Morphologic and Molecular Characterization of Adrenals and Adrenal Rest Affected by Congenital Adrenal Hyperplasia.

Introduction: Adrenocortical hyperplasia and adrenal rest tumor (ART) formation are common in congenital adrenal hyperplasia (CAH). Although driven by excessive corticotropin, much is unknown regarding the morphology and transformation of these tissues. Our study objective was to characterize CAH-affected adrenals and ART and compare with control adrenal and gonadal tissues. Patients/Methods: CAH adrenals, ART and control tissues were analyzed by histology, immunohistochemistry, and transcriptome sequencing. We investigated protein expression of the ACTH receptor (MC2R), steroidogenic (CYP11B2, CYP11B1, CYB5A) and immune (CD20, CD3, CD68) biomarkers, and delta-like 1 homolog (DLK1), a membrane bound protein broadly expressed in fetal and many endocrine cells. RNA was isolated and gene expression was analyzed by RNA sequencing (RNA-seq) followed by principle component, and unsupervised clustering analyses. Results: Based on immunohistochemistry, CAH adrenals and ART demonstrated increased zona reticularis (ZR)-like CYB5A expression, compared to CYP11B1, and CYP11B2, markers of zona fasciculata and zona glomerulosa respectively. CYP11B2 was mostly absent in CAH adrenals and absent in ART. DLK1 was present in CAH adrenal, ART, and also control adrenal and testis, but was absent in control ovary. Increased expression of adrenocortical marker MC2R, was observed in CAH adrenals compared to control adrenal. Unlike control tissues, significant nodular lymphocytic infiltration was observed in CAH adrenals and ART, with CD20 (B-cell), CD3 (T-cell) and CD68 (macrophage/monocyte) markers of inflammation. RNA-seq data revealed co-expression of adrenal MC2R, and testis-specific INSL3, HSD17B3 in testicular ART indicating the presence of both gonadal and adrenal features, and high expression of DLK1 in ART, CAH adrenals and control adrenal. Principal component analysis indicated that the ART transcriptome was more similar to CAH adrenals and least similar to control testis tissue. Conclusions: CAH-affected adrenal glands and ART have similar expression profiles and morphology, demonstrating increased CYB5A with ZR characteristics and lymphocytic infiltration, suggesting a common origin that is similarly affected by the abnormal hormonal milieu. Immune system modulators may play a role in tumor formation of CAH.

Hyperadrenocorticism Caused by a Pituitary Ganglioglioma in a Dog.

An 11-year-old castrated male Chihuahua dog was presented with complaints of polyuria, polydipsia, abdominal enlargement, and alopecia. Hyperadrenocorticism was diagnosed on the basis of clinical signs, blood tests, adrenocorticotropin-stimulation test results, and an elevated serum adrenocorticotropin concentration. Contrast-enhanced magnetic resonance imaging showed that the pituitary gland was enlarged, compatible with a pituitary macroadenoma. Pituitary-dependent hyperadrenocorticism was suspected, and transsphenoidal hypophysectomy was thus performed for complete resection of the tumor. After surgery, the serum adrenocorticotropin concentration normalized and the hyperadrenocorticism resolved. Histological and immunocytochemical analyses revealed a benign tumor composed of mature neuronal cells and glial cells, suggestive of a ganglioglioma with immunolabeling for adrenocorticotropin. Careful analysis of the resected tumor revealed no pituitary adenoma tissue. The clinical and histopathologic findings indicated that the ganglioglioma was directly responsible for the hyperadrenocorticism. This is the first case of hyperadrenocorticism caused by a ganglioglioma in a dog.

Ultrasonographic evaluation of skin thickness in small breed dogs with hyperadrenocorticism.

The purpose of this study was to propose a standard for differentiation between normal dogs and patients with hyperadrenocorticism (HAC) by measuring skin thickness via ultrasonography in small breed dogs. Significant changes in skin thickness of patients treated with prednisolone (PDS) or patients with HAC treated with trilostane were evaluated. Skin thickness was retrospectively measured on three abdominal digital images obtained from small breed dogs weighing ＜ 15 kg that underwent abdominal ultrasonography. Mean skin thickness of normal dogs was 1.03 ± 0.25 mm (mean ± SD). Both the HAC and PDS groups showed significantly thinner skin than that in the normal group. Seven of the 10 HAC patients treated with trilostane had increased skin thickness. The area under the curve value of 0.807 was based on the receiver operating characteristics (ROC) curve for differentiating normal dogs from HAC patients. Sensitivity was 76% and specificity was 73% when skin thickness was less than the 0.83 mm cutoff value. In conclusion, measurement of skin thickness in small breed dogs by using ultrasonography is likely to provide clinical information useful in differentiating HAC patients from normal dogs. However, exposure to PDS, trilostane, and other conditions may have a significant effect on skin thickness.

