J . small Anim. Pruct. (1975) 16, 193-200.

Hyperadrenocorticism in a dog: A case report JOHN A. MULNIX

AND

K E N N E T H W. S M I T H

Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado

ABSTRACT A case of hyperadrenocorticism (Cushing’s Syndrome) in a 7-year-old female Miniature Poodle is presented. The methods of diagnosis and treatment are also described. The case was complicated by respiratory problems associated with probable dystrophic calcification of the lungs. INTRODUCTION The clinical and pathological features of hyperadrenocorticism in dogs have been well documented (Coffin & Munson, 1953; Rijnberk e t al., 1968a; Siegel e t al., 1970). The most common clinical signs are polydipsia, polyuria, pendulous abdomen and changes in the hair coat. It was initially pointed out by Coffin & Munson (1953), that the disease was most common in the Boston Terrier. Siegel et al. (1970), however, listed Toy and Miniature Poodles and Dachshunds as the most frequently affected. A tentative diagnosis of hyperadrenocorticism can usually be based on the clinical signs and laboratory findings of an absolute eosinopenia and lymphopenia. The diagnosis can be confirmed by demonstrating increased 17-hydroxycorticosteroid excretion in the urine (Siegel, 1965; Wilson et al., 1967; Rijnberk et al., 1968b; Siegel, 1968), or elevated plasma corticosteroid levels (Rijnberk et al., 1968b; Halliwell et al., 1971). Since a firm diagnosis based on a single plasma corticosteroid level is difficult to make, it is necessary to%useeither an overnight dexamethasone suppression test or an ACTH response test (Halliwell et al., 1971). METHODS Plasma cortisol levels were determined by a modification of the Competitive Protein Binding (CPB) method as described by Murphy (1967). Thyroid function 193

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J O H N A . MULNIX A N D KENNETH W. SMITH

tests employed were the triiodothyronine uptake test (T3) kit (Abbott Test Kit, Abbott Laboratories, North Chicago, Ill.) in which triiodothyronine is labelled and the total thyroxine (T4) test. with 1251J CASE R E P O R T On 15 June 1972, a 7-year-old female Miniature Poodle was referred to the Colorado State University (CSU) Veterinary Hospital because of chronic hair loss of 21 months’ duration. Past medical history also indicated polyphagia, polydipsia, polyuria and progressive muscle weakness. The last observed oestrous cycle was 33 months previously.

FIG. 1. Seven-year-old female silver bfiniature Poodle prior to surgery. Note the severe generalized alopecia and pendulous abdomen.

On entry, the patient weighed 8.6 kg, was afebrile and had a normal, firm and regular pulse rate. A bilateral symmetrical alopecia was observed on the chest, abdomen, fore and rear limbs, back, and neck (Fig. 1). The hair coat was thin and epilated easily. The skin was scaly, dry and thin, especially over the abdomen. The patient had a markedly pendulous abdomen and upon palpation the liver was enlarged. Auscultation revealed no cardiac abnormalities, however, harsh lung sounds were heard over the entire thorax. The serial findings of blood analyses are tabulated in Table 1. Significant findings in a n initial random urinalysis were a low specific gravity (1.006), negative glucose, and only occasional cells.

(%I

ok-adequate

108 4.7 145

5.0 4.3 144

3.3 144

4.5 146

5.0 145 496

2 20 100 144 4.8 144

1 91 4 3 1

3-5 145

87 7 4 1

4.6 14.2

112 4.0 144

20

3 2

13

83

44 16.6 7.5 ok 9200

.63 21.7 5.7 ok 14300 1 82 7 4 G

11-7

8-23

number of platelets observed on slide per oil immersion field.

150

15

20

30

10

10

5

20 03.3

16 79 2 3

3

3 93

2

I 88 1

85 9 4 1 5 5 1

83 12 4 1

7.1 ok 18800

66 ok 23100

8.7 ok 24000 1 12 80 2

-

62 22.3

8-21

63 23.6

8-1

44

7-3

6 88 4

1

16700

6.1 ok 25300

15100

5.6

6.7 ok 18400

ok 13900

oktt 94.00

8.1

'r

36 -

38 -

36 -

39

55 20.9 7.7

50 17.8 6.9

6-30

6-29

6-27

6-28

6-26

6-19

6-15

-Nr.d-w m

t Serum lipemic, H b values could not be interpreted. t t

Lymphs (%I Monos (yo) Eosino (yo) NUC RBC (yo) Urea Nitrogen (mg yo) Glucose (mg yo) Chloride (rnEq/l) Potassium (mEq/l ) Sodium (mEq/l) Cholesterol (mg yo)

