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Endocrine Specific Diseases Small Animal Notes

Veterinary Medicine Notes > Endocrinology and Integument 2 Notes

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Endocrine specific diseases - small animal CANINE HYPERADRENOCORTICISM (CUSHINGS) Hyperadrenocorticism is a disease of adrenal hyperfunction resulting in excessive levels of endogenous glucocorticoids in the circulation. Hyperadrenocorticism may be due to dysfunction of the pituitary gland, dysfunction of the adrenal gland or due to iatrogenic administration of corticosteroids. Clinical signs????

Usually middle aged to older dogs (7-9 years) Polyuria and polydipsia Polyphagia Abdominal distension
- Due to liver enlargement and muscle weakness Muscle wasting and weakness
- Due to the catabolic effect of glucocorticoids resulting in release of protein from muscle and breakdown of muscle fibres. Lethargy Non-pruritic alopecia
- Usually bilateral
- Usually in smaller dogs, less common in larger dogs. Thinning of the skin

Pathogenesis?

Pituitary dependent hyperadrenocorticism (PDH) is the most common form of Cushing's disease in dogs (80-85% of cases).
- A small pituitary tumour (microadenoma) usually arising from the pars distalis results in excessive ACTH production irrespective of negative feedback control and circulating cortisol levels.
- Both adrenal glands become hypertrophic and produce increased quantities of cortisol. Adrenal dependent hyperadrenocorticism (ADH) caused by adrenal tumours account for 10-20% of cases.

-Approximately 50% are adenomas, 50% are adenocarcinomas. Tumours are usually unilateral - bilateral tumours are rare. The affected adrenal gland produces excessive cortisol independent of ACTH stimulation. N.B ACTH levels do decrease due to negative feedback, but the affecting adrenal gland does not respond to this.
- There may be physical atrophy of the contralateral adrenal gland. Iatrogenic hyperadrenocorticism
- Results from chronic administration of any steroid containing product.
- The exogenous steroid acts like cortisol and so causes negative feedback on the HPA axis. This decreases ACTH production. The adrenal glands are therefore no longer stimulated and shut down.

Diagnosis??Biochemistry
- Marked increase in alkaline phosphatase in dogs
- Mild increase in ALT
- Increased cholesterol Urine sample
- Dilute isothenuric urine with USG <1.015
- Urinary tract infections common due to immunosuppression.
- Urine cortisol:creatinine ratio is a good screening test. Haematology
- Stress leukogram - lymphopaenia, eosinopaenia, neutrophilia, monocytosis. Radiography
- Hepatomegaly - 'slipper liver'.
- Ostreopaenia
- Adrenal mineralisation may be seen Definitive diagnosis: ACTH stimulation test.
- The dog is fasted overnight.
- Cortisol levels are measured at T=0 from a heparinised blood sample.
- A dose of synthetic ACTH (Synacthen at 0.125mg in dogs <5kg, and

0.25mg in dogs >5kg) is given intravenously.
- Cortisol levels are then measured again 30-60 minutes later from a second heparinised blood sample.
- Normal dogs have basal cortisol levels of <200nmol/L and stimulate to
<450nmol/L.
- Results of >600nmol/L are diagnostic of hyperadrenocorticim.
- This test will diagnose 80-90% of PDH and 50-60% of ADH.
- Those stimulating to between 450-600nmol/L should be re-tested.
- It cannot differentiate between ADH and PDH and there is a risk of false negatives.

?

Definitive diagnosis: low dose dexamethasone suppression test (LDDST).
- The dog is starved overnight.
- Cortisol levels are measures at T=0 from a heparinised blood sample.
- Dexamethasone is injected IV at 0.01mg/kg.
- Cortisol levels are measures again from blood samples collected at 3 and 8 hours.
- Normal dogs show cortisol suppression to <50% basal levels at 3 hours which persists at 8 hours.
- A positive result shows an 8 hour cortisol level >40nmol/L.
- Animals that show suppression at 3 hours and escape at 8 hours are likely to have PDH.
- Animals showing no suppression at 3 or 8 hours could be PDH or ADH.
- This test will diagnose 100% of adrenal tumours and 90% of PDH cases.
- It cannot differentiate between PDH and ADH and cannot detect iatrogenic HAC.
- There is a risk of false positives.Definitive diagnosis: high dose dexamethasone stimulation test (HDDST)
- Previously thought to be gold-standard discriminatory test, but actually fails to diagnose 10-15% of PDH cases.

?

The protocol is the same as for the LDDST but 0.1mg/kg of dexamethasone is injected. Combined endogenous ACTH and ultrasound
- Better than HDDST
- Measures endogenous ACTH and perform a good abdominal ultrasound scan.

Treatment??

