FUNCTIONING ADRENOCORTICAL TUMOUR IN A DOG
M. E. VINCE AND A. D. J. WATSON
Department of Veterinary Clinical Studies, The University of Sydney, New South Wales, 2006
SUMMARY: Naturally-occurring hyperadrenocorticism was diagnosed in an 11-year-old female Dachshund with signs of polydipsia, polyuria, pendulous abdomen, weakness, depression and lethargy, and laboratory test abnormalities comprising lymphocytopaenia, eosinopaenia, hypercholesterolaemia and increased plasma alkaline phosphatase concen- tration. While awaiting hormonal test results, an adrenocorticolytic drug (o,p’-DDD) was administered for 14 days, during which the patient deteriorated. Hormonal assays suggested a functioning adrenocortical tumour, but the poor condition of the patient precluded adrenalectomy. An adrenocortical carcinoma with hepatic metastases was found at necropsy.
Introduction
Clinical signs of hyperadrenocorticism develop in dogs with excessive endogenous production of cortisol or as a result of overadministration of glucocorticoid drugs. The naturally-occurring forms of the syndrome are associated with either a functioning adrenocortical tumour or bilateral adrenal hyperplasia. Some of those with adrenal hyperplasia have a pituitary tumour secreting adrenocorticotrophic hormone (ACTH) as the underlying cause.
Naturally-occurring hyperadrenocorticism is a disease of the middle-aged to older dog, with a breed predisposition for Boxers, Boston Terriers, Poodles and Dachshunds evident in some series (Scott 1979). The proportion of cases having a functioning adrenocortical tumour is said to be low, with figures of 5 to 15% generally cited (Schechter 1974; Owens and Drucker 1977; Scott 1979).
The majority of dogs with hyperadrenocorti- cism seen at The University of Sydney Veterinary Hospital and Clinic (USVHC) during the past 10 years have been diagnosed as having adrenal hyperplasia and few functioning adrenocortical tumours or iatrogenic cases have been recognised. This paper reports one case in which a functioning adrenocortical tumour was found.
Case Report
An 11-year-old female Dachshund was referred to the USVHC with a 6-month history of poly- dipsia, polyuria, pendulous abdomen, weakness, depression and lethargy, and more recent devel- opment of polyphagia. There was no history of glucocorticoid administration. Laboratory tests had shown normal blood glucose concentration (4.4 mmol/l), no glucosuria, and total eosinophil
count of 0.150 x 109/1. The referring veterinarian suspected hyperadrenocorticism. On examination (day 1), the dog had palpable hepatomegaly, a systolic murmur loudest over the left atrio-ven- tricular valve area, and a large ulcerating callus involving the right elbow. The skin was otherwise unremarkable. Radiographs confirmed gross hepatomegaly and showed concurrent pulmonary congestion and oedema.
Clinical pathology tests revealed neutrophilia (19.4 x 109/1), lymphocytopenia (0.6 x 109/1) and severe eosinopaenia (total count 0.011 x 109/1). Alkaline phosphatase and cholesterol concentra- tions in plasma were increased (1368 U/1 and 8.0 mmol/1 respectively).
These findings led to a diagnosis of hyperad- renocorticism with unrelated left congestive heart failure. Blood was collected for basal ACTH and cortisol determinations and an ACTH response test was performed. While awaiting these data, treatment with o,p’-DDD [1,1 dichloro-2 (o-chlo- rophenyl)-2-(p-chlorophenyl) ethane]* was com- menced at a dose rate of 50 mg/kg daily. Fru- semide and aminophylline were administered concurrently as treatment for heart failure.
After 10 days treatment with o,p’-DDD, the callus over the right elbow had sloughed, despite bandaging and padded bedding. Also, the skin over the left elbow was beginning to ulcerate and large cutaneous pustules were forming over the lateral thoracic wall. Serum electrolytes showed marked hypokalaemia (2.5 mmol/l) and eosino- paenia persisted (0.011 x 109 eosinophils/1).
o,p’-DDD was continued and the dog was started on intravenous fluids to treat the hypo- kalaemia. Surgery was undertaken on day 12 to
*Lysodren”, Calbio Pharmaceuticals, La Jolla, California, United States of America
excise the necrotic tissue from both elbows. The dog was severely depressed post-operatively and hypokalaemia persisted despite continuing treat- ment with intravenous fluids and oral potassium supplements. During the next two days, the skin over both hocks began to ulcerate and the total eosinophil count decreased to zero.
