- 1 1. Define hypoadrenocorticism.
- 2 2. What is the common signalment of dogs with hypoadrenocorticism?
- 3 3. What are the most common historical complaints made by owners of dogs with hypoadrenocorticism?
- 4 4. Which abnormalities are most commonly noted on physical examination?
- 5 5. Describe the hematologjc abnormalities in patients with hypoadrenocorticism.
- 6 6. List the common serum biochemical and electrolyte abnormalities associated with hypoadrenocorticism.
- 7 7. Why is the azotemia associated with hypoadrenocorticism generally considered prerenal?
- 8 8. How does a low sodium:potassium ratio support the diagnosis of hypoadrenocorticism?
- 9 9. List the differential diagnoses for hyperkalemia and hyponatremia.
- 10 10. What test is used for definitive diagnosis of hypoadrenocorticism?
- 11 11. What is an addisonian crisis?
- 12 12. What are the goals of management of an acute adrenal crisis?
- 13 13. What is the fluid of choice for hypoadrenocorticism? How should it be administered?
- 14 14. When should hyperkalemia be treated with something other than intravenous fluid replacement?
- 15 15. When should an adrenocorticotropic hormone stimulation test be performed in a crisis setting?
- 16 16. When in the course of therapy should glucocorticoids be given?
- 17 17. Which glucocorticoids are recommended for replacement therapy?
- 18 18. When should mineralocorticoid replacement be instituted?
- 19 19. How is maintenance mineralocorticoid replacement assessed?
- 20 20. What other problems need to be addressed in dogs with an adrenal crisis?
- 21 21. What are the principal differences between hypoadrenocorticism in cats and dogs?
1. Define hypoadrenocorticism.
Hypoadrenocorticism is the lack of production of glucocorticoids and mineralocorticoids by the adrenal glands. It may be due to a pathologic process that affects either the adrenal glands directly (primary hypoadrenocorticism) or the production or release of corticotropin-releasing hormone (CRH) by the hypothalamus or adrenocorticotropic hormone (ACTH) by the pituitary (secondary hypoadrenocorticism). Typical hypoadrenocorticism (Addison’s disease) results from combined mineralocorticoid and glucocorticoid deficiency and is characterized by hyponatremia and hyperkalemia.
If only glucocorticoids are deficient, the disease is termed atypical hypoadrenocorticism. Because there are no electrolyte imbalances, diagnosis is more difficult than for typical hypoadrenocorticism. All cases of secondary hypoadrenocorticism are deficient only in glucocorticoids because adrenocorticotropic hormone acts primarily on the adrenal zona fasciculate to stimulate glucocorticoid production and release and has little-to-no effect on mineralocorticoid production. Approximately 10% of dogs with primary hypoadrenocorticism are atypical at presentation, but most also develop mineralocorticoid deficiency.
2. What is the common signalment of dogs with hypoadrenocorticism?
Hypoadrenocorticism occurs most frequently in middle-aged females; the median age is 4 — 5 years. Sexually intact females have a higher risk of developing the disease, and sexually intact males have the lowest risk. Although close to one-third of dogs with hypoadrenocorticism are mixed breed, poodles of any size and flavor, Portuguese water dogs, Leonbergers, and Labrador retrievers have a familial tendency. Other predisposed breeds include Great Danes, Rottweilers, West Highland white terriers, and German shepherd dogs.
3. What are the most common historical complaints made by owners of dogs with hypoadrenocorticism?
Lethargy, anorexia, vomiting, and weight loss are common historical findings. Less frequent complaints are diarrhea, shaking, polyuria and polydipsia, and weakness. An important feature of hypoadrenocorticism is the waxing and waning nature of clinical signs. In general, the owner comments about marked improvement in the pet after administration of fluids and some “injection.”
4. Which abnormalities are most commonly noted on physical examination?
Physical abnormalities include lethargy, weakness, poor body condition, some degree of dehydration, melena, and hypothermia. Approximately 35% of animals present with physical findings consistent with moderate-to-severe shock, including weak pulses, pale mucous membranes, prolonged capillary refill time (CRT), and cold extremities. However, affected animals tend to have bradycardia instead of tachycardia, which is indicative of hyperkalemia.
