Adrenal tumors treated by adrenalectomy following spontaneous rupture carry an overall favorable prognosis: retrospective evaluation of outcomes in 59 dogs and 3 cats (2000-2021).

OBJECTIVE: To conduct a retrospective multi-institutional study reporting short- and long-term outcomes of adrenalectomy in patients presenting with acute hemorrhage secondary to spontaneous adrenal rupture. ANIMALS: 59 dogs and 3 cats. METHODS: Medical records of dogs and cats undergoing adrenalectomy between 2000 and 2021 for ruptured adrenal masses were reviewed. Data collected included clinical presentation, preoperative diagnostics, surgical report, anesthesia and hospitalization findings, histopathology, adjuvant treatments, and long-term outcome (recurrence, metastasis, and survival). RESULTS: Median time from hospital admission to surgery was 3 days, with 34% of surgeries being performed emergently (within 1 day of presentation). Need for intraoperative blood transfusion was significantly associated with emergent surgery and presence of active intraoperative hemorrhage. The short-term (≤ 14 days) complication and mortality rates were 42% and 21%, respectively. Negative prognostic factors for short-term survival included emergent surgery, intraoperative hypotension, and performing additional surgical procedures. Diagnoses included adrenocortical neoplasia (malignant [41%], benign [12%], and undetermined [5%]), pheochromocytoma (38%), a single case of adrenal fibrosis and hemorrhage (2%), and a single case of hemangiosarcoma (2%). Local recurrence and metastasis of adrenocortical carcinoma were confirmed in 1 and 3 cases, respectively. Overall median survival time was 574 days and 900 days when short-term mortality was censored. No significant relationship was found between histopathological diagnosis and survival. CLINICAL RELEVANCE: Adrenalectomy for ruptured adrenal gland masses was associated with similar short- and long-term outcomes as compared with previously reported nonruptured cases. If hemodynamic stability can be achieved, delaying surgery and limiting additional procedures appear indicated to optimize short-term survival.

Multiple endocrine neoplasia in a sheep: insulinoma, adrenocortical carcinoma with myxoid differentiation, and thyroid C-cell carcinoma.

An ~10-y-old male sheep had anorexia and progressive weight loss for ~1 mo. The sheep was emaciated, and 20 d later, became recumbent and lethargic, and was hypoglycemic (0.33 mmol/L; RI: 2.6-4.4 mmol/L). The sheep was euthanized because of poor prognosis, and submitted for autopsy. We found no gross lesions in the pancreas; however, histologically, focal proliferations of round-to-polygonal cells were separated by connective tissue into small nests. These proliferating cells, which had abundant eosinophilic-to-amphophilic cytoplasm and hyperchromatic nuclei, were immunopositive for insulin and negative for glucagon and somatostatin; the lesion was diagnosed as an insulinoma. Insulinoma has not been reported previously in sheep, to our knowledge. In addition, autopsy and histologic examination revealed the presence of an adrenocortical carcinoma with myxoid differentiation and a thyroid C-cell carcinoma. Our case indicates that multiple endocrine neoplasms can occur in sheep, as in other animal species.

Transcriptome sequencing reveals two subtypes of cortisol-secreting adrenocortical tumours in dogs and identifies CYP26B1 as a potential new therapeutic target.

Cushing's syndrome (CS) is a serious endocrine disorder that is relatively common in dogs, but rare in humans. In ~15%-20% of cases, CS is caused by a cortisol-secreting adrenocortical tumour (csACT). To identify differentially expressed genes that can improve prognostic predictions after surgery and represent novel treatment targets, we performed RNA sequencing on csACTs (n = 48) and normal adrenal cortices (NACs; n = 10) of dogs. A gene was declared differentially expressed when the adjusted p-value was <.05 and the log2 fold change was >2 or < -2. Between NACs and csACTs, 98 genes were differentially expressed. Based on the principal component analysis (PCA) the csACTs were separated in two groups, of which Group 1 had significantly better survival after adrenalectomy (p = .002) than Group 2. Between csACT Group G1 and Group 2, 77 genes were differentially expressed. One of these, cytochrome P450 26B1 (CYP26B1), was significantly associated with survival in both our canine csACTs and in a publicly available data set of 33 human cortisol-secreting adrenocortical carcinomas. In the validation cohort, CYP26B1 was also expressed significantly higher (p = .012) in canine csACTs compared with NACs. In future studies it would be interesting to determine whether CYP26B1 inhibitors could inhibit csACT growth in both dogs and humans.

