Hyperadrenocorticism

By | November 16, 2015

Also called Cushing’s syndrome, this is principally a problem of the dog. It is extremely rare in the cat.

Causes

  • pituitary-dependent — 80% of dogs. Excessive ACTH secretion results in adrenocortical hyperplasia and excess secretion of cortisol. According to Peterson et al. (), most of these cases (80%) are due to microadenomas. Only a few dogs have large pituitary tumours and these are slow-growing and not usually malignant. Very occasionally, neurological signs will develop in these cases
  • some pituitary-dependent cases not associated with tumours may be due to a failure of the negative feedback response by cortisol
  • the remaining 15-20% of naturally occurring cases are caused by unilateral or bilateral adrenal tumours
  • a further significant cause of hyperadrenocorticism is gluco-corticoid abuse (‘iatrogenic hyperadrenocorticism’). The commonest cause of this is the excessive use of injectable repositol glucocorticoids. It is difficult to estimate the number of iatrogenic cases of hyperadrenocorticism occurring, but it is likely that they are of equal importance to naturally occurring cases

Clinical features

  • any breed, but particularly toy and miniature poodles, boxers, dachshunds and terrier breeds
  • any sex, but females more likely to develop adrenal tumours
  • any age, but more common in middle to old age

Clinical signs

General

Can be any one of the following:

  • polyuria, probably due to glucocorticoids inhibiting the secretion or action of antidiuretic hormone
  • polydipsia, secondary to the polyuria
  • polyphagia, direct effect of glucocorticoids; a few animals, however, are anorexic
  • skeletal muscle atrophy, particularly the temporal muscles, shoulders, thighs and pelvic muscles
  • weakness, due to the muscle atrophy
  • hepatomegaly: in conjunction with abdominal muscle atrophy this often leads to a pendulous abdomen ()
  • anoestrus, clitoral enlargement
  • testicular atrophy
  • panting in approximately one-third of cases; severe dyspnoea may develop as a consequence of heart failure or pulmonary thrombosis
  • neurological signs (associated with macroadenomas of the pituitary gland or neoplasia of the adrenal cortex with metastasis)
  • lameness, pathological fractures (osteoporosis, osteomalacia)

Cutaneous

  • bilaterally symmetrical non-pruritic alopecia (not the head or the feet)
  • hyperpigmentation
  • very thin skin, particularly on the ventral abdomen; tends to wrinkle ()
  • easy bruising due to the increased fragility of the dermal vasculature
  • calcinosis cutis; most often occurs on the dorsum, gluteal and inguinal region; about 40% of cases
  • comedones
  • secondary pyoderma
  • poor wound healing
  • seborrhoea sicca

Diagnosis

  • history
  • physical examination
  • laboratory investigations

Laboratory findings

General

Routine haematology

This may reveal:

  • eosinopenia (< 200 cells/m3)
  • lymphopenia (< 1200 lymphocytes/m3)
  • neutrophilia
  • monocytosis
  • erythrocytosis
Urinalysis
  • low specific gravity (< 1.012)
  • may be proteinuria
  • bacteriuria in some cases
  • glucose, if diabetes is a complicating factor
Biochemistry

This may reveal:

  • elevated cholesterol (usually > 8 nmol/1)
  • elevation of liver enzymes, particularly alkaline phosphatase, but also alanine transferase
  • increased retention of bromsulphthalein (BSP)
  • increased blood glucose, usually in the high normal range
  • some cases (about 10%) may develop diabetes mellitus
  • decreased levels of T4 due to excessive glucocorticoid levels (TSH response is normal)

SPECIFIC TESTS

ACTH response test
  • starve the dog
  • collect a plasma sample in the morning for cortisol measurement
  • inject 10 units of ACTH gel intramuscularly (Synacthen, Ciba-Geigy) for a dog weighing less than 9 kg, or 20 units for a dog weighing more than 9 kg (0.8 ml Synacthen = 20 units ACTH gel)
  • resample after 2 hours

In normal dogs the post-ACTH concentration of plasma cortisol is two to three times higher than basal levels. In the majority of dogs with pituitary-dependent hyperadrenocorticism, and in approximately half the adrenal tumour cases, there is an exaggerated response to ACTH stimulation (post-ACTH plasma cortisol levels greater than three times the basal level).

