Ultrasound evaluation of adrenal gland size in clinically healthy dogs and in dogs with hyperadrenocorticism.

BACKGROUND: Precise reference intervals of adrenal gland thickness are required for detection of adrenomegaly in dogs with hyperadrenocorticism (HAC). METHODS: Eighty-six clinically healthy dogs were prospectively included, and 91 dogs with untreated HAC were retrospectively evaluated. Dorso-ventral adrenal gland thickness was ultrasonographically measured on the sagittal plane. Dogs were classified into four body weight categories, and those with HAC were also ultrasonographically classified as consistent with pituitary-dependent HAC (PDH), adrenal-dependent HAC (FAT), equivocal adrenal asymmetry (EAA), or normal adrenal thickness. RESULTS: The upper limits for left adrenal gland in clinically healthy dogs were 5.1 mm (≥2.5-5 kg), 5.5 mm (>5-10 kg), 6.4 mm (>10-20 kg), and 7.3 mm (>20-40 kg), and for right adrenal gland the upper limits were 5.3 mm (≥2.5-5 kg), 6.8 mm (>5-10 kg), 7.5 mm (>10-20 kg), and 8.7 mm (>20-40 kg). The sensitivity of ultrasound to detect adrenomegaly in dogs with HAC was 95.6%. Most dogs with HAC (56.0%) had ultrasound findings consistent with either PDH or FAT; however, EAA was commonly occurring in 39.6% of dogs with HAC. CONCLUSIONS: The sensitivity of ultrasonography to detect adrenomegaly in dogs with HAC is high when using four weight categories. EAA is common in dogs with HAC.

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.

Changes of computed tomography-based body composition after adrenalectomy in patients with endogenous hypercortisolism.

CONTEXT: Data on longitudinal changes of computed tomography (CT)-determined visceral fat area (VFA), skeletal muscle area (SMA) and skeletal muscle radiodensity (SMD) after adrenalectomy are limited in patients with hypercortisolism. OBJECTIVE: To examine the association of severity of cortisol excess and improvement of CT-based muscle and fat parameters after adrenalectomy. DESIGN: Retrospective observational cohort study. PATIENTS: One hundred thirty-four patients with overt Cushing's syndrome (CS; n = 39), mild autonomous cortisol excess (MACE; n = 57), or nonfunctioning adrenal tumour (NFAT; n = 38) at a tertiary endocrinology institution between 2006 and 2017 were included. MEASUREMENTS: Changes in CT-determined VFA, visceral-to-subcutaneous fat ratio (VSR), SMA, skeletal muscle index (SMI), and SMD measured at the third lumbar vertebra (L3). RESULTS: At baseline, CS patients had higher VFA, lower SMA, SMI and SMD values, compared to NFAT or MACE patients. Compared to NFAT, significant decreases in VFA and increases in SMA, SMI and SMD was observed in CS 1 year after adrenalectomy. In MACE, adjusted mean changes of SMD but not VFA, SMA or SMI differ significantly compared to NFAT (+8.9% vs -3.4%, P = 0.032). In a multivariate linear regression model, the increase by 1 µg/dL of post-dexamethasone serum cortisol at baseline was independently associated with greater reduction of VFA (-3.95%), VSR (-3.07%), and increase in SMD (+0.92%, P < 0.05 for all) after adrenalectomy. CONCLUSIONS: The severity of cortisol excess was associated with greater improvement of L3 VFA, VSR and SMD 1 year after adrenalectomy. These CT-based markers may allow more objective assessment of treatment benefit at earlier stage.

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.

Ipilimumab-Induced Adrenalitis: A Possible Pitfall in 18F-FDG-PET/CT.

