Complete surgical removal of a very enlarged pituitary corticotroph adenoma in a dog

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CASE REPORTS

Complete Surgical Removal of a Very Enlarged Pituitary Corticotroph Adenoma in a Dog Federico Fracassi, PhD, DVM, DECVIM-CA, Luciana Mandrioli, PhD, DVM, Dardan Shehdula, PhD, DVM, Alessia Diana, PhD, DVM, Guy C.M. Grinwis, PhD, DVM, Bjo¨rn P. Meij, PhD, DVM, DECVS

ABSTRACT A 13 yr old castrated male vizsla was referred to the authors’ institute because of polyuria, polydipsia, polyphagia, and weight loss. Pituitary-dependent hypercortisolism (PDH) was diagnosed by hormone testing and adrenal and pituitary imaging. Computed tomography (CT) revealed a pituitary mass measuring 21 mm in width. Medical therapy was initiated with trilostane. Despite adequate control of the hypercortisolemia, the polyuria and polydipsia persisted and the dog developed neurologic signs due to the pituitary mass effect. Pituitary transsphenoidal debulking surgery was performed and immunocytochemistry confirmed a corticotroph adenoma. The dog survived for 13 mo after surgery. Postmortem examination revealed an empty fossa without pituitary remnants and the presence of a malignant pheochromocytoma in the right adrenal gland. This case report demonstrates, for the first time, that a large pituitary adenoma in the dog may be treated successfully by pituitary surgery. (J Am Anim Hosp Assoc 2014; 50:---–---. DOI 10.5326/JAAHA-MS-5987)

Introduction

tumor size.3,4 In very enlarged pituitary adenomas, with a diame-

Pituitary adenomas in dogs can be classified, based on their size,

ter . 15–20 mm and concurrent development of neurologic

as either nonenlarged pituitaries containing microadenomas

signs, the dog’s owner is informed that the aim of pituitary sur-

1

or enlarged pituitaries, which are also called macroadenomas.

gery is a debulking pituitary surgery. This debulking surgery is

In the human literature, pituitary macroadenomas refer to ade-

considered to be more palliative, removing as much pituitary

nomas with a diameter . 10 mm but this leads to confusion with

tumor tissue as possible within the safe limits of this surgery and

veterinary literature because canine pituitary adenomas may be

resulting in reduction of the mass effect. In those cases, surgery is

enlarged, but can still be , 10 mm. Therefore, the terminology

usually not curative for hypercortisolism and medical treatment

enlarged and nonenlarged pituitary adenomas, as previously

remains necessary to manage the disease.

described, is more appropriate in dogs than the terminology

This case report describes the successful surgical treatment

micro- and macroadenomas, as has been advocated in large

of a dog with hypercortisolism and neurologic abnormalities due

case series.2–4 In humans, giant adenomas comprise a clinical/

to a pituitary corticotroph adenoma. The adenoma measured

therapeutic subset of pituitary adenomas that pose a surgical

. 20 mm.

challenge.5 Giant pituitary adenomas in humans are defined as tumors with a diameter . 50 mm.5

Case Report

Transsphenoidal hypophysectomy is an effective therapy for

A 13 yr old castrated male vizsla weighing 21 kg was presented

pituitary corticotroph adenomas in dogs; however, the survival

to the authors with a 2 mo history of polyuria, polydipsia, poly-

and disease-free fractions after surgery decrease with increasing

phagia, kyphosis, and weight loss. On physical examination, the

From the Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy (F.F., L.M., D.S., A.D.); and Department of Pathobiology, Faculty of Veterinary Medicine (G.G.) and Department of Clinical Sciences of Companion Animals (B.M.), Faculty of Veterinary Medicine, Utrecht University, The Netherlands.

ACTH adrenocorticotropic hormone; CT computed tomography; HU Hounsfield units; P/B pituitary height/brain area ratio; PDH pituitary-dependent hypercortisolism; PO per os; UCCR urinary corticoid/creatinine ratio

Correspondence: [email protected] (F.F.)

