Canine hypoadrenocorticism

Canine hypoadrenocorticism . It is a rare endocrine disease in dogs characterized by adrenocortical hypofunction.

Summary

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• 1Tipos
  • 1 Primary hypoadrenocorticism (PAH)
  • 2 Secondary hypoadrenocorticism (SAH)
• 2Causas
• 3 Symptoms
• 4 Clinical Hallazgos
  • 1 Sex and age
• 5 Pathophysiology
  • 1 Glucocorticoid deficiency
  • 2 Mineralocorticoid deficiency
• 6 Diagnosis
  • 1 History and clinical signs
  • 2Hemograma
  • 3 Electrolyte abnormalities
  • 4 Kidney function
  • 5 Acid/base state
  • 6Glucemia
  • 7 Albuminemia
  • 8 Electrocardiographic abnormalities
  • 9 Radiographic signs
  • 10 Adrenal function tests
• 7 Treatment
  • 1 Serum therapy
  • 2Glucocorticoides
  • 3Mineralocorticoides
  • 4 Treatment of acidosis
  • 5 Treatment of hypoglycemia
  • 6 Treatment of severe hyperkalaemia
  • 7 Maintenance Treatment
  • 8Mineralocorticoides
  • 9Glucocorticoides
• 8 Prognostic
• 9Fuente

types

Primary hypoadrenocorticism (PAH)

It is the most prevalent form; its etiology is unknown, although immune-mediated destruction of the adrenal cortex is the most common histological sign. Other causes are:

• Infectiousdiseases (histoplasmosis, blastomycosis or tuberculosis).
• hemorrhagic infarction.
• metastatic neoplasm.
• Amiloidosis adrenal.
• Ketoconazoleor mitothane (p-DDD) intoxication.
• Megestrol acetate in cats(adrenal suppression).
• Genetic influences ( Standard Poodle , LabradorRetriever, Portuguese Water Spaniel ).

Adrenal destruction, in general, is a gradual process, with symptoms only in times of stress . As adrenal destruction progresses, hormone secretion becomes inappropriate even under non-stressful conditions, leading to a true metabolic crisis.

Secondary hypoadrenocorticism (SH)

It can be natural or iatrogenic. The natural form is due to the absence of normal adrenal stimulation by CRH or ACTH and denotes primary pituitary or hypothalamic failure.

Most of these cases are the result of hypothalamic or pituitary inflammation, tumors , trauma, or congenital defects.

The iatrogenic form is the most common form of SAH in veterinary medicine and occurs due to the exogenous administration of glucocorticoids, which suppress the normal production of pituitary ACTH, which promotes bilateral adrenal atrophy .

Causes

The most common cause of hypoadrenocorticism in the dog is an immune-mediated atrophy or destruction of the adrenal cortex. There are other less frequent causes of destruction of the adrenal cortex such as non-functional adrenal neoplasia , adrenal metastases , hemorrhages or adrenocorticolytic drugs .

Finally, although less frequently, hypoadrenocorticism of secondary (pituitary) origin may also occur, in which insufficient secretion of ACTH is the cause of hypocortisolism. According to the clinical presentation we consider two types of hypoadrenocorticism. The classic form is a deficiency of mineralocorticoids and glucocorticoids that we recognize when there is evidence of hypocortisolism and electrolyte disturbances ( hyponatremia and/or hyperkalemia ). On the other hand, the atypical form is characterized by a single glucocorticoid or single mineralocorticoid deficiency; This presentation is very rare.

Symptoms

• depression.
• Anorexia.
• Others: vomitingand diarrhea and PU/PD.

At the gastrointestinal level, anorexia, weight loss, nausea and vomiting are practically constant in patients and diarrhea is not uncommon, which is why it is often confused with gastrointestinal and/or kidney conditions. We can find bradycardia and weak pulse. In rare cases abdominal pain and hypothermia . Clinical signs may be intermittent, worsen in stressful situations, and improve later. Acute presentation of a hypotensive crisis and shock (Addisonian crisis) is also possible.

Acute adrenal insufficiency is suspected in critically ill patients with inadequate response to fluids and pressor agents. For an accurate diagnosis , not only adrenal hormone dosages but also a complete profile ( blood test ) are recommended.

clinical findings

gender and age

Hypoadrenocorticism is primarily a disease of middle-aged/elderly female dogs (76% of dogs are female). The age of presentation varies from 2 months to 15 years, with a mean of 4 to 5.4 years. Feline cases are exceptional. Differences have been seen in the age of diagnosis when comparing intact and castrated females; the mean age at diagnosis for intact females is 3 or 9 years, while for castrated females it is 5.9 years.