Trilostane (Vetoryl)
- Competitively inhibits 3-beta hydroxysteroid dehydrogenase, thereby decreasing steroid production.
- The effects on cortisol production are reversible.
- Dose is 2-8mg/kg s.i.d. and can be increased further if there is a poor response. Some dogs may require twice daily treatment.
- Regular ACTH stimulation tests (at days 10, 4 weeks, 12 weeks and then every 3 months) need to be performed to ensure correct dosage. ACTH stimulation tests are ideally performed 4 hours post-pill. Mitotane (Lysodren) - not licensed to treat HAC.
- Selectively destroys the zona fasciculate and zona reticularis, thereby decreasing production of cortisol.
- Dose is 50mg/kg (up to a total dose of 1g) given daily until the dog shows signs of reduced cortisol levels (usually 7-10 days). The dog can then be switched to maintenance therapy and be treated once weekly.
- ACTH stimulation tests should be taken to assess control. Good control is indicated by post-stimulation cortisol levels of <100nmol/L. They should be performed every month until the animal is stable and every 3 months thereafter.
- Side effects include vomiting and overdose causing deficiencies of cortisol and sometimes aldosterone. Ketoconazole
- Interferes with cytochrome p450 of various steroidal enzymes.
- Expensive and can cause hepatotoxicity.
- Dose is 5mg/kg b.i.d for 7 days and if no adverse effects increase to 10mg/kg b.i.d. ADH can be treated with surgical removal of the affected adrenal gland.
- Prednisolone would be required post-operatively as the contralateral adrenal gland would not be functioning normally initially (avoids Addisonian crisis).

PrognosisGood - with management many dogs can live >5 years.

N.B Feline hyperadrenocorticism?Uncommon. Dermatological signs common, UTI common. PU/PD and polyphagia may not occur until late in the disease.

??

75-80% PDH. Bilateral adrenalectomy traditionally recommended. Trilostane has been used in cats with PDH and ADH successfully.

CANINE HYPOADRENOCORTICISM (ADDISON'S DISEASE) Hypoadrenocorticism is a syndrome caused by a deficiency in mineralocorticoid and/or glucocorticoid production. It may be primary (true Addison's) or secondary (very uncommon). Clinical signs??

Usually seen in young to middle aged dogs. More likely to be seen in female dogs (70% of cases). Addisonian crisis
- History of intermittent vomiting and diarrhoea
- Collapse
- Depression
- Weakness
- Hypovolaemic shock - weak pulse, poor peripheral perfusion (>2 second CRT), dehtdration, hypothermia.
- Bradycardia
- Abnormal ECG trace.
- Vomiting, diarrhoea and abdominal pain. Chronic onset disease (more common)
- Dehydration
- Low blood pressure
- Anorexia
- Vomiting
- Weight lossPathogenesis??The deficiency of aldosterone results in the body being unable to excrete enough potassium, but excreting excessive amounts of sodium. Excessive sodium loss results in excessive water loss and water follows sodium. The glucocorticoid deficiency means that the animal cannot mount a stress response well. The exact cause of primary hypoadrenocorticism is unknown, but is thought to be mainly caused by immune-mediated destruction of the adrenal cortex. Secondary hypoadrenocorticism is caused by a lack of ACTH or an abnormality in ACTH receptors.

DiagnosisBiochemistry
- Hyperkalaemia
- Hyponatraemia
- Na:K <23:1
- Pre-renal azotaemia
- Hyperphosphataemia
- Hypercalcaemia

???

- Metabolic acidosis Haematology
- Non-regenerative anaemia ECG findings include absence of a P wave and tall T waves.

Radiography may show microcardia, reduced pulmonary vessel size, reduced vena cava size and microhepatica. Ultrasonography may reveal thinner and shorter adrenal glands which may be very difficult to image. Definitive diagnosis: ACTH stimulation test
- Take a heparinised blood sample.
- Synthetic ACTH (Synacthen) is injected IV
- A second heparinised blood sample is collected 30-60 minutes later.

Treatment?

Addisonian crisis is a medical emergency and should be treated with aggressive fluid therapy.
- 0.9% saline infusion at 20-90ml/kg/hour for 1-2 hours.
- Once volume is restored, reduce rate to maintenance of 2ml/kg/hour.
- Continue fluid therapy until hydration status, urine output, serum electrolytes and azotaemia are corrected.
- To reverse hyperkalaemia and hyponatraemia if potassium is >7nmol/L, fluid therapy options include o 5-10ml/kg of 10% glucose over 30-60 minutes. o 0.25iu/kg soluble insulin IV with dextrose (2g per unit insulin). o 0.5-1ml/kg 10% calcium gluconate by slow IV injection with ECG monitoring during administration.
- Replacement of mineralocorticoids and glucocorticoids can be achieved by o Dexamethasone at 0,5mg/kg IV single dose o Methylprednisolone 1-2mg/kg IV single dose. o Hydrocortisone 5-10mg/kg IV q6hours. Chronic Addison's disease can be treated by:
- Initial replacement of mineralocorticoids and glucocorticoids o Dexamethasone at 0,5mg/kg IV single dose o Methylprednisolone 1-2mg/kg IV single dose. o Hydrocortisone 5-10mg/kg IV q6hours.

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