On day 15, o,p’-DDD treatment was discontin- ued because of deterioration of the patient. Abdominal radiographs disclosed a dense mass 6-7 cm in diameter anterior and medial to the left kidney, in the position of the left adrenal gland. The mass was not apparent in previous radi- ographs. The results of hormonal analyses became available later that day. These showed normal basal ACTH concentration, but markedly elevat- ed basal cortisol concentration which increased less than twofold in response to ACTH admin- istration (Table 1). These findings suggested a functioning adrenal tumour, but adrenalectomy was not attempted because of the dog’s poor condition. The dog deteriorated further over the next few days and was killed humanely on day 19 at the owner’s request.
Histological examination of post-mortem spec- imens disclosed a left adrenocortical carcinoma with metastases throughout the liver. The right adrenal gland was searched for but not found.
Discussion
Clinical findings produced commonly by exces- sive endogenous production of cortisol, or exog- enous administration of glucocorticoids, include: polydipsia, polyuria, abdominal distension, hepa- tomegaly, polyphagia, lethargy and cutaneous changes comprising alopecia, thin hypotonic skin, hyperpigmentation, easy bruising, comedones and calcinosis cutis (Ling et al 1979; Scott 1979).
If hyperadrenocorticism is suspected clinically, routine laboratory tests are advisable to confirm the diagnosis. Abnormalities encountered com- monly are: neutrophilia, monocytosis, eosinopa- enia, lymphocytopaenia, low urine specific grav- ity, and increased blood concentrations of
| Observation | Value |
|---|---|
| Basal cortisolt | 453 nmol/1§ |
| Cortisol post ACTH# | 752 nmol/1 |
| Basal ACTHt | 54 pg/mlf |
*measured by radioimmunoassay
tcortisol and ACTH samples collected simultaneously at 9 a.m. #sample collected 2 hours after intramuscular injection of 2.2 units ACTH/kg body weight, as Acthar gel (Armour Pharmaceuticals) §Cortisol reference range for dogs: 17 to 79 nmol/l (Chen et a/ 1978) (ACTH reference range for dogs: 17 to 98 pg/ml (Feldman et al 1977)
cholesterol, alkaline phosphatase and alanine ami- notransferase (Ling et al 1979; Scott 1979).
When investigating hyperadrenocorticism, iatrogenic cases can usually be recognised from the history, but differentiation of the other causes, namely bilateral adrenal hyperplasia and primary adrenocortical tumour, requires hormonal assays. A variety of tests have been used in the past, including urinary steroid or plasma cortisol deter- minations in conjunction with ACTH response or dexamethasone suppression testing, and more recently assay of plasma ACTH has become possible.
In the present case, when clinical and laboratory findings indicated hyperadrenocorticism, iatro- genic disease was excluded by the history and ACTH assay and an ACTH response test (meas- uring plasma cortisol) were performed for further differentiation.
It is generally accepted that basal blood cortisol concentrations may be increased in both naturally- occurring forms, and that ACTH administration will produce a substantial increase (greater than three-fold) in blood cortisol in adrenocortical hyperplasia but only a small increase with adren- ocortical tumours. However, these tests are not perfect because of considerable individual varia- tion and overlap between normal and abnormal animals (Feldman et al 1978).
There are additional problems with functioning adrenocortical tumours, in that some are hyper- responsive to exogenous ACTH (Owens and Drucker 1977; Chastain et al 1978), while basal and post-ACTH cortisol concentrations can fluc- tuate widely on repeated testing (Feldman 1981). However, Feldman (1981) showed that ACTH assays can assist differentiation, as his six dogs with adrenocortical tumours had plasma ACTH concentrations which were normal or low, and always less than those expected with adrenal hyperplasia. In the present case, we considered that the combination of basal hypercortisolaemia and normal plasma ACTH concentration sug- gested a functioning adrenocortical tumour, and that the poor response to exogenous ACTH was compatible with this diagnosis. Although the plasma ACTH concentration in our dog was higher than those reported by Feldman (1981), this discrepancy might be explained by different assay methods.