Ipilimumab is a monoclonal antibody against the inhibitory CTLA-4 receptor expressed on T cells. It provokes an upregulation of the immune system. This substance was approved by the US Food and Drug Administration in 2011 and is since increasingly used as a targeted therapeutic approach for metastasized melanoma. Ipilimumab is known to cause neuroendocrine disorders, such as hypophysitis and adrenal insufficiency. Our case of a 79-year-old patient represents an important imaging pitfall. Imaging findings of newly symmetrically and smoothly enlarged, hypermetabolic adrenal glands in the setting of previous ipilimumab therapy represent drug-induced adrenalitis and not metastatic disease.

Quantitative CT assessment of bone mineral density in dogs with hyperadrenocorticism.

Canine hyperadrenocorticism (HAC) is one of the most common causes of general osteopenia. In this study, quantitative computed tomography (QCT) was used to compare the bone mineral densities (BMD) between 39 normal dogs and 8 dogs with HAC (6 pituitary-dependent hyperadrenocorticism [PDH]; pituitary dependent hyperadrenocorticism, 2 adrenal hyperadrenocorticism [ADH]; adrenal dependent hyperadrenocorticism) diagnosed through hormonal assay. A computed tomogaraphy scan of the 12th thoracic to 7th lumbar vertebra was performed and the region of interest was drawn in each trabecular and cortical bone. Mean Hounsfield unit values were converted to equivalent BMD with bone-density phantom by linear regression analysis. The converted mean trabecular BMDs were significantly lower than those of normal dogs. ADH dogs showed significantly lower BMDs at cortical bone than normal dogs. Mean trabecular BMDs of dogs with PDH using QCT were significantly lower than those of normal dogs, and both mean trabecular and cortical BMDs in dogs with ADH were significantly lower than those of normal dogs. Taken together, these findings indicate that QCT is useful to assess BMD in dogs with HAC.

VARIABILITY IN THE ULTRASONOGRAPHIC APPEARANCE OF THE PANCREAS IN HEALTHY DOGS COMPARED TO DOGS WITH HYPERADRENOCORTICISM.

Anecdotally, an unusually hyperechoic pancreas can be found in seemingly healthy dogs on ultrasound examination and the prevalence and clinical significance of this finding is unknown. The objective of this study was to describe the prevalence of a hyperechoic and/or heterogenous pancreas in healthy dogs and correlate these findings to weight, age, and body condition score (BCS). An additional objective was to describe the prevalence of a hyperechoic and/or heterogenous pancreas in dogs with hyperadrenocorticism and compare this to the healthy dogs. Pancreata of 74 healthy dogs were evaluated prospectively and pancreatic echogenicity and echotexture were graded. Each dog's age, BCS, and weight were recorded. Dogs were screened for health by physical examination, serum chemistry panel, urine specific gravity, and a canine pancreatic lipase immunoreactivity assay. Pancreatic images for 92 dogs having hyperadrenocorticism were also reviewed and pancreatic echogenicity and echotexture were recorded. The prevalence of pancreatic hyperechogenicity in normal dogs was 7% (5 of 74) and heterogeneity was 40% (30 of 74). No correlation existed between pancreatic echogenicity and weight, age, or BCS (P > 0.1 for all sets). A statistically significant increase in the proportion of dogs having a hyperechoic pancreas was found in the hyperadrenocorticism sample of dogs (40%, 37 of 92, P < 0.0001). The underlying cause of pancreatic variability in the few healthy dogs and in dogs with hyperadrenocorticism is unknown and the varying appearance of the pancreas in these samples confounds interpretation of diseases such as chronic pancreatitis.

Hypokalaemia in a hyperthyroid domestic shorthair cat with adrenal hyperplasia.

