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Advances in multimodal imaging for adrenal gland disorders: integrating CT, MRI, and nuclear medicine
Kota Yokoyama1(D . Mitsuru Matsuki2 . Takanori Isozaki3 . Kimiteru Ito4(D . Tomoki Imokawa 1D . Akane Ozawa1 . Koichiro Kimura10 . Junichi Tsuchiya1(D . Ukihide Tateishi1
Received: 16 November 2024 / Accepted: 3 January 2025 / Published online: 11 January 2025 @ The Author(s) 2025
Abstract
Adrenal diseases pose significant diagnostic challenges due to the wide range of neoplastic and non-neoplastic pathologies. Radiologists have a crucial role in diagnosing and managing these conditions by, leveraging advanced imaging techniques. This review discusses the vital role of computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine in adrenal imaging, and focuses on morphological and functional evaluations. First, the anatomy and physiology of the adrenal glands are described, followed by a discussion on ectopic adrenocortical adenomas and how they develop. The concepts and imaging findings of congenital diseases, such as congenital adrenal hyperplasia (CAH), adrenal rest tumors, and adrenocortical nodular disease, considering recent updates to the WHO Classification of Tumours (5th ed.) terminology are highlighted. The diagnostic value of dynamic contrast-enhanced CT and chemical-shift MRI for identifying adrenocortical adenomas are emphasized, alongside the use of adrenocortical scintigraphy such as 131I-adosterol scintigraphy for diagnosing Cushing’s disease, Cushing’s syndrome (CS), subclinical CS, and ectopic adrenocorticotropic hormone-producing tumors. Systemic complications associated with CS, and the diagnosis and treatment of pheochromocytomas, paragangliomas (PPGLs), and neuroblastomas, will also be discussed focusing on 123I-metaiodobenzylguanidine (MIBG) imaging and 131I-MIBG therapy. Pitfalls in 123I-MIBG imaging and the increasing importance of diagnosing hereditary PPGLs due to increased genetic testing are also be discussed. Additionally, the broad differential diagnosis for adrenal masses-including malignancies like adrenal carcinoma, metastases, and malignant lymphoma, as well as benign conditions like myelolipoma and ganglioneuroma, and complications, such as adrenal hemorrhage, infarction, and infections-will be outlined. The goal of this review was to provide an overview of adrenal diseases that includes the most recent information for radiologists to stay updated on the latest imaging techniques and advancements that can ensure accurate diagnosis and effective management.
Keywords Adrenal gland . Multimodal imaging . Computed tomography . Magnetic resonance imaging · Nuclear medicine · Functional imaging
☒ Kota Yokoyama kota1986ky@yahoo.co.jp
1 Department of Diagnostic Radiology, Institute of Science Tokyo, Bunkyo-ku, Tokyo, Japan
2 Department of Pediatric Medical Imaging, Jichi Children’s Medical Center Tochigi, Jichi Medical University, Shimotsuke, Tochigi, Japan
3 Department of Radiology, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
4 Department of Radiology, National Cancer Center, Tokyo, Japan
Introduction
Adrenal gland disorders pose significant diagnostic chal- lenges for radiologists because of their diverse patholo- gies. The WHO classification identifies 18 distinct tumors, including 10 adrenal cortical tumors and 8 adrenal medulla and extra-adrenal paraganglia tumors [1], which requires radiologists to have a comprehensive understanding of adrenal pathology and anatomy for accurate diagno- sis and management. Imaging, particularly computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine, is essential for evaluating adre- nal disorders by assessing function, staging, metastasis, and guiding treatment. Dynamic contrast-enhanced CT
[2, 3] and chemical-shift imaging (CSI) on MRI [4, 5] have improved the diagnosis of adrenocortical adenomas. Functional imaging has traditionally had a crucial role in diagnosing conditions, such as Cushing’s syndrome (CS), Cushing’s disease (CD), and primary aldosteronism (PA), and its importance has increased with advances in nuclear medicine treatments for pheochromocytomas, paraganglio- mas (PPGLs), and neuroblastomas [6-10]. Additionally, the increasing frequency of diagnosing hereditary PPGLs highlights the growing importance of correlating genetic mutations with imaging findings [11-13]. Recent reports have also linked adrenal complications to immune check- point inhibitors (ICIs) [14], adding more complexity to the diagnosis.
Despite these advancements, the broad differential diagnoses of adrenal lesions require not only mastery of diagnostic techniques but also a deeper understanding of each condition. This review discusses the adrenal anatomy, major diseases, and rare but important conditions that radiologists must be familiar with as well as key imaging techniques and advancements critical for their accurate diagnosis and effective management.
Anatomy, development, and physiology of the adrenal glands
Anatomy and abnormalities
Adrenal glands are small, triangular organs located above the kidneys in the retroperitoneal space. Each gland weighs approximately 5-6 g [15] and measures approximately 5 cm in length [15, 16]. Each adrenal gland is supplied by three adrenal arteries and are drained by a single adrenal vein (Fig. 1). On imaging, they typically appear as an inverted Y shape on CT or MRI axial or coronal images [16], and the right- and left-adrenal glands’ maximum widths are approx- imately 6.1 mm and 7.9 mm, respectively [17], and their cranio-caudal lengths are <4 cm [18]. In newborns, the adre- nal glands are relatively large, being about one-third the size of the kidneys, and they gradually shrink during infancy [19, 20]. Variations in adrenal size may depend on the intrauter- ine environment and stress factors [21]. Abnormalities such as ‘pancake’ adrenal occur in various conditions, includ- ing renal agenesis or ectopic kidney [22]. “Pancake” adre- nal also is referred to as “discoid,” “straight,” “elongated,” and “lying down adrenal” (Fig. 2). After nephrectomy, it is
Inferior phrenic artery
Left inferior phrenic vein
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provided by the superior, middle, and inferior suprarenal arteries, and the glands are drained by the left- and right-suprarenal veins. This figure highlights the location of the left- and right-adrenal glands and the vascular connections to both kidneys. Illustration by Akane Ozawa
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important to recognize that structures with such morphol- ogy represent deformed adrenal glands. Horseshoe adrenal gland, a rare congenital anomaly, involves fusion across the midline and is sometimes referred to as a “butterfly” adre- nal gland [23]. This condition is often associated with other congenital anomalies, such as asplenia, neural tube defects, Cornelia de Lange syndrome, and certain renal abnormali- ties [23, 24]. Imaging is critical for identifying this condition and related midline defects.
