Adrenal exhaustion and immunoglobulin suppression: common findings in 54 dogs with Sudden Acquired Retinal Degeneration (SARD)

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1 Adrenal exhaustion and immunoglobulin suppression: common findings in 54 dogs with Sudden Acquired Retinal Degeneration (SARD) Caroline D. Levin RN Copyright July 8, 008. March, 009, The author reviewed the charts of 54 SARD-affected dogs between Dogs were tested/treated by their general practice veterinarian. Results were fairly consistent despite slight variations in hormone replacement therapy and lab facilities (see below). Follow-up lab results represent only a brief window in time; treatment is life-long. Two laboratories revised their reference ranges during this time period and those revisions are reflected below. Note to practioners: reference ranges at are extremely narrow and slight elevations are significant, correlating closely with clinical signs of PU/PP/ lethargy/confusion, etc. Initial evaluation ranged from years post-sard onset (mean =.6 ). 5 of 54 dogs (98%) demonstrated elevations in one or more adrenal sex-hormones (progesterones, androgen, and/or estrogens). Inadequate cortisol production is a common cause of elevated sex-hormones in both dogs and humans. -7 When production of active cortisol fails during adulthood the condition is described as adrenal exhaustion. 8,9 4 dogs had assayed as well. 40 of 4 (9%) demonstrated low levels of IgM, IgG and/or IgA. However, this trend was not consistent between lab facilities. One explanation may involve sample collection or handling technique. If serum samples are permitted to warm, aggregate, yielding high false-positive levels. 0, Sample age, evaporation, and reagent shelf life are also reported to erroneously affect outcomes. Rising estrogen levels are reported to suppress both immunoglobulin production in humans and bone marrow activity in dogs. -5 of the 54 dogs received low-dose cortisol and thyroid hormone replacement therapy. Duration of treatment prior to retest = (mean =.6 ). Of the dogs treated, 95% demonstrated improved sex-hormone levels and 00% demonstrated improved immunoglobulin levels. % of dogs (#0,, 5, 50, 5) demonstrated some degree of functional vision confirmed by GP veterinarian or veterinary ophthalmologist. Recommendations: SARD-affected dogs should be promptly tested and treated for adrenal exhaustion, as hormone replacement therapy improves sex-hormone levels and immunoglobulin production in nearly all dogs and may restore functional vision in some dogs.. Levin C. Sudden Acquired Retinal Degeneration, associated pattern of adrenal activity, and hormone replacement in three dogs a retrospective study. Proceedings of the 8 th Annual Meeting of the College of Veterinary Ophthalmologists 007; 8:.. Guthrie GP, Wilson EA, Quillen DL, Jawad MJ. Adrenal androgen excess and defective -beta-hydroxylation in women with idiopathic hirsutism (abstract). Archives of Internal Medicine 98; 4: Deaton M, Glorioso JE, Mclean, DB. Congenital Adrenal Hyperplasia Not really a zebra. American Family Physician 999; 59: Naessen S, Carlstrom K, Garoff L, Glant R, Hirschberg AL. Polycystic ovary syndrome in bulimic women an evaluation based on new diagnostic criteria (abstract). Gynecological Endocrinology 00; : Derman RJ. Effects of sex steroids on women s health: implications for practitioners (abstract). American Journal of Medicine 995; A: 7S-4S. 6. Plechner AJ. Cortisol abnormality as a cause of elevated estrogen and immune destabilization: Insights for human medicine from a veterinary perspective. Medical Hypothesis 004; 6: Jeffries MK. Safe Uses of Cortisol third edition. Charles C. Thomas Publisher, Ltd, Springfield, Marik PE. Adrenal-exhaustion syndrome in patients with liver disease (abstract). Intensive Care Medicine 006; : Selye H. The Stress of Life revised edition. McGraw-Hill, Incorporated: New York, Yoshida H, Ishikawa H, Honda S, Miura Y, Ogata M. False positive reaction of heat-inactivated sera in enzyme-linked immunosorbent assay for antibody to hepatitis C virus (abstract). Fukushima Journal of Medical Science 99; 8; Luginbühl A, Nikolic M, Beck H. Complement Factor D, Albumin and Immunoglobulin G Anti-Band Protein Antibodies Mimic Serum in Promoting Rosetting of Malaria-Infected Red Blood Cells. Infection and Immunity 007; 75: Key M. Pathology: Immunohistochemical Staining Methods fourth edition. Dako Laboratories, Carpinteria, California, Hart JE. Endocrine pathology of estrogens: species differences (abstract). Pharmacology Therapeutics 990; 47: Zayed I, van Esch E, McConnell R. Systemic and histopathologic changes in beagle dogs after chronic daily oral administration of synthetic or natural estrogens with special reference to the kidney & thyroid. Toxicologic Pathology 998; 6: Blum M, Zacharovich D, Pery J, Kitai E. Lowering effect of estrogen treatment on in menopausal women (abstract). Revue française degynecologie et d obstetrique 990; 4:

