1. Adrenalectomy in a Golden Retriever Betty Lobanov Jan 29 th 2014

2. Signalment & History 10 year old female spayed Golden Retriever Presented to CUHA Soft Tissue Surgery service for adrenalectomy Presenting complaints to rDVM 2 months prior Polyphagia Polyuria Alopecia Muscle atrophy

3. Problem List Alopecia ▫Primary dermatologic, Endocrine, Immune mediated Polyphagia ▫Endocrine Polyuria ▫Endocrine, Renal disease, Hypercalcemia, Diuresis, Pyelonephritis, Psychogenic Muscle atrophy ▫Degenerative, Endocrine, Nutritional, Immune mediated, Neurologic, Orthopedic

4. Diagnostics Senior wellness exam April 2013 ▫CBC: mild lymphopenia ▫Chem: ↑ cholesterol, ↑ triglycerides ▫T4: WNL ▫Urinalysis: 2+ proteinuria ▫USG 1.016 USG & urine protein re-checks recommended ▫3+ proteinuria, USG 1.036 Proteinuria still persisted  recommended urine protein:creatinine (UPC), blood pressure, urine culture/sensitivity ▫UPC 1.3 (normal < 0.5) ▫Culture/Sensitivity: No growth ▫Monitor & re-check in 4 months

5. Diagnostics Re-check August 2013 ▫CBC: lymphopenia, eosinopenia ▫Chem: ↑ cholesterol, ↑ triglycerides ▫Urine culture/sensitivity: E.coli organisms  Amoxicillin 400mg  Re-check 5-7 days after termination of therapy  no growth

6. Problem List Alopecia ▫Primary dermatologic, Endocrine, Immune mediated Polyphagia ▫Endocrine Polyuria ▫Endocrine, Renal disease, Hypercalcemia, Diuresis, Pyelonephritis, Psychogenic Muscle atrophy ▫Degenerative, Endocrine, Nutritional, Immune mediated, Neurologic, Orthopedic

7. But wait, there’s more… Dermatologic punch biopsy 7/12/13  Calcinosis cutis Abdominal ultrasound 7/30/13  adrenal mass ACTH stimulation test ▫Screening test ▫Confirmatory test ▫Evaluates ability of adrenal gland to secrete cortisol after maximal stimulation ▫Protocol  serum cortisol collected for baseline and 1 hour after administering 0.25 mg synthetic ACTH IM  serum cortisol collected for baseline and 2 hours after administering 2.2 U/kg ACTH gel IM

8. Hyperadrenocorticism [HAC] Time vs. Cortisol

9. Patient’s ACTH stim consistent with Cushing’s (hyperadrenocorticism) ▫Pre 5.0ug/dL (ref 1.8-4) ▫Post > 50ug/dL (ref 6-16) Low Dose Dexamethasone Suppression Test (LDDS) ▫Differentiating test ▫Pre 3.8ug/dL ▫Post 4hr: 1.5ug/dL (healthy dog < 1ug/dL) ▫Post 8hr: 2.3ug/dL ▫Protocol  Baseline blood sample for cortisol  Inject 0.01 mg/kg dexamethasone obtain blood sample at 4 & 8hr

10. LDDS Test Time vs. Cortisol

11. Medical management: Trilostane ▫PDH, ADH ▫Competitive inhibition of steroid synthesis  3β-hydroxysteroid dehydrogenase ▫Daily doses needed ▫Cats, Dogs, Birds Re-check cortisol levels post initiating Trilostane ▫ACTH stim  Pre 1.9ug/dL (ref 1.8-4)  Post 2.4ug/dL (ref 6-16) ▫ Trilostane decreased from 60mg to 30mg

12. Hyperadrenocorticism (Cushing’s) 3 types –treated differently and different prognosis Pituitary dependent hyperadrenocorticism (PDH) ▫85%-90%; overproduction ACTH ▫Can live normal lives for many years with medical management (controlling adrenal gland) ▫15% neurological signs  Macroadenomas > 1cm in diameter  Microadenomas < 1cm in diameter Adrenal dependent hyperadrencocorticism (ADH) ▫Functional tumor on the adrenal cortex ▫Adenoma or carcinoma ▫Benign  surgical removal, curative ▫Malignant  surgical removal may help but prognosis guarded- poor Iatrogenic ▫Excessive administration of an oral or injectable steroid

13. Hyperadrenocorticism (Cushing’s)

14. Adrenal Architecture & Products

15. Back to our visit 9/24/13 CUHA Soft Tissue Surgery Physical exam ▫T: 101.8°F P: 108bpm R: 32bpm ▫23.5kg ▫BAR ▫Bilateral alopecia around the elbows ▫Hindlimb muscle atrophy ▫Healing sebaceous cyst on right hindlimb

16. Pre-op Diagnostics CBC Chemistry panel Abdominal ultrasound Thoracic radiograph RESULTS: CBC: no significant findings Chem: ↑ cholesterol 557mg/dL (ref 138-332mg/dL) ↑ triglycerides 314mg/dL (ref 22-125mg/dL) Abdominal U/S: caudal pole of left adrenal gland hyperechoic mass; right adrenal gland normal Thoracic radiographs: no evidence of metastases

18. Surgical Approaches Ventral midline ▫Dorsal recumbency, surgically prepped ▫Xiphoid-pubis incision

19. Surgical Approaches Paralumbar ▫Lateral recumbency, surgically prepped ▫Lateral vertebral process-within 3-4cm of ventral midline incision (caudal to 13 th rib)