Adrenal cortex development and ectopic adrenal cortical adenomas
The adrenal cortex originates from the urogenital ridge, which also forms the kidneys and reproductive organs [25]. Ectopic adrenal cortical adenomas can develop in various locations due to the aberrant migration of adrenal cells dur- ing embryogenesis, such as near the renal hilum (Fig. 3) or within the broad ligament of the uterus [26].
Functional anatomy of the adrenal glands and hyperplasia
The adrenal glands have two distinct parts: the cortex and medulla. The cortex produces steroid hormones critical for physiological functions and is divided into three zones (Fig. 4):
pelvic floor (B: white dotted circle), along with agenesis of the left kidney. The left-adrenal gland is flattened and elongated, displaying the characteristic discoid shape (A, B: black arrow), which is com- monly associated with unilateral renal agenesis
· Zona glomerulosa: Produces mineralocorticoids (e.g., aldosterone) that regulate the fluid and electrolyte balance.
· Zona fasciculata: Produces glucocorticoids (e.g., cortisol), which are critical for glucose and energy metabolism and are regulated by the hypothalamic- pituitary-adrenal (HPA) axis.
· Zona reticularis: Produces adrenal androgens, such as dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), which are involved in sexual development.
Understanding anatomy and feedback mechanisms is crucial for diagnosing and managing CS, CD, PA, and similar conditions as well as adrenocorticotropic hormone (ACTH)-producing tumors. Long-term steroid use may lead to adrenal atrophy, obscuring underlying conditions. Adrenocortical scintigraphy is important for evaluating adrenal conditions (Fig. 5).
The medulla, derived from the neural crest, functions in the sympathetic nervous system by secreting catecholamines (e.g., epinephrine, norepinephrine) in response to stress and regulating blood pressure, heart rate, and metabolism. Metabolic increases during stress are visible in 2-deoxy-2-[18F]fluoroglucose (18F-FDG) positron-emission tomography (PET)/CT. Understanding this anatomy is key to diagnosing PPGLs and neuroblastoma and to interpreting 123I- MIBG (MIBG)
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scintigraphy and nuclear medicine treatments that use 131 31I-MIBG.
Overall, the adrenal glands are critical for homeostasis, regulating fluid balance, stress response, metabolism, and sexual development [27]. Although small in size, the adrenal glands have an important effect on various bodily functions and are essential to overall health. Understanding the structure and function of adrenal glands is key to interpreting imaging and diagnosing adrenal disorders.
Adrenal cortex lesion
Hyperplasia
Congenital adrenal hyperplasia (CAH)
Congenital adrenal hyperplasia (CAH) is a genetic disorder primarily caused by 21-hydroxylase deficiency, which impairs cortisol and aldosterone production [28]. This deficiency often results in adrenal hyperplasia due to the overproduction of adrenal androgens, primarily DHEA and androstenedione, under the influence of elevated adrenocorticotropic hormone ACTH levels. In its
shows slightly low intensity (D: black arrow). On chemical-shift imaging, the lesion exhibits high signal intensity on in-phase images (E: black arrow) and signal loss on opposed-phase images (F: black arrow), indicating the presence of intracytoplasmic fat. The mass was surgically resected and histopathologically diagnosed as an ectopic adrenocortical adenoma
classic form, CAH can present early, often with serious complications, such as salt-wasting crises, which can be life-threatening, and ambiguous genitalia in females. It is characterized by a complete or near-complete deficiency of 21-hydroxylase activity. Conversely, non-classic CAH typically presents later and tends to be milder. It is caused by a partial deficiency of 21-hydroxylase activity, resulting in less severe hormonal imbalances [29].
Ultrasonography is particularly useful in neonates and infants, with key findings including limb length > 20 mm, mean width > 4 mm, and normal corticomedullary differentiation, strongly suggesting CAH [30-32]. Lobulated or cerebriform surfaces and stippled echogenicity are highly sensitive and specific [32]. CT can reveal adrenal enlargement, often caused by persistent ACTH stimulation, while MRI offers superior soft-tissue contrast resolution, enabling a more detailed assessment of adrenal morphology without radiation, allowing safe, repeated evaluations in pediatric patients. Additionally, 23I-MIBG scintigraphy can help differentiate adrenal hyperplasia from other adrenal lesions when the conventional imaging is inconclusive [33] and is useful for detecting testicular adrenal rest tumors (TART) [34].
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TARTs are benign lesions composed of adrenal cortical tissue that can develop in the testes of male patients with CAH. They resemble Leydig cell tumors and are often bilateral are usually small, multiple, and detectable by ultra- sonography, especially in post-pubertal males (Fig. 6) [35].
Early and accurate imaging is crucial for guiding treatment and preventing complications in CAH. It is managed with early and continuous cortisol replacement to prevent adrenal crises and normalize hormone levels [36]. Timely imaging reduces morbidity and mortality in classic CA and helps physicians manage symptoms and monitor outcomes in non-classic CAH [29].
Cushing’s disease (CD)
CD is a form of CS caused by an ACTH-producing pitui- tary adenoma, now referred to as a pituitary neuroendo- crine tumor (PitNET) [37]. CD typically presents in adults between 20 and 50 years of age but can also occur in chil- dren, where it is often associated with growth retardation [38]. Pituitary-driven excess ACTH leads to bilateral adrenal hyperplasia, which can be detected by CT, MRI, or adreno- cortical scintigraphy (Fig. 5C). Pituitary MRI is crucial for identifying PitNET, often a microadenoma < 10 mm. Up to 50% of microadenomas are too small to detect by standard MRI due to their size. Dynamic contrast-enhanced imaging [39] and thin-slice protocols [40] aid in detecting micro- adenomas [41]. The recommended protocol has been dis- cussed elsewhere [41]. Additionally, 3-T MRI has proven to be highly effective in providing a detailed evaluation of both normal pituitary anatomy [42] and microadenomas [41]. If
the MRI results are inconclusive, bilateral inferior petrosal sinus sampling (BIPSS) confirms the pituitary source of ACTH, with high sensitivity and specificity for ACTH- dependent CD [43-45].
