History
A 9-year-old 17.4-kg (38.3-lb) spayed female pit bull–type dog was examined because of signs of mentation change, lethargy, ataxia, and cachexia of 1 week's duration. Three months prior, the dog had been referred to our institution for weight loss and signs of mentation change, and results of thoracic radiography and cranial CT (not shown) indicated a large (2.0 × 1.8 × 1.8-cm) mass arising from the hypothalamus, most consistent with a pituitary macroadenoma. The dog was prescribed prednisone (0.25 mg/kg [0.11 mg/kg], PO, q 12 h) and underwent stereotactic radiation therapy (24 Gy total, delivered in 3 consecutive fractions). Resolution of weight loss and signs of mentation change occurred after radiation therapy, and the owners reported that the dog had acted normal at home since then, until approximately 1 week before the initial examination of the present report.
On physical examination, the dog was ataxic and thin (body condition score of 3 on a scale from 1 to 9) and had pale to light pink mucous membranes, mildly increased respiratory effort but no crackles or wheezes on auscultation, a grade 2/6 to 3/6 left apical systolic heart murmur, and signs of dull mentation. The remainder of the physical examination was unremarkable.
Hematologic abnormalities included leukocytosis (24,700 WBCs/μL; reference range, 8,000 to 14,500 WBCs/μL), characterized by neutrophilia (22,800 neutrophils/μL; reference range, 3,000 to 11,500 neutrophils/μL), monocytosis (1,600 monocytes/μL; reference range, 100 to 1,400 monocytes/μL), and lymphopenia (400 lymphocytes/μL; reference range, 1,000 to 4,800 lymphocytes/μL). Abnormalities detected on serum biochemical analyses included high activities of aspartate aminotransferase (152 U/L; reference range, 0 to 50 U/L), alanine aminotransferase (729 U/L; reference range, 0 to 60 U/L), alkaline phosphatase (3,309 U/L; reference range, 0 to 100 U/L), and γ-glutamyltransferase (226 U/L; reference range, 0 to 8 U/L); hypercholesterolemia (256 mg/dL; reference range, 150 to 240 mg/dL); hypophosphatemia (3.3 mg/dL; reference range, 3.4 to 6.3 mg/dL); and a high anion gap (22.9 mmol/L; reference range, 7.4 to 19.8 mmol/L). Thoracic radiography was performed (Figure 1).
Dorsoventral (A) and right lateral (B) thoracic radiographic images of a 9-year-old 17.4-kg (38.3-lb) spayed female pit bull–type dog examined because of signs of mentation change, lethargy, ataxia, and cachexia of 1 week's duration 3 months after undergoing radiation therapy and being prescribed prednisone for a pituitary macroadenoma.
Citation: Journal of the American Veterinary Medical Association 256, 5; 10.2460/javma.256.5.545
Dorsoventral (A) and right lateral (B) thoracic radiographic images of a 9-year-old 17.4-kg (38.3-lb) spayed female pit bull–type dog examined because of signs of mentation change, lethargy, ataxia, and cachexia of 1 week's duration 3 months after undergoing radiation therapy and being prescribed prednisone for a pituitary macroadenoma.
Citation: Journal of the American Veterinary Medical Association 256, 5; 10.2460/javma.256.5.545
Dorsoventral (A) and right lateral (B) thoracic radiographic images of a 9-year-old 17.4-kg (38.3-lb) spayed female pit bull–type dog examined because of signs of mentation change, lethargy, ataxia, and cachexia of 1 week's duration 3 months after undergoing radiation therapy and being prescribed prednisone for a pituitary macroadenoma.
Citation: Journal of the American Veterinary Medical Association 256, 5; 10.2460/javma.256.5.545
Determine whether additional imaging studies are required, or make your diagnosis from Figure 1—then turn the page →
Radiographic Findings and Interpretation
Thoracic radiography revealed too numerous to count round to irregular soft tissue opaque nodules in all lung lobes (Figure 2). Pulmonary nodules were diagnosed, with a differential diagnosis of metastatic neoplasia or fungal granulomatous disease. Additionally, mild hepatomegaly was evident (additional radiographic images not shown), and the differential diagnoses included iatrogenic cause from prednisone administration, extramedullary hematopoiesis, infectious or inflammatory processes, or primary hepatic or metastatic neoplasia.
The same radiographic images as in Figure 1. There are too numerous to count round to irregular soft tissue opaque nodules (arrows) evident in all lung lobes.
Citation: Journal of the American Veterinary Medical Association 256, 5; 10.2460/javma.256.5.545
The same radiographic images as in Figure 1. There are too numerous to count round to irregular soft tissue opaque nodules (arrows) evident in all lung lobes.
Citation: Journal of the American Veterinary Medical Association 256, 5; 10.2460/javma.256.5.545
The same radiographic images as in Figure 1. There are too numerous to count round to irregular soft tissue opaque nodules (arrows) evident in all lung lobes.
Citation: Journal of the American Veterinary Medical Association 256, 5; 10.2460/javma.256.5.545
Treatment and Outcome
The dog was hospitalized and treated with dexamethasone sodium phosphate (0.10 mg/kg [0.05 mg/lb], IV, once) on admission and isotonic crystalloid fluids (3.5 mL/kg/h [1.6 mL/lb/h], IV) overnight. Because the dog vomited multiple times overnight, maropitant citrate (1.0 mg/kg [0.5 mg/lb], IV, once) was administered. On the second day of hospitalization, the dog's respiratory effort worsened, with crackles and wheezes detected on auscultation of the caudodorsal lung fields. Because of concern for the dog's overall quality of life and lack of response to treatment with supportive care, the owners elected euthanasia and necropsy for the dog.
