Hepatic carcinoid, hypercortisolism and hypokalaemia in a dog
RK CHURCHERª Department of Veterinary Clinical Sciences, The University of Sydney, New South Wales 2006
A German Shepherd dog was diagnosed with periodic myopathy secondary to persistent hypokalaemia. Hormone analysis revealed excess cortisol secretion. A neuroendocrine carcinoma, thought to be a primary hepatic carcinoid, was detected in the liver. Ectopic adrenocorticotrophin hormone secretion was suspected as the cause of hypercorti- solism and hypokalaemia, although this could not be confirmed by immunohistochemical staining.
Aust Vet J 1999;77:641-645
Key words: Dog, Cushing’s syndrome, hypokalaemia, carcinoid, ectopic adrenocorticotrophic hormone.
| ACTH | Adrenocorticotrophic hormone | CRF | Corticotropin releasing factor |
| ADH | Antidiuretic hormone (vasopressin) | NSE | Neuron specific enolase |
| ALP | Alkaline phosphatase | USG | Urine-specific gravity |
| ALT | Alanine aminotransferase | UVCS | University Veterinary Centre, Sydney |
| APUD | Amine precursor uptake and decarboxylation | VIP | Vasoactive intestinal polypeptide |
H yperadrenocorticism is a common canine endocrino- pathy, caused by excess secre- tion of ACTH by the pituitary gland with secondary adrenocortical hyper- plasia, a primary adrenal cortisol excess, or administration of excess glucorticoid or ACTH.1 In people, ectopic produc- tion of ACTH by a variety of neoplasms elaborating neuroendocrine peptides is a well-recognised additional cause and accounts for 15 to 20% of patients suffering from Cushing’s syndrome. Tumours frequently involved include small-cell (oat-cell) bronchogenic carci- nomas, carcinoids, thyroid medullary carcinomas and thymomas.2 Some human patients with Cushing’s syndrome develop marked hypo- kalaemia and metabolic alkalosis, most commonly when ectopic ACTH production results in marked oversecre- tion of cortisol.3-6 In contrast, only mild and clinically insignificant decrease of plasma potassium concentration is seen in about half of Cushingoid dogs. Ectopic ACTH production has not been diagnosed in the dog.1
This article describes a dog presented for polydipsia and periods of muscle weakness and stiffness. Other abnormal- ities were persistent metabolic alkalosis, hypokalaemia due to renal potassium wasting, and non-suppressible hypercor-
tisolism. Detection of a neuroendocrine tumour, thought to be a primary hepatic carcinoid, with marked hypokalaemia and hypercortisolism, led to a presump- tive diagnosis of ectopic ACTH syndrome.
Case report
A 9-year-old, 35 kg, castrated male German Shepherd dog was presented with a history of polydipsia and polyuria of 2 weeks duration. The dog seemed otherwise healthy, alert and active and had normal appetite. Idiopathic epilepsy had been diagnosed 7 years earlier and controlled with phenobarbitone at 2 mg/kg every 12 h. The dog was castrated 12 months earlier because of prostatitis. Clinical examination was unremarkable and laboratory investigations revealed a normal haemogram with serum potas- sium concentration 3.1 mmol/L (refer- ence range 3.9 to 5.7), bicarbonate 27.7 mmol/L (15 to 24) and anion gap of 16.4 mmol/L (17 to 35). Serum urea concentration was 3.9 mmol/L (2.5 to 9.5), creatinine 80 pmol/L (60 to 180), ALP activity 91 IU/L (0 to 140), ALT 78 IU/L (15 to 90) and cholesterol concentration 6.8 mmol/L (3 to 8.5). Urinalysis revealed isosthenuria (USG 1.010) with pH 7.5.
Although there was no biochemical evidence of hepatotoxicosis, the owners were instructed to withdraw phenobar- bitone and to monitor water intake, with a view to performing a water depri- vation test should polydipsia persist.
