• 1. Coleman GL, Barthold W, Osbaldiston GW, et al. Pathological changes during aging in barrier-reared Fischer 344 male rats. J Gerontol 1977; 32: 258278.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Sass B, Rabstein LS, Madison R, et al. Incidence of spontaneous neoplasms in F344 rats throughout the natural life-span. J Natl Cancer Inst 1975; 54: 14491456.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Kroes R, Garbis-Berkvens JM, de Vries T, et al. Histopathological profile of a Wistar rat stock including a survey of the literature. J Gerontol 1981; 36: 259279.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. McComb DJ, Kovacs K, Beri J, et al. Pituitary gonadotroph adenomas in old Sprague-Dawley rats. J Submicrosc Cytol 1985; 17: 517530.

  • 5. Suzuki H, Mohr U, Kimmerle G. Spontaneous endocrine tumors in Sprague-Dawley rats. J Cancer Res Clin Oncol 1979; 95: 187196.

  • 6. Vannevel JY. Clinical presentation of pituitary adenomas in rats. Vet Clin North Am Exot Anim Pract 2006; 9: 673676.

  • 7. Burek JD. Pathology of geriatric rats: a morphological and experimental study of the age-associated lesions in aging BN/Bi, WAG/Rij, and (WAG × BN)F b1 s rats. West Palm Beach, Fla: CRC Press, 1978.

    • Search Google Scholar
    • Export Citation
  • 8. McComb DJ, Hellmann P, Kovacs K, et al. Spontaneous sparsely-granulated prolactin-producing pituitary adenomas in geriatric rats. A prospective study of the effect of bromocriptine. Neuroendocrinology 1985; 41: 201211.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. McComb DJ, Kovacs K, Beri J, et al. Pituitary adenomas in old Sprague-Dawley rats: a histologic, ultrastructural, and immunocytochemical study. J Natl Cancer Inst 1984; 73: 11431166.

    • Search Google Scholar
    • Export Citation
  • 10. Sun B, Fujiwara K, Adachi S, et al. Physiological roles of prolactin-releasing peptide. Regul Pept 2005; 126: 2733.

  • 11. Galas L, Raoult E, Tonon MC, et al. TRH acts as a multifunctional hypophysiotropic factor in vertebrates. Gen Comp Endocrinol 2009; 164: 4050.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Samson WK, Taylor MM, Baker JR. Prolactin-releasing peptides. Regul Pept 2003; 114: 15.

  • 13. Kovacs K, Ilse G, Ryan N, et al. Pituitary prolactin cell hyperplasia. Horm Res 1980; 12: 8795.

  • 14. Kovacs K, Horvath E, Ilse RG, et al. Spontaneous pituitary adenomas in geriatric rats. A light microscopic, immunocytological and fine structural study. Beitr Pathol 1977; 161: 116.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. Taradach C, Greaves P. Spontaneous eye lesions in laboratory animals: incidence in relation to age. Crit Rev Toxicol 1984; 12: 121147.

  • 16. Loh JA, Verbalis JG. Disorders of water and salt metabolism associated with pituitary disease. Endocrinol Metab Clin North Am 2008; 37: 213234.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Chapman PS, Petrus D, Neiger R. Hypodipsic hypernatremia in eight dogs. Tierarztl Prax Ausg K Kleintiere Heimtiere 2009; 37: 1520.

  • 18. Morrison JA, Fales-Williams A. Hypernatremia associated with intracranial B-cell lymphoma in a cat. Vet Clin Pathol 2006; 35: 362365.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Heath SE, Peter AT, Janovitz EB, et al. Ependymoma of the neurohypophysis and hypernatremia in a horse. J Am Vet Med Assoc 1995; 207: 738741.

    • Search Google Scholar
    • Export Citation
  • 20. Bernardis LL, Bellinger LL. The dorsomedial hypothalamic nucleus revisited: 1998 update. Proc Soc Exp Biol Med 1998; 218: 284306.

  • 21. Hayashi T, Murata M, Saito T, et al. Pathogenesis of chronic hypernatremia with dehydrated and non-dehydrated states in hypothalamic space-occupying lesions. Endocr J 2008; 55: 651655.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. vanNesselrooij JH, Bruijntjes JP, van Garderen-Hoetmer A, et al. Magnetic resonance imaging compared with hormonal effects and histopathology of estrogen-induced pituitary lesions in the rat. Carcinogenesis 1991; 12: 289297.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. van Nesselrooij JH, Szeverenyi NM, Ritter-Hrncirik C, et al. Rat pituitary changes observed with magnetic resonance imaging following removal of estrogen stimulus: correlation with histopathology and immunohistology. Carcinogenesis 1992; 13: 277282.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. van Nesselrooij JH, Szeverenyi NM, Tillapaugh-Fay GM, et al. Gadolinium-DTPA-enhanced and digitally subtracted magnetic resonance imaging of estrogen-induced pituitary lesions in rats: correlation with pituitary anatomy. Magn Reson Imaging 1990; 8: 525533.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Rudin M, Briner U, Doepfner W. Quantitative magnetic resonance imaging of estradiol-induced pituitary hyperplasia in rats. Magn Reson Med 1988; 7: 285291.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Balarini Lima GA, Machado Ede O, Dos Santos Silva CM, et al. Pituitary apoplexy during treatment of cystic macroprolactinomas with cabergoline. Pituitary 2008; 11: 287292.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. Magnusson G, Majeed SK, Gopinath C. Infiltrating pituitary neoplasms in the rat. Lab Anim 1979; 13: 111113.

