Clinical Review: The Approach to the Evaluation and Management of Bilateral Adrenal Masses.

OBJECTIVE: This white paper provides practical guidance for clinicians encountering bilateral adrenal masses. METHODS: A case-based approach to the evaluation and management of bilateral adrenal masses. Specific clinical scenarios presented here include cases of bilateral adrenal adenomas, hemorrhage, pheochromocytomas, metastatic disease, myelolipomas, as well as primary bilateral macronodular adrenal hyperplasia. RESULTS: Bilateral adrenal masses represent approximately 10% to 20% of incidentally discovered adrenal masses. The general approach to the evaluation and management of bilateral adrenal masses follows the same protocol as the evaluation of unilateral adrenal masses, determined based on the patient's clinical history and examination as well as the imaging characteristics of each lesion, whether the lesions could represent a malignancy, demonstrate hormone excess, or possibly represent a familial syndrome. Furthermore, there are features unique to bilateral adrenal masses that must be considered, including the differential diagnosis, the evaluation, and the management depending on the etiology. Therefore, considerations for the optimal imaging modality, treatment (medical vs surgical therapy), and surveillance are included. These recommendations were developed through careful examination of existing published studies as well as expert clinical opinion consensus. CONCLUSION: The evaluation and management of bilateral adrenal masses require a comprehensive systematic approach which includes the assessment and interpretation of the patient's clinical history, physical examination, dynamic hormone evaluation, and imaging modalities to determine the key radiographic features of each adrenal nodule. In addition, familial syndromes should be considered. Any final treatment options and approaches should always be considered individually.

Hereditary and Sporadic Pheochromocytoma: Comparison of Imaging, Clinical, and Laboratory Features.

BACKGROUND. A considerable fraction of pheochromocytomas initially suspected to be sporadic, whether or not symptomatic, are a result of germline mutations. OBJECTIVE. The purpose of this article is to compare imaging features between hereditary and sporadic pheochromocytomas. METHODS. This retrospective study included 71 patients (39 women, 32 men; median age, 48 years) who underwent adrenal pheochromocytoma resection from January 2002 to October 2021 after preoperative CT or MRI. Two radiologists independently reviewed examinations to assess features of the largest resected pheochromocytoma. Interreader agreement was assessed by prevalence-adjusted bias-adjusted kappa coefficients; a third radiologist resolved discrepancies for further analysis. Genetic testing was used to classify pheochromocytomas as hereditary or sporadic and to classify hereditary pheochromocytomas by germline mutation clusters. Symptoms associated with pheochromocytomas and preoperative biochemical laboratory values were recorded. Groups were compared using Kruskal-Wallis, Fisher exact, and chi-square tests, and false-discovery rate-adjusted p values were computed to account for multiple comparisons. RESULTS. Hereditary pheochromocytoma (n = 32), compared with sporadic pheochromocytoma (n = 39), was associated with younger median age (38 vs 52 years, p = .001) and smaller median size (24 vs 40 mm, p < .001). Interreader agreement for CT and MRI features, expressed as kappa, ranged from 0.44 to 1.00. Hereditary and sporadic pheochromocytoma showed no difference in frequency of calcifications, hemorrhage, cystic change/necrosis, or macroscopic fat on CT, or in frequency of hemorrhage, cystic change/necrosis, macroscopic fat, or microscopic fat on MRI (p > .05). When combining CT and MRI, cystic change/necrosis was observed in 35% of hereditary versus 67% of sporadic pheochromocytomas (p = .10). Hereditary pheochromocytoma, compared with sporadic, had lower frequency of symptoms (31% vs 74%; p = .004) and lower 24-hour urinary normetanephrines (1.1 vs 5.1 times upper limits of normal, p = .006). Among hereditary pheochromocytomas, cystic change/necrosis (when assessable on imaging) was present in 18% and 45% of those with cluster 1 (n = 11) and cluster 2 (n = 21) germ-line mutations, respectively. CONCLUSION. Hereditary pheochromocytomas, compared with sporadic, are detected at a younger age and smaller size, produce lower 24-hour urinary normetanephrines, are less often symptomatic, and may less frequently show cystic change/necrosis. CLINICAL IMPACT. Imaging findings may complement clinical and biochemical features in raising suspicion for a previously unsuspected germline mutation in patients with pheochromocytoma.

Use of a Continuous Glucose Monitoring System in High-Risk Hospitalized Noncritically Ill Patients With Diabetes After Cardiac Surgery and During Their Transition of Care From the Intensive Care Unit During COVID-19: A Pilot Study.

