Addison's disease is a very serious disease and the changes it causes can be understated in the primary stages. The clinical signs of the illness are variable and most of the time vague. An early diagnosis is important since, with proper management and treatment, affected animals can lead a normal, full life.
Definition of Addison's disease
Addison's disease happens when dogs fail to produce enough of the hormone cortisol, and in some cases, the hormone aldosterone. The disease is therefore referred to as "hypoadrenocorticism" or "hypocortisolaemia" sometimes. The disease was discovered and named after a 19th-century English physician called Thomas Addison.
Ordinarily, cortisol and aldosterone are produced by the adrenal glands (which are located just in front of the kidneys). Cortisol has many possible effects in the body. As such, the amount of cortisol produced by the adrenal glands must be balanced precisely for a healthy body. Cortisol production is controlled by hormones manufactured in the brain (from the pituitary) which stimulate the adrenal glands. Once the adrenal glands receive the signal from the pituitary, the response is by producing cortisol. Cortisol is a stress hormone important in helping the body respond to anxiety, pressure and tension. In Addison's disease, the body is incapable of producing enough cortisol and involved animals become ill at times of stress.
Aldosterone maintains blood pressure, water and salt balance in the body by enabling the kidneys to retain sodium and excrete potassium. When production of aldosterone falls too low, the kidneys cannot regulate salt and water balance, causing blood volume and blood pressure to drop.
Causes of Addison's disease
Addison's disease is usually caused by excessive suppression or damage to the adrenal glands. This leads to the impairment of both mineralocorticoids and glucocorticoids. Immune-mediated destruction of the outer layer of the adrenal glands is very common, though rarely diagnosed. Other probable causes include: -
Necrosis.
Haemorrhage.
Tumour.
Amyloidosis.
Idiopathic.
Drugs, e.g. mitotane, ketoconazole, trilostane (idiosyncratic).
Withdrawal of high-level, prolonged corticosteroid treatment (glucocorticoid insufficiency).
Clinical Signs of Addison's disease
Clinical signs of Addison's disease are awfully variable and subtle in the early stages. The disease generally affects younger dogs and females are more at risk than males at a ratio of 1:2, male:female. The disease is also commonly hereditary in some breeds of dog e.g. e.g. Standard Poodles, Bearded Collies, Rottweilers and West Highland White Terriers. the disease is more common. The disease is not easily recognised by many owners; however, they are aware that their pet is 'not quite right'. Addison’s disease should always be suspected if the pet suffers from recurrent illness (particularly vomiting or diarrhoea) but recovers quickly when treated with intravenous fluids and steroids.
As steroid hormones affect almost every tissue in the body, the signs of Addison's disease can be varied. The signs of adrenal insufficiency usually commence gradually. Chronic, worsening fatigue and muscle weakness, loss of appetite and weight loss are characteristic of the disease. Dogs may be depressed, lethargic or unwilling to exercise (and sometimes it’s not even noticed how quiet they have become, confusing the signs of disease with the dog 'maturing').
Gastrointestinal problems (with vomiting and/or diarrhoea) that get better and then recur is a common sign. Episodes of collapse or muscle weakness may be reported. Addison's disease can cause increased thirst, with the dog drinking more (or suddenly getting up in the night to urinate). Low blood sugar can also be a problem in toy breeds or young dogs. Female dogs may fail to come into season (heat). Because the signs progress slowly, they are usually ignored until a stressful event like an illness or an accident causes them to become worse.
If the disease is unrecognised, a very severe form develops called an Addisonian crisis. Frequently this begins with vomiting or diarrhoea, but progresses rapidly resulting in collapse and possibly coma. Pets can die without urgent treatment. In some dogs, there are no signs at all until an Addisonian crisis develops.
Diagnosing the disease
Addison's disease can be difficult to diagnose in its early stages. A review of the dog's medical history is important to help suspect Addison's disease. The disease can be suspected based on simple blood tests but specific blood tests are needed to confirm the disease. These tests measure the level of cortisol in the blood. However, because the levels of this hormone vary from hour to hour in the normal animal, the disease cannot be diagnosed based on one blood test. Several blood samples (before and after an injection of a hormone which mimics the action of the pituitary to stimulate the dog's adrenal glands to produce cortisol) need to be taken. These blood samples need to be sent to a veterinary laboratory for analysis. If the dog is unable to increase the amount of cortisol in the blood after the injection, then it is clear that its adrenal glands are not working properly.
Other blood tests can also be used which in collaboration with the one above, will confirm Addison’s disease. These include: -
Haematology
Haemoconcentration (increased PCV, increased [plasma protein]).
Chronic form: -non-regenerative anaemia (which may be masked by haemoconcentration).
Severe anaemia if gastrointestinal haemorrhage.
May also develop severe anaemia due to concomitant - immune mediated haemolytic anaemia.
Occasionally lymphocytosis and eosinophilia
Biochemistry
Decreased [sodium] (81%): <135 mmol/l.
