Cortisol homeostasis

When is cortisol released

During times of stressa

What is another name for hyperadrenocorticism

Cushing’s disease

What are the two spontaneous forms of hyperadrenocorticism

• Pituitary dependent hyperadrenocorticism

• Adrenal dependent hyperadrenocorticism

What is iatrogenic hyperadrenocorticism

A form caused by overuse or improper use of corticosteroid medications

What happens in pituitary dependent hyperadrenocorticism

1. ACTH is increased as functional pituitary tumour

2. Stimulates production of cortisol from both adrenals

3. Doesn’t respond to negative feedback

What happens during adrenal dependent hyperadrenocorticism

1. Functional adrenal tumour causes adrenal dependant hyperadrenocorticism

2. Cortisol is increased

3. ACTH is decreased due to negative feedback

4. Unaffected side shrinks due to decreased ACTH

What general blood test pattern is seen in hyperadrenocorticism

Increased cortisol levels

What serum biochemistry changes are often seen with high cortisol

Increased glucose and cholesterol due to insulin impairment and activation of lipolysis

What haematological changes occur with hyperadrenocorticism

Increased neutrophils and decreased lymphocytes and monocytes

Why can neutrophils be increased even though cortisol suppresses immunity

Cortisol decreases cytokine activation and reduces neutrophil migration into tissues so remain more in circulation

What liver enzyme is notably elevated in dogs with Cushing’s disease

Alkaline phosphatase

Why is ALP particularly elevated in dogs

Dogs have unique corticosteroid-induced isoform of ALP not found in other species

How do you test for Cushings

• Give ACTH and assess the response

• Give cortisol and assess the response

What is the purpose of the ACTH stimulation test

To assess adrenal gland response to ACTH and help diagnose hyperadrenocorticism

What happens in a normal animal after ACTH injection

Cortisol levels rise after injection and gradually decrease over time

What happens in pituitary-dependent hyperadrenocorticism (PDH) during the test

There is already excessive ACTH so giving more causes little or no additional cortisol rise only a brief increase

What happens in adrenal-dependent hyperadrenocorticism (FAT) during the test

Cortisol starts high and may increase further after ACTH then decreases slightly but remains above normal baseline

What is the purpose of the dexamethasone suppression test

To assess how cortisol production responds to an external glucocorticoid and help diagnose hyperadrenocorticism

What happens in a normal animal after dexamethasone administration

Cortisol production is suppressed because the negative feedback reduces ACTH release

What does a lack of cortisol suppression after dexamethasone indicate

Hyperadrenocorticism is likely

What does complete cortisol suppression after dexamethasone indicate

HAC is unlikely

How is hyperadrenocorticism treated

• Prevent synthesis of cortisol using medication

• Trilostane is a competitive inhibitor of 11-beta hydroxysteroid h=dehydrogenase 1 so inhibits corticosteroid synthesis

What are the adverse effects of trilostane

• Hypoadrenocorticism

• Electrolyte abnormalities

• Inhibits progesterone synthesis

What is pituitary pars intermedia dysfunction in horses

• Caused by the loss of the dopaminergic inhibition to the intermediate lobe of the pituitary

• Overproduction of ACTH

• Treatment is via a dopamine receptor agonist

What is another name for hypoadrenocorticism

Addison’s disease

What are the main causes of Addison’s disease

Autoimmune destruc tion of the adrenal cortex or sudden withdrawal of corticosteroid therapy

What hormones are deficient in Addison’s disease

Cortisol and aldosterone

What are the main physiological effects of Addison’s disease

• Disrupted metabolism

• Impaired blood pressure regulation

• Poor fluid and electrolyte balance

• Reduced stress response

What blood tests are used to diagnose hypoadrenocorticism (Addison’s disease)

• Serum electrolytes (↓sodium, ↓chloride, and ↑potassium)

• Serum biochemistry (§glucose, ↓cholesterol)

• Haematology (↑lymphocyte)

What drug is used for long-acting mineralocorticoid replacement in Addison’s disease

Desoxycorticosterone (DOCP), marketed as Zycortal

How does DOCP work

It increases sodium retention in the distal renal tubule and upregulates the sodium/potassium pump

Why is prednisolone often given alongside DOCP

TO provide glucocorticoid replacement when both the mineral corticoid and glucocorticoid zones of the adrenal cortex are damaged

What are the adverse effecs of DOCP

• Supression of the response to infection or injury

• Wound healing impaired

• Cushings syndrome

• Osteoporosis

• Hyperglycaemia

• Muscle wasting

• Fluids and electrolye imbalances

• Reduced milk yield in dairy cows

• GI ulceration

• Abortion in late pregancies

• Lamnitis