Top Endocrine Publications of 2013: The Canine Adrenal Gland

I've decide to take a break from my review of the endocrine abstracts presented at the 2014 ACVIM forum and turn back to my review of the canine and feline endocrine publications of 2012. So in the next 2 posts, I'll cover the disorders of the canine and feline adrenal gland.

Listed below are 55 research papers written in 2013 that deal with a variety of adrenal gland issues of clinical importance in dogs.

These range from the investigations of trilostane protocols used in the treatment of dogs with Cushing's disease (1,7,12,23) to the pathogenesis, clinical features, or outcome of dogs with adrenal tumors (2,4,31-34); from adrenal imaging in normal dogs and dogs with Cushing's syndrome (3,16,24,46) to investigations involving diagnosis or treatment of hypoadrenocorticism (5,18,36,37,50); and from studies dealing with diagnostic testing for hyperadrenocorticism (6,8-11,14,42) to research studies investigating the effect of "stress" on adrenal function in dogs (15,45,49,51).

Other research studies involved diagnostic testing for pheochromocytoma in dogs (21,22) to reports of extra-adrenal paraganglioma or chemodectomas in dogs (25,27); and from studies of the renin-angiotensin-aldosterone (38,39) to studies of the complications of Cushing's syndrome, including hypercoagulability (43,44,47,48) and sudden acquired retinal degeneration syndrome (52).

As you can see from all of these many publications, it was a good year to study the canine adrenal gland!

References:

1. 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. 
2. 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 Rec 2013;173:501. 
3. Bargellini P, Orlandi R, Paloni C, et al. Contrast-enhanced ultrasonographic characteristics of adrenal glands in dogs with pituitary-dependent hyperadrenocorticism. Vet Radiol Ultrasound 2013;54:283-292. 
4. Barrera JS, Bernard F, Ehrhart EJ, et al. Evaluation of risk factors for outcome associated with adrenal gland tumors with or without invasion of the caudal vena cava and treated via adrenalectomy in dogs: 86 cases (1993-2009). J Am Vet Med Assoc 2013;242:1715-1721. 
5. Bates JA, Shott S, Schall WD. Lower initial dose desoxycorticosterone pivalate for treatment of canine primary hypoadrenocorticism. Aust Vet J 2013;91:77-82.
6. Behrend EN, Kooistra HS, Nelson R, et al. Diagnosis of spontaneous canine hyperadrenocorticism: 2012 ACVIM consensus statement (small animal). J Vet Intern Med 2013;27:1292-1304. 
7. Braun C, Boretti FS, Reusch CE, et al. Comparison of two treatment regimens with trilostane in dogs with pituitary-dependent hyperadrenocorticism. Schweiz Arch Tierheilkd 2013;155:551-558. 
8. Bromel C, Nelson RW, Feldman EC, et al. Serum inhibin concentration in dogs with adrenal gland disease and in healthy dogs. J Vet Intern Med 2013;27:76-82. 
9. Bryan HM, Adams AG, Invik RM, et al. Hair as a meaningful measure of baseline cortisol levels over time in dogs. J Am Assoc Lab Anim Sci 2013;52:189-196. 
10. Bugbee AC, Smith JR, Ward CR. Effect of dexamethasone or synthetic ACTH administration on endogenous ACTH concentrations in healthy dogs. Am J Vet Res 2013;74:1415-1420. 
11. Burkhardt WA, Boretti FS, Reusch CE, et al. Evaluation of baseline cortisol, endogenous ACTH, and cortisol/ACTH ratio to monitor trilostane treatment in dogs with pituitary-dependent hypercortisolism. J Vet Intern Med 2013;27:919-923. 
12. Cho KD, Kang JH, Chang D, et al. Efficacy of low- and high-dose trilostane treatment in dogs (< 5 kg) with pituitary-dependent hyperadrenocorticism. J Vet Intern Med 2013;27:91-98. 
13. Claude AK, Miller WW, Beyer AM, et al. Quantification and comparison of baseline cortisol levels between aqueous and plasma from healthy anesthetized hound dogs utilizing mass spectrometry. Vet Ophthalmol 2014;17:57-62. 
14. Corradini S, Accorsi PA, Boari A, et al. Evaluation of hair cortisol in the diagnosis of hypercortisolism in dogs. J Vet Intern Med 2013;27:1268-1272. 
15. Dalla Villa P, Barnard S, Di Fede E, et al. Behavioural and physiological responses of shelter dogs to long-term confinement. Vet Ital 2013;49:231-241. 
16. de Chalus T, Combes A, Bedu AS, et al. Ultrasonographic adrenal gland measurements in healthy Yorkshire Terriers and Labrador Retrievers. Anat Histol Embryol 2013;42:57-64. 
17. De Vries F, Leuschner J, Jilma B, et al. Establishment of a low dose canine endotoxemia model to test anti-inflammatory drugs: effects of prednisolone. Int J Immunopathol Pharmacol 2013;26:861-869. 
18. Floettmann JE, Buckett LK, Turnbull AV, et al. ACAT-selective and nonselective DGAT1 inhibition: adrenocortical effects--a cross-species comparison. Toxicol Pathol 2013;41:941-950. 3
19. Frank CB, Valentin SY, Scott-Moncrieff JC, et al. Correlation of inflammation with adrenocortical atrophy in canine adrenalitis. J Comp Pathol 2013;149:268-279. 
20. Frank LA, Watson JB. Treatment of alopecia X with medroxyprogesterone acetate. Veterinary Dermatology 2013;24:624-e154. 
21. Gostelow R, Bridger N, Syme HM. Plasma-free metanephrine and free normetanephrine measurement for the diagnosis of pheochromocytoma in dogs. J Vet Intern Med 2013;27:83-90. 
22. Green BA, Frank EL. Comparison of plasma free metanephrines between healthy dogs and 3 dogs with pheochromocytoma. Vet Clin Pathol 2013;42:499-503. 
23. Griffies JD. Old or new? A comparison of mitotane and trilostane for the management of hyperadrenocorticism. Compend Contin Educ Vet 2013;35:E3. 
24. Haers H, Daminet S, Smets PM, et al. Use of quantitative contrast-enhanced ultrasonography to detect diffuse renal changes in Beagles with iatrogenic hypercortisolism. Am J Vet Res 2013;74:70-77. 
25. Hardcastle MR, Meyer J, McSporran KD. Pathology in practice. Carotid and aortic body carcinomas (chemodectomas) in a dog. J Am Vet Med Assoc 2013;242:175-177. 
26. Huang HP, Lien YH. Treatment of canine generalized demodicosis associated with hyperadrenocorticism with spot-on moxidectin and imidacloprid. Acta Vet Scand 2013;55:40. 
27. Ilha MR, Styer EL. Extra-adrenal retroperitoneal paraganglioma in a dog. J Vet Diagn Invest 2013;25:803-806. 
28. Ishibashi M, Akiyoshi H, Iseri T, et al. Skin conductance reflects drug-induced changes in blood levels of cortisol, adrenaline and noradrenaline in dogs. J Vet Med Sci 2013;75:809-813. 
29. Kemppainen RJ. Inoculation of dogs with a recombinant ACTH vaccine. Am J Vet Res 2013;74:1499-1505. 
30. Kol A, Nelson RW, Gosselin RC, et al. Characterization of thrombelastography over time in dogs with hyperadrenocorticism. Vet J 2013;197:675-681. 
31. Kool MM, Galac S, Kooistra HS, et al. Expression of angiogenesis-related genes in canine cortisol-secreting adrenocortical tumors. Domest Anim Endocrinol 2013. 
32. Kool MM, Galac S, Spandauw CG, et al. Activating mutations of GNAS in canine cortisol-secreting adrenocortical tumors. J Vet Intern Med 2013;27:1486-1492. 
33. Larson RN, Schmiedt CW, Wang A, et al. Adrenal gland function in a dog following unilateral complete adrenalectomy and contralateral partial adrenalectomy. J Am Vet Med Assoc 2013;242:1398-1404. 
34. Lee HC, Jung DI, Moon JH, et al. Clinical characteristics and outcomes of primary adrenal hemangioma in a dog. Res Vet Sci 2013;95:572-575. 
35. Mak G, Allen J. Simultaneous pheochromocytoma and third-degree atrioventricular block in 2 dogs. J Vet Emerg Crit Care (San Antonio) 2013;23:610-614. 
36. Massey J, Boag A, Short AD, et al. MHC class II association study in eight breeds of dog with hypoadrenocorticism. Immunogenetics 2013;65:291-297. 
37. McGonigle KM, Randolph JF, Center SA, et al. Mineralocorticoid before glucocorticoid deficiency in a dog with primary hypoadrenocorticism and hypothyroidism. J Am Anim Hosp Assoc 2013;49:54-57. 
38. Mochel JP, Fink M, Peyrou M, et al. Chronobiology of the renin-angiotensin-aldosterone system in dogs: relation to blood pressure and renal physiology. Chronobiol Int 2013;30:1144-1159. 
39. Mochel JP, Peyrou M, Fink M, et al. Capturing the dynamics of systemic renin-angiotensin-aldosterone system (RAAS) peptides heightens the understanding of the effect of benazepril in dogs. J Vet Pharmacol Ther 2013;36:174-180. 
40. Mongillo P, Prana E, Gabai G, et al. Effect of age and sex on plasma cortisol and dehydroepiandrosterone concentrations in the dog (Canis familiaris). Res Vet Sci 2014;96:33-38.
41. Naan EC, Kirpensteijn J, Dupre GP, et al. Innovative approach to laparoscopic adrenalectomy for treatment of unilateral adrenal gland tumors in dogs. Veterinary Surgery 2013;42:710-715. 
42. Ouschan C, Kuchar A, Mostl E. Measurement of cortisol in dog hair: a noninvasive tool for the diagnosis of hypercortisolism. Vet Derm 2013;24:428-431, e493-424. 
43. Pace SL, Creevy KE, Krimer PM, et al. Assessment of coagulation and potential biochemical markers for hypercoagulability in canine hyperadrenocorticism. J Vet Intern Med 2013;27:1113-1120. 
44. Park FM, Blois SL, Abrams-Ogg AC, et al. Hypercoagulability and ACTH-dependent hyperadrenocorticism in dogs. J Vet Intern Med 2013;27:1136-1142. 
45. Perego R, Proverbio D, Spada E. Increases in heart rate and serum cortisol concentrations in healthy dogs are positively correlated with an indoor waiting-room environment. Vet Clin Pathol 2014;43:67-71. 
46. Pey P, Daminet S, Smets PM, et al. Contrast-enhanced ultrasonographic evaluation of adrenal glands in dogs with pituitary-dependent hyperadrenocorticism. Am J Vet Res 2013;74:417-425. 
47. Romao FG, Campos EF, Mattoso CR, et al. Hemostatic profile and thromboembolic risk in healthy dogs treated with prednisone: a randomized controlled trial. BMC Vet Res 2013;9:268. 
48. Rose L, Dunn ME, Bedard C. Effect of canine hyperadrenocorticism on coagulation parameters. J Vet Intern Med 2013;27:207-211. 
49. Shiverdecker MD, Schiml PA, Hennessy MB. Human interaction moderates plasma cortisol and behavioral responses of dogs to shelter housing. Physiol Behav 2013;109:75-79. 
50. Short AD, Boag A, Catchpole B, et al. A candidate gene analysis of canine hypoadrenocorticism in 3 dog breeds. J Hered 2013;104:807-820. 
51. Siniscalchi M, McFarlane JR, Kauter KG, et al. Cortisol levels in hair reflect behavioural reactivity of dogs to acoustic stimuli. Res Vet Sci 2013;94:49-54. 
52. Stuckey JA, Pearce JW, Giuliano EA, et al. Long-term outcome of sudden acquired retinal degeneration syndrome in dogs. J Am Vet Med Assoc 2013;243:1425-1431. 
53. Winnick JJ, Ramnanan CJ, Saraswathi V, et al. Effects of 11-beta-hydroxysteroid dehydrogenase-1 inhibition on hepatic glycogenolysis and gluconeogenesis. Am J Physiol Endocrinol Metab 2013;304:E747-756. 
54. Yu J, Fu X, Chang M, et al. The effects of intra-abdominal hypertension on the secretory function of canine adrenal glands. PLoS One 2013;8:e81795. 
55. Zeugswetter FK, Neffe F, Schwendenwein I, et al. Configuration of antibodies for assay of urinary cortisol in dogs influences analytic specificity. Domest Anim Endocrinol 2013;45:98-104.

