Die canine Hypothyreose – eine diagnostische Herausforderung?

Zusammenfassung

Die Hypothyreose ist eine der am häufigsten diagnostizierten Endokrinopathien beim Hund. Das klinische Erscheinungsbild, sowie einige hämatologische und blutchemische Veränderungen führen zu einer ersten Verdachtsdiagnose. Diese durch spezifische Hormontests zu bestätigen, kann im Einzelfall zu einer diagnostischen Herausforderung werden. Die Bestimmung des Gesamt-T4-Spiegels hat zwar eine sehr gute Sensitivität, da der Parameter von zahlreichen Faktoren beeinflusst ist, kann eine tiefe T4-Konzentration jedoch nicht zur Diagnosesicherung herangezogen werden. Im Gegensatz zum Menschen ist das endogene TSH (canine TSH) bei bis zu 40% der hypothyreoten Hunde normal, was zu einer extrem schlechten Sensitivität führt. Als Goldstandard hat sich seit Jahren der TSH-Stimulationstest behauptet, der mittlerweile mit rekombinantem humanem TSH (rhTSH, Thyrogen^®) durchgeführt wird. Dabei wird die Substanz bevorzugt intravenös appliziert und vor sowie 6 h nach der Verabreichung das T4 bestimmt. Durch das Ausmaß des T4-Anstiegs kann die Reservekapazität der Schilddrüse abgeschätzt und so eine Aussage über die hormonelle Aktivität gemacht werden. Auch dieser Test kann grundsätzlich durch Medikamente, vor allem Glukokortikoide, oder andere Erkrankungen beeinflusst werden; durch die Verwendung einer deutlich höheren Dosis an rhTSH kann der supprimierende Effekt zwar minimalisiert, jedoch nicht komplett ausgeschaltet werden. In den letzten Jahren haben bildgebende Verfahren wie die Ultraschalluntersuchung und Szintigrafie vermehrt an Bedeutung gewonnen. Werden bei der Sonografie Größe und Echogenität der Schilddrüse kombiniert beurteilt, kann eine Sensitivität von 98% erreicht werden, allerdings mit einer gleichzeitigen Spezifität von nur 77%. Die Resultate der bisher einzig publizierten größeren szintigrafischen Untersuchung zur Unterscheidung zwischen hypothyreoten von euthyreot-kranken Hunden sind viel versprechend. Aufgrund der beschränkten Verfügbarkeit und des großen Aufwands (Narkose, Kosten), wird diese Technik vorerst keinen breiten Einsatz finden. In Fällen, bei denen keine sichere Diagnose gestellt werden kann, sollte der weitere Verlauf abgewartet und die Tests nach einer gewissen Zeit wiederholt werden.

Abstract

Hypothyroidism is one of the most common endocrinopathies in dogs. Clinical symptoms and hematological and biochemical parameters lead to a first suspicion. To confirm diagnosis can be challenging, however. Determination of total serum T4 concentration is accepted as the primary screening test for the disease, and low serum T4 concentrations are intuitively suggestive of hypothyroidism. However it is well known that low T4 concentrations are frequently encountered in euthyroid dogs with various nonthyroidal diseases and in dogs receiving certain pharmacologic agents. Since assessment of endogenous TSH (canine TSH) using current canine TSH assays shows normal values in a high percentage of hypothyroid dogs (up to 40%), its diagnostic value is only limited. The TSH-stimulation test can still be recognized as the gold standard for the diagnosis of hypothyroidism in dogs. Determination of circulating T4 concentration before and 6 hours after the administration of exogenous TSH (recombinant human TSH, Thyrogen^®) provides an assessment of the functional reserve capacity of the thyroid gland with minimal change in post-TSH T4 concentration, compared with the basal concentration, expected in dogs with hypothyroidism. Also this test can be influenced by nonthyroidal illness and by medications known to affect thyroid function. This suppressing influence seems to be less pronounced using a higher dose of TSH. Therefore, to improve the discriminatory power of the TSH stimulation test to differentiate between euthyroid-sick and primary hypothyroidism, the higher dose should be used in cases in which testing cannot be delayed. More recently, ultrasonography and scintigraphy have been used for the diagnosis of primary hypothyroidism. Using ultrasonography, a sensitivity of 98% was reported if size and echogenicity of the gland were combined. However, specificity was as low as 77% and care must be taken when measuring the gland because of a relatively high interobserver variability. Preliminary results using scintigraphy to discriminate between hypothyroid and non-thyroidal illness seem promising. However, due to its limited availability and the high expenditure, to date it cannot be used in clinical practice. Therefore, at present, if test results are obscure and a final diagnosis cannot be made, it is recommended to repeat the tests at a later time point.

