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Adult-Onset Hypothyroidism in a Lynx (Lynx canadensis)Author(s): Leah L. Greer, Mitchell Troutman, Malcolm D. McCracken, Edward C. RamsaySource: Journal of Zoo and Wildlife Medicine, Vol. 34, No. 3 (Sep., 2003), pp. 287-291Published by: American Association of Zoo VeterinariansStable URL: http://www.jstor.org/stable/20460334 .Accessed: 14/04/2011 09:34
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Journal of Zoo and Wildlife Medicine 34(3): 287-291, 2003
Copyright 2003 by American Association of Zoo Veterinarians
ADULT-ONSET HYPOTHYROIDISM IN A LYNX (LYNX CANADENSIS)
Leah L. Greer, D.V.M., Mitchell Troutman, D.V.M., Malcolm D. McCracken, D.V.M., Dipl. A.C.V.P., and Edward C. Ramsay, D.V.M., Dipl. A.C.Z.M.
Abstract: A 19-yr-old female lynx (Lynx canadensis) presented for an acute onset of anorexia and reluctance to
move. Physical examination, radiography, hematology, and serum biochemistry revealed evidence of renal failure,
presumptive uremic gastritis, chronic intervertebral disk disease at T13-LI, and markedly low serum levels of total
thyroxine (1.54 nmolVL) and total triiodothyronine (0.55 nmol/L). Twenty-five hours after its original presentation, the
lynx exhibited horizontal nystagmus, which has been suggested as a clinical sign associated with hypothyroidism in
domestic dogs. The lynx was euthanatized because of poor prognosis, and medical management concerns related to its
chronic renal failure. Necropsy examination substantiated that the lynx had true hypothyroidism with 60-90% of the
thyroid gland replaced with adipose tissue. Although feline adult-onset hypothyroidism may have low incidence, it should still be considered as a cause of nonspecific signs of disease in cats, as well as signs suggestive of hypothy
roidism. Routine monitoring of baseline exotic felid thyroid levels throughout life would help to identify normal values
and diagnose a potential disease that has obscure clinical signs.
Key words: Lynx, Lynx canadensis, hypothyroidism, nystagmus, feline, endocrine.
INTRODUCTION
Hypothyroidism is a complex disease, and clin ical signs are frequently nonspecific because of thy roid hormone's effects on multiple body systems.16 Feline hypothyroidism is typically congenital or iat rogenic but may rarely be of adult onset.20 Low feline serum total thyroxine (TT4) concentrations are frequently attributed to the suppressive effects of nonthyroidal illness, termed euthyroid sick syn drome, and not to true hypothyroidism.4 Clinical signs of feline congenital and iatrogenic hypothy roidism are disproportionate dwarfism and gradu ally decreasing activity accompanied by weight gain, respectively.4 There is little clinical or path ologic information available regarding adult-onset hypothyroidism in cats.
CASE REPORT
A 19-yr-old reproductively intact female lynx (Lynx canadensis) housed at the Knoxville Zoolog ical Gardens since she was 5 mo old was examined after acute onset of anorexia and reluctance to
move. The lynx had been housed alone for the last 6 yr and had a previously unremarkable clinical his tory.