OBJECTIVE: Continuous glucose monitoring (CGM) has demonstrated benefits in managing inpatient diabetes. We initiated this single-arm pilot feasibility study during the COVID-19 pandemic in 11 patients with diabetes to determine the feasibility and accuracy of real-time CGM in patients who underwent cardiac surgery and whose care was being transitioned from the intensive care unit. METHODS: A Clarke error grid analysis was used to compare CGM and point-of-care measurements. The mean absolute relative difference (MARD) of the paired measurements was calculated to assess the accuracy of CGM for glucose measurements during the first 24 hours on CGM, the remaining time on CGM, and for different chronic kidney disease (CKD) strata. RESULTS: Overall MARD between point-of-care and CGM measurements was 14.80%. MARD for patients without CKD IV and V with an estimated glomerular filtration rate (eGFR) of ≥20 mL/min/1.73 m2 was 12.13%. Overall, 97% of the CGM values were within the no-risk zone of the Clarke error grid analysis. For the first 24 hours, a sensitivity analysis of the overall MARD for all patients and those with an eGFR of ≥20 mL/min/1.73 m2 was 15.42% ± 14.44% and 12.80% ± 7.85%, respectively. Beyond the first 24 hours, overall MARD for all patients and those with an eGFR of ≥20 mL/min/1.73 m2 was 14.54% ± 13.21% and 11.86% ± 7.64%, respectively. CONCLUSION: CGM has shown great promise in optimizing inpatient diabetes management in the noncritical care setting and after the transition of care from the intensive care unit with high clinical reliability and accuracy. More studies are needed to further assess CGM in patients with advanced CKD.

A Rare Case of Addison's Disease Presenting With Intermittent Pancytopenia and Cardiac Tamponade.

OBJECTIVE: To report the first case, to our knowledge, of intermittent pancytopenia and cardiac tamponade occurring together in association with Autoimmune Addison's Disease (AAD). METHODS: A 21 year-old woman presented on three different occasions with multiple complaints. Her evaluation was significant for intermittent pancytopenia (white blood cell, 1.3-3.0 × 103/µL [normal 4.5-11 × 103]; hemoglobin, 8.8-9.6 g/dL [11-16]; and platelets, 102-117 × 103/µL [150-400 × 103/µL]) and pericardial effusion with cardiac tamponade. Further investigation including a morning serum cortisol level of 0.6 µg/dL (5.27-22.45 µg/dL), adrenocorticotropic hormone level of 1027 pg/mL (normal 6-50 pg/mL), and positive 21-hydroxylase antibodies confirmed the diagnosis of primary adrenal insufficiency due to AAD. Treatment with steroids resulted in prompt hemodynamic recovery with normalization of all blood cell lines. RESULTS: The diagnosis of AAD is often delayed or overlooked. Pancytopenia occurring in AAD is most likely due to either marrow suppression in the setting of acute illness and exacerbated by hypoadrenalism or possibly an autoimmune-mediated marrow reaction. Pericarditis with cardiac tamponade has been described in AAD occurring in the setting of polyglandular autoimmune syndrome type II. The pathogenesis involves autoimmune inflammation of the pericardium, which precipitates an acute inflammatory reaction and rapid fluid accumulation. CONCLUSION: Pericarditis with cardiac tamponade and intermittent neutropenia may be rare manifestations of an Addisonian crisis.

Regional metastatic paraganglioma of the bladder: a rare cause of myocardial infarction, reversible cardiomyopathy and an intracardiac thrombus.

Sympathetic paragangliomas are rare neuroendocrine tumours that arise from chromaffin cells and secrete catecholamines. On rare occasions, patients with sympathetic paragangliomas can present with symptoms of congestive heart failure. The optimal treatment is surgical to remove all disease and thereby improve survival as well as restore cardiac function. We report a case of a patient with a regional metastatic bladder paraganglioma and a succinate dehydrogenase complex subunit B gene mutation presenting with cardiomyopathy who had significant improvement in his cardiac function with surgical resection despite further progression of metastatic disease. During his 4-year follow-up period, the patient remains free from heart-failure signs and symptoms.

Trends in Avoidable Hospitalizations for Diabetes: Experience of a Large Clinically Integrated Health Care System.