5. Describe the hematologjc abnormalities in patients with hypoadrenocorticism.
Lymphocytosis and eosinophilia (i.e., lack of a stress leukogram in sick animals) occur in approximately 10% and 20% of dogs diagnosed with hypoadrenocorticism disease, respectively. These changes may be the only laboratory clues in the search for the atypical addisonian. A mild normochromic, normocytic nonregenerative anemia is common but often not apparent until dehydration is corrected. In one study, 61% of patients were reported to have anemia after dehydration resolved. In patients with melena, anemia may be severe and ultimately regenerative.
6. List the common serum biochemical and electrolyte abnormalities associated with hypoadrenocorticism.
• Moderate-to-severe azotemia (approximately 80% of patients)
• Hyperkalemia (approximately 90-95%)
• Hyponatremia (approximately 80%)
• Hyperphosphatemia (approximately 70%)
• Low total CO2 (approximately 40%)
• Hypercalcemia (approximately 30%)
• Increased activities of liver enzymes (approximately 30%)
• Hypoglycemia (approximately 17%)
7. Why is the azotemia associated with hypoadrenocorticism generally considered prerenal?
Most addisonians are azotemic at diagnosis and have a urine specific gravity less than 1.030. This finding argues against the assumption that azotemia is due to prerenal causes and supports primary renal failure. However, in most patients, the creatinine levels are typically less elevated than the blood urea nitrogen (BUN) concentrations. In addition, azotemia resolves in most patients with intravenous (IV) fluid administration. The low specific gravity is generally attributed to medullary wash-out from hyponatremia and increased renal excretion of sodium due to the lack of aldosterone, which results in solute diuresis.
8. How does a low sodium:potassium ratio support the diagnosis of hypoadrenocorticism?
A normal sodium:potassium (Na:K) ratio in dogs is 27:1-40:1 with a mean of 30:1. In one study of 225 addisonian dogs, about 95% had a low Na:K ratio; the mean was 19.3:1. However, 20 dogs had a normal Na:K ratio 1-4 weeks previously. Hypoadrenocorticism is placed on the rule-out list of an ill animal with hyponatremia, hyperkalemia, and a Na:K ratio less than 27:1, but hypoadrenocorticism is not the only disease that lowers the Na:K ratio.
9. List the differential diagnoses for hyperkalemia and hyponatremia.
|Anuric or oliguric renal failure||Gastrointestinal disease|
|Urinary obstruction||Congestive heart failure|
|Severe gastrointestinal disease||Hypothyroidism|
|Metabolic acidosis||Diabetes mellitus|
|Drugs (potassium-sparing diuretics, nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors)||Primary polydipsia|
|Inappropriate secretion of antidiuretic hormone|
|Pleural effusion||Third spacing|
|Pseudohyperkalemia of Akitas||Postobstructive diuresis|
10. What test is used for definitive diagnosis of hypoadrenocorticism?
Normal dogs may have low resting cortisol levels and so should not be assessed for the diagnosis of hypoadrenocorticism on this basis alone. An adrenocorticotropic hormone stimulation test is considered the gold standard for diagnosis of hypoadrenocorticism. Dogs with hypoadrenocorticism have low-to-low-normal resting serum cortisol levels and show little-to-no response to adrenocorticotropic hormone administration. The adrenocorticotropic hormone stimulation test does not differentiate between primary and secondary hypoadrenocorticism in atypical populations. Dogs with secondary hypoadrenocorticism have only glucocorticoid deficiency and do not develop electrolyte imbalances, whereas dogs with atypical primary hypoadrenocorticism eventually develop mineralocorticoid deficiency. Measurement of endogenous adrenocorticotropic hormone (eACTH) levels distinguishes between these two groups. Those with secondary hypoadrenocorticism have a low adrenocorticotropic hormone level, whereas those with primary hypoadrenocorticism have an elevated adrenocorticotropic hormone. Electrolytes should be monitored periodically in patients with primary atypical hypoadrenocorticism.
11. What is an addisonian crisis?
The term addisonian crisis refers to the development of clinical and biochemical abnormalities associated with acute hypoadrenocorticism and is characterized by vascular collapse and shock. Many patients also have ECG abnormalities associated with hyperkalemia. Approximately 35% of all dogs with hypoadrenocorticism are presented to the veterinarian with classic signs of shock, including obtundation, prolonged capillary refill times, pale mucous membranes, hypothermia, and weak, thready pulses. An important clinical feature is the presence of bradycardia in the face of vascular collapse, which suggests hyperkalemia. The ECG generally reveals atrial standstill or absence of P-waves, prolonged QRS duration, low R amplitude, and peaked T-waves. A small percentage of dogs exhibit some degree of atrioventricular (AV) block.