The lynx was immobilized with ketamine (Ke taflog, Abbott Laboratories, North Chicago, Illinois 60064, USA; 6.8 mg/kg, i.m.) and xylazine (Phoe nix Pharmaceutical, Inc., St. Joseph, Missouri 64506-0457, USA; 0.4 mg/kg, i.m.) administered by remote injection (Telinject? USA, Inc., Saugus, California 91350, USA). Eleven minutes after dart ing, the lynx vomited a moderate amount of fresh blood in foamy material. Kidneys were palpably small, and hind limb musculature was moderately atrophied. Ocular examination was normal. Radio graphs of the thorax revealed normal, older felid focal pneumonic infiltrates and chronic interverte bral disk herniation between the 13th thoracic and first lumbar vertebrae, with end plate erosions. Ab dominal radiographs showed small kidneys with normal shape and contour. The lynx was treated with Normasol-R (Abbott Laboratories; 300 ml, i.v. and 300 ml, s.c.) and ampicillin (Polyflex?, Fort
Dodge, Iowa 50501, USA; 21 mg/kg, i.m.). Blood and urine samples were collected and submitted to the laboratory for analysis. After the administration of yohimbine (Antagonil?, Wildlife Pharmaceuti cals, Fort Collins, Colorado 80522-2120, USA; 0.1
mg/kg, s.c.), recovery from anesthesia was un
eventful. Abnormal laboratory findings were a degenera
tive left shift (white blood corpuscles = 8.90 X 109/ L, neutrophils = 3.74 X 109/L, and bands = 4.00 X 109/L) and evidence of renal failure with blood urea nitrogen of 23.21 mmol/L (x = 10.71 + 3.57
mmol/L), creatinine of 360 Fmol/L (x = 185.60 + 53.04 pmol/L), and a urine specific gravity of 1.025.8 Urine culture was not performed because urine sediment was unremarkable. Amylase, lipase,
From the Departments of Comparative Medicine (Greer,
Ramsay) and Pathology (Troutman, McCracken), School
of Veterinary Medicine, University of Tennessee, Knox
ville, Tennessee 37901-1071, USA. Present addresses
(Greer): The Los Angeles Zoo, Health Center, 5333 Zoo
Drive, Los Angeles, California 90027, USA; (Troutman):
Department of Pathobiology, College of Veterinary Med
icine, University of Florida, Gainesville, Florida 32610,
USA. Correspondence should be directed to Dr. Greer.
287
288 JOURNAL OF ZOO AND WILDLIFE MEDICINE
and bile acid levels were unremarkable.8 Serologic tests for antibodies to feline infectious peritonitis, feline immunodeficiency viruses, Histoplasma cap sulatum and Blastomyces dermatitidis, and for an
tigen to feline leukemia virus were negative. Serum TT4 and total triiodothyronine (TT3) were low at 1.54 nmol/L and 0.55 nmol/L, respectively (do
mestic feline normal values TT4 = 12.87-51.48 nmol/L, TT3 = 0.77-2.30 nmol/L; Endocrinology Laboratory, School of Veterinary Medicine, Uni
versity of Tennessee, Knoxville, Tennessee 37901, USA). Serum TT4 reference range = 16.73 ? 5.15 nmol/L in four adult Lynx candensis.8 Free thyrox ine (T4) level by equilibrium dialysis in this lynx
was 13 pmol/L (reference interval for domestic fe
line 10-50 pmol/L; Animal Health Diagnostic Lab oratory, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48909, USA). This lynx had multiple problems, and it was tentatively diagnosed with chronic renal failure, uremic gastritis, chronic intervertebral disk disease at T13-LI, and euthyroid sick syndrome.
Twenty-five hours after the initial presentation, the lynx showed reluctance to move, anorexia, and
had pronounced horizontal nystagmus with the fast
phase directed toward the right. The lynx was re immobilized for further diagnostic tests; however, euthanasia was elected due to medical management concerns. Cerebral spinal fluid collected immedi ately antemortem was within normal limits.
Gross necropsy and histopathology found marked glomerulonephritis, moderate erosive gas tritis, and marked parathyroid chief cell hyperplasia consistent with chronic renal failure and secondary renal hyperparathyroidism. Lung cultures grew >100 colonies of Escherichia coli and >500 col onies of Streptococcus zooepidemicus, which were considered to be postmortem contaminants. There were incidental findings of a left, parathyroid chief cell adenoma and multifocal cortical hyperplasia of the adrenal glands. There were no gross or histo logic lesions in the cerebral cortices, eyes, or au
ditory bullae. There were no gross lesions of the spinal cord, and it was not examined histopatholog ically.
The thyroid gland was moderately to markedly,
chronically, and diffusely atrophied. Eighty to 90% of the left gland and 60-70% of the right thyroid gland consisted of very small follicles containing little to no colloid and lined by cuboidal epithelium
with vacuolated cytoplasm containing brown pig ment (lipofuscin). The gland margins were infil trated by adipose tissue (Fig. la, b). Neither extra thyroidal tissue nor a thyroid microadenoma was found.