Top Endocrine Publications of 2013: Hypertension in Dogs and Cats

In my sixth compilation of the canine and feline endocrine publications of 2013, I’m moving on to endocrine hypertension. Listed below are 13 research papers written in 2013 that deal with a variety of hypertensive topics of clinical importance, many of which directly involve one or more hormones.

These range from a review of the hypertension associated with diabetic nephropathy (1) to an overview of guidelines for antihypertensive therapy in dogs and cats (2); from diagnostic testing of primary hyperaldosteronism in cats (3) to the use of plasma metanephrines for diagnosis of pheochromocytoma in dogs (5); and from a case study of a dog that develop severe hypertension secondary to an overdose of phenylpropanolamine (4) to a study of the relationship between the degree of hypertension and the development of ocular changes in cats with chronic kidney disease (6).

Other publications included are a comparison of indirect blood pressure measurements using a non-invasive method, high-definition oscillometry to direct measurements using a radio-telemetry device in awake cats (7) to a study of the effect of body position on indirect measurement of systolic arterial blood pressure in dogs (10);  from a report of a case series of dogs and cats with hypertensive encephalopathy (8) to a study of the effect of intra-abdominal hypertension on the adrenal gland secretion of cortisol, aldosterone, epinephrine, and norepinephrine in dogs (13); and finally, from a report of high dietary salt intake and blood pressure in cats (9) to an investigation of the renin-angiotensin-aldosterone system in the pathogenesis of hypertension associated with hyperthyroidism in cats (12).

References:

1. Bloom CA, Rand JS. Diabetes and the kidney in human and veterinary medicine. Vet Clin North Am Small Anim Pract 2013;43:351-365. 
2. Buoncompagni S, Bowles MH. Treatment of systemic hypertension associated with kidney disease. Compend Contin Educ Vet 2013;35:E1. 
3. Djajadiningrat-Laanen SC, Galac S, Boeve SAEB, et al. Evaluation of the oral fludrocortisone suppression test for diagnosing primary hyperaldosteronism in cats. J Vet Intern Med 2013;27:1493-1499. 
4. Ginn JA, Bentley E, Stepien RL. Systemic hypertension and hypertensive retinopathy following PPA overdose in a dog. J Am Anim Hosp Assoc 2013;49:46-53. 
5. Green BA, Frank EL. Comparison of plasma free metanephrines between healthy dogs and 3 dogs with pheochromocytoma. Vet Clin Pathol 2013;42:499-503. 
6. Karck J, von Spiessen L, Rohn K, et al. Interrelation between the degree of a chronic renal insufficiency and/or systemic hypertension and ocular changes in cats. Tierarztliche Praxis Ausgabe K, Kleintiere/Heimtiere 2013;41:37-45. 
7. Martel E, Egner B, Brown SA, et al. Comparison of high-definition oscillometry -- a non-invasive technology for arterial blood pressure measurement -- with a direct invasive method using radio-telemetry in awake healthy cats. J Feline Med Surg 2013; 15:1104-1115. 
8. O'Neill J, Kent M, Glass EN, et al. Clinicopathologic and MRI characteristics of presumptive hypertensive encephalopathy in two cats and two dogs. J Am Anim Hosp Assoc 2013;49:412-420. 
9. Reynolds BS, Chetboul V, Nguyen P, et al. Effects of dietary salt intake on renal function: a 2-year study in healthy aged cats. J Vet Intern Med 2013;27:507-515. 
10. Rondeau DA, Mackalonis ME, Hess RS. Effect of body position on indirect measurement of systolic arterial blood pressure in dogs. J Am Vet Med Assoc 2013;242:1523-1527. 
11. Tian Z, Shen Y, Liao H, et al. Carotid proliferative plaque formation in a canine model of chronic hypertension. J Investig Med 2013;61:995-1003. 
12. Williams TL, Elliott J, Syme HM. Renin-angiotensin-aldosterone system activity in hyperthyroid cats with and without concurrent hypertension. J Vet Intern Med 2013;27:522-529. 
13. Yu J, Fu X, Chang M, et al. The effects of intra-abdominal hypertension on the secretory function of canine adrenal glands. PLoS One 2013;8:e81795. 

Working Up Cats with an Adrenal Mass

I have a 14 year old DSH cat that has been diagnosed with a 3 cm unilateral adrenal mass by ultrasound. Her triglyceride level has been rising consistently for the past 6 months, and she also has had a history of hypertension and mild hypokalemia that responds only to high dose of Tumil K. 

The cat also has early (Stage 2) chronic renal disease with low urine SG, but otherwise she is pretty healthy. She has no weight loss, diabetes mellitus, or thinning of skin. The only change that the owner reports is increased vocalization and a voracious appetite.

Her owner is considering adrenal surgery, but in case this is not an option, I would like to know about your experience in using trilostane as a medical treatment option, assuming Cushing's syndrome is confirmed.

If the owner does elect for surgery, is it still important to find out what the adrenal mass is secreting?

My Response:
From the cat's history and laboratory work (hypertension and hypokalemia), it sounds like hyperaldosteronism (Conn's syndrome) is most likely in this case (1,2). I'd certainly try to determine what hormone(s) are being secreted by the adrenal mass in order to help in peri-operative care of this cat.

Knowing the tumor's hormone secretion pattern prior to surgery is important in the management of the adrenal tumor. For example, if this cat does have Cushing's syndrome secondary to a cortisol-secreting adrenal mass, the function of the contralateral adrenal gland would be suppressed and postoperative adrenal insufficiency would be expected (3-5). If the cat has a pheochromocytoma, severe hypertension or cardiac arrhythmia could develop during surgery so we ideally would prepare them for surgery with phenoxybenzamine (6,7).

I'd start by measuring a basal aldosterone secretion to help diagnose or rule out Conn's syndrome (1,2). If that is borderline or normal, I'd do a dexamethasone screening test next to rule out hyperadrenocorticism. For cats, we use a dexamethasone dose of 0.1 mg/kg, IV, with cortisol samples collected before, 4, and 8 hours after the dexamethasone injection (8,9). Pheochromocytoma is more difficult to diagnose, but measurement of plasma or urine levels of catecholamines might be helpful (10-12). However, little work has been done in cats with pheochromocytoma, largely due to the fact that this is a very rare adrenal tumor in cats.

Examination of adrenal gland size with ultrasound can also help differentiate cats with Cushing's syndrome due to cortisol-secreting tumor from those with Conn's syndrome or pheochromocytoma. In cats with a unilateral cortisol-secreting tumor, we would expect the contralateral adrenal gland to atrophy as a result of suppression of pituitary ACTH secretion; therefore, the adrenal tumor would be larger than normal, whereas the contralateral adrenal should be small (9,13,14). In cats with Conn's or pheochromocytoma, the size of the contralateral adrenal gland generally remains with normal limits (2,13,14).

If the cat does indeed have Cushing's syndrome, trilostane (Vetoryl) may certainly help to control the excessive cortisol secretion by the adrenal mass. The dose need is quite variable, and can range from 10 mg up to 60 mg per day (9). Obviously, trilostane would not have any effect on hormone secretion if the cat has an aldosterone or catecholamine-secreting tumor.