12. What are the goals of management of an acute adrenal crisis?
Mortality associated with hypoadrenocorticism is usually secondary to shock, hypotension, and hypovolemia rather than hyperkalemia. Therefore, the most important goal of therapy is fluid replacement. Place an intravenous catheter and collect baseline samples for a complete blood count, chemistry profile, serum cortisol levels, and urinalysis before starting intravenous fluids. Once the animal is volume-repleted, replacement of glucocorticoid deficits and correction of electrolyte imbalances, hypoglycemia, and acidosis can be addressed.
13. What is the fluid of choice for hypoadrenocorticism? How should it be administered?
Normal saline (0.9% NaCl) provides the greatest concentration of sodium and chloride in a physiologic intravenous fluid preparation. It has the added advantage of being potassium-free. To achieve volume repletion, to correct hypotension and hypovolemia, and to improve tissue perfusion, saline should be administered intravenous at approximately 40-80 ml / kg in the first hour, with adjustments according to the clinical picture. Fluid administration not only improves vascular parameters but also dilutes extracellular potassium concentrations, decreasing the risk of cardiac arrhythmias. The correction of dehydration with improvement of tissue perfusion may be adequate to correct acidosis. Once heart rate, pulse quality, CRT, and patient attitude improve, the continuing fluid rate is determined by individual requirements (e.g., degree of dehydration, sensible and insensible losses, maintenance needs). If normal saline is not available, a balanced electrolyte solution such as lactated Ringer’s, Normosol, or Plasmalyte may be used. Although these preparations contain potassium, concentrations are minimal, and the volume of fluid administered dilutes potassium concentration in the serum.
14. When should hyperkalemia be treated with something other than intravenous fluid replacement?
Opinions vary. However, it is agreed that if cardiac arrhythmias are present, hyperkalemia should be treated primarily. Others propose that if the potassium concentration is above 7-8 mEq / L, it should be treated with substances that decrease serum potassium concentrations or counteract the cardiac effects of hyperkalemia. Treatment of hyperkalemia is covered in site.
15. When should an adrenocorticotropic hormone stimulation test be performed in a crisis setting?
An adrenocorticotropic hormone stimulation test is a benign procedure and may be performed immediately. The resting cortisol level should be assessed when baseline blood samples are taken, aqueous synthetic adrenocorticotropic hormone is administered intravenous (IV), and poststimulation cortisol level is collected in 1 hour for dogs and in 30 and 60 minutes for cats. Because fluid replacement is the most important aspect of therapy, it is generally not detrimental to wait 1 hour before glucocorticoid therapy is instituted. However, if the clinician believes that glucocorticoids should be given immediately, dexamethasone should be used; it is the only commonly used glucocorticoid that is not detected in cortisol assays.
16. When in the course of therapy should glucocorticoids be given?
Because fluid replacement is the most important aspect of therapy, it generally does no harm to delay glucocorticoids until baseline blood samples are taken, the adrenocorticotropic hormone stimulation test is completed, and the initial shock dose of fluids is administered. Once volume expansion has been accomplished, glucocorticoid replacement should be addressed. Glucocorticoids should not be given until perfusion is improved. If it is not possible to perform an adrenocorticotropic hormone stimulation test during the initial management of an addisonian crisis, dexamethasone is the drug of choice for glucocorticoid replacement, as explained in the previous question.
17. Which glucocorticoids are recommended for replacement therapy?
1. Hydrocortisone hemisuccinate and hydrocortisone phosphate possess glucocorticoid as well as mineralocorticoid activity and therefore are recommended in an acute crisis. They are given at a dose of 2-4 mg / kg intravenous every 6-8 hours until shock is corrected, then at a dose of 0.5-1.0 mg / kg every 6-8 hours.
2. Prednisolone sodium succinate also possesses mild mineralocorticoid activity along with its glucocorticoid activity and is given at a dose of 4-20 mg / kg intravenous every 2-6 hours, depending on the response of the patient.
