The radiological features of canine Cushing s syndrome: a review of forty-eight cases

Transcription

1 J. small Anim. Pract. (1982) 23, The radiological features of canine Cushing s syndrome: a review of forty-eight cases KATRINA HUNTLEY*, JANET FRAZER*, CHRISTINE GIBBS* AND C. J. GASKELLf Departments of Veterinary Surgery* and Medicinet, University of Bristol, School of Veterinary Science, Langford House, Langford, Bristol BS 18 7DU ABSTRACT The radiological signs which have been reported in association with canine Cushing s syndrome are reviewed. The incidence of these changes in 48 dogs affected with this condition is reported and the contribution of radiography to diagnosis, prognosis and management is discussed. INTRODUCTION Certain radiological changes associated with Cushing s syndrome in the dog are well recognized and have been reviewed by Ticer (1977). They include hepatomegaly, adrenal enlargement and mineralization, bronchopulmonary mineralization, calcinosis cutis, dystrophic mineralization of other soft tissue structures and osteoporosis. The incidence of such changes, however, is either variably reported or unrecorded. Hepatomegaly is generally regarded to be a common finding, with reported incidences of 61 per cent (Schechter ef al., 19731, 90 per cent (Rijnberk, Kinderen & Thijssen, 1968) and 91 per cent (Lubberink, 1977). It has also been suggested that the degree of liver enlargement may be directly related to the duration and severity of the disease (Ticer, 1977; Scott, 1979). Opinions vary as to the appearance of the caudo-ventral border of the enlarged liver on lateral abdominal radiographs. Owens & Drucker (1977) state that it is usually rounded, while Ticer (1977) suggests that the hepatomegaly seen in endocrine disorders does not commonly produce rounding of the ventral lobe border. Radiographically detectable adrenomegaly has been reported only in cases of adrenal carcinoma (Kelly & Darke, 1976; Ticer, 1977; Scott, 1979). Such tumours may become mineralized (Kelly & Darke, 1976; Ticer, 1977). Owens & Drucker (1977) mention that the adrenal glands may also be a site of dystrophic calcification /82/ $ BSAVA 369

2 3 70 KATRINA HUNTLEY ETAL. Severe mineralization of the lungs is reported to occur in 90 per cent of cases (Capen, Belshaw & Martin, 1975) and, according to Owens & Drucker (1977), thoracic radiographs usually show an increased interstitial lung density and occasionally calcification of the tracheal rings and main-stem bronchi. However, the authors concede that some of these changes may be due to normal ageing. A B

3 RADIOLOGICAL FEATURES OF CANINE CUSHING S SYNDROME 371 Other authors are less specific with regard to the incidence of radiographically detectable bronchopulmonary mineralization, stating only that it may sometimes be seen (Ticer, 1977; Scott, 1979). The lesions of calcinosis cutis and mineralization of subcutaneous and intermuscular connective tissue may be shown on abdominal radiographs, particularly in the dorsal soft tissues, ventral abdominal wall and inguinal region (Ticer, 1977). Mineral deposition takes the form of either linear striations (Ticer, 1977) or coalescing focal aggregates (Owens & Drucker, 1977). Although Capen, Belshaw & Martin (1975) report the overall incidence of calcinosis cutis as 40 per cent, the proportion of cases in which lesions are radiographically visible has not been determined. There are several other sites in which dystrophic mineralization is reported to have been detected radiographically in Cushingoid dogs, namely, skeletal muscle, stomach wall (Ticer, 1977), kidney and heart (Scott, 1979). Osteoporosis is a well-recognized feature of hyperadrenocorticism in man (Vaughan, 1970) and has also been described in the dog (Dammrich, 1972). Although Rijnberk, Kinderen & Thijssen (1968) report osteoporosis as a frequent pathological finding, Capen, Belshaw & Martin (1975) state that it is not a C FIG. 1. Hepatomegaly. (A) Mild: Staffordshire Bull Terrier, 7 yrs. male. Increase in the vertical dimension of the ventral liver lobe with dorsal displacement of the pyloric antrum. (B) Moderate: Poodle cross. 8 yrs. male. The ventral liver lobe is distinctly enlarged and extends well behind to the costal arch. The pyloric antrum is displaced dorsally and somewhat caudally. (C) Severe: Yorkshire Terrier, 9 yrs. male. The ventral liver lobe is grossly enlarged and the gastric shadow lies almost horizontally.