2 Adrenal exhaustion and immunoglobulin suppression: common findings in 54 dogs with Sudden Acquired Retinal Degeneration (SARD) Caroline D. Levin RN Dog Breed, Age & Gender Interval from SARD onset Lab results : initial Testing facility & normal range Hormone replacement treatment Lab results : post-treatment Interval between tests 0 y/o, M/n estradiol.40 Cornell University estradiol: males < 0 pg/ml triamcinolone acetonide mg IM methylprednisolone mg PO SID levothyroxine 0.mg PO BID estradiol Maltesemix, 9.5 y/o, F/s Newfoundland 6 y/o, M/n Brittany 9 y/o, M/n estradiol 7. IgA 0 IgG 500 IgM 400 estradiol. IgA 5 IgG >5000 IgM 400 estradiol 4.0 IgA 5 IgG 000 IgM 50 Antech Diagnostics estradiol: spayed females and neutered males <5-0 pg/ml (in conjunction with Cornell) IgA: 0-50 mg/dl IgG: mg/dl IgM: mg/dl JRT, 7 y/o, F/s PVGB, y/o, F/s Labradormix, 8 y/o, M/n androstene..6/ 6.4 estradiol 45.7/ 46.4 progesterone 0.5/ OH prog. 0.65/.9 androstene..5/0. estradiol 6.5/ 70.7 progesterone 0.8/ OH prog. 0.04/ 0.6 androstene../7.8 estradiol 49./ 44.4 progesterone 0./.57 7-OH prog. 0.47/. Univ. of Tennessee CVM prior to 5/008 Baseline androstenedione ng/ml estradiol pg/ml progesterone pg/ml 7-OH prog pg/ml Post-ACTH androstene ng/ml estradiol pg/ml progesterone pg/ml 7-OH prog pg/ml triamcinolone acetonide.8mg IM dexamethasone sod phos mg IM methylprednisolone mg PO levothyroxine 0.5mg PO BID androstendione.9/7.4 estradiol 44./ 6.4 progesterone 0./.07 7-OH prog 0.09/.6 4

3 8 Eng. Pointer, 8.5 y/o, F/s androstene..8/ 8.5 estradiol.4/ 6. progesterone 0.6/. 7-OH prog. 0.05/.96 Univ. of Tennessee CVM prior to 5/ Cairn Terrier, Chow-mix, Golden Retr-mix, year 6 baseline only androstene..6 estradiol 8. progesterone OH prog. 0.6 androstene..0/ 0.9 estradiol 45.8/ 59.7 progesterone 0.0/ OH prog. 0.07/ 0.9 androstene..4/ 0. estradiol 84.0/ 77.0 progesterone 0.45/ 4 7-OH prog. 0.4/.68 Baseline androstenedione ng/ml estradiol pg/ml progesterone pg/ml 7-OH prog pg/ml Post-ACTH androstene ng/ml estradiol pg/ml progesterone pg/ml 7-OH prog pg/ml Change in reference range Brittany 6 y/o, F/s androstene. 6.9/.0 estradiol 55.6/ 5.9 progesterone 0./.4 7-OH prog. 0./.98 Univ. of Tennessee CVM after 5/008 prednisone.mg PO SID androstene..8/.4 estradiol 49.0/ 5.7 progesterone 0.5/ OH prog 0.06/ 0.57 Shnauzerpoodle mix, androstene. 7.6/ 45. estradiol 9.9/ 84.5 progesterone 0./.65 7-OH prog. 0.9/.5 Baseline androstenedione ng/ml estradiol pg/ml progesterone pg/ml 7-OH prog pg/ml Post-ACTH androstene ng/ml estradiol pg/ml progesterone pg/ml 7-OH prog pg/ml