ª 2014 by American Animal Hospital Association

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dog was thin and cardiac auscultation revealed a soft systolic murmur (grade 2/6) over the mitral area. Hematology showed lymphopenia and eosinopenia, and serum biochemical analysis revealed elevated concentrations of alkaline phosphatase (27.49 mkat/L; reference range, 0.70–3.01 mkat/L), alanine aminotransferase (1.65 mkat/; reference range, 0.33–0.92 mkat/L), and g-glutamyl transferase (0.44 mkat/L; reference range, 0–0.1 mkat/L). Urinalysis showed a low specific gravity (1.008). Together, those findings supported a preliminary diagnosis of hypercortisolism. The diagnosis was confirmed with the adrenocorticotropic hormone (ACTH) stimulation test (using 0.25 mg tetracosactide esacetatea IV) and the low-dose dexamethasoneb suppression test (0.01 mg/kg IV). The basal and postACTH plasma cortisol concentrations were 195 nmol/L (reference range, 27–132 nmol/L) and 872 nmol/L (reference range, 165– 500 nmol/L), respectively. Both were consistent with hypercortisolism. There was no adequate suppression of plasma cortisol after a low dose of dexamethasone. Plasma cortisol concentration at 0 hr was 199 nmol/L (reference range, 27–132 nmol/L), 135 nmol/L at 4 hr (reference range, , 41 nmol/L), and 132 nmol/L at 8 hr (reference range, , 41 nmol/L). Abdominal ultrasonography revealed bilateral adrenal gland enlargement. The maximum

FIGURE 1 Transverse contrast-enhanced computed tomography

(CT) scan of the skull of a 13 yr old castrated male vizsla with pituitary-dependent hypercortisolism. Note the enlarged pituitary adenoma (*) measuring 21.4 mm in width.

diameter of the caudal pole of the left adrenal gland was 11 mm and that of the right was 10 mm (reference range for both ad-

and 18.3 mm in length. The pituitary height/brain area ratio

renal glands, , 7.5 mm).

(P/B) was .98 (reference range for nonenlarged pituitaries,

Treatment with trilostanec (2.9 mg/kg per os [PO] q 24 hr)

, 0.31).2 The tumor expanded rostrally toward the tuberculum

was started. After 15 days, the ACTH stimulation test was re-

sellae, caudally over the dorsum sellae, and dorsally beyond the

peated 2 hr after trilostane administration. Plasma cortisol con-

sella turcica and into the third ventricle. The ovoid mass had

centration was 52 nmol/L preACTH and 105 nmol/L postACTH.

distinct margins that separated it from the surrounding brain

Those results were consistent with adequate control of the

tissue. The owner was informed about the therapeutic options,

hypercortisolemic state, and the dosage of trilostane was not

such as medical treatment, irradiation, and palliative treatment.

changed. At that time, the dog continued to have polyuria and

Euthanasia was also considered because a 13 yr old vizsla is a

polydipsia. After 2 mo, the dog developed neurologic signs.

geriatric patient and at its normal life expectancy. The owner

Neurologic examination showed an abnormal mental status with

elected surgical treatment.

marked disorientation, a compulsive gait, and head pressing. The

Transsphenoidal hypophysectomy was performed according

posture was normal. The gait was abnormal with pacing and

to a microsurgical technique described previously.6,7 The mass

circling. Postural reaction deficits were detected bilaterally fol-

was removed in multiple large fragments (Figure 2), and hy-

lowing wheel barrowing, hopping, and tactile placing tests. Spinal

pophysectomy was considered complete when the infundibular

reflexes were normal, and cranial nerve examination was normal.

recess at the ventral aspect of the hypothalamus was visualized.