Prevention quality indicators (PQIs) are used in hospital discharge data sets to identify quality of care for ambulatory care-sensitive conditions, such as diabetes. We examined the impact of clinical integration efforts on diabetes-related PQIs in a large community-based health care organization. Inpatient and observation hospitalizations from nine acute care hospitals were trended over 5 years (2012-2016). Using established technical specifications, annual hospitalizations rates were calculated for four diabetes-related PQIs: uncontrolled diabetes, short-term complications, long-term complications, and lower extremity amputations. The mean (±standard error of the mean) annual hospitalization rate for uncontrolled diabetes and short-term complications gradually increased from 1.3 ± 1.1 and 3.2 ± 2.5 per 1,000 discharges to 2.4 ± 1.7 (p < .001) and 7.1 ± 3.2 (p < .001) per 1,000 discharges, respectively. Conversely, the annual hospitalization rate for long-term complications and lower extremity amputations gradually decreased from 12.6 ± 1.1 and 88.6 ± 1.0 per 1,000 discharges to 6.5 ± 1.0 (p = .004) and 82.2 ± 1.0 per 1,000 discharges (p < .001). Trends generally persisted across payers, age, sex, and race. There was an inverse correlation between county income-per-capita and hospitalization rate for short-term complications (p = .04), long-term complications (p = .03), and lower extremity amputations (p < .001). Study limitations included use of administrative data, evolving coding practices, and ecological fallacy. Ambulatory-based efforts to optimize diabetes care can prevent long-term complications and reduce avoidable hospitalizations.

Improved detection and characterization of adrenal disease with PET-CT.

Positron emission tomography (PET)-computed tomography (CT) combines complementary modalities, thereby providing useful structural and functional information for the detection and characterization of a variety of conditions affecting the adrenal gland. The coregistered information provided by PET-CT is often superior to that provided by CT or PET owing to a variety of pitfalls inherent in the use of either modality alone. In addition, PET-CT can prove invaluable in the differentiation between benign and malignant adrenal disease. However, this combined modality also has certain limitations. Benign entities such as lipid-poor adenomas may demonstrate increased uptake at 2-[fluorine 18]fluoro-2-deoxy-d-glucose PET while being indeterminate at standard CT. Moreover, the combined information from PET-CT will not always obviate additional studies or biopsy. Nevertheless, radiologists and nuclear physicians should be familiar with the common as well as the atypical manifestations of adrenal disease at PET and CT. They should also be meticulous in the performance and interpretation of PET-CT, which is crucial for optimal diagnosis and treatment.

Adrenocortical carcinoma: contrast washout characteristics on CT.

OBJECTIVE: The purpose of this study was to characterize pathologically proven adrenocortical carcinoma by examination of washout attenuation characteristics on contrast-enhanced CT images. CONCLUSION: Adrenocortical carcinoma has relative contrast retention on delayed contrast-enhanced CT. All tumors in this series had a relative percentage washout less than 40%, a finding consistent with malignant disease.

Pheochromocytoma: an imaging chameleon.

Pheochromocytomas are rare catecholamine-secreting tumors with many clinical and imaging manifestations. They may produce overwhelming cardiovascular crises if the diagnosis is not made or if appropriate treatment is delayed. It is thus important to recognize both their characteristic and atypical imaging appearances. Pheochromocytomas are encountered, sometimes unexpectedly, across a range of imaging modalities. They are characteristically solid, hypervascular masses with high signal intensity on T2-weighted magnetic resonance (MR) images. A wide spectrum of imaging appearances is seen, however, and pheochromocytomas may mimic other adrenal lesions, both benign and malignant. They may be dark on T2-weighted MR images, in contrast to their more classic bright T2-weighted appearance. Other atypical features include fatty, hemorrhagic, cystic, and calcific changes. Pheochromocytomas may contain sufficient fat to be mistaken for an adenoma at computed tomography (CT) or MR imaging. They may also demonstrate rapid contrast material washout and be mistaken for an adenoma owing to their deenhancement profile; however, their washout pattern can be inconsistent. The appearance of pheochromocytomas at radionuclide imaging is also unpredictable. These characteristics at CT, MR imaging, and scintigraphy pose diagnostic challenges, since they allow pheochromocytomas to mimic many other adrenal masses. Pheochromocytoma is an important, often clinically occult neoplasm with devastating consequences if overlooked. Radiologists must be aware of the various forms that pheochromocytomas can assume at imaging.

A malignant aldosteronoma.