Stored serum samples in the past 3 yr showed serum TT4, TT3, and free T4 levels of 8.49 nmol/ L, 0.71 nmol/L, and 17 pmol/L, respectively. The only clinical signs reported at the date when those samples were drawn were lethargy and inappetence for 7 days, and no abnormalities were found on physical examination, complete blood count, serum biochemistries, or radiographs of chest and abdo men.
DISCUSSION
Primary adult-onset hypothyroidism has been well documented in domestic dogs but not in do mestic cats. In the dog, the most common type of hypothyroidism (>95%) is a progressive loss of functional thyroid tissue due to primary dysfunc tion of the gland itself.21 This loss of functional thyroid tissue is caused by either lymphocytic thy roiditis, which is thought to be immune-mediated, or by idiopathic atrophy of the gland, where the gland is replaced by adipose tissue.4 Less than 5% of canine hypothyroidism is due to nonfunctional thyroid tumors or is secondary to pituitary tumors.'2
There have been no reports of tertiary hypothyroid ism due to deficient thyrotropin-releasing hormone (TRH) in dogs or cats.
Clinical adult-onset hypothyroidism is not well recognized in cats. One cat with adult-onset hypo thyroidism confirmed with a thyroid-stimulating hormone test had clinical signs similar to those of dogs with hypothyroidism, including lethargy, obe sity, cold intolerance, and dermatologic abnormal ities.20 A thyroid biopsy identified lymphocytic thy roiditis, with lesions similar to those found in dogs
with the same condition. Adult-onset feline hypothyroidism has been ex
perimentally studied in two adult cats using thyroid ablation radiation to create thyroid atrophy.23 Hy pothyroidism was confirmed by measuring sera TT3 and TT4 before and after a TSH-stimulation test. These cats were followed for 163 wk and were found to have minimal clinical abnormalities. The only abnormality the cats developed was marked lethargy by week-17 postthyroid ablation, but they adapted and seemed to return to normal activity by
week 40. No changes in body weight or cholesterol were noted, and the only change in hair coat was decreased grooming that resulted in hair mats and seborrhea.
The lynx studied in the present article had thy roid atrophy and replacement of the thyroid gland
with adipose tissue. This lynx had clinical signs that most closely resembled the signs observed in the feline thyroid ablation study (decreased activity).23
Clinical manifestations of canine hypothyroidism
GREER ET AL.-HYPOTHYROIDISM IN A LYNX 289
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290 JOURNAL OF ZOO AND WILDLIFE MEDICINE
have been well documented. The most common clinical findings are lethargy, weight gain, and der
matologic conditions such as alopecia, pyoderma, and seborrhea.'6 Neuromuscular abnormalities, fe
male infertility, myxedema, ocular disorders, and cretinism are less common but well documented.'6 Vestibular disease and lower motor neuron deficits are uncommon neurologic manifestations of pri
mary hypothyroidism.4"10"16 The lynx had acute ves tibular disease and evidence of hind limb atrophy, signs that occur in hypothyroid dogs.4"0"6 There
was no pathologic evidence of disease other than hypothyroidism to explain the lynx's vestibular dis ease. Neurologic deficits may be the only clinical signs in some hypothyroid dogs.'0""'6 The lynx's decreased activity could also have been due to the hind limb atrophy, renal failure, and chronic inter vertebral disk disease.
There are only a few reports on the prevalence of histologic disease of feline thyroid glands. One study evaluated 75 consecutive cat necropsies.'3 Al though none of the cats were suspected to have had thyroid disease, 95% of them had thyroid gland ab normalities, including cystic follicles or adenomas. Lymphocytic thyroiditis and idiopathic thyroid gland atrophy were not identified. Two male cats had thyroid gland amyloidosis with only a few fol licles retaining colloid material. This suggests that both had significant loss of functional thyroid gland. Neither cat had amyloid elsewhere in the body, and they showed no clinical signs of hypo thyroidism. Both had been euthanized for a facial sinus infection and nephritis. Serum thyroid hor
mone levels had not been reported in either cat. The first part of a two-part clinicopathologic
study found that 65% of 54 retrospective feline cas es and 49% of 86 prospective feline cases had his tologic thyroid abnormalities.' The second part of the same study confirmed that only 16% of the 77 cats with any histologic thyroid lesions had clinical signs relating to thyroid disease.'4 Histologic evi dence of feline hypothyroidism was found in five of the 140 cases examined (0.03%), and none of these cats had shown signs of hypothyroidism. Thy roid disease is often unrecognized, apparently. The type of hypothyroid changes in two of these five cats may have been due to carcinomatous effects. In three of the cats, amyloidosis caused thickening of the interstitium and severe amyloid formation that almost obliterated the acini.
