Hyperadrenocorticism diagnosis and treatment

• Types of hyperadrenocorticism types overview

  Pituitary dependent (80-90%)

  • Micro and macro adenomas, adenocarcinomas.
  • Subgroup pars intermedia

  Adrenal dependant (10-20%)

  • Functional adrenal adenomas and carcinomas.

  Iatrogenic

  • Exogenous steroids
• Canine hyperadrenocorticism - presentation and clinical signs

  Middle aged to old dogs.

  More females than males.

  Polydipsia, Polyuria - secondary diabetes insipidus.

  Polyphagia

  Muscle wasting and weakness (pot-belly, panting)

  Skin thinning, calcinosis cutis, pigmentation, bruising.

  Symmetrical hair loss.

  Reproductive dysfunction.
• Canine hyperadrenocorticism - radiographic findings

  Abdominal radiographs:

  • Good contrast
  • Hepatomegaly
  • Pot-bellied appearance
  • Calcinosis bladder
  • Can’t see abdominal contrast due to fat distribution.

  Thoracic radiographs:

  • Tracheal and bronchial mineralisation.
  • Pulmonary metastasis
  • Osteoporosis - animals are demineralised in their bone in general.
• Canine hyperadrenocorticism - screening laboratory tests

  Non-specific findings:

  • Urinalysis
  • Haemotology
  • Biochemistry
  • Supports the diagnosis of HAC
  • Eliminated other diseases
  • May refute HAC.
• Canine hyperadrenocorticism - Haematology

  We could expect:

  • Stress leukogram:
  • Nuetrophila (mature)
  • Lymphopaenia
  • Monocytosis
  • Absolute eosinopaenia

  Cause to question HAC diagnosis or complicated

  • Neutropaenia
  • Lymphocytosis
  • Band neutrophils
  • Eosinophils present
  • Anaemia
• Canine hyperadrenocorticism - clinical chemistry

  Increased alkaline phosphatase activity - there is a steroid induced isoform in the dog.

  Increased ALT activity

  Hyperglycaemia - hepatic gluconeogenesis, insulin sensitivity.

  Elevated phosphorus - steroid effect on bone turnover.

  Increased cholesterol and triglyceride - steroid effect of lipid metabolism.

  Mildly abnormal bile acids.
• Canine hyperadrenocorticism - urinalysis

  We could expect:

  • Urine specific gravity <1.030 despite often mild dehydration.
  • Mild glucosuria in some cases.
  • Proteinuria in some cases.
  • Positive urine culture
  • Reduced immune function
  • Glucosuria
• Endocrine diagnostic tests

  Diagosis:

  • Low dose dexamethasone
  • ACTH response
  • Urinary cortisol: creatinine ration
  • Steroid induced alkaline phosphatase.

  Differentiation:

  • Dexamethasone suppression (low, high and mega)
  • Endogenous ACTH
• Canine hyperadrenocorticism - low dose dexamethasone

  Resistance of abnormal pituitary-adrenal axis to suppression by dexamthasone.

  0.01 to 0.015 mg/kg dexamethasone (Azium) IV.

  Dexamthesone sodium phosphate acceptable but adjust for active ingredient.

  3 samples at 0, 3 to 6 and 8 hours.

  8 hour cortisol result > 30-40 nmol/L is a positive test result
• Canine hyperadrenocorticism - ACTH response test

  Measure of adrenocorticol reserve.

  0.25mg Synacthen IV/IM

  Or 5ug/kg IV/IM - lower dose reported.

  Samples at 0 and 1 hour.

  1 hour cortisol > 500-600nmol/l is positive.

  Subnormal responses suggest exogenous steroid.

  Consider functional adrenal neoplasia in some flat mid-ranged and subnormal responses.
• Canine hyperadrenocorticism - urinary cortisol: creatinine

  One or more morning urine samples at home in non-stressed environment, as car ride to the vets can give false positive results.

