Unusual and uncommon endocrine disorders (Proceedings)

Insulinomas are tumors that arise from the beta cells of the pancreatic islets and secrete excessive amounts of insulin, resulting in hypoglycemia. The secretion of insulin is usually episodic, as are the resulting clinical signs. Insulinomas in dogs are typically malignant and almost always metastasize; even those appearing benign on histopathological evaluation. Insulinomas are rare in dogs. They are typically seen in middle-aged to older dogs but have been reported in dogs ranging from 3.5–15 years of age. There is no apparent sex predilection. Insulinomas appear to be extremely rare in cats.

Clinical signs result from neuroglycopenia or the increased adrenergic tone induced by hypoglycemia. Seizures are the most common presenting complaint. Clinical signs are typically episodic and may be related to fasting, exercise or to feeding in some cases. The duration of clinical signs before diagnosis is usually 1–6 months, with most patients showing signs that increase in severity and frequency as the disease progresses.

The diagnosis of insulinoma is confirmed when a patient with hypoglycemia has an inappropriately elevated serum insulin concentration. Simultaneous serum glucose and insulin concentrations are evaluated in animals suspected of having an insulinoma. Demonstration of a low circulating fructosamine concentration is useful in diagnosing chronic hypoglycemia when blood glucose concentrations are within the reference range. Ultrasonography may be able to detect a pancreatic mass or evidence of metastasis, though in many cases the lesion is too small to image. CT or MRI may be helpful but are not commonly utilized.

Symptomatic hypoglycemia is treated with the intravenous injection of dextrose as a bolus and then glucose (2.5% or 5%) as an intravenous infusion. The goal is to ameliorate the clinical signs of hypoglycemia, but not necessarily to return the blood glucose concentration to normal. Frequent feeding of small meals should be instituted as soon as the animal is stable. The initial treatment of choice for dogs and cats with insulinoma is surgery, which provides histological confirmation of the diagnosis and allows resection of the neoplastic tissue and staging of the disease. Any identifiable pancreatic nodules should be removed by partial pancreatectomy. Cytoreduction of any visible metastatic lesions should be attempted. Even if gross metastatic disease is not evident, biopsy of the liver and appropriate lymph nodes must be done, as occult metastatic disease is common. Long-term medical management can involve a combination of approaches. In some cases, frequent feedings may control clinical hypoglycemia. Diets high in protein, fats and complex carbohydrates are recommended. Prednisolone or prednisone can be given if dietary management alone is not effective. Higher doses can be given if necessary, but the development of iatrogenic Cushing's is ultimately dose limiting. Although infrequently used, diazoxide can be successful in controlling hypoglycemia in patients not responding to diet and glucocorticoids. The long-acting somatostatin analogue octreotide has been successfully used as palliative therapy in a few dogs with insulinoma. Somatostatin inhibits the release of insulin from pancreatic beta cells. Streptozotocin is a nitrosourea alkylating agent that is cytotoxic to pancreatic beta cells. A recent study has shown that multiple doses of streptozotocin can be safely given to dogs with insulinoma if an aggressive saline diuresis protocol is used prior to and following the infusion of the drug. Streptozotocin is efficacious in some dogs with insulinoma and its use should be considered in dogs with non-resectable or metastatic disease (particularly those that remain hypoglycemic).

The long term prognosis for dogs and cats with insulinoma is poor. Tumor burden, presence of metastatic disease and owner willingness to aggressively treat all appear to impact survival time. Approximately two thirds to three quarters of dogs survive 6 months or longer after surgery (often over a year) before intractable hypoglycemia recurs. Reported survival time is longer in dogs initially treated with surgery compared to medical therapy alone.

Hyperaldosteronism or Conn's syndrome is a rare adrenal disorder of cats, characterized by excess secretion of the mineralocorticoid aldosterone. It is usually associated with an adrenal adenoma. It is usually seen in middle-aged to older cats (5-20 years). There is no breed predilection; males are overrepresented. Hyperaldosteronism leads to electrolyte and metabolic disturbances, most notably hypokalemia. Reported clinical signs include ventral neck flexion, weakness, collapse, ataxia, weight loss, PU/PD and blindness. Laboratory findings may include hypokalemia, hypernatremia, increased CPK and hypertension. Diagnosis is by demonstration of a significantly elevated aldosterone level along with low plasma rennin activity. Ultrasonography usually reveals an adrenal mass. Medical therapy is intravenous and oral potassium supplementation, spironolactone and, if hypertension is present, Ca canal blockers. Adrenalectomy is the treatment of choice.

