Adrenal disorders are some of the most fun endocrine diseases we see in practice. These patients require a lot from us, especially when presenting as an emergency or if we are involved in anaesthetising them - they give us a huge amount to think about as nurses!

Today I’m walking you through 3 of the most common adrenal diseases and showing you exactly how to manage these patients in the hospital (and beyond!).

There are also some freebies you can download to accompany the information in this post - head to the downloads page to get your copies.

Hyperadrenocorticism (Cushing's Disease)

Cushing’s disease (hyperadrenocorticism) is a disorder resulting in excessive glucocorticoid levels (excessive cortisol).

This condition can be either adrenal-dependent or pituitary-dependent. Most cases are pituitary-dependent; these patients have a benign mass (macroadenoma) on the pituitary gland, releasing excessive adrenocorticotrophic hormone (ACTH). This stimulates the adrenal glands to produce more cortisol than normal. The negative feedback loop is then disrupted by the ACTH-secreting mass, the adrenal glands enlarge and cortisol release continues.

Adrenal-dependent HAC is less common and is caused by a functional tumour on one of the adrenal glands (functional adrenal tumour or FAT). This tumour releases cortisol directly. The negative feedback loop is activated and the pituitary gland shuts off any ACTH release because of the high cortisol levels, which causes the other (normal) adrenal gland to atrophy.

Clinical Signs

Clinical signs of HAC are caused by excessive steroid levels, and classically include PU/PD, alopecia or coat thinning of the ventral abdomen/flank, thinning of the skin, weight gain with a pot-bellied appearance, and muscle wastage.

Diagnostic Tests

On biochemistry, increases in ALKP/ALP (alkaline phosphatase) is commonly seen, and on haematology, a stress leukogram (neutrophilia, monocytosis, lymphopenia and eosinopenia) may be seen due to the excessive steroid levels.

Several different endocrine tests are used in patients with suspected HAC. These include:

Urine Cortisol:Creatinine Ratio (UCCR)

This test should be performed on a free catch urine sample collected at home, to minimise the effects of stress/the hospital environment on the sample. It is a highly sensitive test but a poorly specific test. A normal result, therefore, rules out HAC, but a positive result needs further investigation.

ACTH Stimulation Test

This test involves the administration of exogenous ACTH to assess the body's response. This typically involves blood sample collection before, and 60 (if given IV) - 90 (if given IM) minutes after administration of 5mcg/kg of ACTH. This test is used to differentiate between spontaneous HAC (i.e. that caused by an actual disease) and iatrogenic HAC (e.g. caused by us - with steroid administration or Addison's disease treatment at an excessive dose).

Low-Dose Dexamethasone Suppression Test

The LDDST is used to evaluate the negative feedback loop and is performed by collecting a baseline blood sample, administering 0.01-0.015mg/kg of dexamethasone IV, and then collecting further samples 4 and 8 hours later. In a normal patient, the dexamethasone administration would activate the negative feedback loop, causing the pituitary gland to shut off ACTH release, resulting in a drop in cortisol levels.

Endogenous ACTH Levels

Endogenous ACTH levels are the body's own ACTH levels. This test can be used to help differentiate between pituitary and adrenal-dependant HAC. Depending on the lab you are sending this to, it often has specific sampling requirements (frozen EDTA plasma).

Other diagnostics which may be performed in these patients include abdominal ultrasound or CT (to assess for a functional adrenal tumour), and urine analysis.

When hospitalising any patients for HAC investigations, we must do as much as possible to minimise any stress. Testing should not be performed on the same day as other investigations, diagnostic imaging, sedation or anaesthesia, and in some cases, it may be helpful to have the client wait with the patient in a consulting room during the test.

Patients undergoing ACTH stimulation tests, or dexamethasone suppression tests, should be starved before and during the test.

Treatment

The treatment for pituitary-dependent hyperadrenocorticism is long-term medical management with trilostane. This drug selectively inhibits the synthesis of adrenal cortex hormones. Dosage is adjusted based on ongoing monitoring (ACTH stimulation tests or 1-hour pre-pill cortisol monitoring) 10 days post-treatment initiation, then after 1 month, 3 months, and 3-monthly ongoing. The test should always be performed at the same time, 4-6 hours after trilostane administration. The medication should continue to be given at the same times each day, even on testing days, and patients should be starved before the test is performed.

Adrenal-dependant HAC (functional adrenal tumours) are typically managed surgically via adrenalectomy. Adrenalectomies have particular considerations and are high-risk procedures, with risks including haemorrhage, and sudden catecholamine release.

