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5-Fluorouracil Toxicosis



AUTHOR: SHARON. WELCH



EDITOR: SAFDAR. KHAN



BASIC INFORMATION image



DEFINITION


Adverse effects caused by exposure to 5-fluorouracil (5-FU), a pyrimidine analog-type antineoplastic antimetabolite drug used for palliative management of certain carcinomas in humans and occasionally in dogs.



SYNONYMS


Common brand names: Efudex, Fluoroplex, and Carac. Generic: 2,4-dioxo-5-fluoropyrimidine; 5-fluoro-2,4(1H,3H); pyrimidinedione; 5-FU; NSC 19893; Ro2-9757; CAS 51-21-8.



EPIDEMIOLOGY



SPECIES, AGE, SEX


Dogs and cats of any age, breed, and either sex. Dog cases are more common. Dogs are more likely to develop neurologic effects (seizures) compared to humans. Cats are more sensitive to toxic effects of 5-FU than dogs.



RISK FACTORS



• Preexisting liver or kidney dysfunction can increase risk of toxicity

• Presence of 5-FU in a pet’s environment


CLINICAL PRESENTATION



HISTORY, CHIEF COMPLAINT



• History of exposure to product containing 5-FU

• Clinical signs begin within 30 minutes to 5 hours of exposure.

• Vomiting, hypersalivation, lethargy, vocalization, diarrhea, tremors, ataxia, seizures

• Some animals show vomiting progressing quickly to seizures; others may show tremors and seizures and no vomiting.


PHYSICAL EXAM FINDINGS



• Seizures (often status epilepticus)

• Vomiting (with or without blood)

• Diarrhea (with or without blood)

• Tremors

• Lethargy

• Ataxia

• Cardiac arrhythmias (all kinds)

• Respiratory depression


ETIOLOGY AND PATHOPHYSIOLOGY


Source


5-FU or similar agents are available for use as injection, topical creams (0.5%-5%) or lotions (1%-5%), and capecitabine (prodrug of fluorouracil) as tablets. Flucytosine is an antifungal agent that must be converted to 5-FU.


Toxicosis occurs after ingestion of products containing 5-FU and occasionally secondary to repeated use in dogs or cats.


Mechanism of Toxicosis


5-FU inhibits RNA processing and function and DNA synthesis and repair, inhibiting cell division. Actively dividing cell lines (bone marrow stem cells, intestinal crypt cells) are most affected.


The mechanism of neurotoxicity may be production of fluorocitrate, which limits cellular energy production by interfering with the Krebs cycle.



DIAGNOSIS image



DIAGNOSTIC OVERVIEW


History of exposure and presence of clinical signs consistent with exposure to 5-FU within 30 minutes to 5 hours after exposure



DIFFERENTIAL DIAGNOSIS


Diseases or intoxications that could cause vomiting (see p. 1173) and/or seizures (see pp. 1009 and 1425)



INITIAL DATABASE



• Serum biochemistry profile (elevated liver enzymes, azotemia possible in 24 hours)

• Electrolytes (hypokalemia possible due to severe vomiting, diarrhea)

• CBC with differential (baseline, monitor q 24-72 hours for 20 days); initial leukocytosis followed by evidence of myelosuppression, leukopenia, pancytopenia in 5-20 days. Hematocrit increased due to dehydration then decreased due to gastrointestinal (GI) bleeding.

• Blood gas analysis

• Urinalysis


ADVANCED OR CONFIRMATORY TESTING



• Analysis of 5-FU and its metabolites in plasma is possible but often difficult to obtain in timely fashion for acute toxicoses.

• Necropsy lesions: hemorrhagic colitis, GI mucosal ulceration (throughout), stomatitis, myocardial ischemia, pulmonary edema, hepatic and renal congestion


TREATMENT image



TREATMENT OVERVIEW


Stabilize the patient first; control vomiting and seizures. Provide supportive care once the animal has been stabilized.