Although there is no increased risk based on breed or size, there is some evidence of a familial tendency in the Standard Poodle , Labrador Retriever , and Portuguese Water Spaniel . Castrated males are more likely to develop hypoadrenocorticism than intact males.

pathophysiology

Glucocorticoid deficiency

The lack of glucocorticoids produces anorexia , vomiting , abdominal pain , lethargy, hypoglycemia , and intolerance to stressful situations . Weight loss is due to anorexia, vomiting , and diarrhea ; if mineralocorticoid deficiency is also present, these signs worsen.

Hypoadrenocortidosis can cause normocytic-normochromic anemia . ACTH and adrenocortical hormones stimulate renal erythropoietin production, thus a cortisol deficiency leads to bone marrow suppression . Severely anemic dogs often have gastrointestinal ulcers that produce melena and hematemesis. Dehydration can mask anemia until fluids are replaced.

There may also be hypoalbuminemia and hypoglycemia ; the latter is due to lower production in the liver and increased sensitivity of peripheral cell receptors to insulin .

Mineralocorticoid deficiency

Mineralocorticoid deficiency may not produce clinical signs, but anorexia can lead to sudden worsening due to changes in potassium , sodium , and glucose concentrations , as well as inadequate cortisol release in response to stress .

Hyperkalemia and hyponatremia are caused by aldosterone deficiency , the inability of the kidneys to retain sodium and excrete potassium , and by movement of potassium from the intracellular to the extracellular compartment. Animals with secondary hypoadrenocorticism can secrete aldosterone and normally have normal serum concentrations of sodium and potassium. In animals that have low sodium concentration, this may be due to a high concentration of hormoneantidiuretic, whose synthesis and release is normally inhibited by glucocorticoids. Cardiac abnormalities are produced by hyperkalemia, and hyponatremia leads to hypovolemia , hypotension , and decreased cardiac output. The increase in liver enzymes may be due to hypoperfusion of the liver and the increase in BUN and creatinine are probably the result of renal hypotension and hypoperfusion.

Urinary density is often paradoxically low, especially in dogs with azotemia; due to sodium loss, the renal medulla loses its ability to concentrate urine, resulting in hyposthenuria versus dehydration. Shivering and esophageal dilation may be manifestations of generalized muscle weakness.

Diagnosis

History and clinical signs

A high index of suspicion is necessary because the history and clinical signs are nonspecific and easily confused with common disorders such as:

• Gastrointestinal diseases .
• Primary kidney failure .
• Other causes of acute collapse or episodic weakness ( cardiovascular disease, neuromuscular disorders, metabolic disturbances).

Blood count

Mild normocytic-normochromic anemia is common in dogs , although it may initially be masked by dehydration . The normal release of cortisol during stressful situations causes lymphopenia, eosinopenia, and neutrophilia . Instead, finding a normal leukogram in a stressed and shocked animal should alert us to the possibility of hypoedrenocorticism.

electrolyte abnormalities

The presumptive diagnosis of hypoadrenocorticism is based on the presence of hyponatremia , hypochloremia , hyperkalemia , and a sodium / potassium ratio . An abnormal ratio is not pathognomonic for hypoadrenocorticism. Any disease associated with severe sodium depletion can cause the ratio to become subnormal, while pathologies with hyperkalaemia also cause ratios and can be confused with hypoadrenocorticism. The most recognized causes for extraadrenal hyperkalemia include:

• Acute renal failure.
• Chronic kidney failure.
• Seriousdigestive diseases.
• metabolic acidosis.

A lesser identified cause for hyperkalemia/hyponatremia is seen in dogs with chylous and nonchylous pleural effusions. Pseudohyperkalemia has been observed in Akitas as a genetic abnormality particular to the breed: their red blood cells contain higher amounts of potassium than in most dogs.

Hyponatremia can occur in many diseases other than hypoadrenocorticism, including:

• Digestive losses due to vomiting.
• Hemorrhagic gastroenteritisand parvoviral enteritis .
• Nephrotic syndrome.
• Post-obstructive
• Primary heart failure or inappropriate HAO secretion.

About one-third of Addisonian dogs are hypercalcemic when they are hyperkalemic; hypercalcemia induces polyuria, polydipsia , and varying degrees of renal failure .

Renal function

Increases in NUS and creatinine and reduced renal concentrating ability are common in Addisonian dogs. NUS concentrations, together with urine specific gravity (which is often less than 1.030) can lead to the erroneous conclusion that primary renal failure exists. However, creatinine increases less than the NUS, supporting the existence of a prerenal component; both values ​​return to normal within 24-48 hours of adequate fluid therapy, and renal concentrating ability also returns to normal in almost all cases after appropriate medical management.