Schlüsselwörter

canine Hypothyreose - cTSH - rhTSH - TSH-Stimulationstest - Spezifität - Sensitivität

Key words

canine hypothyroidism - cTSH - rhTSH - TSH-stimulationtest - specificity - sensitivity

Literatur

• 1 Boretti FS, Breyer-Haube I, Kaspers B. et al . Clinical, hematological, biochemical and endocrinological aspects of 32 dogs with hypothyroidism.  Schweiz Arch Tierheilkd. 2003;  145 149-156 158-159
• 2 Boretti FS, Reusch CE. Endogenous TSH in the diagnosis of hypothyroidism in dogs.  Schweiz Arch Tierheilkd. 2004;  146 183-188
• 3 Boretti FS, Sieber-Ruckstuhl NS, Favrot C. et al . Evaluation of recombinant human thyroid-stimulating hormone to test thyroid function in dogs suspected of having hypothyroidism.  Am J Vet Res. 2006;  67 2012-2016
• 4 Boretti FS, Sieber-Ruckstuhl NS, Wenger-Riggenbach B. et al . Comparison of 2 doses of recombinant human thyrotropin for thyroid function testing in healthy and suspected hypothyroid dogs.  J Vet Intern Med. 2009;  23 856-861
• 5 Boretti FS, Sieber-Ruckstuhl NS, Willi B. et al . Comparison of the biological activity of recombinant human thyroid-stimulating hormone with bovine thyroid-stimulating hormone and evaluation of recombinant human thyroid-stimulating hormone in healthy dogs of different breeds.  Am J Vet Res. 2006;  67 1169-1172
• 6 Bromel C, Pollard RE, Kass H. et al . Ultrasonographic evaluation of the thyroid gland in healthy, hypothyroid, and euthyroid Golden Retrievers with nonthyroidal illness.  J Vet Intern Med. 2005;  19 499-506
• 7 Daminet S, Ferguson DC. Influence of drugs on thyroid function in dogs.  J Vet Intern Med. 2003;  17 463-472
• 8 De Roover KL, Duchateau N, Carmichael C. et al . Effect of storage of reconstituted recombinant human thyroid-stimulating hormone (rhTSH) on thyroid-stimulating hormone (TSH) response testing in euthyroid dogs.  J Vet Intern Med. 2006;  20 812-817
• 9 Diaz Espineira MM, Mol JA, van den Ingh TS. et al . Functional and morphological changes in the adenohypophysis of dogs with induced primary hypothyroidism: loss of TSH hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with transdifferentiation.  Domest Anim Endocrinol. 2008;  35 98-111
• 10 DiazEspineira MM, JA Mol, ME Peeters. et al . Assessment of thyroid function in dogs with low plasma thyroxine concentration.  J Vet Intern Med. 2007;  21 25-32
• 11 Dixon RM, Mooney CT. Evaluation of serum free thyroxine and thyrotropin concentrations in the diagnosis of canine hypothyroidism.  J Small Anim Pract. 1999;  40 72-78
• 12 Dixon RM, Reid SW, Mooney CT. Epidemiological, clinical, haematological and biochemical characteristics of canine hypothyroidism.  Vet Rec. 1999;  145 481-487
• 13 Donadio S, Morelle W, Pascual A. et al . Both core and terminal glycosylation alter epitope expression in thyrotropin and introduce discordances in hormone measurements.  Clin Chem Lab Med. 2005;  43 519-530
• 14 Feldman EC, Nelson RW. Hypothyroidism, p. 68–117.. In: Feldman EC, and, Nelson RW, (ed.) Canine and feline endocrinology and reproduction. W.B. Saunders Company; 1996
• 15 Ferguson DC. Testing for hypothyroidism in dogs.  Vet Clin North Am Small Anim Pract. 2007;  37 647-669 , v
• 16 Frank LA. Comparison of thyrotropin-releasing hormone (TRH) to thyrotropin (TSH) stimulation for evaluating thyroid function in dogs.  J Am Anim Hosp Assoc. 1996;  32 481-487
• 17 Gaskill CL, Burton SA, Gelens HC. et al . Changes in serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs receiving phenobarbital for one year.  J Vet Pharmacol Ther. 2000;  23 243-249