20. Surgical Approaches Laparoscopic ▫Lateral/near-lateral with affected gland up, surgically prepped ▫Endoscopic tower directly opposite surgeon facing patient’s back ▫3 or 4 port technique; Instrument ports are placed in a triangulating pattern around the location of the adrenal gland

21. ApproachProsCons Ventral midline-Standard approach -Enhanced visualization for exploratory/metastatic evaluation -Exposure of both adrenal glands -Dehiscence -Exposure & dissection may be difficult in large dogs Paralumbar-Better access to adrenal gland -Minimal dissection and damage to pancreas -Limited metastatic evaluation -Dehiscence Laparoscopic-Minimally invasive -Decreased pain -Less risk of dehiscence, wound infection -Shorter hospitalization -Ability to address complications compromised - Profuse hemorrhage possible

22. Exposure via Paralumbar

24. 9/25/13 Surgery Day Exploratory laparotomy & Left adrenalectomy ▫Xiphoid-pubis incision ▫Abdominal exploration: unremarkable ▫Mass identified & dissected  Right angle forceps, tenotomy scissors, bipolar electrocautery (hemostasis) ▫Phrenicoabdominal vein ligated with hemoclips ▫2 layer closure ▫Skin staples & Tegaderm patch Intra-op Dexamethasone IV

25. Post-operative Care 9/25/13 ▫Dexamethasone IV ▫Plasmalyte fluids IV ▫Fentanyl CRI ▫Fragmin SQ 9/26/13 ▫Plasmalyte fluids IV ▫Fentanyl patch ▫ACTH stim  Pre 0.25ug/dL (ref 1.8-4)  Post 3.74ug/dL (ref 6-16) ▫Discontinued Fragmin 9/27/13 ▫Discontinued Hetastarch & Fentanyl CRI ▫Prednisone 5mg PO ▫Omeprazole 20mg PO ▫PT/PTT Discharged 9/28/13

26. Complications Addisonian crisis ▫Hypoadrenocorticism ▫Lack of aldosterone Hemorrhage Fluid & electrolyte imbalances Pulmonary thromboembolism Delayed wound healing

27. Histopathology ◦ NORMAL ADRENAL MASS Dx: Locally extensive cortical adenoma

28. Adrenal Neoplasia Adrenocortical ▫Adrenal carcinoma ▫Adrenal adenoma Pheochromocytoma: catecholamine secreting tumors arising from medullary tissue Clinical signs due to nonfunctional tumors are caused by local invasion of the tumor into surrounding tissue, distant metastases, or both Functional tumors secrete excessive amounts of cortisol, which inhibits pituitary ACTH secretion and causes atrophy of the contralateral adrenal gland

29. Adrenal Neoplasia Adrenocortical adenomas and carcinomas appear to occur with equal frequency Usually unilateral Complications ▫Adrenal insufficiency ▫Pulmonary thromboembolism ▫Pancreatitis  Post op 2.5-11% (Schwartz 2008)  Increase in manipulation due to invasive tumor ▫Recurrence  Clinical signs related to HAC within 3 years ~ 33% (Axlund 2003)

30. Cost Visit + Specialty exam = $123 Diagnostics = $579 Surgery & Anesthesia = $1,113 ▫Adrenalectomy = $462 ▫Isoflurane = $206 Hospitalization = $1,219 ▫ICU Maintenance = $165 + $165 ▫Cosynotropin $62 ▫ACTH stim = $29.48 ▫PT/PTT = $80 ▫Fragmin = $110 + $216 ▫BP monitoring = 3 x $32 = $96 ▫Gaslyte monitoring = $64 + $96 + $64 ▫PCV/TP = 2 x $36 Total: $3,780.68

31. Patient follow-up 10/8/13 re-check at CUHA Soft Tissue Surgery Service ▫Ravenous appetite diminished ▫Discontinued Omeprazole and Fentanyl patch ▫Taking Prednisone 10/23/13 ▫rDVM call: doing well clinically, taking Prednisone EOD ▫ACTH stim  Pre 3.4ug/dL (ref 1.8-4)  Post 14.2ug/dL (ref 6-16)

32. Thank you to my advisors: Dr. Harvey Dr. Jay

33. Resources Axlund TW, Behrend EN: Surgical Treatment of Canine Hyperadrenocorticism, Vol. 25, No. 5, May 2003 Feldman EC, Nelson RW: Hyperadrenocorticism (Cushing’s syndrome), in Feldman BF, Nelson RW (eds): Canine and Feline Endocrinology and Reproduction, ed 2. Philadelphia, WB Saunders, 1996, pp 187-265 Fossum, Theresa. Small Animal Surgery, 3 rd edition. St.Louis: Mosby Inc., 2007 http://www.vsso.org/Adrenal_Cortical_Tumor.html Massari F, Nicoli S, et al. Adrenalectomy in dogs with adrenal gland tumors: 52 cases (2002-2008). J Am Vet Med Assoc 2011; 239:216-221 Pelaez MJ, Bouvy BM, Dupre GP: Laparoscopic adrenalectomy for treatment of unilateral adrenocortical carcinomas: Techniques, complications and results in seven dogs. Vet Surg 2008;37:444-453 Schwartz P, Kovak JR, Koprowski A, et al. 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

34. Questions?