OBJECTIVE: To describe a case of primary aldosteronism due to an adrenocortical carcinoma (ACC) and highlight the need for thorough long-term follow-up. METHODS: We present the clinical, laboratory, radiologic, and pathologic findings in a patient with ACC and review the related literature. RESULTS: A 52-year-old woman with a history of hypertension and hypokalemia was referred for evaluation of a 6-cm adrenal mass. Her biochemical studies revealed a serum aldosterone-to-renin ratio of 52 without evidence of cortisol, catecholamine, or androgen excess. She underwent surgical resection of this mass, and histologic analysis showed a focally brisk mitotic rate but no evidence of capsular or vascular invasion. In light of these findings, the biologic nature of the tumor was difficult to predict. Thus, it was thought to be an adrenocortical neoplasm. The patient underwent follow-up clinically, biochemically, and with interval computed tomography. Nine years later, hypertension and hypokalemia redeveloped, and she was found to have metastatic ACC. CONCLUSION: ACC can generally be reliably diagnosed; however, in some cases, the true biologic behavior is difficult to predict. We emphasize the importance of careful clinical, biochemical, and radiologic surveillance in these difficult cases because surgical resection provides the best opportunity for cure in patients with adrenal cancer.

Pituitary apoplexy precipitating diabetes insipidus.

OBJECTIVE: To describe a case of pituitary apoplexy complicated by diabetes insipidus and to review management of patients with pituitary apoplexy and water excretion disturbances associated with transsphenoidal surgery. METHODS: We describe clinical, laboratory, and radiologic findings in a patient with pituitary apoplexy and central diabetes insipidus. RESULTS: A 74-year-old woman presented with severe headache and sudden loss of vision for 12 hours, accompanied by thirst and frequent urination. Visual field examination demonstrated bitemporal hemianopsia. Her laboratory findings were significant for a serum sodium level of 152 mEq/L and urine specific gravity of <1.005. A magnetic resonance imaging scan of her pituitary gland identified a 3.5-cm suprasellar mass compressing the optic chiasm. She subsequently underwent transsphenoidal pituitary surgery with subtotal resection of this mass. Microscopic evaluation of tumor tissue revealed a pituitary adenoma with evidence of recent infarct and hemorrhage. Her clinical and biochemical course was consistent with the triphasic response that may occur after pituitary surgery related to damage to the hypothalamus and supraopticohypophyseal tract. CONCLUSION: Pituitary apoplexy may be rarely associated with diabetes insipidus.

Bone mineral density assessment: comparison of dual-energy X-ray absorptiometry measurements at the calcaneus, spine, and hip.

It is widely accepted that bone mineral density (BMD) measurements obtained by dual-energy X-ray absorptiometry (DXA) at the spine, hip, and calcaneus predict fracture risk. Few published studies to date have examined the relationship between pDXA measurements at the calcaneus to those at the hip and spine. It has been demonstrated that T-score-based criteria cannot be universally applied to all skeletal sites and measurement technologies. Our goal was to define the calcaneal T-score threshold equivalent to low bone mass at the hip or spine. A total of 119 female patients between the ages of 33 and 76 yr of age were recruited at Boston University Medical Center for bone densitometry screening. Bone density measurements were obtained at the calcaneus using the portable Norland Apollo Densitometer (Norland Medical Systems, Fort Atkinson, WI) and at the hip and spine using the Norland Eclipse densitometer. By defining a pDXA T-score < or =-1 as a positive test and DXA scores < or =-1 as the presence of low bone mass, we obtained a specificity of 100% and a sensitivity of 73% (positive predictive value 100% and negative predictive value 80%) in detecting low bone mass at the femoral neck in women over age 65 yr. In women between 40 and 65 yr of age, we obtained a sensitivity of 50% and a specificity of 93% (positive predictive value 93% and negative predictive value 50%) in detecting low bone mass at the femoral neck. In women less than 40 yr of age, we obtained a sensitivity of 13% and a specificity of 100% (positive predictive value 100% and negative predictive value 75%) in detecting low bone mass at the femoral neck. From receiver operating characteristic curves, a calcaneal T-score < or =0.0 detects those with a T-score < or =-1 at the femoral neck and lumbar spine with 100% and 85% sensitivity, respectively. Peripheral DXA of the calcaneus is a sensitive and specific test to diagnose low bone mass in women over 65 yr of age. In women under 65 yr of age, this modality, though not as sensitive, is specific in detecting low bone mass. We conclude that a pDXA calcaneal T-score < or =0 is highly sensitive in predicting osteopenia and osteoporosis at the femoral neck and lumbar spine.

State of the art in adrenal imaging.