ACUTE GENERAL TREATMENT



• Decontamination of asymptomatic patient
○ Emesis using activated charcoal with a cathartic if patient is showing no clinical signs and the ingestion is recent (<1 hour)

○ Hemodialysis, peritoneal dialysis, or fluid diuresis may enhance elimination

• Manage vomiting
○ Maropitant, 1 mg/kg SQ q 24 h for up to 5 consecutive days

○ Do not use metoclopramide (contraindicated with GI hemorrhage and seizure disorder)

• GI protection
○ Sucralfate, 0.5 (small dog) to 1 gram (large dog) PO q 8 h

○ Famotidine, 0.5-1 mg/kg IV or PO q 12-24 h; or omeprazole, 0.5-1 mg/kg PO q 24 h

• Manage tremors and seizures (see p. 1009)
○ Seizures are rarely controlled with diazepam alone (dogs: 2-5 mg/kg IV; cats: 0.5-1 mg/kg IV). If seizures persist after diazepam therapy, give phenobarbital IV bolus, 2-5 mg/kg (can be repeated at 20-minute intervals up to two times). May then add phenobarbital IV infusion (2-10 mg/hour IV, titrated to effect) to diazepam; or

○ Pentobarbital, 3-15 mg/kg IV slowly to effect; or

○ Propofol, 4-6 mg/kg IV or as continuous IV infusion 0.6 mg/kg/min; or

○ Gas anesthesia

• Intravenous fluids

• Thermoregulation (correct hypothermia)

• Ventilatory support as needed

• Maintain normal acid-base status and electrolyte balance

• Manage pain
○ Butorphanol, 0.2-0.4 mg/kg q 2-5 h SQ, IM, or IV (dogs); 0.1-1 mg/kg IM, IV, or SQ q 1-3 h (cats); or tramadol, 1-4 mg/kg PO q 6-8 h; or buprenorphine, 0.005-0.05 mg/kg, IM, IV q 4-8 h; or fentanyl patch

• Consider giving broad-spectrum antibiotics to prevent secondary infection.

• For neutropenia: filgrastim (Neupogen), 4-6 mcg/kg SQ


CHRONIC TREATMENT


Intensive supportive care may be needed for days/weeks, especially if myelosuppression occurs.



NUTRITION/DIET


Tube feeding or bland diet if GI signs



DRUG INTERACTIONS


Metronidazole may increase toxicity of 5-FU by reducing clearance.



POSSIBLE COMPLICATIONS OF TREATMENT OR DISEASE PROCESS



• Severe brain damage from uncontrolled seizures

• Neutropenia, pancytopenia, myelosuppression (in 5-20 days)


RECOMMENDED MONITORING



• Heart rate, blood pressure

• Respiratory rate and character

• CBC (myelosuppression in 5-20 days), serum biochemistry profile (liver and kidney function)

• Blood gases


PROGNOSIS AND OUTCOME image


Guarded to poor, once signs occur. Out of 72 cases of 5-FU toxicosis, 35 dogs died and 11 were euthanized.



PEARLS & CONSIDERATIONS image



COMMENTS



• Severe signs or death can result from 5-FU toxicosis; early decontamination and immediate, intensive treatment are essential, and owners should be advised of the seriousness of exposure to 5-FU.

• Estimated toxic dose likely to cause clinical signs in dogs: 8.6 mg/kg PO. Minimum lethal dose in dogs: 20 mg/kg PO. If a 70-lb dog (32 kg) ingests 1 tablespoon (15 g) from a tube containing 5% 5-FU, the dose of 5-FU in this dog will be approximately 23 mg/kg, a potentially lethal dose.


PREVENTION


Keep medications out of pets’ reach



TECHNICIAN TIPS


Estimating the ingested amount by obtaining a good history of exposure may predict the prognosis early on.



CLIENT EDUCATION


5-FU toxicosis in pets can be life threatening.



