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November/December 2015 | tvpjournal.com HyPERADRENOCORTICISM SERIES Peer Reviewed 44 y-box 2; Tpit = T-box transcription factor References 1. Asa SL, Ezzat S. The cytogenesis and pathogenesis of pituitary adenomas. Endo Rev 1998; 19(6):798-827. 2. Seltzer J, Ashton CE, Scotton TC, et al. Gene and protein expression in pituitary corticotroph adenomas: A systematic review of the literature. Neurosurg Focus 2015; 38:1-13. 3. de Bruin C, Meij BP, Kooistra HS, et al. Cushing's disease in dogs and humans. Horm Res 2009; 71:140-143. 4. Mamelak AN, Owen TJ, Bruyette D. Transsphenoidal surgery using a high defnition video telescope for pituitary adenomas in dogs with pituitary dependent hypercortisolism: Methods and results. Vet Surg 2014; 43(4):369-79. 5. Galac S, Kars VJ, Voorhout G, et al. ACTH- independent hyperadrenocorticism due to food-dependent hypercortisolemia in a dog: A case report. Vet J 2008; 177:141-143. 6. Zimmerman KL, Panciera DL, Panciera RJ, et al. Hyperphosphatasemia and concurrent adrenal gland dysfunction in apparently healthy Scottish Terriers. JAVMA 2010; 237:178-186. 7. Behrend EN, Kennis R. Atypical Cushing's syndrome in dogs: Arguments for and against. Vet Clin North Am Small Anim Pract 2010; 40(2):285-296. 8. Castillo VA, Gallelli MF. Corticotroph adenoma in the dog: Pathogenesis and new therapeutic possibilities. Res Vet Sci 2010; 88:26-32. 9. Dahia PL, Grossman AB. The molecular pathogenesis of corticotroph tumors. Endo Rev 1999; 20:136-155. 10. Lamberts SW. Glucocorticoid receptors and Cushing's disease. Mol Cell Endocrinol 2002; 197:69-72. 11. Karl M, Lamberts SW, Koper JW, et al. Cushing's disease preceded by generalized glucocorticoid resistance. Clinical consequences of a novel dominant negative glucocorticoid receptor mutation. Proc AAP 1996; 108:296-307. 12. Karl M, Von Wichert G, Kempter E, et al. Nelson's Syndrome associated with somatic frame shift mutation in the glucocorticoid receptor gene. 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Curr Gene Ther 2006; 13:1-9. 18. Cola A, Lombardi G, Annunziat L. Cabergoline. Exp Opin Pharmacother 2000; 1:555-574. 19. de Bruin C, Hanson JM, Meij BP, et al. Expression and functional analysis of dopamine receptor subtype 2 and somatostatin receptor subtypes in canine Cushing's disease. Endocrinol 2008; 149:4357-4366. 20. Pivonello R, Ferono D, de Herder W, et al. Dopamine receptor expression and function in corticotroph pituitary tumors. J Clin Endocrinol Metabol 2004; 89:2452-2462. 21. Otte C, Lenoci M, Metzler T, et al. Hypothalamic–pituitary–adrenal axis activity and sleep in posttraumtic stress disorder. Neuropsychopharmacology 2005; 6:1173-1180. 22. Levy A, Lightman S. Molecular defects in the pathogenesis of pituitary tumors. Front Neuroendocrinol 2003; 24:94-127. 23. Herman V, Fagin J, Gonsky R, et al. Clonal origin of pituitary adenomas. J Clin Endocrinol Metabol 1990; 71:1427-1433. 24. Patel J, Eloy JA, Liu JK. 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Fukuoka H, Cooper O, Ben-Shlomo A, D AVID BRUYETTE David Bruyette, DVM, Diplomate ACVIM, is the medical director at VCA West Los Angeles Animal Hospital and President and CEO of Veterinary Diagnostic Investigation and Consultation. He was an assistant professor and head of internal medicine at Kansas State University and director of its Analytical Chemistry Laboratory. Dr. Bruyette received his DVM from University of Missouri and completed an internship at Purdue University and residency in internal medicine at University of California–Davis. He then became a staff internist at West Los Angeles Veterinary Medical Group and member of the Department of Comparative Medicine at Stanford University. VETORYL ® Capsules (trilostane) 10 mg, 30 mg, 60 mg and 120 mg strengths Adrenocortical suppressant for oral use in dogs only BRiEf SummaRY (For Full Prescribing Information, see package insert.) CauTiOn: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. DESCRipTiOn: VETORYL is an orally active synthetic steroid analogue that blocks