Selecting The Best Treatment Option For A Dog With Cushing’S Syndrome

Open access

Abstract

Spontaneous hypercortisolism or Cushing's syndrome is a common endocrinopathy in dogs. Pituitary-dependent and adrenal-dependent hypercortisolism each require specific treatment and diagnostic imaging is very helpful in choosing the treatment that is appropriate. The aims and expectations of the treatment need to be established beforehand and discussed with the owner to avoid unexpected disappointments. The clinical signs of pituitary-dependent hypercortisolism caused by a pituitary microadenoma can be managed with the adrenocorticostatic drug trilostane, but the drug will not affect the pituitary tumor. Hypophysectomy is therefore preferred in those dogs that have an enlarged pituitary but are in good clinical condition and have a long life-expectancy. Inoperable pituitary tumors can be treated by radiotherapy. The best treatment in dogs with cortisol-secreting adrenocortical tumors is adrenalectomy. If surgery is not possible, because of vascular invasion or metastatic spread, mitotane is recommended. Treatment with trilostane can be considered but is only palliative: it does not affect the adrenocortical tumor.

REFERENCES

  • 1. Galac S, Reusch C, Kooistra H, Rijnberk A. Adrenals. In: Clinical Endocrinology of Dogs and Cats. Hannover, Germany:Schlutersche; 2010, 93-154.

  • 2. Galac S, Kars VJ, Voorhout G, Mol JA, Kooistra HS. ACTH-independent hyperadrenocorticism due to food-dependent hypercortisolemia in a dog: A case report. Vet J 2008,177:141-143.

  • 3. Galac S, Kooistra HS, Voorhout G, van den Ingh TS, Mol JA, van den Berg G, Meij BP. Hyperadrenocorticism in a dog due to ectopic secretion of adrenocorticotropic hormone. Domest Anim Endocrinol 2005,28:338-348.

  • 4. Boujon, CE. Ritz, U. Rossi, GL. Bestetti, GE. A clinic-pathological study of canine Cushing's disease caused by pituitary carcinoma. J Comp Path 1991,105:353-365.

  • 5. Labelle P, Kyles E, Farver TB, de Cock HEV. Indicators of malignancy of canine adrenocortical tumors: Histopathology and proliferation index. Vet Pathol 2004,41:490-497.

  • 6. Kooistra HS, Galac S. Recent advances in the diagnosis of cushing's syndrome in dogs. Vet Clin North Am Small Anim Pract 2010,40:259-267.

  • 7. Behrend EN, Kooistra HS, Nelson R, Reusch CE, Scott-Moncrieff JC. Diagnosis of spontaneous canine hyperadrenocorticism: 2012 ACVIM consensus statement (small animal]. J Vet Intern Med 2013,27:1292-1304.

  • 8. Gilor C, Graves TK. Interpretation of laboratory tests for canine cushing's syndrome. Top Companion Anim Med. 2011,26:98-108.

  • 9. van Vonderen IK, Kooistra HS, Rijnberk A. Influence of veterinary care on the urinary corticoid:Creatinine ratio in dogs. J Vet Intern Med 1998,12:431-435.

  • 10. Galac S, Buijtels JJ, Kooistra HS. Urinary corticoid: Creatinine ratios in dogs with pituitary-dependent hypercortisolism during trilostane treatment. J Vet Intern Med 2009,23:1214-1219.

  • 11. Kintzer PP, Peterson ME. Primary and secondary canine hypoadrenocorticism. Vet Clin North Am Small Anim Pract 1997,27:349-357.

  • 12. Ramsey IK. Trilostane in dogs. Vet Clin North Am Small Anim Pract 2010,40:269-283.

  • 13. Auriemma E, Barthez PY, van der Vlugt-Meijer RH, Voorhout G, Meij BP. Computed tomography and low-field magnetic resonance imaging of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism: 11 cases (2001-2003). J Am Vet Med Assoc 2009,15:409-414.

  • 14. van der Vlugt-Meijer RH, Meij BP, Voorhout G. Intraobserver and interobserver agreement, reproducibility, and accuracy of computed tomographic measurements of pituitary gland dimensions in healthy dogs. Am J Vet Res 2006,67:1750-1755.

  • 15. van der Vlugt-Meijer RH, Meij BP, Voorhout G. Dynamic computed tomographic evaluation of the pituitary gland in healthy dogs. Am J Vet Res 2004,65:1518-1524.

  • 16. Kooistra HS, Voorhout G, Mol JA, Rijnberk A. Correlation between impairment of glucocorticoid feedback and the size of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism. J Endocrinol 1997,152:387-394.

