Case Report Rapport de cas A suspected case of Addison’s disease in cattle Bianca Lambacher, Thomas Wittek Abstract — A 4.75-year old Simmental cow was presented with symptoms of colic and ileus. The clinical signs and blood analysis resulted in the diagnosis of suspected primary hypoadrenocorticism (Addison’s disease). Although Addison’s disease has been frequently described in other domestic mammals, to our knowledge, this disease has not previously been reported in cattle. Résumé — Un cas suspecté de la maladie d’Addison chez le bétail. Une vache Simmental âgée de 4,75 ans a été présentée avec des symptômes de coliques et d’occlusion intestinale. Les signes cliniques et l’analyse sanguine ont conduit à un diagnostic d’hypoadrénocorticisme primaire suspecté (maladie d’Addison). Même si la maladie d’Addison a souvent été décrite chez d’autres mammifères domestiques, à notre connaissance, cette maladie n’a pas été décrite antérieurement chez le bétail. (Traduit par Isabelle Vallières) Can Vet J 2015;56:928–930
A
ddison’s disease (AD) or Morbus Addison (primary or secondary hypoadrenocorticism) is characterized by insufficiency of all 3 zones of the adrenal cortex (1). The gland consists of the adrenal cortex (cortex glandulae suprarenalis) and the adrenal medulla (medulla glandulae suprarenalis) where the hormones (aldosterone, androgens, cortisol, epinephrine, norepinephrine) are synthetized and delivered directly into the bloodstream under the control of a hormonal feedback system involving the pituitary gland and the autonomic nervous system (2,3). Well-known diseases of this gland are Cushing’s disease (hyperfunction of the adrenal cortex), AD (hypofunction of the adrenal cortex), and the Waterhouse- Friderichsen- syndrome (acute and complete loss of function of the cortex due to septicemia) (1,4). Addison’s disease may be primary or secondary. The first is characterized by a dysfunction caused by destruction of the adrenal cortex cells (5) and may develop slowly or acutely (4,6). However, only the almost complete destruction of the cortex causes clinical signs of AD, whereas a unilateral or incomplete degeneration usually results in subclinical disease (5). Secondary hypoadrenocorticism develops due to reduced adrenocorticotropic hormone (ACTH) stimulation (2) and may occur as an isolated condition or, more commonly, associated with other disease, e.g., tuberculosis in humans (7,8).
University Clinic for Ruminants of the University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Wien, Austria. Address all correspondence to Dr. Bianca Lambacher; e-mail: [email protected] Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ([email protected]) for additional copies or permission to use this material elsewhere. 928
The absence of mineralocorticoids leads to disturbances in electrolyte metabolism and its consequences (hyperkalemia, hyponatremia, hypotension, tachycardia, and salt hunger). The hyponatremia results in increased antidiuretic hormone (ADH) secretion and free water retention to counteract the hypovolemic state. Fatigue, loss of appetite, nausea, joint and muscle pain and anemia are caused by the effects of decreased cortisol. Androgen deficiency leads to a reduction in libido, depression, and dry skin (4). The condition often remains subclinical but may be exacerbated by stress which may be caused by diseases such as diabetes mellitus (since both the cortisol- and the catecholamine-response are absent), bronchial asthma, primary ovarian insufficiency, infections and even surgery (9,10). In severe cases, when blood cortisol levels do not increase the patient may collapse as part of a cardiovascular crisis due to arterial hypotension — (Addisonian crisis) precipitated by the mineralocorticoid and cortisol deficiency (8,11,12). Further complications occur during the crisis, because of reduced epinephrine synthesis in the adrenal medulla and a response of the vessels to angiotensin II (13–16). The clinical signs of AD are not specific and can only result in a presumptive diagnosis. Misdiagnoses are not uncommon in veterinary and human medicine (12). Clinical biochemistry (sodium and potassium concentrations, Na:K ratio) may suggest hypoadrenocorticism. In humans the repeated occurrence of a decrease in the unstimulated morning serum cortisol concentration (, 8 nmol/L) is considered a reliable parameter for diagnosing adrenal hypofunction (4). There are no reference values for cattle, but they have been established in dogs. In 1 study (17) comprising 110 healthy dogs and 13 dogs with AD, a basal cortisol concentration of , 2.67 nmol/L had a sensitivity of 100% and a specificity of 98.2% for hypoadrenocorticism. It has also been suggested that elevated plasma ACTH CVJ / VOL 56 / SEPTEMBER 2015
Table 1. Hematological and biochemical parameters at the initial examination Hematological and biochemical serum parameters
Patient
Reference range
a 1.00
mg/dL, below the detection limit.