4 372 KATRINA HUNTLEY ETAL. consistent feature of canine Cushing s syndrome. Owen s & Drucker (1977) commented that if extensive, osteoporosis may be appreciated radiographically in the vertebral column, while Scott (1979) mentioned that osteoporosis may cause lameness and occasionally lead to pathological fractures. The purpose of this paper is to record the incidence and nature of the radiographic changes in 48 dogs with Cushing s syndrome presented to the University of Bristol Veterinary School between 1973 and MATERIALS AND METHODS In the forty-eight cases under review, the diagnosis of Cushing s syndrome was based on established criteria with regard to clinical signs, changes in biochemical and haematological parameters and the results of adrenal function tests (Owens & Drucker, 1977). Twelve cases were eventually submitted for post mortem examination, when the underlying cause of the syndrome was established. In all cases, abdominal radiographs taken at, or shortly after, admission were available for review. They were used to evaluate liver size and the conformation of the ventral lobe border and to record the presence or absence of adrenomegaly, calcinosis cutis and dystrophic mineralization of abdominal soft tissue structures. Any additional evidence of pathological change was also noted. The degree of hepatomegaly was classified as mild, moderate or severe according to the radiographic criteria shown in Table 1 and Fig. 1. Liver size was correlated with the duration of the disease in thirty-nine cases in which the time of onset of clinical signs had been recorded. In an attempt to assess the incidence of radiographically detectable osteoporosis, the abdominal radiographs were used to make a subjective evaluation of the density and texture of the lumbar vertebrae. Because of lack of standardization of body size, degree of obesity and exposure factors, each radiograph was compared with a series of compatible films of five dogs of similar age and body conformation in which there was no clinical evidence of disease predisposing to osteoporosis. Any reduction in vertebral density or alteration in trabecular pattern was recorded. TABLE 1. Classification of hepatomegaly MILD MODERATE SEVERE Increase in vertical dimension of ventral liver lobe. Dorsal and slight caudal displacement of pyloric antrum. Overall increase in size of ventral liver lobe, with caudal extension beyond pyloric antrum. Obvious caudo-dorsal displacement of antrum. Massive enlargement of ventral liver lobe; stomach position approaching horizontal.

5 RADIOLOGICAL FEATURES OF CANINE CUSHING S SYNDROME 373 Radiographs of the caudal lung fields were available for review in forty cases, either appearing on separate films or, in smaller dogs, included on the survey film of the abdomen. These were used to estimate the degree of bronchial mineralization which was classified as mild, moderate or extensive according to the peripheral extent of radiographically detectable bronchial wall calcification (Fig. 2). The lung A C FIG. 2. Bronchial wall Calcification. (A) Mild: Poodle cross. 8 yrs. male. Calcification is confined to the walls of the major bronchi and barely extends beyond the hilar region (arrow). (B) Moderate: Boxer. 10 yrs. female. Bronchial wall calcification extends to the mid-parenchymal region (arrow). (C) Severe: Lurcher. 12 yrs. male. Calcified bronchial walls extend into the peripheral lung fields (arrow).

6 3 74 KATRINA HUNTLEY ETAL. parenchyma was examined for evidence of abnormal mineralization or soft tissue density infiltration. In order to establish whether or not the recorded changes could reasonably be attributed to Cushing s syndrome, a similar classification was performed on thoracic radiographs of twenty-five dogs of similar age and breed distribution in which there was no clinical evidence of respiratory disease. To determine whether the underlying cause of Cushing s syndrome might influence radiological findings, for the twelve cases in which the primary lesion was established at post-mortem examination, the radiographic changes associated with pituitary neoplasia were compared with those recorded in primary adrenocorticism (adrenocortical hyperplasia and functional adrenal carcinoma). TABLE 2. Hepatomegaly ~~ Duration of clinical signs (months) Total Hepatomegaly No. of dogs (%) Rounded ventral border no. of dogs None 12 (25) Mild 14 (29) Moderate 12 (25) Severe 10 (21) TOTAL 48 (100) FIG. 3. Functional adrenal carcinoma. Labrador. 12 yrs. female. Lateral radiograph of the cranio-dorsal abdomen showing a clearly defined mineralized mass cranial to the left kidney.