Low-dose dexamethasone

As with the ACTH response test, the low-dose dexamethasone test is a useful screening test for the diagnosis of hyperadrenocorticism.

Suppression test

The test is based on the fact that low doses of dexamethasone, in normal dogs, inhibit the release of pituitary ACTH, resulting in a decrease in the level of plasma cortisol. In dogs with hyperadrenocorticism, plasma cortisol levels are not markedly suppressed. The protocol is:

Starve the dog

  • collect morning plasma sample for cortisol measurement
  • inject o.oi mg/kg dexamethasone intravenously
  • collect further samples after 3 and 8 hours
High-dose dexatnethasone suppression test

This test is based on the fact that high doses of dexamethasone will not suppress cortisol levels in dogs with adrenal tumours. The high levels of cortisol in these cases will have already suppressed ACTH. High levels of dexamethasone can, however, suppress ACTH secretion in dogs with pituitary-dependent hyperadrenocorticism. The protocol is:

  • starve the dog
  • collect plasma sample for cortisol measurement
  • inject 0.1 mg/kg dexamethasone intravenously
  • collect further plasma sample 3 and 8 hours later

If suppression of cortisol levels occurs, this is indicative of pituitary-dependent hyperadrenocorticism. Little or no suppression occurs in adrenal tumour cases.

Whichever method is used, it is necessary to contact the laboratory undertaking measurements since variations exist on the protocols described above, and it is therefore advisable to follow the recommended procedures of the laboratory in question.

Differential diagnosis

  • during the early stages of the disease the differential diagnosis is that of any disease presenting as polydipsia and polyuria, for example, chronic renal disease
  • once alopecia develops, the differential diagnosis includes:
  • hypothyroidism
  • Sertoli’s cell tumour
  • male feminizing syndrome
  • ovarian imbalances

Treatment

Surgical

  • bilateral adrenalectomy has been used as a treatment for pituitary-dependent hyperadrenocorticism. It requires experienced surgeons, and involves considerable risk to the dog. If successful, lifelong treatment for hypoadrenocorticism will be necessary
  • unilateral adrenalectomy is the treatment of choice for adrenal tumour. The surgery is difficult and should only be performed by experienced surgeons
  • approximately half the adrenal tumours are carcinomas, metastasis being principally to the liver
  • hypophysectomy has been reported as a treatment for pituitary-dependent hyperadrenocorticism. The surgery is extremely complex and is of academic interest only

Medical

  • most cases can be satisfactorily treated with o, p’-DDD (Mitotane, Idis Ltd). This drug, a chlorinated hydrocarbon related to DDT, selectively causes necrosis of the zona reticularis and zona fasciculata of the adrenal cortex. The mineralocorticoid-producing zona glomerulosa is relatively resistant in correctly dosed dogs
Method
  • 50 mg/kg of mitotane is given daily by mouth with food until polydipsia stops (when the water intake drops to 60 ml/kg per day or less), or until lymphocyte counts return to iooo/mm3. Alternatively, periodic ACTH tests can be performed and the daily dose of mitotane stopped when both pre- and post-ACTH stimulation levels of cortisol levels are below 200 nmol/1 (). This is usually only necessary if the dog does not present initially with polydipsia
  • the dog is then given a maintenance dose of 50 mg/kg weekly for the remainder of its life. If side-effects occur, half the maintenance dose given twice weekly may be helpful
  • most dogs commence weekly therapy within a month with an average of 10 days, but each case is individual and careful monitoring is essential
Side-effects
  • vomiting (may occur within first few days due to gastric irritation). of mitotane Giving in divided doses with food may help
  • diarrhoea
  • anorexia
  • weakness, lethargy, depression

Feline hyperadrenocorticism

  • hyperadrenocorticism is extremely rare in the cat. In those cases reported the signs were essentially the same as in the dog
  • mitotane is unsuitable for therapy as the cat cannot tolerate this drug
  • adrenalectomy is the treatment of choice for unilateral tumours of the adrenal gland, and bilateral adrenalectomy may be tried on pituitary-dependent hyperadrenocorticism. The surgery is complex and should only be performed by experienced surgeons

 

Selections from the book: “Skin Diseases in the Dog and Cat”. D. I. Grant, BVetMed (1991)