4 4 GSD, 4.5 total estrogen 5.9 IgA 49 IgG 989 IgM 96 methylprednisolone 4mg PO SID Total estrogen 5. IgA 56 IgG 049 IgM 0 month 5 Boxer, 9 y/o, M/n 4 total estrogen 5.5 no assayed prednisone 5mg PO SID total estrogen 5. no assayed month 6 Labradormix, total estrogen 5. IgA 4 IgG 98 IgM 88 triamcinolone acetonide mg IM methylpredniolone 4mg PO SID total estrogen 5.09 IgA 58 IgG 077 IgM y/o, F/s total estrogen 5.9 IgA 7 IgG 96 IgM 0 triamcinolone acetonide.5mg IM dexamethasone sod phos.4mg IM methylprednisolone 4mg PO SID total estrogen 5.6 IgA 89 IgG 4 IgM Springer y/o, M/n Pomeranian, 7 y/o, M/n y/o, M/n total estrogen 5. IgA 4 IgG 78 IgM 80 total estrogen 5.7 IgA 6 IgG 80 IgM 77 total estrogen 5.40 IgA 4 IgG 87 I gm 84 females pg/ml IgA: mg/dl IgG: mg/dl IgM: mg/dl triamcinolone acetonide 0.mg IM methylprednisolone 4mg PO SID levothyroxine 0.5mg PO BID triamcinolone acetonide 0.5mg IM dexamethasone sod phos. 0.5mg IM methylprednisolone 0.5mg PO SID levothyroxine 0.mg PO BID triamcinolone acetonide.5mg IM methylprednisolone mg PO SID levothyroxine 0.mg PO BID total estrogen 5. IgA 6 IgG 06 IgM 4 total estrogen 5.4 IgA 48 IgG 96 IgM 95 total estrogen 4.88 IgA 78 IgG 5 IgM Australian Cattle Dog, total estrogen 5.7 IgA 5 IgG 46 IgM 5 Cocker 6 y/o, M/n total estrogen 5.08 IgA 57 IgG 989 IgM 00

5 Dachshound 9 total estrogen 5.9 IgA 57 IgG 96 IgM 9 4 Labrador Retriever, total estrogen 5.0 IgA 49 IgG 98 IgM 89 5 GSD-mix,.5 y/o, F/s.5 total estrogen 5. IgA 49 IgG 98 IgM 89 6 Australian Shepherd, 0 y/o, F/s 5 total estrogen 5.0 IgA 5 IgG 947 IgM 96 females pg/ml 7 Pug, 5 total estrogen 5.6 IgA 49 IgG 968 IgM 97 IgA: mg/dl IgG: mg/dl IgM: mg/dl 8 Akita-mix, 7 y/o, M/n total estrogen 5. IgA 47 IgG 6 IgM 74 9 Mini Dachshund, y/o, F/s 6 total estrogen 5.68 IgA 5 IgG 97 IgM 9 0 Lhasa- Apso mix, y/o, F/s total estrogen 5.7 IgA 57 IgG 898 IgM 86 triamcinolone acetonide 0.06mg mg IM dexamethasone sod phos 0.8g mg IM levothyroxine 0.mg PO BID total estrogen 5.09 IgA 88 IgG 6 IgM 95

6 Change in reference range Husky-mix, total estrogen 5.7 IgA 58 IgG 77 IgM 96 prednisone 5 mg PO SID Total estrogen 5. IgA 66 IgG 5 IgM 98 Brittany 9 y/o, M/n years total estrogen 5.5 IgA 5 IgG 97 IgM 9 triamcinolone acetonide 0.mg IM dexamethasone sod phos.6mg IM methylprednisolone mg PO SID levothyroxine 0.mg PO BID total estrogen 5.0 IgA 68 IgG 09 IgM 0 6 Springer y/o, M/n weeks total estrogen 5.04 IgA 6 IgG 05 IgM 99 triamcinolone acetonide 0.5mg IM dexamethasone sod phos.mg IM methylprednisolone mg PO SID levothyroxine 0.5mg PO BID total estrogen 4.89 IgA 74 IgG 05 IgM total estrogen 5.9 IgA 5 IgG 0 IgM 05 triamcinolone acetonide 0.4mg IM dexamethasone sod phos.06mg IM methylprednisolone mg PO SID levothyroxine 0.mg PO BID total estrogen 5.7 IgA 58 IgG 5 IgM 08 month 5 Scottish Terrier, 0 y/o, F/s 8 total estrogen 5.7 IgA 50 IgG 089 IgM 8 females pg/ml triamcinolone acetonide mg IM, weekly for 4 weeks levothyroxine mg PO BID total estrogen 5. IgA 58 IgG 5 IgM 87 month 6 Mini Dachshund, tota l estrogen 5.9 IgA 49 IgG 998 IgM 0 IgA: mg/dl IgG: mg/dl IgM: mg/dl triamcinolone acetonide 0.4mg IM dexamethasone sod phos. 0.5mg IM levothyroxine 0.05mg PO BID tota l estrogen 5. IgA 8 IgG 69 IgM 07 7 Shih-tzu, 8.5 y/o, M/n total estrogen 5.9 IgA 47 IgG 98 IgM 9 triamcinolone acetonide.5mg IM, weekly x wks;.mg IM, weekly x wk; then levothyroxine 0.5mg PO BID total estrogen 5.0 IgA 9 IgG 6 IgM 0 8 Mini Dachshund, 7 y/o, F/s 5.5 total estrogen 5.4 IgA 5 IgG 08 IgM 9 9 GSD, y/o, M/n total estrogen 5.6 IgA 5 IgG 08 IgM 94