7 RADIOLOGICAL FEATURES OF CANINE CUSHING S SYNDROME 375 RESULTS The incidence and degree of hepatomegaly, the conformation of the ventral lobe border of enlarged livers and the relationship between duration of clinical signs and liver size are recorded in Table 2. Thirty-six dogs (75 per cent) showed evidence of hepatomegaly, the degree of which was classified as mild in fourteen (29 per cent), moderate in twelve (25 per cent) and severe in ten (21 per cent). The ventral lobe border was rounded in almost half (42 per cent) these animals but this alteration in configuration was not directly related to the degree of liver enlargement. Among the thirty-nine dogs in which time of onset of clinical signs had been recorded, there was no demonstrable association between duration of the disease and degree of hepatomegaly. Unilateral adrenomegaly with mineralization was recorded in two dogs subsequently found at post-mortem examination to have functional adrenal carcinomas (Fig. 3). In a further case of carcinoma, gross unilateral adrenal enlargement, without mineralization, was not detectable radiographically. Radiographic signs of calcinosis cutis and peripheral soft tissue mineralization were recorded in nine cases (1 8 per cent). The configuration of mineral deposition was nodular in four dogs (Fig. 4A) and linear in four (Fig. 4B). One animal showed a combination of nodular densities and linear striations. A B FIG. 4. Calcinosis cutis and connective tissue mineralization. (A) Labrador. 9 yrs. female. Coalescing mineralized nodules in the dorsal subcutaneous tissues. (B) Lurcher. 12 yrs. male. Linear mineralized densities in the dorsal soft tissue.

8 3 76 KATRINA HUNTLEY ETAL. Dystrophic calcification was observed in eight cases (17 per cent) and involved the renal pelvis (five cases), the liver (one case), the gastric mucosa (one case: Fig. 5) and branches of the abdominal aorta (one case: Fig. 6). The only other radiographic evidence of pathological change recorded in the abdomen was the presence of asymptomatic cystic calculi which occurred in three cases (6 per cent). In comparison, among 300 non-cushingoid dogs subjected to abdominal radiography during the period under review, the frequency of this incidental finding was only 1 per cent. Radiographic evidence of osteoporosis, as shown by decrease in density of vertebral medullary bone relative to that of the vertebral end plates was recorded in eight dogs (1 7 per cent). No equivalent changes were observed in the control group of non-cushingoid animals (Fig. 7). The degree of bronchial wall calcification in Cushingoid and non-cushingoid dogs is compared in Table 3 and shows a similar distribution in both groups. No dogs with Cushing s syndrome showed evidence of the granular parenchymal density indicative of alveolar mineralization as described by Capen, Belshaw & Martin (1975). FIG. 5. Gastric mucosal mineralization. Poodle. 8 yrs. female. Lateral radiograph of the cranial abdomen showing linear shadows of mineral density within the gastric lumen.

9 RADIOLOGICAL FEATURES OF CANINE CUSHING S SYNDROME 377 FIG. 6. Abdominal vascular calcification. Lurcher. 12 yrs. male. Lateral radiograph of the dorsal abdomen showing tubular mineral deposits in positions compatible with branches of the abdominal aorta. A B FIG. 7. Osteoporosis. Lateral radiographs of the lumbar vertebral columns of two Cushingoid dogs. (A) a 9-year-old female Mastiff showing normal bone density, and (B) a 9-year-old female Boxer showing a generalized decrease in density of the vertebral bodies and neural arches. N.B. By comparison, the vertebral end3ates are normaen density.

