Hypoadrenokortizismus beim Hund – ein Update zu Pathogenese, Diagnose und Therapie

Katja Kalenyak; Romy M. Heilmann

doi:10.15654/TPK-180351

Tierärztliche Praxis Ausgabe K: Kleintiere / Heimtiere, Inhaltsverzeichnis

Tierarztl Prax Ausg K Kleintiere Heimtiere 2018; 46(03): 163-175
DOI: 10.15654/TPK-180351

Übersichtsartikel – Review Articles

Schattauer GmbH

Hypoadrenokortizismus beim Hund – ein Update zu Pathogenese, Diagnose und Therapie

Canine hypoadrenocorticism – an update on pathogenesis, diagnosis and treatment

Katja Kalenyak

¹Klinik für Kleintiere, Veterinärmedizinische Fakultät der Universität Leipzig

,

Romy M. Heilmann

¹Klinik für Kleintiere, Veterinärmedizinische Fakultät der Universität Leipzig

› Institutsangaben

Abstract

Zusammenfassung

Ein Hypoadrenokortizismus (HoAK) entsteht durch eine in der Regel primäre (immunmediierte) Entzündung der Nebennierenrinde mit der Folge einer unzureichenden Gluko-und Mineralokortikoidproduktion. Als Sonderform können Patienten mit einem “atypischen” HoAK eine reine Glukokortikoidoder eine Glukokortikoid-und Mineralokorti-koiddefizienz mit dabei stabilen Elektrolytkonzentrationen aufweisen. Das klinische Bild eines HoAK ist beim Hund sehr unspezifisch. Die Symptome reichen von Zittern, Schwäche, milden bis rezidivierenden gastrointestinalen Symptomen bis hin zu Anfällen, hypovolämischem Schock und Kollaps. Die ebenfalls unspezifischen Befunde der Routineuntersuchungen gleichen häufig denen anderer Erkrankungen. Ein fehlendes Stressleukogramm, Eosinophilie, Hyponatriämie, Hyperkaliämie, Azotämie und sonographisch kleine Nebennieren stellen die charakteristischsten Befunde eines HoAK dar. Der ACTH-Stimulationstest gilt als Goldstandard zur Diagnosesicherung. Weitere endokrinologische Tests, wie Bestimmung der endogenen ACTH-Konzentration, der basalen und ACTH-stimulierten Aldosteronkonzentration, des Kortisol:ACTH-Verhältnisses sowie des Aldosteron:Renin-Verhältnisses, helfen bei der Differenzierung zwischen primärem, sekundärem und “atypischem” HoAK. In der akuten Krise bestehen die Eckpfeiler der Therapie in einer aggressiven Flüssigkeitstherapie zur Wiederherstellung der Normovolämie und Korrektur der Elektrolytverschiebungen. Die langfristige Therapie besteht in der Supplementierung von Gluko (Prednisolon) und Mineralokortikoiden (Desoxycortonpivalat) mit dem Ziel stabiler Elektrolytkonzentrationen und eines guten Allgemeinbefindens des Hundes. Die Einstellung eines Patienten unter Desoxycortonpivalat erfolgt anhand der Natrium-und Kaliumkonzentration nach einem standardisierten Protokoll. Beim “atypischen” HoAK sind ebenfalls regelmäßige Kontrollen der Elektrolyte zwingend, um einen späteren Substitutionsbedarf an Mineralokortikoiden möglichst frühzeitig zu erkennen. Mit einer adäquaten Therapie und einer guten Besitzercompliance haben Hunde mit HoAK eine exzellente Langzeitprognose.

