Handbook of Small Animal Practice || Miscellaneous Endocrine Disorders

488

HYPERLIPIDEMIA

Defi nition I. Hyperlipidemia is an increased level of lipid in the blood

and is only physiologically relevant when it occurs in the fasted state.A. Hypertriglyceridemia is defi ned as a triglyceride concen-

tration >150 mg/dL in dogs and >100 mg/dL in cats.B. Hypercholesterolemia is defi ned as a cholesterol concen-

tration >300 mg/dL in dogs and >200 mg/dL in cats.C. Hyperchylomicronemia is defi ned as an excessive con -

centration of chylomicrons (see later). II. Visible lipemia is apparent when triglycerides are >400 mg/dL

and the resulting opacity interferes with various laboratory evaluations, depending on the method used.A. Total solids via refractometer: falsely increasedB. Albumin and bilirubin: falsely increasedC. Bile acids, alkaline phosphatase, alanine transaminase,

and aspartate transaminase: ± erroneously increasedD. Sodium: falsely decreasedE. Amylase: falsely decreasedF. Mean corpuscular hemoglobin (MCH) concentration:

falsely increased (possibly marked)G. Also causes in vitro hemolysis

Causes and Pathophysiology

I. Normal lipid metabolismA. Lipids are water insoluble and are transported in the

blood by lipid-protein complexes.B. Types of lipoproteins include the following:

1. Chylomicrons, which are formed in intestines and hydrolyzed in the circulation to triglyceride (available for tissue use and storage) and cholesteryl-ester remnants (taken up by the liver)

2. Very-low-density lipoproteins, which are synthesized in the liver and transport endogenous triglyceride to muscles or fat

3. Low-density lipoproteins, which are formed in the circulation and transport cholesterol to tissues

4. High-density lipoproteins, which are the major cholesterol carrier in dogs and catsa. Synthesized in the intestine and liverb. Transport excess cholesterol to the liver for biliary

excretion

II. Relationship of hyperlipidemia to dietA. Postprandial

1. Persistent hyperchylomicronemia up to 12 hours after a meal

2. Most common cause of lipemiaB. Diet type

1. In normal animals: fasting hyperlipidemia possible with extremely high dietary fat content (>55%)

2. Hypertriglyceridemia or hypercholesterolemia also possible

III. Secondary hyperlipidemia: see Table 46-1 IV. Primary hyperlipidemia associated with inherited metabolic

abnormalities: see Table 46-2

Clinical Signs

I. Clinical signs with secondary hyperlipidemiaA. Signs associated with hypertriglyceridemia

1. Abdominal pain or discomfort: chronic, acute, or episodic

2. Possible seizures with marked hypertriglyceridemia3. Nonspecifi c gastrointestinal (GI) signs: vomiting,

diarrhea, lethargy, anorexia4. Visible lipemia of the vessels of the bulbar conjunc-

tiva, episclera, and retina (lipemia retinalis)5. Lipid deposition in abnormal locations

a. Cutaneous xanthomas: deposits in macrophages forming granulomas

b. Arcus lipoides: corneal lipid depositsc. Lipemic aqueous: lipid in the aqueous humor

B. Signs from hypercholesterolemia1. Atherosclerosis with accompanying thrombosis

and/or loss of vascular supply, seen particularly with hypothyroidism and diabetes mellitus

2. Arcus lipoides II. Signs possible with primary hyperlipidemia

A. Idiopathic schnauzer hyperlipidemia1. May be clinically asymptomatic2. Nonspecifi c signs of discomfort or GI disturbances,

similar to secondary hypertriglyceridemia3. Possible polydipsia4. Acute pancreatitis as a secondary complication (not

well documented but suspected)B. Briard hypercholesterolemia: usually no clinical signs

C H A P T E R 46

Miscellaneous Endocrine Disorders

| Stephanie A. Smith

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CHAPTER 46 | Miscellaneous Endocrine Disorders 489

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Ch046-X3949.indd 489 8/8/07 11:09:28 AM