References:

1. Djajadiningrat-Laanen S, Galac S, Kooistra H. Primary hyperaldosteronism: expanding the diagnostic net. J Feline Med Surg 2011;13:641-650. 
2. Harvey AM, Refsal KR. Feline hyperaldosteronism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;204-214.
3. Peterson ME, Birchard SJ, Mehlhaff CJ. Anesthetic and surgical management of endocrine disorders. Vet Clin North Am Small Anim Prac 1984;14:911-925. 
4. de Brito Galvao JF, Chew DJ. Metabolic complications of endocrine surgery in companion animals. Vet Clin North Am Small Anim Pract 2011;41:847-868.
5. Peterson ME. Feline hypoadrenocorticism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;190-198.
6. Maher ER, Jr., McNiel EA. Pheochromocytoma in dogs and cats. Vet Clin North Am Small Anim Pract 1997;27:359-380. 
7. Herrera MA, Mehl ML, Kass PH, et al. Predictive factors and the effect of phenoxybenzamine on outcome in dogs undergoing adrenalectomy for pheochromocytoma. J Vet Intern Med 2008;22:1333-1339. 
8. Duesberg C, Peterson ME. Adrenal disorders in cats. Vet Clin North Am Small Anim Pract 1997;27:321-347. 
9. Peterson ME. Feline hyperadrenocorticism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;199-203.
10. Gostelow R, Bridger N, Syme HM. Plasma-free metanephrine and free normetanephrine measurement for the diagnosis of pheochromocytoma in dogs. J Vet Intern Med 2013;27:83-90. 
11. Quante S, Boretti FS, Kook PH, et al. Urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or pheochromocytoma, and in healthy dogs. J Vet Intern Med 2010;24:1093-1097. 
12. Kook PH, Grest P, Quante S, et al. Urinary catecholamine and metadrenaline to creatinine ratios in dogs with a phaeochromocytoma. Vet Rec 2010;166:169-174. 
13. Barthez PY, Nyland TG, Feldman EC. Ultrasonography of the adrenal glands in the dog, cat, and ferret. Vet Clin North Am Small Anim Pract 1998;28:869-885. 
14. Tidwell AS, Penninck DG, Besso JG. Imaging of adrenal gland disorders. Vet Clin North Am Small Anim Pract 1997;27:237-254. 

Top Endocrine Publications of 2012: The Canine Adrenal Gland

In my seventh compilation of the canine and feline endocrine publications of 2012, I’m moving on to disorders of the canine adrenal gland.

Listed below are 40 research papers written in 2012 that deal with a variety of adrenal gland issues of clinical importance in dogs. I've already reviewed 4 of these papers; to read my reviews, see the links at the bottom of the reference list.

These range from the investigations of trilostane and dosing (1,11,35) or its effect on steroid hormone metabolism in adrenal glands and corpora lutea (32) to a study of an evaluation of compounded trilostane (6); from investigations of the sudden acute blindness that can develop in dogs with pituitary-dependent hyperadrenocorticism (PDH) (3,4) to the vitamin-D status in dogs with PDH (7); and from studies of the effect of cortisol excess (Cushing's syndrome) on renal function (37-39) to the use of low-dose insulin administration to prevent the onset on overt diabetes in dogs with PDH (27).

Other research studies included a review of the animal models of adrenocortical tumorigenesis (2) to a review of diagnostic tests for Cushing's syndrome (21); from studies to compare IV and IM formulations of ACTH in dogs (5) to ultrasound studies of the adrenal gland in normal dogs, dogs treated with steroids, or dogs with adrenal tumor (8,9,33); from reports of adrenalectomy for treatment of dogs with adrenal tumor causing  hyperaldosteronism (12,15), or pheochromocytoma (17); and finally, from studies of the relationship between gallbladder mucoceles and glucocorticoid excess (22) to a number of studies of the effects of exogenous glucocorticoids and iatrogenic Cushing's syndrome in dogs (18,20,22-24,26,31,33,40)

References:

1. Augusto M, Burden A, Neiger R, et al. A comparison of once and twice daily administration of trilostane to dogs with hyperadrenocorticism. Tierarztl Prax Ausg K Kleintiere Heimtiere 2012;40:415-424. 
2. Beuschlein F, Galac S, Wilson DB. Animal models of adrenocortical tumorigenesis. Mol Cell Endocrinol 2012;351:78-86. 
3. Cabrera Blatter MF, del Prado A, Gallelli MF, et al. Blindness in dogs with pituitary dependent hyperadrenocorticism: relationship with glucose, cortisol and triglyceride concentration and with ophthalmic blood flow. Res Vet Sci 2012;92:387-392. 
4. Cabrera Blatter MF, Del Prado B, Miceli DD, et al. Interleukin-6 and insulin increase and nitric oxide and adiponectin decrease in blind dogs with pituitary-dependent hyperadrenocorticism. Res Vet Sci 2012. 
5. Cohen TA, Feldman EC. Comparison of IV and IM formulations of synthetic ACTH for ACTH stimulation tests in healthy dogs. J Vet Intern Med 2012;26:412-414. 
6. Cook AK, Nieuwoudt CD, Longhofer SL. Pharmaceutical evaluation of compounded trilostane products. J Am Anim Hosp Assoc 2012;48:228-233. 
7. Corbee RJ, Tryfonidou MA, Meij BP, et al. Vitamin D status before and after hypophysectomy in dogs with pituitary-dependent hypercortisolism. Domest Anim Endocrinol 2012;42:43-49. 
8. Davis MK, Schochet RA, Wrigley R. Ultrasonographic identification of vascular invasion by adrenal tumors in dogs. Vet Radiol Ultrasound 2012;53:442-445. 
9. de Chalus T, Combes A, Bedu AS, et al. Ultrasonographic adrenal gland measurements in healthy Yorkshire Terriers and Labrador Retrievers. Anat Histol Embryol 2012. 
10. Donnelly K, DeClue AE, Sharp CR. What is your diagnosis? 12-year-old spayed female Labrador Retriever with a history of polyuria and polydipsia. J Am Vet Med Assoc 2012;240:1283-1285. 
11. Feldman EC, Kass PH. Trilostane dose versus body weight in the treatment of naturally occurring pituitary-dependent hyperadrenocorticism in dogs. J Vet Intern Med 2012;26:1078-1080. 
12. Frankot JL, Behrend EN, Sebestyen P, et al. Adrenocortical carcinoma in a dog with incomplete excision managed long-term with metastasectomy alone. J Am Anim Hosp Assoc 2012;48:417-423. 
13. Fukuta H, Mori A, Urumuhan N, et al. Characterization and comparison of insulin resistance induced by Cushing Syndrome or diestrus against healthy control dogs as determined by euglycemic-hyperinsulinemic glucose clamp profile glucose infusion rate using an artificial pancreas apparatus. J Vet Med Sci 2012;74:1527-1530. 
14. Ginel PJ, Sileo MT, Blanco B, et al. Evaluation of serum concentrations of cortisol and sex hormones of adrenal gland origin after stimulation with two synthetic ACTH preparations in clinically normal dogs. Am J Vet Res 2012;73:237-241. 
15. Gojska-Zygner O, Lechowski R, Zygner W. Functioning unilateral adrenocortical carcinoma in a dog.  Can Vet J 2012;53:623-625. 
16. Gow AG, Gow DJ, Bell R, et al. Insulin concentrations in dogs with hypoadrenocorticism. Res Vet Sci 2012;93:97-99. 
17. Guillaumot PJ, Heripret D, Bouvy BM, et al. 49-month survival following caval venectomy without nephrectomy in a dog with a pheochromocytoma. J Am Anim Hosp Assoc 2012;48:352-358. 
18. Hicks CW, Sweeney DA, Danner RL, et al. Efficacy of selective mineralocorticoid and glucocorticoid agonists in canine septic shock. Crit Care Med 2012;40:199-207. 
19. Hoglund K, Hanas S, Carnabuci C, et al. Blood pressure, heart rate, and urinary catecholamines in healthy dogs subjected to different clinical settings. J Vet Intern Med 2012;26:1300-1308. 
20. Hsu K, Snead E, Davies J, et al. Iatrogenic hyperadrenocorticism, calcinosis cutis, and myocardial infarction in a dog treated for IMT. J Am Anim Hosp Assoc 2012;48:209-215. 
21. Kooistra HS, Galac S. Recent advances in the diagnosis of Cushing's syndrome in dogs. Top Companion Anim Med 2012;27:21-24. 
22. Kook PH, Schellenberg S, Rentsch KM, et al. Effects of iatrogenic hypercortisolism on gallbladder sludge formation and biochemical bile constituents in dogs. Vet J 2012;191:225-230. 
23. Kovalik M, Thoday KL, Berry J, et al. Prednisolone therapy for atopic dermatitis is less effective in dogs with lower pretreatment serum 25-hydroxyvitamin D concentrations. Vet Dermatol 2012;23:125-130, e127-128. 
24. Kovalik M, Thoday KL, Evans H, et al. Short-term prednisolone therapy has minimal impact on calcium metabolism in dogs with atopic dermatitis. Vet J 2012;193:439-442. 
25. Lowrie M, De Risio L, Dennis R, et al. Concurrent medical conditions and long-term outcome in dogs with nontraumatic intracranial hemorrhage. Vet Radiol Ultrasound 2012;53:381-388. 
26. Melamies M, Vainio O, Spillmann T, et al. Endocrine effects of inhaled budesonide compared with inhaled fluticasone propionate and oral prednisolone in healthy Beagle dogs. Vet J 2012;194:349-353. 
27. Miceli DD, Gallelli MF, Cabrera Blatter MF, et al. Low dose of insulin detemir controls glycaemia, insulinemia and prevents diabetes mellitus progression in the dog with pituitary-dependent hyperadrenocorticism. Res Vet Sci 2012;93:114-120. 
28. Miller AG, Dow S, Long L, et al. Antiphospholipid antibodies in dogs with immune mediated hemolytic anemia, spontaneous thrombosis, and hyperadrenocorticism. J Vet Intern Med 2012;26:614-623. 
29. Monroe WE, Panciera DL, Zimmerman KL. Concentrations of noncortisol adrenal steroids in response to ACTH in dogs with adrenal-dependent hyperadrenocorticism, pituitary-dependent hyperadrenocorticism, and nonadrenal illness. J Vet Intern Med 2012;26:945-952. 
30. Muntener T, Schuepbach-Regula G, Frank L, et al. Canine noninflammatory alopecia: a comprehensive evaluation of common and distinguishing histological characteristics. Vet Dermatol 2012;23:206-e244. 
31. O'Neill D, Hendricks A, Summers J, et al. Primary care veterinary usage of systemic glucocorticoids in cats and dogs in three UK practices. J Small Anim Pract 2012;53:217-222. 
32. Ouschan C, Lepschy M, Zeugswetter F, et al. The influence of trilostane on steroid hormone metabolism in canine adrenal glands and corpora lutea-an in vitro study. Vet Res Commun 2012;36:35-40. 
33. Pey P, Daminet S, Smets PM, et al. Effect of glucocorticoid administration on adrenal gland size and sonographic appearance in beagle dogs. Vet Radiol Ultrasound 2012;53:204-209. 
34. Proverbio D, Spada E, Perego R, et al. Potential variant of multiple endocrine neoplasia in a dog. J Am Anim Hosp Assoc 2012;48:132-138. 
35. Reine NJ. Medical management of pituitary-dependent hyperadrenocorticism: mitotane versus trilostane. Top Companion Anim Med 2012;27:25-30. 
36. Schteingart DE, Sinsheimer JE, Benitez RS, et al. Structural requirements for mitotane activity: development of analogs for treatment of adrenal cancer. Anticancer Res 2012;32:2711-2720. 
37. Smets PM, Lefebvre HP, Aresu L, et al. Renal function and morphology in aged Beagle dogs before and after hydrocortisone administration. PLoS One 2012;7:e31702. 
38. Smets PM, Lefebvre HP, Kooistra HS, et al. Hypercortisolism affects glomerular and tubular function in dogs. Vet J 2012;192:532-534. 
39. Smets PM, Lefebvre HP, Meij BP, et al. Long-term follow-up of renal function in dogs after treatment for ACTH-dependent hyperadrenocorticism. J Vet Intern Med 2012;26:565-574. 
40. Van der Heyden S, Croubels S, Gadeyne C, et al. Influence of P-glycoprotein modulation on plasma concentrations and pharmacokinetics of orally administered prednisolone in dogs. Am J Vet Res 2012;73:900-907. 