Based on the neurologic examination, the dog’s signs were con-

Plasma ACTH concentrations within the 2 hr period before sur-

sistent with a lesion involving the cerebrum/thalamus.

gery were 9.24 pmol/L and 8.80 pmol/L. Those levels decreased

Contrast-enhanced computed tomography (CT) with IV

to 3.30 pmol/L, 2.42 pmol/L, 2.20 pmol/L, 2.42 pmol/L, and

administration of contrast mediumd (640 mg/kg) produced an

2.20 pmol/L at 1 hr, 2 hr, 3 hr, 4, hr, and 5 hr after surgery, re-

inhomogeneous enhancement of a pituitary mass (precontrast

spectively. Histopathology and immunohistochemistry of the

density was 55 Hounsfield units [HU] 6 5.58 HU and post-

surgical specimens revealed a pituitary corticotroph adenoma.

contrast density was 118.2 HU 6 5.46 HU) as shown in Figure 1.

Hematoxylin and eosin staining of the neoplastic cells revealed

The pituitary mass measured 15 mm in height, 21.4 mm in width,

a basophilic granular cytoplasm with round to ovoid nuclei with

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Surgical Removal of a Pituitary Adenoma

(2.5 mg/kg PO q 24 hr). After discharge, medication consisted of desmopressin (1 drop [5 mg] q 8 hr in the conjunctival sac), cortisone acetate j (0.3 mg q 12 hr PO for life), and L-thyroxinek (15 mg/kg q 12 hr PO for life). Seven days after surgery, neurologic signs, except for the postural reaction deficits, disappeared. The dog’s water consumption and appetite normalized, and in the following mo, the body weight increased and activity improved. Remission of hypercortisolism was monitored 4 wk, 6 mo, and 1 yr after surgery by measuring basal urinary corticoid/creatinine ratio (UCCR) in two urine samples collected at home (i.e., stressfree). The UCCRs after hypophysectomy were 1 3 1026 at 4 wk, 0.8 3 1026 at 6 mo, and 1 3 1026 at 1 yr (reference range, , 8.3 3 1026), consistent with a complete and persistent remission of hypercortisolism.9 Contrast-enhanced CT of the hypophyseal fossa was repeated 3 mo after surgery, and no residual pituitary tissue was evident (Figure 3). Eight mo after surgery, the dog suddenly developed a severe head tilt to the left and a tendency to fall to the left side. Neurologic examination showed a normal mental status, vestibular ataxia, and mild bilateral postural deficits following tactile placing tests. Mild bilateral postural reaction deficits in the posterior limbs had been FIGURE 2 Intraoperative frontal view during transsphenoidal

detected in several previous physical examinations of the dog. Spinal reflexes were normal, and a spontaneous horizontal nys-

pituitary debulking surgery. Pituitary adenoma fragments are

tagmus with the fast phase to the right side was present. Positional

extracted with a grasping forceps through the dural incision (top).

ventrolateral strabismus of the left eye was detected, and a menace

Top is rostral, the surgeon’s view is frontal, perpendicular to the skull base. prominent nucleoli and rare mitotic figures. Immunohistochemistry of the adenoma using a previously described routine staining protocol, with the addition of appropriate canine positive and negative controls, showed strong staining for ACTH, weak staining for a-melanocyte-stimulating hormone, and no staining for growth hormone.8 Immediately following debulking of the tumor, treatment was started with 0.01% desmopressine 1 drop (z 5 mg) q 8 hr in the conjunctival sac, and hydrocortisonef 1 mg/kg q 8 hr IV was administered 5 hr after surgery. The dog was kept sedated for 24 hr with continuous IV administration of propofolg. The dog was subsequently awakened by slowly decreasing then stopping the propofol administration. Recovery was complicated by cough and tachypnea. Auscultation of the lungs revealed harsh sounds, and thoracic radiographs showed a focal left-sided alveolar infiltrate suggestive of aspiration pneumonia. The dog was empirically and successfully treated with amoxicillin trihydrate/clavulanate

FIGURE 3

potassiumh (12.5 mg/kg PO q 12 hr for 2 wk) and enrofloxacini

CT showed no pituitary remnants.