The primary treatment for CD is the surgical removal of the PitNET, typically via transsphenoidal surgery. If surgery is not successful, additional options include radiation therapy or medical management [46]. Although imaging is key in the diagnosis of CD, clinical information and biochemical testing remain essential for confirming the diagnosis and guiding treatment.
Ectopic ACTH syndrome (EAS)
Ectopic ACTH-producing tumors, which cause CS, are most often associated with malignancies located outside the pitui- tary gland. Common sources include the lungs, particularly in cases of small-cell lung carcinoma, bronchial, and thymic carcinoids [47-49]. Other ectopic sources include medul- lary thyroid carcinoma, pancreatic neuroendocrine tumors (NET), pheochromocytomas, and, less commonly, gastro- intestinal carcinoids [47-49]. EAS typically presents with severe hypercortisolism, including central obesity, purple striae, hypertension, glucose intolerance, osteoporosis, and avascular femoral head necrosis [50]. Steroid-induced myo- pathy, which causes proximal muscle weakness, severely impairs mobility and quality of life [51]. Excessive cortisol also increases the risk of opportunistic infections, such as Pneumocystis jirovecii pneumonia [51]. Diagnosing EAS is challenging because the ACTH source is often hard to iden- tify. Imaging studies, including CT and MRI, are typically
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employed to locate the tumor. Functional imaging, such as octreotide scintigraphy, detects NETs expressing somatosta- tin receptors [50]. In recent years, 68Ga-DOTAº-Tyr3-octreo- tate (DOTATATE) PET/CT has shown promise for identify- ing these tumors with high sensitivity [52, 53], although its availability is limited in certain regions, including Japan. BIPSS is crucial for distinguishing between pituitary and ectopic ACTH sources [45]. Non-invasive tests, such as the desmopressin stimulation test, also show promise in differ- entiating CD from EAS [54].
Managing EAS requires a multidisciplinary approach, focusing on identifying and resecting the primary tumor when possible [55]. When the tumor cannot be resected or remains unidentified, medical therapies, such as ketoconazole or metyrapone [56], are used to control cortisol production. The management of complications, such as steroid-induced myopathy, and prevention of opportunistic infections are crucial for improving patient outcomes.
Adrenal cortex neoplasm
Adrenocortical nodular disease
Adrenocortical nodular disease refers to a group of benign nodular proliferations within the adrenal cortex. Historically, these conditions have been described as “adrenal cortical nodular hyperplasia” or “micronodular and macronodular adrenocortical hyperplasia.” Although ACTH-independent macronodular adrenal hyperplasia was once a familiar term, it is now considered outdated [57]. The latest WHO classification includes sporadic nodular adrenocortical disease and bilateral micronodular adrenocortical disease (BMACD), which encompasses primary pigmented nodular adrenocortical disease (PPNAD) and isolated micronodular adrenocortical disease (i-MAD), replacing ACTH- independent macronodular adrenal hyperplasia (AIMAH) [57].
Adrenal cortical adenomas: Cushing’s syndrome and primary aldosteronism
Adrenal cortical adenomas are common benign tumors that are often incidentally discovered during imaging, and lipid-rich adenomas comprise approximately 70% of these. They show unenhanced CT attenuation of ≤ 10 HU, which is highly specific for adenomas, since other adrenal tumors rarely present with such low attenuation [58]. CSI reliably detects small amounts of fat and distinguishes adenomas from non-adenomas. Recent meta-analyses have highlighted the high sensitivity (94%) and specificity (95%) of CSI for diagnosing adenomas, confirming its diagnostic accuracy [5]. For differentiation, CSI findings should be interpreted by assessing signal loss on opposed-phase images relative
to in-phase images, which is characteristic of adenomas due to their intracytoplasmic lipid content. This interpretation is crucial for distinguishing lipid-rich adenomas from non- adenomas. DWI and apparent diffusion coefficient (ADC) maps have also been assessed for differentiating adrenal masses, but their utility is limited due to overlapping ADC values between adenomas, myelolipomas, and carcinomas [59].
Differentiating lipid-poor adenomas from non-adenomas, such as metastases, is crucial. Traditionally, differentiation relied on calculating the absolute and relative washout rates from contrast-enhanced CT [3]. Adenomas typically exhibit rapid contrast washout, with an absolute washout rate >60% and a relative washout rate> 40%, but these methods require delayed imaging at 15 min after injecting contrast, which can be challenging in routine clinical practice. In response to this challenge, the Relative Enhancement Ratio (RER) has been proposed as a more practical and efficient alter- native [2], using only precontrast and portal venous-phase imaging (Fig. 7). The RER is calculated using the follow- ing formula: {(contrast-enhanced attenuation [HU] minus unenhanced attenuation [HU]) divided by unenhanced attenuation [HU]} ×100%. This method, with a threshold of RER> 210%, has shown 86% sensitivity and 95% speci- ficity for diagnosing lipid-poor adenomas, providing a non- invasive efficient option suited for modern workflows.
Once an adenoma is diagnosed, determining its functional status is crucial, especially for CS and primary aldosteronism (PA). Functional adenomas can produce excess cortisol, leading to CS or excess aldosterone, leading to PA. For CS, guidelines recommend biochemical tests such as the 1-mg overnight dexamethasone suppression test, urinary free cortisol, and late-night salivary cortisol for initial screening [60, 61]. Adrenocortical scintigraphy is not routinely recommended in the current guidelines but remains highly valuable for its functional assessment [62-64], and this technique is helpful in diagnosing CS, characterized by marked radiotracer uptake and contralateral suppression due to negative feedback from elevated ACTH (Fig. 5C, D). This presentation differs from CD, which shows bilateral marked uptake due to elevated ACTH secretion from a pituitary adenoma (Fig. 5E, F). Subclinical CS (SCS) generally shows low radiotracer uptake and contralateral suppression (Fig. 5A, B), aiding in differentiation from overt CS [65]. This differentiation is important because distinctly different management strategies are required. CS often requires surgical removal of the adenoma, whereas SCS may be managed conservatively depending on the symptoms and overall patient health.
