Canine: Hyperadrenocorticism Flashcards
What hormone (and from what organ) stimulates the adrenal gland to produce cortisol?
The hypothalamus releases CRH, this stimulates the anterior pituitary to release ACTH, which stimulates the adrenal glands to produce cortisol
What are the 2 main etiologies of hyperadrenocorticism in dogs?
1) ACTH dependent: Pituitary dependent (80 - 85% of cases), usually neoplastic
2) ACTH independent/ Adrenal dependent: Functional adrenal tumor (15 - 20% of cases)
What is the most common cause of Pituitary dependent hyperadrenocorticism in dogs?
- Adenoma, producing excess ACTH, resulting in bilateral adrenal hyperplasia and excess cortisol release
This adenoma is also unresposive to negative feedback mechanisms and therefore doesn’t stop ACTH production
What is the most common cause of hyperadrenocorticism with origin in the adrenal gland?
- Adenoma (50%)
- Carcinoma (50%)
These will produce excess cortisol, which activates the negative feedback mechanism, decreases ACTH production from the pituitary and leads to atrophy of the contralateral adrenal gland
Small breed dogs such as poodles, dachshund and terriers are predisposed to what underlying cause of hyperadrenocorticism?
Pituitary dependent hyperadrenocorticism (an adenoma in the pituitary gland)
Dogs above the weight of 20kg are more likely to develop what underlying cause of hyperadrenocorticism?
Adenoma or carcinoma on the adrenal gland
What are the clinical signs associated with hyperadrenocorticism?
- Metabolic features: PU/PD, polyphagia, pot belly, panting even at rest, and exercise intolerant
- Dermatological: dull and dry coat that fails to regrow (Bilateral, symmetric, sparing the head and legs and NOT itchy), may see thin skin with a loss of elasticity and comedones, coat colour change and calcinosis cutis
note: excess cortisol is attributed to a reduction in the immune system, which can lead to secondary bacterial or fungal infections- pyoderma, malassezia, seborrhea, demodicosis, dermatophytosis
What is the cause for PU/PD in dogs with hyperadrenocorticism?
Excess cortisol inhibits ADH secretion, increases ADH metabolism and interferes with ADH receptor in the kidney, leading to dilute urine in higher quantities. The dog then drinks more to compensate for this increased loss in water
What is the cause for a pot belly in dogs with hyperadrenocorticism?
- Redistribution of fat into the abdomen and intercostal spaces
- Muscle weakness in the limbs
- Enlarged liver
How can hyperadrenocorticism be diagnosed?
1) Urinalysis: SG isosthenuric (usually between 1.008 - 1.012), proteinuria, blood, bacterial infection
2) Hematology: polycythemia, stress leukogram
3) Biochemistry: increased cholesterol, triglycerides, Glucose and a disproportionate increase of ALP over ALT (but both will be increased)
4) Diagnostic tests: Basal cortisol estimation, ACTH response test, low dose dexamethasone suppression test and urine cortisol:creatinine ratio
5) Ultrasonography
What is the effectiveness of using Basal cortisol estimation for diagnosing hyperadrenocorticism?
“It has no value as a diagnostic test”
There is huge overlap between diseased and non-diseased patients, and therefore does not help in identifying hyperadrenocorticism
What is the effectiveness of using ACTH Stimulation Response test for diagnosing hyperadrenocorticism?
Sensitivity of 80-85% for pituitary adenomas
Sensitivity of 0 - 60% for adrenal tumours
Specificity of 90%
A positive result may indicate hyperadrenocorticism, but a negative result does NOT exclude hyperadrenocorticism
What is the effectiveness of using Low dose dexamethasone suppression test for diagnosing hyperadrenocorticism?
Sensitivity of 90-95% for pituitary adenomas
Sensitivity of 100% for adrenal tumours
Specificity of 45-70%: this means there is several false positive tests in dogs that do NOT have hyperadrenocorticism
What is the effectiveness of using Urine cortisol:creatinine ratio for diagnosing hyperadrenocorticism?