Serum vascular endothelial growth factor in dogs with various proliferative diseases.

Angiogenesis plays an important role in the proliferation and metastasis mechanisms of malignant tumors. Vascular endothelial growth factor (VEGF), a group of cytokines that contribute to angiogenesis and vasculogenesis. This study aimed to investigate the serum VEGF-A concentrations in dogs with various proliferative diseases. A total of 202 dogs that were histopathologically diagnosed with proliferative diseases were included in the study. Serum VEGF-A concentrations were measured using enzyme-linked immunosorbent assay. Median serum VEGF-A concentrations in dogs were as follows: healthy dogs, 4 pg/ml [0-21 pg/ml]; hepatocellular carcinoma, 30 pg/ml [0-158 pg/ml, P=<0.001]; hepatocellular adenoma, 32 pg/ml [0-49 pg/ml, P=0.003]; hepatic nodular hyperplasia, 18 pg/ml [0-51 pg/ml, P=0.595]; adrenal pheochromocytoma, 32 pg/ml [0-187 pg/ml, P=<0.001]; adrenocortical carcinoma, 32 pg/ml [3-161 pg/ml, P=0.002]; adrenocortical adenoma, 27 pg/ml [0-106 pg/ml, P=0.005]; colorectal adenocarcinoma, 36 pg/ml [0-75 pg/ml, P=0.002]; colorectal adenoma, 43 pg/ml [0-48 pg/ml, P=0.144]; inflammatory colorectal polyps, 37 pg/ml [0-111 pg/ml, P=<0.001]; pulmonary adenocarcinoma, 35 pg/ml [4-107 pg/ml, P=0.002]; pulmonary histiocytic sarcoma, 35 pg/ml [0-131 pg/ml, P=0.016]; and follicular thyroid carcinoma, 35 pg/ml [0-106 pg/ml, P=0.009]. The serum VEGF-A concentrations were significantly higher in dogs with neoplastic lesions compared to healthy dogs, except for colorectal adenoma. High serum VEGF-A concentrations were observed in dogs with proliferative diseases. The present study suggests that angiogenesis-inhibiting therapy, which targets VEGF-A, may be useful for canine neoplastic diseases.

18F-FDG PET/CT image findings of a dog with adrenocortical carcinoma.

BACKGROUND: In human medicine, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been used to differentiate between benign and malignant adrenal tumors and to identify metastases. However, canine adrenocortical carcinomas identified by 18F-FDG PET/computed tomography (CT) have not been reported. CASE PRESENTATION: A 13-year-old, castrated male, Cocker Spaniel dog with severe systolic hypertension exhibited an adrenal mass approximately 3.6 cm in diameter on ultrasonography. There was no evidence of pulmonary metastasis or vascular invasion on thoracic radiography and abdominal ultrasonography, respectively. 18F-FDG PET/CT was performed to identify the characteristics of the adrenal mass and the state of metastasis. One hour after injection of 5.46 MBq/kg 18F-FDG intravenously, the peripheral region of the adrenal mass visually revealed an increased 18F-FDG uptake, which was higher than that of the liver, and the central region of the mass exhibited necrosis. The maximal standardized uptake value (SUV) of the adrenal mass was 3.24; and relative SUV, calculated by dividing the maximal SUV of the adrenal tumor by the mean SUV of the normal liver, was 5.23. Adrenocortical carcinoma was tentatively diagnosed and surgical adrenalectomy was performed. Histopathologic examination of the resected adrenal mass revealed the characteristics of an adrenocortical carcinoma. After adrenalectomy, systolic blood pressure reduced to below 150 mmHg without any medication. CONCLUSION: This is the first case report of 18F-FDG PET/CT findings in a dog with suspected adrenocortical carcinoma and may provide valuable diagnostic information for adrenocortical carcinoma in dogs.