Summary

Canine hypoadrenocorticism (HoAC) results from a loss of functional adrenal cortex, the most common etiology of which is an immune-mediated destruction leading to an inadequate production of glucocorticoids and mineralocorticoids. The term “atypical” HoAC is used for a subgroup of dogs with either an isolated glucocorticoid deficiency or a combined glucocorticoid and mineralocorticoid deficiency but normal electrolytes. Dogs with HoAC can present with a large variety of clinical signs, ranging from shaking, weakness, and mild gastrointestinal signs to seizures, hypovolemic shock, and collapse. Routine clinicopathologic and diagnostic imaging findings are usually nonspecific and frequently mimic those of other common diseases. However, the absence of a stress leukogram, eosinophilia, hyponatremia, hyperkalemia, and azotemia and small adrenal glands on abdominal ultrasound are characteristic findings in dogs with HoAC. The ACTH stimulation test is currently the gold standard method for diagnosing HoAC. Other endocrine laboratory diagnostics, including the quantification of endogenous ACTH, basal and ACTH-stimulated aldosterone levels, cortisol:ACTH ratio, and aldosterone:renin ratio, may further aid in differentiating between primary, secondary, and “atypical” HoAC. Aggressive intravenous fluid therapy is the cornerstone of treatment in paients with an acute Addisonian crisis because it restores normovolemia and normal blood electrolytes. Maintenance therapy consists of glucocorticoid (e.g., prednisolone) and mineralocorticoid (e.g., des- oxycortone pivalate) supplementation and aims for stable electrolyte concentrations and a clinically well dog. The optimal dose of desoxy- cortone pivalate for a specific dog is determined based on blood so- dium and potassium concentrations by using a standardized protocol. Regular reevaluation of blood electrolytes is required for early identifi- cation of a mineralocorticoid deficiency in dogs with “atypical” HoAC. The long-term prognosis for dogs with HoAC is excellent provided that patients receive adequate treatment and there is good owner com- pliance.

Schlüsselwörter

Morbus Addison - Glukokortikoiddefizienz - Mineralokortikoiddefizienz - atypischer Morbus Addison - ACTH-Stimulationstest - Aldosteron - Desoxycortonpivalat - Glukokortikoide

Keywords

Addison’s disease - glucocorticoid deficiency - mineralocorticoid deficiency - atypical Addison’s disease - ACTH stimulation test - aldosterone - desoxycortone pivalate - glucocorticoids

