Neurologic signs can be subtle

Signalment

Canine, Boston Terrier, 10-year-old, male castrated, 23 pounds.

Clinical history

The dog presents in March 2001 for the following history. The dog has become selectively fussy with eating and inappetence for the past two months. He had been receiving one-quarter can Prescription Diet Canine L/D & one-quarter cup Prescription Diet Canine K/D dry twice a day. On a begging issue, he would essentially eat anything offered.

The owner has noticed a discontinued liking of anything sweet, such as fruits. In the past month, there has been an increasing difficulty in getting dog food in him. The owner was mixing things such as cooked egg and pancakes to entice the dog to eat something. In the past week, preferences are dropping fast, as the owner can only get the dog to eat turkey lunch meat, some soy chicken patties, cheese crackers, and macaroni and cheese in small amounts.

Table 1

He at times acts partially hungry but will only eat the above foods and, at that point, small amounts with some drooling noted. There have been two episodes of vomiting in February 2000 �� vomitus contained bile and vomiting was not associated with eating. With previous history of increased serum liver enzymes, the owner (who is a veterinarian) is questioning if a degree of hepatic encephalopathy is occurring. The dog was anesthetized in December 2000 to check for any dental disease and TMJ disease, as there has been some difficulty in opening the dog's mouth. In addition, the dog has had acute neck pain from intervertebral disk disease and geriatric vestibular disease.

Physical examination

The findings include rectal temperature 100.0�� F, heart rate 80/min, respiratory rate 20/min, pink mucous membranes, normal capillary refill time, grade 3 systolic murmur on the left side and grade 2 systolic murmur on the right side, and normal lung sounds. The abdomen is somewhat difficult to palpate. The physical examination decreased muscle mass, no evidence of coughing, no known seizure activity and no pain on abdominal palpation.

Therapy

Therapy has included 12/2000 Zenoquin 37.5 mg SID for 30 days for UTI (have not rechecked urine culture yet) and Anipryl 10 mg SID since summer 2000 for failing housebreaking (took two months to notice improvement but did help). In past week, the dog has not received any medications due to difficulty with giving medications and need to prioritize medications. The dog has been receiving Actigall 150 mg SID since winter 1999 (again not received in past week), past week administered Pepcid 10 mg SID, started Zenoquin on 3/12/01 37.5 mg SID, and administered Medrol 2 mg twice a week in morning the past several months to control neck pain discomfort (last Medrol dosing was 1 mg on 3/10/01 and 2 mg 3/11/01). Previous use of Rimadyl had no effect. The work-up so far has the owner questioning the possibility of chronic pancreatitis in the dog, chronic neck pain, stress, use of steroids, and variable diets. Any advice to improve appetite in this older dog?

Laboratory results

A complete blood count, serum chemistry profile and urinalysis were performed and are outlined in Table 1, p. 14S.

Bile acid results

The fasted baseline bile acid is 14 umol/L (normal, 0-10) and two-hour postprandial bile acid is 21 umol/L (normal, 0-15).

Radiographic review

Survey thoracic and abdominal radiographs were done. The thoracic and abdominal radiographs are normal.

Figure 1

Ultrasound examination

Thorough abdominal ultrasonography was performed with the dog positioned in dorsal recumbency. The liver is normal in size and shows a slightly generalized increase in echogenicity in all liver lobes. The gallbladder is mildly distended, and its walls are not thickened or hyperechoic. The gallbladder does contain a moderate amount of sludge material. The spleen was not well imaged. The left kidney shows a slightly echobright cortex and a single cortical cyst. The right kidney shows a slightly echobright cortex and multiple, small mineralized densities in the pelvic region. No masses were noted in either kidney. The urinary bladder is partially distended with urine and contains some urine sediment material. No masses or calculi noted. The stomach wall appears to be normal. The adrenal glands, pancreas and small intestine were not imaged.

Case management

In this case, possible pituitary-dependent hyperadrenocorticism and/or hypothalamic mass/inflammatory disease is the clinical diagnosis.

At this point, I would recommend doing an ACTH stimulation test to rule out adrenal gland dysfunction. If the ACTH test results were normal, then I would proceed with a CT or MRI scan of the brain, especially of the hypothalamic/pituitary gland area.

Brain scan

A brain scan was performed and the transverse views of the post-contrast scan are shown in Figure 1.

My comments

The transverse views of the post-contrast scan shows a densely enhancing mass arising from the pituitary fossa and causing compression of the floor of the overlying third ventricle.

Look for the signs

So, what are the signs for pituitary macro tumors and central nervous system signs?

Pituitary tumors and dogs with pituitary-dependent hyperadrenocorticism may grow to a size exceeding 1 cm in diameter.

Such a mass, whether present at the time of diagnosis or years after beginning treatment for adrenal dysfunction, can cause clinical signs due to dorsal expansion and compression of the hypothalamus, invagination of the pituitary stalk, which connects the hypothalamus with the pituitary gland; or dilatation of the infundibular recess and third ventricle.

The clinical signs exhibited by dogs with pituitary macro tumors often reflect both endocrine and space-occupied effects of the tumor.

When neurologic signs first begin to be recognized, they are almost always subtle. That is obvious to the owner, but not obvious to the veterinarian. Common initial signs are that the dog seems to be dull and listless and has a poor appetite. These signs may progress to anorexia, restlessness, loss of interest in normal household activities and brief episodes of disorientation.

More definitive but late signs exhibited by dogs with pituitary macro tumors include altered mentation, ataxia and aimless pacing. Some of these dogs may be misdiagnosed as being blind because their mental signs result in inappropriate responses to visual stimuli.

Making the diagnosis

The specific diagnosis of a pituitary macro tumor is made with results of CT and MRI scans. The pituitary macro tumor is being recognized with increasing frequency owing to improved diagnostic capabilities of CT and MRI scans and an increasing index of suspicion.

The recognition of typical clinical signs is extremely important. The untreated dog with pituitary-dependent hyperadrenocorticism and a poor appetite but with other signs associated with pituitary-dependent hyperadrenocorticism should be considered a possibility for a large intracranial tumor.

Anorexia in a treated dog with pituitary-dependent hyperadrenocorticism should always be assumed to have hypocortisolism until proven otherwise.

Clinical problems

Conservatively, 15 percent to 20 percent of all dogs with pituitary-dependent hyperadrenocorticism develop clinical problems due to a growing pituitary tumor. The preferred method of treating these dogs is photon irradiation. Success, to date, has been limited. Most of the dogs undergoing photon irradiation have had significant clinical signs and extremely large intracranial masses.

Response to treatment will improve in the future as the ability to identify affected dogs earlier in the course of their disease improves. The results of the photon irradiation will be better when directed at smaller tumors or in dogs less debilitated by the condition. Most dogs with central nervous system signs have masses much too large for surgical extirpation.

Success in resolving some to all of the clinical signs has been achieved with the use of cobalt-60 photon irradiation or with the use of linear accelerator photon irradiation.

Treatment usually involves delivery of a predetermined total dose of radiation given in fractions over a period of several weeks. Irradiation may reduce tumor size and cause a reduction in or elimination of the central nervous system clinical signs.

Reduction of the secretory nature of the pituitary tumor is variable, and secretion may even increase despite a confirmed reduction in tumor size. Therefore, medical therapy with Mitotane may be necessary in addition to pituitary mass irradiation.