Diagnostic contribution of individual components of adrenal function tests to diagnose canine hyperadrenocorticism.

There is limited information regarding the value of constitutive components of the ACTH stimulation test (ACTHST) and low-dose dexamethasone suppression test (LDDST) including serum baseline cortisol (BC), difference between post-ACTH stimulation cortisol (PC) and BC (ΔACTHC), cortisol concentration 4h after dexamethasone administration (4HC), difference between 4HC and BC (Δ4C), and the difference between cortisol concentration 8h after dexamethasone administration and 4HC (Δ8C). Therefore, the objective of this study was to determine if these components can predict hyperadrenocorticism, pituitary-dependent hyperadrenocorticism (PDH), or functional adrenocortical tumor (FAT) in dogs. Cortisol concentrations were normalized, as fold change (FC), to the PC reference interval upper limit. A total of 1267 dogs were included, with hyperadrenocorticism diagnosed in 537 (PDH, n=356; FAT, n=28; undetermined, n=153) and excluded in 730. The area under the receiver operating curves for BC, ΔACTHC, 4HC, Δ4C, and Δ8C to predict hyperadrenocorticism were 0.76 (95% confidence interval (CI), 0.73-0.79), 0.91 (95% CI, 0.89-0.93), 0.83 (95% CI, 0.80-0.87), 0.55 (95% CI, 0.50-0.60), and 0.67 (95% CI, 0.62-0.72), respectively. A diagnostic limit of ≥0.78 FC for ΔACTHC had excellent sensitivity (1.00; 95% CI, 0.74-1.00), but poor specificity (0.67; 95% CI, 0.64-0.71), to predict FAT in dogs with a positive ACTHST. A diagnostic limit of ≥-0.26 FC for Δ4C had excellent sensitivity (1.00; 95% CI, 0.79-1.00), but poor specificity (0.21; 95% CI, 0.18-0.26), to predict FAT in dogs with a positive LDDST. In hyperadrenocorticoid dogs that have positive ACTHST or LDDST results, ΔACTHC or Δ4C, respectively, could be used to exclude FAT.

Molecular markers of prognosis in canine cortisol-secreting adrenocortical tumours.

Hypercortisolism is caused by a cortisol-secreting adrenocortical tumour (ACT) in approximately 15%-20% of cases in dogs. Little is known about which molecular markers are associated with malignant behaviour of canine ACTs. The objective of this study was to identify molecular markers of prognosis, which could be useful to refine prognostic prediction and to identify potential treatment targets. Cortisol-secreting ACTs were included from 40 dogs, of which follow-up information was available. The ACTs were classified as low risk of recurrence tumours (LRT; n = 14) or moderate-high risk of recurrence tumours (MHRT; n = 26), based on the novel histopathological Utrecht score. Normal adrenals (NAs) were included from 11 healthy dogs as reference material. The mRNA expression of 14 candidate genes was analysed in the 40 ACTs and in 11 NAs with quantitative RT-PCR. The genes' expression levels were statistically compared between NAs, LRTs and MHRTs. Univariate and multivariate analyses were performed to determine the association of the genes' expression levels with survival. Seven genes were differentially expressed between NAs and ACTs, of which pituitary tumour-transforming gene-1 (PTTG1) and topoisomerase II alpha (TOP2A) were also differentially expressed between LRTs and MHRTs. In survival analyses, high expression levels of Steroidogenic factor-1 (SF-1), PTTG1 and TOP2A were significantly associated with poor survival. In conclusion, we have identified several genes that are part of the molecular signature of malignancy in canine ACTs. These findings can be used to refine prognostic prediction, but also offer insights for future studies on druggable targets.

Sex-hormone producing adrenal tumors causing behavioral changes as the sole clinical sign in 3 cats.

Three neutered cats with adrenocortical tumors that were presented with behavioral changes but no evidence of hyperaldosteronism or hypercortisolism are described. All 3 cats had resolution of their clinical signs following adrenalectomy. For neutered cats presenting with behavior changes, a sex-hormone secreting adrenal tumor should be considered as a differential diagnosis.

