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Background: The use of adrenocorticotropic hormone stimulation test as method to monitor efficacy of trilostane treatment of hypercortisolism (HC) in dogs has been questioned. Objectives: To evaluate and compare 12 methods with which to monitor efficacy of trilostane treatment in dogs with HC. Animals: Forty-five client-owned dogs with HC treated with trilostane q12h. Methods: Prospective cross-sectional observational study. The dogs were categorized as well-controlled, undercontrolled, and unwell through a clinical score obtained from an owner questionnaire. The ability to correctly identify trilostane-treatment control of dogs with HC with the following variables was evaluated: before trilostane serum cortisol (prepill), before-ACTH serum cortisol, post-ACTH serum cortisol, plasma endogenous ACTH concentrations, prepill/eACTH ratio, serum haptoglobin (Hp) concentration, serum alanine aminotransferase (ALT), gamma-glutamyl transferase (γGT) and alkaline phosphatase activity, urine specific gravity, and urinary cortisol:creatinine ratio. Results: Ninety-four re-evaluations of 44 dogs were included; 5 re-evaluations of 5 unwell dogs were excluded. Haptoglobin was significantly associated with the clinical score (P

Objectives The aim of this study was to collect clinical information from owners of cats with hypersomatotropism (HS) distributed worldwide, assessing the impact of HS and its treatments on cats’ quality of life (QoL) and survival time. Methods A survey focused on clinical presentation, diagnostic procedures, treatments, cats’ QoL and disease progression was distributed worldwide to owners of cats with HS. The owner’s perception of the cats’ QoL before and after or during treatment was defined using a score ranging from 1 (poor) to 5 (excellent). Improvement following treatment (IFT) was quantified using a score ranging from 1 (absent) to 5 (obvious). Different treatment groups, including at least five cases, were compared. Results A total of 127 cats were included from at least 11 different countries. Among these, 120 (95%) were diabetic and 7 (5%) were not. Out of 120 diabetic cats, 55 (46%) were treated with insulin as a single treatment (INS). Other treatments were not mentioned to owners in 35/120 (29%) cases. The median QoL score at diagnosis was 2 (range 1–5) and improved after treatment in all groups. Cabergoline (4; range 1–5), radiotherapy (4; range 2–5) and hypophysectomy (5; range 4–5) showed better median IFT scores compared with INS (3; range 1–5) ( P = 0.046, P Conclusions and relevance Not all cats with HS will have diabetes mellitus. Causal treatments seem associated with the greatest improvements in perceived cats’ QoL and survival; such treatments should therefore be discussed with owners. Cabergoline could be an effective alternative management option.

Supplemental material, sj-docx-1-jfm-10.1177_1098612X221098718 for Quality of life and response to treatment in cats with hypersomatotropism: the owners’ point of view by Andrea Corsini, Stijn JM Niessen, Diego D Miceli, Sarah Caney, Florian K Zeugswetter, Nadja S Sieber-Ruckstuhl, Carolina Arenas, Linda M Fleeman, Rodolfo O Leal, Martina Battellino and Federico Fracassi in Journal of Feline Medicine and Surgery

Supplemental material, sj-docx-2-jfm-10.1177_1098612X221098718 for Quality of life and response to treatment in cats with hypersomatotropism: the owners’ point of view by Andrea Corsini, Stijn JM Niessen, Diego D Miceli, Sarah Caney, Florian K Zeugswetter, Nadja S Sieber-Ruckstuhl, Carolina Arenas, Linda M Fleeman, Rodolfo O Leal, Martina Battellino and Federico Fracassi in Journal of Feline Medicine and Surgery

Retroperitoneal paragangliomas are rare tumors of the neuroendocrine system. Only a few canine case reports are available with rare descriptions of their imaging features. The objectives of this multi-center, retrospective case series study were to describe the diagnostic imaging features of confirmed retroperitoneal paragangliomas and specify their location. Medical records and imaging studies of 10 affected dogs with cytological or histopathologic results concordant with retroperitoneal paragangliomas were evaluated. Dogs had a median age of 9 years. Four of them had clinical signs and laboratory reports compatible with excessive production of catecholamines. Six ultrasound, four CT, four radiographic, and one MRI studies were included. The paragangliomas did not have a specific location along the aorta. They were of various sizes (median 33 mm, range: 9-85 mm of length). Masses had heterogeneous parenchyma in six of 10 dogs, regardless of the imaging modality. Strong contrast enhancement was found in all CT studies. Encircling of at least one vessel was detected in six of 10 masses, clear invasion of a vessel was identified in one of 10 masses. In five of 10 cases, the masses were initially misconstrued as lymph nodes by the on-site radiologist. Retroperitoneal paragangliomas appear along the abdominal aorta, often presenting heterogeneous parenchyma, possibly affecting the local vasculature, and displaying strong contrast enhancement on CT. Clinical signs can be secondary to mass effects or excessive catecholamine production. Underdiagnosis and misdiagnosis of this tumor are suspected as they can be silent, of small size, or confused with other structures.