Prior Reviews:
I've already reviewed a few of the papers from the list above (5,6,11,39). To read these prior reviews, see links below:

• Reference 5: How Does the New Generic Cosyntropin Compare to Cortrosyn for ACTH Stimulation Testing?
• Reference 6: Characteristics of Commercially Manufactured and Compounded PZI Insulin
• Reference 11: Low-Dose, Twice-Daily Trilostane Treatment for Dogs with Hyperadrenocorticism
• Reference 39:  Hypertension and Proteinuria: Frequent Complications of Cushing's Disease in Dogs

Top 10 Clinical Endocrinology Research Abstracts Presented at the 2013 ACVIM Meeting

Last month, I spent a week in Seattle, Washington attending the the 2013 American College of Veterinary Internal Medicine Forum.  As part of that meeting, a number of research abstracts were presented (oral and poster presentations) that dealt with various aspects of canine and feline endocrinology. I plan to spend the next three blogs discussing some of the newest and best research findings featured at the ACVIM meeting.

Of all of the excellent endocrine research abstracts presented, I've selected a "top 10 list" of the ones that have the most potential to change what I do in my clinical practice.  To do this, I've enlisted the help of Dr. Rhett Nichols, a well-known expert in endocrinology and internal medicine whose day-job is senor member of the veterinarian consulting service for Antech Diagnostics, the world's largest laboratory dedicated to animal health.  However, since Rhett also serves as a consultant for the Animal Endocrine Clinic (my practice), it was not that difficult to get him involved in this project!

In this post, we will review 4 of these top 10 abstracts, followed by the remaining 6 in the upcoming 2 posts. We hope you agree with our selections, but if you don't, remember that you can always post a comment and add your opinion.

Niessen S, Scudder C, Forcada Y, et al. Pasireotide (SOM230) opens doors to medical management of feline hypersomatotropism. J Vet Intern Med 2013:685.

Feline hypersomatotropism (HS) appears to be a significant cause of feline diabetes mellitus. However, successful treatment of HS is currently challenging. Radiotherapy and hypophysectomy seem the only effective therapeutic modalities, yet come with significant disadvantages. Medical options would be desirable although somatostatin (sst) analogues and dopamine agonists have thus far proven largely ineffective. Pasireotide (SOM230), a novel multi-receptor ligand sst analogue with high binding affinity for sst receptor subtypes 1, 2, 3 and 5 has been shown to suppress growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in rodents as well as humans suðering from HS. Additionally, direct and indirect anti-tumor activity has been observed in vitro including sst receptor-mediated apoptosis and anti-angiogenesis. The current study aimed to assess the potential of SOM230 as a treatment modality for naturally occurring feline HS. Feline HS was diagnosed in eight diabetic cats by documenting serum IGF-1 concentration >1000 ng/ml (radioimmunoassay) and presence of a pituitary enlargement (computed tomography). On day 1 and 5, serum IGF-1 concentration was established and glycemic control assessed using a 12-hour blood glucose (BG) curve, measuring BG every 2 hours. On day 2, 3 and 4, the cats were injected with 0.03 mg/kg SOM230 s.c. BID. The initial insulin dose was dictated by the choice of the attending clinician, although was reduced according to regular BG measurements during the treatment period to avoid hypoglycemia. Pre- and post-treatment IGF-1, average 12-hour BG and insulin dose were compared using a paired t-test (significance at P < 0.05). All eight cats showed a significant decrease in serum IGF-1 (mean+/-SD day 1: 1884 + /-218 ng/ml; day 5: 1169 + /-395 ng/ ml, p = 0.001) and average 12-hour BG (day 1: 20 + /-5 mmol/l; day 5: 13 + /-4 mmol/l; p = 0.002). A significant insulin dose reduction was necessary in all cats (day 1: 10.8 + /-6 iu/injection; day 5: 3.1 + /-2 iu/injection; p = 0.015). No side effects were noticed during or after the 3 day treatment period, apart from hypoglycemia in one cat, which resolved after provision of food and reduction of insulin dose. The current study indicates that SOM230 is able to rapidly decrease GH and IGF-1 concentrations in feline HS. This, therefore, suggests that sst receptors are present in most feline somatotrophinomas, which has previously been unclear given the disappointing results during somatostatins and sst analogue therapy attempts. A return of insulin sensitivity was seen, enabling improved glycemic control to be established with reduced doses of exogenous insulin in all cats. In light of these results, a clinical trial with a longer-acting formulation of SOM230 is currently being conducted to establish long-term effects and potential for diabetic remission. 

Comments— Pasireotide (SOM230, trade name Signofor, Novartis) is an orphan drug approved for the treatment of Cushing’s disease in adult human patients when surgery has failed or is not an option (1). The drug is a somatostatin analog that targets multiple somatostatin receptors with high affinity. The result is apoptosis of those cells that produce ACTH, with significant lowering of plasma ACTH levels (2,3).

In addition, pasireotide has been shown to suppress GH and IGF -1 in rodents and human patients with acromegaly (4). Moreover, recent results of a phase III study of human patients with acromegaly treated with a long-acting release form of pasireotide show that this novel form of therapy is significantly more effective than the current standard therapy with octreotide (5).

This study by Niessen et al indicates that pasireotide is able to rapidly decrease GH and IGF-1 concentrations in feline acromegaly and suggests that somatostain receptors are present in most cats with pituitary tumors that produce excessive GH. In light of these results, a clinical trial with the long-acting release form of pasireotide is currently being conducted to establish long-term effects and potential for diabetic remission in cats with acromegaly.

The Bottom Line—It is great to finally have a medical treatment that may actually work for cats with acromegaly. Unfortunately, administration of pasireotide SC twice daily may not be a practical or affordable therapeutic option for many of our cat owners.

References:

1. Signifor Official Site - Signifor® (pasireotide) Injection. Signifor.US‎. 
2. Colao A, Petersenn S, Newell-Price J, et al. A 12-month phase 3 study of pasireotide in Cushing's disease. N Engl J Med 2012;366:914-924. 
3. McKeage K. Pasireotide: a review of its use in Cushing's disease. Drugs 2013;73:563-574. 
4. Petersenn S, Farrall AJ, Block C, et al. Long-term efficacy and safety of subcutaneous pasireotide in acromegaly: results from an open-ended, multicenter, Phase II extension study. Pituitary 2013. DOI 10.1007/s11102-013-0478-0 
5. Colao A, Bronstein M, Freda P, et al. Pasireotide LAR is significantly more effective than octreotide LAR at inducing biochemical control in patients with acromegaly: Results of a 12-month randomized, double-blind, multicenter, Phase III study. Joint 15th International Congress of Endocrinology and 14th European Congress of Endocrinology. Abstract #OC1.1. 2012 

De Marco V, Noronha KSM, Casado TC, et al. Therapy of canine hyperlipidemia with bezafibrate. J Vet Intern Med2013;27:694.

The primary and secondary hyperlipidemia are common in dogs and its treatment is necessary to prevent clinical complications such as pancreatitis, seizures, liver disease and diabetes. The therapy of mild hyperlipidemia comprising a fat restricted diet, but in more severe cases pharmacological treatment is necessary. Bezafibrate (BZF) is effective in the treatment of hypertriglyceridemia in humans, however there are no clinical studies in dogs. The objectives of this study were to assess the efficacy of BZF in reducing serum triglyceride (TG) and cholesterol (CHO) in hyperlipidemic dogs, identify a therapeutic protocol for this drug and assess possible side eðects such as muscle pain, emesis, diarrhea and elevated CK and TGP levels. Only animals with moderate to severe hypertriglyceridemia (TG> 350 mg/dL) were treated with BZF every 24 hours for 30 days before introduction of any other therapy according to the protocol: tablet 200 mg for dogs weighting less than 12 kg, tablet 200 mg for dogs weighing between 13 and 25 kg, 1 tablet 200 mg for dogs weighing over 25 kg. We studied 46 dogs (26 females and 20 males) with a mean age of 9 years. Fifteen dogs (32.6%) had primary hyperlipidemia and 31 (67.4%) secondary hyperlipidemia, which included hyperadrenocorticism (41.3%), hypothyroidism (15.2%) and chronic corticoideterapia (10.8%). All 46 (100%) dogs had hypertriglyceridaemia and 33 (71.7%) had both hypertriglyceridaemia and hypercholesterolemia. After 30 days using BZF, normalization of serum TG (TG <150 mg/dL) was observed in 91.3% of cases (n = 42/46) and of CHO (CHO < 270 mg/dL) in 66 7% (n = 22/33) of cases. Means and standard deviations of serum TG and COL before (752 ± 663 mg/dL and 428 ± 217 mg/dL) and after therapy (110 ± 82 and 244 ± 71 mg /dL) were significantly lower (p < 0.005, paired Student t test). The bezafibrate dose most used with a 95% confidence interval was 5.3 to 6.1 mg/kg (range: 4–10 mg/kg). No side effects were observed, and there was no statistical difference between the values of ALT and CK before and after therapy. It can be concluded that bezafibrate is a safe and effective drug for the canine hyperlipidemia therapy.
  

Comments—Bezafibrate is a fibrate drug used for the treatment of hyperlipidemia (1-3). In people, fibrates are used as an accessory drug in many forms of hypercholesterolemia, usually along with statins. Bezafibrate helps lower cholesterol and triglycerides in the blood and increase high density lipoproteins (HDL). The main toxicity is hepatic, myopathy, and rarely rhabomyolysis.

