Hypoadrenocorticism

• Rare endocrine disease in cats.
• Cause: insufficient mineralocorticoid and glucocorticoid production.
• Diagnosis: ACTH stimulation test ACTH stimulation test.
• Treatment: hormonal replacement therapy.

• Weight loss.
• Anorexia.
• Lethargy/depression.
• Vomiting Vomiting.
• Collapse.
• Muscle weakness.
• Polyuria.
• Polydipsia.
• Dysphagia.

• Young to middle-aged (mean 6 years).

• Impaired adrenocortical function.
• Thought to be immune-mediated.
• Other reported causes:
  • Adrenal infiltration by lymphoma.
  • Trauma-induced.
  • Secondary hypoadrenocorticism caused by lymphocytic panhypophysitis has been reported in one case.
  • Iatrogenic secondary hypoadrenocorticism can occur following cessation of chronic corticosteroid treatment.
  • Atyical hypoadrenocorticism (lack of glucocorticoid production but not mineralocorticoids) reported in one case BUT aldosterone levels were not checked.

General

• Iatrogenic:
  • Bilateral adrenal excision (for treatment of hyperadrenocorticism Hyperadrenocorticism).
  • Withdrawal of high-level, prolonged corticosteroid treatment.

Aldosterone deficiency

• Reduced ability to conserve sodium and chloride and excrete potassium and hydrogen ions.
• Sodium loss may be further increased by vomiting/diarrhea and intake reduced by anorexia.  
• Depletion of total body salt stores leads to volume depletion.
• Reduced renal perfusion  → further increase in hyperkalemia  →  reduced myocardial excitability.

Glucocorticoid deficiency

• Reduced gluconeogenesis + fat metabolism may  →  hypoglycemia  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.

• Days to months.

• Depression.
• Weakness.
• Anorexia.
• Circulatory collapse.

• Lethargy/depression.
• Anorexia.
• Weight loss.
• Vomiting.
• Weakness (usually episodic).
• Waxing and waning clinical signs.
• Polyuria/polydipsia (adipsia also reported but rare).
• Dysphagia (rare).

• Depression.
• Weakness.

• Dehydration.
• Hypothermia Hypothermia.

• Weak pulse/slow capillary refill time.
• Collapse/inability to rise.

• Bradycardia.
• Abdominal pain.

Hematology

• Mild anemia (but may be masked by hemoconcentration): mean PCV 29.5% Hematology: packed cell volume.
• Lymphocytosis and eosinophilia can be seen (rare).

Biochemistry

(the mean value of biochemical parameters from a study that assessed 10 cats with hypoadrenocorticism are shown in brackets)

• Decreased [sodium] Blood biochemistry: sodium (130.6 mmol/L).
• Increased [potassium] Blood biochemistry: potassium (6.2 mmol/L).
• Na: K ratio (21.1).
• Decreased chloride Blood biochemistry: chloride (96.3 mmol/L).
• Increase in BUN Blood biochemistry: urea  (19.8 mmol/L).
• Increase in creatinine Blood biochemistry: creatinine (282.9 µmol/L).
• Increased phosphate Blood biochemistry: phosphate (2.4 mmol/L).
• Increased creatine kinase Blood biochemistry: creatinine phosphokinase.
• Acidosis.
• Increased calcium Blood biochemistry: ionized calcium (2.18 mmol/L).

Urinalysis

• SG Urinalysis: specific gravity: <1.030 (due to impaired concentrating mechanism) in the presence of azotemia.
  Some cats retain the ability to concentrate urine.

Hormonal assay

• ACTH stimulation test ACTH stimulation test (definitive).
• Plasma [cortisol] undetectable or low normal initially with a minimal to no response to ACTH.
• Normal levels:
  • Pre-ACTH 10-140 nmol/L.
  • Post-ACTH 140-415 nmol/L.
• Endogenous [ACTH] will be elevated in primary hypoadrenocorticism due to lack of negative feedback.

Radiography

• Microcardia - due to dehydration and hypovolemia.
• Hypoperfusion of lungs

ECG 

• Sinus bradycardia (not common) ECG: overview .
• Atrial premature complexes (not common).

• Adrenocortical atrophy and destruction.
• Adrenocortical infiltration and destruction (lymphoma).