Segs (%)

Metamyelo (%) Bands (Yo)

WBC

pcv Hb (gm %) Tot. Protein (gm/l00 rnl) Platelets

Date

therapy

TABLE 1. Results of hematological and blood chemistry analysis on 7-year-old female Poodle before and after andrelectomy and maintenance

IN A DOG

0

0

v1

2

z n 0

HYPERADRENOCORTICISM

195

196

JOHN A. MULNIX AND K E N N E T H W. SMITH

Plasma cortisol levels before and 1 hour after administration of 10 units of ACTH (Corticotropin Injection USP-Parke-Davis, Detroit, Michigan) solution intramuscularly, were 10.07 and 20.52 ,ug/lOOml respectively. The result of the T 3 test was 46% (42-58% normal) and the T 4 test revealed a thyroxine level of 2.1 pg per 100 ml. Thoracic and abdominal radiographs revealed slight liver enlargement, markedly increased density throughout the lung field (Fig. 4) suggesting a generalized pneumonia and moderate generalized osteoporosis.

I40 Pulse

I20

\$

-

100I

0

E

80-

60 40

2o

-

t

Antibiotic therapy was initiated the day following entry to the hospital and was continued through hospital day 20 (Fig. 2). Further pre-operative preparation of the patient consisted of 10 units of ACTH intramuscularly on days 10 and 11 and intramuscular prednisolone on day 12. Intramuscular deoxycorticosterone acetate (DOCA) at a rate of 0.5 mg per day was initiated on day 11 and continued after surgery at varying dosages adjusted to maintain a normokalaemia and normonatraemia through the remainder of hospitalization. On the day of surgery (day 14) an intravenous (IV) drip of 2+% dextrose and 0.45% sodium chloride with 100 mg of prednisolone sodium succinate (Solu-DeltaCortef-Upjohn Co., Kalamazoo, Michigan) was started. Anaesthesia was induced with neurolept analgesia (0.75 cc Inovar-Vet Pitman-Moore, Washington

HYPERADRENOCORTICISM IN A DOG

197

Crossing, New Jersey) and 0.25 mg Atropine IV. T h e patient was intubated and anaesthesia was maintained on a non-rehreathing system using methoxyflurane to effect. The paracostal approach similar to that described by Siege1 et al. (1970) was used for surgical removal of the adrenal glands. Both adrenal glands appeared grossly enlarged and on microscopic study, a thickening of the cortical area was observed. There were numerous nodules, cystlike spaces containing eosinophilic material, and focal haemorrhages in the zona fasciculata which extended into zona reticularis and medulla. T h e histopathological diagnosis was hyperplasia of the zona fasciculata and reticularis.

FIG.3. Seven-year-old female Miniature Poodle 4 months after operation. Note the new hair growth over the entire body. The new hair growth was black.

Following surgery the IV drip of 23% dextrose and 0.45% sodium chloride was continued through the 12 hour post-operative period. During post-operative monitoring urine flow remained steady at an average of 30 drops per minute, respiratory rate was approximately 42 per minute and heart rate 145 per minute. The patient was able to stand 5 hours post-operatively. Five days after surgery the patient had shown only marginal clinical improvement (Fig. 2). On day 16, 0.075 mg oral digoxin and 25 mg oral furosamide was instituted to relieve severe pulmonary congestion and respiratory difficulty. Clinical recovery was uneventful after day 18. O n day 26, 50 mg of desoxycorticosterone pivalate (DOCP) (Percorten Pivalate -Ciba Pharmaceutical Co. Summit, New Jersey) was administered I M to replace

198

J O H N A . MULNIX AND KENNETH W. SMITH

the daily DOCA therapy. T h e patient was discharged on 5 mg oral prednisolone daily and with instructions for the owner to apply table salt liberally to the food daily. Three weeks after the DOCP, 4 x 125 mg DOCA pellets (Percorten AcetateCiba Pharmaceutical, Summit, New Jersey) were implanted subcutaneously under neurolept analgesia IV and a 2 % lidocaine HCl (Med-Tech Inc., St. Joseph, Mo.) local infiltration block. T h e implant site was 2 inches posterior to and above the left scapula. T h e patient was discharged upon recovery from anaesthesia. On 21 August 1972, the patient was re-admitted because of restlessness and 'arching of the neck'. Rectal temperature was 39.1"C and the neck was deviated ventrally and to the left. No cervical pain was detected. The only abnormality found was a marginally low serum potassium concentration (Table 1). One of the four DOCA pellets was surgically removed. T h e patient made an uneventful recovery and has remained normal since, receiving DOCA pellet implants approximately every 10 months.