Results of necropsy indicated necrotizing and pyogranulomatous pneumonia, with widespread, firm, white nodules ≤ 2 cm in diameter, consistent with the radiographic findings. Histologic evaluation of the pulmonary nodules revealed intrahistiocytic protozoal organisms (eg, Toxoplasma gondii or Neospora caninum), and PCR assay results confirmed the presence of T gondii. The previously suspected pituitary macroadenoma was confirmed as a chromophobe adenoma of the pars distalis and measured 2.0 × 1.0 × 1.0 cm, which was smaller compared with findings on CT at the time of diagnosis 3 months earlier. No histologic evidence of adverse effects from radiation therapy was noted. In addition, steroid hepatopathy and a unilateral right thyroid adenocarcinoma were identified on necropsy.
Comments
Because the dog in the present report was returned 3 months after stereotactic radiation therapy with similar signs of mentation change and weight loss as it had when its pituitary macroadenoma was diagnosed, an initial concern was the possibility of tumor recurrence. Thus, diagnostic procedures were aimed to clarify whether the clinical signs were related to the previously diagnosed and treated pituitary tumor or the result of a new condition. When thoracic radiography revealed pulmonary nodules too numerous to count, the radiographic images were compared with those obtained of the dog 3 months earlier (at the time of radiation therapy). No such abnormalities were evident on the earlier images.
Although pulmonary metastasis from the pituitary neoplasm was considered unlikely,1 it was a differential diagnosis for the pulmonary nodules observed in the dog of the present report. Chromophobe adenomas are considered hormonally inactive; however, physical expansion of the tumor can result in progressive neurologic signs.2 Such neurologic signs are variable but those most frequently reported include stupor, lethargy, circling, disorientation, wandering, anorexia, ataxia, pacing, tetraparesis, and head pressing.2,3 Although we could not completely rule out metastatic neoplasia arising from the pituitary tumor, the possibility of recurrence or metastasis was thought to be unlikely because recurrence of the tumor to the extent to cause clinical signs would not have been expected 3 months after radiation therapy, and pituitary tumors are thought not to metastasize.
In addition to metastatic neoplasia, we considered granulomatous fungal disease as a differential diagnosis for the pulmonary lesions in the dog of the present report. However, T gondii, a common protozoan parasite found throughout the world, was confirmed with a PCR assay after necropsy. Dogs are intermediate hosts of T gondii, with ingestion of undercooked meat containing the encysted stage or ingestion of cat feces containing oocysts being the most common routes of infection.4 Exposed adult animals with adequate immune systems are thought to develop subclinical infections; however, juvenile animals and animals with weakened immune systems are extremely susceptible to developing clinical disease with signs including fever, diarrhea, cough, dyspnea, icterus, seizures, and death, alone or in combination.4,5 Across human and animal hosts, T gondii is the most frequent protozoa to cause opportunistic infections in immunocompromised patients,5 and detection is generally through use of serologic assays, including ELISAs and, indirect fluorescent antibody, indirect hemagglutination, and latex agglutination tests. Testing for the presence of IgM or IgG against T gondii can help detect either recent infection or chronic exposure, respectively; however, false-positive and false-negative results may occur.4
Because the dosage of prednisone prescribed to the dog in the present report after radiation therapy was an anti-inflammatory dosage and not an immunosuppressive dosage, it was unclear regarding when the dog may have become infected with T gondii, or to what extent prednisone may have contributed to the dog's immunosuppression. The clinical importance of subclinical infection in dogs undergoing radiation therapy is not known. Nonetheless, given that chromophobe adenomas do not produce cortisol, it is unlikely that hyperadrenocorticism was a contributing factor to the dog's immunosuppression.
The radiographic finding of pulmonary nodules too numerous to count that developed within a 3-month time frame in this dog with a benign pituitary tumor was unexpected. Results for the dog in the present report highlighted that toxoplasmosis and other opportunistic infections should not be dismissed as potential differential diagnoses in patients that develop a radiographically evident nodular pulmonary pattern after being treated for neoplasia.
References
1. Pollard RE, Reilly CM, Uerling MR, et al. Cross-sectional imaging characteristics of pituitary adenomas, invasive adenomas and adenocarcinomas in dogs: 33 cases (1988–2006). J Vet Intern Med 2010;24:160–165.
2. Greco DS. The pituitary gland. In: Aiello SE, Mays A, eds. Merck veterinary manual. 8th ed. Readington, NJ: Merck & Co Inc, 1998;405–414
3. Ihle SL. Pituitary corticotroph macrotumors—diagnosis and treatment. Vet Clin North Am Small Anim Pract 1997;27:287–297.
4. Rottman JB. Toxoplasmosis. In: Merck veterinary manual. 8th ed. Readington, NJ: Merck & Co Inc, 1998;488–489.
5. Cong W, Liu GH, Meng QF, et al. Toxoplasma gondii infection in cancer patients: prevalence, risk factors, genotypes, and association with clinical diagnosis. Cancer Lett 2015;359:307–313.