Hyperlipidemia is a relatively commonly recognized disorder in dogs but management can be frustrating (4). In this study, 46 dogs with primary or secondary hyperlipidemia (diabetes mellitus, Cushing’s syndrome. hypothyroidism) were treated with bezafibrate once a day over a 30-day period; triglycerides and cholesterol were significantly lowered in the majority of dogs. In addition, there was no evidence of untoward side effects (e.g., no clinical issues and ALT and CK levels were not altered).

There are 2 preparations of bezafibrate available: 200 mg tablets and 400 mg sustained-release tablets. The sustained-release preparation is taken once a day; the non-sustained release tablets are taken with each meal. For dogs, the average dose used in this study was 5 to 6 mg/kg once a day. The dosing protocol was ¼ of a 200 mg tablet for dogs < 12 kg, ½ of a 200 mg tablet for dogs weighing between 12 and 25 kg, and one 200 mg tablet for dogs > 25 kg.

The Bottom Line—Bezafibrate given once a day appears to be a safe and effective drug for the treatment of hyperlipidemia in the dog.

References:

1. Goa KL, Barradell LB, Plosker GL. Bezafibrate. An update of its pharmacology and use in the management of dyslipidaemia. Drugs 1996;52:725-753.  
2. Goldenberg I, Benderly M, Goldbourt U. Update on the use of fibrates: focus on bezafibrate. Vasc Health Risk Manag 2008;4:131-141.  
3. Teramoto T, Shirai K, Daida H, et al. Effects of bezafibrate on lipid and glucose metabolism in dyslipidemic patients with diabetes: the J-BENEFIT study. Cardiovasc Diabetol 2012;11:29. 
4. Xenoulis PG, Steiner JM. Lipid metabolism and hyperlipidemia in dogs. Vet J 2010;183:12-21.

Salesov E, Boretti FS, Sieber-Ruckstuhl NS, et al. Urinary and plasma catecholamine and metanephrine in dogs with pheochromocytoma, hyperadrenocorticism and in healthy dogs. J Vet Intern Med 2013 27:688-689.

Pheochromocytoma (PHEO) is a rare malignant catecholamine-secreting tumor of the adrenal medulla. Catecholamines and metanephrines in plasma and in 24-h urine are approved biomarkers for the detection of the disease in humans, however, the question which of the tests is best is controversial. We previously demonstrated that measurement of urinary catecholamine and metanephrine to creatinine ratios is helpful for the diagnosis of PHEO in dogs and that urinary normetanephrine to creatinine ratio may be the best test to discriminate between PHEO and hypercortisolism (HC). Knowledge on plasma catecholamines and metanephrines in dogs is scarce and no comparison between urinary and plasma parameters has been performed. The objective of the study was to measure urinary as well as plasma catecholamines and metanephrines in dogs with PHEO, HC and in healthy dogs and to determine the test with the least overlap between the group. Six dogs with PHEO, 9 dogs with HC (6 with ATH, 3 with PDH) and 10 healthy dogs were included. Urine samples were collected into HCL containing tubes to ensure a pH 2, blood samples were collected on ice, centrifuged at 4°C and immediately snap frozen in liquid nitrogen. All samples were stored at – 80°C. Urinary epinephrine (U-Epi), norepinephrine (U-Norepi), metanephrine (U-Meta) and normetanephrine (U-Normeta), and epinephrine (P-Epi), norepinephrine (P-Norepi), free and total metanephrine (PF-Meta and PT-Meta) and free and total normetanephrine (PF-Normeta and PT-Meta) were analysed by HPLC. Urinary catecholamines and metanephrines were expressed as ratios to urine creatinine concentrations. Data were analysed by non-parametric tests (P < 0,05). Similar to our previous findings U-Epi, U-Norepi, U-Meta and U-Normeta were significantly higher in dogs with PHEO and U-Norepi and U-Normeta were significantly higher in dogs with HC compared to healthy dogs. Comparison between dogs with HC and dogs with PHEO revealed significantly higher U-Meta and U-Normeta in the latter group. U-Normeta was the only parameter with no overlap. In dogs with PHEO P-Norepi, PF-Meta, PT-Meta, PF-Normeta, PT-Normeta were significantly higher and in dogs with HC P-Norepi, PF- Normeta and PT-Normeta were significantly higher than in healthy dogs. Comparison between dogs with HC and dogs with PHEO showed significant higher PF-Meta, PT-Meta, PF- Normeta, PT-Normeta in the PHEO group. Overlap was present with all 4 parameters, but was least with PF-Normeta and PT-Normeta. According to our results U-Normeta, PF- Normeta and PT-Normeta are valuable parameters for the diagnosis of PHEO, so far U-Normeta performed better than the plasma parameters. 

Comments—In some recent studies, up to one in five adrenal tumors has been a pheochromocytoma. In the past, a presumptive diagnosis of a pheochromocytoma was based on history which was often a vague, sometimes episodic description of illness, documentation of hypertension, an adrenal mass noted on abdominal ultrasound, and ruling out adrenal-dependent Cushing’s syndrome with an endogenous ACTH level or the results of dexamethasone suppression testing. This current research adds additional data to the idea that measurement of urinary and plasma catecholamine and metanephrine can also be used to aid in diagnosis.

The Bottom Line—Currently, a urine normetaphrine/creatinine level, appears to be the most sensitive and specific test to document a pheochromocytoma.  This test requires that the urine sample is acidified at the time of collection and a control urine sample from a normal dog (also acidified) is submitted. A urine normetaphrine/creatinine level at least 4-times the control is consistent with pheochromocytoma.

In the US, the test for urine normetaphrine/creatinine can be performed at Marshfield Labs (www.marshfieldlabs.com). Acid pellets for urinary acidification are available from the laboratory.

References:

1. Quante S, Boretti FS, Kook PH, et al. Urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or pheochromocytoma, and in healthy dogs. J Vet Intern Med 2010;24:1093-1097. 
2. Kook PH, Grest P, Quante S, et al. Urinary catecholamine and metadrenaline to creatinine ratios in dogs with a phaeochromocytoma. Vet Rec2010;166:169-174. 
3. Kook PH, Boretti FS, Hersberger M, et al. Urinary catecholamine and metanephrine to creatinine ratios in healthy dogs at home and in a hospital environment and in 2 dogs with pheochromocytoma. J Vet Intern Med2007;21:388-393. 

Sangster K, Panciera JL, Abbott A, et al. Cardiac biomarkers in hyperthyroid cats. J Vet Intern Med 2013:637. 

Differentiation of hyperthyroid heart disease from primary myocardial disease is challenging. The cardiac biomarkers NT- proBNP and troponin I (cTNI) have proven useful in identifying cats with myocardial disease and may provide a method by which hypertrophic cardiomyopathy (HCM) and hyperthyroid heart disease can be discriminated. The primary purpose of this study was to compare plasma concentrations of NT-proBNP and cTNI in three groups of cats: cats with naturally occurring hyperthyroidism, cats with primary cardiomyopathy, and healthy older cats to determine if biomarkers differ between groups and if bio-marker concentrations in hyperthyroid cats change after resolution of the thyroid disease. We prospectively evaluated 61 client-owned cats: 23 hyperthyroid cats, 19 cats with HCM without congestive heart failure, and 19 euthyroid, normotensive healthy cats eight years of age or older. Fourteen of the hyperthyroid cats were re-evaluated three months after administration of I-131. A complete history, physical examination, CBC, serum biochemistries, urinalysis, blood pressure measurement, serum T4 concentration, plasma concentrations of NT-proBNP and cardiac troponin I, and echocardiography was obtained for each cat. Hyperthyroid and HCM cats had plasma NT-proBNP and cTNI concentrations that were significantly greater than healthy older cats, but there was no significant difference between hyperthyroid and HCM cats with respect to concentration of either biomarker. Plasma NT-proBNP and cTNI concentrations decreased in each cat that was examined three months after I-131 treatment. Plasma cTNI was within the reference interval for all cats at the three month recheck. Severely thickened myocardium persisted in one formerly hyperthyroid cat at the three month recheck, and this cat’s plasma NT-proBNP remained elevated. Although there may be a role for NT-proBNP in monitoring the cardiac response to treatment of hyperthyroidism, neither NT-proBNP nor cTNI can be used to distinguish hyperthyroid cats from cats with HCM. Therefore, the thyroid status of older cats should be ascertained prior to interpreting results of cardiac biomarker testing.
  

 Comments—Although it is well established that hyperthyroid cats will commonly develop secondary heart disease (1), it can sometimes be difficult to distinguish thyroid-induced cardiac disease from primary myocardial disease (cardiomyopathy). Over the last few years, a number of studies have confirmed the usefulness of plasma cardiac biomarkers (especially N-terminal pro-brain natriuretic peptide or NT-proBNP) to help detect hypertrophic cardiomyopathy in cats and to distinguish primary cardiac from non-cardiac causes of dyspnea in cats (2-5). Previous studies have found that hyperthyroid cats can have high circulaing levels of either troponin I or NT-proBNP; both biomarkers fall after successful treatment of the hyperthyroid state (6,7).

This research study confirmed that hyperthyroid cats can have high plasma NT-proBNP and troponin I (cTNI) concentrations, which decreased after I-131 treatment. However, there was no significant difference between hyperthyroid and HCM cats with respect to concentration of either biomarker.

The Bottom Line— Although hyperthyroid cats can have high plasma NT-proBNP and cTNI concentrations, there was no significant difference between hyperthyroid and HCM cats with respect to concentration of either biomarker. Therefore, neither of these cardiac biomarkers can be used to distinguish hyperthyroid cats from cats with HCM. Since hyperthyroidism can result in high levels of both biomarkers (6,7), the thyroid status of older cats should always be ascertained prior to interpreting results of cardiac biomarker testing.

