Diagnosis Of Adrenal Incidentalomas Research Articles

Diagnosis and management of adrenal incidentaloma: use of clinical judgment and evidence in dialog with the patient

AbstractThe prevalence of adrenal incidentaloma (AI) in imaging studies, including those of the adrenal glands, is estimated to be 1–5%. Essential factors for the proper management of AI include a correct diagnosis, adequate surgical skills, appropriate perioperative management, and sound dialogue with the patient. Aside from the possibility of overdiagnosis, patients with apparent signs or symptoms attributable to adrenal hormone excess have reasonable indications for surgery. At the same time, milder patients may be candidates for active surveillance without intervention. Even individuals with nonfunctioning AI may benefit from surgery if imaging studies depict the tumor as suggestive of malignancy. However, a differential diagnosis of AI may not be easy for surgeons with little experience in seeing such patients.Furthermore, a patient without a correct diagnosis may miss the window of opportunity for a cure or incur a greater risk of developing complications, such as adrenal insufficiency or cardiovascular events during or after surgery, due to inadequate management. The clinical practice guidelines for AI from around the world may be helpful for shared decision-making; however, Japan lacks established guidelines. In this review article, we propose practical guidelines relevant to management by summarizing the evidence for five key questions that are often asked in dialog with patients with AI.

Bone density in patients with nonfunctional adrenal incidentaloma

Aims: Adrenal incidentalomas (AI) are adrenal masses that are detected incidentally in imaging studies performed for different reasons in people who do not have any complaints suggestive of adrenal gland disease. The overall prevalence, approximately just over 4%, increases with age. AI is detected in approximately 10% of people over the age of 70. In this context, we thought that CT imaging, which is already used in the diagnosis and follow-up of AI, can contribute to the evaluation of muscle and bone mass without creating additional costs. Methods: In this retrospective study, 39 patients who were followed up with NFAI by the endocrinology department and 30 healthy individuals with normal adrenal imaging in the abdominal CT examination as the control group were included. Patients with chronic diseases or drug use that may affect bone and muscle mass, and individuals in the postmenopausal period were excluded in this study. Endocrine tests performed to exclude autonomous cortisol secretion, pheochromocytoma and primary hyperaldosteronism; VMA and fractionated metanephrines in 24-hour urine, cortisol values after 1 mg dexamethasone suppression test, baseline serum dehydroepiandrosterone sulfate (DHEAS) levels and plasma aldosterone (ng/dl)/renin (ng/ml/hour) ratio were measured. Autonomous cortisol production was excluded in patients with serum cortisol below 1.8 mcg/dl after 1 mg dexamethasone suppression. Results: 39 patients with NFAI and 30 healthy volunteers participated in the study. In the NFAI group, 69.2% (n= 27) were female and 30.8% (n=12) were male. In the healthy control group 63.3% (n=19) of the people were female and 37.7% (n=11) were male. There was no statistically significant difference between the two groups in terms of gender (p=061). The mean age of the NFAI group is 43 and the mean age of the control group is 49, and there was no statistically significant difference in age between the two groups (p=0.06) Conclusion: No decrease was found in BMD and paravertebral muscle mass values in the measurements made at L1-3 vertebral level with CT in NAFI patients. Further studies are needed in a larger patient population where the results are evaluated together with the femur and vertebral BMD measurements by DXA method, and muscle strength and performance are evaluated in addition to muscle mass in terms of sarcopenia.

Prevalence, Diagnosis and Management of Adrenal Incidentalomas

Adrenal incidentalomas (AIs) are defined as adrenal masses incidentally discovered on imaging studies performed for unrelated reasons. AIs have become a common finding in clinical practice, particularly with the widespread application of high-resolution imaging techniques. While most AIs are nonfunctioning and benign, some cases can represent a clinical concern due to the risk of malignancy or hormone hyperfunction. The prevalence of AIs varies depending on the source of data and patient selection. The diagnosis of AIs relies on a combination of radiological, biochemical, and clinical evaluation to determine the functional status of the tumor and the potential for malignancy. The management of AIs remains a subject of controversy, with guidelines providing conflicting recommendations on the indications for surgical intervention and follow-up. Most AIs do not require surgical intervention, but appropriate follow-up is essential to detect any potential growth or functional changes. In cases where surgery is indicated, laparoscopic adrenalectomy is the gold standard, with open adrenalectomy reserved for masses highly suspicious for adrenal cortical carcinoma. A multidisciplinary approach involving endocrinologists, radiologists, and surgeons is crucial for optimal management of AIs.