• 18 Gaughan KR, Bruyette DS. Thyroid function testing in Greyhounds.  Am J Vet Res. 2001;  62 1130-1133
• 19 Graham PA, Nachreiner RF, Refsal KR. et al . Lymphocytic thyroiditis.  Vet Clin North Am Small Anim Pract. 2001;  31 915-933 , vi–vii
• 20 Graham PA, Refsal KR, Nachreiner RF. Etiopathologic findings of canine hypothyroidism.  Vet Clin North Am Small Anim Pract. 2007;  37 617-631 , v
• 21 Li WI, Chen CL, Tiller AA. et al . Effects of thyrotropin-releasing hormone on serum concentrations of thyroxine and triiodothyronine in healthy, thyroidectomized, thyroxine-treated, and propylthiouracil-treated dogs.  Am J Vet Res. 1986;  47 163-169
• 22 Lothrop Jr CD, Tamas PM, Fadok VA. et al . Canine and feline thyroid function assessment with the thyrotropin-releasing hormone response test.  Am J Vet Res. 1984;  45 2310-2313
• 23 Nachreiner RF, Refsal KR, Graham PA. et al . Prevalence of serum thyroid hormone autoantibodies in dogs with clinical signs of hypothyroidism.  J Am Vet Med Assoc. 2002;  220 466-471
• 24 Panakova L, Koch H, Kolb S. et al . Thyroid testing in Sloughis.  J Vet Intern Med. 2008;  22 1144-1148
• 25 Panciera DL. Hypothyroidism in dogs: 66 cases (1987–1992).  J Am Vet Med Assoc. 1994;  204 761-767
• 26 Reese S, Breyer U, Deeg C. et al . Thyroid sonography as an effective tool to discriminate between euthyroid sick and hypothyroid dogs.  J Vet Intern Med. 2005;  19 491-498
• 27 Reusch CE, Gerber B, Boretti FS. Serum fructosamine concentrations in dogs with hypothyroidism.  Vet Res Commun. 2002;  26 531-536
• 28 Sauve F, Paradis M. Use of recombinant human thyroid-stimulating hormone for thyrotropin stimulation test in euthyroid dogs.  Can Vet J. 2000;  41 215-219
• 29 Schaaf L, Trojan J, Helton TE. et al . Serum thyrotropin (TSH) heterogeneity in euthyroid subjects and patients with subclinical hypothyroidism: the core fucose content of TSH-releasing hormone-released TSH is altered, but not the net charge of TSH.  J Endocrinol. 1995;  144 561-571
• 30 Scott-Moncrieff JC. Clinical signs and concurrent diseases of hypothyroidism in dogs and cats.  Vet Clin North Am Small Anim Pract. 2007;  37 709-722 , vi
• 31 Scott-Moncrieff JC, Nelson RW, Bruner JM. et al . Comparison of serum concentrations of thyroid-stimulating hormone in healthy dogs, hypothyroid dogs, and euthyroid dogs with concurrent disease.  J Am Vet Med Assoc. 1998;  212 387-391
• 32 Skopek E, Patzl M, Nachreiner RF. Detection of autoantibodies against thyroid peroxidase in serum samples of hypothyroid dogs.  Am J Vet Res. 2006;  67 809-814
• 33 Taeymans O, Duchateau L, Schreurs E. et al . Intra- and interobserver variability of ultrasonographic measurements of the thyroid gland in healthy Beagles.  Vet Radiol Ultrasound. 2005;  46 139-142
• 34 Tani H, Nabetani T, Sasai K. et al . Proliferative responses to canine thyroglobulin of peripheral blood mononuclear cells from hypothyroid dogs.  J Vet Med Sci. 2005;  67 363-368
• 35 Trojan J, Theodoropoulou M, Usadel KH. et al . Modulation of human thyrotropin oligosaccharide structures – enhanced proportion of sialylated and terminally galactosylated serum thyrotropin isoforms in subclinical and overt primary hypothyroidism.  J Endocrinol. 1998;  158 359-365
• 36 vanGeffen C, Bavegems V, Duchateau L. et al . Serum thyroid hormone concentrations and thyroglobulin autoantibodies in trained and non-trained healthy whippets.  Vet J. 2006;  172 135-140

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