BACKGROUND:The high-frequency ultrasonographic appearance of skin of dogs with atopic dermatitis (cAD) has not been described.OBJECTIVES:To compare high-frequency ultrasonographic findings among lesional, macroscopically nonlesional skin of dogs with cAD, and the macroscopically nonlesional skin of healthy dogs. Additionally, to determine whether there is any correlation between the ultrasonographic findings in lesional skin and local Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) or its domains (erythema, lichenification, excoriations/alopecia). As a secondary aim, six cAD dogs were re-evaluated after management intervention.ANIMALS:Twenty dogs with cAD (six were re-examined after treatment) and six healthy dogs.MATERIALS AND METHODS:In all dogs, ultrasonographic examination was performed on the same 10 skin sites, using a 50 MHz transducer. Wrinkling of skin surface, presence/width of subepidermal low echogenic band, hypoechogenicity of dermis and thickness of the skin were evaluated and scored/measured blindly.RESULTS:Dermal hypoechogenicity was more common and severe in lesional compared to macroscopically nonlesional skin of dogs with cAD. In lesional skin, presence/severity of wrinkling of skin surface and of dermal hypoechogenicity were positively correlated with presence/severity of lichenification, while severity of dermal hypoechogenicity was positively correlated with local CADESI-04. A positive correlation between the change in skin thickness and the change in the severity of erythema during treatment was noted.CONCLUSIONS AND CLINICAL RELEVANCE:High-frequency ultrasound biomicroscopy may be useful for the evaluation of skin of dogs with cAD and for evaluating the progression of skin lesions during treatment.

BACKGROUND There is a lack of information regarding magnetic resonance imaging (MRI) features of polyostotic vertebral lesions in dogs. The aim of this retrospective study was to identify and differenciate low-field MRI features of aggressive versus benign multifocal vertebral diseases in dogs. METHODS MRI examinations from 49 dogs with polyostotic vertebral lesions were reviewed. Images were evaluated for vertebral intensity changes, expansile lesions, new bone formation, cortical bone interruption, paravertebral musculature changes, lymphadenomegaly, spinal cord compression and spinal cord signal changes. RESULTS Twenty-nine dogs with non-aggressive bone lesions and 20 dogs with aggressive vertebral lesions were included. Non-aggressive lesions had variable T2-weighted fast spin-echo (T2W) signal intensity and the majority displayed low signal intensity on short tau inversion recovery (STIR). Aggressive lesions predominantly had high T2W and STIR signal intensity, with variable signal intensity on T1-weighted spin-echo and contrast enhancement. Aggressive lesions were associated with spinal pain (p < 0.01), new bone formation (p = 0.02), spinal cord compression (p < 0.01) and lymphadenomegaly (p < 0.01). Cortical interruption (p < 0.01) and paravertebral musculature changes (p < 0.01) were the strongest indicative imaging features for aggressive lesions. CONCLUSION Spinal pain, spinal cord compression, new bone formation, lymphadenomegaly and especially cortical interruption and paravertebral musculature signal intensity changes were the best discriminators for differentiating malignant from benign vertebral lesions.

There is no available measuring protocol and reference range for the normal canine trigeminal nerve. This can be problematic in cases of suspected bilateral trigeminal neuropathy since contralateral nerves cannot be a usefully compared. Trigeminal nerves and brain measurements were retrospectively assessed via multiplanar reconstruction (MPR) of 3DT1 post-contrast MR sequences from 137 dogs with no signs or diagnosis of trigeminal disease. Direct measurements of vertical brain height (BH), trigeminal nerves transverse height (TTH) and trigeminal nerves width in dorsal reconstruction (TDW) were made in a plane immediately caudal to the foramen ovale and used to derive trigeminal nerve-to-brain (NB) ratios, including height-to-brain ratio (HBR) and width-to-brain ratio (WBR). HBR (0.09, IQR = 0.08-0.09) and WBR (0.10, IQR = 0.09-0.11) maintained more consistent values across the study population compared to direct measurements of TTH (3.72, IQR = 3.42-4.07) and TDW (4.35 +/- 0.63). Calculated normal reference intervals for HBR and WBR were 0.07-0.11 and 0.08-0.13, respectively and the largest NB ratios recorded in normal dogs were 0.13 and 0.14 for HBR and WBR, respectively. All measurements varied proportionally with weight, including HBR (r = 0.41, p < 0.0001) and small dogs had a significantly smaller HBRs compared to medium (p = 0.0294), large (p < 0.0049) and giant dogs (p < 0.0044). Median HBR was the same across skull types (0.09), however post-hoc analysis detected significantly smaller HBRs in brachycephalic compared to mesaticephalic dogs (p = 0.0494). In conclusion, trigeminal NB ratios may allow for accurate, objective assessment of the canine trigeminal nerves on MRI but further quantification of the effects of weight and skull type on suggested reference intervals is needed.

A 3‐year‐old male neutered domestic shorthair cat was referred with 1‐month history of three generalised tonic‐clonic epileptic seizures and left‐sided thoracic limb knuckling. Nine months previously, the cat was bitten on the right upper palpebral region without manifesting neurological signs. On admission, physical and neurological examination revealed left‐sided postural reaction deficits and absent menace response. Thus, a right‐forebrain neurolocalisation was reached. Haematology, biochemistry, bile acid stimulation test, infectious diseases serology and cerebrospinal fluid analysis were unremarkable. Cerebral MRI revealed extension of brain and meninges into the right frontal sinus. Final diagnosis of a right‐sided traumatic frontoethmoidal meningoencephalocele was made. The cat remained seizure free under phenobarbital treatment with residual left‐sided postural reaction deficits at 9 months follow‐up. This is the first report of presumptive traumatic meningoencephalocele in a cat, which emphasises the importance of complete neurological investigation and regular long‐term follow‐up checks in patients with historical head trauma despite the absence of initial neurological signs.