Adrenal Incidentaloma Needs thorough Biochemical Evaluation - An Institutional Experience.

Context:Adrenal incidentalomas (AIs) are seen in around 2% of apparently healthy individuals. These require careful evaluation for the hormone excess state and the presence of malignancy prior to intervention.Aims:To study the clinical, biochemical, and imaging characteristics of the patients with AI and correlate the diagnosis with the histopathology findings in patients undergoing surgery.Settings and Design:Retrospective observational study.Methods and Material:Patients with adrenal incidentaloma presenting between January 2017 and January 2021 were evaluated as per guidelines provided by the European Society of Endocrinology and the European Network for the Study of Adrenal Tumors. Patients were given final diagnosis on the basis of imaging impression, hormonal activity, and biopsy results (when applicable).Results:Forty-eight patients were evaluated, with 25 being male, the mean age being 40.9 years (8–71), and the mean size of the mass being 6.21 (1.4–13.7) cm. Thirty-five (72.9%) of them underwent surgical excision. The most common diagnosis was myelolipoma (16), followed by pheochromocytoma (10) and adenoma (9). Nineteen patients were found to have hormone-secreting masses. Two patients with pheochromocytoma were normotensive. There was discordance between imaging diagnosis and hormonal status in two patients, with final diagnosis of pheochromocytoma. One patient with extramedullary erythropoiesis of the adrenal gland was subsequently diagnosed with sickle cell anemia and adrenal insufficiency.Conclusions:The study highlights the rare possibility of discrepancy between non-contrast CT diagnosis and functional status of AI. There is also a rare possibility of extramedullary erythropoiesis presenting as AI with adrenal insufficiency. Specific evaluation for such rare possibilities should be considered in AI cases as per clinical scenario.

Attenuation Value in Adrenal Incidentalomas: A Longitudinal Study.

ContextA tendency to grow has been reported in adrenal incidentalomas. However, long-term data regarding attenuation value, a measure of lipid content, are not available.AimThis study aims to collect radiological data (diameter in mm and attenuation value in Hounsfield units, HU) with computed tomography (CT) in adrenal incidentalomas, in order to compare baseline characteristics with the last follow-up imaging.DesignThis is a longitudinal study which included patients with a new diagnosis of adrenal incidentaloma, evaluated from January 2002 to June 2020.SettingReferral University-Hospital center.PatientsTwo hundred seventy-seven patients with 355 different cortical adenomas (baseline group) were evaluated at the first outpatient visit; the follow-up cohort consists of 181 patients with 234 adenomas (12–175 months after baseline). Inclusion criteria were conservative management and radiological features able to minimize malignancy or risk of progression.Main Outcome MeasureCT modification according to endocrine function: autonomous cortisol secretion (ACS) if cortisol >50 nmol/L after 1-mg dexamethasone test (DST).ResultsAt baseline CT, mean diameter was 18.7 mm and attenuation value was 0.8 HU (higher in ACS, 66 cases >10 HU), without modification in early imaging (12–36 months). The size increased over time (r = 0.289), achieving the largest differences after at least 60 months of follow-up (mean diameter, +2 mm; attenuation value, −4 HU), combined with a reduction in the attenuation value (r = −0.195, especially in patients with ACS). Lipid-poor adenomas (>10 HU) presented a reduced cortisol suppression after 1-mg DST, an increase in size and the largest decrease in attenuation value during follow-up. Univariate analysis confirmed that larger adenomas presented reduced suppression after DST and increase in size during follow-up.ConclusionsGrowth is clinically modest in adrenal incidentaloma: the first follow-up CT 5 years after baseline is a reasonable choice, especially in ACS. Mean density is increased in patients with ACS and overt hypercortisolism. Mean density reduces during follow-up in all adrenal adenomas, suggesting an increase in lipid content, especially in those with ACS.