SUGGESTED READING



Albretson J. 5-Fluorouracil Toxicosis in dogs. Vet Med. 2001;96:270-274.



Abdominal Compartment Syndrome



AUTHOR: CATHERINE. SUMNER



EDITOR: ELIZABETH. ROZANSKI



1ST EDITION AUTHOR: SHARON. DRELLICH



BASIC INFORMATION image



DEFINITION


Impaired organ function resulting from increased intraabdominal pressure (IAP >20 mm Hg). This syndrome is likely underrecognized in veterinary medicine and has a high prevalence in human ICU patients.



SYNONYMS


ACS, increased IAP, intraabdominal hypertension (IAH)



EPIDEMIOLOGY



SPECIES, AGE, SEX


No species, age, sex, genetic, or breed predisposition



RISK FACTORS



• Any patient with abdominal disease or accumulations of fluid, gas, or tissue in the abdominal cavity can develop elevated IAP.

• Specific risk factors include underlying diseases that lead to gas or fluid accumulation in the abdominal compartment (within organs, viscera or as free fluid) or interfere with the abdominal wall’s ability to expand and compensate for increased abdominal contents.
○ Abdominal effusion

○ Abdominal neoplasia

○ Abdominal surgery or trauma (most common causes)

○ Abdominal wraps/bandages

○ Decreased abdominal wall compliance (edema, hematoma, muscle activity)

○ Hepatic abscess

○ High-volume fluid resuscitation

○ Ileus

○ Pancreatitis

○ Peritonitis

○ Sepsis


CLINICAL PRESENTATION



DISEASE FORMS/SUBTYPES



• Primary ACS: intraabdominal cause, most commonly postoperative or trauma patients

• Secondary ACS: extraabdominal cause, most commonly sepsis or burn patients that require aggressive fluid resuscitation

• Recurrent ACS: redevelopment of ACS after surgical or medical treatment for primary or secondary ACS


HISTORY, CHIEF COMPLAINT



• Frequent history of abdominal trauma or surgery

• Indications to check IAP are (usually in combination):
○ New or progressive organ failure

○ Particularly azotemia, reduced urine output

○ Elevated central venous, mean arterial, right and left atrial pressures

○ Rising intracranial pressure, altered mentation

○ New vomiting and diarrhea

○ Acidosis, rising blood lactate levels


PHYSICAL EXAM FINDINGS



• Physical examination and abdominal perimeter (girth) measurements are insensitive for detecting elevated IAP.

• Progressive abdominal distension or tympany, jugular vein distension, tachypnea, tachycardia are possible


ETIOLOGY AND PATHOPHYSIOLOGY



• IAP in healthy adults is subatmospheric − 0 mm Hg; IAP in critically ill adults is 5-7 mm Hg.

• IAH is defined as a sustained elevation in IAP = 12 mm Hg.

• ACS (sustained IAP > 20 mm Hg with new organ dysfunction/failure) develops if IAH is not recognized and treated.

• ACS is not a disease, but a distinct syndrome of clinical signs and abnormalities that can have multiple causes.

• At low intraabdominal volumes, the abdominal wall is very compliant. Large increases in abdominal volume result in minor increases in IAP. At higher abdominal volumes, abdominal wall compliance decreases, and even small increases in volume can cause major increases in IAP.

• Increased pressure in the abdomen leads to hypoperfusion and ischemia of abdominal organs and, when severe, direct compression of blood vessels. This leads to alterations in renal (most recognized), hepatic, and gastrointestinal functions. Anuria can occur with IAP > 30 mm Hg. Liver function, including cytochrome P450 function, is impaired. Intestinal edema can develop, as well as bacterial translocation through gastrointestinal walls.

• Reduced ability for the diaphragm to contract against the tense abdomen impairs tidal volume and compromises ventilation, resulting in hypoxia and hypercapnia. Mechanical/positive pressure ventilation is similarly affected.

