with hyperparathyroidism, with 73% of cases reported to have a normal PTH in one large series.

• A normal PTH in the face of hypercalcemia is an abnormal finding because PTH should be suppressed as serum calcium increases. The lack of suppression of PTH indicates loss of the normal neg- ative feedback effects of calcium due to autonomous hormone secretion by hyperplastic or neoplastic parathyroid tissue.
• Case series, the mean blood urea nitrogen (BUN) and serum creatinine both were significantly lower in dogs with primary hyperparathyroidism compared with control dogs.

o In addition, 95% of the hyperparathyroid dogs had BUN and serum creatinine values within or below the reference range. This partly may be a result of the secondary nephrogenic diabetes insipidus that causes polyuria/polydipsia in these patients.

Question 26

Definitive therapy for primary hyperparathyroidism?

Answer 26

Removal of the hyperfunctioning glands parathyroid glands in the dog are small (2–5 mm × 0.5–1 mm), disk shaped, and tan in color. They are distinct from thyroid tissue.

Question 27

How many parathyroid glands can be removed?

Patients with involvement of all four glands present a dilemma, and it is important to ensure that ___ in these cases is not secondary.

Answer 27

Up to three of the four parathyroid glands can be removed without risk of permanent hypoparathyroidism.

Hyperplasia

Question 28

Ultrasound-guided ethanol ablation also has been reported as a minimally invasive method to treat primary hyperparathyroidism. This technique first was reported in eight dogs, with seven dogs requiring one treatment and one dog requiring two treatments.

o Hypercalcemia resolved in all cases, but one dog developed recurrent hypercalcemia 1 month later and was treated with surgical removal of the mass.3

• Another larger study reported ethanol ablation of parathyroid nodules in 27 dogs; hypercalcemia resolved in 85% of the cases, but three dogs required a second treatment.371
• That study found that control of hypercalcemia was achieved in 94%, 72%, and 90% of cases treated with parathyroidectomy, ethanol ablation, and RFA, respectively.339

Question 29

The long-term prognosis after surgical or ablative treatment for hyperparathyroidism is very good both for control of hyperalcemia and for the tumor itself.

• In rare cases a para- thyroid adenocarcinoma has been diagnosed. These are functional parathyroid nodules, and in a report of 19 dogs with parathyroid adenocarcinoma, no features of the disease differed from those of a benign functional adenoma except for the finding of carcinoma on histopathology.
• The prognosis in these cases was excellent both for tumor control and for resolution of hyperparathyroidism.
• Approximately 10% of dogs treated for hyperparathyroidism experience a recurrence of the disease.

Question 30

What is the hallmark of insulinoma?

Answer 30

normal or increased blood insulin concentration in the presence of low blood glucose levels

Question 31

Pancreatic B cell tumors can produce what 6 other hormones?

Metastatic lesions are detected in approximately ___% of canine insulinomas, with the ____ and ____ most commonly affected

Answer 31

glucagon, somatostatin, pancreatic polypeptide, GH, IGF-1, and gastrin.

A more recent study demonstrated that some canine insulinomas express genes more typically associated with the exocrine pancreas; the study also revealed that these tumors contain small subpopulations of cells with mixed endocrine-exocrine features, termed amphicrine cells.

50%, regional lymph nodes, liver

Question 32

Pancreatic Beta-Cell Tumors (Insulinomas)

Stage 1?

Stage 2?

Stage 3?

Answer 32

Stage I tumors involve only the pancreas, with no evidence of local or distant lymph node involvement and no distant metastasis (T1N0M0); stage II tumors have lymph node involvement (T1N1M0); and stage III tumors have distant metastasis (T1N1M1 or T1N0M1).

Question 33

Canine insulinomas have been shown to express _____, which may have implications for both diagnosis and therapy

Answer 33

somatostatin receptors

Question 34

Local production of ____ also have been demonstrated in canine insulinomas, with a higher level of expression of ____ mRNA in metastases compared to primary tumors.

o It has been suggested that the locally produced hormones may have autocrine or paracrine effects on cell proliferation, and tumor growth and progression.

o Furthermore, it is speculated that locally produced somatostatin has inhibitory effects on insulinomas within the pancreas, but that these effects are decreased in metastases leading to increased GH production

Answer 34

GH and IGF-1, GH and IGF-1

Question 35

In studies of potential prognostic biomarkers for canine insulinoma, predictive for DFI and/or ST, depending on the model used in analysis

Answer 35

§ tumor size,

§ TNM stage,

§ Ki67 index (a marker of proliferation),

§ presence of necrosis,

§ nuclear atypia,

§ stromal fibrosis

Question 36

How is insulinoma diagnoses?

Answer 36

Hypoglycemia (blood glucose <60 mg/dL) with a concurrent normal or increased serum insulin concentration

Question 37

CT findings have been reported in a small number of dogs with insulinoma. In a study comparing ultrasound, CT, and single-photon emission CT (SPECT), CT was found to be the most sensitive technique, identifying 10 of 14 confirmed primary insulinomas.

o CT also identified a significant number of false positive metastatic lesions.

Question 38

Chemotherapy drug most often used in canine insulinoma?

Why is its use limited? How can this be reduced?

Other side effects of drug?

Answer 38

Streptozocin (streptozotocin)

Nephrotoxic, saline siuresis

vomiting during administration, diabetes mellitus, hypoglycemia, increased liver enzyme activity, and mild hematologic change

Question 39

What kind of diet should be fed to dogs with canine insulinoma?

Dose of prednisone recommended?

Answer 39

Diets high in fat, protein, and complex carbohydrates should be fed in small, frequent meals, and simple sugars should be avoided.