Caudal cruciate ligament (CaCL) rupture is uncommon in dogs and usually occurs with a concurrent rupture of the cranial cruciate ligament (CrCL). A 10-month-old cross-bred dog was presented with left hind limb lameness. Orthopaedic examination revealed positive craniocaudal drawer sign in the left stifle. Arthrotomy confirmed CrCL rupture, and showed CaCL avulsion fracture at its origin. The stifle was stabilized using extracapsular lateral fabellotibial suture. Eight months postoperatively the dog was free of obvious lameness and remained sound until the last re-evaluation (3 years). This case raises the possibility that restoration of the CaCL function is not always essential for animals’ successful outcome.

An 11-month-old neutered female cocker spaniel was referred for two generalised tonic-clonic epileptic seizures with a one-week interval of mild depression. On admission, physical and neurological examinations were unremarkable. Neurolocalisation was forebrain. Haematology, biochemistry, serology for infectious diseases, urinalysis and urine culture were unremarkable. Cerebral MRI revealed T1-weighted hyperintensity in the lentiform nuclei. Cerebrospinal fluid analysis was unremarkable. Idiopathic epilepsy was mistakenly diagnosed and phenobarbital was started. A delayed blood film examination revealed metarubricytosis, polychromasia and basophilic stippling, raising the suspicion of lead intoxication. Abdominal radiography revealed a metallic lead foreign body (lead curtain weight), which removed endoscopically. Treatment with CaEDTA, thiamine and D-penicillamine was started. This report highlights the importance of including haematology, blood smear examination, biochemistry and urinalysis in the diagnostic workup of acute epileptic seizures particularly in young dogs. Lead intoxication should be included in the differential diagnosis in these patients, as modern lead sources still exist in our environment.

A 6.5-year-old male neutered Trailhound was admitted for hyperacute, nonprogressive, left-sided hemiparesis. Physical and neurologic examination revealed nonpainful, left-sided poorly ambulatory hemiparesis, decreased left-sided postural reactions and thoracic limbs hyporeflexia. Neuroanatomic localisation was consistent with a left-sided C6-T2 myelopathy. Haematology and biochemistry revealed nonspecific abnormalities. Magnetic resonance imaging of the neck revealed a focal intramedullary lesion at the level of C6-C7 vertebrae compatible with acute hydrated noncompressive nucleus pulposus extrusion or ischemic myelopathy. During the second day of hospitalization, the dog developed convergence-retraction nystagmus, up-gaze palsy and eyelid retraction (Collier's sign) compatible with dorsal midbrain syndrome. Magnetic resonance imaging of the brain revealed a focal lesion compatible with dorsal midbrain ischemic infarct. Further clinicopathologic testing, thoracic and abdominal imaging were unremarkable. Ischemic encephalopathy of unknown etiology was additionally diagnosed. Physiotherapy was performed therapeutically. At 1-year follow-up the dog was normal. This is an unusual report of a dog with myelopathy followed by ischemic encephalopathy with manifestation of convergence-retraction nystagmus in the absence of vestibular signs. This saccadic intrusion is a characteristic clinical manifestation of a dorsal midbrain syndrome localization. The importance of a complete differential diagnoses list formation in a dog with ischemic encephalopathy which leads to a thorough diagnostic investigation plan is highlighted. Moreover, this report contributes to the enrichment of the clinical reasoning veterinary literature on convergence-retraction nystagmus. To the authors' knowledge, this is the second case report (fourth dog) to describe convergence-retraction nystagmus in dogs as a manifestation of dorsal midbrain syndrome.

Meningoencephalocele is a protrusion of meninges and brain through an opening in the cranium; in humans it may be congenital, traumatic, neoplastic or idiopathic, whilst in small animals only congenital form has been reported. A 3-year-old, client-owned, neutered male DSH cat was referred with one-month history of three generalized tonic-clonic seizures and intermittent left thoracic limb spontaneous knuckling. Nine months ago, the animal had been bitten on the head by a wild carnivore. Prior to the traumatic event the cat was reported to be neurologically normal. On admission, physical examination was unremarkable. Neurological examination revealed left hemi-neglect syndrome, characterised by decreased postural reactions on the left thoracic and pelvic limb, and absent menace bilaterally, most likely post-ictal. Neuroanatomical localisation was right forebrain. Haematology, biochemistry and bile acid stimulation test were unremarkable. Blood serology for Toxoplasma gondii, FIV, FeLV and FCoV were all negative. MRI of the head revealed protrusion of brain and meninges into the right frontal sinus, mild meningeal contrast uptake of the protruding tissue and the adjacent brain in the calvarium. CSF analysis was unremarkable. Final diagnosis was traumatic frontoethmoidal meningoencephalocele with late-onset forebrain syndrome due to presumptive post-traumatic encephalomalacia. The cat remained seizure-free on the four-month follow-up. This is the first report of traumatic meningoencephalocele in small animals. The finding in this case emphasizes the importance of a complete neurological investigation in patients with history of head trauma despite the absence of initial neurological signs. Differentials for delayed neurological signs after traumatic meningoencephalocele include encephalomalacia, recurrent meningitis with/without CSF rhinorrhea or cerebral ischaemic infarction.

