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Radiation to treat pituitary tumors associated with acromegaly

Wormhoudt TL, Boss MK, Lunn K, Griffin L, Leary D, et al. Stereotactic radiation therapy for the treatment of functional pituitary adenomas associated with feline acromegaly. J Vet Intern Med. 2018 Jul;32(4):1383-1391. PubMed PMID: 29782043.

Acromegaly is a disease characterized by a mass on the pituitary gland that secretes excessive growth hormone and leads to an increase in Insulin-Like Growth Factor (IGF-1). This results in increased appetite and weight gain, increased drinking and urinating, large head and paws, and increased respiratory noise, and occasionally neurologic disease. The classic syndrome associated with acromegaly is insulin-resistant diabetes. Males are more commonly affected than females, and it has been estimated that up to 18% of male diabetic cats may be afflicted with acromegaly. Diagnosis is made by a combination of clinical signs, elevated IGF-1 levels, and advanced neuroimaging demonstrating a pituitary tumor.

Management of acromegaly is traditionally focused on control of secondary issues (ie diabetes). Pasireotide is a somatostatin analogue that has been used to specifically treat elevated growth hormone, however it is extremely expensive and has undesirable side effects. Definitive therapy with trans-sphenoidal hypophysectomy may be curative, but is an extremely technically challenging surgery with a high mortality rate.

Stereotactic radiation therapy (SRT) allows for the delivery of high doses of radiation to a specific, targeted area with minimal damage to surrounding tissue. This allows a curative intent radiation protocol to be performed in few radiation sessions, though advanced equipment and training are needed. The purpose of this paper was to describe the outcome for 53 cats treated with SRT at a university teaching hospital.

Cats were recruited retrospectively from the cohort of animals presenting for curative intent SRT with a diagnosis of acromegaly and diabetes mellitus in an 8 year period. Recorded information included signalment, clinical signs before and after therapy, insulin dose before and after therapy, acute and late radiation effects, response to therapy, and overall survival time. Diagnostic test results (radiographs bloodwork, advanced imaging, etc) were also recorded. CT was used for radiation planning, and therapy was performed with a linear accelerator.

56 cats with pituitary tumors were identified, of which 53 were diagnosed with acromegaly. Median age at time of treatment was 10 years. 43 cats (81%) were neutered males, and 10 (19%) neutered females. 43 were domestic shorthairs, 8 domestic longhairs, and 2 Maine Coons. All cats had poorly insulin responsive diabetes mellitus.

40 patients had an IGF-1 level evaluated, all of which were elevated. All cats received a CT scan- 4 cats (8%) had a presumed microadenoma, with the remainder having a visible macroadenoma.

The radiation protocol changed over the 8 year course of the study, with a general trend towards higher doses per fraction as time progressed. Cats received between 18 and 24 Gy total dose over 3-4 sessions.

The median survival after radiotherapy was 1072 days. Causes of death included heart disease (13%), neurologic disease (13%), CKD (11%), and 15% unrelated to acromegaly. There was no association between IGF-1 level or tumor volume and survival.

Information on insulin requirements were available for 77% of cats. 95% experienced a decrease in their insulin requirement, and 32% went into full remission. 38% of the cats that remitted later relapsed. The median decrease in insulin requirement was 72%. Two-thirds of cats with neurologic signs experienced improvement.

Acute radiation effects were seen in 18% of cats including mental dullness, photophobia, and mydriasis. 14% of cats developed hypothyroidism and required supplementation. One cat lost vision in both eyes 25y after treatment without the formation of cataracts (presumably due to optic chiasm damage).

Overall, SRT was associated with excellent survival in this population of cats with acromegaly. There was a significant decrease in insulin requirement seen in most cats, and ~1/3 experienced diabetic remission. Long term survival and decrease in insulin requirement were improved in this study compared to traditional radiation protocols. SRT shows promise as a treatment option for acromegaly in cats. (MRK)

See also:

Brearley MJ, Polton GA, Littler RM, Niessen SJ. Coarse fractionated radiation therapy for pituitary tumours in cats: a retrospective study of 12 cases. Vet Comp Oncol. 2006; 4:209–217