Tumeurs surrénaliennes produisant des hormones sexuelles causant des changements de comportement comme seul signe clinique chez 3 chats. Les cas de trois chats stérilisés ayant des tumeurs surrénaliennes qui ont été présentés avec des changements comportementaux mais aucun signe d'hyperaldostéronisme ou hypercortisolisme sont décrits. Les trois chats ont eu une résorption de leurs signes cliniques après une surrénalectomie. Pour les chats stérilisés présentant des changements comportementaux, une tumeur surrénalienne sécrétant des hormones sexuelles devrait être considérée comme un diagnostic différentiel.(Traduit par Isabelle Vallières).

The Utrecht Score: A novel histopathological scoring system to assess the prognosis of dogs with cortisol-secreting adrenocortical tumours.

A cortisol-secreting adrenocortical tumour (ACT) is the cause of naturally occurring canine hypercortisolism in approximately 15% to 20% of cases. The differentiation between an adrenocortical adenoma and carcinoma is usually based on histopathology. However, histopathological parameters have never been linked to the dogs' survival. Moreover, in human medicine the inter-observer variability of some histopathological parameters that are used for ACTs is high. The objective of this study was to establish a reliable and easy-to-use histopathological scoring system for cortisol-secreting ACTs that can assess the prognosis of dogs after adrenalectomy. Cortisol-secreting ACTs of 50 dogs, collected between 2002 and 2015, were included in this study. Twenty histopathological features were assessed by one veterinary pathologist and one resident in veterinary pathology. In addition, the Ki67 proliferation index was assessed by two observers. Only parameters with intra- and inter-observer agreement scores (intra-class correlation or Cohen's kappa coefficient) of ≥0.40 were included in survival analyses. Use of multivariate forward stepwise regression analysis with associated hazard ratios led us to a scoring system which we call the Utrecht score: the Ki67 proliferation index, +4 if more than 33% of the tumour cells have clear/vacuolated cytoplasm and + 3 if necrosis is present. Using cut-off values of 6 and 11, we could distinguish three groups that had significantly shorter survival times with increasing Utrecht scores. We conclude that the Utrecht score can be used to assess the prognosis of dogs with cortisol-secreting ACTs after adrenalectomy, which can help to select high-risk dogs that might benefit from adjuvant treatment or additional monitoring.

Aldosterone-producing adrenocortical carcinoma with myxoid differentiation in a cat.

A 10-year-old male neutered Persian cat was presented with an abdominal mass and history of weakness. Blood smear examination found marked elliptocytosis, and serum biochemical analysis revealed hypokalemia, hypochloremia, increased creatine kinase activity, and a high aldosterone concentration. Cytologic examination of the mass revealed neoplastic endocrine cells with moderate criteria of malignancy, favoring adrenocortical neoplasia. The adrenal mass was surgically excised and histologically characterized by lobules of mildly pleomorphic, polygonal neoplastic cells with moderate to abundant, occasionally granular, eosinophilic cytoplasm. Lobules were separated by fine fibrovascular trabeculae, and numerous cystic cavities containing amorphous eosinophilic material that stained positive with Alcian blue and periodic acid-Schiff were seen. Neoplastic cells were multifocally positive for cytochrome P450 aldosterone synthase. Based on clinicopathologic and immunohistochemical findings the present case was diagnosed as an aldosterone-producing adrenocortical carcinoma with myxoid differentiation. While this entity has not been reported in cats, myxoid differentiation of adrenocortical carcinomas has been found in other species and can pose a major diagnostic challenge on microscopic examination.

Clinical and pathological features and outcome of bilateral incidental adrenocortical carcinomas in a dog.

A 9-year-old, spayed female Chihuahua was presented with a 1-week history of lethargy and anorexia. Abdominal ultrasonography and computed tomography found bilateral adrenal masses without metastasis. Serum cortisol levels that were sampled before and after an adrenocorticotropic hormone stimulation test were within reference ranges. Lethargy and anorexia completely resolved after short-term fluid therapy; the clinical signs did not occur for approximately 8 months until her sudden death. A postmortem examination revealed bilateral adrenocortical carcinomas and liver metastasis. Primary adrenocortical carcinomas developed in the dog met the definition of bilateral incidental adrenal gland masses (IAGMs). This is the first case report to demonstrate based on histological identification that adrenocortical carcinomas cause bilateral IAGMs in dogs.