  • 17. van der Vlugt-Meijer RH, Meij BP, van den Ingh TS, Rijnberk A, Voorhout G. Dynamic computed tomography of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism. J Vet Intern Med 2003,17:773-780.

  • 18. van der Vlugt-Meijer RH, Meij BP, Voorhout G. Thin-slice three-dimensional gradient-echo magnetic resonance imaging of the pituitary gland in healthy dogs. Am J Vet Res 2006,67:1865-1872.

  • 19. Rodriguez Pineiro MI, de Fornel-Thibaud P, Benchekroun G, Garnier F, Maurey-Guenec C, Delisle F, et al. Use of computed tomography adrenal gland measurement for differentiating ACTH dependence from ACTH independence in 64 dogs with hyperadenocorticism. J Vet Intern Med 2011,25:1066-1074.

  • 20. Bertolini G, Furlanello T, De Lorenzi D, Caldin M. Computed tomographic quantification of canine adrenal gland volume and attenuation. Vet Radiol Ultrasound 2006,47:444-448.

  • 21. Bertolini G, Furlanello T, Drigo M, Caldin M. Computed tomographic adrenal gland quantification in canine adrenocorticotroph hormone-dependent hyperadrenocorticism. Vet Radiol Ultrasound 2008,49:449-453.

  • 22. Mogicato G, Layssol-Lamour C, Conchou F, Diquelou A, Raharison F, Sautet J, Concordet D. Ultrasonographic evaluation of the adrenal glands in healthy dogs: Repeatability, reproducibility, observer-dependent variability, and the effect of bodyweight, age and sex. Vet Rec 2011,168:130-134.

  • 23. Barthez PY, Nyland TG, Feldman EC. Ultrasonographic evaluation of the adrenal glands in dogs. J Am Vet Med Assoc 1995,1:1180-1183.

  • 24. Choi J, Kim H, Yoon J. Ultrasonographic adrenal gland measurements in clinically normal small breed dogs and comparison with pituitary-dependent hyperadrenocorticism. J Vet Med Sci. 2011,73:985-959.

  • 25. Benchekroun G, de Fornel-Thibaud P, Rodriguez Pineiro MI, Rault D, Besso J, Cohen A, et al. Ultrasonography criteria for differentiating ACTH dependency from ACTH independency in 47 dogs with hyperadrenocorticism and equivocal adrenal asymmetry. J Vet Intern Med2010,24:1077-1085.

  • 26. Pey P, Vignoli M, Haers H, Duchateau L, Rossi F, Saunders JH. Contrast-enhanced ultrasonography of the normal canine adrenal gland. Vet Radiol Ultrasound. 2011,52:560-567.

  • 27. Pey P, Rossi F, Vignoli M, Duchateau L, Marescaux L, Saunders JH. Use of contrastenhanced ultrasonography to characterize adrenal gland tumors in dogs. Am J Vet Res 2014, 75:886-892.

  • 28. Bargellini P, Orlandi R, Paloni C, Rubini G, Fonti P, Peterson ME, Boiti C. Contrast-enhanced ultrasonographic characteristics of adrenal glands in dogs with pituitary-dependent hyperadrenocorticism. Vet Radiol Ultrasound 2013,54:283-292.

  • 29. Greco DS, Peterson ME, Davidson AP, Feldman EC, Komurek K. Concurrent pituitary and adrenal tumors in dogs with hyperadrenocorticism: 17 cases (1978-1995). J Am Vet Med Assoc 1999,214:1349-1353.

  • 30. Thuroczy J, van Sluijs FJ, Kooistra HS, Voorhout G, Mol JA, van der Linde-Sipman JS, Rijnberk A. Multiple endocrine neoplasias in a dog: Corticotrophic tumour, bilateral adrenocortical tumours, and pheochromocytoma. Vet Q 1998,20:56-61.

  • 31. Meij BP, Voorhout G, van den Ingh TS, Hazewinkel HA, Teske E, Rijnberk A. Results of transsphenoidal hypophysectomy in 52 dogs with pituitary-dependent hyperadrenocorticism. Vet Surg 1998,27:246-261.

  • 32. Hanson JM, van ‘t HM, Voorhout G, Teske E, Kooistra HS, Meij BP. Efficacy of transsphenoidal hypophysectomy in treatment of dogs with pituitary-dependent hyperadrenocorticism. J Vet Intern Med 2005,19:687-694.

  • 33. Hanson JM, Teske E, Voorhout G, Galac S, Kooistra HS, Meij BP. Prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism. J Neurosurg 2007,107:830-840.