References:

1. Syme HM. Cardiovascular and renal manifestations of hyperthyroidism. Vet Clin North Am Small Anim Pract 2007;37:723-743, vi. 
2. Wells SM, Sleeper M. Cardiac troponins. J Vet Emerg Crit Care 2008;18:235–245. 
3. Boswood A. Biomarkers in cardiovascular disease: beyond natriuretic peptides. J Vet Cardiol 2009;11 Suppl 1:S23-32. 
4. Fox PR, Oyama MA, Reynolds C, et al. Utility of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to distinguish between congestive heart failure and non-cardiac causes of acute dyspnea in cats. J Vet Cardiol 2009;11 Suppl 1:S51-61. 
5. Wess G, Daisenberger P, Mahling M, et al. Utility of measuring plasma N-terminal pro-brain natriuretic peptide in detecting hypertrophic cardiomyopathy and differentiating grades of severity in cats. Vet Clin Pathol 2011;40:237-244. 
6. Connolly DJ, Guitian J, Boswood A, et al. Serum troponin I levels in hyperthyroid cats before and after treatment with radioactive iodine. J Feline Med Surg 2005;7:289-300. 
7. Menaut P, Connolly DJ, Volk A, et al. Circulating natriuretic peptide concentrations in hyperthyroid cats. J Small Anim Pract 2012;53:673-678.  

Top Endocrine Publications of 2011: The Canine Adrenal Gland

In my seventh compilation of the canine and feline endocrine publications of 2011, I’m moving on to disorders of the canine adrenal gland.

Listed below are 35 research papers written in 2011 that deal with a variety of adrenal gland issues of clinical importance in dogs.

These range from the investigations of typical (13,27), atypical (24,28), or pseudo-hypoadrenocorticism (32) to a case report of hyporeninemic hypoaldosteronism (16); from diagnostic testing for Cushing's syndrome (5,10,11,34) to imaging studies for evaluation and differentiation of adrenal disease (4,23,25); from studies of the relationship between gallbladder mucoceles and glucocorticoid excess (15,21) to and to dermatologic aspects of Cushing's disease (35).

Other research studies investigated the use of trilostane (3,8,12,20) to an overview of adrenalectomy for dogs with adrenal gland tumors (17,19); from complications associated with transsphenoidal surgery (31) to the effect of lignans and melatonin treatment on adrenocortical secretion (7); and finally, the report of an experimental new medical approach to treating Cushing's disease using a tyrosine kinase inhibitor to block epidermal growth factor receptor located on the pituitary adenoma, which inhibited corticotroph tumor cell proliferation and induced apotosis (9,33).

Other studies include the investigation of a radionuclide therapy for canine pheochromocytoma (2) to a case report of pheochromocytoma diagnosed by use of magnetic resonance imaging (29).

References:

1. Blois SL, Dickie E, Kruth SA, et al. Multiple endocrine diseases in dogs: 35 cases (1996-2009). J Am Vet Med Assoc 2011;238:1616-1621. 
2. Bommarito DA, Lattimer JC, Selting KA, et al. Treatment of a malignant pheochromocytoma in a dog using 131I metaiodobenzylguanidine. J Am Anim Hosp Assoc 2011;47:e188-194. 
3. Burkhardt WA, Guscetti F, Boretti FS, et al. Adrenocorticotropic hormone, but not trilostane, causes severe adrenal hemorrhage, vacuolization, and apoptosis in rats. Domest Anim Endocrinol 2011;40:155-164. 
4. 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;73:985-989. 
5. Cisneros LE, Palumbo MI, Mortari AC, et al. What is your neurologic diagnosis? Hyperadrenocorticism. J Am Vet Med Assoc 2011;238:1247-1249. 
6. de Brito Galvao JF, Chew DJ. Metabolic complications of endocrine surgery in companion animals. Vet Clin North Am Small Anim Pract 2011;41:847-868. 
7. Fecteau KA, Eiler H, Oliver JW. Effect of combined lignan phytoestrogen and melatonin treatment on secretion of steroid hormones by adrenal carcinoma cells. Am J Vet Res 2011;72:675-680. 
8. 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. 
9. Fukuoka H, Cooper O, Ben-Shlomo A, et al. EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas. J Clin Invest 2011;121:4712-4721. 
10. Gilor C, Graves TK. Interpretation of laboratory tests for canine Cushing's syndrome. Top Companion Anim Med 2011;26:98-108. 
11. Graves TK. When normal is abnormal: keys to laboratory diagnosis of hidden endocrine disease. Top Companion Anim Med 2011;26:45-51. 
12. Helm JR, McLauchlan G, Boden LA, et al. A comparison of factors that influence survival in dogs with adrenal-dependent hyperadrenocorticism treated with mitotane or trilostane. J Vet Intern Med 2011;25:251-260. 
13. Hughes AM, Bannasch DL, Kellett K, et al. Examination of candidate genes for hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers. Vet J 2011;187:212-216. 
14. Klose TC, Creevy KE, Brainard BM. Evaluation of coagulation status in dogs with naturally occurring canine hyperadrenocorticism. J Vet Emerg Crit Care (San Antonio) 2011;21:625-632. 
15. Kook PH, Schellenberg S, Rentsch KM, et al. Effect of twice-daily oral administration of hydrocortisone on the bile acids composition of gallbladder bile in dogs. Am J Vet Res 2011;72:1607-1612. 
16. Kreissler JJ, Langston CE. A case of hyporeninemic hypoaldosteronism in the dog. J Vet Intern Med 2011;25:944-948. 
17. Lang JM, Schertel E, Kennedy S, et al. Elective and emergency surgical management of adrenal gland tumors: 60 cases (1999-2006). J Am Anim Hosp Assoc 2011;47:428-435. 
18. Martin LG. Critical illness-related corticosteroid insufficiency in small animals. Vet Clin North Am Small Anim Pract 2011;41:767-782.
19. Massari F, Nicoli S, Romanelli G, et al. Adrenalectomy in dogs with adrenal gland tumors: 52 cases (2002-2008). J Am Vet Med Assoc 2011;239:216-221. 
20. McGraw AL, Whitley EM, Lee HP, et al. Determination of the concentrations of trilostane and ketotrilostane that inhibit ex vivo canine adrenal gland synthesis of cortisol, corticosterone, and aldosterone. Am J Vet Res 2011;72:661-665. 
21. Norwich A. Gallbladder mucocele in a 12-year-old cocker spaniel. Can Vet J 2011;52:319-321. 
22. Notari L, Mills D. Possible behavioral effects of exogenous corticosteroids on dog behavior: a preliminary investigation. J Vet Behavior 2011;6:321-327. 
23. Pey P, Vignoli M, Haers H, et al. Contrast-enhanced ultrasonography of the normal canine adrenal gland. Vet Radiol Ultrasound 2011;52:560-567. 
24. Richartz J, Neiger R. Hypoadrenocorticism without classic electrolyte abnormalities in seven dogs. Tierarztl Prax Ausg K Kleintiere Heimtiere 2011;39:163-169. 
25. Rodriguez Pineiro MI, de Fornel-Thibaud P, Benchekroun G, 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. 
26. Ryan VH, Trayhurn P, Hunter L, et al. 11-Hydroxy-beta-steroid dehydrogenase gene expression in canine adipose tissue and adipocytes: stimulation by lipopolysaccharide and tumor necrosis factor alpha. Domest Anim Endocrinol 2011;41:150-161. 
27. Seth M, Drobatz KJ, Church DB, et al. White blood cell count and the sodium to potassium ratio to screen for hypoadrenocorticism in dogs. J Vet Intern Med 2011;25:1351-1356. 
28. Snead E, Vargo C, Myers S. Glucocorticoid-dependent hypoadrenocorticism with thrombocytopenia and neutropenia mimicking sepsis in a Labrador retriever dog. Can Vet J 2011;52:1129-1134. 
29. Spall B, Chen AV, Tucker RL, et al. Imaging diagnosis-metastatic adrenal pheochromocytoma in a dog. Vet Radiol Ultrasound 2011;52:534-537. 
30. Taoda T, Hara Y, Masuda H, et al. Magnetic resonance imaging assessment of pituitary posterior lobe displacement in dogs with pituitary-dependent hyperadrenocorticism. J Vet Med Sci 2011;73:725-731. 
31. Teshima T, Hara Y, Taoda T, et al. Central diabetes insipidus after transsphenoidal surgery in dogs with Cushing's disease. J Vet Med Sci 2011;73:33-39. 
32. Venco L, Valenti V, Genchi M, et al. A dog with pseudo-Addison disease associated with trichuris vulpis Infection. J Parasitol Res 2011;2011:682039. 
33. Wondisford FE. A new medical therapy for Cushing disease? J Clin Invest 2011;121:4621-4623. 
34. Zeugswetter F, Pagitz M, Hittmair K, et al. Diagnostic efficacy of plasma ACTH-measurement by a chemiluminometric assay in canine hyperadrenocorticism. Schweiz Arch Tierheilkd 2011;153:111-116. 
35. Zur G, White SD. Hyperadrenocorticism in 10 dogs with skin lesions as the only presenting clinical signs. J Am Anim Hosp Assoc 2011;47:419-427. 

Top Endocrine Publications of 2010: The Feline Adrenal Gland

In my seventh compilation of the canine and feline endocrine publications of 2010, I’m moving on to disorders of the feline adrenal gland.

Listed below are 8 research papers written in 2010 that deal with a variety of adrenal gland topics of issues of clinical importance in cats.

These range from a report of a cat with concurrent adrenal pheochromocytoma and contralateral adrenocortical tumor (1) to investigation of plasma catecholamines in diagnoses of feline pheochromocytoma (8); from a review of primary hyperaldosteronism (Conn's syndrome) to a overview of endocrine hypertension in cats (3,4); from a report of Cushing's syndrome in a cat with generalized toxoplasmosis (6) to reports on the risks of human estrogen sprays to cats through contact with treated skin (7).

References:

1. Calsyn JD, Green RA, Davis GJ, et al. Adrenal pheochromocytoma with contralateral adrenocortical adenoma in a cat. Journal of the American Animal Hospital Association 2010;46:36-42.
2. Cohn LA, DeClue AE, Cohen RL, et al. Effects of fluticasone propionate dosage in an experimental model of feline asthma. Journal of feline medicine and surgery 2010;12:91-96.
3. Reusch CE, Schellenberg S, Wenger M. Endocrine hypertension in small animals. The Veterinary clinics of North America Small animal practice 2010;40:335-352.
4. Schulman RL. Feline primary hyperaldosteronism. The Veterinary clinics of North America Small animal practice 2010;40:353-359.
5. Sieber-Ruckstuhl NS, Zini E, Osto M, et al. Effect of hyperlipidemia on 11-beta-hydroxysteroid-dehydrogenase, glucocorticoid receptor, and leptin expression in insulin-sensitive tissues of cats. Domestic Animal Endocrinology 2010;39:222-230.
6. Spada E, Proverbio D, Giudice C, et al. Pituitary-dependent hyperadrenocorticism and generalised toxoplasmosis in a cat with neurological signs. Journal of feline medicine and surgery 2010;12:654-658.
7. Voelker R. Estrogen spray poses risks to children, pets through contact with treated skin. Journal of the American Medical Association 2010;304:953.
8. Wimpole JA, Adagra CF, Billson MF, et al. Plasma free metanephrines in healthy cats, cats with non-adrenal disease and a cat with suspected phaeochromocytoma. Journal of feline medicine and surgery 2010;12:435-440.

