Canis ISSN: 2398-2942

Hypoadrenocorticism

Synonym(s): Addison's disease

Contributor(s): David Bruyette, Ian Ramsey, Emma Roberts

Introduction

  • Uncommon (reported prevalence 0.06-0.28%).
  • Cause: insufficient mineralocorticoid and/or glucocorticoid production.
  • Signs: inappetence, lethargy/depression, vomiting/diarrhea, weakness, shivering, polyuria, polydipsia, collapse.
  • Diagnosis: aldosterone and/or cortisol suppression on an ACTH stimulation test.
  • Treatment: hormonal supplementation (mineralocorticoids and glucocorticoids).
  • Prognosis: excellent once controlled.
Print off the owner factsheet on Addison's disease (hypoadrenocorticism) Addison's disease (hypoadrenocorticism) to give to your client.

Pathogenesis

Etiology

  • Destruction (spontaneous hypoadrenocorticism) of adrenal cortex leads to impaired secretion of mineralocorticoids and glucocorticoids.
  • Immune-mediated destruction is thought to be the most common cause though usually not diagnosed.
  • Other possible causes:
    • Idiopathic.
    • Necrosis.
    • Hemorrhagic infarction.
    • Metastatic neoplasia.
    • Amyloidosis Amyloidosis.
    • Granulomatous destruction, eg blastomycosis Blastomycosis, histoplasmosis Histoplasmosis, cryptococcosis Cryptococcosis.
    • Drug induced, eg mitotane, ketoconazole, trilostane (idiosyncratic).
  • Secondary hypoadrenocorticism also reported both spontaneous and iatrogenic (rapid withdrawal of chronic corticosteroid treatment).
  • Hypoadrenocorticism may form part of a polyglandular autoimmune syndrome in some dogs, which can also include hypothyroidism, hypoparathyroidism and diabetes mellitus.

Predisposing factors

General

  • Breed.
  • Drug therapy, eg mitotane, or withdrawal of drug therapy, eg prednisolone.

Pathophysiology

Aldosterone deficiency

  • Leads to a reduced ability to conserve sodium and chloride and excrete potassium and hydrogen ions.
  • Sodium loss may be further increased by vomiting/diarrhea and reduced intake, ie anorexia.
  • Loss of sodium and chloride leads to loss of water concurrently and volume depletion, reduced cardiac output and decreased glomerular filtration rate.
  • Reduced perfusion to the gastrointestinal tract can potentially lead to gastrointestinal ulceration, and acute pancreatitis.
  • Reduced renal perfusion → increased hyperkalemia → reduced myocardial and muscle excitability → bradycardia and weakness.

Glucocorticoid deficiency

  • Reduced glucogenesis + fat metabolism may → hypoglycemia.
  • Reduced cortisol to the CNS may lead to lethargy and depression.
  • Cortisol also required for intestinal integrity and reduction contributes to vomiting, diarrhea and inappetence.
  • Cortisol stimulates appetite and red blood cell production, therefore deficiency can result in inappetence and anemia.
  • In 1° adrenal insufficiency → increased ACTH secretion from pituitary → impaired tolerance to stress.

Atypical hypoadrenocorticism

  • Cases of hypoadrenocorticism in which only glucocorticoid deficiency is present. Previously classified as atypical when the typical electrolyte changes were not present, ie hyperkalemia and/or hyponatremia, however recent work has shown that cases of typical hypoadrenocorticism do not always have electrolyte abnormalities.
  • These cases tend to be older at the time of diagnosis and have a longer duration of clinical signs when compared to cases of typical hypoadrenocorticism.
  • More likely to be anemic, hypoalbuminemic and hypocholesterolemic than typical hypoadrenocorticism cases.
  • Diagnosis in these cases is particularly difficult and clinical signs can include lethargy, severe gastrointestinal disease (often hemorrhage), weight loss and regurgitation secondary to megaesophagus.
  • Diagnosis is based on evidence on lack of cortisol but not aldosterone stimulation on an ACTH stimulation test.
  • These cases may progress over time to become deficient in mineralocorticoids as well, however, in some cases animals have been monitored for several years with no development of electrolyte abnormalities.

