The ADR (Ain’t Doing Right) Dog: Endocrine Emergencies

Lucky, a 6-year-old, 20-kg, female spayed, mixed-breed dog was presented due to a 1-week history of progressive “ADR” (ain’t doing right).

History

Lucky was presented to the emergency referral veterinary clinic because her primary care veterinarian was closed for the evening.

The owner reported that Lucky vomited in the car a week earlier when coming home from the groomer. Over the past week, Lucky’s appetite diminished but she seemed thirstier. Lucky had become progressively more lethargic and anorectic over the past 2 days.

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Note: The first annual Today’s Veterinary Practice symposium—Insights from Experts—took place at the NAVC Conference 2016 in Orlando, Florida. This article reviews the information provided by Dr. Justine Lee and Dr. Garret Pachtinger in the session, Emergency Management of Hypoadrenocorticism.

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Lucky was up-to-date on vaccines, receiving seasonal flea and tick medication and heartworm preventative, and healthy until a week ago.

Physical Examination

The physical examination findings for Lucky upon presentation to the referral facility are listed in Table 1. Doppler blood pressure measurement revealed that Lucky’s systolic blood pressure was 80 mm Hg.

Initial Diagnostics

Due to the combination of Lucky’s dehydration and hypovolemia (based on poor pulse quality), a peripheral 18-gauge, 6-cm cephalic IV catheter was placed. A small amount of blood from the catheter hub was obtained for analysis of packed cell volume, total solids, blood urea nitrogen (Azostix, usa.healthcare.siemens.com), blood glucose, and venous blood gas/electrolytes. Laboratory results are listed in Table 2.

Due to the severe hyperkalemia (see INITIAL DIAGNOSIS, Electrolyte Abnormalities), an electrocardiogram (ECG) was obtained immediately. A sinoventricular rhythm was observed, with absent P waves and widened QRS complexes (Figure 1). Typical ECG findings in hyperkalemic patients include bradycardia; tall, tented T waves; prolonged QRS intervals; prolonged PR intervals; absent P waves; and deviation of the ST segment.

Initial Diagnosis

Electrolyte Abnormalities

Lucky’s sodium:potassium ratio was 16:1, which is most often seen in veterinary patients as a result of hypoadrenocorticism and mineralocorticoid deficiency. The hyperkalemia can potentially be life-threatening, resulting in severe arrhythmias. The hypoglycemia can result in clinical signs of weakness, tremors, vomiting, seizures, collapse, and death. Prompt treatment of the electrolyte abnormalities and hypoglycemia in this patient was imperative.

Dehydration & Hypovolemic Shock

This patient had both dehydration and hypovolemic shock. While the patient was only mildly bradycardiac, this was likely an inappropriate response to hypovolemia secondary to a life-threatening hyperkalemia. The presence of both dehydration and hypovolemia are likely due to both glucocorticoid and mineralocorticoid deficiencies.

Differential Diagnosis

Differential diagnosis—in addition to glucocorticoid/mineralocorticoid deficiencies—includes underlying metabolic conditions (eg, ascites, pericardial effusion, severe metabolic acidosis), gastrointestinal disease (eg, whipworm infection), acute kidney injury (AKI), neoplasia, trauma (eg, uroabdomen, rhabdomyolysis), and sepsis.^1-6

Initial Therapy

Therapy for Electrolyte Abnormalities

Hyperkalemia decreases resting potential, which makes it less negative and initially results in more hyperexcitable cells.⁷ To increase the normal threshold membrane potential, thereby normalizing the difference between the 2 potentials, a bolus of 50 mg/kg 10% calcium gluconate, delivered slowly over 15 minutes, was administered to Lucky.⁷

Alternatively, use of sodium bicarbonate or insulin:dextrose can be considered. Although calcium gluconate has the most rapid stabilizing effect in hyperkalemic patients, it does not address the hyperkalemia itself. Both sodium bicarbonate and insulin therapy result in a transient lowering of serum potassium, promoting its translocation from the extracellular to the intracellular fluid compartment (Figure 2).

Lucky received continuous ECG monitoring during calcium gluconate administration and until she was more cardiovascularly stable. It is important to remember that calcium gluconate does not directly affect potassium levels.

Therapy for Dehydration & Hypovolemic Shock

Lucky received an initial IV bolus of 0.5 g/kg dextrose (10 mL of 50% dextrose diluted in 20 mL of 0.9% saline) over 2 to 3 minutes to address the hypoglycemia. An additional bolus of 400 mL (20 mL/kg) of warmed lactated Ringer’s solution was administered over 15 minutes.

Ongoing Fluid Therapy

1. Replacement fluids: Lucky’s estimated dehydration was 5%. To correct this deficit over the next 8 hours, Lucky needed to receive fluids at a rate of 125 mL/H:

1000 mL (deficit)/8 H = 125 mL/H
20 kg (body weight) × 0.05 (dehydration) = 1000 mL fluid deficit

2. Maintenance fluids: Lucky also needed to concurrently receive maintenance fluids at a rate of 42 mL/H:

20 kg (body weight) × 50 mL Q 24 H = 1000 mL Q 24 H
1000 mL /24 H = 42 mL/H

More information on the dosage of 50 mL Q 24 H can be found at aaha.org/public_documents/professional/guidelines/fluidtherapy_guidlines_toolkit.pdf.