Age-dependent effects of Armc5 haploinsufficiency on adrenocortical function.

Inactivating mutations in the Armadillo repeat-containing 5 (ARMC5) gene have recently been discovered in primary macronodular adrenal hyperplasia (PMAH), a cause of Cushing syndrome. Biallelic ARMC5 inactivation in PMAH suggested that ARMC5 may have tumor suppressor functions in the adrenal cortex. We generated and characterized a new mouse model of Armc5 deficiency. Almost all Armc5 knockout mice died during early embryonic development, around 6.5 and 8.5 days. Knockout embryos did not undergo gastrulation, as demonstrated by the absence of mesoderm development at E7.5. Armc5 heterozygote mice (Armc5+/-) developed normally but at the age of 1 year, their corticosterone levels decreased; this was associated with a decrease of protein kinase A (PKA) catalytic subunit α (Cα) expression both at the RNA and protein levels that were also seen in human patients with PMAH and ARMC5 defects. However, this was transient, as corticosterone levels normalized later, followed by the development of hypercorticosteronemia in one-third of the mice at 18 months of age, which was associated with increases in PKA and Cα expression. Adrenocortical tissue analysis from Armc5+/- mice at 18 months showed an abnormal activation of the Wnt/ß-catenin signaling pathway in a subset of zona fasciculata cells. These data confirm that Armc5 plays an important role in early mouse embryonic development. Our new mouse line can be used to study tissue-specific effects of Armc5. Finally, Armc5 haploinsufficiency leads to Cushing syndrome in mice, but only later in life, and this involves PKA, its catalytic subunit Cα, and the Wnt/ß-catenin pathway.

Concurrent hyperadrenocorticism and diabetes mellitus in dogs.

Hyperadrenocorticism (HAC) and diabetes mellitus (DM) are two diseases that can occur concurrently in dogs. The objective of this study was to evaluate the coexistence of HAC and DM, and the risk factors involved that could contribute to the development of DM in dogs with HAC. A total of 235 dogs with HAC were studied and, according to their fasting glycemia, they were divided into three groups: <5.6mmol/L, between 5.6 and 10.08mmol/L and >10.08mmol/L. The following parameters were evaluated: age, gender, cause of HAC, body condition, glycemia, total cholesterol, triglycerides, urinary cortisol:creatinin ratio (UCCR) and survival time. A 13.61% concurrence of HAC and DM was observed. Dogs with a fasting glycemia >5.6mmol/L, with dislipemia, with Pituitary-Dependent Hyperadrenocorticism, UCCR >100×10-6 and non-castrated females showed a higher risk of developing DM. The development of DM in dogs with HAC reduces the survival time.

Lack of association between clinical signs and laboratory parameters in dogs with hyperadrenocorticism before and during trilostane treatment.

INTRODUCTION: Trilostane therapy, the treatment of choice for pituitary- dependent hyperadrenocorticism (HAC) in dogs, is monitored by assessing resolution of clinical signs and measuring adrenocortical reserve capacity with an ACTH-stimulation test. The aim of this prospective study was to evaluate agreement between clinical signs reported by owners and cortisol or ACTH concentrations before and during trilostane therapy (starting dose 1-2 mg/kg once daily). A questionnaire on signs of HAC was used and a clinical score calculated as the sum of the 9 questions. Eighteen questionnaires at diagnosis and 97 during therapy were filled out by owners of 32 dogs. An ACTH-stimulation test was performed at each reevaluation. There were weak correlations between abdominal girth, appetite or weight gain and cortisol concentrations during therapy. However, the clinical score did not correlate with cortisol or cACTH values. In 50% of dogs, trilostane application had to be changed from once daily to twice daily during the study. Clinical signs reported by owners matched poorly with cortisol or cACTH concentrations at any time point. If low-dose trilostane is used, treatment frequency often has to be increased.