Convergence-retraction pulses (or “nystagmus) are a highly localizing saccadic abnormality of the dorsal midbrain syndrome in humans and dogs. Ischaemic encephalomyelopathy attributed to presumptive fibrocartilaginous embolism (FCE) has been reported in human, dog and lamb, whilst FCE encephalopathy was reported recently in a cat. The aim of this study is to report the clinical and imaging findings of a rare case of ischaemic encephalomyelopathy due to presumptive FCE with manifestation of convergence-retraction pulses and an excellent outcome. A 6.5-year-old client-owned male neutered Trailhound was admitted for hyperacute non-progressive non-painful left-sided hemiparesis developed during exercise. Physical examination revealed obesity and bilateral conjunctival hyperaemia. Neurological examination revealed non-painful left-sided poorly-ambulatory hemiparesis; decreased left-sided postural reactions and left thoracic limb spontaneous knuckling; thoracic limbs hyporeflexia; and no evidence of spinal pain. Neuroanatomical localisation was consistent with C6-T2 myelopathy. Haematology revealed stress-leukogram, whilst serum biochemistry revealed mild stress-hyperglycaemia, hypotriglyceridemia and mildly decreased alkaline phosphatase. The patient underwent a low-field magnetic resonance imaging (MRI) of the C1-T2 spinal segments which revealed a focal intramedullary lesion at C6-C7 spinal segments compatible with FCE. On the second day of hospitalisation, the patient suddenly developed “nystagmus”. Neurological examination revealed spontaneous-and-positional convergence-retraction pulses accompanied by synchronous blinking, mydriasis and upward gaze palsy (Collier’s sign) bilaterally. Ambulation and postural reactions were unchanged. The neuroanatomical localisation now was consistent with an additional dorsal midbrain syndrome. MRI of the brain revealed a focal, poorly-marginated, left-lateralized, hyperintense lesion on T2-weighted and fluid fluid-attenuated inversion recovery (FLAIR) sequences, at the level of the rostral midbrain. In transverse images, this lesion was visible adjacent to the midline (left-sided) and lateral to the rostral part of the mesencephalic aqueduct. This area was hyperintense on diffuse-weighting imaging (DWI) sequence, but did not suppress on apparent diffusion coefficient (ADC) mapping or uptake contrast. These findings were compatible with an ischaemic infarct in the rostral aspect of the dorsal midbrain. Cisternal cerebellomedullary cerebrospinal fluid (CSF) analysis revealed albuminocytological dissociation, with occasional monocytes, rare neutrophils and small lymphocytes. The finding of neutrophils in the absence of pleocytosis could be associated with cerebrovascular accident. Oscillometric arterial blood pressure revealed an average of 147/93 (mean106) mmHg. Ophthalmological examination, ophthalmoscopy, endocrine profile (TT4, TSH, basal cortisol, ACTH stimulation test), coagulation profile (BMBT, PT, APTT, D-dimers), ANA serology, extended infectious agents panel (blood serology and CSF PCR), urinalysis, urine culture, abdominal ultrasound and thoracic computed tomography were all unremarkable. Consequently, ischaemic encephalomyelopathy due to presumptive multifocal FCE was diagnosed. The dog was kept hospitalised for one week while received physiotherapy. At the time of discharge, the dog was ambulatory hemiparetic with normal haematology. On a three-week follow-up the dog was normal. The “nystagmus” was reported to have resolved within two weeks from onset. This is a rare report of a dog with multiple simultaneous central nervous system ischaemic infarctions which manifested convergence-retraction pulses and had an excellent outcome. This neuro-ophthalmological sign should be considered as a guide to localise precisely. FCE should be considered in the differential diagnoses for a dog with ischaemic encephalomyelopathy.

OBJECTIVES:The aims of the study were to identify the ultrasonographic findings in cats with acute kidney injury (AKI) and to assess whether they had prognostic value. METHODS:This was a descriptive case series. A search of the computerised records of the Queen Mother Hospital for Animals (Hatfield, UK) was performed for cats presenting with AKI between 2007 and 2016. Patients were excluded if they had historical data consistent with chronic kidney disease. Ultrasound images were reviewed for the presence of six renal ultrasonographic abnormalities: nephromegaly, cortical and medullary echogenicity, pyelectasia, and retroperitoneal and peritoneal fluid. Ultrasonographic findings were assessed individually and cumulatively to give an ultrasound score out of 6. Ultrasonographic findings were assessed for association with oligouria/anuria and survival. RESULTS:Forty-five cats with AKI fulfilled the inclusion criteria. In total, 6.7% (3/45) of cats had normal renal size and architecture. The most common renal ultrasonographic findings were nephromegaly, pyelectasia and increased renal echogenicity. The presence of retroperitoneal fluid was associated with oligouria/anuria. Total ultrasound score (out of 6) was significantly associated with oligouria/anuria and 6 month survival. CONCLUSIONS AND RELEVANCE:Ultrasonographic findings are common in cats presenting with AKI. The increasing number of renal ultrasonographic abnormalities and the presence of retroperitoneal fluid alone are associated with oligouria/anuria and a higher ultrasound score may suggest a poorer long-term prognosis.

A 9 year old, neutered male, mixed breed dog had epistaxis from the right nostril, right epiphora and marked upper respiratory noise. Initial radiographs revealed lesions typical of primary nasal neoplasia, but the biopsy was non-diagnostic. Subsequent radiographs, obtained one and two months later when the dog did not show any clinical signs, revealed radiographic signs typical of destructive rhinitis. Clinical signs recurred three months later and radiographic signs were again typical of advanced primary nasal neoplasia. Nasal adenocarcinoma was confirmed histopathologically. The principal reason for this unusual sequence of the radiographic findings is considered to be the temporary disappearance of a nasal mass, possibly because it became dislodged and was swallowed.

The clinical records of dogs with urinary incontinence, examined at the Queen Mother Hospital for animals between November 1995 and January 2006, were reviewed. Only dogs that had at least one contrast radiographic study, ultrasonographic examination of the ureters and surgical diagnosis were included. All the cases were examined on an individual ureter basis and on a case basis. The sensitivity, specificity and accuracy were calculated for intravenous urography, retrograde urethrography or retrograde vaginourethrography and ultrasonographic examination of the ureterovescicular junctions. Ultrasonographic examination of the ureterovescicular junctions had the higher sensitivity, specificity and accuracy from the imaging methods with only intravenous urography having mildly higher sensitivity when examined on a ureter base. The main failure of ultrasonographic examination of the ureterovescicular junctions was the identification of the correct side of ectopia. When evaluated on a case basis ultrasonographic examination of the ureterovescicular junctions had perfect sensitivity, specificity and accuracy. The lower mainly specificity and accuracy of intravenous urography and retrograde urethrography or retrograde vaginourethrography were probably related to the difficulty in identifying the location of the ureterovesicular junction.