One month later, while on holiday, the dog was presented to another veteri- narian because of a stiff neck and reluc- tance to walk following vigorous exercise on the beach. For 1 week before presen- tation the owners had observed the dog’s gait was stiff and slightly unsteady. The dog was panting, rectal temperature was 39.1ºC and heart rate was 112 beats/min. The dog held its neck low. Mild pain and cervical muscle spasms were elicited when the neck was extended or rotated laterally. Apart from sluggish hindlimb conscious propriocep- tion, the dog seemed neurologically normal. A tentative diagnosis of cervical intervertebral disk protrusion was made and flunixin 40 mg was administered intravenously with prescription of oral flunixin 40 mg every 24 h for 3 days and three oral doses of methocarbamol 1.5 g every 12 h, then 1 g every 12 h for 2 days. The dog improved clinically but was re-presented to the author 3 weeks later with a further episode of stiffness, reluctance to move and continuing poly- dipsia and polyuria.
On physical examination, the dog seemed weak and reluctant to move and held its head low to the ground. Muscle pain and occasional cervical muscle tremors were noted. Gait was slow and stiff. Rectal temperature was 38.9℃, heart and pulse rate was 116 per min and mucous membranes were pink with capillary refill time of 1 s. The dog was panting but heart and lung sounds appeared normal. No abnormalities were detected on neurological examination.
aCurrent address: North Shore Veterinary Hospital, 94 Alexander Street, Crows Nest, New South Wales 2065
Laboratory investigations again revealed hypokalaemia (3.1 mmol/L), but normal bicarbonate concentration (19.1 mmol/L) with ALP activity 251 IU/L and ALT 186 IU/L. A stress leuko- gram was present, with neutrophil count of 24.5 x 109/L (reference range 4.06 to 9.36), lymphocytes 0 (0.91 to 3.6), monocytes 0.5 x 109/L (0.21 to 0.96) and eosinophils 0 (0.14 to 1.2). The dog now had hyposthenuria (USG 1.003). Oral potassium gluconate 10 mmol every 8 h was given and the following day the dog was much improved with normal strength, posture and gait. The dog was admitted to UVCS 3 days later for further assessment.
At that time the dog appeared clini- cally normal. Laboratory findings included hypokalaemia (2.4 mmol/L), increased bicarbonate (25.1 mmol/L), creatinine 84 pmol/L, ALP activity 178 IU/L and ALT 142 IU/L. Fasting serum bile acid concentration was 8.5 umol/L (reference range 1 to 10). Leukocyte count was 19.2 x 109/L, with 16.5 x 109/L neutrophils, 1.4 x 109/L lympho- cytes, 1.4 x 109/L monocytes and 0 eosinophils. USG was 1.003. Urinary concentrations of sodium, potassium and creatinine were 49.9 mmol/L, 24.8 mmol/L and 3.4 mmol/L, respectively. Fractional excretions of sodium and potassium were less than 1% (reference range 0 to 0.7) and 25% (0 to 20), respectively, suggesting renal potassium wasting in the face of hypokalaemia. Evidence of excess mineralocorticoid activity promoted measurement of the dog’s plasma renin and aldosterone concentrations, together with those of a control dog. The patient’s plasma concentration of renin was < 20 fm/L/s (100 to 1500, control 440) and that of aldosterone 96 pmol/L (80 to 1040, control 260). These findings did not support a diagnosis of primary or secondary hyperaldosteronism.
Serial measurements of blood pressure following placement of an arterial catheter revealed a mean systolic pres- sure of 118 mm Hg (114 to 122), mean diastolic pressure of 65 mm Hg (61 to 69), and mean average pressure of 81 mm Hg (79 to 82).
To further assess adrenal function, a low-dose dexamethasone suppression test and abdominal ultrasonography were performed. Plasma cortisol concen- trations measured before, and 4 and 8 h
after intravenous administration of 0.01 mg/kg dexamethasone were 97 nmol/L (25 to 75), 119 nmol/L (< 20) and 130 nmol/L (< 20), respectively, suggesting non-suppressible hypersecretion of cortisol. Plasma basal ACTH concen- tration was 10.6 pmol/L (6.6 to 17.6). Abdominal ultrasonography revealed a mass up to 10 cm in diameter within the right lateral liver lobe. The mass extended caudally to lie cranial and ventral to the right kidney. Remaining liver lobes demonstrated diffusely increased echogenicity. The right adrenal gland could not be imaged due to impingement of the hepatic mass on the cranial pole of the right kidney. The caudal pole of the left adrenal gland measured 4 mm in transverse section and was considered ultrasonographically normal. No mass could be seen in the pancreas, lymphadenomegaly was not detected and kidneys appeared ultra- sonographically normal. The liver mass was not biopsied.