• Increase in central venous pressure (CVP) and drop in cardiac output (increased systemic vascular resistance, decreased venous return to the heart, compression of vascular structures from increased intrathoracic pressure) result in altered cardiovascular function.

• Intracranial pressure elevations can occur because of elevated CVP.

• Hormonal changes occur in response to the altered cardiovascular state, including elevations in renin-angiotensin activity, antidiuretic hormone, and catecholamine levels.

• Ischemia-reperfusion injury occurs after shock resuscitation and can affect distant organ function.

• Abdominal wall complications can occur secondary to hypoperfusion, including delayed or impaired wound healing, dehiscence, and surgical site infection.

• Recognition of increasing IAP and prevention of ACS are crucial to reducing morbidity and mortality.

• There is no single threshold IAP that will result in organ dysfunction or failure in all patients and can be used for decision making. The critical IAP in most patients is between 10 and 15 mm Hg; at this pressure, initial organ dysfunction develops.


DIAGNOSIS image



DIAGNOSTIC OVERVIEW


IAP must be measured to confirm the diagnosis of abdominal compartment syndrome.



INITIAL DATABASE


Most common method of measuring IAP is the intravesicular or “bladder” technique, which is an indirect measurement.


• A water manometer is attached to a stopcock in the evacuation line from a standard urinary (urethral) catheter.

• The urinary bladder is emptied, and a few milliliters of isotonic sterile saline are placed in the bladder (3-10 mL, depending on patient size).

• After 30-60 seconds (to allow the saline to warm and the detrusor muscle to relax, avoiding a falsely elevated reading), the zero mark on the manometer is held at the level of the cardiac atria (level of the umbilicus in lateral recumbency).

• The manometer is filled with saline.

• The stopcock is then opened to the bladder.

• The reading (in mm Hg) is taken when the column of saline reaches a stable level.

• The measurement should be taken at end expiration.

• Abdominal muscle contractions can increase IAP readings. Obese patients may have a higher baseline IAP.

• Alternative measurement techniques include nasogastric balloon catheter (good for continuous measurement), direct intraabdominal catheter/abdominal drain, and venous catheter in the caudal vena cava. These techniques give similar information but can be more cumbersome to place and maintain.

• Trends in pressure parameters may be more important than any single number. It is important to use the same positioning each time a measurement is taken.

• The IAP measured at one point in the abdominal cavity can be assumed to be the pressure throughout the abdominal cavity.

• Imaging can be helpful for looking for underlying causes of IAH but is insensitive at detecting increased IAP.


ADVANCED OR CONFIRMATORY TESTING



• Repeated IAP measurements are essential for monitoring.

• Lactate levels, liver enzyme changes, urine output, blood urea nitrogen, and creatinine levels to identify abdominal organ dysfunction associated with ACS

• Measurements of cardiac output and other cardiovascular parameters and monitoring mentation and intracranial pressure give a more extensive assessment of cardiovascular function and perfusion.

• Abdominal perfusion pressure (APP; mean arterial pressure minus IAP) has been proposed as a more accurate predictor of visceral perfusion. It assesses the severity of IAP, as well as the adequacy of abdominal blood flow, and should be maintained at 50-60 mm Hg in patients with IAH/ACS.


TREATMENT image



TREATMENT OVERVIEW


Medical management is crucial to prevention and treatment of IAH. Surgical decompression is the definitive treatment if medical management fails to prevent further increases in IAP and organ dysfunction and failure.



ACUTE, GENERAL TREATMENT



• IAP of 10-20 mm Hg is a mild elevation and should be monitored.

• IAP of 20-35 mm Hg is a moderate to severe elevation.
○ Consider active (centesis or surgical) decompression if pressure continues to rise or if other parameters continue to deteriorate.

• IAP > 35 mm Hg is a severe elevation.
○ ACS is extremely likely.

○ Abdominal decompression is required.

○ If a correctible source is not identified, surgical exploratory laparotomy is indicated.