POSTMORTEM FINDINGS IN CETACEANS FOUND STRANDED IN THE PELAGOS SANCTUARY, ITALY, 2007-14.

Between 2007 and 2014, 83 cetaceans were found stranded along the Ligurian coast of Italy, in the Pelagos Sanctuary, the largest marine protected area in the Mediterranean basin. Forty-nine (59%) were submitted to complete or partial necropsy, depending on the conservation status of the carcass. Based on gross and histological pathology and ancillary testing, the cause of death was determined and categorized as anthropogenic or natural (i.e., nonanthropogenic) in origin for 33 animals (67%) and of undetermined origin in the remaining 16 (33%). Natural causes of death, accompanied by either poor or good nutritional status, were attributed to 29 animals (59%), whereas four (8%) were diagnosed with an anthropogenic cause of death, consisting of interaction with fishing activities. Infectious and noninfectious disease was the most common cause of death, involving 29 cetaceans (59%). These data are valuable for understanding health and mortality trends in cetacean populations and can provide information for establishing policies for cetacean conservation and management in such an important protected area of the Mediterranean basin.

Outcome of laparoscopic adrenalectomy for resection of unilateral noninvasive adrenocortical tumors in 11 cats.

OBJECTIVE: To describe the technique and outcomes of laparoscopic adrenalectomy (LA) in cats with adrenocortical neoplasia. STUDY DESIGN: Retrospective case series. ANIMALS: Eleven client-owned cats with unilateral adrenal tumors. METHODS: Medical records of cats that underwent LA for unilateral functional adrenal tumors at 3 veterinary teaching hospitals were reviewed. Data collected included signalment, clinical signs, physical examination findings, diagnostic imaging results, preoperative laboratory tests, laparoscopic port placement and techniques, duration of anesthesia and surgery, complications, concomitant procedures, need for conversion to an open celiotomy, histopathological diagnosis, and postoperative survival. RESULTS: Eleven cats were included, 5 with right-sided and 6 with left-sided tumors. Tumors were aldosterone-secreting (n = 8), progesterone-secreting (n = 2), or testosterone-secreting (n = 1). Adrenalectomy was successfully performed in all 11 cats although 4 cases required conversion to an open celiotomy, due to poor visualization (n = 2), close adherence of the tumor to the caudal vena cava (n = 1), and inability to maintain adequate pneumoperitoneum (n = 1). Ten of the 11 cats were discharged from the hospital, with a median survival time of 803 days (range 467-1123 days). One cat died from severe pancreatitis and cardiogenic pulmonary edema. CONCLUSION: Adrenalectomy can be performed in cats via laparoscopy but is technically challenging, and associated with a relatively high conversion rate (36%).

Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma.

A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior.

Développement mammaire, hyperœstrogénémie et hypocortisolémie chez un chat mâle atteint d'un corticosurrénalome malin. Un corticosurrénalome malin, causant l'hyperœstrogénémie et produisant une hyperplasie mammaire et un comportement sexuel, a été diagnostiqué chez un chat domestique à poil court mâle stérilisé âgé de 14 ans. Une surranélectomie droite et une biopsie de la glande mammaire ont été réalisées. Un diagnostic de corticosurrénalome devrait être éliminée chez tout chat stérilisé ayant un développement mammaire et/ou manifestant un comportement sexuel.(Traduit par Isabelle Vallières).

Volumetric-modulated arc stereotactic radiotherapy for canine adrenocortical tumours with vascular invasion.