10 ~~ ~ ~~ ~ ~~~~ ~ 378 KATRINA HUNTLEY ETAL. TABLE 3. Radiographic signs of bronchial wall calcification Cushingoid dogs Non-Cushingoid dogs No. (96) No. (%) Mild 15 (37.5) 7 (28) Moderate 16 (40) 12 (48) Extensive 9 (22.5) 6 (24) TOTAL 40 (100) 25 (100) TABLE 4. Radiographic findings in twelve dogs in which the cause of Cushing s syndrome was established Rounded Soft ventral Calcinosis tissue Bronchial Age Sex Hepatomegaly lobe cutis calcification Adrenomegaly Osteoporosis calcification Pituitary neaplasia Staffs. Bull Terrier 7 M Moderate Mild Labrador I1 M Mild Severe Norwich Temer I2 M Severe Severe ~ Boxer 8 M Moderate Moderate Boxer 9 F Mild Moderate Whippet 10 F Moderate Moderate + Primary hyperadrenocorticism Adrenocortical hyperplasia Retriever 9 F Mild N.R. Labrador 7 M Moderate Moderate Yorkshire Terrier 5 M Severe + - Liver - - Mild Adrenal carcinoma Staffs. Bull Terrier 11 F Moderate Moderate Jack Russell Terrier 10 M Severe N.R. Labrador 12 F Mild Moderate + - N.R. = Not recorded. The radiographic findings in the twelve cases in which the cause of Cushing s syndrome was determined at post-mortem examination are shown in Table 4. The incidence of the various radiological signs did not differ significantly between dogs with pituitary and adrenal mediated disease. D I S C U S S I0N With the exception of dystrophic calcification of the non-neoplastic adrenal gland, pulmonary alveolar mineralization and pathological fractures, all reported radiological signs associated with canine Cushing s syndrome are represented in this series. The incidence of hepatomegaly (75 per cent) falls between the extremes of 6 1 per cent (Schechter et al., 1973) and 91 per cent (Lubberink, 1977) reported from

11 RADIOLOGICAL FEATURES OF CANINE CUSHING S SYNDROME 379 previous series. Even allowing for the potential for inaccuracy in determining the time of onset of a gradually developing disorder, no correlation could be established between duration of clinical signs and degree of hepatomegaly. No attempt was made to relate liver size to the severity of the disease, which is difficult to assess objectively. In contrast to the opinions of Owens & Drucker (1977) and Ticer (1977), the shape of the ventral lobe borders of enlarged livers varied between distinctly rounded and sharply wedge-shaped, showing that the configuration of this radiographic shadow is not a helpful indicator of Cushingoid hepatomegaly. Adrenomegaly could be detected in only two cases, in both of which the gland was heavily mineralized and subsequently found to be neoplastic. However, the absence of radiographic evidence of an abdominal mass in a further case of carcinoma, in which the left adrenal was grossly enlarged, but not mineralized, indicates that plain radiography does not provide a reliable method for the identification of functional adrenal neoplasia. Owens & Drucker (1977) mention that contrast studies, such as angiography, pneumoperitoneography or pneumoretroperitoneography may permit evaluation of the adrenal glands but give no detailed information regarding the results of these procedures in dogs. Mulnix et al. (1976), however, found that gamma camera imaging following intravenous injection of 1-19-iodo-cholesterol satisfactorily demonstrated hyperplastic or neoplastic adrenal glands in eight dogs. It is not surprising that the radiographic incidence of calcinosis cutis (18 per cent) was lower than the overall 40 per cent incidence quoted by Capen, Belshaw & Martin (1975), since clinical examination is a more sensitive method of demonstrating this change. Dystrophic calcification within abdominal soft tissue structures was seen most frequently in the renal pelvis (five cases) and occurred only sporadically at other sites. Mineralization of blood vessel walls has not previously been reported. The slightly increased incidence of asymptomatic cystic calculi in Cushingoid dogs might reasonably be accounted for by an increased susceptibility to low-grade urinary tract infection due to immunosuppression by hyper adrenocorticism. The finding of no significant difference in the frequency and severity of bronchial wall mineralization between Cushingoid and non-cushingoid dogs supports the observation of Owens & Drucker (1977) that such changes may merely be the effect of ageing. Although Capen, Belshaw & Martin (1975) suggested that severe bronchopneumonia is a common sequel to Cushing s syndrome, no clinical or radiographic evidence of lower respiratory tract infection was found in any case in the present series. Objective radiographic evaluation of skeletal demineralization is notoriously difficult and, in dogs, is complicated by the wide range in size and variations in the thickness and composition of the dorsal soft tissues. The use of densitometry is therefore precluded. Nevertheless, it was possible to recognize a distinct reduction in the radiographic density of the lumbar vertebral bodies, relative to the vertebral end plates, in a significant proportion (17 per cent) of the dogs in this series.