  • 28. Plumb DC. Plumb's veterinary drug handbook. 5th ed. Stockholm, Wis: Pharma Vet Inc, 2005.

  • 29. Eguchi K, Kawamoto K, Uozumi T, et al. In vivo effect of cabergoline, a dopamine agonist, on estrogen-induced rat pituitary tumors. Endocr J 1995; 42: 153161.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Dall'Ara A, Lima L, Cocchi D, et al. Inhibitory effect of cabergoline on the development of estrogen-induced prolactin-secreting adenomas of the pituitary. Eur J Pharmacol 1988; 151: 97102.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Colao A, Di Sarno A, Guerra E, et al. Drug insight: cabergoline and bromocriptine in the treatment of hyperprolactinemia in men and women. Nat Clin Pract Endocrinol Metab 2006; 2: 200210.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Sabuncu T, Arikan E, Tasan E, et al. Comparison of the effects of cabergoline and bromocriptine on prolactin levels in hyperprolactinemic patients. Intern Med 2001; 40: 857861.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33. Gillam MP, Molitch ME, Lombardi G, et al. Advances in the treatment of prolactinomas. Endocr Rev 2006; 27: 485534.

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Extralabel use of cabergoline in the treatment of a pituitary adenoma in a rat

Jörg Mayer Dr MED Vet, MSc, DABVP1, Amy Sato DVM DACVR2, Matti Kiupel PhD, DACVP3, Julie DeCubellis DVM, MS4, and Thomas Donnelly DVM, DACLAM5
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  • 1 Department of Clinical Sciences, Foster Hospital for Small Animals, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.
  • | 2 Department of Clinical Sciences, Foster Hospital for Small Animals, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.
  • | 3 Department of Pathobiology and College of Veterinary Medicine, Diagnostic Investigation and Diagnostic Center for Population and Animal Health, Michigan State University, Lansing, MI 48910.
  • | 4 Department of Clinical Sciences, Foster Hospital for Small Animals, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.
  • | 5 Department of Clinical Sciences, Foster Hospital for Small Animals, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.

Abstract

Case Description—A 0.65-kg (1.43-lb) 24-month-old sexually intact male albino pet rat was examined because of a 3-week history of hypodipsia, apparent blindness, and sudden change in behavior.

Clinical Findings—The rat was able to move around its cage but appeared unaware of its surroundings, was visually unresponsive, and seemed unusually aggressive. The rat's hind limbs appeared mildly paretic, and it had sporadic difficulty placing its hind limbs on a flat surface. Given the rat's age, history, and physical examination findings, the primary differential diagnosis was a pituitary tumor. Magnetic resonance imaging (MRI) of the rat's brain was performed and revealed a large pituitary mass, which was indicative of a tumor.

Treatment and Outcome—Cabergoline (0.6 mg/kg [0.27 mg/lb], PO, q 72 h) was administered. On follow-up MRI 2 months later, the pituitary mass had substantially decreased in size. For 6 months following the second MRI study, the rat continued to receive the same dosage of cabergoline and had no clinical signs of disease or unusual behavior. However, at 8.5 months after the start of the treatment, the rat was in poor condition and had clinical signs similar to those initially. A third MRI study was performed and revealed substantial regrowth of the mass. The rat was euthanized and a necropsy was performed; a histopathologic diagnosis of pituitary adenoma was made.

Clinical Relevance—Pituitary adenomas have long been recognized as a common finding in geriatric rats (> 18 months old). Affected rats may respond favorably to oral administration of cabergoline.

Abstract

Case Description—A 0.65-kg (1.43-lb) 24-month-old sexually intact male albino pet rat was examined because of a 3-week history of hypodipsia, apparent blindness, and sudden change in behavior.

Clinical Findings—The rat was able to move around its cage but appeared unaware of its surroundings, was visually unresponsive, and seemed unusually aggressive. The rat's hind limbs appeared mildly paretic, and it had sporadic difficulty placing its hind limbs on a flat surface. Given the rat's age, history, and physical examination findings, the primary differential diagnosis was a pituitary tumor. Magnetic resonance imaging (MRI) of the rat's brain was performed and revealed a large pituitary mass, which was indicative of a tumor.

Treatment and Outcome—Cabergoline (0.6 mg/kg [0.27 mg/lb], PO, q 72 h) was administered. On follow-up MRI 2 months later, the pituitary mass had substantially decreased in size. For 6 months following the second MRI study, the rat continued to receive the same dosage of cabergoline and had no clinical signs of disease or unusual behavior. However, at 8.5 months after the start of the treatment, the rat was in poor condition and had clinical signs similar to those initially. A third MRI study was performed and revealed substantial regrowth of the mass. The rat was euthanized and a necropsy was performed; a histopathologic diagnosis of pituitary adenoma was made.

Clinical Relevance—Pituitary adenomas have long been recognized as a common finding in geriatric rats (> 18 months old). Affected rats may respond favorably to oral administration of cabergoline.

Contributor Notes

Dr. Mayer's present address is Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

Dr. DeCubellis's present address is Ocean State Veterinary Specialists, Exotic Service, 1480 S County Trail, East Greenwich, RI 02818.

Supported by the Henry and Lois Foster Hospital for Small Animals of the Tufts Cummings School of Veterinary Medicine.

Presented at the annual meeting of the Association of Exotic Mammal Veterinarians, Milwaukee, August 2009.

The authors thank Dennis Katz for technical assistance.

Address correspondence to Dr. Mayer (mayerj@uga.edu).