1. health and fitness
2. disease

Dr Phil Rees BVSc (Hons) MMedVet (Med)
Hillcrest, KZN
SAVA KZN Conference 2014
Adrenal Diseases: an endocrine perspective
Adrenal gland anatomy and physiology
Zona Glomerulosa responsible for the production of aldosterone, while the zona
fasciculata/reticularis secretes cortisol and androgens under the influence of ACTH from the
hypophysis. Aldosterone secretion is under primary control of the renin-angiotensin-aldosterone
system (RAAS).
Adrenomegaly may result from hypertrophy or hyperplasia due to chronic stress/illness, pituitarydependent hyperadrenocorticism (PDH), or ectopic ACTH secretion; adrenal adenoma, or neoplasia
(adrenocortical carcinoma, phaeochromocytoma).
Conditions arising from adrenal disease:
Hyperadrenocorticism
‘Atypical’ hyperadrenocorticism
Hypoadrenocorticism
Hyperaldosteronism
Phaeochromocytoma
Hyperadrenocorticism (HAC)
Hypercortisolism is a SYNDROME, since excess cortisol secretion may result from a number of
pathological processes where the common endpoint is hypercortisolaemia. Cortisol concentration is
controlled by the HPA axis. 85% of dogs with HAC have PDH. Most of these due to pituitary
adenomas (macro- or micro-adenomas). 15% of dogs with HAC have hypercortisolaemia
independent of pituitary ACTH secretion, as a result of adrenocortical tumours. Some adrenal
masses may however be an incidental finding during routine exam or US, and concurrent pituitary
and adrenocortical tumours may occur. A rare form of HAC exists which develops as a result of ACTH
secretion from sources other than the pituitary gland. Ectopic ACTH secretion usually originates from
a range of tumours such as adenomas.
Diagnostic testing for HAC
When should I be testing for HAC?
Patient selection NB!!! Suggestive signalment, history and clinical signs? (PU/PD? Polyphagia?)
Without these you are already on shaky ground! A high index of suspicion is vital for improved
accuracy of diagnostic tests for hyperadrenocorticism.
When should I NOT be testing for HAC?
The clinician should be disinclined to perform diagnostic testing for HAC in the presence of clinical
signs not usually associated with HAC, e.g.: decreased appetite, vomiting, diarrhoea, sneezing
coughing, icterus, pruritus, pain, seizures, bleeding. These signs suggest the presence of conditions
which may affect the sensitivity and specificity of endocrine tests, and very well could simply
confound the situation. The clinician should first search for other diseases and diagnose/treat these
before attempting endocrine testing.
Urine cortisol-creatinine ratio (UCCR): This static test has a high sensitivity but low specificity of
HAC, and therefore has a high negative predictive value. Such a test is useful for RULING OUT a
disease, and the UCCR is thus the test of choice for RULING OUT HAC when the index of suspicion is
low. Use free-catch samples collected at home to avoid effect of stress are advocated.
SIGNALMENT
HAC is common in smaller breeds (<20kg) e.g. Poodles, Dachshund, terriers. These dogs usually have
PDH. Larger breed dogs (>20kg) more commonly develop ADH (except Boxers which more commonly
develop PDH). Most dogs with HAC are older than 6 years at the time of diagnosis (mean 11 years).
HISTORY HISTORY HISTORY!!!
PU/PD is common, occurring in 80-90% of cases. Polyphagia is also a common finding (about 50%of
cases). Dermatologic changes including bilaterally symmetrical alopecia (esp. later in the disease),
comedones, thinning of the skin, and calcinosis cutis. Many dogs will present with a pendulous
abdomen, in part due to hepatomegaly, abdominal fat accumulation, and weakening of the
abdominal muscles.
CLINICAL PATHOLOGY
The haemogram may reveal erythrocytosis, thrombocytosis and a stress leukogram. Serum
chemistry often reveals raised ALP activity (85%), and many cases also have a less prominent rise in
ALT. A low urea, hyperlipidaemia/hypercholesterolaemia, and hyperglycaemia may be noted. Mild
hyperglycaemia or overt diabetes mellitus may occur in 5% of dogs with HAC. This is due to the
antagonistic effects of cortisol on the insulin receptor.
URINALYSIS
Inadequately concentrated urine is the hallmark of HAC. In addition, proteinuria is a common
finding, as well as glucosuria.
RADIOGRAPHY
Abdominal radiographs may reveal hepatomegaly, and rarely calcification of the bronchi and lung
parenchyma. Adrenal calcification may also be noted. Generalised osteopenia may be noted in a few
cases due to the calciuretic effects of cortisol.
ULTRASOUND
Hepatomegaly is a common finding, with the liver often appearing hyperechoic. The adrenal glands
may be bilaterally enlarged in PDH, whereas an adrenal tumour causing ADH will often be noted
with atrophy of contralateral gland. Caution should be exercised however, since many adrenal
masses are non-functional and do not secrete active hormones (so-called incidentaloma). Signs of
tumour invasion into surrounding structures (e.g. CVC) should be assessed. Normal adrenal size is
regarded as <7.4mm in thickness. However, as much as 23% of PDH cases have normal adrenal size!
In addition, 20% of normal dogs have adrenal glands of >7.4mm in thickness!
Functional adrenal tumours may be adrenocortical adenomas
Phaeochromocytomas and metastatic tumours are also possible.
or
adenocarcinomas.
ACTH stimulation test
This test has a relatively low sensitivity, and cannot differentiate PDH from FAT. It is, however,
commonly used as a screening test for HAC. This test can differentiate between iatrogenic and
naturally occurring HAC. It is also the test of choice for monitoring medical therapy of HAC.
LDDST:
More accurate than ACTH stim, 0.01mg/kg dexamethasone suppresses the secretion of ACTH from a
healthy pituitary gland for over 24 hours. In normal dogs, serum cortisol concentrations typically fall
below 20nmol/L by 4 hours and remain at that level at 8 hours.
Differentiating tests:
Ultrasound + Endogenous ACTH, not practical and not always available.
HDDST
Treatment
Mitotane (Lysodren): 50mg/kg divided for 5-7 days then ACTH stimulation test.
Trilostane: starting dose 2 to 5 mg/kg OID (BID in some cases).
Monthly monitoring for first 3 months, then every 3 months for the first year and every 4 to 6
months thereafter. Recommended target range for post-ACTH cortisol concentration: 40 to 120
nmol/L, ACTH stimulation test started 2 to 4 hours after dosing of trilostane.
Complications of HAC
Hypertension
Glomerulopathy/proteinuria
DM/pancreatitis
UTI
Thromboembolic disease
Feline adrenal disorders
Feline Cushing’s Syndrome
Cushing’s syndrome is a rare entity in cats. This syndrome is caused by a pituitary adenoma. DD’s
include: diabetes mellitus, insulin resistance, acromegaly, hepatopathy, renal disease, sex hormonesecreting adrenal tumours, and hyperthyroidism. The median age at diagnosis is 10y.
Clinical signs:
Insulin-resistant DM, cutaneous atrophy, polydipsia, polyuria, polyphagia, lethargy, abdominal
enlargement or potbelly, panting, obesity, muscle weakness, and recurrent upper respiratory and
urinary tract infections. ALP is not elevated, unless poorly-controlled DM present.
Screening tests include UCCR with home-collected morning samples for 2-3 consecutive days. The
LDDST is preferred to ACTH stim in cats for the diagnosis of HAC.
Treatment:
Trilostane 30 to 60 mg per cat per day
Monitoring weekly