OBJECTIVES : To describe the CT findings in a population of dogs with multi-centric lymphoma that involved the spleen and liver. MATERIALS AND METHODS : Clinical records between January 2008 and June 2015 were reviewed. Thoracic and abdominal CT examinations of patients diagnosed with multi-centric lymphoma were evaluated by a board-certified radiologist. A diagnosis of multi-centric lymphoma with splenic and hepatic involvement was based upon cytological identification and immunophenotyping of neoplastic lymphocytes in cellular samples harvested from a peripheral lymph node, the spleen and the liver. RESULTS : Twelve dogs were included in this study, of which 11 had B-cell lymphoma; immunophenotyping was inconclusive in one dog. The spleen appeared normal in seven dogs and nodules were identified in five dogs. Splenic nodules were hypoattenuating in four of five dogs and isoattenuating in one of five. After contrast administration, three of five appeared hypoattenuating and two of five isoattenuating. The liver appeared normal in 10 dogs and hepatic nodules were identified in two dogs. All hepatic nodules were isoattenuating before contrast and hypoattenuating following contrast administration. CLINICAL SIGNIFICANCE : The CT appearance of the spleen and liver was normal in the majority of dogs with multi-centric lymphoma. Fine needle aspiration of the spleen and liver is recommended when using CT to stage dogs with multi-centric lymphoma.

Ability to noninvasively differentiate malignant from nonmalignant abdominal masses would aid clinical decision making. The aim of this retrospective, cross-sectional study was to identify features in dual-phase computed tomographic (CT) studies that could be used to distinguish malignant from nonmalignant hepatic and splenic masses in dogs. Medical records were searched for dogs that had an abdominal dual-phase CT examination, a hepatic or splenic mass, and subsequent histopathologic diagnosis. Computed tomographic images for all included dogs were acquired prior to and <30 s (early phase) and >60 s (delayed phase) after intravenous contrast administration. Fifty-two dogs with 55 masses were studied: 24 hepatic, including 14 (58%) malignant and 10 (42%) non-malignant; 31 splenic, including 18 (58%) malignant and 13 (42%) nonmalignant. There was substantial overlap in the pre- and postcontrast CT features of malignant and nonmalignant hepatic and splenic masses. Regardless of histologic diagnosis, hepatic masses most frequently showed marked, generalized enhancement in early phase images that persisted in the delayed phase. Splenic hemangiosarcoma and nodular hyperplastic lesions most frequently showed marked, generalized enhancement in early phase images that persisted in delayed images whereas most splenic hematomas had slight enhancement in early phase images. All splenic hematomas and 77% of the hemangiosarcomas had contrast accumulation compatible with active hemorrhage. There were no other significant differences in quantitative or categorical CT data between malignant and nonmalignant hepatic or splenic masses. Dual-phase CT of dogs with hepatic or splenic masses provides limited specific diagnostic information.

Real time B-mode ultrasonography is a non-invasive diagnostic imaging modality that does not use radiation and allows examination of various soft tissue structures. For many years it is used in human dermatology and in the last decade it has entered the canine dermatology arena. Based on the frequency employed, cutaneous ultrasonography may be classified as intermediate-(7-15 MHz) or high-frequency (20 MHz or higher). Using intermediate frequency, the ultrasonographic features of normal canine skin are consistent and three distinct visible layers can be seen. Using a 50 MHz transducer, the epidermis and hair follicles are also identified and accurate measurements of skin thickness can be obtained. The aim of this article is to review the available published knowledge regarding ultrasonographic examination of the canine skin.