Prednisone is used for its insulin antagonizing, gluconeogenic, and glycogenolytic effects.A starting dose of 0.25 mg/kg by mouth (PO) twice daily is recommended, with gradual dose increases as needed to control hypoglycemia.

Question 40

How does diazoxide work

o Diazoxide is not ___ and does not ___

o ____ is recommended, and the dose can be increased gradually to 30 mg/kg daily dose ose can be ates hepatic glucon.

o Approximately 70% of canine insulinoma patients respond to diazoxide therapy. Adverse effects are uncommon but may include ptyalism, vomiting, anorexia, and diarrhea.

Answer 40

Diazoxide is a nondiuretic benzothiadiazine that suppresses insulin release from beta cells, stimulates hepatic gluconeogenesis and glycogenolysis and inhibits cellular uptake of glucose.

cytotoxic, inhibit insulin synthesis

5 mg/kg PO twice daily

Question 41

Octreotide is a ____ that ____ and _____ by pancreatic beta cells.

o It has been reported to alleviate hypoglycemia in up to ___% of dogs with insulinoma, although some may become refractory to treatment. The suggested dose is 10 to 50 μg SQ 2 or 3 times daily, and side effects appear to be rare.

o In a more recent study a single 50 μg dose of octreotide was administered to 12 dogs with insulinoma. Plasma insulin concentrations decreased significantly after administration of octreotide in dogs with insulinoma, but GH, ACTH, cortisol, and glucagon levels did not change, and glucose levels increased

Answer 41

somatostatin receptor ligand, inhibits synthesis and secretion of insulin

50%

Question 42

MST for canine insulinoma after partial pancreatectomy?

The prognosis after surgery depends on the _____

50% of dogs with stage I disease are free of hypoglycemia 14 months after surgery,

§ whereas less than 20% of dogs in stage II and III disease are free of hypoglycemia at this time.384

§ Dogs with stage III disease have a significantly shorter ST than dogs with stage I and II disease – approximately 50% of dogs with metastasis are dead by 6 months.

Answer 42

12-14 months

clinical stage of the disease.

Question 43

A more recent retrospective study showed an improved ST in dogs with insulinoma compared to earlier reports with a median DFI and MST of 496 days and 785 days, respectively, for 19 dogs undergoing partial pancreatectomy

o A subset of nine dogs treated with partial pancreatectomy and postoperative prednisolone had an MST of 1316 days.

o For eight dogs that received medical therapy alone, the MST was 196 days.

o When all the dogs that received medical therapy were considered as a group, the MST after institution of the medical treatment was 452 days.

Question 44

Beta-Cell Tumors in Cats

• Surgical management has been reported in cats, with STs ranging from ___ months.
• Conservative therapy with dietary management and prednisolone also has been used in cats. Octreotide may be considered, although little evidence supports its use, and no evidence supports the use of diazoxide or strepto- zotocin in this species.

Answer 44

1 to 32 months

Question 45

What are gastrinomas?

Answer 45

neuroendocrine tumors that secrete excessive amounts of gastrin

Question 46

Zollinger-Ellison syndrome refers to the triad of a non–beta-cell neuroendocrine tumor in what 3 organs?

Answer 46

pancreas, hypergastrinemia, and GI

Question 47

Gatrinomas are identified in whar organ?

Answer 47

Identified in the pancreas, although one report exists of a duodenal gastrinoma in a dog

Question 48

Metastatic rate of gstrinoma?

Common location (7) for mets?

Answer 48

85% in dogs and cats

liver, regional lymph nodes, spleen, peritoneum, small intestine, omentum, or mesentery

Question 49

Age distributions for gastrinoma?

Answer 49

middle-aged dogs and older cats

Question 50

How can you diagnose gastrinoma?

Answer 50

The diagnosis may be supported by measuring basal serum gastrin levels or levels after provocative testing or by scintigraphy using radiolabeled pentetreotide.

Basal gastrin levels have been significantly increased in dogs and cats with gastrinoma; however, gastrin levels also can be increased in renal or gastric disease, and no specific cutoff values for diagnosis have been determined.

Question 51

What medications are recommended for animals with gastrinoma?

Answer 51

treatment with medications such as proton pump inhibitors and H2-antihistamines can lead to increased serum gastrin concentrations, recent studies indicate that these effects are mild and short-lived and may not in fact inhibit the diagnosis of gastrinoma

Question 52

Glucagonomas usually arise from ___ in the pancreas; however, extrapancreatic glucagon-secreting crusting dermatologic condition termed ___

Answer 52

alpha cells, necrolytic migratory erythema (NME)

Other associated problems include hyperglycemia or overt diabetes mellitus, hypoaminoacidemia, and increased liver enzyme activity. Skin lesions associated with NME include hyperkeratosis, crusting, and ulceration and erosions of the footpads, mucocutaneous junctions, external genitalia, dis- tal extremities, pressure points, and ventral abdomen

Question 54

Treatment for glucagonoma?

Answer 54

Surgical resection or debulking is the treatment of choice for canine glucagonoma. Rare reports exist of the use of somatostatin analogs.

Question 55

The dermatologic lesions of NME may improve after surgery or medi- cal therapy, but metastasis is common at the time of diag- nosis and the prognosis is generally poor.

When NME is suspected, it is important to rule out liver disease, a more common cause of this dermatologic condition in dogs.

Question 56

Intestinal carcinoid arise from what cells?

4 common locations where they can arise?

Metastasis?

Treatment?

Answer 56

neuroendocrine cells that are found in a variety of locations

GI tract, liver, gallbladder, and pancreas.

Common at time of diagnosis

Surgical removal is recommended; a single case report has described adjuvant chemotherapy in a dog.