INTRODUCTION: Le traitement au trilostane, médicament de choix dans les cas d'hyperadrénocorticisme hypophyso-dépendant chez le chien, est évalué sur la base de la disparition des symptômes cliniques et des résultats des tests de stimulation à l'ACTH. Le but de la présente étude prospective était de comparer les symptômes cliniques (évalués par les propriétaires) avec les concentrations de cortisol et d'ACTH endogène avant et durant un traitement au trilostane (dose initiale 1­2 mg/kg, 1× par jour). On a utilisé un questionnaire composé de 9 questions relatives aux symptômes cliniques sur la base desquels on a calculé un score clinique total. Dix-huit questionnaires ont été remplis au moment du diagnostic et 97 durant le traitement par les propriétaires de 32 chiens. Un test de stimulation à l'ACTH a été réalisé lors de chaque contrôle. Il existait de faibles corrélations entre le périmètre abdominal, l'appétit et la prise de poids et les taux de cortisol durant le traitement. Le score clinique total n'était toutefois pas corrélé avec les concentrations de cortisol ou d'ACTH. Chez la moitié des chiens, la dose de trilostane a du être répartie en deux prises journalières. Les symptômes cliniques jugés par les propriétaires montraient une mauvaise corrélation avec les taux de cortisol et d'ACTH durant le traitement au trilostane. Si on dose ce médicament de façon faible, il y a souvent lieu d'augmenter la fréquence des prises.

Serum cortisol concentrations in dogs with pituitary-dependent hyperadrenocorticism and atypical hyperadrenocorticism.

BACKGROUND: Atypical hyperadrenocorticism (AHAC) is considered when dogs have clinical signs of hypercortisolemia with normal hyperadrenocorticism screening tests. HYPOTHESIS/OBJECTIVES: To compare cortisol concentrations and adrenal gland size among dogs with pituitary-dependent hyperadrenocorticism (PDH), atypical hyperadrenocorticism (AHAC), and healthy controls. ANIMALS: Ten healthy dogs, 7 dogs with PDH, and 8 dogs with AHAC. METHOD: Dogs were prospectively enrolled between November 2011 and January 2013. Dogs were diagnosed with PDH or AHAC based on clinical signs and positive screening test results (PDH) or abnormal extended adrenal hormone panel results (AHAC). Transverse adrenal gland measurements were obtained by abdominal ultrasound. Hourly mean cortisol (9 samplings), sum of hourly cortisol measurements and adrenal gland sizes were compared among the 3 groups. RESULTS: Hourly (control, 1.4 ± 0.6 µg/dL; AHAC, 2.9 ± 1.3; PDH, 4.3 ± 1.5) (mean, SD) and sum (control, 11.3 ± 3.3; AHAC, 23.2 ± 7.7; PDH, 34.7 ± 9.9) cortisol concentrations differed significantly between the controls and AHAC (P < .01) and PDH (P < .01) groups. Hourly (P < .01) but not sum (P = .27) cortisol concentrations differed between AHAC and PDH dogs. Average transverse adrenal gland diameter of control dogs (5.3 ± 1.2 mm) was significantly less than dogs with PDH (6.4 ± 1.4; P = .02) and AHAC (7.2 ± 1.5; P < .01); adrenal gland diameter did not differ (P = .18) between dogs with AHAC and PDH. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum cortisol concentrations in dogs with AHAC were increased compared to controls but less than dogs with PDH, while adrenal gland diameter was similar between dogs with AHAC and PDH. These findings suggest cortisol excess could contribute to the pathophysiology of AHAC.

Clinical findings, diagnostic test results, and treatment outcome in cats with spontaneous hyperadrenocorticism: 30 cases.