A 13-year-old female domestic shorthair cat presented with polyphagia and weight loss. Marked systolic hypertension was found on examination. Elevated total thyroxine levels confirmed hyperthyroidism, and hypokalaemia was also documented. A euthyroid state and normotension were achieved following 4 weeks of treatment with carbimazole and amlodipine. Despite potassium supplementation, the hypokalaemia worsened. Abdominal ultrasonography revealed left adrenomegaly. Plasma aldosterone concentrations were initially in the lower half of the reference interval and, when repeated 2 months later, were undetectable. Urea and creatinine remained in the lower half of the reference interval throughout treatment, and urine specific gravity suggested good urine concentrating ability. The fractional excretion of potassium confirmed a renal source of potassium loss. Blood gas analysis was unremarkable. It was theorised that an aldosterone precursor was causing signs of mineralocorticoid excess and undetectable plasma aldosterone levels. Treatment with an aldosterone receptor antagonist successfully increased the serum potassium concentration. Owing to difficulties administering medication and associated effects on life quality the cat was euthanased. Adrenal hyperplasia was apparent on post-mortem histopathology.

Assessment of left ventricular function by two-dimensional speckle-tracking echocardiography in small breed dogs with hyperadrenocorticism.

BACKGROUND: Hyperadrenocorticism (HAC) is associated with an increased prevalence of hypertension. This study investigated the left ventricular function using two-dimensional speckle-tracking echocardiography (2D-STE) in small breed dogs affected with spontaneous HAC. Age-matched healthy controls (n = 9), dogs with pituitary-dependent hyperadrenocorticism (PDH, n = 10), and dogs with adrenal-dependent hyperadrenocorticism (ADH, n = 9) were included in this study. Conventional echocardiography, global longitudinal and circumferential strain, and strain rate were assessed. RESULTS: On group-wise comparison, left ventricular free wall (LVFWd) and interventricular septal thickness in diastole (IVSd) were thickest in the ADH group, followed by the PDH and controls (P = 0.014 and P = 0.001, respectively). Neither LVFWd nor IVSd was correlated with systemic blood pressure (P = 0.238 and P = 0.113, respectively). The values of all variables derived from the global strain and strain rate in longitudinal and circumferential directions followed the same pattern: highest in the controls, followed by PDH and then ADH (all P < 0.05, respectively). On multiple regression analyses, global longitudinal strain, global longitudinal strain rate in systole and early diastole, and global circumferential strain all decreased linearly with increased IVSd (all P < 0.05). CONCLUSIONS: Left ventricular hypertrophy (LVH) was more prevalent in the HAC group compared to the control group. Association between hypertension and development of LVH was not identified. Decreased global longitudinal and circumferential strains were associated with increased IVSd. 2D-STE revealed significant decreases in systolic functions that were undetected using conventional echocardiography in the ADH and PDH groups.

Trilostane therapy for treatment of spontaneous hyperadrenocorticism in cats: 15 cases (2004-2012).

BACKGROUND: Medical treatment with trilostane improves clinical signs, causes unclear insulin requirement changes, and variable survival times in cats. OBJECTIVES/HYPOTHESIS: To characterize the long-term efficacy of trilostane in treating cats with hyperadrenocorticism (HAC). ANIMALS: Fifteen client-owned cats with spontaneous HAC. METHODS: Multicenter descriptive retrospective study with a search performed on all medical records for cats diagnosed with spontaneous HAC. RESULTS: Clinical signs (13 of 15 cats) and ACTH stimulation testing results (13 of 15) improved with trilostane therapy. Diabetes mellitus was reported in 9/15 cases. Insulin requirements decreased by 36% within 2 months in 6/9 diabetic cats. Median survival time was 617 days for all cats (range 80-1,278 days). Complications included weight loss, urinary tract infections, chronic kidney disease, seizures, and recurrent pancreatitis. Hypocortisolemia was documented in 1 case. Cause of death occurred as a result of nonadrenal or nondiabetic illnesses (renal failure, seizures [caused by hypoglycemia or unknown]), or lymphoma. CONCLUSIONS AND CLINICAL IMPORTANCE: Trilostane ameliorates clinical signs of HAC in cats, is tolerated well in the long term, and can lead to improved regulation of diabetes.

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.

Assessment of the value of quantitative thyroid scintigraphy for determination of thyroid function in dogs.