Top Endocrine Publications of 2010: The Canine Adrenal Gland

In my sixth compilation of the canine and feline endocrine publications of 2010, I’m moving on to disorders of the canine adrenal gland.

Listed below are 31 research papers written in 2010 that deal with a variety of adrenal gland issues of clinical importance in dogs.

These range from the investigations of hypoadrenocorticism (1, 14-16, 19, 29) to typical (3, 5, 8-10, 13, 17, 20, 24, 26, 30) and atypical (4, 6) hyperadrenocorticism; from diagnostic tests for Cushing's syndrome (17, 30) to studies of ultrasonography for evaluation  and differentiation of adrenal disease (5, 28);  and from trilostane (3,8, 9, 24) to studies of the efficacy of transsphenoidal surgery as treatment for Cushing's disease (13.

In addition, other studies include the investigation of urine and plasma catecholamines in diagnoses of canine pheochromocytoma (7, 11, 18,  23) to a review of canine chemodectoma (22); and from  studies of the endocrine hypertension (19, 25) to reports on the risks of human estrogen sprays to pets through contact with treated skin (28).

References:

1. Adissu HA, Hamel-Jolette A, Foster RA. Lymphocytic adenohypophysitis and adrenalitis in a dog with adrenal and thyroid atrophy. Veterinary Pathology 2010;47:1082-1085.
2. Adissu HA, Hayes G, Wood GA, et al. Cardiac myxosarcoma with adrenal adenoma and pituitary hyperplasia resembling Carney complex in a dog. Veterinary Pathology 2010;47:354-357.
3. Arteaga A, Dhand NK, McCann T, et al. Monitoring the response of canine hyperadrenocorticism to trilostane treatment by assessment of acute phase protein concentrations. The Journal of Small Animal Practice 2010;51:204-209.
4. Behrend EN, Kennis R. Atypical Cushing's syndrome in dogs: arguments for and against. The Veterinary Clinics of North America: Small Animal Practice 2010;40:285-296.
5. Benchekroun G, de Fornel-Thibaud P, Rodriguez Pineiro MI, et al. Ultrasonography criteria for differentiating ACTH dependency from ACTH independency in 47 dogs with hyperadrenocorticism and equivocal adrenal asymmetry. Journal of Veterinary Internal Medicine 2010;24:1077-1085.
6. Bromel C, Feldman EC, Davidson AP, et al. Serum 17-alpha-hydroxyprogesterone concentrations during the reproductive cycle in healthy dogs and dogs with hyperadrenocorticism. Journal of the American Veterinary Medical Association 2010;236:1208-1214.
7. Cameron KN, Monroe WE, Panciera DL, et al. The effects of illness on urinary catecholamines and their metabolites in dogs. Journal of Veterinary Internal Medicine 2010;24:1329-1336.
8. Cook AK, Bond KG. Evaluation of the use of baseline cortisol concentration as a monitoring tool for dogs receiving trilostane as a treatment for hyperadrenocorticism. Journal of the American Veterinary Medical Association 2010;237:801-805.
9. Galac S, Buijtels JJ, Mol JA, et al. Effects of trilostane on the pituitary-adrenocortical and renin-aldosterone axis in dogs with pituitary-dependent hypercortisolism. Veterinary Journal 2010;183:75-80.
10. Galac S, Kool MM, Naan EC, et al. Expression of the ACTH receptor, steroidogenic acute regulatory protein, and steroidogenic enzymes in canine cortisol-secreting adrenocortical tumors. Domestic Animal Endocrinology 2010;39:259-267.
11. Gostelow R, Syme H. Plasma metadrenalines in canine phaeochromocytoma. The Veterinary Record 2010;166:538.
12. Hanson JM, Mol JA, Meij BP. Expression of leukemia inhibitory factor and leukemia inhibitory factor receptor in the canine pituitary gland and corticotrope adenomas. Domestic Animal Endocrinology 2010;38:260-271.
13. Hara Y, Teshima T, Taoda T, et al. Efficacy of transsphenoidal surgery on endocrinological status and serum chemistry parameters in dogs with Cushing's disease. The Journal of Veterinary Medical Science 2010;72:397-404.
14. Hughes AM, Jokinen P, Bannasch DL, et al. Association of a dog leukocyte antigen class II haplotype with hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers. Tissue Antigens 2010;75:684-690.
15. Klein SC, Peterson ME. Canine hypoadrenocorticism: part I. The Canadian Veterinary Journal 2010;51:63-69.
16. Klein SC, Peterson ME. Canine hypoadrenocorticism: part II. The Canadian Veterinary Journal 2010;51:179-184.
17. Kooistra HS, Galac S. Recent advances in the diagnosis of Cushing's syndrome in dogs. The Veterinary Clinics of North America: Small Animal Practice 2010;40:259-267.
18. Kook PH, Grest P, Quante S, et al. Urinary catecholamine and metadrenaline to creatinine ratios in dogs with a phaeochromocytoma. The Veterinary Record 2010;166:169-174.
19. Kook PH, Grest P, Raute-Kreinsen U, et al. Addison's disease due to bilateral adrenal malignancy in a dog. The Journal of Small Animal Practice 2010;51:333-336.
20. Lien YH, Hsiang TY, Huang HP. Associations among systemic blood pressure, microalbuminuria and albuminuria in dogs affected with pituitary- and adrenal-dependent hyperadrenocorticism. Acta Veterinaria Scandinavica 2010;52:61.
21. Mori N, Lee P, Muranaka S, et al. Predisposition for primary hyperlipidemia in Miniature Schnauzers and Shetland sheepdogs as compared to other canine breeds. Research in Veterinary Science 2010;88:394-399.
22. Noszczyk-Nowak A, Nowak M, Paslawska U, et al. Cases with manifestation of chemodectoma diagnosed in dogs in Department of Internal Diseases with Horses, Dogs and Cats Clinic, Veterinary Medicine Faculty, University of Environmental and Life Sciences, Wroclaw, Poland. Acta Veterinaria Scandinavica 2010;52:35.
23. Quante S, Boretti FS, Kook PH, et al. Urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or pheochromocytoma, and in healthy dogs. Journal of Veterinary Internal Medicine 2010;24:1093-1097.
24. Ramsey IK. Trilostane in dogs. The Veterinary clinics of North America Small Animal Practice 2010;40:269-283.
25. Reusch CE, Schellenberg S, Wenger M. Endocrine hypertension in small animals. The Veterinary Clinics of North America: Small Animal Practice 2010;40:335-352.
26. Trapani F, Del Basso De Caro ML, Insabato L, et al. Type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog. Folia histochemica et Cytobiologica 2010;48:403-406.
27. van Rijn SJ, Grinwis GC, Penning LC, et al. Expression of Ki-67, PCNA, and p27kip1 in canine pituitary corticotroph adenomas. Domestic Animal Endocrinology 2010;38:244-252.
28. Voelker R. Estrogen spray poses risks to children, pets through contact with treated skin. Journal of the American Medical Association 2010;304:953.
29. Wenger M, Mueller C, Kook PH, et al. Ultrasonographic evaluation of adrenal glands in dogs with primary hypoadrenocorticism or mimicking diseases. The Veterinary Record 2010;167:207-210.
30. Zeugswetter F, Bydzovsky N, Kampner D, et al. Tailored reference limits for urine corticoid:creatinine ratio in dogs to answer distinct clinical questions. The Veterinary Record 2010;167:997-1001.
31. Zimmerman KL, Panciera DL, Panciera RJ, et al. Hyperphosphatasemia and concurrent adrenal gland dysfunction in apparently healthy Scottish Terriers. Journal of the American Veterinary Medical Association 2010;237:178-186.

Adrenal Tumors in Cats

Click here to view the slides as you read through this lecture.

Adrenal tumors are an uncommon finding in cats. Based on available data, it is estimated that approximately 0.03% of the feline population (representing 0.2% of all cat tumors) develop a primary adrenal gland tumour. Metastasis to the adrenal glands from other organs is uncommon but when it does occur, lymphoma seems to be the most common (1).

An adrenal tumour may be functional (i.e., producing and secreting a hormone) or nonfunctional. In cats, adrenocortical tumors can secrete excessive amounts of cortisol, progesterone and other sex steroid hormones, or aldosterone. Feline adrenal medullary tumors (pheochromocytoma), although extremely rare, secrete excessive amounts of catecholamines.

Cortisol-Secreting Adrenal Tumors
A cortisol-secreting adrenal mass causing hyperadrenocorticism is the most common functional adrenal tumour identified in cats. Naturally occurring hyperadrenocorticism (Cushing’s syndrome) is rare in cats (2-4). Pituitary-dependent hyperadrenocorticism accounts for the majority of cases, but cortisol-secreting adrenocortical neoplasia is responsible in approximately 20% of cats. About one-third of theses adrenal tumors in cats are malignant.

Historical and clinical findings in cats with cortisol-secreting adrenal tumors may include lethargy, weakness, pendulous abdomen, thin fragile skin, bilaterally symmetric alopecia, dull haircoat, seborrhea sicca, muscle atrophy, polyuria, polydipsia, and polyphagia (2-4). In contrast to dogs with hyperadrenocorticism, polyuria and polydipsia in affected cats appear to be secondary to concurrent diabetes mellitus in the vast majority of cases. Hyperglycemia and glycosuria are seen in up to 90% of cats and hypercholesterolemia and elevated serum ALT activity are common. However, a high serum alkaline phosphatase activity is not a consistent finding in cats with hyperadrenocorticism.