BACKGROUND: Spontaneous hyperadrenocorticism (HAC) is rare in cats. Clinical findings, diagnostic test results, and response to various treatment options must be better characterized. OBJECTIVES: To report the clinical presentation, clinicopathologic findings, diagnostic imaging results, and response to treatment of cats with HAC. ANIMALS: Cats with spontaneous HAC. METHODS: Retrospective descriptive case series. RESULTS: Thirty cats (15 neutered males, 15 spayed females; age, 4.0-17.6 years [median, 13.0 years]) were identified from 10 veterinary referral institutions. The most common reason for referral was unregulated diabetes mellitus; dermatologic abnormalities were the most frequent physical examination finding. Low-dose dexamethasone suppression test results were consistent with HAC in 27 of 28 cats (96%), whereas ACTH stimulation testing was suggestive of HAC in only 9 of 16 cats (56%). Ultrasonographic appearance of the adrenal glands was consistent with the final clinical diagnosis of PDH or ADH in 28 of 30 cats (93%). Of the 17 cats available for follow-up at least 1 month beyond initial diagnosis of HAC, improved quality of life was reported most commonly in cats with PDH treated with trilostane. CONCLUSIONS AND CLINICAL IMPORTANCE: Dermatologic abnormalities or unregulated diabetes mellitus are the most likely reasons for initial referral of cats with HAC. The dexamethasone suppression test is recommended over ACTH stimulation for initial screening of cats with suspected HAC. Diagnostic imaging of the adrenal glands may allow rapid and accurate differentiation of PDH from ADH in cats with confirmed disease, but additional prospective studies are needed.

Risk of concomitant malignancy in hyperfunctioning adrenal incidentalomas.

BACKGROUND: Adrenal masses are common incidental findings on radiologic imaging. The association between malignancy and hormonal hyperactivity found in incidentally discovered adrenal tumors, however, remains unclear. METHODS: A retrospective analysis of prospectively collected data from patients who underwent adrenalectomy for incidentally discovered adrenal tumors at a single institution. Outcomes and operative data were compared by univariate analysis. Area under the curve was used to analyze the effect of tumor size in predicting malignancy. RESULTS: There were 49 patients who initially presented with adrenal incidentalomas that underwent adrenalectomy. Most patients were Caucasian women with an average age of 51 ± 14 years. Of this group, 24 patients underwent resection for hyperfunctioning adrenal glands. There were no significant differences in malignancy rates between hyperfunctional and nonfunctional tumors (4.1% vs. 12.0%, P = 0.32). On final histopathology, there were four patients with adrenal malignancies: two adrenocortical carcinomas and two metastatic from renal carcinoma. Only one patient with a hyperfunctioning adrenal tumor had underlying malignancy. Overall, invasion of adjacent structures (P < 0.001), presence of lymphadenopathy (P = 0.02), metastasis (P = 0.03), irregular tumor margins (P = 0.01), heterogeneity (P = 0.05), and tumor size >6 cm (P = 0.04) on radiologic imaging were strongly associated with malignancy in adrenal incidentalomas. CONCLUSIONS: The risk of concomitant malignancy and hormonal hyperactivity in adrenal incidentalomas is very low. Tumor size (>6 cm) and radiographic features remain the most important predictors of adrenal malignancy, regardless of tumor function.

Contrast-enhanced ultrasonographic characteristics of adrenal glands in dogs with pituitary-dependent hyperadrenocorticism.

A noninvasive method for quantifying adrenal gland vascular patterns could be helpful for improving detection of adrenal gland disease in dogs. The purpose of this retrospective study was to compare the contrast-enhanced ultrasound (CEUS) characteristics of adrenal glands in 18 dogs with pituitary-dependent hyperadrenocorticism (PDH) vs. four clinically healthy dogs. Each dog received a bolus of the contrast agent (SonoVue®, 0.03 ml/kg of body weight) into the cephalic vein, immediately followed by a 5 ml saline flush. Dynamic contrast enhancement was analyzed using time-intensity curves in two regions of interest drawn manually in the caudal part of the adrenal cortex and medulla, respectively. In healthy dogs, contrast enhancement distribution was homogeneous and exhibited increased intensity from the medulla to the cortex. In the washout phase, there was a gradual and homogeneous decrease of enhancement of the adrenal gland. For all dogs with PDH, there was rapid, chaotic, and simultaneous contrast enhancement in both the medulla and cortex. Three distinct perfusion patterns were observed. Peak perfusion intensity was approximately twice as high (P < 0.05) in dogs with PDH compared with that of healthy dogs (28.90 ± 10.36 vs. 48.47 ± 15.28, respectively). In dogs with PDH, adrenal blood flow and blood volume values were approximately two- to fourfold (P < 0.05) greater than those of controls. Findings from the present study support the use of CEUS as a clinical tool for characterizing canine adrenal gland disease based on changes in vascular patterns.