  Definition of positive depends on laboratory

  Can combine with repeat after several doses of oral dexamethasone for differentiation
• Canine hyperadrenocorticism - when should I test?

  Only test if you could believe a positive results.

  • Presenting tests
  • Age
  • ALKP
  • Eosinophils

  Potentially misdiagnosed as hyperadrenocorticism

  • Young miniature Schnauzers hypertriglyceridaemia
  • Scottish terriers progressive vacuolar hepatopathy.
• Canine hyperadrenocorticism - HAC in DM

  To make diagnosis of HAC in diabetics

  • Can’t rely on usual evidence
  • ALKP, ALT, Chol, PUPD
  • Need to look for things we would not expect in a regular diabetic - hair loss, thin skin, bruising at venepuncture, persistent high insulin requirement.
  • Treat DM first
  • Provide data on insulin requirement
  • Improves confidence in positive endocrine diagnostic tests.
• Canine hyperadrenocorticism - Differentiating origin

  Low dose dexamethasone - sufficient for differentiation in 60% of positive LDDST

  High dose dexamethasone - fallen out of favor

  Endogenous ACTH

  Imaging (ultrasound/CAT/MRI).
• Canine hyperadrenocorticism - adrenal imaging

  PDH: symmetrically enlarged and normal conformation.

  ADH: one enlarged gland and one atrophied gland.

  May see invasion if a malignant tumour

  Complicated by incidentalomas.
• Canine hyperadrenocorticism - pituitary imaging


  CT or MRI

  Size of a normal vs enlarged pituitary not clearly defined.

  Useful if neurological signs to detect the presence of a large pituitary tumour.
• Canine hyperadrenocorticism - medical treatment options

  Trilostane (only licensed medicine in the UK)

  Mitotane (opDDD; Lysodren) - not licensed for animals (special import scheme).

  Selegiline (not effective in majorit’s, possible in combination with trilostane).
• Canine hyperadrenocorticism - surgical treatment options

  Adrenalectomy for ADH (remove associated adrenal glands)

  Hypophysectomy for PDH
• Canine hyperadrenocorticism - other adrenal - cortex

  Functional adrenal neoplasia (non-cortisol)

  Aberrant adrenal receptor activity - food (GIP) associated.

  Atypical hyperadrenocorticism

  Ectopic ACTH

  Congenital adrenal hyperplasia

  Alopecia X
• Canine hyperadrenocorticism - other adrenal - medulla

  Phaeochromocytoma

  • Produces catecholamines (adrenaline).
• Canine hyperadrenocorticism - functional adrenocortical tumours - classic

  Cortisol secreting - adrenal dependant hyperadrenocorticism.

  Aldosterone secreting - aldosteronoma, Conn’s syndrome
• Canine hyperadrenocorticism - functional adrenocortical tumours - glucocorticoid like


  Presentation:

  • Similar to HAC including stress leukogram, ACTH suppression.

  Diagnosis:

  • ACTH stim

  Treatment:

  • Surgical (preferred)
  • Medical
• Canine hyperadrenocorticism - functional adrenocortical tumours - mineralcorticoid like

  Presentation:

  • Related to hypokalaemia
  • Muscle weakness
  • Cats ventroflexion of neck.

  Diagnosis:

  • ACTH stimulation
  • Aldosterone

  Treatment:

  • Surgical (preferred)
  • Medical - Spironolactone)
• Canine hyperadrenocorticism - Phaechromocytoma

  Maybe confused hyperadrenocorticism

  • PUPD/ panting
  • Adrenal mass on imaging.
  • Hyperglycaemia
  • Weight loss.

  May be diagnosed post-surgically

  Pre-surgical diagnosis

  • Urinary catecholamines metabolites.

  Treatment - surgical

  • Local vessel invasion.

  Medical - symptomatic and pre-surgical

  • Adrenoreceptor antagonists
  • Phenoxylbenzamine