Secondary hypoadrenocorticism

  • Caused by lack of production of ACTH by the pituitary gland. This can be idiopathic or due to lesions in the hypothalamus or pituitary caused by head trauma, neoplasia or inflammation.
  • This can also occur due to rapid withdrawal of chronic corticosteroid treatment (iatrogenic).
  • Results in lack of glucocorticoid production only.

Timecourse

  • May have an insidious onset over months to years with waxing and waning clinical signs.
  • Often present in acute crisis with circulatory collapse.

Diagnosis

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Treatment

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Gunn E, Shiel R E, & Mooney C E (2016) Hydrocortisone in the management of acute hypoadrenocorticism in dogs: a retrospective series of 30 cases. JSAP, 57 (5), 227-233 PubMed.
  • Roberts E, Boden L A & Ramsey I K (2016) Factors that affect stabilisation times of canine spontaneous hypoadrenocorticism. Vet Rec 179 (4), 98 PubMed.
  • Boretti F S, Meyer F, Burkhardt W A, Riond B, Hofmann-Lehmann R, Reusch C E & Sieber-Ruckstuhl N S (2015) Evaluation of the cortisol-to-ACTH ratio in dogs with hypoadrenocorticism, dogs with diseases minicking hypoadrenocorticism and in healthy dogs. JVIM 29 (5), 1335-1341 PubMed.
  • Baumstark M E, Nussberger J, Boretti F S, Baumstark M W, Riond B, Reusch C E & Sieber-Ruckstuhl N S (2014) Use of plasma renin activity to monitor mineralcorticoid treatment in dos with primary hypoadrenocorticism: desoxycorticosterone versus fludrocortisone. JVIM 28 (5), 1471-1478 PubMed.
  • Baumstark M E, Sieber-Ruckstuhl N S, Muller C, Wenger M, Boretti F S & Reusch C E (2014) Evaluation of aldosterone concentrations in dogs with hypoadrenocorticism. JVIM 28 (1), 154-159 PubMed.
  • Bovens C, Tennant K, Reeve J & Murphy K F (2014) Basal serum cortisol concentration as a screening test for hypoadrenocorticism in dogs. JVIM 28 (5), 1541-1545 PubMed.
  • Lathan P, Scott-Moncrieff J C & Wills R W (2014) Use of the Cortisol-to-ACTH Ratio for Diagnosis of Primary Hypoadrenocorticism in Dogs. JVIM 28 (5), 1546-1550 PubMed.
  • Zeugswetter F K & Schwendenwein I (2014) Diagnostic efficacy of the leukogram and the chemiluminometric ACTH measurement to diagnose canine hypoadrenocorticism. Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere, 42 (4), 223-230 PubMed.
  • Wenger M, Mueller, C, Kook, P H & Reusch C E (2010) Ultrasonographic evaluation of adrenal glands in dogs with primary hypoadrenocorticism or mimicking diseases. Vet Rec 167 (6), 207-210 PubMed.
  • Neilsen L, Bell R, Zoia A, Mellor D, Neiger R & Ramsey I (2008) Low ratios of sodium to potassium in the serum of 238 dogs. Vet Rec 162 (14), 431-435 PubMed.
  • Tag T L & Day T K (2008) Electrocardiographic assessment of hyperkalemia in dogs and cats. Journal of Veterinary Emergency and Critical Care 18 (1), 61-67 VetMedResource.
  • Adler J A, Drobtaz K J & Hess R S (2007) Abnormalities of serum electrolyte concentrations in dogs with hypoadrenocorticism. JVIM 21 (6), 1168-1173 PubMed.
  • Hughes A M, Nelson R W, Famula T R, & Bannasch D L (2007) Clinical features and heritability of hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers: 25 cases (1994-2006). JAVMA 231 (3), 407-412 PubMed.