Journal of Veterinary Internal MedicineVolume 30, Issue 4 p. 1216-1221 Case ReportOpen Access Hypersomatotropism in 3 Cats without Concurrent Diabetes Mellitus J.M. Fletcher, Corresponding Author J.M. Fletcher Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Corresponding author: J.M. Fletcher, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70810; e-mail: jmfletcher@lsu.eduSearch for more papers by this authorC.J. Scudder, C.J. Scudder Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorM. Kiupel, M. Kiupel Department of Pathobiology and Diagnostic Investigation, Diagnostic Center for Population and Animal Health, Michigan State University, Lansing, MI, 48910Search for more papers by this authorH.N. Pipe-Martin, H.N. Pipe-Martin Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Search for more papers by this authorP.J. Kenny, P.J. Kenny Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorP. Mantis, P. Mantis Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorJ. Fenn, J. Fenn Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorK. Smith, K. Smith Department of Pathology and Pathogen Biology, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorR.V. Blair, R.V. Blair Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Search for more papers by this authorL.A. Granger, L.A. Granger Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Search for more papers by this authorS.J.M. Niessen, S.J.M. Niessen Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this author J.M. Fletcher, Corresponding Author J.M. Fletcher Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Corresponding author: J.M. Fletcher, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70810; e-mail: jmfletcher@lsu.eduSearch for more papers by this authorC.J. Scudder, C.J. Scudder Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorM. Kiupel, M. Kiupel Department of Pathobiology and Diagnostic Investigation, Diagnostic Center for Population and Animal Health, Michigan State University, Lansing, MI, 48910Search for more papers by this authorH.N. Pipe-Martin, H.N. Pipe-Martin Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Search for more papers by this authorP.J. Kenny, P.J. Kenny Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorP. Mantis, P. Mantis Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorJ. Fenn, J. Fenn Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorK. Smith, K. Smith Department of Pathology and Pathogen Biology, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorR.V. Blair, R.V. Blair Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Search for more papers by this authorL.A. Granger, L.A. Granger Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Search for more papers by this authorS.J.M. Niessen, S.J.M. Niessen Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this author First published: 03 June 2016 https://doi.org/10.1111/jvim.14360Citations: 12AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abbreviations CSF cerebrospinal fluid CT computed tomography DM diabetes mellitus FSH follicle-stimulating hormone GH growth hormone HCM hypertrophic cardiomyopathy IGF-1 insulin-like growth factor 1 MRI magnetic resonance imaging MSH melanocyte-stimulating hormone TSH thyroid-stimulating hormone USG urine specific gravity Case 1 A 16-year-old, 6.8 kg, castrated male Domestic Short-haired cat was presented to Louisiana State University Veterinary Teaching Hospital with a 3-day history of progressive ataxia, tetraparesis, and altered mentation. The owner did not report having observed evidence of polyuria or polydipsia. The cat had been diagnosed with hypertrophic cardiomyopathy (HCM) 4 years earlier and was receiving atenolol, benazepril, and aspirin. Dull mentation, patchy truncal alopecia, and a grade III of VI systolic heart murmur were noted during the physical examination. The neurologic examination revealed ambulatory tetraparesis that was more severe in the pelvic limbs, plantigrade stance, proprioceptive deficits in all limbs, and positional vertical nystagmus. The CBC, biochemistry profile, and abdominal ultrasound were unremarkable. The blood glucose concentration measured with the chemistry analyzer was 130 mg/dL (7.2 mmol/L). Subsequent blood glucose measurements (n = 6) using a glucometer validated for use in cats1 ranged from 122 mg/dL (6.7 mmol/L) to 159 mg/dL (8.7 mmol/L) during the 5-day period the cat was hospitalized. These blood glucose concentrations combined with a normal serum fructosamine concentration (228 μmol/L, RI 192–288) ruled out overt diabetes mellitus (DM). Two-dimensional echocardiogram revealed severe asymmetric septal hypertrophy (8.7 mm in diastole). The left atrium was normal in size and all valves appeared normal. Continuous wave Doppler through the left ventricular outflow tract revealed dynamic outflow tract obstruction. Color Doppler demonstrated marked turbulence in the left ventricular outflow tract and a narrow eccentric jet of mitral regurgitation associated with systolic anterior motion of the mitral valve. Magnetic resonance imaging (MRI)2 images of the head were obtained in multiple planes prior to and following contrast3 administration at a dose of 0.1 mmol/kg. In the region of the pituitary gland, there was a T2 hyperintense, T1 hypointense nodule having marked uniform contrast enhancement (Fig 1). This nodule had moderate extension dorsal to the sella turcica and was increased in size compared to a normal pituitary gland: length (0.63 cm), width (0.83 cm), and height (0.85 cm). On T2* weighted (gradient recalled echo) images, some regions of reduced signal and small signal voids were present within the pituitary gland, mostly on the left side, consistent with magnetic susceptibility likely due to regions of hemorrhage within the nodule. Additionally, there was moderate dilation of the entire ventricular system with most severe ventricular enlargement occurring in the fourth ventricle, which caused dorsal elevation and compression of the cerebellum. Findings were most consistent with a pituitary macroadenoma, hydrocephalus, and hydrosyringomyelia. The degree of pituitary enlargement and severity of 4th ventricular dilation did not support obstruction due to the pituitary mass. A cystic accumulation of cerebrospinal fluid (CSF) within the 4th ventricle or obstructive hydrocephalus due to an additional lesion not visible on the MRI could not be ruled out. Figure 1Open in figure viewerPowerPoint Axial MRI images of the brain show a large nodule that is hyperintense on T2W images (A, white arrow), mildly hypointense on T1W images (C, white arrow), and strongly uniformly contrast enhancing (D, white arrow) in the region of the pituitary gland. A T2* gradient recalled echo sequence shows patchy regions of indistinct hypointensity (B, white arrow) with a small region of marked hypointensity or signal void (B, black arrow). A clinical diagnosis of hypersomatotropism was supported by the presence of a pituitary mass and a total serum Insulin-like growth factor 1 (IGF-1) concentration (radioimmunoassay) consistent with the presence of excess growth hormone (GH) secretion (855 ng/mL, RI <700). The cat was humanely euthanized approximately 8 days after the initial presentation due to a lack of response to medical management, which included corticosteroid treatment, mannitol, furosemide, and a proton-pump inhibitor. Histology revealed expansion of the pars distalis by a 0.5 cm diameter, unencapsulated densely cellular neoplasm. The neoplasm was composed of cords and packets of polygonal cells separated by blood filled sinusoids and supported on a fine fibrovascular stroma. Neoplastic cells had oval nuclei with finely stippled chromatin, and a variable amount of finely granular eosinophilic cytoplasm with indistinct cell borders (Fig 2). The cells exhibited mild to moderate anisocytosis and anisokaryosis with a low mitotic index (<1/10 high powered fields), consistent with a pituitary adenoma. Figure 2Open in figure viewerPowerPoint Neoplastic cells vary in their intensity of eosinophilic cytoplasmic staining with many cells resembling acidophils (A). Hematoxylin eosin staining, bar = 200 μm. Neoplastic cells have diffuse cytoplasmic labeling for growth hormone (B), adrenocorticotropic hormone (C), and follicle-stimulating hormone (D). Small numbers of cells within the neoplasm were positively labeled for melanocyte-stimulating hormone (E), while labeling for thyroid-stimulating hormone (F) was not observed. DAB, hematoxylin counterstain, bar = 100 μm. Immunohistochemistry of the neoplasm (Fig 2) revealed strong positive cytoplasmic labeling for GH, which supports a diagnosis of hypersomatotropism caused by a GH secreting pituitary adenoma. Additionally, there