12 3 80 KATRINA HUNTLEY ETAL. However, none of the affected animals showed clinical signs of lameness and no pathological fractures were recorded. Since radiographic changes can be attributed principally to the metabolic effects of hyperadrenocorticism, it was predictable that the spectrum of radiological signs recorded in animals with pituitary neoplasia would not differ significantly from that seen in those with primary adrenal disease. The comparative data merely serve to emphasize that radiographic examination cannot be expected to contribute to elucidating the underlying cause of the disorder. Although neither consistent nor specific, the number and frequency of radiological changes which may be associated with Cushing s syndrome suggest that survey radiographs may provide a useful aid to diagnosis as do results of haematological and biochemical examination. Positive diagnostic information, however, will be obtained only in the small number of cases in which adrenomegaly can be detected. ACKNOWLEDGEMENTS The authors are indebted to colleagues in the Departments of Veterinary Medicine and Pathology, University of Bristol for making available clinical and pathological data. The photographs were taken by Mr J. Conibear and the script was typed by Mrs V. Beswetherick and Mrs C. Fr, ncis. REFERENCES CAPEN, C.C., BELSHAW, B.E. & MARTIN, S.L. (1975) In: Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat (Ed. S. J. Ettinger), VoI. 2, p W. B. Saunders Co., London. DAMMRICH, K. (1962) Die Beeinflussung des Skeletts durch die Hormone der Nebeunierenrinde unter besonderer Berucksichtigung des Morbus Cushing beim Hund. Berf. Munch. tierarztl. Wschr. 75,33 1. KELLY, D.F. & DAME, P.G.G. (1976) Cushing s syndrome in the dog. Vet. Rec. 98,28. LUBBERMK, A.A.M.E. (1977) Diagnosis and Treatment of Canine Cushing s Syndrome. Utrecht, Drukkerig, Elinkwijk, B. V. MULNIX, J.A., VAN DEN BROM, W.E., LUBBERINK, A.A.M.E., DE BRUIJNE, J.J. & RUNBERK, A. (1976) Gamma camera imaging of bilateral adrenal cortical hyperplasia and adrenal tumours in the dog. Am. J. vet. Res. 37, OWENS, J.M. & DRUCKER, W.D. (1977) Hyperadrenocorticism in the dog: canine Cushing s syndrome. Vet. Clin. N. Amer. 7,583. RUNBERK, A., DER KINDEREN, P.J. & THUSSEN, J.H.H. (1968) Spontaneous hyperadrenocorticism in the dog. J. Endocr. 41,397. SCHECHTER, R.D., STABENFELDT, G.H., GRIBBLE, D.H. & LING, G.V. (1973) Treatment of Cushing s syndrome in the dog with an adrenocorticolytic agent (0,P -DDD). J. Amer. vet. med. Ass. 162,629. Scorn, D.W. (1979) Hyperadrenocorticism. Vet. CZin. N. Amer. Small Animal Practice, 9,3. TICER, J.W. (1977) Roentgen signs of endocrine disease. Vet. Clin. N. Amer. 7,465. VAUGHAN, J.M. (1970) The Physiology of Bone, p Oxford University Press.