ABSTRACT: Hypoadrenocorticism or Addison's disease is a condition affecting the adrenal glands, whereby the production of hormones from the adrenal cortices is reduced as a result of immune-mediated destruction of the glandular tissue. This leads to clinical disease including malaise, gastro-intestinal upset and potentially life-threatening shock and electrolyte disturbance. Presentation can be vague which requires good clinical awareness to be alert to the diagnosis, but treatment is straightforward and often rewarding.
Hypoadrenocorticism, or Addisons disease, is an uncommon endocrine disease of dogs and, very occasionally, cats which involves an atrophy and under-activity of the adrenal glands. Despite its rarity, it is essential that veterinary professionals are alert to its clinical signs, which are often vague, as failure to diagnose this life-threatening condition can lead to avoidable death.
What are the adrenal glands?
The adrenal glands are a pair of hormone-producing glands, located in the abdomen just in front of each kidney. Each gland has two parts – cortex and medulla. Hypoadrenocorticism affects the adrenal cortex and comprises a deficiency of glucocorticoid hormones and mineralocorticoid hormones (including aldosterone).
Cortisol is an important hormone in the body having a wide range of roles including normal function of the immune system, muscles and nerves, gastro-intestinal tract and the healing process. Aldosterone is integral to the regulation of the body’s water, sodium and potassium balance via the kidneys.
What causes hypoadrenocorticism?
The majority of cases of hypoadrenocorticism are thought to occur as a result of immune- mediated destruction of the adrenal cortex, where the body produces auto¬antibodies against the glandular tissue. Other causes may include trauma and vascular disease. The lack of cortisol will stimulate production of more and more adrenocorticotrophic hormone (ACTH) by the pituitary gland; however, this has no effect as the tissue of the adrenal glands is dysfunctional.
Very occasionally, hypoadrenocorticism may occur as the result of a brain lesion that destroys the pituitary gland and its ability to produce ACTH, leading to a lack of stimulation of the adrenal glands. Such cases are termed secondary hypoadrenocorticism.
What are the clinical signs?
Hypoadrenocorticism can be a difficult disease to diagnose because, often, the clinical signs are very vague and, once they become more obvious, the patient may be critically ill.
Lack of cortisol leads to significant dysfunction of the gastro-intestinal system, with anorexia, vomiting and diarrhoea being common sequelae. Affected animals are very depressed and are often presented with the owner reporting them to be “severely off-colour”, possibly without other signs (Figure 1).
Figure 1: Affected animals are very depressed and are often presented with the owner reporting them to be “severely off-colour
These signs may be mistaken for gastroenteritis and affected animals given corticosteroids (such as dexamethasone) for treatment. This temporarily replaces cortisol and alleviates the clinical signs. Animals with hypoadrenocorticism often have a history of repeated bouts of vomiting and diarrhoea.
Lack of aldosterone leads to an inability to regulate the balance of water, sodium and potassium. Levels of sodium (hyponatraemia) and water fall, so that the circulating blood volume falls and the animal becomes shocked – this may be observed as a small heart silhouette if chest radiography is performed.
Meanwhile, potassium levels rise (hyperkalaemia) and cause disturbance of cardiac rhythm which can be seen on ECG – the heart rate slows markedly and the pattern shows characteristic loss of P waves, widened QRS complexes and tall, spiked T waves (Figure 2).
Figure 2: The heart rate slows markedly and the pattern shows characteristic loss of P waves, widened QRS complexes and tall, spiked T waves
Some patients with hypoadrenocorticism present with a vague history of inappetence, vomiting or diarrhoea, but those that become shocked, hyponatraemic and hyperkalaemic are usually collapsed and this state is termed an Addisonian crisis’.
How is the diagnosis confirmed?
The challenge of diagnosis is to screen patients with appropriate histories of repeated malaise and gastro-intestinal disturbance in order to achieve diagnosis before an Addisonian crisis develops. Once more severe signs develop; the slow heart rate, shock and collapse often highlight the diagnosis more clearly.