• Medical Management
○ Sedation, analgesia, and/or neuromuscular blockade to reduce muscle tone secondary to pain, agitation, and ventilator dyssynchrony, which result in increased IAP

○ Not effective at treating severe IAH/ACS

○ Nasogastric or colonic decompression can reduce IAP and treat mild/moderate IAH.

○ Prokinetic motility agents useful in decreasing visceral volume

○ Aim for euvolemia.

○ Hypervolemia can lead to ACS development.

○ Hypertonic crystalloid and colloid resuscitation shown to reduce IAP and decrease risk of ACS

○ Diuretics to mobilize third space fluid accumulation

○ Percutaneous decompression to remove free abdominal fluid or air

○ If this fails to resolve IAH, patient must undergo surgical decompression.

• Surgical Management (VERY rare in companion animals, barring arterial hemorrhage)
○ Direct removal of the fluid or tissue causing the problem

○ Performed when organ dysfunction/failure and IAH are refractory to medical management

○ Open abdomen or temporary abdominal closure techniques often employed in human medicine


CHRONIC TREATMENT



• Placement of abdominal drains or repeated drainages/centeses in chronic conditions to maintain reduced pressure may be necessary. Treatment of the underlying disease is essential.


DRUG INTERACTIONS


Hepatic and renal elimination of drugs may be altered by ACS, requiring dosage adjustment or alternative drug choices.



RECOMMENDED MONITORING


IAP, CVP, blood pressure, blood chemistry, lactate, urine output, diagnostic imaging as indicated by underlying cause and progression of IAP over time



PROGNOSIS AND OUTCOME image


Prognosis depends on underlying cause and associated abnormalities, organ dysfunction, and disease. In human medicine, ACS is a significant cause of morbidity and mortality (approaching 70%). Disregard for elevated IAP and delay of surgery are associated with further increases in patient mortality.



PEARLS & CONSIDERATIONS image



COMMENTS



• Most critically ill patients should have urethral catheters in place to monitor urine output, which allows for IAP monitoring and early detection of ACS.

• IAH may falsely elevate indirect intracardiac pressure readings due to abdominothoracic transmission of pressure.

• Monitoring and management of patients this ill requires 24-hour care.


TECHNICIAN TIP


IAP is most easily measured in recumbent patients. If the patient is conscious and mobile, care must be taken to prevent the patient from chewing the catheter and retaining the proximal portion in the abdomen or bladder (Elizabethan collar essential).



PREVENTION


Avoid excessive fluid volume resuscitation. Careful monitoring essential, with early preventive action taken if IAP rises.



SUGGESTED READING



Cheatham ML. Abdominal compartment syndrome. Curr Opin Crit Care. 2009;15:154-162.


Drellich S. Intraabdominal pressure and abdominal compartment syndrome. Compend Contin Educ Prac Vet. 2000;22:764-769.



Abdominal Distention



AUTHOR: KIRSTIE A. BARRETT



EDITOR: ETIENNE. CÔTÉ



BASIC INFORMATIONimage



DEFINITION


Enlargement of the abdominal cavity



EPIDEMIOLOGY


SPECIES, AGE, SEX: Dependent on underlying cause



CLINICAL PRESENTATION



HISTORY, CHIEF COMPLAINT



• Abdominal enlargement (rate of distention is extremely variable, varies from acute to chronic and insidious)

• Perceived weight gain

• Decreased activity

• Anorexia

• Tachypnea

• Abdominal discomfort/pain

• When ascites is present and the fluid accumulation is rapid, clinical signs of weakness and dyspnea are more likely to be apparent.

• History may include clinical signs associated with the primary disease (e.g., repeated, unproductive attempts at vomiting if gastric dilatation and volvulus; dyspnea, cough if cardiac disease; icterus if liver disease).


PHYSICAL EXAM FINDINGS



• Visible abdominal enlargement

• Abdominal palpation:
○ Fluid wave may be present (ballottement) with ascites.