The purposes of this article were to outline the current state of adrenal imaging, to highlight new developments, and to review the current radiologic advances that provide improved functional and structural information about adrenal disorders.

Comparison of the effects of a new conjugated oral estrogen, estradiol-3beta-glucoside, with oral micronized 17beta-estradiol in postmenopausal women.

The objective of this article is to evaluate the pharmacokinetics of serum estrone and estradiol levels in women who were taking either 17beta-estradiol-3beta-glucoside (E(2)-3beta-glucoside) or 17beta-estradiol (E(2)) daily and to examine the effects of E(2)-3beta-glucoside and E(2) on postmenopausal symptoms, gonadotropins, hepatic metabolism, and coagulation factors. Healthy postmenopausal women on estrogen who had undergone a hysterectomy were recruited. Subjects were randomly assigned to receive equivalent doses of either E(2)-3beta-glucoside or micronized E(2) for 28 days. Pharmacokinetic studies of estrone and estradiol were performed on days 1, 2, 28, and 29. Gonadotropin levels and Kupperman Index (KI) scores were determined at baseline and on treatment day 28. Mean serum estradiol and estrone concentrations in those taking E(2)-3beta-glucoside were comparable with those taking E(2). Mean baseline follicle stimulating hormone (FSH) levels were 84 +/- 27 mIU/mL and 71 +/- 24 mIU/mL in the E(2)-3beta-glucoside and E(2) groups, respectively, with significant decreases (P < 0.01) of 54 +/- 21 mIU/mL and 38 +/-18 mIU/mL, respectively, by treatment day 28. Baseline KI scores in the E(2)-3beta-glucoside group were 10 +/- 6 compared with 5 +/- 4 on treatment day 28, which is equivalent to a 50% reduction in menopausal symptoms (P = 0.003). The change in KI scores in the E(2) group was not statistically significant. Total serum estradiol and estrone levels in women taking E(2)-3beta-glucoside are comparable with those in women taking E(2). E(2)-3beta-glucoside reduces serum gonadotropin levels to the premenopausal range and is effective at reducing postmenopausal symptoms. E(2)-3beta-glucoside is a novel synthetic estrogen that is well tolerated and has promise as a hormone replacement therapy.

Distinguishing benign from malignant adrenal masses: multi-detector row CT protocol with 10-minute delay.

PURPOSE: To retrospectively evaluate the accuracy of precontrast attenuation, relative percentage washout (RPW), and absolute percentage washout (APW) in distinguishing benign from malignant adrenal masses at multi-detector row computed tomography (CT). MATERIALS AND METHODS: This HIPAA-compliant retrospective study had institutional review board approval; the need for informed consent was waived. One hundred twenty-two adrenal masses were evaluated in 99 patients (51 men, 48 women; age range, 37-86 years) who had undergone CT performed according to the study protocol and who either were given a pathologic diagnosis or underwent follow-up imaging. Unenhanced images were obtained before administration of 120 mL of an intravenous contrast agent with a 75-second scan delay. Delayed images were obtained after 10 minutes. RPW and APW were computed. Receiver operating characteristic (ROC) analysis was performed to compare mean attenuation and both RPW and APW. Analysis was first performed with the exclusion of pheochromocytomas, myelolipomas, and cysts. Precontrast attenuation criteria specific for benignity or malignancy were determined, and ROC analysis of results for the entire nonpheochromocytoma group was then performed. RESULTS: By using an RPW of 37.5% and excluding cysts and myelolipomas, all malignant lesions were detected with a sensitivity of 100% (17 of 17 lesions) and a specificity of 95% (90 of 95 lesions). Area under the binomial ROC curve (A(z)) values were 0.912, 0.985, and 0.892 for precontrast attenuation, RPW, and APW, respectively. Precontrast attenuation of less than 0 or more than 43 HU indicated benign and malignant entities, respectively. Incorporation of these criteria into the APW analysis yielded a sensitivity of 100% (17 of 17 lesions) and a specificity of 98% (93 of 95 lesions) for a threshold washout value of 52.0%. This attenuation-corrected APW generated the greatest A(z) value (ie, 0.988). Combining all the information available from the protocol yielded a sensitivity of 100% (17 of 17 lesions) and a specificity of 98% (98 of 100 lesions) for differentiating benign from malignant masses. CONCLUSION: Precontrast attenuation of less than 0 HU supercedes the washout profile in the evaluation of an individual adrenal mass. Noncalcified, nonhemorrhagic adrenal lesions with precontrast attenuation of more than 43 HU should be considered suspicious for malignancy.