490 SECTION 6 | Endocrine and Metabolic System

C. Rough collie hypercholesterolemia: may be associated with corneal lipidosis

D. Inherited hyperchylomicronemia1. Inappropriate lipid deposition in skin, eye, and other

soft tissues2. Peripheral neuropathies (Horner’s syndrome, radial

or tibial palsy) owing to nearby compression from xanthomas

Diagnosis and Differential Diagnosis

I. Postprandial hyperlipidemiaA. Confi rmed by evaluating triglyceride and cholesterol

levels following a ≥12-hour fastB. Duration of fast important

II. Secondary hyperlipidemiaA. History of signs suggestive of underlying disease processB. Minimum database

1. Complete blood count (CBC)2. Serum biochemistry panel with pancreatic enzymes3. Urinalysis (UA)

C. Additional tests to consider1. Total thyroxine (thyroid concentration) ± other

thyroid testing (see Chapter 42)2. Adrenocorticotropin (ACTH) stimulation or dexa-

methasone suppression test (see Chapter 45)

3. Urine protein: creatinine ratio if proteinuric (see Chapter 48)

4. For suspected pancreatic disease: abdominal ultra-sonography, possibly pancreatic lipase immuno-reactivity (cPLI)

5. For suspected cholestatic liver disease and/or bile duct obstruction (icteric animal): abdominal ultra-sonography

III. Primary hyperlipidemiaA. Exclude all causes of secondary hyperlipidemia.B. Measure fasting serum triglycerides and cholesterol.C. Consider lipoprotein electrophoresis for further charac-

terization of idiopathic schnauzer hyperlipidemia and inherited chylomicronemia.

D. No further testing needed for hypercholesterolemia of briard or rough collies.

Treatment

I. Secondary hyperlipidemiaA. Manage any diagnosed underlying disorder.B. Provide nutritional support by selecting a fat-restricted

enteral or parenteral diet. II. Primary hyperlipidemia

A. Intervention is indicated when hyperlipidemia is associated with clinical signs.

TABLE 46-2

Primary Hyperlipidemia Associated with Inherited Metabolic Abnormalities

DISORDER REPORTED BREEDS TYPE OF HYPERLIPIDEMIA ADVERSE EFFECTS NOTES

Idiopathic Frequent in miniature Marked hypertriglyceridemia May be associated with hyperlipidemia schnauzers Cholesterol usually normal increased risk for Occasionally in beagles or mildly elevated, rarely pancreatitis and Shetland markedly elevated sheepdogsHypercholesterolemia Briards Triglycerides normal Not associated with any Likely caused by Rough collie (one Cholesterol elevated pathologic increased apoprotein family) accumulation of E containing high- cholesterol density lipoprotein May be linked to development of retinal pigment epithelial dystrophy in the briard Corneal lipidosis in the collieHyperchylomicronemia Domestic cats (20 Fasting lipemia, Lipid deposition in eye Suspected autosomal related cats in hypertriglyceridemia, Lipid granulomas in recessive inheritance New Zealand) and hypercholesterolemia abdomen and skin causing defi cient Sporadic in some Peripheral neuropathies lipoprotein lipase breeds and domestic activity cats Affected cats may not Single 4-week-old show signs until mixed-breed puppy maturity Two related Brittany spaniels

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B. Dietary management with fat restriction is the mainstay of treatment.1. Keep fasting triglyceride <500 mg/dL and cholesterol

<400 mg/dL.2. See Table 46-3 for fat-restricted diet information.

C. Lipid-lowering drugs have not been well evaluated in the dog and cat, and are used with caution.1. Dogs: gemfi brozil 200 mg/day PO2. Dogs: niacin 100 mg/day PO3. Dogs: fi sh oil (eicosapentaenoic, docosahexaenoic

acid) 200 mg/kg/day PO

Monitoring of Animal

I. Secondary hyperlipidemiaA. Most secondary hyperlipidemias resolve with proper

management of the primary disorder.B. Reevaluate for lipemia once the underlying disease is

well controlled, and consider instituting dietary fat restriction if needed.

II. Primary hyperlipidemiaA. Evaluate fasting serum triglycerides and cholesterol 4

to 6 weeks after dietary change and every 3 to 4 months thereafter.