Three mo after hypophysectomy, contrast-enhanced

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response was normal. Based on the neurologic examination, the

abundant fibrovascular stroma (Figure 4C). Neoplastic cells var-

dog’s signs were most consistent with a peripheral vestibular

ied from round to polygonal, containing ample slightly granular

disease. CT of the head was unchanged from the previous

eosinophilic cytoplasm with a round to oval nucleus that was

postoperative study (Figure 3). The origin of the vestibular

often eccentrically placed. Immunohistochemistry was per-

dysfunction was not identified, and geriatric vestibular disease

formed using a streptavidin/biotin complex method and dia-

was considered the most likely diagnosis. After a few days, the

minobenzidine as the chromogen. The panel included the

clinical condition improved markedly, and after 1 mo the only

primary antibodies (antichromogranin Al, synaptophysinm, neuron-

abnormality was a mild head tilt.

specific enolasen, S100 proteino, keratin AE1/AE3p) as described

Thirteen mo after surgery, the dog developed weakness, in-

in another case.10 The cytoplasm of neoplastic adrenal cells

appetence, then anorexia with weight loss. The dog showed acute

displayed a strong, diffuse immunoreactivity to chromogranin A

severe respiratory distress and collapsed and died before arriving

and neuron-specific enolase (Figure 4D), confirming the his-

at the clinic.

tologic diagnosis of pheochromocytoma.

A complete postmortem examination was performed. Macroscopic examination of the skull revealed no evidence of pituitary

Discussion

tissue remnants in either the hypophyseal fossa at the surgical site

Clinical signs exhibited by dogs with very enlarged pituitary tumors

or at the base of the brain at the opening to the third ventricle

may reflect endocrine and space occupying effects. The endocrine

(Figure 4A). At the microscopic level, no pituitary tumor rem-

manifestations are those typical of Cushing’s syndrome. The first

nants could be detected in either location. Macroscopic exami-

neurologic signs are almost always subtle. Common initial signs

nation of the adrenal glands revealed a 3 cm 3 2 cm 3 2 cm right

include dullness, listlessness, and decreased appetite. Those signs

adrenal gland and a focally distended wall of the caudal vena cava

may progress to anorexia, restlessness, loss of interest in normal

(Figure 4B). No abnormalities were found in other endocrine

activities, delayed response to stimuli, and episodes of disori-

tissues. Histologic examination of the right adrenal gland showed

entation. Signs exhibited by dogs with very enlarged pituitary

a solid neoplasm arranged in lobules that were separated by

tumors include obtundation, stupor, ataxia, tetraparesis, and

FIGURE 4

A: Postmortem sagittal midline view of the brain. There are no pituitary tissue remnants ventral to the hypothalamic region

(arrow). B: The right adrenal gland is uniformly enlarged and bosselated (arrow). A concurrent marked distension of caudal vena cava is evident (arrowhead). C: The right adrenal gland has a pheochromocytoma. The neoplastic tissue is arranged in lobules separated by abundant fibrovascular stroma. Hematoxylin and eosin staining, bar ¼ 50mm. D: Neoplastic cells of the pheochromocytoma display a strong, diffuse cytoplasmic immunoreactivity to neuron-specific enolase. Diaminobenzidine chromogen and hematoxylin counterstaining, bar ¼ 50mm.

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Surgical Removal of a Pituitary Adenoma

aimless pacing.11 Less frequently observed problems include

pituitary tumor regrowth.4 In the case reported herein, complete

nystagmus, circling, head pressing, behavior changes, blindness,

tumor removal was monitored with postoperative UCCRs and

seizures, and coma.

11

complemented with periodic CT scans of the pituitary region and

The most common treatment in dogs with pituitary-

ultimately confirmed by an empty fossa on postmortem exami-

dependent hypercortisolism (PDH) has been the medical ther-

nation. This case shows, for the first time, that even in the case of

apy with either mitotane or with a competitive inhibitor of adrenal

a pituitary adenoma . 20 mm in width, complete tumor removal

3b-hydroxysteroid dehydrogenase (trilostane).