Contrast-enhanced ultrasonographic evaluation of adrenal glands in dogs with pituitary-dependent hyperadrenocorticism.

OBJECTIVE: To assess vascular changes induced by hyperadrenocorticism of hyperplastic adrenal glands in dogs via contrast-enhanced ultrasonography. ANIMALS: 12 dogs with pituitary-dependent hyperadrenocorticism (PDH) and 7 healthy control dogs ≥ 7 years old. PROCEDURES: Dogs were assigned to the PDH and control groups and to small-breed (n = 6), medium-breed (4), and large-breed (9) subgroups. Contrast-enhanced ultrasonography of both adrenal glands in each dog was performed with IV injections of contrast agent. Time-intensity curves for the adrenal cortex, adrenal medulla, and ipsilateral renal artery of both adrenal glands were generated. Perfusion variables (time to peak [TTP], upslope of wash-in phase, and downslope of washout phase) were calculated. RESULTS: Contrast-enhanced ultrasonography revealed no qualitative difference between PDH and control groups. Quantitatively, TTPs were longer in the adrenal cortex and adrenal medulla of the PDH group, compared with values for the control group, particularly in the adrenal cortex and adrenal medulla of the small-breed subgroup. Washout downslopes were lower for the renal artery, adrenal cortex, and adrenal medulla of the small-breed subgroup between the PDH and control groups. No other perfusion variables differed between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Contrast-enhanced ultrasonography of the adrenal glands in dogs with PDH revealed a delayed TTP in the adrenal cortex and adrenal medulla, compared with values for control dogs. Contrast-enhanced ultrasonography was able to detect vascular changes induced by hyperadrenocorticism. Further studies are needed to evaluate whether reference ranges for clinically normal dogs and dogs with PDH can be determined and applied in clinical settings.

Single-incision laparoscopic adrenalectomy at Viet Duc University Hospital.

INTRODUCTION: Laparoscopic adrenalectomy is the technique of choice in the treatment of adrenal tumors. SILS has recently been introduced in this field and applied in Viet Duc University Hospital. Herein, we report our experience with single-incision transperitoneal adrenalectomy. METHODS: Between August 2010 and January 2012, 61 patients (23 men, 38 women) underwent SILS adrenalectomy at our institution. The diagnoses consisted of 20 patients with pheochromocytoma, 17 with nonfunctioning adenoma, 16 with Conn syndrome, 4 with Cushing syndrome and 4 with adrenal cysts. The mean age was 47.8 years (range, 21-68 years). There were 29 right-sided and 32 left-sided tumors; their mean diameter was 30.7 mm (range, 8-59 mm). Patients were in the flank position with the operated side up. A 2.5-cm pararectal incision at the level of the umbilicus was made to insert the SILS Port. RESULTS: The mean operating time was 78 min (range, 50-120 min), and mean blood loss was approximately 70 mL. Left-sided tumors were excised entirely with the SILS technique. Right-sided lesions sometimes required an additional trocar (hybrid technique). No drainage was needed at the operating site. There were no intraoperative or postoperative complications, but one case was converted to the conventional three-port technique. The mean length of hospital stay was 3.4 days (range, 2-6 days). CONCLUSION: Our preliminary results show that SILS adrenalectomy is safe and technically feasible. It should be considered among the surgical managements for selected patients with adrenal tumors.

Activation of cyclic AMP signaling leads to different pathway alterations in lesions of the adrenal cortex caused by germline PRKAR1A defects versus those due to somatic GNAS mutations.