Deficient circulating thyroid hormone level af fects almost the entire metabolic function;4 hence, clinical signs can be variable and their onset subtle, gradual, and mistaken for signs of old age. Many people with adult-onset hypothyroidism also have
nonspecific clinical signs that may be attributed to aging and remain undiagnosed for years. Although indices for scoring clinical symptoms were devel oped in the 1960s, clinical symptoms are being used less as criteria for treatment because of con cern about the effects of untreated subclinical hy
pothyroidism.3,15
Diagnostic tests for hypothyroidism can yield confusing results. Numerous factors, such as con current illness, drugs, and random fluctuations of hormone concentration, can falsely lower baseline thyroid hormone concentrations. 15"17 Breed, species, and age can introduce variability as well.9 Hypo thyroidism can only be diagnosed definitively by histologic examination of the thyroid gland, and this complex and invasive procedure is rarely per formed antemortem.4'5
Hypothyroidism in cats was historically diag nosed using history, clinical signs, and blood tests. Nonregenerative anemia (in cats with iatrogenic and congenital hypothyroidism), hypercholesterol emia, low baseline serum TT4 concentration, and a lack of response to TSH stimulation or TRH stim ulation testing were suggestive.4 However, bovine TSH (b-TSH) is not currently available to perform function testing.22 Intravenous use of TRH, a hy pothalamic peptide that stimulates pituitary TSH release for diagnosing feline hypothyroidism, is of questionable value because the test has only been evaluated for diagnosing feline hyperthyroidism and salivation, vomiting, tachypnea, and uncon trolled defecation can follow such administra tion.7'24
A combination of serologic tests is used to di agnose human and canine hypothyroidism. High TSH, low TT4, and low free T4 (by dialysis) levels suggest hypothyroidism in dogs, particularly in the cases of suspected nonthyroidal illness.2"8 Assays for TSH are species specific, and there are no TSH assays developed from materials of feline origin.6
No assays have been validated for cats or exotic species. The commercially available immunoradi ometric assay for canine TSH may, however, detect feline TSH.6 Although it appears to distinguish nor
mal from elevated TSH concentrations in feline sera, it is not able to differentiate normal from path ologically suppressed values and is therefore an un reliable indicator of hyperthyroidism in cats.
There was not enough banked serum to measure our lynx's TSH levels. Although direct equilibrium dialysis measurement of free T4 has been validated in cats, 17.2% of cats with nonthyroidal illness have false low levels and 6.3% have false eleva tions.19 And although the lynx's free T4 concentra tions were within the domestic feline reference in
GREER ET AL.-HYPOTHYROIDISM IN A LYNX 291
terval, the previous free T4 value of 17 pmol/L in
this lynx decreased during 3 yr to 13 pmol/L at the
time of its clinical presentation. These free T4 val ues cannot be fully interpreted until lynx reference intervals are established.
CONCLUSIONS
Although clinical descriptions of adult-onset hy pothyroidism in domestic cats are scarce, histopa
thology studies support its occurrence. Although not prevalent, it should be considered as a possible
diagnosis in older cats with nonspecific signs of
disease. Serum TT4 and free T4 levels should be measured and thyroid biopsy considered in sus
pected cases. Serologic TSH testing in felids may
become more valuable as more data are acquired. Once nonthyroid illness has been ruled out, thera peutic trials can be performed. Routine life-long monitoring of TT4, free T4, and (potentially) TSH concentrations in exotic cat species would help to better establish normal value ranges and to diag
nose hypothyroidism.
Acknowledgments: We thank Dr. Jack Oliver and the staff at The University of Tennessee, College of Veterinary Medicine, Endocrinology Laboratory,
and the West Mammal Keepers at The Knoxville Zoo.
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Received for publication 22 August 2001