11,12

Although ef-

and remission of hypercortisolism are possible.

fective, those treatments are not directed at the elimination of the

In humans, giant pituitary tumors are defined by some

primary pituitary lesion. Early diagnosis, pituitary imaging, and

authors based on extension on the local structures.21 A recent study

treatment at the pituitary level should be the hallmarks of a di-

in dogs demonstrated that pituitary masses with a vertical height

agnostic and treatment protocol for canine PDH. Surgery,

. 19 mm were more likely to be invasive adenomas; however, in

medication, and radiotherapy are used to treat various types of

the case reported herein, the authors did not detect any evidence

2

pituitary adenomas in humans.

13

Selective pituitary adenomec-

of invasive behavior of the adenoma.22

tomy is still considered the first line of treatment of Cushing’s

There are no detailed studies on outcome after trans-

disease in humans. Radiotherapy is also an option for treatment

sphenoidal hypophysectomy in dogs with pituitary adenomas

of pituitary corticotroph adenomas in humans and companion

with a diameter . 20 mm. In a large study including 181 dogs

animals.

14–19

It can be used as either a secondary treatment after

that underwent hypophysectomy, there was only 1 dog with

unsuccessful pituitary surgery or as a primary treatment in

a pituitary tumor with a P/B of 1.1 and a diameter of 18 mm that

patients when surgery is contraindicated (i.e., invasive macro-

was successfully removed, which was comparable to the case

adenoma) or in the presence of a more aggressive malignant tu-

reported here.4 However, in the latter case, no detailed follow-up

mor (adenocarcinoma).15,18,20 In one study, 24 dogs with enlarged

information was available except that there was remission of

pituitary tumors (diameter $ 10 mm) were irradiated and had

disease. In two recent case series of dogs with PDH treated with

mean and median overall survival times of 15.7 mo 6 2.9 mo and

transsphenoidal hypophysectomy, the dimensions of the pitui-

11.7 mo 6 5.9 mo, respectively. The authors of that study con-

tary adenomas were not reported; however, the biggest pituitary

cluded that radiation therapy is effective in dogs with mild to

adenomas had a P/B of .69 and .70, respectively.23,24

moderate neurologic signs, but did not improve survival in dogs 17

Pheochromocytoma is a tumor of the chromaffin cells of the

In a more recent study, 19 dogs

adrenal medulla or sympathetic paraganglia.1 A variety of vague

with pituitary masses (median height, 13 mm; range, 7–21 mm)

and nonspecific clinical signs attributed to excessive secretion of

with severe neurologic signs.

were irradiated. Mean survival time was 46.8 mo (95% confidence

catecholamines has been reported in dogs with pheochromocy-

interval, 35.1–58.4 mo) and the tumor size was identified as

toma, and antemortem diagnosis is difficult.25 Similarly, in the

a negative prognostic factor for survival.19 In dogs with PDH,

case reported herein, the pheochromocytoma was only discovered

pituitary irradiation was more effective in delaying tumor growth

at necropsy.

15,17,18

than in controlling ACTH secretion.

Excessive panting, acute respiratory distress, weakness, and

An extended follow-up of 181 dogs treated with PDH

clinical deterioration are commonly reported clinical signs of

over a 12 yr period proved the effectiveness of transsphenoidal

pheochromocytoma.25 Those signs were present in this dog and

hypophysectomy for canine PDH.