concentration can be used to diagnose primary AD (2). Plasma aldosterone and renin concentrations are also increased (18). The ACTH stimulation test is most frequently used resulting in a low-grade increase in cortisol levels after ACTH stimulation (2). The serum cortisol:ACTH ratio, which is decreased in AD has been recently described as an equally reliable diagnostic parameter (19). Other diagnostic procedures are histological examination, advanced techniques to visualize changes of the adrenal gland, e.g., magnetic resonance imaging (MRI) and finally pathological findings following postmortem (20).
Case description A 4 years and 9 months old, heavily pregnant (9 months) Simmental cow with a presumptive diagnosis of intestinal ileus was referred to the University Clinic for Ruminants of the University of Veterinary Medicine Vienna. The cow was dull and the feed intake was reduced; however, she was constantly licking the mineral block. The patient showed abdominal pain, dehydration and decreased body temperature (35.9°C). The pulse wave had medium strength, the vessels were moderately filled and tensed, and the heart sounds were normally audible, but had an irregular rhythm. The feces contained blood and mucus on rectal examination. Ultrasonographic examination of the abdomen revealed a cessation of reticular contraction but no signs of intestinal ileus such as distended intestinal loops or increased fluid in the abdominal cavity. The serum biochemical parameters (Table 1) indicated an electrolyte imbalance and hypoglycemia. The serum sodium concentration was decreased and the potassium level was increased. The Na:K ratio was therefore also decreased (15.6; physiological range: 27 to 40). The urea and creatinine concentrations were also increased (urea: 13.49 mmol/L; creatinine: 167.96 mmol/L). The concentrations of calcium (2.04 mmol/L) and phosphorus (0.98 mmol/L) were mildly reduced. Hematological parameters showed eosinopenia, lymphopenia, and neutrophilia (Table 1). The laboratory findings resulted in a presumptive diagnosis of AD and subsequently the basal value for cortisol in the blood was determined to be below the detection limit of 27.6 nmol/L (1.00 mg/dL) (Table 1). This low concentration strongly supported the diagnosis. A urinalysis was not performed. CVJ / VOL 56 / SEPTEMBER 2015
Discussion The laboratory tests, clinical signs, and response of the cow to treatment indicate an insufficiency of the adrenal cortex (AD), which is related to the lack of mineralocorticoids and glucocorticoids (2). The ACTH stimulation-test could not be performed legally in the cow since there is no ACTH preparation licensed for food-producing animals. The initial causes for referring the cow to the veterinary hospital were abdominal pain and intestinal ileus. This is similar to many human AD patients who exhibit diffuse abdominal pain of unknown source (22). The hypoglycemia was due to the decreased gluconeogenesis (23). The lack of mineralocorticoids (mainly aldosterone) causes a loss of sodium by renal excretion, resulting in blood volume depletion (24). The urea and creatinine concentrations were elevated, which could be a result of decreased renal perfusion due to hypovolemia. The low Na:K ratio, pronounced salt craving, dehydration, and bradycardia in the cow, mirror commonly described clinical patterns in humans and other animals (2,4,25). The bradycardia in AD patients is considered to be the result of hyperkalemia (2,4). The decreased cortisol concentration and increased ACTH concentration in the cow, compared to the control group, are indicative of hypoadrenocorticism (2). The lack of a stress response in the blood (eosinophilia, lymphocytosis, neutropenia), however, does not support the diagnosis. Lathan et al 929
CA S E R E P O R T
Sodium 120 mmol/L 130–150 mmol/L Potassium 7.7 mmol/L 4.4–5.7 mmol/L Na:K ratio 15.6 mmol/L 27–40 mmol/L Calcium 2.04 mmol/L 2.30–3.00 mmol/L Phosphorus 0.98 mmol/L 1.60–2.30 mmol/L Urea 6.3 mmol/L 3.5–5.0 mmol/L Creatinine 167.96 mmol/L 92.82–156.47 mmol/L a Cortisol 27.6 mmol/L Not available Eosinophils (3 10⁹/L) 0.03 0.06–0.67 Lymphocytes (3 10⁹/L) 2.54 3.29–6.37 Neutrophils (3 10⁹/L) 8.32 1.43–3.52