Volltext

Referenzen

Literatur
1 Adamantos S, Boag A. Total and ionised calcium concentrations in dogs with hypoadrenocorticism. Vet Rec 2008; 163: 25-26.
2 Adissu HA, Hamel-Jolette A, Foster RA. Lymphocytic adenohypophysitis and adrenalitis in a dog with adrenal and thyroid atrophy. Vet Pathol 2010; 47: 1082-1085.
3 Adler JA, Drobatz KJ, Hess RS. Abnormalities of serum electrolyte concentrations in dogs with hypoadrenocorticism. J Vet Intern Med 2007; 21: 1168-1173.
4 Allon M, Copkney C. Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients. Kidney Int 1990; 38: 869-872.
5 Bartges JW, Nielson DL. Reversible megaesophagus associated with atypical primary hypoadrenocorticism in a dog. J Am Vet Med Assoc 1992; 201: 889-891.
6 Bates JA, Shott S, Schall WD. Lower initial dose desoxycorticosterone pivalate for treatment of canine primary hypoadrenocorticism. Aust Vet J 2013; 91: 77-82 discussion 81-72.
7 Baumstark ME, SieberRuckstuhl NS, Muller C, Wenger M, Boretti FS, Reusch CE. Evaluation of aldosterone concentrations in dogs with hypo adrenocorticism. J Vet Intern Med 2014; 28: 154-159.
8 Baumstark ME, Nussberger J, Boretti FS, Baumstark MW, Riond B, Reusch CE, SieberRuckstuhl NS. Use of plasma renin activity to monitor minera locorticoid treatment in dogs with primary hypoadrenocorticism: desoxy corticosterone versus fludrocortisone. J Vet Intern Med 2014; 28: 1471-1478.
9 Behrend EN, Kemppainen RJ, Bruyette DS, Busch KA, Lee HP. Intramuscu lar administration of a low dose of ACTH for ACTH stimulation testing in dogs. J Am Vet Med 2006; 229: 528-530.
10 Białkowska J, Zygmunt A, Lewiński A, Stankiewicz W, Knopik-Dąbrowicz A, Szubert W, Jabłkowski M. Hepatitis and the polyglandular autoimmune syndrome, type 1. Arch Med Sci 2011; 07: 536-539.
11 Boag AM, Catchpole B. A review of the genetics of hypoadrenocorticism. Top Companion Anim Med 2014; 29: 96-101.
12 Boag AM, Christie MR, McLaughlin KA, Syme HM, Graham P, Catchpole B. Autoantibodies against cytochrome P450 sidechain cleavage enzyme in dogs (Canis lupus familiaris) affected with hypoadrenocorticism (Addison’s disease). PLoS ONE 2015; 10: e0143458.
13 Boretti FS, Meyer F, Burkhardt WA, Riond B, HofmannLehmann R, Reusch CE, SieberRuckstuhl NS. Evaluation of the cortisoltoACTH ratio in dogs with hypoadrenocorticism, dogs with diseases mimicking hypoad renocorticism and in healthy dogs. J Vet Intern Med 2015; 29: 1335-1341.
14 Boujon CE, BornandJaunin V, Scharer V, Rossi GL, Bestetti GE. Pituitary gland changes in canine hypoadrenocorticism: a functional and immuno cytochemical study. J Comp Pathol 1994; 111: 287-295.
15 Bovens C, Tennant K, Reeve J, Murphy KF. Basal serum cortisol concen tration as a screening test for hypoadrenocorticism in dogs. J Vet Intern Med 2014; 28: 1541-1545.
16 Bowen D, Schaer M, Riley W. Autoimmune polyglandular syndrome in a dog: a case report. J Am Anim Hosp Assoc 1986; 649-654.
17 Brady CA, Vite CH, Drobatz KJ. Severe neurologic sequelae in a dog after treatment of hypoadrenal crisis. J Am Vet Med Assoc 1999; 215: 222-225 210.
18 Cartwright JA, Stone J, Rick M, Dunning MD. Polyglandular endocrino pathy type II (Schmidt’s syndrome) in a Dobermann pinscher. J Small Anim Pract 2016; 57: 491-494.
19 Chase K, Sargan D, Miller K, Ostrander EA, Lark KG. Understanding the genetics of autoimmune disease: two loci that regulate late onset Addison’s disease in Portuguese Water Dogs. Int J Immunogenet 2006; 33: 179-184.
20 DiBartola SP. Disorders of sodium and water: hypernatremia and hypo natremia. In: Fluid, Electrolyte, and AcidBase Disorders in Small Animal Practice. DiBartola SP. St. Louis, Missouri, USA: Saunders Elsevier; 2012: 45-79.