○ An abdominal mass or organomegaly (liver, spleen, kidney, etc.) may be palpable.

• Physical abnormalities associated with primary disease may be present:
○ Cardiovascular abnormalities (heart murmur, arrhythmia, gallop sound, jugular distention) should warrant further investigation into the possibility of right heart failure.

○ Marked generalized lymphadenopathy may suggest lymphoma.

○ Muffled heart sounds are consistent with pericardial effusion and tamponade if ascites is present.


ETIOLOGY AND PATHOPHYSIOLOGY



• Ascites: all causes

• Hyperadrenocorticism/Cushing’s disease

• Cyst (renal, hepatic)

• Gastrointestinal dilation (food, air, water, foreign material)

• Lipoma

• Lymphadenopathy

• Mass, non-neoplastic (hematoma, granuloma, abscess)

• Neoplasia


image ABDOMINAL DISTENTION Dorsal view of a young English bulldog with marked ascites caused by right-sided congestive heart failure due to severe pulmonic stenosis. The abdominal distention hides the dog’s weight loss and may be mistaken by the owner as an increase in lean body mass. This degree of abdominal distention was associated with poor appetite, lethargy, and dyspnea in this dog.


image ABDOMINAL DISTENTION Same dog 2 hours later when large-volume abdominal drainage was complete. The dog was breathing normally, was more active, and appeared markedly more comfortable. The extent of cardiac cachexia is revealed.

• Pancreatitis

• Parasitic (Mesocestoides)

• Peritonitis

• Pneumoperitoneum (peritonitis or postsurgical)

• Pyometra/hydrometra

• Obstipation

• Organomegaly (hepatomegaly, splenomegaly, renomegaly)

• Torsion (splenic, gastric dilation/volvulus, etc.)

• Urinary obstruction/bladder distention


DIAGNOSISimage



DIAGNOSTIC OVERVIEW


Apparent on physical examination alone. Careful abdominal palpation and diagnostic imaging help to elucidate the cause.



DIFFERENTIAL DIAGNOSIS



• Normal variation

• Obesity

• Pregnancy


INITIAL DATABASE



• Abdominal radiographs
○ Loss of serosal detail (focal or generalized) is common if ascites is present.

○ May have “ground-glass” appearance (carcinomatosis, peritonitis)

○ Mass lesions, fat, or organomegaly may be apparent or suggested by displacement of gas-filled organs.

○ Free air may be present with peritonitis (ruptured viscus).

• Thoracic radiographs
○ Enlarged cardiac silhouette and/or caudal vena cava if congestive heart failure or pericardial effusion (rule out as cause of ascites)

○ Metastatic pulmonary disease

○ Pleural effusion

• CBC, biochemistry panel, and urinalysis are indicated for any animal with ascites or abnormal abdominal distention. Abnormalities depend on underlying cause and extent of organ damage.

• Abdominal ultrasonography
○ Confirms presence of fluid if present and differentiates fluid from soft tissue or fat

○ Identification of mass lesions, organomegaly, cyst, etc.

• Echocardiography
○ Confirms diagnosis of right heart enlargement or pericardial effusion (rule out as cause of ascites)

• Abdominal paracentesis (see p. 1194) if ascites; obtain fluid for cytology and biochemical evaluation.