The treatment was directed towards 3 therapeutic aims: correction of the electrolyte imbalance by IV infusion and oral hydration, restoration of the acid-base balance as a consequence of rehydration, and correction of the hyperkalemia along with the restoration of the acid-base balance (2). Consequently, the cow was rehydrated by continuous IV infusion (10 L of NaCl 0.9%) and orally with 40 L of water by stomach tube. After the cow had been rehydrated its behavior improved instantly and it showed a good appetite. The clinical condition and the laboratory parameters improved rapidly and the animal was discharged from the clinic after 3 d. Due to the rare occurrence of this case it was decided to follow this animal’s progress with a farm visit 37 d after discharge from the clinic. The animal was in healthy condition and had given birth to a premature but live calf. The hematological and biochemical examinations were repeated. The concentration of sodium and potassium, and the cortisol hormones and ACTH were determined. The serum Na:K-ratio (57.5) was above the physiological range (Na: 138 mmol/L, K: 2.4 mmol/L). The serum cortisol concentration was again below the detection limit (, 1.00 mg/dL) and the serum ACTH value was 21 pg/mL. Since no reference values for basal ACTH concentration in cattle were available, the ACTH serum concentrations of 5 clinically healthy cows were used for comparison. Three of the controls were below the detection limit (10 pg/mL), 1 was 12 pg/mL and 1 was 16 pg/mL. For horses, there is a wide physiological range for plasma ACTH (17.6 1/2 1.6 to 60.0 1/2 4.0 pg/mL) (21). Since the serum cortisol concentration of the cow was below the detection limit of 1.00 mg/dL, the ratio could not be calculated exactly but it would be , 0.047 [dividing the detection limit for cortisol (1 mg/dL) by the ACTH concentration of 21 pg/mL].
R A P P O R T D E CA S
(19) suggested that the cortisol:ACTH ratio is equal or even preferable to the ACTH stimulation test. The ratio in healthy dogs was 2.27 on average, dogs with AD had an average ratio of 0.000714. These authors did not consider the different units for ACTH (pg/mL) and cortisol (mg/dL) before calculating the cortisol:ACTH ratio. We have done the same in the present case report to allow for comparison. The ratio of , 0.047 is considerably below the reference value for dogs (19). Due to the high costs and technical limitations we did not perform further diagnostic procedures described in human medicine (e.g., transperitoneal adrenalectomy for histological analysis, computed tomography, or detection of tuberculosis in the adrenal glands) (20). Lymphomas are a potential cause of neoplasia in the adrenal glands in cattle (26). Tuberculosis and leucosis, however, are not likely, as Austria is free from these diseases (27). Usually, the treatment of AD requires lifelong administration of mineralocorticoids (aldosterone) and cortisol, in which case priority must be given to the natural hydrocortisone (cortisol). Although prednisolone acts longer (approximately 12 to 18 h) and has a 5- to 6-fold stronger effect, it does not have sufficient mineralocorticoid effects (8,28). Treatment options were discussed with the farmer but not started for economic reasons. Ten months later the cow was still in good health. There have been no further noticeable clinical symptoms since. For cases of primary AD it is not unusual to have episodes during which no clinical or laboratory signs are present, since most patients only appear clinically noticeable under stressful conditions. In summary, due to the relatively non-specific clinical signs, a diagnosis of an intestinal problem leading to AD is possible. We would be interested to know if any clinicians have had a similar experience. To the best of our knowledge no cases of AD, whether primary or secondary, in cattle have been described in the literature. CVJ
References 1. Hansen MP, Erlich M, Kahaly GJ. Morbus Addison und pluriglanduläre Syndrome. Journal für Klinische Endokrinologie und Stoffwechsel — Austria 2013;6:5–11. 2. Gaydos CA, De Clue AE. Updates on hypoadrenocorticism. Vet Med 2008;103:320–332. 3. Woenckhaus U, Vasold A, Bollheimer LC. Akute Nebennierenin suffizienz (“Addison-Krise”). Intensivmed 2005;42:345–354. 4. Quinkler M. Morbus Addison. Med Klin Intensivmed Notfallmed 2012;107:454–459. 5. Martinez-Albaladejo M, Garcia-Lopez B, Serrano-Corredor S, AlguacilGarcia G. Adrenal mass and adrenal insufficiency. An Med Interna 1996;13:595. 6. Freissmuth M, Offermanns S, Böhm S. Pharmakologie und Toxikologie. 1. Aufl., Berlin: Springer Verlag, 2012:107–111.