In addition to the typical clinical signs and clinicopathologic findings associated with hyperadrenocorticism, diagnosis of hyperadrenocorticism due to a functional adrenal tumour is confirmed using tests of pituitary-adrenocortical axis (ie, high dose dexamethasone suppression test and endogenous ACTH concentrations). Finally, imaging studies (ie, abdominal ultrasound, CT, MR) should be used to confirm the presence of an adrenal tumour in these cats (2-4). In cats with adrenal-dependent hyperadrenocorticism, the contralateral adrenal gland is expected to be small or atrophied as a result of suppressed pituitary ACTH secretion.

Unilateral adrenalectomy is most successful method of treating cats with cortisol-secreting adrenocortical tumour (2-5). In cats with adrenal adenoma or adrenal carcinoma that has not yet metastasized, adrenalectomy may be curative. If tumour resection is successful, circulating cortisol fall to low concentrations and these cats generally require glucocorticoid supplementation for approximately two months postoperatively until the glucocorticoid secretory function of the atrophied contralateral gland recovers.

Because of the deleterious effects of chronic cortisol excess on skin fragility as well as on immune and cardiovascular function, many cats with untreated hyperadrenocorticism are poor surgical candidates. Surgery has been difficult to perform owing to the debilitated condition of these cats. Although further investigation needs to be done, trilostane (5-15 mg/kg) appears to be useful in the preoperative preparation of these cats prior to adrenalectomy (3,6). In those cats that are not surgical candidate or have adrenal tumour metastasis, trilostane (Vetoryl. Dechra Veterinary Products) may also be useful in their long-term management, at least for a few weeks to months.

Sex hormone Secreting Adrenal Tumors
A functional tumour arising from the adrenal cortex could secrete excessive amounts of adrenal progestagens, androgens, or estrogens. Progesterone-secreting adrenal tumors have been the most common sex hormone secreting adrenal tumour reported in cats (6-10). Clinical signs are similar to those in cats with cortisol-secreting tumors. Excessive progesterone secretion in affected cats causes diabetes mellitus and feline fragile skin syndrome, which is characterized by progressively worsening dermal and epidermal atrophy, endocrine alopecia, and easily torn skin. In most of these cats with progesterone-secreting adrenal tumors, results of tests of the pituitary-adrenocortical axis are normal to suppressed and the contralateral adrenal gland is normal in size and shape on abdominal ultrasound. Diagnosis requires documenting an increased concentration of one or more adrenal sex steroids, ideally measured before and after ACTH stimulation.
Recently, a male cat that had developed strong urine order and aggressive behaviour was documented to have a functional adrenal adenoma associated with high circulating concentration of androstenedione and testosterone (11). After adrenalectomy, serum concentrations of the androgens decreased and urine spraying urine aggression resolved.

Aldosterone Secreting Adrenal Tumors
Primary hyperaldosteronism (Conn's syndrome) appears to be a relatively rare but greatly underdiagnosed disease of older cats. This syndrome is characterized by excessive autonomous secretion of aldosterone from one or both adrenal glands, resulting in clinical signs relating to hypertension and/or hypokalemia (13-16).

About half of cases have been due to unilateral aldosterone-secreting adrenal adenomas, whereas most of the remaining cats have unilateral adrenal carcinomas. Less commonly, bilateral adrenal adenomas or bilateral adrenal hyperplasia (17) have been reported. Occasionally, an aldosterone-secreting adrenal tumour is also found to be hypersecreting another adrenocortical hormone, most commonly progesterone (9,11); these cats also had diabetes mellitus and dermatologic changes, both attributed to progesterone excess rather than hyperaldosteronism.
Aldosterone is the major mineralocorticoid secreted by the adrenal cortex and is responsible for regulation of sodium and potassium balance. Therefore, the hormone helps maintain intravascular fluid volume and acid-base balance. Historical findings are generally nonspecific can include generalized weakness (sometimes episodic), lethargy, stiffness, muscle pain, polyuria/polydipsia, and blindness (13-17). Physical examination findings might include ventroflexion of the neck, hypertension, blindness, and retinal vessel tortuosity.

Cats with hyperaldosteronism commonly have moderate to severe hypokalemia and metabolic alkalosis. The sodium concentration is normal to mildly elevated. Demonstration of an inappropriately elevated serum aldosterone concentration along with a low plasma renin concentration provides a definitive diagnosis of hyperaldosteronism. Ideally a diagnosis is made on the basis of marked hyperaldosteronemia in conjunction with hypertension, hypokalemia, inappropriate kaliuresis (high urinary fractional excretion of potassium), and low plasma renin activity (14-17). The presence of renal failure presents a particular diagnostic dilemma, as renal failure itself can lead to a similar constellation of abnormalities. The magnitude of aldosterone elevation may be the key (ie, aldosterone is only about 2-3 times normal with renal failure).

A recent report assessed changes of the urinary aldosterone-to-creatinine ratio in normal cats in response to increased dietary salt or administration of fludrocortisone acetate (18). In that study, normal cats showed the most consistent decrease of the urinary aldosterone-to-creatinine ratio with administration of fludrocortisone acetate as compared with dietary salt supplementation. One cat with an aldosterone-secreting adrenal carcinoma had an elevated ratio and no suppression in response to fludrocortisone acetate. Such mineralocorticoids function tests may prove useful as more cats are diagnosed with this syndrome.

Initial treatment of cats with hyperaldosteronism should be directed toward provision of parenteral or oral potassium supplementation and correction of any fluid deficits and acid-base imbalances. For this purpose, potassium gluconate is generally given at the dosage of 2-6 mEq/day, with the dose adjusted as necessary to maintain normokalemia. If necessary, the diuretic spironolactone, which acts as an aldosterone receptor antagonist, can also be administered at the dosage of 2-4 mg/kg/day.

Surgical adrenalectomy is the treatment of choice in most cats with hyperaldosteronism that do not have evidence of metastatic disease. For those cats that have bilateral adrenal hyperplasia, metastatic disease, or whose owners have declined surgery, medical management with oral spironolactone and potassium can be continued indefinitely.


Catecholamine Secreting Adrenal Tumors
Pheochromocytoma is a catecholamine-producing tumour derived from the chromaffin cells of the adrenal medulla that is extremely rare in cats (1, 2). Clinical signs and physical examination findings develop as a result of the space-occupying nature of the tumour and its metastases, or as a result of excessive secretion of catecholamines and their impact on blood pressure and cardiac function. A diagnosis of pheochromocytoma prior to surgery is usually one of exclusion. Unlike a cortisol-secreting adrenal tumour, the contralateral adrenal gland should be normal in size and shape with a catecholamine-producing adrenal tumour. Catecholamine secretion by the tumour, and thus systemic hypertension, tends to be episodic; failure to document systemic hypertension does not rule out pheochromocytoma. Measurement of urinary catecholamine concentrations or their metabolites can strengthen the tentative diagnosis of pheochromocytoma but is not commonly performed in cats. Because many of the clinical signs and blood pressure alterations are similar for pheochromocytoma and adrenal-dependent hyperadrenocorticism, it is important to rule out adrenal-dependent hyperadrenocorticism before focusing on pheochromocytoma.

References
1. Withrow Stephen J, and David M. Vail. Small Animal Clinical Oncology. St Louis: Saunders Elsevier, 2007.

2. Peterson ME, Randolph JF, Mooney CT. Endocrine diseases. In: Sherding RG eds. The Cat: Siagnosis and Clinical Management (2nd ed). New York: Churchill Livingstone, 1984; 1404-1506.
3. Duesberg C. Peterson ME. Adrenal disorders in cats. Vet Clin North Am Small Anim Pract 1997;27:321-347.

4. Peterson ME. Feline hyperadrenocorticism. In: Mooney CT, Peterson ME (eds). BSAVA Manual of Endocrinology (Third Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association, pp 205-212, 2004.

5. Duesberg CA, Nelson RW, Feldman EC, et al. Adrenalectomy for treatment of hyperadrenocorticism in cats: 10 cases (1988-1992). J Am Vet Med Assoc 1995;207:1066-1070.

6. Boag AK, Neiger R, Church DB. Trilostane treatment of bilateral adrenal enlargement and excessive sex steroid hormone production in a cat. J Small Anim Pract 2004;45: 263-266.

7. Boord M, Griffin C. Progesterone-secreting adrenal mass in a cat with clinical signs of hyperadrenocorticism. J Am Vet Med Assoc 1999; 214: 666-669.

8. Rossmeisl JH, Scott-Moncrieff JC, Siems J, et al. Hyperadrenocorticism and hyper-progesteronemia in a cat with an adrenocortical adenocarcinoma. J Am Anim Hosp Assoc 2000; 36: 512-517.

9. Declue AE, Breshears LA, Pardo ID, et al: Hyperaldosteronism and hyperprogesteronism in a cat with an adrenal cortical carcinoma. J Am Vet Med Assoc 2005:19: 355-358.

10. Quante S, Sieber-Ruckstuhl N, Wilhelm S, et al. Hyperprogesteronism due to bilateral adrenal carcinomas in a cat with diabetes mellitus. Schweizer Archiv fur Tierheilkunde 2009; 151: 437-442.

11. Millard RP, Pickens EH, Wells KL. Excessive production of sex hormones in a cat with an adrenocortical tumour. J Am Vet Med Assoc. 2009;234:505-508.

12. Briscoe K, Barrs VR, Foster DF, et al. Hyperaldosteronism and hyperprogesteronism in a cat. J Fel Med Surg 2009; 11: 758-762.

13. Rose SA, Kyles AE, Labelle P. Adrenalectomy and caval thrombectomy in a cat with primary hyperaldosteronism. J Am Anim Hosp Assoc. 2007; 43: 209-214.

14. Ash RA, Harvey Am, Tasker S. Primary hyperaldosteronism in the cat: a series of 13 cases. J Feline Med Surg 2005; 7: 173-82.

15. Gunn-Moore D. Feline endocrinopathies. Vet Clin North Am Small Anim Pract 2005; 35: 171-210.

16. Rijnberk A, Voorhout G, Kooistra HS, et al: Hyperaldosteronism in a cat with metastasised adrenocortical tumour. Vet Q 2001; 23: 38-43.

17. Javadi S, Djajadiningrat-Laanen SC, Kooistra HS et al. Primary hyperaldosteronism, a mediator of progressive renal disease in cats. Domestic Animal Endocrinol 2005; 28: 85-104.

18. Djajadiningrat-Laanen SC, Galac S, Cammelbeeck SE, et al. Urinary aldosterone to creatinine ratio in cats before and after suppression with salt or fludrocortisone acetate. J Vet Intern Med 2008;22:1283-2388.