Radiation Therapy for Pituitary Macrotumors in Dogs

Stallion is a 12 ½ year old male castrated Chihuahua mix who presented for possible seizures and weakness. Approximately 6 months earlier he started to lose his balance and stumble, stare into space and became polyuric and polydypsic (PU/PD). On neurologic exam neck pain, left facial nerve paresis and occasional knuckling on the right thoracic limb were noted. Neuroanatomic localization was multifocal CNS disease.   Blood work revealed mildly increased in Alkaline Phosphatase of 352 and ALT of 137. Further bloodwork including a serum cortisol, Accuplex (Lyme/Hearworm/Anaplasma/Ehrlichia ), thyroid panel and Rocky Mountain Spotted Fever titers were submitted. A low TSH was noted on the thyroid panel (TSH 1.46 ng/ml, normal 0-0.6). Serum cortisol, RMSF titer and the Accuplex were all normal. Treatment with thyroxine was initiated.   Possible seizure like episodes continued at home and magnetic resonance imaging (MRI) of the brain was elected.

Standard MRI sequences of the brain were performed including sagittal T2-weighted series, transverse T2-weighted, FLAIR, T1-weighted and T2*-GRE series and T1-weight series in transverse, dorsal and sagittal planes following intravenous contrast administration of gadolinium.

The MRI demonstrated a large sellar/suprasellar mass which was hyperintense to adjacent white matter of the brain in T2-W images (Figure 1), isointense in T1-W images and strongly contrast enhancing. The mass was causing marked dorsal and lateral displacement of the overlying hypothalamus and thalamus.

Differential diagnoses for a suprasellar mass include a pituitary tumor, meningioma, craniopharyngioma, germ cell tumor, and hypothalamic glial tumor. Pituitary tumors are by far the most common suprasellar neoplasia and include both adenomas and adenocarcinomas. These originate from the pars intermedius or pars distalis of the pituitary. In general pituitary masses greater than 1 cm in diameter are considered pituitary macroadenomas/adenocarcinomas. Pituitary tumors may be functional or nonfunctional .

The most common clinical signs associated with pituitary macrotumors include those signs indicative of Cushing’s disease. When neurologic signs develop they are consistent with intra-cranial disease with lethargy, anorexia, stupor and tetraparesis most common. Ataxia circling and behavioral changes are also frequently noted (Sarfaty 1988). Blindness is uncommon in contrast to what is seen in people and seizures are actually also uncommon. Disorders of water metabolism and thermoregulation may occur secondary to invasion of the hypothalamus.

Treatment options for pituitary macrotumors include medical treatment for pituitary dependent hyperadrenocorticism (Cushing’s disease) if present with either Mitotane or Trilostane. Neither has been shown to be superior to the other. An anticonvulsant such as phenobarbital to control seizures may be necessary and prednisone can help control peri-tumoral edema and inflammation.

Surgical treatment via a transphenoidal hypophysectomy has been described and is technically difficult but can lead to successful clinical outcome with 2 year survival rates reaching 80% (Meij 1988). Possible complications include tumor recurrence because of incomplete removal, mild post-operative hyponatremia or permanent diabetes insipidus post-operatively.   There is also certainly an upper limit as to size of tumor which can be removed and hypophysectomy has most often been performed in dogs with microadenomas rather than macroadenomas.

Radiation therapy is becoming more common in veterinary medicine as availability at Universities and referral practices increases. Median survival time for dogs with pituitary tumors treated with radiation therapy can reach 22-43 month in patients with no neurologic signs at time of presentation. In patients presenting with neurologic signs median survival is lower but can still reach 11.7-22 months (Bley 2005, Dow 1990, Theon 1998), demonstrating the benefit of early intervention in cases of pituitary dependent hyperadrenocorticism. Advanced diagnostic imaging such as CT or MRI in cases of pituitary dependent hyperadrenocorticism can identify those patients with macrotumors who would benefit most from radiation therapy. The diagnostic imaging studies also then are used for radiation therapy treatment planning with fusion of CT and MRI images allowing for precise localization for the delivery of radiation (Figure 2). The recent availability of Cyberknife (stereotatic radiation therapy) also provides exciting and promising new treatment options with many advances over tradition radiation therapy including a much shorter treatment course and improved sparing of normal tissue adjacent to a tumor.

Stallion received a full coarse of traditional radiation therapy (51 Gy) divided over 17 treatments. Repeat MRI 10 months later when neurologic signs recurred showed a marked reduction in tumor size however significant peri-tumoral edema had developed (Figure 3). A second course of radiation therapy was elected utilizing Cyberknife and consisted of a single dose of 15 Gy.

Christopher T Ryan, VMD, DABVP, DACVR

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Figure 2

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References:

Bley CR, Sumova A, Roos M, Kaser-Hotz B.   Irradiation of brain tumors in dogs with neurologic disease. J Vet Intern Med 2005;19:849-854

Dow SW, LeCouteur RA, Rosychuck RAW, et al. Response of dogs with functional pituitary macroadenomas and macrocarcinomas to radiation. JSAP 1990;31:287-294

Meij BP, Voorhout G, Ingh TS, et al. Results of transphenoidal hypophysectomy in 52 dogs with pituitary dependent hyperadrenocorticism. Vet Surg 1988;27:246-261

Sarfaty D, Carillo JM, Peterson ME. Neurologic, endocrinologic and pathologic findings associated with large pituitary tumors in dogs: eight cases (1976-1984). JAVMA 1988;193:651-656

Theon AP, Feldman EC. Megavoltage irradiation of pituitary macrotumors in dogs with neurologic signs. J Am Vet Med Assoc 1998;213:225-231

 

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