930
7. Addison T. On the constitutional and local effects of disease of the supra-renal capsules. London, UK: Samuel Highley, 1855. 8. Arlt W, Allolio B. Adrenal insufficiency. Lancet 2003;361:1881–1893. 9. Hahner S, Löffler M, Bleiken B, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency — the need for new prevention strategies. Eur J Endocrinol 2010;162:597–602. 10. White K, Arlt W. Adrenal crisis in treated Addison’s disease: A predictable but under-managed event. Eur J Endocrinol 2010;165:115–120. 11. Allolio B, Ehses W, Steffen HM, Müller R. Reduced lymphocyte beta 2-adrenoceptor density and impaired diastolic left ventricular function in patients with glucocorticoid deficiency. Clin Endocrinol 1994; 40:769–775. 12. Bleicken B, Hahner S, Ventz M, Quinkler M. Delayed diagnosis of adrenal insufficiency is common: A cross-sectional study in 216 patients. Am J Med Sci 2010;339:525–531. 13. Zuckerman-Lavin N, Tiosano D, Eisenhofer G, Bornstein S, Hochberg Z. The importance of adrenocortical glucocorticoids for adrenomedullary and physiological response to stress: A study in isolated glucocorticoid deficiency. J Clin Endocrinol Metab 2001;86:5920–5924. 14. Bornstein SR, Breidert M, Ehrhart-Bornstein M, Kloos B, Scherbaum WA. Plasma catecholamines in patients with Addison’s disease. Clin Endocrinol 1995;42:215–218. 15. Ishikawa S, Schrier RW. Vascular effects of arginine vasopressin, angiotensin II, and norepinephrine in adrenal insufficiency. Am J Physiol 1984;246:H104–H113. 16. Yagil Y, Krakoff LR. The differential effect of aldosterone and dexamethasone on pressor response in adrenalectomized rats. Hypertension 1988;11:174–178. 17. Lennon EM, Boyle TE, Hutchins RG. Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000–2005). J Am Vet Med Assoc 2007;231:413–416. 18. Oelkers W. Morbus Addison, Diagnostik und Therapie. Medizinische Klinik 1998;30:683. 19. Lathan P, Scott-Moncrieff JC, Wills RW. Use of cortisol-to-ACTH ratio for diagnosis of primary hyposdrenocorticism in dogs. J Vet Intern Med 2014;28:1546–1550. 20. Pinocy J, Ruck P, Aepinus CH, Jenss H. Nebennierentuberkulose als seltene Ursache einer adrenocorticalen Insuffizienz (Morbus Addison). Der Chirurg 1999;70:92–95. 21. Bradaric’ Z. Untersuchung zum Equinen Cushing Syndrom und Prüfung der Wirksamkeit von Vitex agnus-castus (Mönchspfeffer) bei der Behandlung des Equinen Cusing Syndroms (dissertation). Berlin, Deutschland: Freie Universität Berlin, 2012. 22. Tobin MV, Aldridge SA, Morris AI, Belchetz PE, Gilmore IT. Gastrointestinal manifestations of Addison’s disease. Am J Gastroenterol 1989;84:1302–1305. 23. Atavia-Loria E, Chaussain JL, Bougneres PF, Job JC. Frequency of hypoglycemia in children with adrenal insufficiency. Acta Endocrinol (Suppl) 1986;279:275–278. 24. Diederich S, Franzen NF, Bahr V, Oelkers W. Severe hyponatremia due to hypopituitarism with adrenal insufficiency: Report on 28 cases. Eur J Endocrinol 2003;148:609–617. 25. Richartz J, Neiger R. Hypoadrenokortizismus ohne klassische Elektro lytveränderungen bei sieben Hunden. Tierärztl Prax 2011;39:163–169. 26. LaBell P, De Cock HEV. Metastatic tumors to the adrenal glands in domestic animals. Vet Pathol 2005;42:52–58. 27. Bundesgesetzblatt für die Republik Österreich. 304.Verordnung: Rinderleukose-Untersuchungsverordnung 2008. 5.Nov.2007, Teil II, Nr.304. 28. Koetz KR, Ventz M, Dietrich S, Quinkler M. Bone mineral density is not significantly reduced in adult patients on low-dose glucocorticoid replacement therapy. J Clin Endocrinol Metab 2012;97:85–92.