For PA, diagnostic evaluation includes measuring the plasma aldosterone concentration and plasma renin activ- ity, with an elevated aldosterone-renin ratio suggesting PA [66, 67]. Confirmatory tests, such as the saline infusion
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test or captopril challenge test, verify autonomous aldos- terone secretion. Adrenal venous sampling (AVS), the gold standard for distinguishing unilateral from bilateral disease, provides critical insights for management, while CT imaging complements AVS by identifying struc- tural abnormalities [66]. Adrenocortical scintigraphy is particularly useful when AVS and CT are inconclusive [68]. In PA, no abnormal adrenal accumulation is typi- cally observed. However, functional adenomas can be visualized using dexamethasone suppression, which sup- presses ACTH production and physiological radiotracer uptake, enabling the detection of functioning adenomas [69]. Surgery is recommended for unilateral cases, while mineralocorticoid receptor antagonists are used for bilat- eral cases [67]. Appropriate diagnosis and treatment can reduce long-term health risks.
In summary, imaging techniques, such as unenhanced CT and chemical-shift MRI, are critical for diagnosing adrenal adenomas. The RER offers a useful alternative if the lipid content is low, and although DWI and ADC maps have been explored, they have limited diagnostic value. For functional assessment, combining biochemical testing with imaging tools like AVS and adrenocortical scintigraphy ensures comprehensive evaluation and tailored management of these entities.
HU on the portal venous phase (with a relative enhancement ratio of 250%), exceeding the cutoff value of 210%, consistent with a cortical adenoma. C A subtraction image of chemical-shift imaging suggests lipid content within the lesion. Adrenal venous sampling confirmed this region as an aldosterone-producing adenoma, and the patient underwent surgical resection for definitive treatment
Adrenal cortical carcinoma
Adrenal cortical carcinoma (ACC) is a rare highly malig- nant tumor of the adrenal cortex that typically appears as a large irregular mass with heterogeneous enhancement, necrosis, and hemorrhage, often exceeding 6 cm (Fig. 8) [70-72]. Calcifications are also commonly encountered [71, 72]. The masses show delayed contrast washout of <40%, which distinguishes them from benign adenomas that usually show rapid washout [2]. ACCs tend to aggres- sively invade surrounding structures, such as the renal vein, inferior vena cava (IVC), and liver, with invasion often visible on imaging. MRI is particularly useful for detailed evaluation of IVC [73] and hepatic invasion [74], and CSI helps detect the lipid content typical of adenomas but not of ACCs [75, 76]. 18F-FDG PET/CT shows higher uptake in ACCs than in adenomas, and studies have high- lighted its good diagnostic performance [77]. ACC may be discovered incidentally, especially when hormonally inac- tive, but symptoms related to hormone excess often lead to its diagnosis when active. Pathologically, ACC is char- acterized by increased mitotic activity, atypical mitotic figures, and necrosis, with the Weiss [78] or Helsinki score [79, 80] used to differentiate between benign and malig- nant tumors. A study found a significant correlation (77%, p <0.0001) between 18F-FDG uptake and Weiss scores,
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underscoring the role of 18F-FDG PET/CT in evaluating malignancy [81].
The prognosis is poor, with a 5-year survival rate between 10 and 65% depending on the stage at diagnosis and surgical success [82]. Complete surgical excision is the primary treatment, often followed by adjuvant therapies, such as mitotane and radiation. Early and accurate diagnosis based on imaging is critical for improving outcomes [83].
Adrenal medulla and extra-adrenal paraganglia tumors
Pheochromocytomas and paragangliomas (PPGLs)
PPGLs are rare NETs that originate from chromaffin cells. Pheochromocytomas typically arise in the adrenal medulla, whereas paragangliomas develop in extra-adrenal paragan- glia. These tumors secrete catecholamines, causing episodic hypertension, palpitations, headaches, and sweating. With advancements in imaging and genetic screening, many PPGLs are now detected incidentally, particularly in patients with hereditary syndromes. PPGLs are frequently associated with hereditary syndromes driven by key genetic mutations in the Von Hippel-Lindau (VHL), neurofibromatosis type 1 (NF1), rearranged during transfection (RET), and succi- nate dehydrogenase B (SDHB) genes. These mutations cor- respond to specific syndromes, including VHL syndrome (Fig. 9), NF1 (Fig. 10), multiple endocrine neoplasia type 2 (Fig. 11), and pheochromocytoma/paraganglioma syndrome type 4 (Fig. 12), respectively [84].
raphy/computed tomography showing intense accumulation in the lesion with a maximum standardized uptake value of 19.27, indicat- ing high metabolic activity consistent with adrenocortical carcinoma
On CT, PPGLs often appear as highly vascular masses, showing intense enhancement during the arterial phase (Fig. 9 A). On MRI, PPGLs appear as well-defined, hyperintense masses on T2-weighted imaging (T2WI), often showing the characteristic “lightbulb” sign (Fig. 10D) [85, 86]. T1WI shows a “salt-and-pepper” appearance [86-88], indicating microhemorrhages and high vascular flow. For succinate dehydrogenase (SDH)-related paraganglioma, especially those with SDHB mutations, ADC values on MRI can serve as a useful biomarker. These tumors typically show lower ADC values than those of non-SDH-mutated tumors, which aids in differentiation and management decisions and reflects their more clinically aggressive behavior and poorer prognosis [89, 90].