During the 3 days the dog was in hospital, plasma potassium concentra- tion ranged from 2.2 to 3.0 mmol/L and mild metabolic alkalosis persisted. The dog appeared bright, alert and active, although vigorous exercise was avoided. Appetite was normal but polydipsia and polyuria were noticeable. The dog was discharged with oral potassium supple- mentation and returned 3 days later for attempted stabilisation of plasma potas- sium concentration prior to exploratory laparotomy. Plasma potassium concen- tration at readmission was 2.5 mmol/L and bicarbonate concentration 30.1 mmol/L. Spironolactone was adminis- tered at 2 mg/kg every 12 h, but the next day plasma concentrations of potas- sium and sodium were 2.0 mmol/L and 134 mmol/L, respectively. Intravenous fluid therapy was given as 0.9% NaCl containing 60 mmol/L of KCI at 70 mL/h. After 5 h, plasma potassium concentration remained at 2.0 mmol/L, at which time an additional 30 mmol of KCl were given intravenously over 3 h. This increased plasma potassium concentration to 2.6 mmol/L. On day 8, another 30 mmol bolus of KCl in 3 h, together with 80 mmol/L KCl added to 0.9% NaCl at 70 mL/h, corrected the hypokalaemic alkalosis.
Exploratory laparotomy was performed on the afternoon of day 8 after premedication with acepromazine
and morphine, anaesthetic induction with thiopentone and maintenance with isoflurane in oxygen. Intravenous cephalexin was administered preopera- tively and fentanyl and morphine were administered intravenously during surgery. A large hepatic mass involving the entire right lateral lobe was identi- fied. The right adrenal gland appeared normal, as did the pancreas. The tumour was debulked with difficulty due to its intimate association with caudal vena cava and major hepatic vascular struc- tures. The dog recovered from anaes- thesia, but became pyrexic, tachypnoeic and restless 5 h after surgery and died 4 h later. Necropsy was not permitted.
Histopathological examination revealed a hepatic neuroendocrine carcinoma, with neoplastic cells of pancreatic islet, adrenal or hepatic enterochromaffin cell origin (Figure 1). Diffuse hepatocellular changes resembling glucocorticoid hepatopathy were present. Immuno- histochemical stains specific for ACTH, VIP, gastrin and NSE were negative.
Based on ultrasonic, histopathological and intraoperative findings, a tentative diagnosis of primary hepatic carcinoid was made. The final presumptive diag- nosis was Cushing’s syndrome due to ectopic ACTH secretion by a neuroen-
S
docrine carcinoma, causing hypo- kalaemic myopathy.
Discussion
Hormone secretion by tumours of nonendocrine tissue was first recognised in humans more than 60 years ago.2 The concept that certain hormone-secreting cells, characterised by the ability to take up and decarboxylate precursors of biogenic amines, were part of a ‘diffuse endocrine system’ was proposed in the 1960s.7 These cells, ostensibly of neuroectoderm or neural crest origin, were denoted by the acronym APUD (amine precursor uptake and decarboxy- lation) and tumours arising from these cells were known as APUDomas. Although in many respects now invali- dated,2,8 APUD theory helps clarify the concept that tumours arising from a variety of tissues can produce biologi- cally active substances normally found only in endocrine and nervous tissue. With the advent of electron microscopy and, in more recent times, immunohis- tochemical staining techniques, identifi- cation of secretory granules containing a range of biologically active amines and peptides has been possible in various tumour types.2 Although many tumours express hormone-secreting ability, most are clinically silent.2,9 Tumours most frequently associated with ectopic hormone secretion resulting in clinically recognisable syndromes are small-cell lung carcinomas, carcinoids and pancre- atic islet tumours.2 Although hyper- calcemia secondary to tumour secretion of parathormone-related peptide is well recognised in companion animals, 10 clinically evident ectopic secretion of specific neuropeptides such as ACTH, ADH, VIP, somatostatin, gastrin and glucagon has not as yet been described.1,11
Ectopic ACTH syndrome is relatively common in humans, accounting for 15 to 20% of patients with Cushing’s syndrome. Tumours implicated include small-cell lung carcinomas, thymomas, pancreatic islet tumours, carcinoids, thyroid medullary carcinomas and phaeochromocytomas.2 Primary hepatic carcinoid causing ectopic ACTH syndrome has been reported.12