CVJ / VOL 56 / SEPTEMBER 2015
A
ddison’s disease (AD) or Morbus Addison (primary or secondary hypoadrenocorticism) is characterized by insufficiency of all 3 zones of the adrenal cortex (1). The gland consists of the adrenal cortex (cortex glandulae suprarenalis) and the adrenal medulla (medulla glandulae suprarenalis) where the hormones (aldosterone, androgens, cortisol, epinephrine, norepinephrine) are synthetized and delivered directly into the bloodstream under the control of a hormonal feedback system involving the pituitary gland and the autonomic nervous system (2,3). Well-known diseases of this gland are Cushing’s disease (hyperfunction of the adrenal cortex), AD (hypofunction of the adrenal cortex), and the Waterhouse- Friderichsen- syndrome (acute and complete loss of function of the cortex due to septicemia) (1,4). Addison’s disease may be primary or secondary. The first is characterized by a dysfunction caused by destruction of the adrenal cortex cells (5) and may develop slowly or acutely (4,6). However, only the almost complete destruction of the cortex causes clinical signs of AD, whereas a unilateral or incomplete degeneration usually results in subclinical disease (5). Secondary hypoadrenocorticism develops due to reduced adrenocorticotropic hormone (ACTH) stimulation (2) and may occur as an isolated condition or, more commonly, associated with other disease, e.g., tuberculosis in humans (7,8).
University Clinic for Ruminants of the University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Wien, Austria. Address all correspondence to Dr. Bianca Lambacher; e-mail: [email protected] Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ([email protected]) for additional copies or permission to use this material elsewhere. 928
The absence of mineralocorticoids leads to disturbances in electrolyte metabolism and its consequences (hyperkalemia, hyponatremia, hypotension, tachycardia, and salt hunger). The hyponatremia results in increased antidiuretic hormone (ADH) secretion and free water retention to counteract the hypovolemic state. Fatigue, loss of appetite, nausea, joint and muscle pain and anemia are caused by the effects of decreased cortisol. Androgen deficiency leads to a reduction in libido, depression, and dry skin (4). The condition often remains subclinical but may be exacerbated by stress which may be caused by diseases such as diabetes mellitus (since both the cortisol- and the catecholamine-response are absent), bronchial asthma, primary ovarian insufficiency, infections and even surgery (9,10). In severe cases, when blood cortisol levels do not increase the patient may collapse as part of a cardiovascular crisis due to arterial hypotension — (Addisonian crisis) precipitated by the mineralocorticoid and cortisol deficiency (8,11,12). Further complications occur during the crisis, because of reduced epinephrine synthesis in the adrenal medulla and a response of the vessels to angiotensin II (13–16). The clinical signs of AD are not specific and can only result in a presumptive diagnosis. Misdiagnoses are not uncommon in veterinary and human medicine (12). Clinical biochemistry (sodium and potassium concentrations, Na:K ratio) may suggest hypoadrenocorticism. In humans the repeated occurrence of a decrease in the unstimulated morning serum cortisol concentration (, 8 nmol/L) is considered a reliable parameter for diagnosing adrenal hypofunction (4). There are no reference values for cattle, but they have been established in dogs. In 1 study (17) comprising 110 healthy dogs and 13 dogs with AD, a basal cortisol concentration of , 2.67 nmol/L had a sensitivity of 100% and a specificity of 98.2% for hypoadrenocorticism. It has also been suggested that elevated plasma ACTH CVJ / VOL 56 / SEPTEMBER 2015
Table 1. Hematological and biochemical parameters at the initial examination Hematological and biochemical serum parameters
Patient
Reference range
a 1.00
mg/dL, below the detection limit.
concentration can be used to diagnose primary AD (2). Plasma aldosterone and renin concentrations are also increased (18). The ACTH stimulation test is most frequently used resulting in a low-grade increase in cortisol levels after ACTH stimulation (2). The serum cortisol:ACTH ratio, which is decreased in AD has been recently described as an equally reliable diagnostic parameter (19). Other diagnostic procedures are histological examination, advanced techniques to visualize changes of the adrenal gland, e.g., magnetic resonance imaging (MRI) and finally pathological findings following postmortem (20).