Functional imaging, such as 123I-MIBG scintigraphy, is crucial for identifying PPGLs and metastatic lesions and guiding treatment (Fig. 10, 11) [91, 92]. 123I-MIBG accu- mulates in catecholamine storage granules, so it can effec- tively visualize these tumors. Despite its widespread use, the sensitivity of 123I-MIBG for detecting PPGLs varies widely, ranging from 30 to 90% [7, 8, 93], with a specificity of about 94% [8]. However, the effectiveness of 123I-MIBG scintig- raphy can be compromised, leading to false-negative results in certain scenarios, which include SDH-related PPGLs, especially those with SDHB mutations [94] in which the tumor biology affects 123I-MIBG uptake (Fig. 12). Other fac- tors contributing to false negatives include tumors < 7 mm, cystic degeneration, necrosis, hemorrhage, and low VMAT1 expression in poorly differentiated PPGLs. Additionally, medications used to control hypertension or tachyarrhyth- mias in PPGL patients can influence the results [95]. In such cases, alternative imaging modalities, such as 18F-FDG PET/
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CT or 68 Ga-DOTATATE PET/CT, may offer more accurate detection and characterization, particularly for SDH-related tumors [95]. Although advances in CT and MRI have limited 123I-MIBG’s utility [96], it remains a practical option if more advanced imaging is unavailable. 123I-MIBG scintigraphy can be broadly performed in various regions to evaluate PPGLs, particularly for identifying metastatic lesions and determining treatment strategies (Fig. 13).
Regarding prognosis, all PPGLs are thought to have malignant potential, with a metastatic risk of 10-20% [84]. The primary treatment remains complete surgical excision, complemented by lifelong monitoring due to the risk of recurrence and metastasis. If the disease is metastatic or inoperable, adjuvant therapies, such as radiotherapy with 131I-MIBG, and targeted therapies are utilized [97, 98]. The efficacy of 131I-MIBG therapy in treating patients with advanced PPGLs varies significantly depending on several factors, including tumor burden and MIBG avidity. According to a multicenter phase 2 trial, high- dose 131I-MIBG therapy resulted in a partial response (PR) or stable disease (SD) in 92% of patients, with a median overall survival of approximately 37 months [99]. In a meta-analysis, the tumor response rates for conventional 131I-MIBG therapy were found to be 27% for PR and 52% for SD [100]. The variability in response highlights the importance of personalized treatment approaches, considering that 131I-MIBG therapy offers a viable option for controlling disease progression and managing symptoms
in a significant proportion of patients with advanced PPGLs (Fig. 13). This comprehensive approach, which combines advanced imaging, genetic testing, and personalized clinical management, is essential for optimizing outcomes in patients with PPGLs.
Neuroblastic tumors
Neuroblastoma
Neuroblastoma is a highly aggressive pediatric malignancy originating from the adrenal medulla or sympathetic chain. It is the most common extracranial solid tumor in children, accounting for a significant percentage of childhood cancer deaths [101]. Most cases are diagnosed before 5 years of age, often presenting as large heterogeneous masses with necrosis, hemorrhage, and calcification, so imaging is crucial for diagnosis and staging [102, 103].
Ultrasonography is typically the first imaging technique used, followed by CT or MRI for further characterization and staging. On ultrasonography, neuroblastomas appear as solid heterogeneous masses with calcifications in 30-90% of cases. Doppler ultrasonography can assess the vasculature as these tumors tend to encase or displace ves- sels [104]. On CT, neuroblastomas present as poorly cir- cumscribed masses with heterogeneous attenuation due to necrosis and calcification, with the latter seen in 80-90%
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of cases [103-105]. They often encase structures, such as vessels or kidneys without infiltrating them, and bone involvement, including bone marrow metastases, is com- mon (Fig. 14). MRI is useful for assessing tumor extent, particularly in cases with intraspinal involvement [102]. Neuroblastomas show heterogeneous signal intensity on T2WI, and contrast-enhanced MRI helps delineate tumor margins [104]. Wilms’ tumor (WT) is a critical differential diagnosis for adrenal neuroblastoma. Unlike neuroblas- toma, which tends to displace the kidney inferiorly and cross the midline, WT affects the kidney and often extends into the renal vein or IVC and forms a tumor thrombus [106]. Both neuroblastoma and WT exhibit lower ADC values, but the presence of calcifications are characteristic of neuroblastomas, which can help distinguish them from WT [107].
123I-MIBG scintigraphy is the gold standard for detecting primary tumors and metastases, showing uptake in 67-100% of neuroblastomas, although poorly differentiated tumors
may yield false negatives [108]. 18F-FDG-PET/CT is useful when 123I-MIBG is negative. Bone metastases are the most common form of neuroblastoma spread, and their presence is strongly associated with prognosis, so their accurate evaluation is essential [109]. Both modalities are also use for monitoring treatment response and detecting residual or recurrent disease because MRI abnormalities often persist after treatment and are not ideal for assessing therapeutic efficacy [102, 110]. Staging and risk classification rely on both imaging and clinical factors, with the International Neuroblastoma Risk Group Staging System [111] or revised classification system [112] incorporating imaging-defined risk factors, such as vascular encasement and intraspinal extension to guide treatment.
Radiologists are essential in the management of neuro- blastoma from diagnosis to follow-up by helping with tumor staging, treatment planning, and monitoring for metastasis,
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recurrence, or treatment complications. A multidisciplinary approach is often necessary for comprehensive patient care.
Ganglioneuroma
Ganglioneuromas are rare benign tumors arising from neural crest cells, and primarily composed of well-differentiated ganglion cells, Schwann cells, and fibrous tissue. These tumors are the mature benign counterpart of neuroblastomas but lack the immature neuroblasts found in more malignant variants, such as ganglioneuroblastomas [113], which explains their favorable prognosis and low recurrence rate, even after incomplete resection. Ganglioneuromas typically occur in the sympathetic nervous system, particularly in the posterior mediastinum and retroperitoneum [114], but they also can be found in the adrenal glands [114], cervical region [115], and spinal canal [116]. The median age at diagnosis was reported as 7.5 years, with a slight female predominance [115]. These tumors are usually asymptomatic and often found incidentally, although large tumors may compress nearby structures and cause symptoms requiring surgery [114].