CONTEXT: The overwhelming majority of benign lesions of the adrenal cortex leading to Cushing syndrome are linked to one or another abnormality of the cAMP or protein kinase pathway. PRKAR1A-inactivating mutations are responsible for primary pigmented nodular adrenocortical disease, whereas somatic GNAS activating mutations cause macronodular disease in the context of McCune-Albright syndrome, ACTH-independent macronodular hyperplasia, and, rarely, cortisol-producing adenomas. OBJECTIVE AND DESIGN: The whole-genome expression profile (WGEP) of normal (pooled) adrenals, PRKAR1A- (3) and GNAS-mutant (3) was studied. Quantitative RT-PCR and Western blot were used to validate WGEP findings. RESULTS: MAPK and p53 signaling pathways were highly overexpressed in all lesions against normal tissue. GNAS-mutant tissues were significantly enriched for extracellular matrix receptor interaction and focal adhesion pathways when compared with PRKAR1A-mutant (fold enrichment 3.5, P < 0.0001 and 2.1, P < 0.002, respectively). NFKB, NFKBIA, and TNFRSF1A were higher in GNAS-mutant tumors (P < 0.05). Genes related to the Wnt signaling pathway (CCND1, CTNNB1, LEF1, LRP5, WISP1, and WNT3) were overexpressed in PRKAR1A-mutant lesions. CONCLUSION: WGEP analysis revealed that not all cAMP activation is the same: adrenal lesions harboring PRKAR1A or GNAS mutations share the downstream activation of certain oncogenic signals (such as MAPK and some cell cycle genes) but differ substantially in their effects on others.

Potential variant of multiple endocrine neoplasia in a dog.

This report describes multiple endocrine neoplasia in a dog, which is a rare hereditary disorder characterized by the presence of two or more neoplasms of different endocrine tissues within a patient. A 14 yr old dog was evaluated for polyuria/polydipsia, polyphagia, and abdominal enlargement. Adrenal-dependent hyperadrenocorticism with concomitant left thyroid enlargement and a presumed abdominal metastatic lesion were diagnosed by an adrenocorticotropic hormone stimulation test, ultrasonography, and computed tomography. Trilostane therapy was initiated and resolved the clinical signs for 2 yr at which time the dog presented with left testicular enlargement. The dog was euthanized and was diagnosed with adrenocortical carcinoma, thyroid carcinoma, an abdominal mass compatible with a metastatic lymph node, and bilateral interstitial cell testicular adenomas. To the authors' knowledge, this is the first report to describe the concomitant association of these types of endocrine neoplasms in a dog. The concomitant presence of these neoplasms could represent a potential variant of multiple endocrine neoplasia; however, the presence of the interstitial cell testicular adenomas may have only been an incidental finding. If any of these tumors are diagnosed, veterinarians should perform a thorough clinical assessment to evaluate for the presence of additional endocrine neoplasms or hyperplasia.

Use of computed tomography adrenal gland measurement for differentiating ACTH dependence from ACTH independence in 64 dogs with hyperadenocorticism.

BACKGROUND: The measurement of adrenal gland size on computed tomography (CT) scan has been proposed for the etiological diagnosis of hyperadrenocorticism (HAC) in dogs. Symmetric adrenal glands are considered to provide evidence for ACTH-dependent hyperadrenocorticism (ADHAC), whereas asymmetry suggests ACTH-independent hyperadrenocorticism (AIHAC). However, there are currently no validated criteria for such differentiation. OBJECTIVE: The aim of this retrospective study was to compare various adrenal CT scan measurements and the derived ratios in ADHAC and AIHAC cases, and to validate criteria for distinguishing between these conditions in a large cohort of dogs. ANIMALS: Sixty-four dogs with HAC (46 ADHAC, 18 AIHAC). METHODS: Dogs with confirmed HAC and unequivocal characterization of its origin were included. Linear measurements of adrenal glands were made on both cross-sectional and reformatted images. RESULTS: An overlap was systematically observed between the AIHAC and ADHAC groups for all measurements tested. Overlaps also were observed for ratios tested. For the maximum adrenal diameter ratio derived from reformatted images (rADR), only 1/18 AIHAC dogs had a rADR within the range for ADHAC. For a threshold of 2.08, the 95% confidence intervals for estimated sensitivity and specificity extended from 0.815 to 1.000 and from 0.885 to 0.999, respectively, for AIHAC diagnosis. CONCLUSION AND CLINICAL IMPORTANCE: Measurements from cross-sectional or reformatted CT scans are of little use for determining the origin of HAC. However, rADR appears to distinguish accurately between ADHAC and AIHAC, with a rADR > 2.08 highly suggestive of AIHAC.

Ultrasonographic adrenal gland measurements in clinically normal small breed dogs and comparison with pituitary-dependent hyperadrenocorticism.

