The adrenal glands… and all things Cushing’s disease!
The Adrenal Glands
The adrenal glands are paired glands sitting in close proximity to the kidneys. They have an outer cortex and inner medulla. The cortex is responsible for the synthesis/release of cortisol, aldosterone and androgens. The medulla is responsible for the release of our ‘fight or flight’ hormones - adrenaline, noradrenaline and dopamine. The release of cortisol from the adrenals is triggered by ACTH release from the pituitary gland. The whole system is regulated by a negative feedback mechanism, so if there are sufficient circulating cortisol levels the pituitary ‘shuts off’ ACTH release until levels fall. Aldosterone release is regulated by the Renin - Angiotensin - Aldosterone System (RAAS).
The release of our catecholamines from the adrenal medulla is mediated by the sympathetic nervous system.
Hyperadrenocorticism (Cushing's Disease)
Cushings 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 adrenocorticotrophoic 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 the 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.
A number of 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 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 prior to, 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 prior to 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 shouold 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 prior to the test being 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 in relation to 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.
References
Merrill L. Small Animal Internal Medicine for Veterinary Technicians and Nurses. Iowa: Wiley-Blackwell, 2012.
Nelson, R W. and Couto, C G. Small Animal Internal Medicine. 5th ed. Missouri: Elsevier Mosby, 2014.