On CT, ganglioneuromas appear as oval or lobulated, well-defined, encapsulated, hypo-attenuating masses [117] with calcification in approximately 20% of cases [103], usually fine and punctate, although coarse calcification may occasionally occur [118]. On MRI, ganglioneuromas show heterogeneous intermediate-to-high intensity on T2WI, with
a characteristic “whorl sign” or “stripe sign,” representing the intersection of Schwann cells and collagen fibers within hyperintense areas (Fig. 15) [117, 119]. The mucous-like matrix leads to delayed enhancement on post-contrast imag- ing, and larger tumors may exhibit cystic degeneration. DWI typically shows hyperintensity, which helps differentiate ganglioneuroma from cystic lesions. Large ganglioneuromas can occasionally mimic malignant tumors, but they can usu- ally be distinguished from neuroblastomas based on imaging findings, as neuroblastomas tend to exhibit more amorphous calcifications and higher uptake of 123I-MIBG and 18FDG [120, 121].
Other tumors: commonly encountered diseases or diseases that require differentiation by diagnostic imaging
Myelolipoma
Myelolipomas are benign tumors consisting of mature adipose tissue and hematopoietic cells, accounting for 3.3-6.5% of all primary adrenal tumors [122, 123]. They are usually asymptomatic and incidentally discovered on imaging, but large tumors may cause nonspecific abdomi- nal pain due to compression, and those > 10-cm risk rup- ture or hemorrhage [124], potentially requiring surgery (Fig. 16).
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The pathogenesis of myelolipomas is unclear, but theories involve progenitor-cell interactions, metaplastic changes due to stress or inflammation, and hormonal factors, such as ACTH overexpression [125, 126]. Approximately 10% of cases are associated with CAH, often presenting bilaterally [126].
On imaging, myelolipoma appeared as well- circumscribed, heterogeneous masses. US shows hypoechoic lesions, and CT reveals mixed fat and soft tissue with low attenuation due to macroscopic fat [124]. Calcifications and contrast enhancement of soft-tissue components can
bone, and bilateral femurs) and liver metastasis. B Unenhanced and enhanced computed tomography (CT) images showing a large left- retroperitoneal mass with calcification (arrows). C Enhanced CT showing peripheral enhancement (arrowhead) with extensive internal necrosis, characteristic of advanced neuroblastoma
occasionally be observed [124]. MRI shows hyperintense fatty components on T1WI with signal loss on fat-suppressed sequences [127, 128]. Hemorrhage may be visible on CT or MRI, depending on the blood degradation products [129, 130].
In most cases, encapsulated lesions with fat and soft tissue are confidently diagnosed as myelolipomas. However, extra-adrenal myelolipomas account for 10-15% of cases, and those found in the retroperitoneum and other areas present diagnostic challenges. The differential diagnosis includes liposarcomas, angiolipomas, neurogenic tumors, and extramedullary
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hematopoiesis [124, 131-133]. Unlike liposarcomas, myelolipomas lack irregular margins and heterogeneous enhancement, which aids in differentiation. Importantly, 99mTc-sulfur colloid scintigraphy has proven useful in
distinguishing myelolipomas from other fat-containing masses, particularly extra-adrenal lesions [134].
In summary, adrenal and extra-adrenal myelolipomas are stable, nonmalignant tumors that are generally managed by monitoring with appropriate follow-up
if needed. However, tumors > 8 cm or symptomatic cases may require surgical excision due to the risk of hemorrhage or rupture, and differentiating them from other adrenal or retroperitoneal masses is crucial for the appropriate management.
Lymphoma
Adrenal lymphoma, a rare extranodal non-Hodgkin lymphoma subtype that comprises < 1% of cases, primarily presents as diffuse large B-cell lymphoma [135]. It can occur as primary adrenal lymphoma (PAL) or as secondary involvement in systemic lymphoma. PAL typically presents bilaterally and with abdominal pain, followed by B symptoms, such as fever, weight loss, or night sweating, and less commonly, adrenal insufficiency [135, 136]. Secondary adrenal involvement is more common and usually associated with widespread systemic lymphoma.
Adrenal lymphoma typically presents as a large mass, with an average tumor size of 8-10 cm, appearing as a
well-defined soft-tissue density mass on CT and showing diffusion restriction on MRI (Fig. 17) [137, 138]. Lesions show mild progressive contrast enhancement without marked necrosis or hemorrhage. Immune deficiency/ dysregulation-associated lymphoid proliferative disor- ders (LPDs), such as methotrexate-associated LPD, are often Epstein-Barr virus related [139], and necrosis and hemorrhage are more common, complicating differentia- tion from infections [140]. 18F-FDG PET/CT is useful for diagnosing lymphoma and is superior to CT in visualizing extra-adrenal lesions [141]. However, bilateral high 18F- FDG uptake is not specific and can also be seen in other conditions, such as infections (e.g., tuberculosis) or vagal reflexes. The prognosis is generally poor, with chemo- therapy, often using the R-CHOP regimen, as the primary treatment [142].
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Metastasis
Metastases are the most common adrenal malignant lesions, typically discovered during the staging or follow-up of malignancies. Primary cancers that frequently metastasize to the adrenal glands include lung, breast, melanoma, renal, gastrointestinal, and pancreatic cancers [143, 144].
Metastases appear bilaterally in 32-73% of cases and are often incidentally discovered on imaging [143]. On CT and MRI, adrenal metastases appear as large well-defined masses with heterogeneous enhancement and areas of necrosis or hemorrhage (Fig. 18). They often show delayed contrast washout relative to that of adenomas, which show rapid washout [3]. 18F-FDG PET/CT helps differentiate adrenal metastases from benign lesions [145] since metastases typi- cally show significantly higher 18F-FDG uptake [143]. How- ever, false positives can occur in benign or inflammatory lesions, such as adrenalitis caused by ICIs, which may also show high 18F-FDG uptake [14, 143-147]. The combination
the left-adrenal mass, suggesting retroperitoneal hemorrhage (arrow). C Enhanced computed tomography showing irregular tumor enhance- ment in the left-adrenal mass (arrow), consistent with metastasis. Adrenal metastasis can occasionally be complicated by hemorrhage
of PET with CT or MRI improves differentiation. If biopsy is required, ruling out PPGLs is essential to avoid hypertensive complications.
