Addison's Disease in a Gray Seal (Halichoerus grypus)
IAAAM 2000
Cynthia E. Stringfield1, DVM; Michael Garner2, DVM, DACVP; H.J. Holshuh3, DVM, DACVP
1Los Angeles Zoo, Los Angeles, CA, USA; 2Northwest ZooPath, Snohomish, WA, USA; 3PATHVET Consultation Services, Long Beach, CA, USA

Abstract

Introduction

Hypoadrenocorticism, or Addison's disease, is classified into primary (resulting from atrophy or destruction of the adrenal cortices) or secondary (due to insufficient adrenocorticotropic hormone [ACTH] production from the pituitary gland). Primary hypoadrenocorticism results in inadequate glucocorticoid and mineralocorticoid (aldosterone) secretion. The effect of aldosterone is to increase sodium and water resorption with expansion of the extracellular fluid volume coincident with loss of potassium and hydrogen ion in the urine. Thus, aldosterone deficiency, as in Addison's disease, causes a loss of sodium and water with a reduction in extracellular fluid volume and hyperkalemia. Addison's disease is usually attributed to an immune-mediated process in both dogs and humans.1,4,5 In dogs, it is an uncommon endocrinopathy typically occurring in young to middle-aged females.5 Infectious, iatrogenic, vascular, infiltrative and congenital causes are also recognized in people.1

Definitive diagnosis of hypoadrenocorticism requires demonstration of inadequate adrenal reserve characterized by a low resting serum cortisol concentration coupled with a subnormal or negligible response to exogenous ACTH administration.1,5 In dogs, electrolyte abnormalities (hyperkalemia and hyponatremia) coupled with a subnormal cortisol response to ACTH indicate primary adrenocorticism. A plasma ACTH level is used to differentiate primary from secondary adrenal insufficiency in dogs with normal electrolyte levels.5 Treatment requires provision of appropriate mineralocorticoid and/or glucocorticoid replacement.1,5

This report is the first of primary Addison's disease in a gray seal.

Case Report

A 16-mo-old male gray seal presented severely obtunded, twitching and shuddering, with myotic pupils, very rapid and shallow (almost imperceptible) respirations, bradycardia (42 BPM), hypothermia (93°F), poor mm color and good body condition (64 kg). Electrolytes were run STAT and showed a sodium of 110 mEq/L and a potassium of 4.2 mEq/L. Emergency treatment consisted of 100 mg dexamethasone SP i.v., i.v. 5% dextrose/lactated ringers solution, switching to 0.9% NaCl when blood results were evaluated. Diazepam (15 mg i.v.) temporarily ceased the shuddering. Then violent thrashing commenced and ceased with 150 mg meperidine i.m. The seal's breathing became smooth, deep and regular, mucous membranes were pink, but he remained non-responsive.

This animal had a 3-mo history of abnormal behavior during feeding consisting of: crossing the hind flippers, paddling backwards with the pectoral flippers and holding the mouth slightly open in a "grimace," cessation of eating, floating and paddling abnormally, then reverting to normal behavior. This occurred sporadically along with normal behavior and appetite. The day before presentation, he became weak and lethargic approximately 3 hr after a normal noontime feeding. He appeared to be trying to beach unsuccessfully, sunk to the bottom of the pool twice, and then experienced a violent thrashing episode and period of lordosis. He was treated with 300 mg thiamin and left in shallow water for the night where he continued to twitch, roll, and shudder, eventually developing shallow respirations and fixed pupils.

The animal was born at the zoo from a mother who had been treated with medroxyprogesterone acetate as a contraception attempt. The animal was housed in fresh water with a group of sea lions and received oral multivitamin (Seatab) and salt (2 mg/kg fish) supplements daily.

Initial rule-outs for the severe hyponatremia included: GI disease or obstruction, metabolic disease, lack of supplementation, and primary neurologic disease (viral, bacterial, congenital, toxic).

The work-up proceeded with plain GI films, abdominal ultrasound, GI endoscopy, and a barium series, all of which were normal. Prior to endoscopy, his abdomen appeared painful; he would frequently arch his back and pass gas and feces. He was treated with saline i.v., p.o. and s.c., and tubed 25 g salt tabs and 2 g sucralfate. He was given 80 mg dexamethasone SP s.c. in the afternoon, and started on antibiotics and cimetidine. Major concerns at the end of the day were permanent neurologic damage from hyponatremia, and myopathy. The next day the animal was lifting his head up, had good vital signs, and fought the stomach tube, but was still very depressed with miotic pupils. Flunixin and vitamins E and B complex, were added to the treatment regime. In the afternoon his sodium was 130 mEq/L. On day 3 he was more responsive and eating fish when hand-fed. He continued to improve and on day 4 his sodium was 138 mEq/L. On day 5 his i.v. was removed and he was moved to an empty shallow pool, his sodium was 139 mEq/L. Physical therapy commenced on day 7; he was still blind, and had trouble staying upright.

During the course of physical therapy, use of his mouth came back first, then his front flippers, then the rear. The seal dramatically improved over the next 3 wk and resumed swimming and eating relatively normally. His eyesight never returned. He was supplemented with increasing amounts of salt, up to 100 g/day, prednisone 0.2-0.4 mg/kg p.o. per day and fludrocortisone acetate 0.3-1.0 mg p.o. b.i.d. over the next 1.5 yr, and his electrolytes were monitored. His sodium eventually reached a high of 156 mEq/L. Unfortunately, he continued to have worsening clinical signs of the "seizures" described at presentation and finally developed a non-responsive fungal dermatitis and severe unilateral uveitis and was euthanatized.