A Mass in Disguise: A Rare Case of High-Attenuation Adrenal Myelolipoma

Abstract Background: Adrenal incidentalomas are common, and imaging studies play a large role in reaching the diagnosis in many cases. Adrenal myelolipomas are classically diagnosed by CT as a hypodense well circumscribed heterogenous mass with low attenuation. Clinical Case: A 51-year-old man with history of resistant hypertension presented with neck pain after a motor vehicle crash. After a cervical X-ray revealed an odontoid fracture, a whole body CT was obtained. The CT incidentally identified a massive heterogeneous left adrenal mass measuring 22.3 × 15.5 × 20.6 cm, with multiple attenuation measurements ranging from 20 to 53 Hounsfield units (HU). The patient’s physical examination and hormonal assessment were both unrevealing, with normal catecholamine, androgen, and an unremarkable renin aldosterone ratio. Inpatient urinary cortisol levels were elevated, however a repeat urinary cortisol as an outpatient weeks after repair of the odontoid fracture showed normal levels, suggesting physiologic stress response. Positron emission tomography showed a metabolically inactive adrenal mass without metastatic diseases. The patient eventually underwent a left adrenalectomy, and pathology revealed a myelolipoma measuring 24.2 × 20.5 × 8.3 cm. Imaging characteristics for adrenal incidentalomas are considered useful diagnostic information according to most clinical guidelines. Lesions with high HU are typically pheochromocytomas, adrenocortical carcinoma, metastatic disease, or lipid poor adenomas. Myelolipomas are identified on CT by their characteristically low HU (often -30). In this case of a massive myelolipoma with high HU, the unique imaging characteristics posed a diagnostic challenge. The patient’s history of resistant hypertension combined with the high HU led to the patient undergoing extensive testing for a functional mass or cancer. Conclusion: This is a rare case of a massive myelolipoma with low attenuation. The role of imaging studies in the diagnosis of adrenal incidentalomas is not definitive, and detailed exam along with hormonal assessment may be warranted in atypical cases. Providers should consider myelolipoma in the differential diagnosis of a large adrenal mass with a negative hormonal evaluation even in the setting of high HU.

Multispiral Computed Tomography in the Diagnosis of Adrenal Incidentalomas

Many years of experience in identifying patients with various pathologies of the adrenal glands using multispiral computed tomography are presented. Multispiral CT is a highly informative method of choice in the diagnosis of adrenal tumors. Multispiral CT in the perfusion version of the tumor of the adrenal gland increases the accuracy of diagnosis, which optimizes the tactics of treatment. Improving the algorithm for assessing perfusion indices of the adrenal gland incidentalomas using multispiral CT will allow to evaluate the histological nature of the pathological process. It is justified to conduct perfusion MSCT studies in patients with volumetric adrenal masses with the purpose of differential diagnosis of hyperplastic and tumor processes in them. An attempt was made to develop an algorithm for MSCT diagnostics of the adrenal glands and determine its effectiveness. The radiological characteristic of the adrenal glands incidentalomas is a reflection of their morphological structure. There are statistically significant differences in aldosterone-producing and cortisol-producing adenomas in size and CT density. Morphological signs of adrenal tumor degeneration correlate with functional activity. Surgical treatment is absolutely indicated for patients with incidentalomas corresponding to the radiological phenotype of malignant tumors, as well as for patients who have revealed hormonal activity during a comprehensive examination. Dynamic observation is indicatedfor patients with hormonal-inactive incidental small-sized (< 4 cm) in the absence ofradiological signs of malignancy. In patients with an extremely high risk of surgical treatment, endovascular interventions aimed at suppressing adrenal hyperfunction are advisable. The main prognostic factors for adrenal glands incidentalomas are: radiological phenotype, hormonal activity, duration of the disease, the choice of adequate treatment tactics. In surgical treatment, the prognosis depends on the morphological characteristics of adrenal gland incidentalomas.

MANAGEMENT OF ENDOCRINE DISEASE: Differential diagnosis, investigation and therapy of bilateral adrenal incidentalomas.

The investigation and management of unilateral adrenal incidentalomas have been extensively considered in the last decades. While bilateral adrenal incidentalomas represent about 15% of adrenal incidentalomas (AIs), they have been less frequently discussed. The differential diagnosis of bilateral incidentalomas includes metastasis, primary bilateral macronodular adrenal hyperplasia and bilateral cortical adenomas. Less frequent etiologies are bilateral pheochromocytomas, congenital adrenal hyperplasia (CAH), Cushing's disease or ectopic ACTH secretion with secondary bilateral adrenal hyperplasia, primary malignancies, myelolipomas, infections or hemorrhage. The investigation of bilateral incidentalomas includes the same hormonal evaluation to exclude excess hormone secretion as recommended in unilateral AI, but diagnosis of CAH and adrenal insufficiency should also be excluded. This review is focused on the differential diagnosis, investigation and treatment of bilateral AIs.

Diagnostic accuracy of computed tomography to identify adenomas among adrenal incidentalomas in an endocrinological population.