  • Thompson A L, Scott-Moncrieff J C & Anderson J D (2007) Comparison of classic hypoadrenocorticism with glucocorticoid-deficient hypoadrenocorticism in dogs: 46 cases (1985-2005). JAVMA 230 (8), 1190-1194 PubMed.
  • Javadi S, Galac S, Boer P, Robben J H, Teske E & Kooistra H S (2006) Aldosterone-to-renin and cortisol-to-adrenocorticotropic hormone ratios in healthy dogs and dogs with primary hypoadrenocorticism. J Vet Intern Med 20 (3), 556-561 PubMed.
  • Oberbauer A M, Bell J S, Belanger J M, & Famula T R (2006) Genetic evaluation of Addison’s disease in the Portuguese Water Dog. BMC Veterinary Research, 2, 15 PubMed.
  • Famula T R, Belanger J M & Oberbauer A M (2003) Heritability and complex segregation analysis of hypoadrenocorticism in the standard poodle. JSAP 44 (4), 8-12 PubMed.
  • Oberbauer A M, Benemann K S, Belanger J M, Wagner D R, Ward J H, & Famula T R (2002) Inheritance of hypoadrenocorticism in Bearded Collies. Am J Vet Res 63 (5), 643-647 PubMed.
  • Schaer M, Halling K B, Collins K E & Grant D C (2001) Combined hyponatremia and hyperkalemia mimicking acute hypoadrenocorticism in three pregnant dogs. JAVMA 218 (6), 897-900 PubMed.
  • Melián C, Stefanacci J, Peterson M E, & Kintzer P P (1999) Radiographic findings in dogs with naturally-occurring primary hypoadrenocorticism. JAAHA 35 (3), 208-212 PubMed.
  • Syme H M & Scott-Moncrieff J C (1998) Chronic hypoglycemia in a hunting dog due to secondary hypoadrenocorticism. JSAP 39 (7), 348-351 PubMed.
  • Kintzer P P & Peterson M E (1997) Treatment and long-term follow-up of 205 dogs with hypoadrenocorticism. JVIM 11 (2), 43-49 PubMed.
  • Lifton S J, King L G & Zerbe C A (1996) Glucocorticoid deficient hypoadrenocorticism in dogs - 18 cases (1986-1995). JAVMA 209 (12), 2076-2081 PubMed.
  • Peterson M E, Kintzer P P & Kass P H (1996) Pretreatment clinical and laboratory findings in dogs with hypoadrenocorticism - 225 cases (1979-1993). JAVMA 208 (1), 85-91 PubMed.
  • Sadek D S & Schaer M (1996) Atypical Addison's disease in the dog - a retrospective survey of 14 cases. JAAHA 32 (2), 159-163 PubMed.
  • Schaer M & Chen C L (1983) A clinical survey of 48 dogs with adrenocortical hypofunction. JAAHA 19 (4), 443-452 VetMedResource.

Other sources of information

  • Scott-Moncrieff J C (2015) Hypoadrenocorticism. In: Canine and Feline Endocrinology. 4th edn. Eds Feldman E C, Nelson R W, Reusch C E & Scott-Moncrieff J C. St Louis, Missouri: Elsevier Saunders. pp 485-514
  • Scott-Moncrieff J C (2010) Hypoadrenocorticism. In: Textbook of Veterinary Internal Medicine, 7th edn. Eds Ettinger S J & Feldman E C. St Louis, Missouri: Elsevier Saunders. pp 1847-1857
  • Feldman E C & Nelson R W (2004) Hypoadrenocorticism Addisons Disease. In: Canine and Feline Endocrinology and Reproduction. 3rd edn. St Louis, Missouri, Saunders Elsevier, pp 394-439.
  • Ramsey I (2003) Diagnosis and treatment of canine hypoadrenocorticism. In Practice 25, 18-25.
  • Feldman E C & Peterson M E (1984) Hypoadrenocorticism. Vet Clin N Am 14, pp 751.


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