Adrenal hemorrhage and adrenal infarction
Adrenal hemorrhage and infarction are rare but potentially life-threatening conditions associated with various causes. Adrenal hemorrhage is caused by trauma, anticoagulation, coagulopathies, infections, or severe stress [148]. Hemorrhage following sepsis, known as Waterhouse-Friderichsen syndrome, commonly causes bilateral adrenal involvement [149]. Coagulopathy-related causes include disseminated intravascular coagulation, antiphospholipid syndrome (APS), heparin-induced thrombocytopenia, and adrenal tumors. In neonates, the causes include birth trauma, hypoxia, hemorrhagic disorders, and maternal diabetes [148]. Adrenal-vein thrombosis is another recognized cause. Symptoms range from nonspecific
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abdominal or back pain to adrenal crisis with bilateral involvement. On CT, the acute hemorrhage appears as a round or oval high-attenuation mass, which decreases over time. MRI is particularly useful for estimating the timing of the hemorrhage, with subacute hemorrhages appearing hyperintense on T1WI and T2WI. Chronic hemorrhages may show calcification and can appear as pseudocysts on imaging [150].
Adrenal infarction, although rare, can result from cer- tain conditions, such as APS, myelodysplastic syndrome (Fig. 19), and TAFRO syndrome [151]. APS, which is often associated with adrenal infarction, leads to venous throm- bosis and subsequent hemorrhagic infarction. CT typically shows adrenal enlargement with fat stranding and a lack of enhancement, characteristic of infarction. In TAFRO syn- drome, adrenal infarction can be accompanied by systemic symptoms, such as pleural effusion and lymphadenopathy, and bilateral adrenal enlargement is often observed on
imaging [151]. Severe acute respiratory syndrome corona- virus 2 (SARS-CoV-2), or coronavirus 2019 (COVID-19) infection can also cause adrenal infarction due to throm- boembolic complications, worsening prognosis in critically ill patients [152]. Both conditions require prompt diagnosis and management, especially in bilateral cases, to prevent adrenal insufficiency. Treatment is often conservative, with adrenal replacement therapy needed in cases of significant insufficiency. Interventional procedures, such as emboliza- tion, may be required for ongoing hemorrhage or infarction unresponsive to medical management.
Infectious disease
Infections involving the adrenal glands, although uncom- mon, can cause significant adrenal pathology. Tuberculo- sis remains one of the leading infectious causes, particu- larly in regions where it is endemic. Adrenal involvement
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typically occurs bilaterally and may lead to adrenal insuf- ficiency [147]. On CT, tuberculosis often presents as bilat- eral enlargement with low attenuation [153]. Calcification or atrophy may occur in the chronic stage [147]. MRI may reveal mixed signal intensities, with central hypointensity on T2WI and peripheral rim enhancement (Fig. 20) [154]. Generally, caseous necrosis can sometimes show high signal intensity on T1WI [155].
Fungal infections, especially disseminated histoplasmosis in immunocompromised patients, occasionally involve the adrenal glands, presenting as bilateral adrenal masses with peripheral enhancement on imaging. CT may show enlarged glands with low attenuation, and MRI often reveals heterogeneous signal intensity.
Viral infections such as cytomegalovirus occur in neonates or immunocompromised individuals, causing adrenal enlargement and sometimes insufficiency [156]. Although imaging findings for viral infections are nonspecific, adrenal involvement may be incidentally detected by 18F-FDG PET/CT during evaluations for other conditions in immunocompetent individuals [157].
Infections, although rare causes of adrenal disease, should be considered in immunocompromised patients or in areas with endemic infectious diseases. Imaging has a key role in identifying these conditions, but clinical correlation and histopathological confirmation, when necessary, remain essential for accurate diagnosis.
Conclusion
Adrenal imaging requires a multifaceted approach that uses CT, MRI, and nuclear medicine to accurately diagnose and manage a wide spectrum of adrenal disorders. This review highlighted the key imaging features of various conditions and the complementary roles of different modalities, providing a valuable resource for radiologists and trainees in clinical prac- tice. To gain a comprehensive understanding of adrenal imag- ing, it is essential to first have a solid grasp of the anatomy and physiology of the adrenal glands. A thorough knowledge of adrenal cortical adenomas, endocrine abnormalities, PPGL, and neuroblastomas through CT, MRI, and nuclear medicine studies is critical. Staying updated on recent advancements including evolving terminology, such as adrenal cortical dis- ease, genetic correlations, hereditary tumor syndromes, and the use of nuclear medicine therapies, is equally important. Finally, understanding the differential diagnoses, key condi- tions, and systemic diseases involving the adrenal glands is fundamental to ensuring accurate imaging interpretation and effective diagnosis of adrenal disorders.
Author contributions K.Y., M.M., J.T., and U.T. conceptualized this review. K.Y., M.M., and K.K. conducted the literature search and review. K.Y., M.M., T.I., K.I., T.I., A.O., and J.T. contributed to data collection. M.M. and U.T. supervised the work. K.Y. prepared the first draft of the manuscript, which was critically revised by all co-authors. All authors approved the final version of the manuscript for submission.
Funding No funding was received by any of the authors.
Declarations
Conflict of interest The authors declare no competing interests that are relevant to the content of this article.
Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors.
Open Access This article is licensed under a Creative Commons Attri- bution 4.0 International License, which permits use, sharing, adapta- tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
References
1. Lori A, Erickson AJG, de Krijger RR, Papotti M. Endocrine and neuroendocrine tumors. 5th ed. Lyon (France): International Agency for Research on Cancer; 2022.
2. Nagayama Y, Inoue T, Kato Y, Tanoue S, Kidoh M, Oda S, et al. Relative enhancement ratio of portal venous phase to unenhanced CT in the diagnosis of lipid-poor adrenal adenomas. Radiology. 2021;301:360-8.
3. Korobkin M, Brodeur FJ, Francis IR, Quint LE, Dunnick NR, Londy F. CT time-attenuation washout curves of adrenal adeno- mas and nonadenomas. AJR Am J Roentgenol. 1998;170:747-52.