The recent recommendations of the European Endocrine Society states that the performance of computed tomography (CT) to characterize 'true' adrenal incidentalomas (AIs) remains debatable. To determine relevant thresholds for usual CT parameters for the diagnosis of benign tumors using robust reference standard among a large series of 'true' AIs recruited in an endocrinological setting. Retrospective study of 253 AIs in 233 consecutive patients explored in a single university hospital: 183 adenomas, 33 pheochromocytomas, 23 adrenocortical carcinomas, 5 other malignant tumors and 9 other benign tumors. Reference standard was histopathology in 118 AIs, biological diagnosis of pheochromocytoma in 2 AIs and size stability after at least 1 year of follow-up in 133 AIs. Sensitivity, specificity and positive and negative predictive values were estimated for various thresholds of size, unenhanced attenuation (UA), relative and absolute wash-out (RPW, APW) of contrast media. 197 scans were reviewed independently in a blinded fashion by two expert radiologists to assess inter-observer reproducibility of measurements. Criteria associated with a 100% positive predictive value for the diagnosis of benign AI were: a combination of size and UA: 30 mm and 20 HU or 40 mm and 15 HU, respectively; RPW >53%; and APW >78%. Non-adenomatous AIs with rapid contrast wash-out were exclusively benign pseudocysts and pheochromocytomas, suggesting that classical thresholds of 60% and 40% for APW and RPW, respectively, can be safely used for patients with normal metanephrine values. Inter-observer reproducibility of all parameters was excellent (intra-class correlation coefficients: 0.96-0.99). Our study, the largest conducted in AIs recruited in an endocrinological setting, suggests safe thresholds for quantitative CT parameters to avoid false diagnoses of benignity.

Optimal follow-up strategies for adrenal incidentalomas: reappraisal of the 2016 ESE-ENSAT guidelines in real clinical practice.

Recently, the European Society of Endocrinology (ESE), in collaboration with the European Network for the Study of Adrenal Tumors (ENSAT), asserted that adrenal incidentalomas (AIs) <4 cm and ≤10 Hounsfield units (HU) do not require further follow-up imaging. To validate the clinical application of the follow-up strategies suggested by the 2016 ESE-ENSAT guidelines, we explored the clinical characteristics and natural course of AIs in a single center over 13 years. This retrospective cohort study included a total of 1149 patients diagnosed with AIs between 2000 and 2013 in a single tertiary center. Hormonal examination and radiological evaluations were performed at the initial diagnosis of AI and during the follow-up according to the appropriate guidelines. The mean age at diagnosis was 54.2 years, and the majority of AIs (68.0%) were nonfunctional lesions. Receiver operating curve analysis was used to discriminate malignant from benign lesions; the optimal cut-off value for mass size was 3.4 cm (sensitivity: 100%; specificity: 95.0%), and that for the pre-contrast HU was 19.9 (sensitivity: 100%; specificity: 67.4%). The majority of nonfunctional lesions did not change in size during the 4-year follow-up period. Applying a cut-off value of 1.8 μg/dL after a 1-mg overnight dexamethasone suppression test, 28.0% of all nonfunctional AIs progressed to autonomous cortisol secretion during the follow-up period. However, we observed no development of overt Cushing's syndrome in the study. We advocate that no follow-up imaging is required if the detected adrenal mass is <4 cm and has clear benign features. However, prospective studies with longer follow-up are needed to confirm the appropriate follow-up strategies.

Challenges in differential diagnosis of adrenal incidentaloma or clinical case of multiple myeloma

Challenges in differential diagnosis of adrenal incidentaloma or clinical case of multiple myeloma

DIFFERENTIAL DIAGNOSTICS OF ADRENOCORTICAL INCIDENTALOMASWITH DIFFERENT LABORATORY TECHNOLOGIES

The article provides an analysis of the use of immunoassay methods, high performance liquid chromatography and gas chromatography-mass spectrometry in the differential diagnosis of adrenal incidentalomas. Criteria of subclinical Cushing’s syndrome, primary hyperaldosteronism, adrenal incidentalomas without hypersecretion of hormons, early signs of malignant tumors of the adrenal glands are obtained.