B. Primary disorders are much more diffi cult to treat.

ERYTHROPOIETIN ABNORMALITIES

Defi nition I. Erythropoietin (EPO) is a glycoprotein produced by renal

interstitial cells that stimulates red blood cell (RBC) production in the bone marrow.

II. Abnormal EPO concentrations cause abnormal circulating RBC mass.

Causes and Pathophysiology

I. Decreased EPO productionA. Chronic renal failure

1. As senescent RBCs are removed from the circu lation, renal hypoxia triggers EPO production.

2. Nephron loss prevents adequate response to decreas-ing RBC mass, resulting in gradual development of anemia.

B. Polycythemia vera (primary polycythemia)1. Myeloproliferative disease with clonal proliferation

of erythroid progenitors leads to increased peripheral RBC mass.

2. Marrow production of RBCs is autonomous and not subject to EPO-negative feedback.

3. EPO production is appropriately decreased. II. Appropriately increased EPO production from renal stim-

ulusA. Decreased renal perfusion associated with aberrant

renal blood vasculature or compression of blood fl ow1. Renal neoplasia2. Parenchymal disease

a. Cystic kidneys: polycystic or single renal cystsb. Hydronephrosis

3. Congenital abnormality of renal vasculature4. Compressive neoplasm5. Thrombus obstructing renal arterial fl ow

B. Decreased renal oxygen delivery1. Anemia2. Hemoglobinopathy

C. Hypoxemia (decreased blood oxygen)1. Right-to-left cardiovascular shunting, particularly

reversed patent ductus arteriosus2. Chronic pulmonary disease3. High altitudes: decreased inspired oxygen content4. Hypothalamic disease: depressed respiration

III. Autonomous secretion of EPO or EPO-like substances by tumorsA. Renal neoplasia

1. Lymphosarcoma2. Renal carcinoma

B. Extrarenal neoplasia (paraneoplastic effect)1. Hepatoma2. Uterine or cecal leiomyosarcoma3. Ovarian carcinoma4. Nasal fi brosarcoma5. Pheochromocytoma and other adrenal tumors6. Granular cell tumor7. Schwannoma

TABLE 46-3

Fat-Restricted Commercial Pet Foods

% kcal FROM FAT

Canine Diets

Canned Hill’s Prescription Diet w/d 31.0Canned Purina CNM-OM 28.1Dry Iams Less Active 28.0Dry Purina ProPlan Reduced Calorie 24.1Dry Hill’s Prescription Diet r/d 24.0Canned Hill’s Prescription Diet r/d 24.0Canned Iams Less Active 23.1Dry Hill’s Prescription Diet w/d 23.0Dry Eukanuba Reduced Fat Formula 23.0Dry Waltham/Pedigree Calorie Control 22.7Canned Hill’s Science Diet Maintenance Light 22.0Dry Purina One Reduced Calorie 20.4Dry Purina CNM-OM 17.7Dry Purina Fit and Trim 17.4Dry Eukanuba Restricted Calorie 15.0

Feline Diets

Canned Hill’s Prescription Diet w/d 38.0Dry Iams Less Active 29.0Canned Hill’s Prescription Diet r/d 24.0Dry Hill’s Prescription Diet r/d 24.0Dry Purina ProPlan Reduced Calorie 23.4Dry Hill’s Prescription Diet w/d 23.0Dry Eukanuba Restricted Calorie 23.0Dry Hill’s Science Diet Maintenance Light 22.0

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Clinical Signs

I. Anemia and decreased tissue oxygen delivery: weakness, collapse, exercise intolerance, pallor, ± soft heart murmur (see Chapter 64)

II. Polycythemia (primary or secondary): hyperemia of mucous membranes, skin, sclera, signs of hyperviscosity (see Chapter 64)


I. Anemia of EPO defi ciencyA. Evaluate for chronic renal failure.B. See Chapter 48 for discussion of appropriate laboratory

tests. II. Polycythemia

A. Confi rm increased RBC mass to rule out relative poly-cythemia from dehydration.

B. Investigate causes of hypoxemia causing excessive EPO secretion.1. Confi rm hypoxemia.

a. Pulse oximetry: arterial oxygen saturation <90% on room air

b. Arterial blood gas: Pao2 <80 mm Hg on room air2. Evaluate cardiopulmonary status.

a. Thoracic radiographyb. Echocardiographyc. Electrocardiography

3. Measure serum EPO concentration (should be nor-mal to increased).

C. Normal oxygenation with excessive EPO secretion warrants investigation for renal disease or masses.1. CBC, serum biochemistry profi le, UA, radiographs,

abdominal ultrasonography2. Serum EPO concentration: normal or high despite

polycythemiaD. Polycythemia vera is a diagnosis of exclusion.