was strong positive labeling for ACTH and follicle-stimulating hormone (FSH) as well as a small number of cells within the neoplasm that were positively labeled for melanocyte-stimulating hormone (MSH). Cells with positive labeling for thyroid-stimulating hormone (TSH) were not identified in the neoplasm. The immunohistochemistry findings are consistent with a plurihormonal adenoma. Case 2 A 9-year-old, 7 kg, castrated male Domestic Short-haired cat was presented to Queen Mother Hospital for Animals at the Royal Veterinary College with a 2-month history of weight gain despite a normal appetite. The owner elected to have the cat evaluated for this reason and because a sibling had been previously diagnosed with hypersomatotropism-induced DM. The physical examination was unremarkable except for broad facial features. The CBC and biochemistry profile were unremarkable. The blood glucose measured at the time of admission using a handheld glucometer1 was 251 mg/dL (13.8 mmol/L). The serum fructosamine concentration measured initially and approximately 3 weeks later were both within reference range (233 and 259 μmol/L, respectively, RI 205–322 μmol/L). A repeat blood glucose concentration measured on a chemistry analyzer4 prior to surgery was 165 mg/dL (9.1 mmol/L). The urinalysis revealed a urine specific gravity (USG) of 1.038 and no detectable glucose. The recheck blood glucose concentration, normal fructosamine concentrations, absence of clinical signs compatible with DM, and lack of glucosuria support stress hyperglycemia as the likely cause of isolated hyperglycemia. Two-dimensional echocardiogram revealed mild left ventricular free wall hypertrophy (6.5 mm in diastole). A diagnosis of hypersomatotropism was supported by an increased IGF-1 concentration (1468 ng/mL, RI <700) and subsequent documentation of increased pituitary length (0.63 cm), width (0.65 cm), and height (0.4 cm) with contrast-enhanced5 (2 mL/kg by hand injection) computed tomography6 (CT) (Fig 3). Hypophysectomy was performed, and the pituitary was removed in several pieces. The small pieces were submitted for histology, which revealed nervous tissue most consistent with pars nervosa bordered by a densely cellular proliferation of acidophilic cells. The cells had indistinct borders, finely vacuolated eosinophilic cytoplasm, and large round to oval nuclei, with stippled chromatin and variably prominent nucleoli. The cells were arranged in sheets and displayed mild to moderate anisocytosis, anisokaryosis, and cellular pleomorphism. Immunohistochemistry of the pituitary mass revealed positive cytoplasmic labeling for GH as well as strong positive labeling for ACTH, FSH, and MSH consistent with a plurihormonal adenoma. A clinical diagnosis of hypersomatotropism caused by a GH secreting pituitary adenoma was established on the basis of an increased IGF-1 concentration, pituitary enlargement on CT scan, and the histopathology findings. An inability to control progressive epistaxis that developed post-hypophysectomy resulted in humane euthanasia. A postmortem examination was declined. Figure 3Open in figure viewerPowerPoint Postcontract CT image shows mild enlargement of the pituitary gland (white arrow). Case 3 A 16-year-old, 7 kg, castrated male Domestic Short-haired cat was presented to Queen Mother Hospital for Animals at the Royal Veterinary College with a 5-day history of generalized seizures. The owner had not observed and did not report polyuria or polydipsia. The physical examination revealed mild palmigrade and plantigrade stance and mild pelvic limb muscle atrophy. The neurological examination was unremarkable. The CBC and biochemistry profile were unremarkable with the exception of hyperglycemia 345 mg/dL (19 mmol/L). The urinalysis revealed glucosuria (3+) and a USG of 1.031. Absence of clinical signs suggestive of DM (i.e., weight loss, polyphagia, polyuria, and polydipsia) at the time of presentation and a normal serum fructosamine concentration (253 μmol/L, RI 205–322) make stress the most likely cause of hyperglycemia and resultant glucosuria. MRI7 images of the head before and after the administration of gadolinium8 at a dose of 28 mg/kg revealed pituitary enlargement: length (0.76 cm), width (0.65 cm), and height (0.59 cm). The region of the pituitary was mildly T2 hyperintense, T1 hyperintense, and strongly contrast enhancing (Fig 4). A round area within the left aspect of the pituitary gland was hypointense to surrounding region of the pituitary on the T1 and T2 weighted images. This same region had reduced contrast enhancement on postcontrast T1 weighted images when compared to the surrounding pituitary. Additionally, a focal extra-axial intracranial mass overlying the left temporal lobe, demonstrating marked contrast enhancement with a dural tail sign, compatible with a meningioma was seen. Pituitary enlargement combined with an increased IGF-1 concentration (1902 ng/mL, RI <700) supported a diagnosis of concurrent hypersomatotropism. Approximately 1 month after the initial evaluation, a craniotomy was performed to resect the left temporal lobe tumor. Histology of the tumor was consistent with a fibroblastic meningioma. Phenobarbital was administered postoperatively for approximately 4 weeks. Transition to a high protein and low carbohydrate diet9 was attempted but was not successful due to an unwillingness of the cat to consume the diet. The cat subsequently developed DM 3 months after the initial presentation and insulin treatment was prescribed. The owner declined treatment specifically targeting hypersomatotropism and the cat was humanely euthanized approximately 17 months later. A postmortem examination was declined. Figure 4Open in figure viewerPowerPoint Axial MRI images of the brain show enlargement of the pituitary gland that is mixed hyper and hypo intense on T2W images (A, white arrow), predominantly hyperintense on T1W images (B, white arrow), and strongly contrast enhancing (C, white arrow). A region within the left aspect of the pituitary gland was hypointense to surrounding pituitary on both the T1 and T2 W images. This same region had reduced contrast enhancement on postcontrast T1W images when compared to the surrounding pituitary. A focal, broad based, mildly T2 hypointense, T1 isointense, markedly uniformly contrast enhancing extraaxial mass with regional vasogenic edema is also noted in the left temporal lobe and internal capsule (A–C, black arrow). This case series presents three cats with GH-secreting pituitary adenomas that developed hypersomatotropism without concurrent DM. Hypersomatotropism is a state of excessive production and secretion of GH, which in the cat has been described to be the result of a pituitary acidophilic adenoma, carcinoma, or hyperplasia.1-4 Currently, most cats are diagnosed with hypersomatotropism once they are found to be insulin-resistant unless the clinician routinely screens all diabetic cats for hypersomatotropism shortly after DM is diagnosed. According to screening studies performed in the UK that measured IGF-1 concentrations in a large number of diabetic cats, as many as 26–32% were determined to have hypersomatotropism-induced DM.2, 4, 5 The reason that hypersomatotropism has not been previously reported in cats that are not diabetic is likely because there is a strong and long-standing clinical association between DM and the recognizable physical characteristics of acromegaly. The non-diabetic aspects of this clinical image are slow to appear, often subtle, and can go unrecognized.4 It was not possible to directly demonstrate increased GH concentrations in these cases because a validated method for measuring feline GH was not commercially available at the time these cases were evaluated; however, the diagnosis of hypersomatotropism in both people and cats is routinely made by demonstrating an increased IGF-1 concentration and presence of a pituitary mass or enlargement. In fact, recent practice guidelines for physicians recommend against relying on random GH concentrations to diagnose acromegaly in people.6 Human assays for feline IGF-1 have been validated, are readily available, and are useful for screening because IGF-1 reflects 24-hour GH secretion, parallels changes in GH, and is a sensitive marker for GH excess.4, 7-10 Unlike GH, IGF-1 secretion is not pulsatile which allows a single sample collected at any point during the day to have diagnostic utility. It is generally accepted that an IGF-1 concentration >1000 ng/mL is strongly suggestive of acromegaly in cats, with a positive predictive value of 95%.1, 2, 4 The first cat in this series had immunohistopathologic confirmation of a GH producing pituitary adenoma, but had an IGF-1 below this cutoff. This