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.

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.

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.

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.

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.

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.

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.

Ultrasonographic visualization of the adrenal glands of healthy ferrets and ferrets with hyperadrenocorticism.

A protocol was developed to compare the ultrasonographic characteristics of the adrenal glands of 21 healthy ferrets and 37 ferrets with hyperadrenocorticism. By using specific landmarks, the adrenal glands were imaged in 97% of the cases. The adrenal glands of ferrets with hyperadrenocorticism had a significantly increased thickness, with changes in shape, structure, and echogenicity compared to the adrenal glands of healthy ferrets. Based on the findings of the study, adrenal glands may be classified as abnormal when they have a rounded appearance, increased size of the cranial/caudal pole (thickness >3.9 mm), a heterogeneous structure, increased echogenicity, and/or signs of mineralization.

Clinical utility of noncontrast computed tomography attenuation value (hounsfield units) to differentiate adrenal adenomas/hyperplasias from nonadenomas: Cleveland Clinic experience.

Radiological characterization of an adrenal tumor as adenoma may decrease the need for follow-up imaging studies, biopsies, and unnecessary adrenalectomies. We retrospectively reviewed 299 adrenalectomies in 290 patients at Cleveland Clinic Foundation over a recent 5-yr period to assess the value of noncontrast Hounsfield units (HU) in characterizing whether an adrenal mass is adenoma or nonadenoma. The mean (+/- SD) HU value for the adrenocortical adenoma/hyperplasia group was 16.2 +/- 13.6 and significantly lower (P < 0.0001) than primary adrenocortical cancers (36.9 +/- 4.1), metastases (39.2 +/- 15.2), and pheochromocytomas (38.6 +/- 8.2). The sensitivity and specificity for 10- and 20-HU cutoff values to differentiate adenomas/hyperplasias from nonadenomas were 40.5 and 100% and 58.2 and 96.9%, respectively. The size of the adrenal tumor had less value with only 40.7 and 81.3% sensitivity and 94.7 and 61.4% specificity for 2- and 4-cm cutoff values. A combination of less than or equal to 4-cm adrenal mass size and noncontrast computed tomography HU less than or equal to 20 had 42.1% sensitivity and 100% specificity. Our study, the largest with surgical histopathology as the gold standard for diagnosis, supports a noncontrast computed tomography attenuation value of 10 HU as a safe cutoff value to differentiate adrenal adenomas/hyperplasias from nonadenomas.

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.

Quantitation of iodine-123 MIBG uptake by normal adrenal medulla in hypertensive patients.

Eighteen hypertensive patients with a clinical suspicion of pheochromocytoma and raised or borderline raised plasma catecholamine and urinary vanillyl mandelic acid (VMA) levels were studied by scintigraphy using 123I-labeled metaiodobenzylguanidine (MIBG). None of these patients had any scintigraphic evidence of pheochromocytoma at the time of study or on subsequent clinical follow-up. A quantitative approach was taken to calculate the adrenal medullary uptake of [123I]MIBG in these patients. Three different methods of quantitation were evaluated using data acquired from an anthropomorphic phantom and analysed by three independent observers. In the patient studies 34 out of 35 adrenal medullas were visualized with uptake in the range of 0.01-0.22% of the administered dose 22 hr postinjection which was calculated using the preferred quantitation method. This is an appropriate control group range for comparison with patients who have proven norepinephrine and epinephrine secreting tumors. A quantitative approach to [123I]MIBG imaging provides an important tool for studying adrenomedullary pathophysiology.

The normal dexamethasone-suppression adrenal scintiscan.