21 DiBartola SP. Introduction to acidbase disorders. In: Fluid, Electrolyte, and AcidBase Disorders in Small Animal Practice. DiBartola SP. St. Louis, Missouri, USA: Saunders Elsevier; 2012: 231-252.
22 DiBartola SP. Metabolic acidbase disorders. In: Fluid, Electrolyte, and AcidBase Disorders in Small Animal Practice. DiBartola SP. St. Louis, Missouri, USA: Saunders Elsevier; 2012: 253-286.
23 Elliott MJ, Ronksley PE, Clase CM, Ahmed SB, Hemmelgarn BR. Manage ment of patients with acute hyperkalemia. CMAJ 2010; 182: 1631-1635.
24 Famula TR, Belanger JM, Oberbauer AM. Heritability and complex segre gation analysis of hypoadrenocorticism in the standard poodle. J Small Anim Pract 2003; 44: 8-12.
25 Frank CB, Valentin SY, ScottMoncrieff JC, Miller MA. Correlation of in flammation with adrenocortical atrophy in canine adrenalitis. J Comp Pathol 2013; 149: 268-279.
26 Gagnon RF, Halperin ML. Possible mechanisms to explain the absence of hyperkalaemia in Addison’s disease. Nephrol Dial Transplant 2001; 16: 1280-1284.
27 Gold AJ, Langlois DK, Refsal KR. Evaluation of basal serum or plasma cor tisol concentrations for the diagnosis of hypoadrenocorticism in dogs. J Vet Intern Med 2016; 30: 1798-1805.
28 Gow AG, Gow DJ, Bell R, Simpson JW, Chandler ML, Evans H, Berry JL, Herrtage ME, Mellanby RJ. Calcium metabolism in eight dogs with hypo adrenocorticism. J Small Anim Pract 2009; 50: 426-430.
29 Gunn E, Shiel RE, Mooney CT. Hydrocortisone in the management of acute hypoadrenocorticism in dogs: a retrospective series of 30 cases. J Small Anim Pract 2016; 57: 227-233.
30 Hansen BL. Synthetic ACTH (cosyntropin) stimulation tests in normal dogs: comparison of intravenous and intramuscular administration. J Am Anim Hosp Assoc 1994; 30: 38-41.
31 Hanson JM, Tengvall K, Bonnett BN, Hedhammar Å. Survival analysis of dogs with adrenocortical insufficiency. J Vet Intern Med 2015; 29: 423-483.
32 Hanson JM, Tengvall K, Bonnett BN, Hedhammar Å. Naturally occurring adrenocortical insufficiency - an epidemiological study based on a Swe dishinsured dog population of 525,028 dogs. J Vet Intern Med 2016; 30: 76-84.
33 Hess RS. Hypoadrenocorticism. In: Textbook of Veterinary Internal Medi cine. 8th edn. Ettinger SJ, Feldman EC, Côté E. eds St. Louis, Missouri, USA: Saunders Elsevier; 2017: 1825-1833.
34 Hoerauf A, Reusch C. Ultrasonographic evaluation of the adrenal glands in six dogs with hypoadrenocorticism. J Am Anim Hosp Assoc 1999; 35: 214-218.
35 Hughes AM, Nelson RW, Famula TR, Bannasch DL. Clinical features and heritability of hypoadrenocorticism in Nova Scotia Duck Tolling Retrie vers: 25 cases (1994-2006). J Am Vet Med Assoc 2007; 231: 407-412.
36 Husebye E, Løvås K. Pathogenesis of primary adrenal insufficiency. Best Pract Res Clin Endocrinol Metab 2009; 23: 147-157.
37 Jaffey JA, Nurre P, Cannon AB, DeClue AE. Desoxycorticosterone pivalate duration of action and individualized dosing intervals in dogs with primary hypoadrenocorticism. J Vet Intern Med 2017; 31: 1649-1657.
38 Javadi S, Galac S, Boer P, Robben JH, Teske E, Kooistra HS. Aldosteroneto renin and cortisoltoadrenocorticotropic hormone ratios in healthy dogs and dogs with primary hypoadrenocorticism. J Vet Intern Med 2006; 20: 556-561.
39 Johnson CM, Kass PH, Cohen TA, Feldman EC. Effect of intravenous or perivascular injection of synthetic adrenocorticotropic hormone on stimu lation test results in dogs. J Vet Intern Med 2017; 31: 730-733.
40 Kemppainen RJ, Sartin JL, Peterson ME. Effects of single intravenously ad ministered doses of dexamethasone on response to the adrenocorticotropic hormone stimulation test in dogs. Am J Vet Res 1989; 50: 1914-1917.