Nursing Considerations

The veterinary nurse plays a large role in the ongoing management of the Cushingoid patient. Nurses should provide support regarding medication dosing/compliance and when to dose regarding ongoing testing, monitor the patient's response to treatment by regularly assessing clinical signs, quality of life and the client's perception of their pet's care/disease, and carry out follow-up testing as directed by the veterinary surgeon.

In the hospital, nursing considerations include sufficient water intake (which is measured to quantify the degree of PU/PD), regular toileting opportunities (walking at least q2-4 hours), careful application of bandages, dressings and adhesive materials due to thinning skin and alopecia, and careful venous access due to the dynamic testing protocols used. As these patients require 2-3 blood samples in addition to an IV injection for each test, consider using a butterfly catheter or IV catheter to obtain the first sample and administer the drug, to preserve veins and minimise patient stress.

Addison’s Disease

Hypoadrenocorticism or Addison’s disease is characterized by low circulating steroid levels. In most cases, this is caused by immune-mediated adrenalitis, but in rare cases can be caused by necrosis or amyloidosis. It is also seen in patients on excessive doses of Cushing’s treatment (trilostane).

When we talk steroids, we are focussing on two main types:

1) Glucocorticoids, e.g. cortisol, produced by the zona fasciculata in the adrenal cortex, and

2) Mineralocorticoids, e.g. aldosterone, produced by the zona glomerulosa in the adrenal cortex.

The clinical signs we see in our Addisonian patients depend on whether cortisol, aldosterone or both hormones are deficient.

Clinical Signs

Addisons disease is termed 'The Great Pretender' as many clinical signs are initially non-specific and easily mistaken for gastrointestinal disease. These include diarrhoea, lethargy, anorexia, dehydration and vomiting, and are associated with cortisol loss. Other signs include PU/PD, abdominal pain and signs of shock. Classically, the Addisonian crisis patient presents with lethargy and dehydration/hypovolaemia, and signs of hyperkalaemia/hyponatraemia may be apparent, such as bradycardia and cardiac arrhythmias. This is associated with the loss of aldosterone, as this hormone is responsible for retaining sodium and excreting potassium in the kidney. The loss of aldosterone, therefore, causes increased sodium loss, and reduced potassium excretion, causing hyponatraemia and hyperkalaemia.

Diagnosis

There are several tests performed in a patient with suspected Hypoadrenocorticism, including:

• Basal cortisol levels: These can be used as an initial 'screening' test. A low result (<55mmol/L) should be followed up with confirmatory testing such as an ACTH stimulation test.

• ACTH stimulation test: This is the collection of a baseline serum cortisol sample, followed by a 5mcg/kg injection of synthetic ACTH, and a repeat cortisol sample collected 1-hour post-injection. A failure to stimulate will be seen in an Addisonian patient.

• Serum electrolyte levels: These may be within normal limits or hyponatraemia and hyperkalaemia may be seen, depending on the degree of aldosterone loss. The ratio of sodium to potassium should also be evaluated even if the electrolyte results are within the reference range. A Na:K ratio of <27:1 (27mmol sodium for every 1mmol potassium) is seen in 95% of Addisonian dogs.

• Haematology: these patients may have mild non-regenerative anaemia and lack a stress leukogram (neutrophilia, monocytosis, lymphopenia and eosinopenia).

• Serum biochemistry: Addisonian patients may have any of the following biochemical changes: hypoglycaemia, hypercalcaemia, hyperphosphataemia, hypoalbuminaemia and increased liver enzymes.

• Abdominal imaging may show small adrenal glands.

Stabilising the Crisis Patient

Stabilisation of the Addisonian crisis patient includes some or all of the following, depending on the patient's presentation:

• Protection of the heart from high potassium levels (calcium gluconate administration)⁠

• Fluid resuscitation to correct fluid deficits and metabolic acidosis⁠ with an appropriate crystalloid solution

• Administration of glucose to correct hypoglycaemia⁠

• Collection of samples to confirm the diagnosis⁠ (before steroids are given as most of these will cross-react with cortisol testing - dexamethasone can be given in an emergency and will not cross-react with an ACTH stimulation test)

• Slow correction of hyponatraemia with fluid therapy (rate of sodium correction should not exceed 0.5mmol/kg/hour)⁠

• Administration of steroids⁠

Treatment

Treatment of the Addisonian patient includes the administration of exogenous glucocorticoid (prednisolone) and mineralocorticoid (desoxycorticosterone pivalate or DOCP) to replace those deficient hormones. Response to treatment is monitored with regular blood samples for serum electrolyte (Na:K) levels, alongside clinical examination and client history collection. Dosages may need to be adjusted long-term during periods of increased stress, such as during illness, injury or planned anaesthesia/surgery.

