Hind limb ataxia, proprioceptive deficits, and weakness can be a common presentation in geriatric rats greater than 18 months of age.[i] Head tilt, head shaking, and circling may also occur, although generally without nystagmus. Difficulty prehending food with the front paws, fore limb proprioceptive deficits, and weight loss may sometimes also be seen. Signs may be continuous or intermittent, stable or progressive. Other behavioral or mentation changes are usually not seen.
As in any other patient, a thorough history should be obtained, and a neurologic examination should be performed as completely as possible to attempt to localize the lesion. Hind limb tactile and visual placing cannot always be reliably assessed in normal rats, although fore limb placing is usually consistent.[ii] Proprioception may often be most reliably assessed by observing ambulation.
While trauma and other neoplasias may occur, when proprioceptive deficits with or without vestibular signs occur, by far the most common underlying etiology is a pituitary tumor, reported in 83-85% of some strains of laboratory rats.i Clinical signs are due either to compression of the brain stem or as an endocrine peripheral polyneuropathy.
Pituitary tumors are extremely common in geriatric rats, and adenomas are the most common of these. Pituitary adenomas in rats are usually associated with increased prolactin secretion, resulting in mammary hyperplasia as well as stimulation of mammary neoplasia growth.[iii],[iv] Hind limb neurological signs can occur prior to obvious mammary masses, concurrent with them, or after masses have been identified and removed. One report suggests that pituitary adenomas are less common in ovariectomized female laboratory rats, possibly due to disruption of the pituitary/hypothalamic-gonadal feedback axis, although it is not known whether this is strain-specific or also true for common breeds of pet rats. Overweight rats also appear to be anecdotally over-represented.i
While magnetic resonance imaging is often thought of as the modality of choice for imaging of the central nervous system, MRI is not frequently utilized for pet rats due to the expense to the client and the prolonged anesthetic time required. Several studies have demonstrated the utility of contrast computed tomography for detection of pituitary enlargement and specifically pituitary adenomas in dogs,[v],[vi]and in a case series presented for the Association of Exotic Mammal Veterinarians at ExoticsCon in 2016, we have demonstrated that contrast CT may be used instead of MRI to identify pituitary enlargement in the client-owned pet rat. Our single case of confirmed pituitary carcinoma in a pet rat did not enhance well with contrast, which is similar to what is seen in dogs.
Tranverse and sagittal views of contrast CT of a pituitary mass in a pet rat:
Depending on the temperament of the individual patient, either sedation or anesthesia is required. Generally, an intravenous catheter is placed in the lateral tail vein for the administration of a nonionic iodinated contrast agent such as Optiray. In the very petite individual, an intraosseous catheter may be used if placement of an intravenous catheter is not possible. However, our experience and a recent study both suggest that contrast-enhancement may be more challenging to interpret when delivered intraosseously.
CT images are obtained before and after administration of contrast, and any masses are located and identified. At Angell, we have identified pituitary masses in pet rats ranging from 5 x 4 mm to 10.6 x 6 mm.
If a prolactin-secreting pituitary adenoma is suspected, cabergoline may be prescribed through a compounding pharmacy at 0.6 mg/kg PO 72h. Cabergoline is dopamine receptor agonist which increases hypothalamic dopamine; this inhibits prolactin secretion.i The drug has good oral absorption with minimal side effects and has been shown to reduce both prolactin secretion and tumor size in rats with experimentally induced prolactin-secreting pituitary adenomas. Individual response in pet rats with spontaneous tumors may vary.
Bromocriptine may be considered in cases that do not respond to cabergoline. Although it seems to be well-tolerated in rats, other species experience adverse effects more commonly than they do with cabergoline, including vomiting and other GI signs, CNS depression, and hypotension. Dosing is not as convenient, as both oral absorption and duration are poor, necessitating daily subcutaneous injections at 3 mg/kg.
In one of our pituitary tumor cases, vertigo seemed to be subjectively present, and we found meclizine hyclate at 24 mg/kg PO q8-12hr to be helpful in restoring quality of life.
Potential medical treatment (cabergoline, bromocriptine) can be expensive (up to $200 per month). Because medication is not always successful and prognosis can be quite poor, CT with contrast has often been useful in confirming a diagnosis of pituitary mass for owners struggling with decisions regarding continuing medical treatment vs. euthanasia, and has helped provide owners with peace of mind when making end-of-life decisions for their pet.
For more information, please contact Angell’s Avian/Exotic Medicine Service at 617-989-1561 or firstname.lastname@example.org.
[i] Mayer J, Sato A, et al. Extralabel use of cabergoline in the treatment of a pituitary adenoma in a rat. JAVMA. 2011;239:656-660.
[ii] Vannevel JY. Clinical presentation of pituitary adenomas in rats. VCNA:Exotic Animal Practice. 2006;9:673-676.
[iii] Uchida K, Matsuzawa H, Kusano N, Mutai M. Spontaneous pituitary changes and their influences on mammary glands in SD female rats. Jikken Dobutsu. 1981;30:421-433.
[iv] Pearson OH, Llerena O, Llerena L et al. Prolactin-dependent rat mammary cancer: a model for man? Transactions Assoc Amer Phys. 1969;82:225-238.
[v] Auriemma E, Barthez PY, van der Vlugt-Meijer RH et al. Computed tomography and low-field magnetic resonance imaging of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism: 11 cases (2001-2003). JAVMA. 2009;235:409-414.
[vi] 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.