3. Ongoing losses: Ongoing losses (eg, vomiting, urinary losses) were estimated at 30 mL/H.

4. Crystalloid fluid therapy: Crystalloid fluid rate for the first 8 hours—after the initial fluid bolus—was calculated:

Replacement (125 mL/H) + maintenance (42 mL/H) + ongoing losses (30 mL/H)
= approximately 200 mL/H

Once the dehydration deficit had been replaced, the fluid rate was adjusted to reflect maintenance and ongoing losses. Based on blood glucose monitoring results, glucose supplementation (2.5%–5% dextrose supplementation) was adjusted to maintain normoglycemia.

Patient Monitoring

Reassessment of perfusion parameters showed improvement after the initial crystalloid and dextrose bolus, and Lucky was carefully and frequently assessed while receiving fluid therapy (Table 3). Blood glucose was measured Q 8 H in order to guide glucose supplementation.

Additional Diagnostics

While the patient was stabilized, further diagnostics were pursued, including a complete blood count (CBC), serum biochemical profile, urinalysis (Table 4), and baseline and resting cortisol levels.

CBC results revealed:

• Eosinophilia and lymphocytosis: May be due to glucocorticoid deficiency (eg, lack of a stress leukogram)¹
• Mild anemia: In the face of dehydration, may be due to gastrointestinal bleeding or anemia of chronic disease.

Biochemistry revealed:

• Hypoglycemia: Rarely seen in adult dogs secondary to anorexia; may be due to glucocorticoid deficiency, insulinoma, iatrogenic insulin administration, hunting dog hypoglycemia, neoplasia, or sepsis
• Electrolyte abnormalities, with a sodium:potassium ratio of 16:1
• Azotemia: May be due to prerenal or primary AKI
• Hypercalcemia: May be due to underlying metabolic disease (eg, hypoadrenocorticism, hyperparathyroidism), toxicosis (eg, cholecalciferol, calcipotriene), or neoplasia
• Isosthenuria: May be due to medullary washout secondary to excessive sodium loss into the urine or underlying renal disease.

Lucky’s baseline cortisol (< 2 mcg/dL) was consistent with hypoadrenocorticism. Due to concern regarding the low baseline cortisol, a complete adrenocorticotropic hormone (ACTH) stimulation test was submitted. Both pre-ACTH (< 2 mcg/dL) and post-ACTH (< 2 mcg/dL) stimulation test results were consistent with hypoadrenocorticism.

Definitive Diagnosis

Based on the baseline cortisol and ACTH stimulation tests, all the clinicopathologic tests were consistent with a diagnosis of hypoadrenocorticism. Additional diagnostics may include fecal testing (to rule out whipworms) and advanced diagnostic imaging, such as ultrasound (to rule out signs and disease, such as gastrointestinal bleeding, ascites, and neoplasia).

Therapy for Hypoadrenocorticism

Typical supportive therapies for the patient with hypoadrenocorticism include:^8,9

• Crystalloid fluids, along with dextrose supplementation as needed
• Steroids, such as dexamethasone, due to lack of adequate glucocorticoid levels; other types of steroids (eg, prednisone, prednisolone, hydrocortisone) should not be used before diagnostic testing (eg, ACTH stimulation, baseline cortisol) because they interfere with the radioimmunoassay for glucocorticoid measurement
• Gastric protectants, such as famotidine or pantoprazole, if gastric ulceration is suspected
• Antiemetics, such as maropitant, dolasetron, ondansetron, or metoclopramide, if vomiting is present
• Mineralocorticoids, such as desoxycorticosterone pivalate (DOCP) or fludrocortisone acetate (Florinef, bms.com), to help normalize electrolytes; they should be administered once the patient is stable, with life-threatening electrolyte abnormalities corrected, and can tolerate oral medication.

Lucky’s therapeutic approach included:

1. Initial therapy for electrolyte abnormalities and arrhythmias (calcium gluconate), with continuous ECG monitoring
2. Initial therapy for dehydration and hypovolemia (dextrose and fluid boluses, then fluid therapy)
3. Rapid diagnosis of, and therapy for (Table 5), hypoadrenocorticism.

Lucky’s hydration and hypovolemic state improved with fluid therapy and her blood pressure returned to normal after 2 crystalloid boluses. Within 12 hours, Lucky was eating and drinking, and her electrolyte abnormalities had resolved.

Prognosis & Follow-Up Care

Lucky was discharged the day after presentation—once she was appropriately hydrated, her electrolytes were corrected, and she was eating and drinking voluntarily.

Lucky’s owner was instructed on the long-term management of hypoadrenocorticism, taught how to administer medications (including extra dosing during stressful events), and counseled to follow up with the veterinarian for long-term mineralocorticoid management (eg, DOCP).

The primary care veterinarian performed a recheck examination 3 days after discharge and noted that the physical examination and electrolyte findings were normal; follow-up was scheduled for 3 weeks later to recheck electrolytes and administer DOCP (Table 6).

The owner was pleased with the outcome and rapid improvement in Lucky’s condition.

In Summary

Clinicians should be able to rapidly recognize hypoadrenocorticism on the basis of history, signalment, clinical signs, and classic clinicopathologic testing. Rapid and appropriate diagnostic workup should be performed (eg, baseline cortisol, ACTH cortisol evaluation) to rule out other “look-alike” diseases, such as metabolic disorders (eg, renal disease, pancreatitis), toxicosis (eg, from ingestion of grapes, cholecalciferol), and infectious disease (eg, Leptospira infection, urinary tract infection, pyelonephritis).

While long-term management may be cumulatively expensive (eg, prednisone, periodic electrolyte monitoring, and mineralocorticoid supplementation), with medical management, the prognosis for hypoadrenocorticism is good to excellent.

ACTH = adrenocorticotropic hormone; AKI = acute kidney injury; CBC = complete blood count; ECG = electrocardiogram