OBJECTIVE: To assess the value of thyroid scintigraphy to determine thyroid status in dogs with hypothyroidism and various non-thyroidal illnesses. METHODS: Thyroid hormone concentrations were measured and quantitative thyroid scintigraphy performed in 21 dogs with clinical and/or clinicopathological features consistent with hypothyroidism. RESULTS: In 14 dogs with technetium thyroidal uptake values consistent with euthyroidism, further investigations supported non-thyroidal illness. In five dogs with technetium thyroidal uptake values within the hypothyroid range, primary hypothyroidism was confirmed as the only disease in four. The remaining dog had pituitary-dependent hyperadrenocorticism. Two dogs had technetium thyroidal uptake values in the non-diagnostic range. One dog had iodothyronine concentrations indicative of euthyroidism. In the other, a dog receiving glucocorticoid therapy, all iodothyronine concentrations were decreased. Markedly asymmetric technetium thyroidal uptake was present in two dogs. All iodothyronine concentrations were within reference interval but canine thyroid stimulating hormone concentration was elevated in one. Non-thyroidal illness was identified in both cases. CLINICAL SIGNIFICANCE: In dogs, technetium thyroidal uptake is a useful test to determine thyroid function. However, values may be non-diagnostic, asymmetric uptake can occur and excess glucocorticoids may variably suppress technetium thyroidal uptake and/or thyroid hormone concentrations. Further studies are necessary to evaluate quantitative thyroid scintigraphy as a gold standard method for determining canine thyroid function.

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.

Ultrasonography criteria for differentiating ACTH dependency from ACTH independency in 47 dogs with hyperadrenocorticism and equivocal adrenal asymmetry.

BACKGROUND: Adrenal ultrasonography (US) in dogs with hyperadrenocorticism (HAC) is commonly used to distinguish adrenocorticotropic hormone (ACTH)-independent (AIHAC) and ACTH-dependent hyperadrenocorticism (ADHAC). To date, no cut-off values for defining adrenal atrophy in cases of adrenal asymmetry have been determined. Given that asymmetrical hyperplasia is sometimes observed in ADHAC, adrenal asymmetry without ultrasonographic proof of adrenocortical tumor such as vascular invasion or metastasis can be equivocal. OBJECTIVE: The purpose of this study was to compare adrenal US findings between cases of ADHAC and AIHAC in dogs with equivocal adrenal asymmetry (EAA), and to identify useful criteria for their distinction. ANIMALS: Forty dogs with EAA were included. METHODS: Ultrasound reports of HAC dogs with adrenal asymmetry without obvious vascular invasion or metastases were reviewed. Dogs were classified as cases of ADHAC (n = 28) or AIHAC (n = 19), determined by plasma ACTH concentration. The thickness, shape, and echogenicity of both adrenal glands and presence of adjacent vascular compression were compared between AIHAC and ADHAC groups. RESULTS: The maximal dorsoventral thickness of the smaller gland (SDV) ranged from 2.0 to 5.0 mm in AIHAC and from 5.0 to 15.0 mm in ADHAC. The 95% confidence intervals for estimated sensitivity and specificity of a SDV cut-off set at 5.0 mm in the diagnosis of AIHAC were 82-100 and 82-99%, respectively. Other tested US criteria were found to overlap extensively between the 2 groups, precluding their usefulness for distinction. CONCLUSION AND CLINICAL IMPORTANCE: In EAA cases, an SDV ≤5.0 mm is an appropriate cut-off for AIHAC ultrasonographic diagnosis.

Diagnosis and outcome of a dog with iatrogenic hyperadrenocorticism and secondary pulmonary mineralization.

A 6-year-old, spayed female dog was evaluated for a history of chronic coughing, excessive panting, and lethargy. Iatrogenic hyperadrenocorticism was diagnosed, and pulmonary mineralization was documented with a 99m Technitium-methylene diphosphonate (99mTc-MDP) scan. Blood gas analysis showed hypoxia. Clinical signs resolved and blood gas values returned to normal when corticosteroid therapy was discontinued.