Total lesion glycolysis as the best 18F-FDG PET/CT parameter in differentiating intermediate–high risk adrenal incidentaloma

Characterization of intermediate-high risk adrenal incidentaloma (AI) is important because biopsy or surgery should be performed to confirm the malignancy. We investigated which parameters of F-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (CT) had an additive role in distinguishing malignancies in patients with incidental adrenal masses of intermediate-high risk. From January 2008 to July 2013, 52 patients with a pathologically proven diagnosis of AI were retrospectively enrolled (age=56.4±12.7 years, M : F=34 : 18; benign : malignant=14 : 38). Volumetric parameters were size and volume according to combined CT, and metabolic parameters were peak standardized uptake value (SUV(peak)), maximum SUV (SUV(max)), mean SUV (SUV(mean)), and tumor-to-background ratio (SUV(max) of adrenal mass/SUV(mean) of liver). Metabolovolumetric parameters of metabolic tumor volume and total lesion glycolysis (TLG, SUV(mean)×metabolic tumor volume) were also included and compared with the diagnostic value. In addition, the highest diagnostic parameters among volumetric and metabolic parameters were combined and compared in terms of diagnostic accuracy. Compared with benign adrenal adenoma, malignant lesions showed significantly higher values of all (18)F-FDG PET/CT volumetric, metabolic, and metabolovolumetric parameters. Size showed the highest area under the curve (AUC) of 0.759 among the volumetric parameters, and SUV(peak) showed the highest AUC of 0.853 among the metabolic parameters. Among all the PET/CT parameters, TLG showed the highest AUC of 0.900, with a sensitivity of 92.1% and specificity of 78.6% at a cutoff of 12.0. The combined value of size and SUV(peak) showed lower diagnostic value than TLG. We found that TLG showed the best result in distinguishing intermediate-high risk AI among PET/CT parameters. TLG can be a useful PET/CT parameter for differential diagnosis of AI.

Unexpected adrenocortical carcinoma 8 years after diagnosis of adrenal incidentaloma

Unexpected adrenocortical carcinoma 8 years after diagnosis of adrenal incidentaloma

Multi-Detector-Row CT Diagnosis of Adrenal Incidentaloma in Patients with Hepatocellular Carcinoma

We investigate the diagnostic reliability of differentiating between lipid-poor adrenal adenomas and metastatic adrenal tumors originating from hepatocellular carcinoma (HCC) using a routine dynamic CT protocol for liver imaging. Eighteen metastatic adrenal tumors originating from HCC and 13 lipid-poor adrenal adenomas were identified. Dynamic CT data were analyzed for CT attenuation of adrenal lesions before and after contrast administration. When a cutoff of 36 HU was set for adrenal lesions at pre-contrast attenuation, the sensitivity and specificity for the diagnosis of metastatic lesions were 94.4%and 92.3%, respectively. Attenuation criteria on pre-contrast CT may help optimize the differentiation between these lesions.

Guidelines for the management of the incidentally discovered adrenal mass

With advances in modern imaging technology, the presentation of an incidentally found adrenal mass (or incidentaloma) has become an increasingly common management scenario for endocrinologists and urologists. The prevalence of adrenal incidentalomas (AI) has been reported as high as 8% in autopsy series and 4% in radiologic series.1,2 As improved imaging techniques become available and the frequency of abdominal imaging increases, the radiologic prevalence is expected to continue escalating, approaching the autopsy series. Also concerning is the evidence supporting an increased prevalence with age, with the risk of finding an AI being more common in the later years of life.3 In a rapidly aging society, the diagnosis and management of AI will become a more frequent task. As such, guidelines are useful to guide appropriate treatment.

Clinical analysis of 128 cases of adrenal incidentalomas

Objective To improve the early diagnosis and differential diagnosis of adrenal incidentalomas to guide clinical management of this disease. Methods One hundred and twenty-eight cases were diagnosed as adrenal incidentalomas due to health examination or treatment of other than adrenal disease,including 60 males and 68 females,whose ages were between 20 and 75 years,with a mean age of 50 years.Tumor diamer:＜3 cm 63 cases,3-6 cm 6 cases,＞6 cm 10 cases.128 patients all had biochemical and electrolyte examination,adrenal cortex and medulla biochemical testing,abdominal ultrasound and CT examination,6 cases with MRI examination.Surgery and post operative pathological examination were performed in all patients. Results Post operative pathology finally diagnosed adrenocortical adenoma in 85 cases,pheochromocytoma in 13 cases,adrenal cyst in 8 cases,paraganglioma and myeiolipoma in 7 eases respectively,adrenal nodular hyperplasia in 4 cases,adrenocortical carcinoma in 2 cases,adrenoconical oncocytoma,cellular Schwannoma and adrenal liposarcoma in 1 case,respectively.One case of pheochromocytoma patients died of intraoperative hypotension,which is not included in the total number. Conclusions The preperative diagnosis of adrenal incidentalomas is difficult.For adrenal incidentalomas with diameter more than 6 cm and those with endocrine function,early surgicM treatment is recommended. Key words: Adrenal neoplasms; Incidentaloma; Pheochromocytorna; Cushing syndrome; Laparoscopies