Nursing Considerations

Patients in Addisonian crisis should be intensively monitored including continuous ECG and regular blood pressure assessment. All patients should receive a regular clinical examination, assessment of hydration and perfusion parameters, regular toileting opportunities in case of PU/PD, grooming and coat care in case of gastrointestinal signs, and other appropriate symptomatic treatment and nursing care depending on the individual patient.

Steps should be taken to minimise stress during hospitalisation as Addisonian patients cannot surmount an appropriate stress response. Anaesthesia should be avoided wherever possible, especially in an unstable or crisis patient. Where anaesthesia is required in a stable or previously diagnosed patient, they should be appropriately fluid resuscitated and have appropriate electrolyte derangement correction, and premedicated with steroids in addition to analgesic/sedative medications as prescribed by the veterinary surgeon.

Pheochromocytoma

A pheochromocytoma is a neuroendocrine tumour of the sympathetic nervous system, arising from chromaffin cells within the adrenal medulla.

The tumour secretes catecholamines (‘fight or flight’ hormones such as adrenaline, dopamine and noradrenaline). These have significant effects on the body, causing tachycardia and hypertension, mydriasis and increased smooth muscle tone.

Pheochromocytomas are identified most commonly in older dogs and rarely in cats. They are slow-growing and highly vascular tumours and can range from 0.5 to > 10cm in diameter.

Clinical Signs

Clinical signs are often vague and are intermittent, usually seen when the tumour secretes catecholamines.

Signs are generally associated with hypertension and tachycardia, and can include:

• Intermittent collapse

• Generalised weakness

• Excessive panting

• ‘Pounding’ heart

• Syncope

• PU/PD

• Lethargy

• Vomiting

• Anxiety

• Inappetance

Rarely, acute onset blindness (due to hypertensive retinopathy and retinal detachment), spontaneous haemorrhage and sudden death (from massive sustained catecholamine release) may also be seen.

Smaller tumours generally result in less severe clinical signs, whereas larger tumours are associated with more severe signs and a poorer prognosis.

Diagnostics

These tumours can be challenging to diagnose since the clinical signs are often vague and episodic. Routine blood tests and urine analysis are generally not helpful as they may not show any significant abnormalities.

Arterial blood pressure measurement should be performed in all cases where a pheochromocytoma is suspected, with multiple measurements collected and an average reading calculated.

PS. you can download a blood pressure monitoring form to record these in the VIMN freebie library here!

Diagnostic imaging such as abdominal ultrasound, or preferably CT should be performed to examine the mass, assess vascular involvement and estimate the size of the mass. Thoracic imaging should be included to check for metastases at the same time.

Urine metanephrines (the product of catecholamine breakdown) can be measured to help confirm a diagnosis of pheochromocytoma. Urine submitted for this test requires specialised handling - the urine should be acidified immediately after collection until it reaches a pH of 3-4, or if this is not possible, frozen to -20*C immediately after collection.

Treatment

Treatment includes stabilisation with medical therapy ahead of surgical removal of the affected adrenal gland.

The medications we use help to control the effects of the catecholamines, normalise blood pressure and expand extracellular fluid volume.

For 1-3 weeks before surgery, an alpha-1 adrenergic antagonist called phenoxybenzamine is given.

Surgery is complicated and carries significant risks, including severe haemorrhage, and massive catecholamine release especially when the tumour is handled. Postoperative complications can include cardiac arrhythmias, hypertension, hypotension, respiratory distress and ongoing haemorrhage.

Nursing Care

Nursing care following surgery is varied and these patients have intensive monitoring requirements, especially in the acute postoperative period.

Regular monitoring of heart rate, respiratory rate, blood pressure and ECG is required; ideally, a continuous ECG should be placed and an arterial catheter used to monitor direct blood pressure for the first 24 hours.

If blood products are required to manage haemorrhage, careful monitoring is required to promptly identify and manage a transfusion reaction.

Analgesia is a key consideration in these patients as they are often painful postoperatively. Regular pain assessments should be performed using a validated pain assessment tool, and appropriate analgesia should be given.

So that’s a review of Cushing’s disease, Addison’s disease and pheochromocytoma - as you can see, these patients have really varied requirements and there is a lot we can do to treat and care for them effectively!

Want to learn more about nursing the adrenal patient? I have a guide that shows you exactly how. Learn more here!

References

1. Lotatti, M. 2014. Canine hypoadrenocorticism: overview, diagnosis and treatment. Today's Veterinary Practice, [Online], Available from: https://todaysveterinarypractice.com/canine-hypoadrenocorticism-overview-diagnosis-treatment/

2. Merrill, L. 2012. Small Animal Internal Medicine for Veterinary Technicians and Nurses. Iowa: Wiley-Blackwell.

3. Nelson, R W. and Couto, C G. Small Animal Internal Medicine. 5th ed. Missouri: Elsevier Mosby, 2014.