To establish the parameters of adrenal imaging under dexamethasone suppression (DS), 18 normotensive, normal male volunteers underwent dexamethasone-suppression adrenal scintiscanning. Five control groups were established and given dexamethasone, either 8 mg for 2 days or 4 mg for 7 days before 6 beta-[131I]iodomethyl-norcholesterol (NP-59) administration. NP-59 was given in doses of 2, 1, or 0.5 mCi. Early visualization (3--5 days) of the adrenals was noted in the groups on the 8 mg DS regimen with either 1 or 2 mCi of NP-59. Late visualization (5--7 days) was noted in the groups that received 4 mg DS and either 2, 1, or 0.5 mCi of NP-59, respectively. The normal adrenal will demonstrate uptake of NP-59 under DS, and the duration of DS before imaging is the critical factor as to when discernible adrenal visualization will occur. The documentation of the noraml suppression interval on these DS regimens provides a basis for the correct diagnostic interpretation of adrenal hyperfunction as seen on the dexamethasone-suppression NP-59 adrenal scan.

Imaging of medullary thyroid carcinoma and hyperfunctioning adrenal medulla using iodine-131 metaiodobenzylguanidine.

Scintigraphy with radiolabeled metaiodobenzylguanidine was performed in a patient with MEN Type IIa having a pheochromocytoma of the right adrenal gland, adrenomedullary hyperplasia of the left adrenal gland and a primary medullary thyroid carcinoma. The scintigraphic findings demonstrate visualization of all the above mentioned pathologies.

Imaging of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism.

Detailed imaging of the pituitary gland is a prerequisite for a successful outcome of transsphenoidal hypophysectomy in dogs because it allows for accurate preoperative localization and assessment of the size of the pituitary gland. Cisternography allows assessment of even small increases in the height of the pituitary gland, but the magnitude of suprasellar expansion of pituitary tumors cannot be assessed with this technique. Large pituitary tumors with suprasellar expansion can readily be detected with conventional contrast-enhanced computed tomography (CT), while pituitary microadenomas can be localized with dynamic contrast-enhanced CT. Dynamic examination of the entire pituitary may be possible with spiral dynamic CT. Magnetic resonance imaging (MRI) of the canine pituitary gland provides a clear differentiation between the pituitary gland and the surrounding structures, but it remains to be investigated whether in dogs MRI can replace dynamic CT for the detection of microadenomas and whether it allows accurate localization of the pituitary gland relative to the surgical landmarks.

Systemic disorders affecting the thoracic cage.

Conventional chest roentgenograms provide an opportunity to study changes in the thoracic cage produced by systemic or localized disorders. Careful evaluation of abnormalities often gives a clue to the diagnosis of clinically unsuspected disorders. In this article, the authors present a review of developmental, granulomatous, collagen vascular, hematopoietic, metabolic, endocrine, and neoplastic disorders affecting the thoracic cage.

Surgical management of aldosterone-producing adrenal adenomas: a review of 16 patients.

Tabulation of the diagnostic evaluation and operative treatment of 16 patients with aldosterone-producing adrenal adenomas is presented. The diagnosis of primary aldosteronism was confirmed in all patients by biochemical and radiologic studies. Selective venous sampling of adrenal vein aldosterone localized the adenoma in 14 patients and proved to be the single most helpful diagnostic procedure. Computed tomography was used recently to confirm the localization of these interesting lesions and may become the initial noninvasive diagnostic study. Confidence in the accuracy of preoperative localization has led to the choice of the posterior approach to the involved adrenal gland. Postoperative morbidity has been low regardless of the operative approach; however, subjective patient acceptance of posterior adrenalectomy suggests a more comfortable convalescence and a more rapid return to normal activity.

[Supra-renal venography in patients with suspected endocrine hypertension (author's transl)]. / Nebennierenvenographie bei Patienten mit Verdacht auf endokrine Hypertonie

In forty patients suspected clinically of having an endocrine cause for hypertension, an adrenal cortical adenoma was confirmed histologically in five. Hyperaldosteronism with enlarged or normal adrenals was demonstrated in three patients. The diagnosis in a further eight patients with an abnormal hormone pattern and/or an abnormal venogram has not yet been confirmed. Adrenal glands show considerable variation in their size, shape and localisation on venography.