1. Dyserythropoiesis on bone marrow evaluation2. Low serum EPO concentration

Treatment

I. Anemia of EPO defi ciency: see Chapter 48 II. Polycythemia from excessive EPO secretion

A. Therapeutic phlebotomy is indicated for polycythemic animals experiencing clinical signs associated with hyperviscosity.1. Place a peripheral and jugular IV catheter or large-

bore butterfl y catheter.2. Slowly withdraw 10% to 25% blood volume from

the jugular catheter, with a goal of reducing packed cell volume (PCV) to 55% to 60%.

3. Replace removed blood volume with a similar volume of IV crystalloid fl uids via the peripheral catheter.

4. Possible complications include catheter clotting, acute hypotension, and volume overload.

B. Treatment of EPO secretion associated with hypoxemia requires management of the underlying cardiopulmo-nary disease.

C. Elevated EPO secretion from renal disease may require the following:

1. If only one kidney is abnormal (cysts, neoplasia, vascular disorder), surgical removal of the affected kidney is indicated.

2. Chemotherapy may be tried for bilateral renal lymphosarcoma.

D. EPO secretion caused by extrarenal neoplasia may improve with surgical removal of the neoplasm.


I. Anemia of EPO defi ciency with chronic renal failure (see Chapter 48)A. Defi ciency is life-long, so continued EPO administra-

tion is required.B. Prognosis is guarded but depends on the rate of

advancement of renal failure. II. Polycythemia from excessive EPO secretion

A. Complications from recurring hyperviscosity include neurological signs, hemorrhage, and stroke.

B. PCV is monitored weekly to biweekly initially, but long-term observation is based on rapidity of recurrence of polycythemia.

C. Hypoxemia-induced secondary polycythemia is highly manageable with use of intermittent phlebotomy, with prognosis and monitoring dependent on the underlying cardiopulmonary disorder.

D. When renal disease is present, monitoring is dependent on the underlying cause.1. Prognosis is good for resolution of polycythemia if

a cyst or tumor is completely resected or remission is induced with chemotherapy.

2. Prognosis is guarded with nonresectable disease.E. With extrarenal neoplasia, monitoring and prognosis

vary with the etiology.1. Monitoring depends on tumor type, with a good

prognosis if the tumor is completely resectable and guarded prognosis if it is nonresectable.

2. If polycythemia recurs postoperatively (suggesting recurrence and/or metastasis), the prognosis is worse.

HYPOGLYCEMIA

Defi nition I. In the normal dog and cat, blood glucose (BG) is main-

tained within a fairly small normal range. II. Unlike people, normal dogs and cats do not become

hypoglycemic even in the face of fasting or starvation. III. Hypoglycemia is defi ned as resting serum glucose

<60 mg/dL, but varies slightly depending on the laboratory methodology.

IV. Hypoglycemia is defi ned as low serum BG on repeated assays, rather than a single assay.

Causes

I. Spurious hypoglycemiaA. Serum not promptly separated from cellsB. Poor technique or poor quality control of in-house

analyzers

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C. Underestimation of BG by cage-side glucometers mea-suring whole BG instead of serum glucose

II. Neonatal and toy-breed juvenile hypoglycemiaA. Insuffi cient muscle mass glycogen reserves and body

fat stores to provide substrate for glycogenolysis and gluconeogenesis

B. Diffi culty maintaining euglycemia1. Nutritional stressors, such as inadequate nursing,

fasting, and poor diet2. Physiological stressors, such as parasitism, diarrhea,

and hypothermia III. Ingestion of oral hypoglycemic agents

A. Ingestion may be accidental or intentional.B. Sulfonylureas (glipizide, glyburide) cause hypogly-

cemia by stimulating increased release of insulin from b cells.