Acid/base state

In many dogs, there is a mild to moderate degree of metabolic acidosis , due to decreased renal excretion of protons in animals with mineralocorticoid deficiency. Fluid therapy and mineralocorticoid replacement correct the abnormality in most cases.

blood glucose

Hypoglycemia is rare, despite the importance of cortisol in maintaining baseline blood glucose concentrations . Hyperglycernia is sometimes recorded.

Albuminemia

Mild hypoalbuminemia has been reported on some occasions. The exact mechanism is speculative; It is now known that glucocorticoids influence hepatic albumin synthesis, and cortisol deficiency could impair such production.

Electrocardiographic abnormalities

ECG changes tend to parallel in magnitude with potassium; however, hyponatremia , hypercalcemia , hypoxia , and metabolic acidosis can also impair myocardial performance. Mild hyperkalemia (5.5 – 6.5 meq/L) is usually associated with a peaked T wave. When potassium levels reach values ​​of 8.5 meq/L, there is widening and flattening of the QRS complex, prolongation of the PR interval, reduction in the amplitude of the P wave and its longer duration. At levels >8.5 meq/L there is atrial arrest and ST-segment deviation, and when serum potassium is 11-14 meq/L, asystole or ventricular fibrillation is common.

radiographic signs

Chest radiographs may show microcardia and pulmonary hypoperfusion due to hypovolemia, and both the descending aorta and caudal vena cava appear reduced in size. Megaesophagus can sometimes be found, which resolves with corticosteroid therapy.

Adrenal function tests

Although the results of the complete blood count, biochemical profile, urinalysis, and ECG can support the diagnosis , the definitive diagnosis requires assessment of the integrity of the hypothalamic-pituitary-adrenal axis. The main tests to reach a definitive diagnosis are:

• ACTH stimulation test.

If the diagnosis is suspected and it is necessary to administer glucocorticoids before the test, the use of dexamethasone is recommended because it does not interfere with the analysis. For the study, ACTH gel of animal or synthetic origin can be used, and the protocol to follow is as follows:

1. In dogs, obtain a plasma or serum sample for cortisol analysis before and two hours after injecting 2.2 U/Kg of 1M ACTH gel. In cats, samples are collected at 60 and 120 minutes.
2. Synthetic aqueous ACTH (Fig. 2) is administered at a dose of 0.25 mg/dog or 0.125 mg/cat 1M, and post-dose plasma samples are obtained at 0 and 1 hour in dogs and at 30 and 60 minutes in dogs. cats.
3. The results of this test in Addisonian dogs and cats give basal levels in the low normal range that do not increase after the dose of ACTH. Normally, post- stimulation cortisolvalues ​​are less than 5 micrograms/dl’

• Endogenous ACTH concentration.

The results of stimulation with ACTH do not differentiate between PAH and SAH, for this it is necessary to measure the concentration of endogenous ACHT. The handling of the sample is decisive since this hormone is more labile than cortisol. Endogenous ACTH values ​​should be high in dogs with PAH, because there is no negative servomechanism from cortisol. Normal values ​​of endogenous ACTH are 20-100 pg/ml and the range in animals with PAH varies from 554 to 4950 pg/ml. Animals with natural or iatrogenic SAH have low or undetectable levels of endogenous ACTH.

• Cortisolemia basal.

This test should not be used as the sole criterion for establishing the diagnosis. Normal dogs can have a basal cortisol of zero, and Addisonian dogs occasionally show concentrations in the low normal range.

Treatment

The treatment will depend on whether it is an acute or chronic case, in chronic cases without crises, oral supplementation with corticosteroids (gluco and/or mineral) is generally established, however, once the diagnosis of acute adrenal insufficiency has been made, treatment should begin immediately.

Treatment must be aggressive, so that replacement begins after hydroelectrolytic therapy and the administration of hydrocortisone. Once severe manifestations are controlled, the steroid dose is gradually reduced and an oral maintenance dose of hydrocortisone or an equivalent dose of prednisone is instituted . A mineralocorticoid (fluorohydrocortisone 0.1 to 0.5 mg/day) is often used in canines.

Suerotherapy

Rapid intravenous administration of isotonic fluid is essential in the treatment of dogs with adrenal crisis because it helps correct hypovolemia, hyperkalemia, and acidosis. Circulating potassium concentrations are reduced both by simple dilution and by improved renal perfusion and glomerular filtration. Normal saline (0.9% NaCl) is the fluid of choice, because it does not contain potassium . Fluid therapy should be started at 20-40 ml/kg/hour for one or two hours. During the remainder of the 24-hour period, 60 mL/kg of saline should be administered. Fluid therapy is maintained until hydration, electrolytes, and azotemia return to normal, usually after 2 or 3 days of hospitalization .