• Hemolysis of sample may falsely elevate [potassium] with some automated analyzers.
• Urinary disease including acute renal failure Kidney: acute renal failure and urethral outflow obstruction.
• Gastrointestinal disease.
• Ascites/pleural effusion.
• Endocrine disease (including diabetes mellitus).

Causes of hypovolemia or shock can include

• Gastrointestinal disease.
• Acute and chronic blood loss.
• Repeated drainage of chylous and non-chylous pleural effusions Pleural effusion.

Acute crisis

• Rapid infusion of 0.9% saline over 2-4 hours to restore blood pressure and replace fluid deficits.
• Intravenous glucocorticoids: Perform ACTH stimulation test before administering glucocorticoids.
  • Hydrocortisone sodium succinate (2-4 mg/kg q4-8 h extrapolated from dogs) Hydrocortisone.
  • Dexamethasone sodium phosphate (0.1-2 mg/kg IV or IM q12 h) Dexamethasone.
• Continue IV fluids until electrolytes are stabilized and animal eating again.

Chronic

• Additional prednisolone may be needed at times of stress Prednisolone.
• If truly an atypical case, then glucocortocoids supplementation needed only.
• Water ad lib.

• Usually show rapid response to therapy (within 1-2 hours).
  Lethargy, weakness and anorexia may persist for 3-5 days after treatment started.
• [Sodium] and [potassium]: normalizing.
• Azotemia resolving.

Treatment

• Lifelong therapy.
• Regular monitoring of Na: K ratio.
• Increased dose of glucocorticoid during periods of stress.

• Excellent once adrenal crisis is controlled and not caused by lymphoma.
• If induced by trauma, hypoadrenocorticism may be transient.

• Initial therapy and monitoring not sufficiently aggressive.
• Owner not realizing importance of:
  • Lifelong therapy.
  • Regular monitoring.
  • Need to increase glucocorticoid dose during stress.

Refereed papers

• Recent references from PubMed and VetMedResource.
• Rudinsky A J, Clark E S, Russell D S et al (2015) Adrenal insufficiency secondary to lymphocytic panhypophysitis in a cat. Aus Vet J 93 (9), 327-331 PubMed.
• Woolcock A D & Ward C (2015) Successful treatment of a cat with primary hypoadrenocorticism and severe hyponatremia with desoxycorticosterone pivalate (DOCP). Can Vet J 56 (11), 1158-1160 PubMed. 
• Sicken J & Neiger R (2013) Addisonian crisis and severe acidosis in a cat: a case of feline hypoadrenocorticism. J Fel Med Surg 15 (10), 941-944 PubMed.
• Hock C E (2011) Atypical hypoadrenocorticism in a Birman cat. Can Vet J 52 (8), 893-896 PubMed.
• Bell R, Mellor D J, Ramsey I et al (2005) Decreased sodium:potassium ratio in cats: 49 cases. Vet Clin Pathol 34 (2), 110-114 PubMed.
• Gunn-Moore D (2005) Feline endocrinopathies. Vet Clin North Am Sm Anim Pract 35 (1), 171-210 PubMed.
• Smith S A, Freeman L C & Bagladi-Swanson M (2002) Hypercalcemia due to iatrogenic secondary hypoadrenocorticism and diabetes mellitus in a cat. JAAHA 38 (1), 41-44 PubMed.
• Stonehewer J & Tasker S (2001) Hypoadrenocorticism in a cat. JSAP 42 (4), 186-190 PubMed.
• Parnell N K, Powell L L, Hohenhaus A E et al (1999) Hypoadrenocorticism as the primary manifestation of lymphoma in two cats. JAVMA 214 (8), 1200, 1208-1211 PubMed.
• Peterson M E, Greco D S, Orth D N (1989) Primary hypoadrenocorticism in ten cats. JVIM 3 (2), 55-58 PubMed.

Other sources of information

• Scott-Moncrieff J C (2015) Hypoadrenocorticism. In: Canine and Feline Endocrinology. 4th edn. Feldman E C, Nelson R W, Reusch C R & Scott-Moncrieff J C (eds). St Louis, Missouri. Elsevier Saunders. pp 514-516.
• Scott-Moncrieff J C (2010) Hypoadrenocorticism. In: Textbook of Veterinary Internal Medicine. 7th edn. Ettinger S J & Feldman E C (eds). St Louis, Missouri. Elsevier Saunders. p 1857.