  • 34. Meij BP, Mol JA, van den Ingh TS, Bevers MM, Hazewinkel HA, Rijnberk A. Assessment of pituitary function after transsphenoidal hypophysectomy in beagle dogs. Domest Anim Endocrinol 1997, 14:81-97.

  • 35. Meij BP. Hypophysectomy as a treatment for canine and feline Cushing's disease. Vet Clin North Am Small Anim Pract 2001, 31:1015-1041.

  • 36. den Hertog E, Braakman JC, Teske E, Kooistra HS, Rijnberk A. Results of non-selective adrenocorticolysis by o,p’-DDD in 129 dogs with pituitary-dependent hyperadrenocorticism. Vet Rec 1999,144:12-17.

  • 37. Peterson ME, Kintzer PP. Medical treatment of pituitary-dependent hyperadrenocorticism. mitotane. Vet Clin North Am Small Anim Pract 1997,27:255-272.

  • 38. Rijnberk A, Belshaw BE. An alternative protocol for the medical management of canine pituitary-dependent hyperadrenocorticism. Vet Rec 1988,122:486-488.

  • 39. Kintzer PP, Peterson ME. Diagnosis and management of canine cortisol-secreting adrenal tumors. Vet Clin North Am Small Anim Pract 1997,27:299-307.

  • 40. Neiger R, Ramsey I, O'Connor J, Hurley KJ, Mooney CT. Trilostane treatment of 78 dogs with pituitary-dependent hyperadrenocorticism. Vet Rec 2002,150:799-804.

  • 41. Witt AL, Neiger R. Adrenocorticotropic hormone levels in dogs with pituitary-dependent hyperadrenocorticism following trilostane therapy. Vet Rec 2004,154:399-400.

  • 42. Galac S, Buijtels JJ, Mol JA, Kooistra HS. Effects of trilostane on the pituitary-adrenocortical and renin-aldosterone axis in dogs with pituitary-dependent hypercortisolism. Vet J 2010,183:75-80.

  • 43. Sieber-Ruckstuhl NS, Boretti FS, Wenger M, Maser-Gluth C, Reusch CE. Serum concentrations of cortisol and cortisone in healthy dogs and dogs with pituitary-dependent hyperadrenocorticism treated with trilostane. Vet Rec 2008,163:477-481.

  • 44. Wenger M, Sieber-Ruckstuhl NS, Muller C, Reusch CE. Effect of trilostane on serum concentrations of aldosterone, cortisol, and potassium in dogs with pituitary-dependent hyperadrenocorticism. Am J Vet Res 2004,65:1245-1250.

  • 45. Griebsch C, Lehnert C, Williams GJ, Failing K, Neiger R. Effect of trilostane on hormone and serum electrolyte concentrations in dogs with pituitary-dependent hyperadrenocorticism. J Vet Intern Med 2014,28:160-165.

  • 46. Ruckstuhl NS, Nett CS, Reusch CE. Results of clinical examinations, laboratory tests, and ultrasonography in dogs with pituitary-dependent hyperadrenocorticism treated with trilostane. Am J Vet Res 2002,63:506-512.

  • 47. Chapman PS, Kelly DF, Archer J, Brockman DJ, Neiger R. Adrenal necrosis in a dog receiving trilostane for the treatment of hyperadrenocorticism. J Small Anim Pract 2004, 45:307-310.

  • 48. Ramsey IK, Richardson J, Lenard Z, Tebb AJ, Irwin PJ. Persistent isolated hypocortisolism following brief treatment with trilostane. Aust Vet J 2008,86:491-495.

  • 49. Burkhardt WA, Guscetti F, Boretti FS, Ivos Todesco A, Aldajarov N, Lutz TA, Reusch CE, Siber-Ruckstuhl NS. Adrenocorticotropic hormone, but not trilostane, causes severe adrenal hemorrhage, vacuolization, and apoptosis in rats. Domest Anim Endocrinol 2011,40:155-164.

  • 50. Teshima T, Matsumoto H, Kumagai T, Kurano M, Koyama H. Expression of 11beta-hydroxysteroid dehydrogenase isoforms in canine adrenal glands treated with trilostane. Vet J 2014,200:452-455.

  • 51. Arenas C, Melian C, Perez-Alenza MD. Evaluation of 2 trilostane protocols for the treatment of canine pituitary-dependent hyperadrenocorticism: Twice daily versus once daily. J Vet Intern Med 2013,27:1478-1485.

  • 52. Augusto M, Burden A, Neiger R, Ramsey IK. A comparison of once and twice daily administration of trilostane to dogs with hyperadrenocorticism. Tierarztl Prax Ausg Kleintiere Heimtiere 2012,40:415-424.