An important reason for differentiating adrenal hyperplasia from functioning adrenocortical tumours is that different treatments are favoured for each. Adrenal hyperplasia can be treated by bilateral adrenalectomy, hypophysectomy, or administration of the adrenocorticolytic drug o,p’-DDD. Lubberink (1980) discussed the merits of these three methods and preferred hypophy-
sectomy, but we have only used o, p’-DDD therapy in our cases. For adrenal tumours, surgical removal of the affected adrenal gland (Johnston 1977) is recommended, provided the tumour has not already metastasised (Lubberink 1980). In human patients, o,p’-DDD is used mainly against inoperable adrenal tumours to alleviate pain associated with metastases in bone. However, the efficacy of the drug against canine adrenal tumours is uncertain, and the few cases so treated have relapsed after an initial improvement (Lor- enz et al 1973; Owens and Drucker 1977).
In this case, we initiated o,p’-DDD therapy immediately because experience indicated that adrenal hyperplasia was more likely than an adrenocortical tumour, the patient’s condition was poor and deteriorating rapidly, and a delayed return of the hormonal test results was anticipat- ed. Such a precipitate approach is not advisable generally, because damage to the non-neoplastic adrenal gland by o,p’-DDD would complicate management if adrenalectomy was undertaken later to remove a tumour. In retrospect, it did not affect the outcome here as the presence of metastases made adrenalectomy unwarranted.
When hyperadrenocorticism is suspected clini- cally in a dog, routine haematological and bio- chemical tests should be performed initially to verify the diagnosis. If confirmed, and iatrogenic disease is excluded by history, further investiga- tion is indicated using appropriate hormonal tests (for example, basal cortisol and ACTH assays, and either an ACTH-response or dexamethasone
- suppression test). Plain abdominal radiographs may further assist detection of an adrenal tumour. Once the cause of hyperadrenocorticism is deter- mined, appropriate medical or surgical treatment can be applied.
Acknowledgments
We thank A.O. Johnson for referring the case and C.R. Bellenger and D.B. Church for assistance with its management. The senior author was supported financially by a Lionel Lonsdale Clinical Fellowship.
References
Chastain, C. B., Mitten, R. W. and Kluge J. P. (1978) - J. Am. vet. med. Ass. 172: 586.
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Feldman, E. C., Bohannon, N. V. and Tyrrell, J. B. (1977) - Am. J. vet. Res. 38: 1643.
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Lorenz, M. D., Scott, D. W. and Pulley, L. T. (1973) - Cornell Vet. 63: 646.
Lubberink, A. A. M. E. (1980) - In Current Veterinary Therapy VII, Ed. R. W. Kirk, W. B. Saunders, Philadel- phia, p. 979.
Owens, J. M. and Drucker, W. D. (1977) - Vet. Clin. N. Am. 7: 583.
Schechter, R. D. (1974) - In Current Veterinary Therapy V, Ed. R. W. Kirk, W. B. Saunders, Philadelphia, p. 783.
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(Accepted for publication 27 January 1982)
BOOK REVIEW
THE PHARMACEUTICAL CODEX
The Pharmaceutical Codex* is a renamed and rearranged BPC. The amount of useful information is considerably increased, but only a small proportion (perhaps one per cent of the book) is directed specifically at veterinary medicine.
Entries are arranged in alphabetical order; about 900 are monographs on drug substances with about 400 statements of
* The Pharmaceutical Codex (pages xxil + 1101), published by The Pharmaceutical Press, London and available in Australia from The Austra- lian Pharmaceutical Publishing Co Ltd, 35 Walsh Street, West Melbourne. Price $67.50.
variable length on topics like Abortion, Acne, Contact Lenses, Driving and Drugs, and Drug Dependence.
Many of the drug entries include well-researched data about absorption, tissue distribution, excretion, half life and ther- apeutic blood levels in humans; pharmacists and medical practitioners will find it an invaluable reference. Veterinarians would find only short paragraphs on “veterinary uses” (and doses) for those drugs included in the British Pharmacopoeia (Veterinary).
R.A. Anderson