7 40 Brittany 4 total estrogen 5.4 IgA 9 IgG 8 IgM 6 4 Pug, 7 y/o, F/s 7 total estrogen 5. IgA 58 IgG 0 IgM Staffordshire Terrier, 4y/o, F/s Sheltland Sheepdog, 8.5 y/o, M/n Chow-mix, 0.5 y/o, M/n Mini- Shnauzer, 9 y/o, M/n 7 weeks total estrogen 5.05 IgA 68 IgG 858 IgM total estrogen 5. IgA 58 IgG 09 IgM 04 total estrogen 5.4 IgA 4 IgG 89 IgM 58 total estrogen 5. IgA 57 IgG 6 IgM 97 females pg/ml IgA: mg/dl IgG: mg/dl IgM: mg/dl

8 Return to original reference range 46 Pug, 6 y/o, F/s total estrogen 5.07 IgA 5 IgG 978 IgM 9 Depo medrol 5mg IM dexamethasone sod phos 0.5mg IM levothyroxine 0.mg PO BID total estrogen 5.04 IgA 65 IgG 08 IgM Miniature Poodle, 0 y/o, F/s total estrogen 5. IgA 57 IgG 6 IgM Mini- Dachshund, 9y/o, F/s 7 total estrogen 5. IgA 5 IgG 080 IgM 94 females pg/ml triamcinolone acetonide 0.08mg IM dexamethasone sod phos 0.7mg IM levothyroxine 0.05mg PO BID total estrogen 5.06 IgA 59 IgG IgM Wheaton Terrier, 9 y/o, M/i 7 total estrogen 5.09 IgA 5 IgG 6 IgM 9 IgA: mg/dl IgG: mg/dl IgM: mg/dl triamcinolone acetonide 0.mg IM dexamethasone sod phos.6mg IM methylprednisolone mg PO SID levothyroxine 0.5mg PO BID total estrogen 5.07 IgA 59 IgG 68 IgM Spaniel-mix, 7 y/o, M/n total estrogen 5.9 IgA 57 IgG 84 IgM 96 triamcinolone acetonide 0.57 mg IM dexamethasone sod phos.57 mg IM methylprednisolone mg PO SID levothyroxine 0.mg PO BID total estrogen 5.06 IgA 66 IgG 05 IgM 0 5 Mini- Dachsund mix 6 y/o, M/n total estrogen 5.09 IgA 57 IgG 99 IgM 98 triamcinolone acetonide 0.05 mg IM dexamethasone sod phos 0.8 mg IM methylprednisolone.5mg PO SID levothyroxine 0.mg PO BID retest pending 5 Australian Shepherdmix y/o, M/n total estrogen 5. IgA 48 IgG 9 IgM 90 Course of antiinflammatory-level prednisone: 0mg PO qod tapered to: prednisone 5g PO SID levothyroxine 0.6mg PO BID total estrogen 5.09 IgA 57 IgG 984 IgM weeks total estrogen 5.9 IgA 5 IgG 9 IgM 9 54 Mini- Dachsund 0 y/o, F/s.5 total estrogen 5.07 IgA 6 IgG 05 IgM 00 triamcinolone acetonide 0.07 mg IM dexamethasone sod phos 0.6 mg IM levothyroxine 0.mg PO BID retest pending

In the past few years, a new disease has been identified called Sudden Acquired Retinal Degeneration Syndrome (SARDS).

SARDS CLINCAL CASE STUDIES In the past few years, a new disease has been identified called Sudden Acquired Retinal Degeneration Syndrome (SARDS). The disease manifests itself as a loss of vision which