case supports recent speculation that the currently used arbitrary IGF-1 cutoff value of 1000 ng/mL is too high, underestimates the true prevalence of hypersomatotropism, and leads to underdiagnosis of mild or early forms of the disease.1, 7 This has led some authors to recently suggest considering 800–1000 ng/mL as a "gray zone" that warrants further investigation.7 Although the negative predictive value of an IGF-1 < 1000 ng/mL is low, a case of hypersomatotropism-induced DM with a lower IGF-1 was recently reported4 further supporting the existence of cats with hypersomatotropism that have IGF-1 concentrations below the currently accepted cut-off. It could be argued that the cats being reported were not diabetic because they had incidental or nonfunctional pituitary enlargement; however, the elevated serum IGF-1 concentrations and immunohistochemistry findings argue against such theory, as does the low incidence of incidental pituitary enlargements found in cats. A recent study reported on a cohort of 62 cats undergoing CT imaging for reasons other than pituitary visualization found only one cat (1.6%) with incidental pituitary enlargement.4 Finally, cat 3 ultimately became diabetic. There were also clinical features that could be compatible with the presence of hypersomatotropism: the weight gain seen in cat 2 and the ventricular myocardial hypertrophy and cardiac changes in cats 1 and 2. Additionally, on retrospective MRI assessment of the head features of cat 3, there was increased parietal bone thickness and increased distance between the lateral aspects of the zygomatic arches. These changes have been described in cats with hypersomatotropism.11 The immunohistochemistry findings of cat 1 and cat 2 were consistent with plurihormonal expression across three lineages of adenohypophysial differentiation (ie, corticotrophs, somatotrophs, gonadotrophs). Although plurihormonal expression in pituitary adenomas has been described in people and other domestic animals, there is only a single report of a somatotroph and corticotroph pituitary double adenoma in a cat with DM and hyperadrenocorticism.12, 13 It has been speculated that plurihormonal expression may be more common, but tumors are rarely analyzed immunohistochemically and instead classified by the hormone that dominates the clinical picture. It is important to note that although cat 1 and cat 2 had strong positive labeling for ACTH, neither cat had characteristic features associated with hyperadrenocorticism or ultrasonographic evidence of adrenomegaly. In addition, adrenomegaly was not identified during the postmortem examination of cat 1. To our knowledge, the only discussion of a nondiabetic acromegalic cat was an author's personal experience that was included in a textbook chapter.14 This has resulted in the dogma that all hypersomatotropic cats are insulin-resistant diabetics. It is this dogma and the idea of a "typical" acromegalic phenotype that has likely resulted in very few cats being screened for hypersomatotropism prior to the development of insulin-resistant DM and an acromegalic phenotype. As a result, the true prevalence in nondiabetic cats remains unknown. As in humans, feline hypersomatotropism likely has a gradual-onset and a period during which the GH and IGF-1 concentrations are increased, but DM and signs constituting the syndrome of acromegaly have yet to occur. If the cat does not have dysfunctional pancreatic beta cells, as is suggested to be the case in Type 2 DM, it is likely able to withstand a period of increasing insulin resistance without developing overt DM. This is further substantiated by the fact that most diabetic cats with hypersomatotropism will enter diabetic remission once the somatotrophinoma is removed.5, 15 It is also worth noting that approximately 2/3 of people diagnosed with hypersomatotropism do not become diabetic,16 further suggesting that by focusing only on the diabetic population, we could be missing hypersomatotropic cats prior to the development of overt DM as well as those that may never become diabetic. With recent evidence of a much higher prevalence of hypersomatotropism in diabetic cats than once realized1, 2, 4, 17-19 and an unknown prevalence in cats without DM, more work needs to be done to accurately determine the significance of this endocrinopathy in the general cat population. Hopefully, increased awareness and screening will lead to earlier detection and may allow the occurrence of the syndrome of acromegaly, DM, and conditions associated with progressive pituitary enlargement to be delayed or prevented. Finally, recent advances in our ability to treat hypersomatotropism (e.g., increasing availability of hypophysectomy, stereotactic radiation and Gamma Knife technology, and pasireotide) make early diagnosis and intervention more desirable. Acknowledgments Conflict of Interest Declaration: Authors disclose no conflict of interest. Off-label Antimicrobial Declaration: Authors declare no off-label use of antimicrobials. Footnotes 1 AlphaTrak and AlphaTrak2, Zoetis, Florham Park, NJ 2 Echelon 1.5T, Hitachi Medical Systems America, Twinsburg, OH 3 Magnevist, Bayer Healthcare, Wayne, NJ 4 Stat Profile pHOx Ultra, Nova Biomedical Corporation, Waltham, MA 5 Omnipaque 350, GE Healthcare Ireland, Cork, Ireland 6 Mx8000 IDT 16, Philips, Amsterdam, NL 7 Intera 1.5T, Philips Healthcare, Eindhoven,NL 8 Dotarem, Guerbet, Milton Keynes, UK 9 Hill's Prescription Diet m/d Feline, Hill's (registered trademark) Pet Nutrition, Inc., Topeka, KS, USA References 1Niessen SJM, Church DB, Forcada Y. Hypersomatotropism, acromegaly, and hyperadrenocorticism and feline diabetes mellitus. Vet Clin North Am Small Anim Pract 2013; 43: 319– 350. 2Niessen SJM, Petrie G, Gaudiano F, et al. Feline acromegaly: An underdiagnosed endocrinopathy? J Vet Intern Med 2007; 21: 899– 905. 3Niessen SJM, Khalid M, Petrie G, Church DB. Validation and application of a radioimmunoassay for ovine growth hormone in the diagnosis of acromegaly in cats. Vet Rec 2007; 160: 902– 907. 4Niessen SJM, Forcada Y, Mantis P, et al. Studying cat (Felis catus) diabetes: Beware of the acromegalic imposter. PLoS ONE 2015; 10: e0127794. 5Kenny PJ, Scudder C, Keyte SV, et al. Experiences of a newly established hypophysectomy clinic for treatment of feline hypersomatotropism. J Vet Intern Med 2015; 29: 423– 484 (Abstract). 6Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: An endocrine society clinical practice guideline. J Clin Endocr Metab 2014; 99: 3933– 3951. 7Feldman EC, Nelson RW, Reusch C, Scott-Moncrieff JC. Canine and Feline Endocrinology. St. Louis, MO: Elsevier Saunders; 2014. 8Le Roith D, Bondy C, Yakar S, et al. The somatomedin hypothesis: 2001. Endocr Rev 2001; 22: 53– 74. 9Freda PU. Current concepts in the biochemical assessment of the patient with acromegaly. Growth Horm IGF Res 2003; 13: 171– 184. 10Ribeiro-Oliveira A Jr, Barkan A. The changing face of acromegaly—advances in diagnosis and treatment. Nat Rev Endocrinol 2012; 8: 605– 611. 11Lamb CR, Ciasca TC, Mantis P, et al. Computed tomographic signs of acromegaly in 68 diabetic cats with hypersomatotropism. J Feline Med Surg 2014; 16: 99– 108. 12Kiupel M, Capen C, Miller M, Smedley R. Histological Classification of Tumors of the Endocrine System of Domestic Animals. Washington, DC: Armed Forces Institute of Pathology in cooperation with the CL Davis DVM Foundation and the World Health Organization Collaborating Center for Worldwide Reference on Comparative Oncology; 2008. 13Meij BP, van der Vlugt-Meijer RH, van den Ingh TSGAM, Rijnberk A. Somatotroph and corticotroph pituitary adenoma (double adenoma) in a cat with diabetes mellitus and hyperadrenocorticism. J Comp Pathol 2004; 130: 209– 215. 14Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction. St. Louis, MO: Elsevier Saunders; 2004. 15Kenny P, Scudder C, Keyte S, et al. Treatment of feline hypersomatotropism- efficacy, morbidity and mortality of hypophysectomy. J Vet Intern Med 2015; 29: 1257– 1283 (Abstract). 16Wass JAH, Stewart PM. Oxford Textbook of Endocrinology and Diabetes, 2nd ed. Oxford: Oxford University Press; 2011. 17Elliott DA, Feldman EC, Koblik PD, et al. Prevalence of pituitary tumors among diabetic cats with insulin resistance. J Am Vet Med Assoc 2000; 216: 1765– 1768. 18Berg RIM, Nelson RW, Feldman EC, et al. Serum insulin-like growth factor-I concentration in cats with diabetes mellitus and acromegaly. J Vet Intern Med 2007; 21: 892– 898. 19Niessen SJM, Forcada K, Jensen B, et al. Routine screening of diabetic cats for acromegaly: Overdue or overkill? J Vet Intern Med 2011; 25: 1470– 509 (Abstract). Citing Literature Volume30, Issue4July/August 2016Pages 1216-1221 FiguresReferencesRelatedInformation