FIG. 4. Lateral thoracic radiograph before surgery of patient shown in Fig. 1. Note minimal osteoporosis (A), subcutaneous dystrophic calcification (B), possible changes of pulmonary dystrophic calcification (C), and hepatomegaly (D).

DISCUSSION The initial plasma corticosteroid level of 10.07 pg per 100 ml represents a significant elevation. Halliwell et al. (1971) demonstrated that animals with hyperfunctional adrenals had a mean resting level of 3.5 pg/lOO ml using the CPB method, with a

HYPERADRENOCORTICISM

IN A DOG

199

range of 1.9 to 4.8 ,ug/lOO nig. The 1 hour post ACTH response of 20.5 ,ug/lOO ml represents approximately 100% increase. Using a Cortrophin-Gel preparation, Halliwell e t al. (1971) found ‘Cushing’ dogs to respond 5 hours later in a range of 17.5 to 30.0 ,ug/lOO ml. These results cannot be accurately compared due to difference in technique. The elevated plasma cholesterol concentration of 496 mg% was within the expected range for dogs with hyperadrenocorticism (Venzke, 1967). Siegel et al. ( 1970) found a range of 2 16 mg % to 509 mg% and a median of 359 % in twentyseven affected dogs. The initial blood glucose concentration was normal in this patient, although approximately half of the affected patients may have diabetic values (Rijnberk et al., 1968; Siegel et al., 1970).

FIG.5 . Lateral thoracic radiograph 1 1 months after surgery of patient shown in Fig. 1. Note subcutaneous dystrophic calcification (A), and areas of possible pulmonary dystrophic calcification (B).

The pre-operative administration of corticosteroid therapy (DOCA and prednisolone) follows closely a previously described technique (Siegel et al., 1970). The pre-operative administration of ACTH in this case was not necessary and could have even been detrimental. Pre-operative corticosteroids are considered to be unnecessary by others (Forsham, 1968). The respiratory complications in this patient may have been associated with dystrophic calcification of the lungs. Although dystrophic calcification of the lungs of dogs with hyperadrenocorticism has been recognized histologically by others (Capen et al., 1967; Kelly e t al., 1971), it is not a commonly reported clinical

200

J O H N A . M U L N I X AND K E N N E T H W. SMITH

finding. The changes in this patient were severe enough to cause a n initial radiographic interpretation of possible pneumonia. I n the absence of a noticeable cough, febrile response, cardiac murmurs or significant pre-operative leucocytosis, neoplasia, pneumonia and congestive heart failure were considered unlikely, Following adrenalectomy and maintenance therapy, the increased respiratory rate returned to a more normal range; however, radiographic evidence of pulmonary dystrophic calcification was still evident l l months post-operatively (Fig. 5), although some radiographic improvement was noted.

REFERENCES CAPEN,C.C., MARTIN, S.L. & KOESTNER, A. (1967) Path. Vet. 4, 301. T.D. (1953) 3. Am. Vet. Med. Ass. 123, 402. COFFIN, D.L. & MUNSON, FORSHAM, P.H. (1968) I n : Textbook qfEndocrinologv, W. B. Saunders Go., London. HALLIWELL, R.E.W., SCHWARTZMAN, R.M., HOPKINS, L. & MCEVOY,D. (1971) 3.small Anzm. Pract. 12, 453. KELLY, D.F., SIEGEL,E.T. & BERG, P. (1971) Vet. Path. 8, 385. MURPHY, B.E.P. (1967) J. Clin. Endocr. 27, 973. RIJNBERK, A., DER KINDEREN, P.J. & THIJSSEN, J.H.H. (1968a) 3. Endocr. 41, 397. A., DER KINDEREN, P. J. & THIJSSEN, J.H.H. (1968b) 3.Endocr. 41, 387. RIJNBERK, SIEGEL, E.T. (1965) Am. J . Vet. Res. 25, 1152. SIEGEL,E.T. (1968) Am. 3. Vet. Res. 29, 173. SIEGEL, E.T., KELLY,D.F. & BERG,P. (1970) 3. Am. Vef.Med. Ass. 157, 2081. THORN, G.W. (1966) New Eng. 3. of Med. 274, 775. T.J., HENDRICKS, E.C. & GROSSMAN, M.S. (1967) Am. 3. WILSON, R.B., KLEINE,L.J., CLARKE, Vet. Res. 28, 313. VENZKE, W.G. (1967) 3. Am. Vet. Med. Ass. 151, 1706.