Sensitivity of 90% +
Specificity of 20-77%
If a positive test result, proceed to investigate hyperadrenocorticism further with other tests
If negative test result, hyperadrenocorticism is unlikely
What would you expect to find on ultrasonography of the adrenal glands for a dog with pituitary tumor, and a dog with an adrenal tumor?
Pituitary tumor: Bilateral adrenal hyperplasia (width > 0.75mm), and are symmetrical
Adrenal tumor: one large adrenal (4+cm), one atrophic adrenal gland (<5mm) or evidence of metastases (usually in the liver)
What is the ideal way to collect and store a blood sample needed for the diagnosis of hyperadrenocorticism?
- Collect blood in cooled plastic EDTA tube
- Separate plasma in cooled centrifuge immediately
- Transfer plasma to cooled plastic tube
- Freeze at < -15C immediately
- Dispatch in special transport pack with ice packs
The reason for this is because ACTH will degrade almost immediately
An owner is unsure of treating their dog with hyperadrenocorticism, what should you let them know if they choose NOT to treat?
- Decreased survival rate
- Increased risk of:
UTI + Pyelonephritis + Other infections
Urolithiasis
Diabetes mellitus
Gallbladder mucocoele
Pancreatitis
Thromboembolic disease
What are the potential treatment options for a dog with hyperadrenocorticism?
1) Adrenalectomy: tx of choice for adrenal tumour
2) Hypophysectomy: tx of choice for a pituitary tumour
3) Medical management: low dose o,p-DDD (Mitotane) or Trilostane
4) Chemical destruction of the adrenal glands with a high dose of o,p-DDD: an adrenocorticolytic drug
How does o,p-DDD (Mitotane/ Lysodren) work?
- Is an adrenocorticolytic drug
- Selectively destroys the zona reticularis/fasciculata at low dosing
- Fat soluble drug: administer with food to enhance absorption
note: at high dosing it will also destroy the zona glomerulosa
You start a dog on low dose o,p-DDD (Mitotane/ Lysodren), what is the initial therapy dose?
50 mg/kg daily UNTIL one of the following occurs:
1) Water intake is < 50-60 ml/kg a day
2) Notice signs of hypocortisolemia (anorexia, depression, V/D)
3) 10 days of treatment has passed
note: An ACTH stimulation test MUST be performed when adverse effects are seen OR at the end of the 10 day treatment period
What cortisol concentration is ideally achieved after the initial therapy dose of Mitotane?
< 150 nmol/L
Once a dog has completed its initial therapy dose, what is the maintenance therapy dose?
50 mg/kg once weekly
note: ACTH stimulation tests are required one month after starting the maintenance dose and every 3-6 months after that
What are the adverse effects/ complications of using Mitotane?
- Gastrointestinal upset: split the dogs dose into 2 and give every 12 hours (during initial phase)
- Ataxia: split the dogs dose into 2
- Hypocortisolemia
- Addison’s disease
- Nelsons phenomenon: During the disorder the patient develops macroadenomas that secrete adrenocorticotropic hormone (ACTH)
- Recurrence of hyperadrenocorticism is possible (20-40%)
- Severe headaches in humans: owner must wear gloves when dosing their dog
A dog develops Hypocortisolemia while on Mitotane, what should you do next?
- Temporarily suspend Mitotane
- Supplement with preniso(lo)ne for 2-4 weeks at 0.2 mg/kg (or 0.5 mg/kg if the animal is stressed e.g. undergoing surgery, trauma or acute illness)
An owner elects to start their dog on Trilostane (Vetoryl), but wants to know what efficacy, survival time and chance of relapse is
Efficacy: 80%+
Survival time: 1.7 - 2 years
Relapse: 40%+
An owner wants to treat their dog with Trilostane (Vetoryl), how does this drug work?