production of hormones produced in the adrenal cortex of dogs. inDiCaTiOnS: VETORYL CAPSULES are indicated for the treatment of pituitary-dependent hyperadrenocorticism in dogs. VETORYL CAPSULES are indicated for the treatment of hyperadrenocorticism due to adrenocortical tumor in dogs. C O nTRainDiCaT i OnS: The use of VETORYL CAPSULES is contraindicated in dogs that have demonstrated hypersensitivity to trilostane. Do not use VETORYL CAPSULES in animals with primary hepatic disease or renal insuffciency. Do not use in pregnant dogs. Studies conducted with trilostane in laboratory animals have shown teratogenic effects and early pregnancy loss. WaRningS: In case of overdosage, symptomatic treatment of hypoadrenocorticism with corticosteroids, mineralocorticoids and intravenous fuids may be required. Angiotensin converting enzyme (ACE) inhibitors should be used with caution with VETORYL CAPSULES, as both drugs have aldosterone-lowering effects which may be additive, impairing the patient's ability to maintain normal electrolytes, blood volume and renal perfusion. Potassium sparing diuretics (e.g. spironolactone) should not be used with VETORYL CAPSULES as both drugs have the potential to inhibit aldosterone, increasing the likelihood of hyperkalemia. Human WaRningS: Keep out of reach of children. Not for human use. Wash hands after use. Do not empty capsule contents and do not attempt to divide the capsules. Do not handle the capsules if pregnant or if trying to conceive. Trilostane is associated with teratogenic effects and early pregnancy loss in laboratory animals. In the event of accidental ingestion/overdose, seek medical advice immediately and take the labeled container with you. pRECauTiOnS: Hypoadrenocorticism can develop at any dose of VETORYL CAPSULES. In some cases, it may take months for adrenal function to return and some dogs never regain adequate adrenal function. A small percentage of dogs may develop corticosteroid withdrawal syndrome within 10 days of starting treatment. This phenomenon results from acute withdrawal of circulating glucocorticoids; clinical signs include weakness, lethargy, anorexia, and weight loss 1 . These clinical signs should be differentiated from an early hypoadrenocortical crisis by measurement of serum electrolyte concentrations and performance of an ACTH stimulation test. Corticosteroid withdrawal syndrome should respond to cessation of VETORYL CAPSULES (duration of discontinuation based on the severity of the clinical signs) and restarting at a lower dose. Mitotane (o,p'-DDD) treatment will reduce adrenal function. Experience in foreign markets suggests that when mitotane therapy is stopped, an interval of at least one month should elapse before the introduction of VETORYL CAPSULES. It is important to wait for both the recurrence of clinical signs consistent with hyperadrenocorticism, and a post-ACTH cortisol level of > 9.1 μg/dL (> 250 nmol/L) before treatment with VETORYL CAPSULES is initiated. Close monitoring of adrenal function is advised, as dogs previously treated with mitotane may be more responsive to the effects of VETORYL CAPSULES. The use of VETORYL CAPSULES will not affect the adrenal tumor itself. Adrenalectomy should be considered as an option for cases that are good surgical candidates. The safe use of this drug has not been evaluated in lactating dogs and males intended for breeding. aDVERSE REaCTiOnS: The most common adverse reactions reported are poor/reduced appetite, vomiting, lethargy/dullness, diarrhea, and weakness. Occasionally, more serious reactions, including severe depression, hemorrhagic diarrhea, collapse, hypoadrenocortical crisis or adrenal necrosis/rupture may occur, and may result in death. Distributed by: Dechra Veterinary p roducts 7015 College Boulevard, Suite 525 Overland Park, KS 66211 VETORYL is a trademark of Dechra Ltd. © 2011, Dechra Ltd. NADA 141-291, Approved by FDA 1 Greco DS, Behrend EN (1995) Corticosteroid withdrawal syndrome. In: Kirk's Current Veterinary Therapy XII; Bonagura, J. (ed); WB Saunders, Philadelphia PA: pp 413-5.