Routine blood panels will show hyperkalaemia and hyponatraemia; but whilst these changes are highly suggestive of hypoadrenocorticism, they do not confirm the diagnosis, as this electrolyte pattern can be seen with other conditions, such as severe vomiting and diarrhoea or acute renal failure.
Affected animals usually show raised urea and creatinine, reflecting the reduction in blood flow into the kidneys. This and the frequency of gastro-intestinal signs can lead to confusion as to whether they are cause’ or ‘effect’ of the electrolyte disturbance.
Diagnosis, therefore, always requires confirmation with an ACTH stimulation test. Blood cortisol levels are measured before and one hour after the injection of synthetic ACTH (Synacthen, Alliance Pharmaceuticals).
A normal response involves a significant increase in cortisol, but cases of hypoadrenocorticism will show a flat-line response, because the adrenal tissue is not functioning properly to produce cortisol in response to ACTH.
The previous use of corticosteroid drugs can lead to false positive diagnoses for hypoadrenocorticism as the medication can suppress the adrenal glands such that they cannot respond to ACTH. This should be taken into account by the clinician when attempting to confirm a diagnosis.
What is the treatment?
Whilst diagnosis may be a challenge, treatment is, thankfully, relatively straightforward and, provided the diagnosis is made quickly, is usually successful.
Critically ill animals will require intensive care. Intravenous preparations of corticosteroids are administered to replace the absent cortisol. Administration of normal saline fluid therapy corrects the lack of sodium and water, whilst starting to dilute the excessive potassium.
Potassium may be reduced further by the administration of soluble insulin intravenously, which stimulates the movement of potassium as well as glucose from the circulation and into cells – glucose must be administered concurrently to avoid hypoglycaemia.
Once the animal is able to receive oral medication, glucocorticosteroid replacement is continued with oral prednisolone or cortisone acetate. In the long term, however, this may only continue to be necessary at times ot stress, such as kennelling or surgery.
Aldosterone is substituted by oral fludrocortisone (Florinef, Bristol Meyer Squibb) which stimulates the kidneys to continue to retain water and sodium, whilst excreting potassium; additionally fludrocortisone has some glucocorticoid activit
y and so may minimise the need for oral prednisolone or cortisone acetate as well. Therapy with fludrocortisone will be required forever.
An alternative to fludrocortisone is monthly depo-injections of desoxycorticosterone which has the same effect, but is less commonly used.
Patients receiving treatment should be monitored regularly, in particular with respect to relapse in electrolyte levels and renal function, so that dose alterations can be made before another Addisonian crisis develops. Nonetheless, even with close monitoring, further crises can occur, usually at times of stress, and owners should be educated as to the early signs so that they may present their pet to the surgery in good time.
Prognosis
Addison’s disease is a life-threatening condition and mortality rates will be high if the diagnosis is not made promptly. However, once diagnosed, treatment is extremely rewarding in most cases and, with proper care and monitoring, most patients will live their normal lives.
Conclusion
This article gives an overview of a rare, but important, disease seen in veterinary practice. The possibility of hypoadrenocorticism can easily be overlooked and diagnoses are often made unexpectedly when routine panels from patients with non-specific signs show appropriate electrolyte changes. The presence of a veterinary nurse with an awareness of the disease can be very helpful in provoking consideration of the diagnosis in the whole veterinary team.
Author
Mark Maltman BVSc CertSAM CertVC MRCVS
Mark Maltman qualified in 1997 from the University of Bristol and has practised for 13 years in Horsham, West Sussex. He has gained the RCVS Certificates in Small Animal Medicine [2001) and Veterinary Cardiology [2004). He is now a partner at Maltman Cosham Veterinary Clinic in Horsham.
To cite this article use either
DOI: 10.1111/j.2045-0648.2011.00050.x or Veterinary Nursing Journal Vol 26 pp 201-203
• VOL 26 • June 2011 • Veterinary Nursing Journal