41 Kemppainen RJ, Behrend EN. Adrenal physiology. Vet Clin North Am Small Anim Pract 1997; 27: 173-186.
42 Kintzer PP, Peterson ME. Treatment and longterm followup of 205 dogs with hypoadrenocorticism. J Vet Intern Med 1997; 11: 43-49.
43 Klein SC, Peterson ME. Canine hypoadrenocorticism: part I. Can Vet J 2010; 51: 63-69.
44 Klein SC, Peterson ME. Canine hypoadrenocorticism: part II. Can Vet J 2010; 51: 179-184.
45 Labelle P, De Cock HE. Metastatic tumors to the adrenal glands in do mestic animals. Vet Pathol 2005; 42: 52-58.
46 Lathan P, Tyler J. Canine hypoadrenocorticism: diagnosis and treatment. Comp Cont Educ Pract 2005; 27: 121-132.
47 Lathan P, Moore GE, Zambon S, ScottMoncrieff JC. Use of a lowdose ACTH stimulation test for diagnosis of hypoadrenocorticism in dogs. J Vet Intern Med 2008; 22: 1070-1073.
48 Lathan P, ScottMoncrieff JC, Wills RW. Use of the cortisoltoACTH ratio for diagnosis of primary hypoadrenocorticism in dogs. J Vet Intern Med 2014; 28: 1546-1550.
49 Lathan P. Confirming the diagnosis of Addison’s disease and how to avoid pitfalls in diagnostic workup. European Zycortal Symposium 2017. Skipton: United Kingdom.;
50 Lennon EM, Boyle TE, Hutchins RG, Friedenthal A, Correa MT, Bissett SA, Moses LS, Papich MG, Birkenheuer AJ. Use of basal serum or plasma corti sol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000-2005). J Am Vet Med Assoc 2007; 231: 413-416.
51 Lens XM, Montoliu J, Cases A, Campistol JM, Revert L. Treatment of hy perkalaemia in renal failure: salbutamol v. insulin. Nephrol Dial Transplant 1989; 04: 228-232.
52 Levy JK. Hypoglycemic seizures attributable to hypoadrenocorticism in a dog. J Am Vet Med Assoc 1994; 204: 526-528 discussion 528-530.
53 McGonigle KM, Randolph JF, Center SA, Goldstein RE. Mineralocorticoid before glucocorticoid deficiency in a dog with primary hypoadrenocorti cism and hypothyroidism. J Am Anim Hosp Assoc 2013; 49: 54-57.
54 Melian C, Peterson ME. Diagnosis and treatment of naturally occurring hy poadrenocorticism in 42 dogs. J Small Anim Pract 1996; 37: 268-275.
55 Melian C, Stefanacci J, Peterson ME, Kintzer PP. Radiographic findings in dogs with naturallyoccurring primary hypoadrenocorticism. J Am Anim Hosp Assoc 1999; 35: 208-212.
56 Michele TM, Fleckenstein J, Sgrignoli AR, Thuluvath PJ. Chronic active hepatitis in the type I polyglandular autoimmune syndrome. Postgrad Med J 1994; 70: 128-131.
57 Nagler EV, Vanmassenhove J, van der Veer SN, Nistor I, Van Biesen W, Webster AC, Vanholder R. Diagnosis and treatment of hyponatremia: a systematic review of clinical practice guidelines and consensus statements. BMC Med 2014; 12: 231.
58 Neufeld M, Maclaren NK, Blizzard RM. Two types of autoimmune Addis on’s disease associated with different polyglandular autoimmune (PGA) syndromes. Medicine (Baltimore) 1981; 60: 355-362.
59 O’Brien DP, Kroll RA, Johnson GC, Covert SJ, Nelson MJ. Myelinolysis after correction of hyponatremia in two dogs. J Vet Intern Med 1994; 08: 40-48.
60 Oberbauer AM, Benemann KS, Belanger JM, Wagner DR, Ward JH, Famula TR. Inheritance of hypoadrenocorticism in bearded collies. Am J Vet Res 2002; 63: 643-647.
61 Peterson ME, Feinman JM. Hypercalcemia associated with hypoadrenocor ticism in sixteen dogs. J Am Vet Med Assoc 1982; 181: 802-804.
62 Peterson ME, Kintzer PP, Kass PH. Pretreatment clinical and laboratory findings in dogs with hypoadrenocorticism: 225 cases (1979-1993). J Am Vet Med Assoc 1996; 208: 85-91.
63 Pikula J, Pikulova J, Bandouchova H, Hajkova P, Faldyna M. Schmidt’s syn drome in a dog: a case report. Vet Med (Praha) 2007; 52: 419.