Naturally occurring diabetes mellitus (DM) is common in domestic cats (Felis catus). It has been proposed as a model for human Type 2 DM given many shared features. Small case studies demonstrate feline DM also occurs as a result of insulin resistance due to a somatotrophinoma. The current study estimates the prevalence of hypersomatotropism or acromegaly in the largest cohort of diabetic cats to date, evaluates clinical presentation and ease of recognition. Diabetic cats were screened for hypersomatotropism using serum total insulin-like growth factor-1 (IGF-1; radioimmunoassay), followed by further evaluation of a subset of cases with suggestive IGF-1 (>1000 ng/ml) through pituitary imaging and/ or histopathology. Clinicians indicated pre-test suspicion for hypersomatotropism. In total 1221 diabetic cats were screened; 319 (26.1%) demonstrated a serum IGF-1>1000 ng/ml (95% confidence interval: 23.6-28.6%). Of these cats a subset of 63 (20%) underwent pituitary imaging and 56/63 (89%) had a pituitary tumour on computed tomography; an additional three on magnetic resonance imaging and one on necropsy. These data suggest a positive predictive value of serum IGF-1 for hypersomatotropism of 95% (95% confidence interval: 90-100%), thus suggesting the overall hypersomatotropism prevalence among UK diabetic cats to be 24.8% (95% confidence interval: 21.2-28.6%). Only 24% of clinicians indicated a strong pre-test suspicion; most hypersomatotropism cats did not display typical phenotypical acromegaly signs. The current data suggest hypersomatotropism screening should be considered when studying diabetic cats and opportunities exist for comparative acromegaly research, especially in light of the many detected communalities with the human disease.