3,4,7

In one of these studies,

prognostic factors for the outcome after transsphenoidal hy-

could be explained by the presence of a functional pheochromocytoma.

pophysectomy were determined.4 The results of that study

Previous reports of the coexistence of PDH and pheochro-

showed that, among others factors, pituitary size negatively af-

mocytoma suggest that the combination is not rare in dogs and,

fects survival and remission of disease after hypophysectomy

therefore, should not be regarded as an incidental finding.25–28

in dogs with PDH. In the present case, remission of hyper-

In humans, the occurrence of those tumors in the same pa-

cortisolism was confirmed by repeated measurements of UCCRs

tients has been speculated to be related to aberrant neural crest

and postoperative CT scanning. That finding was surprising be-

development.29

cause the primary aim of surgery was debulking of the pituitary mass to alleviate the neurologic signs. Postoperative UCCRs can

Conclusion

be used to monitor surgical outcome and recurrence of hyper-

This case report demonstrates, for the first time, that an enlarged

cortisolism in the case of Cushing’s disease and, indirectly,

pituitary adenoma . 20 mm, causing neurologic deficits due to

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the mass effect, may be treated successfully by transsphenoidal hypophysectomy. FOOTNOTES a Synacthen; Novartis, Origgio, Italy b Dexadreson; Intervet, Peschiera Borromeo, Italy c Modrenal; Wanskerne, St. Austell, England d Visipaque320; Amersham Health AS, Cork, Ireland e Minrin; Ferring, Hoofddorp, The Netherlands f Solu-Cortef; Upjohn, Ede, The Netherlands g Propofol-Lipuro; Braun Medical Supplies, Melsungen, Germany h Synulox; Pfizer Animal Health, Capelle a/d IJssel, The Netherlands i Baytril; Bayer, Kiel, Germany j Cortisoni acetate; Genfarmam, Maarssen, The Netherlands k L-thyroxine; Aesculaap; Boxtel, The Netherlands l Chromogranin A; Dako Cytomation, Glostrup, Denmark m Synaptophysin; Dako Cytomation, Glostrup, Denmark n Neuron-specific enolase; Dako Cytomation, Glostrup, Denmark o S100; Dako Cytomation, Glostrup, Denmark p Cytokeratin clones AE1/AE3; Dako Cytomation, Glostrup, Denmark REFERENCES 1. Kiupel M, Capen C, Miller M, et al. Histological classification of tumors of the endocrine system of domestic animals. World Health Organization international histological classification of tumors of domestic animals, second series, vol. 12. Gurnee (IL):Charles Louis Davis DVM Foundation; 2008:17. 2. Kooistra HS, Voorhout G, Mol JA, et al. Correlation between impairment of glucocorticoid feedback and the size of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism. J Endocrinol 1997;152(3):387–94. 3. Hanson JM, van ’t HM, Voorhout G, et al. Efficacy of transsphenoidal hypophysectomy in treatment of dogs with pituitarydependent hyperadrenocorticism. J Vet Intern Med 2005;19(5): 687–94. 4. Hanson JM, Teske E, Voorhout G, et al. Prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism. J Neurosurg 2007;107 (4):830–40. 5. Chacko G, Chacko AG, Lombardero M, et al. Clinicopathologic correlates of giant pituitary adenomas. J Clin Neurosci 2009;16(5): 660–5. 6. Meij BP, Voorhout G, Van den Ingh TSGAM, et al. Transsphenoidal hypophysectomy in beagle dogs: evaluation of a microsurgical technique. Vet Surg 1997;26(4):295–309. 7. Meij BP, Voorhout G, van den Ingh TSGAM, et al. Results of transsphenoidal hypophysectomy in 52 dogs with pituitarydependent hyperadrenocorticism. Vet Surg 1998;27(3):246–61. 8. Fracassi F, Mandrioli L, Diana A, et al. Pituitary macroadenoma in a cat with diabetes mellitus, hypercortisolism and neurological signs. J Vet Med A Physiol Pathol Clin Med 2007;54(7): 359–63. 9. van Vonderen IK, Kooistra HS, Rijnberk A. Influence of veterinary care on the urinary corticoid:creatinine ratio in dogs. J Vet Intern Med 1998;12(6):431–5.