Ultrasonography is a sensitive and specific screening method for assessing the adrenal glands. The upper limit of the normal adrenal gland width is used as 7.5 mm. It is not known if adrenal gland width remains consistent with body weight. A reliable criterion of adrenal gland width in small breed dogs should be established. Small breed dogs with body weights of less than 10 kg were divided into two groups: 189 normal dogs and 22 dogs with pituitary-dependent hyperadrenocorticism (PDH). A retrospective study was conducted on dogs seen between January 1, 2006, and February 10, 2008. One hundred eighty-nine dogs of 14 different small breeds were enrolled in the normal adrenal gland group; the median gland width was 4.20 mm. Twenty-two dogs were in the PDH group; the median gland width was 6.30 mm. The cut-off value between normal adrenal glands and PDH was 6.0 mm. This figure gave a sensitivity and specificity of 75 and 94%, respectively, for detecting PDH. The adrenal gland appeared as a peanut shape with homogeneous hypoechoic parenchyma in normal dogs and in most dogs with PDH as well. This study was performed in a large population of small breed dogs and suggests that the normal adrenal gland size in small breed dogs is smaller than previously reported. We believe that a cut-off of 6.0 mm may be used as the criterion for differentiating a normal adrenal gland from adrenal hyperplasia.

Magnetic resonance imaging assessment of pituitary posterior lobe displacement in dogs with pituitary-dependent hyperadrenocorticism.

The displacement and signal intensity (SI) of the pituitary posterior lobe were evaluated on T1 weighted magnetic resonance (MR) images in 28 dogs with pituitary dependent hyperadrenocorticism (PDH). Compared with normal dogs, the posterior lobe was displaced dorsally in the pituitary of the PDH dogs. Correlation between the pituitary height/brain area (P/B) ratio and the displacement of the posterior lobe in the PDH dogs suggests that dorsal displacement of the posterior lobe increases in accordance with enlargement of the pituitary. As to the SI of the posterior lobe, the PDH dogs showed significantly lower SI in comparison to the normal dogs. Taken together, these results suggest that assessment of the displacement and SI of the posterior lobe of the pituitary on T1-weighted MR images is useful for the diagnosis of pituitary adenoma. In pituitary microadenoma that presents no apparent tumorigenesis on MRI, evaluation of these values may be useful for diagnosis and selection of an appropriate therapy.

Insulin resistance in cats.

Insulin resistance is defined as decreased sensitivity to insulin. Insulin resistance is an important component of the pathogenesis of type 2 diabetes mellitus (DM), and resolution of peripheral insulin resistance in cats with type 2 DM together with good glycemic control may result in diabetic remission. In insulin-dependent diabetic cats, insulin resistance is manifested clinically as an inadequate response to an appropriate pharmacologic dose of insulin. This article focuses on the clinical problem of insulin resistance in insulin-dependent diabetic cats.

Insulin resistance in dogs.

In diabetic dogs, many concurrent diseases can cause resistance to exogenous insulin. The most common concurrent disorders in diabetic dogs are hyperadrenocorticism, urinary tract infection, acute pancreatitis, neoplasia, and hypothyroidism. When a concurrent disorder is treated, the insulin dose should be decreased to avoid possible hypoglycemia when an underlying cause of insulin resistance is removed. Hormonal disturbances have been observed in obese dogs, but the clinical significance of these changes is not known.

A comparative study by age and gender of the pituitary adenoma and ACTH and alpha-MSH secretion in dogs with pituitary-dependent hyperadrenocorticism.

Pituitary-dependent hyperadrenocorticism (PDH) is frequent in dogs. Little is known about its presentation in different age groups and its characteristics. Dividing the population under study (n=107) into three age groups we observed that 11.2% were young, 51.4% adults and 37.4% aged. Using magnetic resonance, pituitary tumours were intra-sellar (IS) in 30.8% and extra-sellar (ES) in 62.6% and the pars intermedia (PI) was affected in 6.5%. ES are predominant in females and IS in males (p<0.0001). In the adult-aged population, the ES and PI are predominant, while in the young, the IS predominate (p<0.0001). ACTH concentration was greater in the ES vs. IS (p<0.05). alpha-MSH did not present significant differences according to tumour size, showing a negative correlation (r=-0.47; p<0.01) vs. ACTH. Differences in adenoma size according to gender and their age-related frequency of apparition could be because of different origins of the corticotrophinoma.