Objectives The aims of this study were to validate a commercially available chemiluminescent assay for measurement of feline plasma adrenocorticotropic hormone concentration (ACTH), to determine the normal reference interval (RI) of plasma ACTH in healthy cats, to assess plasma ACTH in cats with naturally occurring hypercortisolism (HC), primary hypoadrenocorticism (PH) and other diseases (OD), and to evaluate the effect of aprotinin on plasma ACTH degradation. Methods Forty healthy cats, 10 with HC, 11 with PH and 30 with OD, were included. The chemiluminescent enzyme immunometric assay was evaluated by measurement of intra-assay precision, interassay precision and linearity. The RI for plasma ACTH in healthy cats was established using robust methods. Plasma ACTH of samples collected with and without aprotinin, stored at 4°C and assayed over a 6-day period, was measured. Results The intra-assay coefficients of variance (CVs) ranged from 2.7% to 4.3% and interassay CVs from 3.3% to 10.7%. Dilution studies showed excellent accuracy (R2 >0.99). The RI for plasma ACTH in healthy cats was 32–370 pg/ml. Plasma ACTH was not significantly different between healthy cats and the OD group. Cats with pituitary-dependent hypercortisolism (PDH) and PH had significantly higher plasma ACTH than the other groups. Plasma ACTH did not show significant differences when samples collected with and without aprotinin were compared. Conclusions and relevance The Immulite chemiluminescent assay is a valid technique for measuring plasma ACTH in cats and the RI of plasma ACTH is quite wide. Owing to the low overlap between healthy or OD cats and cats with HC or PH, the measurement of plasma ACTH appears to be useful and should be included in the diagnostic work-up when HC or PH are suspected. Furthermore, the measurement of plasma ACTH may be an accurate test for differentiating PDH from adrenal-dependent hypercortisolism.

OBJECTIVE To explore sources of serum aldosterone concentration variability in a population of healthy and diseased ferrets, determine a preliminary 1 -sided reference interval for serum aldosterone concentration in healthy ferrets, and identify a decision limit to differentiate healthy from diseased ferrets on the basis of serum aldosterone concentration. DESIGN Prospective threshold definition and diagnostic accuracy study. ANIMALS 78 healthy (n = 56) and diseased (22) ferrets. PROCEDURES Serum aldosterone concentrations were measured on consecutively admitted ferrets, and an upper reference limit for aldosterone concentrations was established. Sensitivity and specificity of aldosterone concentration cutoffs to differentiate healthy from diseased ferrets were estimated with receiver operating characteristic curve analysis. RESULTS Measurements of serum aldosterone concentrations in the ferrets showed wide variability, with a median concentration of 4.75 pg/mL (interquartile range, 0.55 to 17.9 pg/mL; range, 0.02 to 283.9 pg/mL) and 76% (59/78) of samples having concentrations < 18 pg/mL. Ferrets that were healthy, older, or sexually inactive had significantly lower aldosterone concentrations. The upper limit of the reference interval for healthy ferrets was 13.3 pg/mL (90% confidence interval, 9.9 to 16.9 pg/mL). Analysis of receiver operating characteristic curves indicated that an aldosterone concentration cutoff value of 7.6 pg/mL differentiated healthy ferrets from diseased ferrets with a sensitivity of 72.7% and specificity of 73.2% (area under the curve, 0.79; 95% confidence interval, 0.67 to 0.91). CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that high aldosterone concentrations should not be considered diagnostic of primary hyperaldosteronism in ferrets. A need exists to develop better tests to identify primary hyperaldosteronism.

Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, non-invasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as diagnostic (presence of PDH or csACT) and/or prognostic (disease recurrence, histological grade) non-invasive biomarkers for canine Cushing's syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were differentially expressed compared to healthy dogs. Of one miRNA, miR-122-5p, the expression levels did not overlap between healthy dogs and dogs with PDH (p = 2.9x10−4), significantly decreased after hypophysectomy (p = 0.013), and were significantly higher (p = 0.017) in dogs with recurrence (n = 3) than in dogs without recurrence for at least one year after hypophysectomy (n = 7). In dogs with csACTs, two miRNAs (miR-483-3p and miR-223-3p) were differentially expressed compared to healthy dogs. Additionally, miR-141-3p was expressed significantly lower (p = 0.009) in dogs with csACTs that had a histopathological Utrecht score of ≥ 11 compared to those with a score of

Background Successful treatment of cats with hypersomatotropism by transsphenoidal hypophysectomy is described in small numbers of cats. Objectives To describe the endocrine profile, survival, and remission rates of hypersomatotropism and diabetes mellitus in a cohort of cats with hypersomatotropism that underwent hypophysectomy between 2008 and 2020. Animals Twenty-five client-owned cats with spontaneous hypersomatotropism. Methods Retrospective study. Diagnosis of hypersomatotropism was based on clinical signs, plasma insulin-like growth factor-1 (IGF-1) concentration, and imaging of the pituitary gland. Growth hormone (GH) and IGF-1 concentrations were measured repeatedly after surgery. Survival times were calculated based on follow-up information from owners and referring veterinarians. Results Median postoperative hospital stay was 7 days (range, 3-18 days). One cat died within 4 weeks of surgery. Median plasma GH concentration decreased significantly from 51.0 ng/mL (range, 5.0-101.0 ng/mL) before surgery to 3.8 ng/mL (range, 0.6-13.0 ng/mL) at 5 hours after surgery. Remission of hypersomatotropism, defined as normalization of plasma IGF-1 concentration, occurred in 23/24 cats (median, 34 ng/mL; range, 14-240 ng/mL) and 22/24 cats entered diabetic remission. Median survival time was 1347 days (95% confidence interval, 900-1794 days; range, 11-3180 days) and the overall 1-, 2-, and 3-year all-cause survival rates were 76%, 76%, and 52%, respectively. Conclusions and clinical importance This study shows the beneficial outcome of hypophysectomy in cats with hypersomatotropism, marked by low death rate and a high percentage of diabetic remission and definitive cure.

Background: Percutaneous ultrasound (US)-guided fine-needle aspiration (FNA) of adrenal gland lesions is controversial in veterinary medicine. Objective: To evaluate the frequency and radiologists' perception of the risk of the procedure as well as determining the incidence of complications. Methods: Retrospective study. A first survey was submitted by e-mail to all board-certified radiologists of the American College of Veterinary Radiology (ACVR) and European College of Veterinary Diagnostic Imaging (ECVDI). A second survey was sent to radiologists who declared having performed the procedure at least once in their career (observational cross-sectional case study). Results: The first survey was sent to 977 diplomates and answered by 138. Of 138 diplomates, 40 currently performed the procedure and 98 did not; 44 of the 98 gave the hypertensive crisis risk in pheochromocytoma as a reason. To the second survey, 12 of 65 responded positively; 50 dogs with 58 lesions were recruited, including 23 pheochromocytomas. Complications were reported in 4 of 50 dogs; 3 hemorrhages (1 mild and 1 moderate) and 1 death from acute respiratory distress syndrome (possibly related to laryngeal paralysis). No hypertensive crisis was reported. There was no relationship between the method of FNA/type of needle used and occurrence of complications. Based on the recollection of these 65 radiologists, who performed approximately 200 FNA of adrenal lesions, a death rate of approximately 1% was estimated. Conclusions and Clinical Importance: Percutaneous US-guided FNA of adrenal lesions can be considered a minimally risky procedure, despite the negative perception by radiologists.

8658860258318000Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D (SDHB and SDHD) were identified in pet dogs that presented with spontaneously arising pheochromocytomas (PCC) and paragangliomas (PGL, together PPGL), suggesting dogs might be an interesting comparative model for the study of human PPGL. To study whether canine PPGL resembled human PPGL, we investigated a series of 50 canine PPGLs by immunohistochemistry to determine the expression of synaptophysin (SYP), tyrosine hydroxylase (TH) and succinate dehydrogenase subunit A (SDHA) and B (SDHB). In parallel, 25 canine PPGLs were screened for mutations in SDHB and SDHD by Sanger sequencing. To detect large chromosomal alterations, single nucleotide polymorphism (SNP) arrays were performed for 11 PPGLs, including cases for which fresh frozen tissue was available. The immunohistochemical markers stained positive in the majority of canine PPGLs. Genetic screening of the canine tumors revealed the previously described variants in four cases, SDHB p.Arg38Gln (n = 1) and SDHD p.Lys122Arg (n = 3). Furthermore, the SNP arrays revealed large chromosomal alterations of which the loss of chromosome 5, partly homologous to human chromosome 1p and chromosome 11, was the most frequent finding (100% of the six cases with chromosomal alterations). In conclusion, canine and human PPGLs show similar genomic alterations, suggestive of common interspecies PPGL-related pathways.