6

JAAHA |

50:3 May/Jun 2014

10. Mandrioli L, Biserni R, Panarese S, et al. Immunohistochemical profiling and telomerase activity of a canine medulloblastoma. Vet Pathol 2011;48(4):814–6. 11. Canine and feline endocrinology and reproduction. 3rd ed. Feldman EC, Nelson RW, eds. Philadelphia (PA): WB Saunders; 2004. 12. Ruckstuhl NS, Nett CS, Reusch CE. Results of clinical examinations, laboratory tests, and ultrasonography in dogs with pituitarydependent hyperadrenocorticism treated with trilostane. Am J Vet Res 2002;63(4):506–12. 13. Chanson P, Salenave S. Diagnosis and treatment of pituitary adenomas. Minerva Endocrinol 2004;29(4):241–75. 14. Ghostine S, Ghostine MS, Johnson WD. Radiation therapy in the treatment of pituitary tumors. Neurosurg Focus 2008;24(5):E8. 15. Dow SW, LeCouteur RA, Rosychuk RA, et al. Response of dogs with functional pituitary macroadenomas and macrocarcinomas to radiation. J Small Anim Pract 1990;31:287–94. 16. Mauldin GN, Burk RL. The use of diagnostic computerized tomography and radiation therapy in canine and feline hyperadrenocorticism. Probl Vet Med 1990;2(4):557–64. 17. Théon AP, Feldman EC. Megavoltage irradiation of pituitary macrotumors in dogs with neurologic signs. J Am Vet Med Assoc 1998; 213(2):225–31. 18. de Fornel P, Delisle F, Devauchelle P, et al. Effects of radiotherapy on pituitary corticotroph macrotumors in dogs: a retrospective study of 12 cases. Can Vet J 2007;48(5):481–6. 19. Kent MS, Bommarito D, Feldman E, et al. Survival, neurologic response, and prognostic factors in dogs with pituitary masses treated with radiation therapy and untreated dogs. J Vet Intern Med 2007; 21(5):1027–33. 20. Mahmoud-Ahmed AS, Suh JH. Radiation therapy for Cushing’s disease: a review. Pituitary 2002;5(3):175–80. 21. Goel A, Nadkarni T, Muzumdar D, et al. Giant pituitary tumors: a study based on surgical treatment of 118 cases. Surg Neurol 2004; 61(5):436–45 [discussion: 445–6]. 22. Pollard RE, Reilly CM, Uerling MR, et al. Cross-sectional imaging characteristics of pituitary adenomas, invasive adenomas and adenocarcinomas in dogs: 33 cases (1988–2006). J Vet Intern Med 2010; 24(1):160–5. 23. Hara Y, Teshima T, Taoda T, et al. Efficacy of transsphenoidal surgery on endocrinological status and serum chemistry parameters in dogs with Cushing’s disease. J Vet Med Sci 2010;72(4):397–404. 24. Teshima T, Hara Y, Taoda T, et al. Central diabetes insipidus after transsphenoidal surgery in dogs with Cushing’s disease. J Vet Med Sci 2011;73(1):33–9. 25. Barthez PY, Marks SL, Woo J, et al. Pheochromocytoma in dogs: 61 cases (1984–1995). J Vet Intern Med 1997;11(5):272–8. 26. von Dehn BJ, Nelson RW, Feldman EC, et al. Pheochromocytoma and hyperadrenocorticism in dogs: six cases (1982–1992). J Am Vet Med Assoc 1995;207(3):322–4. 27. van Sluijs FJ, Sjollema BE, Voorhout G, et al. Results of adrenalectomy in 36 dogs with hyperadrenocorticism caused by adrenocortical tumour. Vet Q 1995;17(3):113–6. 28. Thuróczy J, van Sluijs FJ, Kooistra HS, et al. Multiple endocrine neoplasias in a dog: corticotrophic tumour, bilateral adrenocortical tumours, and pheochromocytoma. Vet Q 1998;20(2):56–61. 29. Breckenridge SM, Hamrahian AH, Faiman C, et al. Coexistence of a pituitary macroadenoma and pheochromocytoma—a case report and review of the literature. Pituitary 2003;6(4):221–5.

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