OBJECTIVES: To evaluate the feasibility and efficacy of hypofractionated stereotactic volumetric-modulated arc radiotherapy in treating canine adrenal tumours with vascular invasion. METHODS: A single-arm clinical study was performed. The dogs underwent total body computed tomography, brain and abdomen magnetic resonance imaging and endocrine assay. Adrenal masses were classified as cortisol-secreting adrenal tumour or non-secreting adrenal tumour. Radiotherapy treatments were delivered by hypofractionated stereotactic volumetric-modulated arc radiotherapy via a linear accelerator. The overall survival was estimated by the Kaplan-Meier method. The overall response and radio-toxicity effects were determined. RESULTS: Nine dogs were enrolled. Three dogs were affected by cortisol-secreting adrenal tumours and the remaining dogs had non-secreting adrenal tumours. The prescribed doses ranged from 30 to 45 Gy in three or five consecutive daily fractions. The median overall survival time was 1030 days, and the overall mean reduction of the diameter and volume were ~32 and 30% respectively. The endocrine profile normalised in two dogs with cortisol-secreting adrenal tumours. Radio-toxicities were mild and self-limiting. Seven deaths were recorded during the follow-up period and two dogs were censored. CLINICAL SIGNIFICANCE: Hypofractionated stereotactic volumetric-modulated arc radiotherapy should be considered as a feasible and effective therapeutic option for adrenal tumours with vascular invasion.

Cortisol-secreting adrenocortical tumours in dogs and their relevance for human medicine.

Spontaneous cortisol-secreting adrenocortical tumours in pet dogs are an attractive animal model for their human counterparts. Adrenal morphology and function are similar in dogs and humans, and adrenocortical tumours have comparable clinical and pathological characteristics. Their relatively high incidence in pet dogs represents a potential source of adrenocortical tumour tissue to facilitate research. The molecular characteristics of canine cortisol-secreting adrenocortical tumours suggest that they will be useful for the study of angiogenesis, the cAMP/protein kinase A pathway, and the role of Steroidogenic Factor-1 in adrenal tumourigenesis. Pet dogs with spontaneous cortisol-secreting adrenocortical tumours may also be useful in clinical testing of new drugs and in investigating the molecular background of adrenocortical tumours.

Left ventricular structural and functional abnormalities in dogs with hyperadrenocorticism.

OBJECTIVES: Hyperadrenocorticism has been reported to cause left ventricular (LV) structural and functional abnormalities in human patients. The purpose of the present study was to assess the incidence and features of LV structural and functional changes in dogs with hyperadrenocorticism. ANIMALS: Twenty-two client-owned dogs with pituitary-dependent hyperadrenocorticism (n = 15) and cortisol-secreting adrenocortical tumors (n = 7) and 6 control dogs were enrolled in this study. METHODS: Echocardiographic examinations were performed and non-invasive measurements of systolic blood pressure (SBP) were obtained. RESULTS: The normalized LV wall thickness and LV mass index of the affected dogs differed significantly from those of control dogs. Using a published reference value for M-mode measurements, 15 of the 22 dogs (68%) were found to have increased LV wall thickness. Eleven of the 15 (73%) dogs with increased LV wall thickness were normotensive, and no significant correlation between LV wall thickness and SBP was found. CONCLUSIONS: Regardless of the presence of systemic hypertension, hyperadrenocorticism should be included in the differential diagnosis of underlying disorders that may cause LV hypertrophy in dogs.

Therapeutic approach to Class II, Division 1 malocclusion with maxillary functional orthopedics

INTRODUCTION: Interceptive treatment of Class II, Division 1 malocclusion is a challenge orthodontists commonly face due to the different growth patterns they come across and the different treatment strategies they have available.OBJECTIVE: To report five cases of interceptive orthodontics performed with the aid of Klammt's elastic open activator (KEOA) to treat Class II, Division 1 malocclusion.METHODS: Treatment comprehends one or two phases; and the use of functional orthopedic appliances, whenever properly recommended, is able to minimize dentoskeletal discrepancies with consequent improvement in facial esthetics during the first stage of mixed dentition. The triad of diagnosis, correct appliance manufacture and patient's compliance is imperative to allow KEOA to contribute to Class II malocclusion treatment.RESULTS: Cases reported herein showed significant improvement in skeletal, dental and profile aspects, as evinced by cephalometric analysis and clinical photographs taken before, during and after interceptive orthodontics.