Muscle stiffness, weakness and pain with polydipsia and polyuria were the only clinical signs in this dog. Polyuria and polydipsia are commonly associated
with hyperadrenocorticism, but the cause remains obscure. Although ADH resistance at a renal tubule level has been proposed as the cause of polyuria, a form of ADH deficiency (central diabetes insipidus) seems more likely.1 As ADH is co-secreted from paraventricular neurons in association with CRF,13 it seems feasible that negative feedback inhibition of CRF secretion due to cortisol excess could, in turn, impair ADH secretion.14 Hypokalaemia in this dog would have exacerbated polyuria, as intracellular potassium depletion impedes the physiological effects of ADH in renal tubule cells by reducing cyclic AMP generation. Hypokalaemia- induced countercurrent dysfunction, secondary to impairment of the Na-K- 2Cl co-transporter in the thick ascending limb of the loop of Henle, may also have contributed to urine- concentrating defects.15 The presence of hyposthenuria in this dog indicates actively dilute urine.
The well-recognised association between potassium depletion and muscular weakness, together with rapid resolution of this sign following potas- sium supplementation, strongly suggests hypokalaemia as the cause of muscle dysfunction. Plasma potassium concen- tration, or, more specifically, the intra- cellular-to-extracellular ratio of potas- sium, plays a key role with sodium in establishing and maintaining cell- membrane resting potential. Perturbation of electrical gradients impede generation of action potentials and delay conduction, resulting in muscle weakness. This is much more likely to occur with acute transcellular shifts of potassium; by contrast, chronic potassium loss creates a concentration gradient which promotes passive diffu- sion of potassium from intracellular to extracellular compartments, diminishing the potassium concentration in both and lessening the alteration in the tran- scellular ratio.3,16 In this setting, chroni- cally hypokalaemic animals can remain clinically unaffected.
Clinically apparent hypokalaemia is not a feature of hyperadrenocorticism in dogs.1 In humans, it is most frequently seen in association with ectopic ACTH secretion and subsequent severe hyper- cortisolism. Cortisol can potentially bind as avidly as aldosterone to miner- alocorticoid receptors on renal collecting
tubule cells, thereby exerting significant mineralocorticoid effects. This does not occur in a normal setting, as cortisol is rapidly inactivated to cortisone by the enzyme 11 beta-hydroxysteroid dehydro- genase within aldosterone target cells. In situations of sustained cortisol hyper- secretion, such as ectopic ACTH syndrome, exhaustion of 11 beta- hydroxysteroid dehydrogenase capability allows cortisol to bind to aldosterone receptors, resulting in substantial renal potassium losses.3,5,6
Cortisol inactivation overload has been implicated in the expression of the more severe mineralocorticoid manifes- tations of ectopic ACTH syndrome, such as hypokalaemic alkalosis and hypertension.5 The latter effects may occur due to cortisol-induced increased pressor responsiveness to endogenous pressors such as catecholamines and angiotensin II, rather than sodium retention and volume expansion.6 Direct measurement of arterial blood pressure in this dog did not reveal hypertension.
Laboratory findings in this case supported the possibility of ectopic ACTH syndrome. Neutrophilia, lymphopenia and eosinopenia suggest cortisol hypersecretion, confirmed by hormone analyses. The normal plasma concentration of ACTH mitigates against pituitary-dependent hypera- drenocorticism (pathological or physio- logical) as the cause of hypercortisolism. However, in human ectopic ACTH syndrome, plasma ACTH concentra- tions are usually high as ectopically produced ACTH is detected by the assay. Low values are occasionally encountered, presumably due to episodic secretion.2 This may have been the case in this dog, or perhaps ectopic ACTH may not have had complete structural homology with pituitary- derived ACTH, and was not detected. An obvious alternative is that hypercor- tisolism was due to primary adrenal hypersecretion, but ultrasonic findings did not support this, and no adrenal mass was seen at laparotomy.