• Characterize fluid based on protein concentration, specific gravity, and total cell count.
○ Transudate (pure)
▪ Clear and colorless

▪ Protein <2.5 g/dL

▪ Specific gravity <1.018

▪ Cells <1000/mm3: neutrophils and mesothelial cells

○ Modified transudate
▪ Red or pink; may be slightly cloudy

▪ Protein 2.5-5.0 g/dL

▪ Specific gravity >1.018

▪ Cells <5000/mm3: neutrophils, mesothelial cells, erythrocytes, and lymphocytes

○ Exudate (nonseptic)
▪ Pink or white; cloudy

▪ Protein 2.5-5.0 g/dL

▪ Specific gravity >1.018

▪ Cells 5000-50,000/mm3: neutrophils, mesothelial cells, macrophages, erythrocytes, and lymphocytes

○ Exudate (septic)
▪ Red, white, or yellow; cloudy

▪ Protein >4.0 g/dL

▪ Specific gravity >1.018

Cells 5000-100,000/mm3: neutrophils, mesothelial cells, macrophages, erythrocytes, lymphocytes, and bacteria


○ Hemorrhage
▪ Red

▪ Protein >5.5 g/dL

▪ Specific gravity 1.007-1.027

▪ Cells consistent with peripheral blood; usually does not clot

○ Chyle
▪ Pink, straw, or white

▪ Protein 2.5-7.0 g/dL

▪ Specific gravity 1.007-1.040


ADVANCED OR CONFIRMATORY TESTING



• Fine-needle aspirate or needle biopsy (mass, enlarged organs, etc.). Biopsy not recommended if area is infected (abscess, pyometra) or likely to hemorrhage (e.g., suspected hemangiosarcoma).

• Prothrombin time if anticoagulant intoxication is suspected as cause of ascites (paracentesis contraindicated if coagulopathy is suspected)

• CT, MRI

• Abdominal exploratory may be indicated.


TREATMENTimage



TREATMENT OVERVIEW


Treatment of underlying disease and therapeutic abdominal drainage if large-volume ascites is causing the abdominal compartment syndrome (see p. 4)



ACUTE GENERAL TREATMENT



• Treatment of underlying disease:
○ Chemotherapy if lymphoma

○ Pericardiocentesis if pericardial effusion is present

○ Drug therapy for congestive heart failure

• Removal of fluid if discomfort or respiratory difficulty is present (see p. 1192).

• Surgery may be indicated for neoplasia, pyometra, peritonitis, and some causes of hemorrhage (e.g., ruptured splenic or hepatic hemangiosarcoma).


PROGNOSIS AND OUTCOMEimage


Dependent on underlying cause



PEARLS & CONSIDERATIONSimage



COMMENTS



• Approach to patient with abdominal distention is to determine the nature of the primary problem.

• Thoracic radiographs should be part of the routine evaluation for a patient with ascites so as not to overlook the possibility of cardiac, pericardial, or metastatic disease–or pleural effusion.

• The cause of abdominal distention may be benign (obesity, intraabdominal lipoma, cyst).


SUGGESTED READING



Chambers G. Abdominal distension, ascites, and peritonitis. In: Ettinger SJ, Feldman EC, editors. Textbook of veterinary internal medicine. ed 7. St Louis: Saunders Elsevier; 2010:144-148.




Aberrant Adrenocortical Disease (Increased Adrenal Sex Hormone Production) image



AUTHOR: KATE. HILL



EDITOR: SHERRI. IHLE



BASIC INFORMATION image



DEFINITION


Clinical signs of hyperadrenocorticism are present, but cortisol test results are normal, and one or more of the adrenal sex hormones is/are increased.



SYNONYMS


Atypical hyperadrenocorticism, sex hormone abnormality



EPIDEMIOLOGY



SPECIES, AGE, SEX


Middle-aged/old dogs and cats



ASSOCIATED CONDITIONS AND DISORDERS


Hyperadrenocorticism



CLINICAL PRESENTATION



DISEASE FORMS/SUBTYPES



• Pituitary dependent

• Adrenal dependent: adrenal carcinoma has mainly been reported (two cats and six dogs with hyperprogesteronism)


HISTORY, CHIEF COMPLAINT


Identical to hyperadrenocorticism (see p. 548)



PHYSICAL EXAM FINDINGS


Identical to hyperadrenocorticism (see p. 548)



ETIOLOGY AND PATHOPHYSIOLOGY



• The adrenal gland(s) secretes an excessive amount of one or more adrenal sex hormones.