3. Dexamethasone sodium phosphate has only glucocorticoid activity and may be given initially at a dose of 0.5-2.0 mg / kg. Once the patient is no longer in shock, this dose is decreased to 0.04-0.1 mg / kg twice daily.
4. Once the patient is stable and eating voluntarily, maintenance glucocorticoid replacement is begun. Prednisone or prednisolone is given orally at an initial dose of 0.5-1.0 mg / kg, divided every 12 hours. This dose is decreased by 50% every week until the lowest dose that maintains the patient is reached. For animals with atypical hypoadrenocorticism, glucocorticoid therapy is lifelong. Patients that require mineralocorticoid therapy and receive fludrocortisone acetate, which also has some glucocorticoid activity, may not require daily prednisone. Patients receiving desoxycorticosterone pivilate (DOCP) require prednisone therapy for life. If signs of lethargy, anorexia, or depression recur, prednisone should be reinstituted at the physiologic dose of 0.22 mg / kg given daily or divided every 12 hours.
In times of stress animals with hypoadrenocorticism require additional glucocorticoids; thus, owners should keep either prednisone or prednisolone on hand.
18. When should mineralocorticoid replacement be instituted?
In the case of a crisis, saline administration corrects hyponatremia and hypochloremia and improves hyperkalemia while expanding the blood volume. Life-threatening hyperkalemia has already been addressed. Usually, nothing more is needed until the patient is rehydrated and eating voluntarily. However, in cases that are slow to respond to saline administration, hydrocortisone hemisuccinate or phosphate provides the mineralocorticoid activity needed to improve electrolyte imbalances until a maintenance mineralocorticoid regimen can be instituted.
19. How is maintenance mineralocorticoid replacement assessed?
Maintenance mineralocorticoid replacement may be given in one of two ways:
1. Fludrocortisone acetate, 0.1 mg / 10 lb / day orally in divided doses every 12 hours. (This drug has glucocorticoid activity and may not require the addition of prednisone.)
2. Desoxycorticosterone pivalate (DOCP), 1 mg / lb every 25-30 days IM.
Initially, electrolytes should be monitored every 5-7 days until they are stable. Once therapy is adequate, patients receiving fludrocortisone may be monitored every 4 — 6 months. After the first 1-2 weeks, animals receiving desoxycorticosterone pivalate are monitored on the 25th day of therapy. If electrolytes are normal at that time, the animal may need injection only every 28 or 30 days. Response to desoxycorticosterone pivalate is variable, and dosage and dosing interval must be tailored to each patient.
20. What other problems need to be addressed in dogs with an adrenal crisis?
1. Approximately 17% of patients are hypoglycemic at presentation; some have seizures. Hypoglycemia may be treated by adding dextrose to the saline infusion.
2. Metabolic acidosis is usually mild and may be corrected by volume expansion and improved tissue perfusion. However, if the acidosis is severe, sodium bicarbonate therapy may be required.
3. Renal function should be monitored closely by measuring urine output. If urine production does not meet or exceed 2-4 ml / kg / hr, diuresis with a constant-rate infusion of dopamine, 2-4 μg / kg / min, and furosemide, 2-4 mg / kg intravenous (IV), may be necessary.
4. Approximately 15% of hypoadrenal dogs present with melena. In some cases, gastrointestinal bleeding may be severe enough to be life-threatening and require blood transfusion. Such animals should be placed on gastric protectants such as sucralfate, H2 blockers, proton pump inhibitors, or synthetic prostaglandins. Packed cell volumes, platelet counts, and activated clotting times should be monitored closely. As odd as it seems, glucocorticoid therapy should not be withheld. It is postulated that the lack of physiologic glucocorticoids is the cause for loss of gastro-mucosal integrity and is necessary for healing.
21. What are the principal differences between hypoadrenocorticism in cats and dogs?
• There is no sex predilection in cats with hypoadrenocorticism.
• Diarrhea has not been reported in cats with hypoadrenocorticism.
• ECG abnormalities are uncommon in cats with hyperkalemia but present in 80% of dogs.
• Cats take 3-5 days to respond to therapy as opposed to 1-2 days for dogs.
• Serum cortisol concentrations in cats must be measured at 30 and 60 minutes after administration of aqueous adrenocorticotropic hormone and at 60 and 120 minutes after intramuscular administration of adrenocorticotropic hormone gel.