C. Xylitol sweetened products (sugar-free gum and foods) promote insulin release in dogs.

IV. Hypoadrenocorticism (cortisol defi ciency) (see Chapter 45)A. Cortisol is the main hormonal antagonist to insulin.B. Cortisol defi ciency (with or without aldosterone defi -

ciency) may lead to hypoglycemia. V. Iatrogenic insulin administration (see Chapter 44)

A. Otherwise well-regulated diabetics may become hypo-glycemic from the following:1. Accidental insulin overdose2. Excessive exercise3. Lack of food ingestion4. Effects of a concurrent illness

B. Insulin needs may vary considerably in some poorly regulated diabetics, with hypoglycemia being a fre-quent complication.

C. Diabetic cats occasionally revert from insulin-depen-dent to non–insulin-dependent, so insulin adminis -tration results in hypoglycemia.

VI. Insulinoma (see Chapter 73)A. This is a functional b cell tumor of the pancreas that

secretes insulin.B. Increased BG may provoke insulin release.C. Hypoglycemia does not suppress insulin release from

neoplastic b cells.D. Clinical signs of hypoglycemia are often precipitated

by fasting, eating, excitement, or exercise. VII. Paraneoplastic hypoglycemia (see Chapter 73)

A. Nonpancreatic neoplasms may cause hypoglycemia as a paraneoplastic effect through secretion of poly-peptides that behave like insulin.

B. Possible tumor types include hepatocellular carcinoma, renal adenocarcinoma, hepatoma, leiomyoma, and leiomyosarcoma, although any tumor has the potential to cause hypoglycemia.

VIII. Glycogen storage diseasesA. Inherited errors in the glycogenolytic pathway inhibit

normal glucose homeostasis secondary to a lack of production of glucose from glycogen.

B. Defi ciencies of glucose-6-phosphatase or a-1,4-glucosidase lead to hypoglycemia and abnormal de-position of glycogen in soft tissues.

IX. SepsisA. Gluconeogenesis may become impaired with over-

whelming sepsis through poorly understood mecha-nisms.

B. Sepsis is also associated with increased peripheral glu-cose utilization associated with a hypermetabolic state.

X. Hepatic failure (see Chapter 37)A. Markedly decreased hepatic function (>70% lost) can

lead to hypoglycemia from impaired gluconeogenesis.B. When hypoglycemia is present, other substances syn-

thesized in the liver (albumin, cholesterol, and blood urea nitrogen [BUN]) are also decreased.

XI. Hunting dog (exertional) hypoglycemiaA. Active, lean-bodied hunting dogs may become hypo-

glycemic after extreme exercise.B. Exertional hypoglycemia occurs from depletion of

stored glycogen or increased glucose utilization.

Pathophysiology

I. Maintenance of normal BG is a balance between absorp-tion, production, and utilization of glucose.A. Glucose from dietary intake is absorbed from the

intestine.B. Glucose can be synthesized or released from degrada-

tion of stored carbohydrate.1. Substrates for gluconeogenesis: amino acids (espe-

cially alanine), fatty acids, and lactate2. Conversion of stored hepatic and muscular

glycogen to glucose via glycogenolysisC. Glucose uptake and utilization by most peripheral

tissues is dependent on insulin. II. Insulin is a hypoglycemic hormone.

A. Secreted by pancreatic islet b cells in response to hyper-glycemia

B. Impairs glycogenolysisC. Impairs gluconeogenesis directly by inhibition of

enzymes necessary for amino acid mobilizationD. Suppresses glucagon secretionE. Suppression of adipocyte lipolysis and increased fatty

acid esterifi cation via lipoprotein lipaseF. Stimulates uptake and utilization of glucoseG. Tissues dependent on insulin for glucose uptake:

brain, RBCs, leukocytes, hepatocytes, renal tubular cells, and pancreatic b cells

III. Other hyperglycemic hormones include the following:A. Glucagon

1. Actions directly opposed to those of insulin2. Secreted by pancreatic islet b cells in response to

hypoglycemia3. Increases hepatic glycogenolysis4. Dramatically increases hepatic gluconeogenesis