The relation of adiponectin and tumor necrosis factor α levels between endothelial nitric oxide synthase, angiotensin-converting enzyme, transforming growth factor β, and tumor necrosis factor α gene polymorphism in adrenal incidentalomas

The aim of our study was to demonstrate demographic characteristics, presence of inflammatory markers, distribution of angiotensin-converting enzyme (ACE), tumor necrosis factor (TNF), endothelial nitric oxide synthase (eNOS) genotypes and relations among these parameters in these patients and control subjects. Study samples were collected from 50 patients with adrenal mass and 30 control groups. The eNOS, ACE, TNF-alpha, transforming growth factor (TGF)-beta genes polymorphisms, TNF-alpha, adiponectin levels were analysed in 50 unrelated Turkish patients with a diagnosis of adrenal incidentaloma (AI). There was statistically significant difference between TNF-alpha levels of patient and controls (p=0.048). We have not detected the connection between TGF-beta, TNF-alpha, ACE, eNOS gene polymorphism with serum TNF-alpha and adiponectin levels. In this study, we demonstrated that there were significant differences for ACE genotypes in the patients when compared to the controls (p<0.05). The percentages of the ID, DD, II genotypes for ACE gene polymorphism in the patients group were 30.0, 13.0, 7.0%, respectively. According to different cases of eNOS, TGF-beta, ACE, and TNF-alpha gene genotypes; no statistical significant difference was found between basal cortisol, ACTH, DHEAS, metanephrine, renin, aldosterone, normetanephrine, 17-hydroxyprogesterone, 1 mg low-dose dexamethasone suppression test-cortisol response and AI size. In this study, I/D genotype was determined to be statistically higher in ACE gene in patients with AI (p=0.014).

Problems in the diagnosis of the adrenals with incidental

The paper analyzes the case records of 123 patients with a primary diagnosis ofadrenal incidentaloma who were treated at the Endocrinology Research Center, Russian Academy of Medical Sciences, in the past 5 years. Ofthem, 87patients were operated on at the surgical department of the Center. Thirty six patients with a clinically verified diagnosis ofhormonally inactive adrenal tumor without signs ofmalignant growth werefollowed up. All the patients underwent comprehensive clinical and instrumental studies (ultrasonography, magnetic resonance imaging, computed tomography, hormonalstudies). Theirresults were comparedwith the morphological data on distal adrenal changes. The hormonal activity ofadrenal tumors was morphologically determined by histochemical techniques. The study revealed true hormonally inactive tumors only in 12 cases. It is concluded that the concepts of adrenal incidentaloma and of true hormonally tumor are not equivalent and that it is necessary to make a comprehensive clinical and morphobiochemical analysis in adrenal tumors to establish a final nosological diagnosis.

Congenital adrenal hyperplasia presenting as massive adrenal incidentalomas in the sixth decade of life: report of two patients with 21-hydroxylase deficiency.

Divergent recommendations exist regarding the evaluation of adrenal incidentalomas. Recent data have indicated a prevalence of adrenal tumors of 71% in nonclassical congenital adrenal hyperplasia (CAH) and unmasked heterozygotes. These data expand the differential diagnosis of such incidental tumors and substantially modify the approach to their evaluation. We present two patients, female pseudohermaphrodites with the simple virilizing form of CAH and 21-hydroxylase deficiency, who functioned successfully as married phenotypic males. Both came to medical attention in the sixth decade by virtue of massive adrenal incidentalomas encountered in the evaluation of recurrent urinary tract infections. Each had a 46, XX karyotype, no palpable testes, and markedly elevated baseline levels of 17-hydroxyprogesterone (17-OH Prog) of 6086 ng/dL and 6750 ng/dL. Both responded appropriately to dexamethasone suppression with reduction of 17-OH Prog, androgens and, in the second patient, ACTH to normal or near normal levels. Histologic and autopsy examination of the first patient's tumor and computed tomographic characteristics of the second revealed a benign adenoma and myelolipoma respectively. We extend and confirm previous recommendations that CAH be included in the differential diagnosis of adrenal incidentaloma and that baseline 17-OH Prog. levels be obtained, with ACTH stimulation if necessary, to diagnose the presence of nonclassical CAH.