Case description A 4 years and 9 months old, heavily pregnant (9 months) Simmental cow with a presumptive diagnosis of intestinal ileus was referred to the University Clinic for Ruminants of the University of Veterinary Medicine Vienna. The cow was dull and the feed intake was reduced; however, she was constantly licking the mineral block. The patient showed abdominal pain, dehydration and decreased body temperature (35.9°C). The pulse wave had medium strength, the vessels were moderately filled and tensed, and the heart sounds were normally audible, but had an irregular rhythm. The feces contained blood and mucus on rectal examination. Ultrasonographic examination of the abdomen revealed a cessation of reticular contraction but no signs of intestinal ileus such as distended intestinal loops or increased fluid in the abdominal cavity. The serum biochemical parameters (Table 1) indicated an electrolyte imbalance and hypoglycemia. The serum sodium concentration was decreased and the potassium level was increased. The Na:K ratio was therefore also decreased (15.6; physiological range: 27 to 40). The urea and creatinine concentrations were also increased (urea: 13.49 mmol/L; creatinine: 167.96 mmol/L). The concentrations of calcium (2.04 mmol/L) and phosphorus (0.98 mmol/L) were mildly reduced. Hematological parameters showed eosinopenia, lymphopenia, and neutrophilia (Table 1). The laboratory findings resulted in a presumptive diagnosis of AD and subsequently the basal value for cortisol in the blood was determined to be below the detection limit of 27.6 nmol/L (1.00 mg/dL) (Table 1). This low concentration strongly supported the diagnosis. A urinalysis was not performed. CVJ / VOL 56 / SEPTEMBER 2015
Discussion The laboratory tests, clinical signs, and response of the cow to treatment indicate an insufficiency of the adrenal cortex (AD), which is related to the lack of mineralocorticoids and glucocorticoids (2). The ACTH stimulation-test could not be performed legally in the cow since there is no ACTH preparation licensed for food-producing animals. The initial causes for referring the cow to the veterinary hospital were abdominal pain and intestinal ileus. This is similar to many human AD patients who exhibit diffuse abdominal pain of unknown source (22). The hypoglycemia was due to the decreased gluconeogenesis (23). The lack of mineralocorticoids (mainly aldosterone) causes a loss of sodium by renal excretion, resulting in blood volume depletion (24). The urea and creatinine concentrations were elevated, which could be a result of decreased renal perfusion due to hypovolemia. The low Na:K ratio, pronounced salt craving, dehydration, and bradycardia in the cow, mirror commonly described clinical patterns in humans and other animals (2,4,25). The bradycardia in AD patients is considered to be the result of hyperkalemia (2,4). The decreased cortisol concentration and increased ACTH concentration in the cow, compared to the control group, are indicative of hypoadrenocorticism (2). The lack of a stress response in the blood (eosinophilia, lymphocytosis, neutropenia), however, does not support the diagnosis. Lathan et al 929
CA S E R E P O R T
Sodium 120 mmol/L 130–150 mmol/L Potassium 7.7 mmol/L 4.4–5.7 mmol/L Na:K ratio 15.6 mmol/L 27–40 mmol/L Calcium 2.04 mmol/L 2.30–3.00 mmol/L Phosphorus 0.98 mmol/L 1.60–2.30 mmol/L Urea 6.3 mmol/L 3.5–5.0 mmol/L Creatinine 167.96 mmol/L 92.82–156.47 mmol/L a Cortisol 27.6 mmol/L Not available Eosinophils (3 10⁹/L) 0.03 0.06–0.67 Lymphocytes (3 10⁹/L) 2.54 3.29–6.37 Neutrophils (3 10⁹/L) 8.32 1.43–3.52