Renal excretion tests confirmed inap- propriately high potassium excretion in a hypokalaemic animal, suggesting mineralocorticoid excess. Primary and secondary hyperaldosteronism were major alternative diagnoses in this dog. Subnormal serum renin concentration ruled out secondary hyperaldosteronism
caused by juxtaglomerular hyperactivity (as in diminished renal perfusion or Bartter’s syndrome3) and low normal aldosterone concentration suggested appropriate suppression of aldosterone secretion by an alternative mechanism of mineralocorticoid excess, rather than primary hypersecretion of aldosterone by an hyperplastic or neoplastic adrenal gland.
Metabolic alkalosis, detected in this dog, commonly accompanies hypo- kalemia, as a result of transcellular hydrogen ion shift. Intracellular potas- sium moves out of cells down a favourable concentration gradient as extracellular potassium concentration declines. Electroneutrality is maintained by a reciprocal shift of hydrogen ion (and sodium) into cells, creating extra- cellular alkalosis.17 Mineralocorticoid- induced stimulation of the H+-ATPase pump throughout the distal nephron helps perpetuate alkalemia.18
Treatment options for this dog included potassium supplementation, use of a potassium-sparing diuretic such as spironolactone, adrenolytic therapy with mitotane, adrenal enzyme inhibi- tion with ketoconazole, and partial hepatectomy. Spironolactone competi- tively inhibits aldosterone at the miner- alocorticoid receptor in principal cells of the renal cortical collecting tubule.19 Administration of this drug to the dog seemed to have no effect on serum potassium concentration, however the medication was only started 24 h prior to laparotomy. Surgical intervention appeared to offer the best chance of long-term palliation or cure for this patient as well as providing tissue for assessment of tumour type. Unfortun- ately, surgery proved more complex than initially suggested by ultrasonic findings and prolonged surgery time with unavoidable prolonged retraction and compression of vena cava may have contributed to the dog’s demise. Carcinoids may also secrete vasoactive substances such as serotonin and bradykinin which can complicate post- operative recovery.20 Pulmonary throm- boembolism may have played a role in the dog’s death, although confirmation by necropsy was not possible.
A tentative histopathological diagnosis of primary hepatic carcinoid was made based on light microscopic and ultra- sonographic findings, as well as intra- operative observation. Carcinoids are
diffuse endocrine system tumours, and are either benign or have a more favourable prognosis than carcinomas. They have typical growth patterns, one of which (glandular or rosette-like)21,22 was present in this dog. Silver affinity, positive immunohistochemical reaction with neurone-specific markers and expression of different peptides and biogenic amines are standard findings.22 Carcinoids are often solitary, grow slowly and, in the case of primary hepatic carcinoids, probably arise from enterochromaffin cells in the intrahep- atic biliary epithelium. As such, they are classified as foregut tumours, as the liver and biliary system evolve embryologi- cally from the liver diverticulum, a proliferative protrusion of foregut endo- derm.23 Foregut carcinoids exhibit an argyrophil, but no argentaffin, reaction with Grimelius silver stain,22 a feature which may be able to further assist in accurate histopathological diagnosis. Primary hepatic carcinoids have been reported in both dog and cat.21,24,25 with a surprisingly high frequency in dogs compared to that in man. Argyrophilia with Grimelius stain is a consistent finding, but in dogs metastatic potential may be higher than in man.21
Failure of immunohistochemical staining to demonstrate presence of neuropeptides or markers for neuroen- docrine cells and their tumours was disappointing. These stains are designed for human tissue and possibly may not cross-react with canine neuropeptides or cell markers. Alternatively, the tumour may not have been biologically active.
In addition to silver staining, electron microscopy may have assisted in further defining this tumour as a foregut carci- noid.23 Antemortem diagnosis of neuro- endocrine tumours and their metastases, including those causing Cushing’s syndrome, has been enhanced in humans by the use of radiolabelled octreotide scintigraphy, with many tumours expressing large numbers of high-affinity somatostatin binding sites.26
In the absence of immunohistochem- ical evidence of ACTH secretion by the tumour in this dog, the diagnosis of ectopic ACTH syndrome can only be presumptive. Criteria for establishing the diagnosis of ectopic hormone secre- tion are documented2 and this dog satis- fies many, but not all, of these. An alter- native cause for the clinical signs, results of preoperative investigations, intra-
operative observations and histopatho- logical findings, is difficult to hypothe- sise.