On gross necropsy examination, his thyroid and pituitary glands were normal. Both adrenal glands were grossly small, flat and flabby (the right weighed 1 g and the left 2 g). There was little discernible white cortex, mainly all brown medulla. On histopathology there was bilaterally severe atrophy of the zona fasciculata and zona reticularis, with mild atrophy occasionally detected in the zona glomerulosa. The brain was grossly very irregular with distorted cerebral gyri and marked widening of the sulci. Histopathology showed laminar necrosis (polioencephalomalacia) in the cerebrum.

Discussion

This animal showed clinicopathologic signs of hypoadrenocorticism similar to those of people and dogs: weakness, waxing and waning course, collapse, bradycardia, painful abdomen, and hyponatremia.1,5 What was surprising is that he showed no hyperkalemia, the hallmark of Addison's disease which occurs in 95% of canine cases.1, 5 The strange seizure-type behavior seemed induced by the stress of eating. Aldosterone and cortisol levels were run and were very low compared to normal data for grey seals and dogs.3,5,6 The cause of the adrenal atrophy remains unknown, but congenital or iatrogenic (raised in fresh water) origins remain suspect. Likely causes for the polioencephalomalacia, assumed to be the cause of blindness in this animal, include anoxia from the first night of seizures, and chronic metabolic imbalances.

Acute adrenocortical insufficiency (Addisonian crisis) is a life-threatening emergency and requires immediate intervention. Of primary importance is the rapid administration of large volumes of intravenous fluids, preferably 0.9% NaCl and a rapidly acting glucocorticoid.1,5 Treatment of dogs and humans in hypoadrenal crisis must be directed at restoring perfusion and cardiovascular stability, however experience with humans suggests that clinicians should monitor serum sodium concentration and limit the increase of sodium concentration to less than 25 mEq/L in the first 48 hr of treatment or risk neurologic sequelae from myelinolisis.2 Histologic changes in the brain were more consistent with chronic pre-existing polioencephalomalacia than the generalized demyelination and loss of glial cells seen in animals with sodium hyperperfusion.

ACTH stimulation and ACTH levels would have been helpful diagnostics in this case but were not run in this animal due to anesthetic time and special laboratory/sample handling required.

Conclusions

Addison's disease, or hypoadrenocorticism, can occur in a gray seal, and may present as a profound hyponatremia with a normokalemia. More investigation into these deep diving marine mammal's normal electrolyte balance mechanisms and the effect of aldosterone may explain this clinical phenomenon.

Acknowledgments

The staffs and volunteers of the Animal Care and Animal Health departments put an incredible effort into this very challenging case. Thanks also to Dr. Marilyn Koski and Dr. Brent Whittaker for their consultations on this case.

References

1.  Andreoli TE, JC Bennett, CC J. Carpenter, F Plum. 1997. Adrenal Gland. Cecils Essentials of Medicine, 4th Ed., Pp. 497-450.

2.  Brady CA, CH Vite, KJ Drobatz. 1999. Severe neurologic sequelae in a dog after treatment of hypoadrenal crisis. J. Am. Vet. Med. Assoc. 215(2):222-225.

3.  Engelhardt FR, JM Ferguson. 1980. Adaptive hormone changes in harp seals, Phoca groenlandica, and gray seals, Halichoerus grypus, during the postnatal period. Gen. Comp. Endocrinol. 40:434-445.

4.  Kemppainen RJ, E Behrend. 1997. Adrenal physiology. Vet. Clin. N.A. Sm. Anim.. Pract. 27(2):173-186.

5.  Kintzer PP, ME Peterson. 1997. Primary and secondary canine hypoadrenocorticism. Vet. Clin. N.A. Sm. Anim. Pract. 27(2).

6.  Kirby VL. 1990. Endocrinology of marine mammals. In: Handbook of Marine Mammal Medicine, 1st Ed. Dieraf, L. A. (Ed.), CRC Press, Boca Raton, Florida, Pp. 316-321.

7.  Sangalang GB, HC Freeman. 1976. Steroids in the plasma of the gray seal, Halichoerus grypus. Gen. Comp. Endocrinol. 29:419-422.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Cynthia E. Stringfield, DVM


MAIN : All : Addison's Disease
Powered By VIN

Friendly Reminder to Our Colleagues: Use of VIN content is limited to personal reference by VIN members. No portion of any VIN content may be copied or distributed without the expressed written permission of VIN.

Clinicians are reminded that you are ultimately responsible for the care of your patients. Any content that concerns treatment of your cases should be deemed recommendations by colleagues for you to consider in your case management decisions. Dosages should be confirmed prior to dispensing medications unfamiliar to you. To better understand the origins and logic behind these policies, and to discuss them with your colleagues, click here.

Images posted by VIN community members and displayed via VIN should not be considered of diagnostic quality and the ultimate interpretation of the images lies with the attending clinician. Suggestions, discussions and interpretation related to posted images are only that -- suggestions and recommendations which may be based upon less than diagnostic quality information.

CONTACT US

777 W. Covell Blvd., Davis, CA 95616

vingram@vin.com

PHONE

  • Toll Free: 800-700-4636
  • From UK: 01-45-222-6154
  • From anywhere: (1)-530-756-4881
  • From Australia: 02-6145-2357
SAID=27