The treatment was directed towards 3 therapeutic aims: correction of the electrolyte imbalance by IV infusion and oral hydration, restoration of the acid-base balance as a consequence of rehydration, and correction of the hyperkalemia along with the restoration of the acid-base balance (2). Consequently, the cow was rehydrated by continuous IV infusion (10 L of NaCl 0.9%) and orally with 40 L of water by stomach tube. After the cow had been rehydrated its behavior improved instantly and it showed a good appetite. The clinical condition and the laboratory parameters improved rapidly and the animal was discharged from the clinic after 3 d. Due to the rare occurrence of this case it was decided to follow this animal’s progress with a farm visit 37 d after discharge from the clinic. The animal was in healthy condition and had given birth to a premature but live calf. The hematological and biochemical examinations were repeated. The concentration of sodium and potassium, and the cortisol hormones and ACTH were determined. The serum Na:K-ratio (57.5) was above the physiological range (Na: 138 mmol/L, K: 2.4 mmol/L). The serum cortisol concentration was again below the detection limit (, 1.00 mg/dL) and the serum ACTH value was 21 pg/mL. Since no reference values for basal ACTH concentration in cattle were available, the ACTH serum concentrations of 5 clinically healthy cows were used for comparison. Three of the controls were below the detection limit (10 pg/mL), 1 was 12 pg/mL and 1 was 16 pg/mL. For horses, there is a wide physiological range for plasma ACTH (17.6 1/2 1.6 to 60.0 1/2 4.0 pg/mL) (21). Since the serum cortisol concentration of the cow was below the detection limit of 1.00 mg/dL, the ratio could not be calculated exactly but it would be , 0.047 [dividing the detection limit for cortisol (1 mg/dL) by the ACTH concentration of 21 pg/mL].
R A P P O R T D E CA S
(19) suggested that the cortisol:ACTH ratio is equal or even preferable to the ACTH stimulation test. The ratio in healthy dogs was 2.27 on average, dogs with AD had an average ratio of 0.000714. These authors did not consider the different units for ACTH (pg/mL) and cortisol (mg/dL) before calculating the cortisol:ACTH ratio. We have done the same in the present case report to allow for comparison. The ratio of , 0.047 is considerably below the reference value for dogs (19). Due to the high costs and technical limitations we did not perform further diagnostic procedures described in human medicine (e.g., transperitoneal adrenalectomy for histological analysis, computed tomography, or detection of tuberculosis in the adrenal glands) (20). Lymphomas are a potential cause of neoplasia in the adrenal glands in cattle (26). Tuberculosis and leucosis, however, are not likely, as Austria is free from these diseases (27). Usually, the treatment of AD requires lifelong administration of mineralocorticoids (aldosterone) and cortisol, in which case priority must be given to the natural hydrocortisone (cortisol). Although prednisolone acts longer (approximately 12 to 18 h) and has a 5- to 6-fold stronger effect, it does not have sufficient mineralocorticoid effects (8,28). Treatment options were discussed with the farmer but not started for economic reasons. Ten months later the cow was still in good health. There have been no further noticeable clinical symptoms since. For cases of primary AD it is not unusual to have episodes during which no clinical or laboratory signs are present, since most patients only appear clinically noticeable under stressful conditions. In summary, due to the relatively non-specific clinical signs, a diagnosis of an intestinal problem leading to AD is possible. We would be interested to know if any clinicians have had a similar experience. To the best of our knowledge no cases of AD, whether primary or secondary, in cattle have been described in the literature. CVJ
References 1. Hansen MP, Erlich M, Kahaly GJ. Morbus Addison und pluriglanduläre Syndrome. Journal für Klinische Endokrinologie und Stoffwechsel — Austria 2013;6:5–11. 2. Gaydos CA, De Clue AE. Updates on hypoadrenocorticism. Vet Med 2008;103:320–332. 3. Woenckhaus U, Vasold A, Bollheimer LC. Akute Nebennierenin suffizienz (“Addison-Krise”). Intensivmed 2005;42:345–354. 4. Quinkler M. Morbus Addison. Med Klin Intensivmed Notfallmed 2012;107:454–459. 5. Martinez-Albaladejo M, Garcia-Lopez B, Serrano-Corredor S, AlguacilGarcia G. Adrenal mass and adrenal insufficiency. An Med Interna 1996;13:595. 6. Freissmuth M, Offermanns S, Böhm S. Pharmakologie und Toxikologie. 1. Aufl., Berlin: Springer Verlag, 2012:107–111.
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