B. Cortisol1. Secreted by zona fasciculata of the adrenal cortex in

response to stimulation by ACTH from the pitui-tary gland

2. Stimulates hepatic gluconeogenesis3. Decreases the uptake and utilization of glucose by

peripheral tissues

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C. Epinephrine1. Increases hepatic and muscle glycogenolysis2. Promotes lipolysis

D. Growth hormone1. Promotes lipolysis2. Decreases peripheral tissue uptake and utilization of

glucose

Clinical Signs

I. The severity of clinical signs is dependent on the degree of hypoglycemia, duration of hypoglycemia, and rapidity of the decline in BG.A. Episodic signs of neuroglycopenia (inadequate central

nervous system glucose) occur.B. Apparent lack of clinical signs occurs from neural

adaptation to chronic hypoglycemia.C. Lack of mental abnormalities in a profoundly hypo-

glycemic animal suggests previous episodes or chronic occurrence of low BG.

II. Neuroglycopenia occurs because brain cells are profoundly affected by hypoglycemia, owing to their inability to store glycogen and requirement for glucose as an energy source.A. Signs include tremors, seizures, depression or mental

dullness, weakness, collapse, increased appetite, and bizarre behavior.

B. Severe or prolonged neuroglycopenia causes brain injury and alterations in nervous system function that persist beyond the correction of the hypoglycemia.1. Temporary or permanent cortical blindness2. Chronic seizures following neural hypoxic injury3. Peripheral nerve demyelination


I. Suggestive clinical signs and history II. Laboratory confi rmation

A. Evaluate BG immediately with rapid whole-blood glucometer assessment.

B. Confi rm hypoglycemia on serum biochemical analyzer. III. Defi nitive diagnosis of hypoglycemia via Whipple’s triad

A. Clinical signs of hypoglycemiaB. Laboratory confi rmation of hypoglycemiaC. Resolution of signs with dextrose administration

IV. Further assessment of underlying causeA. History: known administration or accidental exposure

to insulin or oral hypoglycemic agentsB. CBC

1. Sepsis: marked infl ammatory leukogram2. Cortisol defi ciency: eosinophilia, lymphocytosis, or

lack of stress leukogramC. Serum biochemistry profi le

1. Hepatic failure: decreased albumin, BUN, or chole-sterol; or increased hepatic enzyme activity

2. Hypoadrenocorticism: hyponatremia with hyper-kalemia

D. Serum insulin concentration1. A sample for insulin evaluation is collected during

confi rmed hypoglycemia.

2. If hypoglycemia is present, normal or increased insulin concentration confi rms hyperinsulinism.a. Iatrogenic administration must be ruled out.b. Hyperinsulinism may develop with insulin

secretion by either pancreatic or extrapancreatic neoplasms.

E. Miscellaneous secondary testing1. Urinalysis2. ACTH stimulation test to rule out cortisol defi ciency3. Bile acids to assess hepatobiliary function4. Thoracic or abdominal radiography, or both, to

search for neoplasia or metastatic disease5. Abdominal ultrasonography to identify a pancreatic

mass, although b cell neoplasms often small and not identifi able

6. Abdominal computed tomography for detection and localization of pancreatic or metastatic masses

7. Exploratory laparotomy for positive identifi cation of a cause in hyperinsulinism where other tests are inconclusive

Treatment

I. Neuroglycopenic crisisA. Feed animal.B. Give enteral glucose.

1. Apply a monosaccharide (50% dextrose, corn syrup, fruit juice, or honey) to the oral cavity.

2. Perform orogastric intubation and give 10 to 20 mL/kg of 20% dextrose to the neonate or tract-able animal when IV access is limited.

C. Give dextrose IV.1. Dextrose 50% via central IV line2. Dextrose ≤20% for peripheral vein administration3. Initial dose: 0.5 g/kg dextrose or 1 mL/kg of a 50%

solution4. Administration of a constant-rate infusion (CRI) of

2.5% to 10% dextrose until resolution of signs or cause

D. Consider glucagon CRI.1. Indicated for iatrogenic insulin shock unresponsive

to dextrose infusion, or prevention of rebound hypo-glycemia with hyperinsulinism and paraneoplastic hypoglycemia.