INTRODUÇÃO: o tratamento interceptor da má oclusão de Classe II primeira divisão é um desafio comum para os ortodontistas, em função dos diferentes padrões de crescimento que podem ser encontrados e das estratégias de tratamento disponíveis.OBJETIVO:apresentar cinco casos de interceptação da má oclusão de Classe II primeira divisão usando o ativador aberto elástico de Klammt (AAEK).MÉTODOS: o tratamento dessa má oclusão pode ser realizado em uma ou duas fases; e a utilização dos aparelhos ortopédicos funcionais, de acordo com suas indicações, pode minimizar as discrepâncias dentoesqueléticas, melhorando, consequentemente, a estética facial na primeira fase da dentição mista. O diagnóstico, a correta confecção do aparelho e a cooperação do paciente são a tríade indispensável para que o AAEK seja um coadjuvante no tratamento dessa má oclusão.RESULTADOS: os casos clínicos apresentaram melhora significativa nos aspectos esquelético, dentário e de perfil, evidenciada pelas análises cefalométricas e, no aspecto clínico, pelas fotografias pré- e trans-tratamento e após a interceptação.

Expression of somatostatin, dopamine, progesterone and growth hormone receptor mRNA in canine cortisol-secreting adrenocortical tumours.

Cortisol-secreting adrenocortical tumours (AT) in dogs are characterised by uncontrolled growth and excessive cortisol secretion. Dysregulated hormone receptor expression might be involved in tumour growth and hypersecretion of cortisol. The relative mRNA expression of growth hormone receptor, progesterone receptor, somatostatin receptors (SSTR1-3) and dopamine receptors (DRD1-2 and DRD5) was evaluated in 36 canine ATs and 15 adrenal glands obtained from healthy dogs. Compared with normal adrenal tissue, DRD2 mRNA expression was relatively lower in carcinomas, while SSTR1 mRNA expression was lower in both adenomas and carcinomas. Both of these features might contribute to loss of inhibition of tumour growth and upregulation of cortisol secretion. In canine ATs that had recurred within 30 months of surgical adrenalectomy, a marked increase in expression of DRD1 mRNA was observed. Targeting of specific hormone receptors, expressed by ATs, might be exploited for therapy.

Insulin-like growth factor--phosphatidylinositol 3 kinase signaling in canine cortisol-secreting adrenocortical tumors.

BACKGROUND: Hypercortisolism is a common endocrine disorder in dogs, caused by a cortisol-secreting adrenocortical tumor (AT) in approximately 15% of cases. In adrenocortical carcinomas of humans, activation of the phosphatidylinositol 3 kinase (PI3K) signaling pathway by insulin-like growth factor (IGF) signaling represents a promising therapeutic target. OBJECTIVES: To investigate the involvement of PI3K signaling in the pathogenesis of ATs in dogs and to identify pathway components that may hold promise as future therapeutic targets or as prognostic markers. ANIMALS: Analyses were performed on 36 canine cortisol-secreting ATs (11 adenomas and 25 carcinomas) and 15 normal adrenal glands of dogs. METHODS: mRNA expression analysis was performed for PI3K target genes, PI3K inhibitor phosphatase and tensin homolog (PTEN), IGFs, IGF receptors, IGF binding proteins and epidermal growth factor receptors. Mutation analysis was performed on genes encoding PTEN and PI3K catalytic subunit (PIK3CA). RESULTS: Target gene expression indicated PI3K activation in carcinomas, but not in adenomas. No amino acid-changing mutations were detected in PTEN or PIK3CA and no significant alterations in IGF-II or IGFR1 expression were detected. In carcinomas, ERBB2 expression tended to be higher than in normal adrenal glands, and higher expression of inhibitor of differentiation 1 and 2 (ID1 and ID2) was detected in carcinomas with recurrence within 2.5 years after adrenalectomy. CONCLUSIONS AND CLINICAL IMPORTANCE: Based on these results, ERBB2 might be a promising therapeutic target in ATs in dogs, whereas ID1 and 2 might be valuable as prognostic markers and therapeutic targets.