- Is a competitive inhibitor of 3 Beta-hydroxysteroid dehydrogenase, which is an enzyme needed for cortisol production
- Is fat soluble, absorption is better when given with a meal
- Daily therapy for life is needed
What is the starting dose of Trilostane for dogs with Hyperadrenocorticism?
2.0 mg/kg SID with food for 10-14 days
What is the greatest risk of starting medical therapy on a dog with hyperadrenocorticism?
- The dog can become Hypoadrenocortical at any dose and at any time during therapy
- Animals should ALWAYS be sent home with predniso(lo)ne in the event of an Addisonian crisis
An owner elects to start their dog on Mitotane, but wants to know what efficacy, survival time and chance of relapse is
Efficacy: 70-90%
Survival time: 1.5 - 2.5 years
Relapse: 30%+
You start a dog on Trilostane (Vetoryl), when should the dog be assessed ?
- 10 days after starting
- 4 weeks after starting
- 12 weeks after starting
- Every 3 months after
Monitor clinical progress of the patient, and perform either:
- ACTH stimulation test, must be done 4 hours AFTER trilostane is given: ideally want <130 nmol/L of cortisol
- 3 or 24 hours post-pill cortisol level: ideally want pre-pill <138 nmol/L and post-pill <62 nmol/L
A dog on Trilostane, comes in for an ACTH stimulation test, it is performed and the cortisol level is <40 nmol/L (hypocortisolemia), what should be done?
- Temporary cessation of Trilostane for 7 days
- Prednisolone 0.2-0.5 mg/kg/day for the 7 days
- Re-introduce Trilostane at a lower dose
What are the contraindications of starting Trilostane?
Dont use in animals who have:
- Primary hepatic disease
- Chronic renal disease
- Are pregnant
note: animals taking concurrent medications: Potassium-sparing diuretics and /or ACE inhibitors will need dose adjustments
You suspect a dog has Addison’s disease after starting Trilostane for its hyperadrenocorticism, how can you confirm Addison’s and what is the treatment for it?
Diagnose: ACTH response test + serum electrolytes (looking for hyperkalemia and hyponatremia)
Tx:
- Stop Trilostane
- Monitor by ACTH response tests
- Hydrocortisone infusion in early stages when the patient has hyperkalemia and hyponatremia
An owner reports that her Cushingnoid dog is starting to show clinical signs again after starting Trilostane, what should be considered?
- Need for an increased dose: assess clinical signs and clinicopathological changes
- Twice daily dosing: assess by 24h ACTH stimulation test
- Possible development of concurrent disorders: UTI’s urolithiasis, DM, Hypothyroidism, Diabetes insipidus
- Consider alternate therapy
An owner wishes to do a Bilateral adrenalectomy in order to cure her dogs Pituitary-dependent hyperadrenocorticism, what does she need to be warned of?
Removal of BOTH adrenal glands will induce Addison’s disease, and therefore the dog will need to be medically managed for it for the rest of its life
A dog has just undergone a unilateral adrenalectomy of the right adrenal gland due to a functional tumor, what is the medical protocol for this dog once the tumor is removed?
1) Dexamethasone 0.1 - 2.0 mg/kg IV infusion for 6 hours
2) Dexamethasone SQ 2-4x daily for 2-3 days
3) Prednisolone oral 0.2 - 0.5 mg/kg as replacement to stress doses
A dog has undergone a unilateral adrenalectomy due to a functional tumor, when should the patient return for ACTH stimulation tests?
- 1 week post-surgery
- 2 weeks post-surgery
- 6 weeks post-surgery
A dog has undergone a successful hypophysectomy for the curative treatment of a pituitary tumor, what additional treatment is required and why?
- Vasopressin: the dog will temporarily be affected by diabetes insipidus
- Thyroxine + Cortisol: long term hypothyroid and hypocortisolemic