  • 53. Vaughan MA, Feldman EC, Hoar BR, Nelson RW. Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism. J Am Vet Med Assoc 2008,232:1321-1328.

  • 54. Feldman EC. Evaluation of twice-daily lower-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism. J Am Vet Med Assoc 2011,238:1441-1451.

  • 55. Barker EN, Campbell S, Tebb AJ, Neiger R, Herrtage ME, Reid SW, Ramsey IK. A comparison of the survival times of dogs treated with mitotane or trilostane for pituitarydependent hyperadrenocorticism. J Vet Intern Med 2005,19:810-815.

  • 56. Clemente M, De Andres PJ, Arenas C, Melian C, Morales M, Perez-Alenza MD. Comparison of non-selective adrenocorticolysis with mitotane or trilostane for the treatment of dogs with pituitary-dependent hyperadrenocorticism. Vet Rec 2007,161:805-809.

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

  • 58. Goossens MM, Feldman EC, Theon AP, Koblik PD. Efficacy of cobalt 60 radiotherapy in dogs with pituitary-dependent hyperadrenocorticism. J Am Vet Med Assoc 1998,212:374-376.

  • 59. de Fornel P, Delisle F, Devauchelle P, Rosenberg D. Effects of radiotherapy on pituitary corticotroph macrotumors in dogs: A retrospective study of 12 cases. Can Vet J 2007, 48:481-486.

  • 60. Kent MS, Bommarito D, Feldman E, Theon AP. Survival, neurologic response, and prognostic factors in dogs with pituitary masses treated with radiation therapy and untreated dogs. J Vet Intern Med 2007,21:1027-1033.

  • 61. Massari F, Nicoli S, Romanelli G, Buracco P, Zini E. Adrenalectomy in dogs with adrenal gland tumors: 52 cases (2002-2008). J Am Vet Med Assoc 2011,239:216-221.

  • 62. Schwartz P, Kovak JR, Koprowski A, Ludwig LL, Monette S, Bergman PJ. Evaluation of prognostic factors in the surgical treatment of adrenal gland tumors in dogs: 41 cases (1999-2005). J Am Vet Med Assoc 2008,232:77-84.

  • 63. Kyles AE, Feldman EC, De Cock HE, Kass PH, Mathews KG, Hardie EM, et al. Surgical management of adrenal gland tumors with and without associated tumor thrombi in dogs: 40 cases (1994-2001). J Am Vet Med Assoc 2003,223:654-662.

  • 64. van Sluijs FJ, Sjollema BE, Voorhout G, van den Ingh TS, Rijnberk A. Results of adrenalectomy in 36 dogs with hyperadrenocorticism caused by adreno-cortical tumour. Vet Q. 1995,17:113-116.

  • 65. Jimenez Pelaez M, Bouvy BM, Dupre GP. Laparoscopic adrenalectomy for treatment of unilateral adrenocortical carcinomas: Technique, complications, and results in seven dogs. Vet Surg 2008,37:444-453.

  • 66. Naan EC, Kirpensteijn J, Dupre GP, Galac S, Radlinsky MG. Innovative approach to laparoscopic adrenalectomy for treatment of unilateral adrenal gland tumors in dogs. Vet Surg. 2013,6:710-715.

  • 67. Eastwood JM, Elwood CM, Hurley KJ. Trilostane treatment of a dog with functional adrenocortical neoplasia. J Small Anim Pract 2003,44:126-131.

  • 68. Benchekroun G, de Fornel-Thibaud P, Lafarge S, Gomez E, Begon D, Delisle F, Moraillon R, Heripret D, Maurey C, Rosenberg D. Trilostane therapy for hyperadrenocorticism in three dogs with adrenocortical metastasis. Vet Rec 2008,163:190-192.

  • 69. Helm JR, McLauchlan G, Boden LA, Frowde PE, Collings AJ, Tebb AJ, Elwood CM, Herrtage ME, Parkin TD, Ramsey IK. A comparison of factors that influence survival in dogs with adrenal-dependent hyperadrenocorticism treated with mitotane or trilostane. J Vet Intern Med 2011,25:251-60.

  • 70. Arenas C, Perez-Alenza D, Melian C. Clinical features, outcome and prognostic factors in dogs diagnosed with non-cortisol-secreting adrenal tumours without adrenalectomy: 20 cases (1994-2009]. Vet Rec2013,173:501-504.

Acta Veterinaria

The Journal of University of Belgrade

Journal Information


CiteScore 2016: 0.65

SCImago Journal Rank (SJR) 2016: 0.388
Source Normalized Impact per Paper (SNIP) 2016: 0.605

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 15 15 15
PDF Downloads 2 2 2