2. Add contents of a 1-mg reconstituted vial of glu-cagon to 1 L of 0.9% NaCl to make a 1000 ng/mL solution.

3. Administer glucagon as an initial bolus of 50 ng/kg IV, then a CRI of 10 to 15 ng/kg/min IV to maintain euglycemia.

E. Monitor BG frequently. II. Treatment of specifi c underlying causes

A. Juvenile hypoglycemia and hunting dog (exertional) hypoglycemia: frequent feeding

B. Accidental or intentional ingestion of oral hypoglycemic agents: maintenance of glucose support as needed until drug has been completely metabolized

C. Hypoadrenocorticism (see Chapter 45)

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D. Iatrogenic insulin administration1. Maintain glucose support as needed until drug has

been completely metabolized.2. Adjust insulin protocol (see Chapter 44).

E. Insulinoma1. Surgical resection2. Frequent feeding of small meals3. Prednisone

a. A dosage of 0.5 to 1.0 mg/kg/day PO temporarily counteracts the insulin effects.

b. The dose may be gradually increased to 4 mg/kg/day PO, but expect adverse effects.

4. Diazoxidea. Inhibits secretion of insulin from pancreatic

b cellsb. Inhibits peripheral uptake of glucosec. Dose: 5 to 10 mg/kg PO BID initially, then in-

creased to 20 mg/kg PO BIDd. Limited availability, expensivee. Possible adverse effects: anorexia, vomiting,

diarrhea, tachycardia, hematological changes5. Streptozocin

a. Cytotoxic to pancreatic b cellsb. Indication: known metastatic disease or non-

resectable tumorsc. Seven-hour administration protocol (1) Pretreatment fl uid diuresis for 3 hours with

NaCl 18.3 mL/kg/hr 0.9% IV (2) Streptozocin at 500 mg/m2 mixed into

NaCl 36.6 mL/kg 0.9% and administered at 18.3 mL/kg/hr over 2 hours IV

(3) Posttreatment fl uid diuresis for 2 hours with NaCl 18.3 mL/kg/hr 0.9% IV

(4) Posttreatment butorphanol 0.4 mg/kg IM as needed for emesis

d. Adverse effects (1) Transient anorexia and/or vomiting for 24

hours after dose: common (2) Mild neutropenia: rare (3) Nephrotoxicity: extremely rare with diuresis

protocol (4) Secondary diabetes mellitus: transient or

permanent, in up to 33% of treated dogs6. Octreotide: use and effi cacy not well documented

F. Paraneoplastic hypoglycemia1. Surgical resection of tumor whenever possible2. Prednisone and frequent feeding, as noted previously

G. Glycogen storage diseases: no specifi c therapyH. Sepsis

1. Nutritional support: enteral or total parenteral2. CRI of dextrose3. Elimination of underlying cause of sepsis with

surgery and/or antibioticsI. Hepatic failure

1. Nutritional support: enteral or total parenteral2. CRI of dextrose3. Treatment of specifi c underlying hepatic disease


I. Neuroglycopenic crisisA. Monitor vital signs every 1 to 2 hours until clinically

alert and stable.B. Monitor BG every 1 to 2 hours until euglycemia is

established and maintained for >4 hours.C. Monitor neurological status hourly.D. If seizure activity recurs once euglycemic, diazepam or

phenobarbital is indicated (see Chapter 22). II. Specifi c monitoring for postoperative insulinoma cases

A. Measure BG intraoperatively, immediately postopera-tively, and every 2 to 4 hours thereafter until stable euglycemia is maintained for >12 hours.

B. If animal is persistently hypoglycemic postoperatively, tumor was incompletely resected and other therapy (described earlier) is warranted.

C. If animal becomes hyperglycemic postoperatively, tran-sient regular insulin therapy 0.5 U/kg SC, IM is indi-cated, and continue to monitor BG every 2 to 4 hours.

D. Discharge animal when clinically stable, euglycemic, and eating.

E. Recheck for metastatic disease with fasting BG evaluated monthly.

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Handbook of Small Animal Practice || Miscellaneous Endocrine Disorders