• Adrenal tumors (particularly adenocarcinomas) may secrete adrenal sex hormones owing to disruption of adrenal tissue.

• Progestagens can act as glucocorticoid agonists.

• Cortisol concentrations may be normal to subnormal with sex hormone-secreting adrenal tumors, as high progestagen concentrations can suppress cortisol secretion.


DIAGNOSIS image



DIAGNOSTIC OVERVIEW


The disorder is suspected when typical signs of hyperadrenocorticism are identified, but specific diagnostic tests (e.g., ACTH stimulation) are inconsistent with hyperadrenocorticism. Confirmation is obtained with identification of elevated serum levels of adrenal sex hormones.



DIFFERENTIAL DIAGNOSIS



• Polyuria/Polydipsia (see p. 902)

• Polyphagia (see p. 899)

• Alopecia (see pp. 54 and 56)


INITIAL DATABASE


Hyperadrenocorticism (see p. 548)



ADVANCED OR CONFIRMATORY TESTING



• Adrenocorticotropic hormone (ACTH) stimulation test with sex hormone panel (progesterone, 17-hydroxyprogesterone, estradiol, androstenedione, testosterone):
○ Dogs with nonadrenal illness may have mildly increased adrenal sex hormones.

○ Substantial overlap in sex hormone serum concentrations between healthy, nonadrenally ill, and hyperadrenocorticism patients make sex hormone assays ineffective screening tests for hypercortisolism.

○ Approximately 71% sensitivity and specificity for 17-hydroxyprogesterone concentrations if a cutoff greater than 8.5 ng/mL is used for diagnosing atypical hyperadrenocorticism

• Low-dose dexamethasone suppression test to rule out typical hyperadrenocorticism ± endogenous ACTH concentrations, CT, MRI (see p. 548)


TREATMENT image



TREATMENT OVERVIEW


Resolution of clinical signs is the goal of treatment; medications are typically used for controlling pituitary-based disease, and surgical excision is the treatment of choice for primary adrenal tumors.



ACUTE GENERAL TREATMENT



• See Adrenal Neoplasia (Adenoma/Carcinoma), p. 43

• Pituitary-dependent (see p. 548)


CHRONIC TREATMENT



• As for hyperadrenocorticism, p. 548

• The following recommended by some, with anecdotally supported results (see http://www.vet.utk.edu/diagnostic/endocrinology/pdf/TreatmentInfoAtypicalCushingsRevised201001.pdf):
○ Melatonin (3-6 mg/dog PO q 12 h, based on body weight); inhibits aromatase and 21-hydroxylase enzymes

○ Melatonin implants (www.melatek.net) 8, 12, 18 mg for dogs weighing <25, 25-50, and >50 lb, respectively

○ Lignan (from flaxseed hulls or HMR lignan) ≈ 2 mg/kg PO q 24 h; phytoestrogenic activity inhibits aromatase

• Elimination of exogenous (e.g., hormone cream) or endogenous (ovarian remnant, cryptorchid testicle) sources of androgens


DRUG INTERACTIONS


See Hyperadrenocorticism, p. 548; Adrenal Neoplasia (Adenoma/Carcinoma), p. 43



POSSIBLE COMPLICATIONS


See Hyperadrenocorticism, p. 548; Adrenal Neoplasia (Adenoma/Carcinoma), p. 43



RECOMMENDED MONITORING


Medical therapy: ACTH stimulation testing every 3 months


• Mitotane (o, p ‘-DDD) therapy: sex hormone concentrations (and cortisol if also increased) should decrease to normal.

• Trilostane therapy: progesterone and 17-hydroxyprogesterone concentrations may increase concurrent with resolution of clinical signs and a decrease in cortisol concentrations.


PROGNOSIS AND OUTCOME image



• Survival data unknown but subjectively similar to dogs with typical hyperadrenocorticism
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