Acknowledgments
Thanks to colleagues at UVCS for their assistance, to Dr T Rothwell, Department of Veterinary Anatomy and Pathology, The University of Sydney and Dr A Patnaik, The Caspary Institute for Veterinary Research, The Animal Medical Center, New York for review of histopathology and to Dr S Rainer, Department of Anatomical Pathology, St Vincent’s Hospital, Sydney for assistance with immunohistochemistry.
References
1. Feldman EC, Nelson RW. Hyperadrenocorti- cism (Cushing’s syndrome). In: Feldman EC, Nelson RW, editors. Canine and feline endocrinology and reproduction. 2nd edn. Saunders, Philadelphia, 1996:187-261.
2. Frohman LA. Endocrine manifestations of neoplasia. In: Isselbacher KJ, Braunwald E, Wilson JD et al, editors. Harrison’s principles of internal medicine. 13th edn. McGraw-Hill, New York, 1994:1874-1877.
3. Rose BD. Hypokalemia. In: Rose BD, editor. Clinical physiology of acid-base and electrolyte disorders. 4th edn. McGraw-Hill, New York, 1994:776-822.
4. Christy NP, Laragh JH. Pathogenesis of hypokalemic alkalosis in Cushing’s syndrome. New Engl J Med 1961;265:1083-1088.
5. Ulick S, Wang JZ, Blumenfeld JD, Pickering TG. Cortisol inactivation overload: a mechanism of mineralocorticoid hypertension in the ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 1992;74:963-967.
6. Whitworth JA. Adrenocorticotrophin and steroid- induced hypertension in humans. Kidney Int 1992;41:S34-S37.
7. Pearse AGE. The cytochemistry and ultrastruc- ture of polypeptide hormone-producing cells of the APUD series and the embryonic, physiologic and pathologic implications of the concept. J Histochem Cytochem 1969;17:303.
8. Speciale J. Neuroendocrine update - part 1. Compend Contin Educ Pract Vet 1990;12:970-974.
9. Morrison WB. The clinical relevance of APUD cells. Compend Contin Educ Pract Vet 1984;6:884-890.
10. Matus RE, Weir EC. Hypercalcemia of malig- nancy. In: Kirk RW, editor. Current veterinary therapy X. Saunders, Philadelphia, 1989:988-993. 11. Willard MD, Schall WD. APUDomas. In Kirk RW, editor. Current veterinary therapy VIII. Saunders, Philadelphia, 1983:771-773.
12. Johnson FD. Ectopic ACTH syndrome in APUD tumors. Oncology 1982;39:358-361.
13. Wolfson B, Manning RW, Davis LG et al. Co- localisation of corticotropin releasing factor and vasopressin in RNA in neurons after adrenalec- tomy. Nature 1985;315:59.
14. Raff H. Glucocorticoid inhibition of neurophy- pophyseal vasopressin secretion. Am J Physiol 1987;252:R635.
15. Rose BD. Hyperosmolal states - hyperna- traemia. In: Rose BD, editor. Clinical physiology of acid-base and electrolyte disorders. 4th edn. McGraw-Hill, New York, 1994:695-736.
16. Rose BD. Introduction to disorders of potas- sium balance. In: Rose BD, editor. Clinical physi- ology of acid-base and electrolyte disorders. 4th edn. McGraw-Hill, New York, 1994:763-775.
17. Rose BD. Metabolic alkalosis. In: Rose BD, editor. Clinical physiology of acid-base and elec- trolyte disorders. 4th edn. McGraw-Hill, New York, 1994:515-539.
18. Rose BD. Regulation of acid-base balance. In: Rose BD, editor. Clinical physiology of acid-base and electrolyte disorders. 4th edn. McGraw-Hill, New York, 1994:300-345.
19. Rose BD. Clinical use of diuretics. In: Rose
BD, editor. Clinical physiology of acid-base and electrolyte disorders. 4th edn. McGraw-Hill, New York, 1994:418-446.