Increased [potassium] (96%).
Na:K ratio <27:1
Other causes of electrolyte abnormalities include GI, renal and cardiac disease.
At higher concentrations of potassium (more than 6.5), lower concentrations of sodium (less than 135) and lower Na:K ratios (less than 19) the diagnosis of Addison’s becomes more likely. However, cannot rely on electrolyte concentrations to confirm the diagnosis of Addison’s.
Decreased chloride. Serum electrolytes may be normal if dog evaluated when clinical signs minimal.
Increased [urea]; normal excretory index (prerenal failure).
Mild to moderate acidosis.
Increased [calcium].
Hypoglycaemia
X-rays may also be needed to show other potential problems caused by the disease.
Treatment
Treatment of Addison's disease encompasses replacing, or substituting, the hormones that the adrenal glands are not making. Oral steroid tablets (prednisone, prednisolone, dexamethasone) are given to replace cortisol, and Desoxycorticosterone pivalate (DOCP) injections or Florinef tablets to replace aldosterone. Tablets are administered daily to supplement the missing hormones. The doses of each of these medications are adjusted to meet the needs of individual patients.
During an Addisonian crisis, low blood pressure, low blood sugar and high levels of potassium can be life-threatening. Standard therapy involves intravenous injections of hydrocortisone and a saline (salt water) drip. This treatment usually brings rapid improvement. When the patient can take fluids and medications by mouth, the intravenous treatment is decreased until and maintenance therapy is begun. In fact, once stabilised, many dogs require only Florinef tablets daily. If injectable DOCP is used to replace aldosterone, the pet will likely also require supplemental oral replacement steroid tablets.
Most dogs with Addison's disease are comparatively young and the signs of disease will get worse as they get older. Even if a problem hasn't been noticed with your dog, you may see dramatic improvement when treatment starts. Routine blood tests are taken two or three times a year to ensure that treatment does not need to be altered. Many dogs will go on to live a normal lifespan. Without treatment, the complications can be significant and will seriously affect the quality of your pet's life.
References
Pre-trilostane and three-hour post-trilostane cortisol to monitor trilostane therapy in dogs. Macfarlane L, Parkin T, Ramsey I. Vet Rec. 2016 Nov 1. pii: vetrec-2016-103744. doi:10.1136/vr.103744.
Evaluation of Basal Serum or Plasma Cortisol Concentrations for the Diagnosis of Hypoadrenocorticism in Dogs.Gold AJ, Langlois DK, Refsal KR. J Vet Intern Med. 2016 Oct 7. doi: 10.1111/jvim.14589.
Cardiogenic Pulmonary Edema in a Dog Following Initiation of Therapy for Concurrent Hypoadrenocorticism and Hypothyroidism. Paik J, Kang JH, Chang D, Yang MP. J Am Anim Hosp Assoc. 2016 Sep 29.
[Transient, secondary hypoadrenocorticism after treatment with delmadinone acetate (Tardastrex®) in a two year old male dog]. Kempker K, Güssow A, Neiger R. Schweiz Arch Tierheilkd. 2016 Mar;158(3):193-7. doi: 10.17236/sat00056. German.
Polyglandular endocrinopathy type II (Schmidt's syndrome) in a Dobermann pinscher. Cartwright JA, Stone J, Rick M, Dunning MD. J Small Anim Pract. 2016 Sep;57(9):491-4. doi: 10.1111/jsap.12535.
Hypoadrenocorticism mimicking protein-losing enteropathy in 4 dogs. Lyngby JG, Sellon RK. Can Vet J. 2016 Jul;57(7):757-60.
Perioperative Management and Outcome of Bilateral Adrenalectomy in 9 Dogs. Oblak ML, Bacon NJ, Covey JL. Vet Surg. 2016 Aug;45(6):790-7. doi: 10.1111/vsu.12514.
Factors that affect stabilisation times of canine spontaneous hypoadrenocorticism. Roberts E, Boden LA, Ramsey IK. Vet Rec. 2016 Jul 23;179(4):98. doi: 10.1136/vr.103663.
Hydrocortisone in the management of acute hypoadrenocorticism in dogs: a retrospective series of 30 cases. Gunn E, Shiel RE, Mooney CT. J Small Anim Pract. 2016 May;57(5):227-33. doi:10.1111/jsap.12473.
Clinical features of hypoadrenocorticism in soft-coated wheaten terrier dogs: 82 cases (1979-2013). Haviland RL, Toaff-Rosenstein RL, Reeves MP, Littman MP. Can Vet J. 2016 Apr;57(4):387-94.
Naturally Occurring Adrenocortical Insufficiency--An Epidemiological Study Based on a Swedish-Insured Dog Population of 525,028 Dogs. Hanson JM, Tengvall K, Bonnett BN, Hedhammar Å. J Vet Intern Med. 2016 Jan-Feb;30(1):76-84. doi: 10.1111/jvim.13815.