Feline hyperadrenocorticism is an uncommon endocrine disorder that typically affects middle-aged to older cats (5-18 years). There is no obvious breed or sex predilection. About 80% of cases are pituitary-dependent and 20% due to adrenal tumors of which 1/3 are malignant. Three-quarters of reported cases have had concurrent diabetes mellitus so PU/PD is a common complaint. Other clinical signs can include a pendulous abdomen, hepatomegaly, weight gain or loss, lethargy, muscle atrophy and integumentary changes including hair loss and fragile, easily torn skin. Laboratory abnormalities include hyperglycemia, glucosuria, hypercholesterolemia, elevated ALT and a stress leukogram. Elevated SAP is not typical. An ACTH stimulation test can be used for diagnosis but 2/3 of cats with naturally-occurring HAC have a normal result. The LDDST is not used due to low specificity. The HDDST (0.1 mg/kg IV) is preferred. Imaging studies and ACTH levels can be used to differentiate PDH from AT. Various medical treatments have been described for feline PDH. Trilostane appears to be the current medical treatment of choice. Surgery is indicated for unilateral benign adrenal tumors and bilateral adrenalectomy for PDH has been described.

Primary feline hypoadrenocorticism is an uncommon disorder that typically affects young to middle-aged cats without any breed or sex predilection. The historical and clinical findings are similar to those described for dogs. Laboratory findings can include absence of a stress leukogram, mild anemia, hyperkalemia, hyponatremia, hypochloremia, hypercalcemia, azotemia, acidosis and isosthenuria or low USG. Diagnosis is based on demonstration of inadequate adrenal reserve with an ACTH stimulation test. Treatment of an Addisonian crisis is similar to treatment of dogs. However, cats tend to respond slower and spend more days in the ICU. Maintenance therapy requires mineralocorticoid replacement with Percorten or Florinef and glucocorticoid replacement with predisolone. The long-term prognosis is good.

Gastrinomas are gastrin secreting neuroendocine non-beta cell tumors of the pancreas. The excessive production of gastrin results in parietal cell growth and hypersecretion of hydrochloric acid in the stomach. Metastasis involving regional lymph nodes, omentum and/or liver is identified in approximately 75% of patients. Patients have been seen ranged in age from 3 to 12 years old. Clinical signs result from the effects of the excessive gastrin secretion, which can lead to ulceration of the esophagus, stomach and duodenum and disruption of intestinal function. Demonstration of an elevated fasting serum gastrin level is an important component of establishing the diagnosis. The assay is available at a few veterinary diagnostic laboratories. Ultrasound of the abdomen may reveal evidence of a pancreatic tumor or metastatic disease, but is unremarkable in many cases. Advanced imaging (CT and MR) may be more sensitive.

Exploratory laparotomy is indicated in most patients with gastrinoma. The surgeon should remove the primary pancreatic lesion, repair any perforated or severe GI ulcers, evaluate for metastatic disease and debulk metastatic lesions. Omeprazole is given to decrease gastric acid production and control clinical signs. Long term therapy and subsequent dose increases may be necessary. Sucralfate may be added to bind to and protect the gastric mucosal surface while active ulceration is present. Misoprostol may be indicated in some patients. The somatostatin analogue octreotide may be effective in decreasing gastrin secretion and controlling clinical signs and its use has been reported in a few patients. Chemotherapy has not been adequately evaluated in dogs and cats. The long term prognosis for dogs and cats with gastrinoma is poor. Median survival is reported to be 5.5 months with a reported range of 1 week to 2.8 years. Nonetheless, with appropriate surgical and medical therapy many patients enjoy a good quality of life and short term prognosis until the disease becomes widespread.