20. Mason R. Anaesthesia in carcinoid syndrome. Anaesthesia 1979;34:391.
21. Patnaik AK, Lieberman PH, Hurvitz AI, Johnson GF. Canine hepatic carcinoids. Vet Pathol 1981;18:445-453.
22. Creutzfeldt W. Historical background and natural history of carcinoids. Digestion 1994;55(suppl 3):3-10.
23. Sioutos MD, Virta S, Kessimian N. Primary hepatic carcinoid tumor. An electron microscopic
and immunohistochemical study. Am J Clin Pathol 1991;95:172-175.
24. Patnaik AK. A morphologic and immunocyto- chemical study of hepatic neoplasms in cats. Vet Pathol 1992;29:405-415.
25. Alexander RW, Kock RA. Primary hepatic carcinoid (APUD cell carcinoma) in the cat. J Small Anim Pract 1982;23:767-771.
26. Krenning EP, Kwekkeboom DJ, Oei HY et al. Somatostatin receptor scintigraphy in carcinoids, gastrinomas and Cushing’s syndrome. Digestion 1994;55(suppl 3):54-59.
(Accepted for publication 19 October 1998)
Surgical removal of an ependymoma from the third ventricle of a cat
DJ SIMPSONª, GB HUNTª, PLC TISDALLª, M GOVENDIRª, S ZAKIª, MP FRANCEb and R MALIKª Faculty of Veterinary Science, The University of Sydney, New South Wales 2006
A 10-year-old spayed domestic shorthaired cat was presented for behavioural changes, signs suggestive of visual deficits and aimless circling. Neuro-ophthalmological examination suggested the cat had central blindness. CT scans following administration of iohexol demonstrated a contrast-enhancing mass in the vicinity of the third ventricle result- ing in obstructive hydrocephalus. Following rostral tentorial craniotomy and incision through the cerebral cortex, the third ventricle was approached via the dilated left lateral ventricle. An ependymoma was seen through a dorsocau- dolateral incision into the third ventricle, and removed by gentle manipulation and suction. The cat recovered unre- markably, regaining normal vision and behaviour.
Aust Vet J 1999;77:645-648
Key words: Cat, ependymoma, computerised tomography, neurosurgery.
| CNS | Central nervous system | IV | Intravenously |
| CSF | Cerebrospinal fluid | PO | Orally |
| CT IM | Computed tomography Intramuscularly | SC | Subcutaneously |
T The third ventricle is a portion of the ventricular system of the brain through which CSF flows. It lies in the median plane encircling the interthalamic adhesion. The third ventricle communicates with each lateral ventricle in the cerebral hemispheres by way of interventricular foramina and opens caudally into the mesencephalic aqueduct. CSF produced by choroid plexuses of the lateral and third ventri- cles normally flows through the aque- duct of the midbrain to the fourth ventricle. Subsequently, CSF passes through either the lateral recesses of the fourth ventricle to the subarachnoid space or to the central canal of the spinal
cord.1
Space-occupying lesions of the third ventricle may block normal flow of CSF from lateral and third ventricles into the aqueduct of the midbrain leading to secondary hypertensive hydrocephalus. Clinical signs of hydrocephalus are refer- able to derangements of cerebral cortical function and include lethargy and depression, compulsive circling, head pressing, changes in behaviour and bilat- eral visual deficits with normal pupillary light responses.1
Lesions in the third ventricle might be expected to have a poor prognosis irre- spective of their aetiology because of this region’s critical position in relation to CSF dynamics and relative inaccessi- bility to surgical intervention. This article reports on a cat with an ependy-
moma of the third ventricle that was successfully treated using a relatively simple neurosurgical approach and instruments available in most veterinary referral centres.
Case report
History, physical findings and diagnostic investigation
A 10-year-old spayed domestic short- haired cat (3.9 kg) was presented because it had been walking around in a disorientated state for 2 weeks. The cat had defecated inappropriately outside the litter box on several occasions and ‘got lost’ in the corners of rooms. The cat had reduced appetite and was reported by the owner to have abnormal behaviour and attitude. General physical examination was unremarkable, except