Glucocorticoids

Intravenous administration of glucocorticoids is also essential in dogs with adrenal crisis. Fast-acting glucocorticoids, such as dexamethasone sodium phosphate (0.5 mg/kg), are recommended. This glucocorticoid can be used while performing the ACTH test, because dexamethasone is the only glucocorticoid that does not cross-react with serum cortisol determination. When the animal does not vomit and tolerates oral medication, a maintenance dose of 0.2 mg/kg/day with prednisone or prednisolone will be started.

Mineralocorticoides

Currently, we do not have a fast-acting parenteral mineralocorticoid to correct hyperkalaemia. However, the administration of serum and glucocorticoids will correct the potentially more lethal complications (hyperkalaemia, hypovolemia, hypotension, etc). Once vomiting and anorexia subside, oral mineralocorticoid supplementation can be instituted using fludrocortisone 0.01-0.02 mg/kg/day.

Treatment of acidosis

Mild to moderate metabolic acidosis is common in dogs with adrenal crisis and usually resolves with fluid administration and glucocorticoids. Although less frequent, severe metabolic acidosis (pH<7.15) may also occur, requiring treatment with sodium bicarbonate . A quarter of the calculated bicarbonate dose is administered with the serum for the first 6-8 hours, and then the acid-base status is reassessed.

Hypoglycemia treatment

Mild to moderate hypoglycemia is relatively common in dogs with hypoadrenocorticism and can be treated by adding dextrose to saline to a concentration of 2.5-5% dextrose . Symptomatic severe hypoglycemia should be treated with a slow intravenous dose of 0.5-1.0 mL/kg of 50% dextrose, followed by an infusion of 2.5-5% dextrose to maintain normoglycemia.

Treatment of severe hyperkalaemia

In most dogs with hypoadrenocorticism, rapid administration of intravenous fluids is sufficient to lower serum potassium concentration within 1 to 2 hours. However, if myocardial toxicity from hyperkalaemia is life-threatening, and in severe cases, regular intravenous insulin (0.25-0.5 u/kg) and glucose (2-3 grams per unit of insulin administered) are used to lower the potassium concentration. Half of the glucose is administered as a bolus and the rest in the intravenous fluid over 6-8 hours. In these cases, we must monitor hypoglycemia, since hypoadrenocorticism makes them extremely sensitive to the hypoglycemic action of insulin .

Maintenance Treatment

Most dogs with hypoadrenocorticism have chronic progressive disease and do not require hospitalization . Maintenance treatment consists of lifelong mineralocorticoid supplementation, usually coupled with glucocorticoid replacement therapy. The response to treatment is excellent in most cases.

Mineralocorticoides

Two alternatives are available for mineralocorticoid treatment: oral fludrocortisone therapy or deoxycorticosterone pivilate injections. Fludrocortisone is administered at an initial dose of 0.01-0.02 mg/kg/day in two divided doses, and the daily dose is adjusted based on clinical response and determination of urea and electrolytes (sodium and potassium). Initially, electrolytes are monitored weekly until they stabilize within the normal range.

Subsequently, during the following 3 to 6 months, monthly reviews should be carried out; then semi-annual controls will be carried out. Most dogs ultimately need 0.02 to 0.03 mg/kg/day. Adverse effects (polyuria and polydipsia) or inadequate disease controldespite normal or high doses may necessitate a switch from fludrocortisone to DOCP. DOCP treatment is started with an initial dose of 2.2 mg/kg intramuscularly or subcutaneously administered approximately at 4- week intervals . Serum electrolyte levels are determined at 2, 3, and 4 weeks post-injection to establish drug efficacy and duration of action . Once electrolytes are stabilized, levels should be determined just prior to each injection and the dose and frequency of DOCP administration adjusted to the lowest effective dose. Although most dogs require the drug at 3-4 week intervals, a few need injections every two weeks . This protocol satisfactorily controls most dogs and has no adverse effects.

Glucocorticoids

Glucocorticoid therapy (prednisone 0.2 mg/kg/day or hydrocortisone 0.5-1.0 mg/kg/day) is added to mineralocorticoid therapy. Because fludrocortisone has some glucocorticoid activity, the glucocorticoid dose can be decreased progressively until it is stopped indefinitely in half of the dogs . However, it is recommended to administer glucocorticoids during periods of stress (travel, etc).

Forecast

In general, the prognosis for dogs with hypoadrenocorticism treated with adequate hormonal support is excellent. The median survival time for these dogs is approximately 5 years and this is not affected by the type of mineralocorticoid, the cause of the hypoadrenocorticism, or the age, sex , or breed of the dog . Most of these dogs live normal lives and die of causes unrelated to Addison’s disease.