64 Platt SR, Chrisman CL, Graham J, Clemmons RM. Secondary hypoadreno corticism associated with craniocerebral trauma in a dog. J Am Anim Hosp Assoc 1999; 35: 117-122.
65 Ramsey I. Fludrocortisone. In: BSAVA Small Animal Formulary. 7th edn. Ramsey I. ed. Gloucester: BSAVA; 2011: 146.
66 Ramsey I. Treatment of Addison’s disease with Zycortal and glucocorti coids. European Zycortal Symposium 2017. Skipton: United Kingdom.;
67 Reusch CE, Fracassi F, SieberRuckstuhl NS, Burkhardt WA, HoferInteeworn N, Schuppisser C, Stirn M, HofmannLehmann R, Boretti FS. Altered serum thyrotropin concentrations in dogs with primary hypoadrenocorti cism before and during treatment. J Vet Intern Med 2017; 31: 1643-1648.
68 Reusch CE. Redefining ‘atypical’ Addison’s disease. European Zycortal Symposium 2017. Skipton: United Kingdom.;
69 Richartz J, Neiger R. Hypoadrenokortizismus ohne klassische Elektrolyt veränderungen bei sieben Hunden. Tierärztl Prax 2011; 39 (K): 163-169.
70 Rogers W, Straus J, Chew D. Atypical hypoadrenocorticism in three dogs. J Am Vet Med Assoc 1981; 179: 155-158.
71 Schaer M. The treatment of acute adrenocortical insufficiency in the dog. J Vet Emerg Crit Care 2001; 11: 7-14.
72 ScottMoncrieff JC. Hypoadrenocorticism. In: Textbook of Veterinary In ternal Medicine. 7th edn. Ettinger Sj, Feldman EC. eds. St. Louis, Missouri, USA: Saunders Elsevier; 2010: 1847-1857.
73 Seth M, Drobatz KJ, Church DB, Hess RS. White blood cell count and the sodium to potassium ratio to screen for hypoadrenocorticism in dogs. J Vet Intern Med 2011; 25: 1351-1356.
74 Surawicz B. Relationship between electrocardiogram and electrolytes. Am Heart J 1967; 73: 814-834.
75 Syme HM, ScottMoncrieff JC. Chronic hypoglycaemia in a hunting dog due to secondary hypoadrenocorticism. J Small Anim Pract 1998; 39: 348-351.
76 Tag TL, Day TK. Electrocardiographic assessment of hyperkalemia in dogs and cats. J Vet Emerg Crit Care 2008; 18: 61-67.
77 Thompson AL, ScottMoncrieff JC, Anderson JD. Comparison of classic hypoadrenocorticism with glucocorticoiddeficient hypoadrenocorticism in dogs: 46 cases (1985-2005). J Am Vet Med Assoc 2007; 230: 1190-1194.
78 Tyler RD, Qualls Jr CW, Heald RD, Cowell RL, Clinkenbeard KD. Renal concentrating ability in dehydrated hyponatremic dogs. J Am Vet Med Assoc 1987; 191: 1095-1100.
79 Van Lanen K, Sande A. Canine hypoadrenocorticism: pathogenesis, diag nosis, and treatment. Top Companion Anim Med 2014; 29: 88-95.
80 Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, Thompson CJ. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med 2013; 126: S1-42.
81 Wakayama JA, Furrow E, Merkel LK, Armstrong PJ. A retrospective study of dogs with atypical hypoadrenocorticism: a diagnostic cutoff or continu um?. J Small Anim Pract 2017; 58: 365-371.
82 Wenger M, Mueller C, Kook PH, Reusch CE. Ultrasonographic evaluation of adrenal glands in dogs with primary hypoadrenocorticism or mimicking diseases. Vet Rec 2010; 167: 207-210.
83 Whitley NT. Megaoesophagus and glucocorticoiddeficient hypoadreno corticism in a dog. J Small Anim Pract 1995; 36: 132-135.
84 Zeugswetter F, Willmann M, Teinfalt M, Benesch T. Physical exercise in dogs with primary adrenocortical insufficiency. Vet Med Austria/Wien Tierärztl Mschr 2006; 93: 29-31.
85 Zeugswetter FK, Schwendenwein I. Diagnostic efficacy of the leukogram and the chemiluminometric ACTH measurement to diagnose canine hypoadreno corticism. Tierarztl Prax Ausg K Kleintiere Heimtiere 2014; 42 (04) 223-230.
86 Zeugswetter FK, Haninger T. Prednisolondosierung bei Hunden mit Hypo adrenokortizismus nach Integration der ACTHMessung in die Therapie überwachung. Tierarztl Prax Ausg K Kleintiere Heimtiere 2018; 46 (02) 90-97.