4. Korobkin M, Giordano TJ, Brodeur FJ, Francis IR, Siegel- man ES, Quint LE, et al. Adrenal adenomas: relationship between histologic lipid and CT and MR findings. Radiology. 1996;200:743-7.
5. Platzek I, Sieron D, Plodeck V, Borkowetz A, Laniado M, Hoffmann RT. Chemical shift imaging for evaluation of adre- nal masses: a systematic review and meta-analysis. Eur Radiol. 2019;29:806-17.
6. Timmers HJ, Taieb D, Pacak K. Current and future anatomical and functional imaging approaches to pheochromocytoma and paraganglioma. Horm Metab Res. 2012;44:367-72.
7. Bhatia KS, Ismail MM, Sahdev A, Rockall AG, Hogarth K, Cani- zales A, et al. 123I-metaiodobenzylguanidine (MIBG) scintig- raphy for the detection of adrenal and extra-adrenal phaeochro- mocytomas: CT and MRI correlation. Clin Endocrinol (Oxf). 2008;69:181-8.
8. Timmers HJ, Chen CC, Carrasquillo JA, Whatley M, Ling A, Havekes B, et al. Comparison of 18F-fluoro-L- DOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of
pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2009;94:4757-67.
9. Janssen I, Chen CC, Millo CM, Ling A, Taieb D, Lin FI, et al. PET/CT comparing (68)Ga-DOTATATE and other radiopharma- ceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging. 2016;43:1784-91.
10. Kroiss AS. Current status of functional imaging in neuroblas- toma, pheochromocytoma, and paraganglioma disease. Wien Med Wochenschr. 2019;169:25-32.
11. Nölting S, Ullrich M, Pietzsch J, Ziegler CG, Eisenhofer G, Grossman A, et al. Current management of pheochromocytoma/ paraganglioma: a guide for the practicing clinician in the era of precision medicine. Cancers (Basel). 2019;11:1505.
12. Nockel P, El Lakis M, Gaitanidis A, Yang L, Merkel R, Patel D, et al. Preoperative genetic testing in pheochromocytomas and paragangliomas influences the surgical approach and the extent of adrenal surgery. Surgery. 2018;163:191-6.
13. Bausch B, Wellner U, Bausch D, Schiavi F, Barontini M, Sanso G, et al. Long-term prognosis of patients with pediatric pheo- chromocytoma. Endocr Relat Cancer. 2014;21:17-25.
14. Shroff GS, Strange CD, Ahuja J, Altan M, Sheshadri A, Unlu E, et al. Imaging of immune checkpoint inhibitor immunotherapy for non-small cell lung cancer. Radiographics. 2022;42:1956-74.
15. Lam KY, Chan AC, Lo CY. Morphological analysis of adrenal glands: a prospective analysis. Endocr Pathol. 2001;12:33-8.
16. Gurun E, Kaya M, Gurun KH. Evaluation of normal adrenal gland volume and morphometry and relationship with waist cir- cumference in an adult population using multidetector computed tomography. Sisli Etfal Hastan Tip Bul. 2021;55:333-8.
17. Vincent JM, Morrison ID, Armstrong P, Reznek RH. The size of normal adrenal glands on computed tomography. Clin Radiol. 1994;49:453-5.
18. Ryan S, McNicholas M, Eustace SJ. Anatomy for diagnostic imaging. Saunders/Elsevier; 2011.
19. Kangarloo H, Diament MJ, Gold RH, Barrett C, Lippe B, Gef- fner M, et al. Sonography of adrenal glands in neonates and children: changes in appearance with age. J Clin Ultrasound. 1986;14:43-7.
20. van Vuuren SH, Damen-Elias HA, Stigter RH, van der Doef R, Goldschmeding R, de Jong TP, et al. Size and volume charts of fetal kidney, renal pelvis and adrenal gland. Ultrasound Obstet Gynecol. 2012;40:659-64.
21. Karsli T, Strickland D, Livingston J, Wu Q, Mhanna MJ, Shek- hawat PS. Assessment of neonatal adrenal size using high resolution 2D ultrasound and its correlation with birth demo- graphics and clinical outcomes. J Matern Fetal Neonatal Med. 2019;32:377-83.
22. Planz VB, Dyer RB. The “pancake” adrenal. Abdom Imaging. 2015;40:2041-3.
23. Minshew LJ, Williams HJ, DiSantis DJ. The “butterfly” adrenal gland. Abdom Radiol (NY). 2017;42:661-2.
24. Sargar KM, Khanna G, Hulett BR. Imaging of nonmalignant adrenal lesions in children. Radiographics. 2017;37:1648-64.
25. Barwick TD, Malhotra A, Webb JA, Savage MO, Reznek RH. Embryology of the adrenal glands and its relevance to diagnostic imaging. Clin Radiol. 2005;60:953-9.
26. Ors F, Lev-Toaff A, O’Kane P, Qazi N, Bergin D. Paraovarian adrenal rest with MRI features characteristic of an adrenal ade- noma. Br J Radiol. 2007;80:e205-8.
27. Rushworth RL, Torpy DJ, Falhammar H. Adrenal Crisis. N Engl J Med. 2019;381:852-61.
28. Yau M, Khattab A, Yuen T, New M. Congenital Adrenal Hyper- plasia. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al., editors. Endotext. South Dartmouth
(MA): MDText.com, Inc. Copyright @ 2000-2024, MDText.com, Inc .; 2000
29. Ng SM, Stepien KM, Krishan A. Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia. Cochrane Database Syst Rev. 2020;3:Cd012517.
30. Aderotimi TS, Kraft JK. Ultrasound of the adrenal gland in chil- dren. Ultrasound. 2021;29:48-56.
31. Hernanz-Schulman M, Brock JW 3rd, Russell W. Sonographic findings in infants with congenital adrenal hyperplasia. Pediatr Radiol. 2002;32:130-7.
32. Al-Alwan I, Navarro O, Daneman D, Daneman A. Clinical utility of adrenal ultrasonography in the diagnosis of congenital adrenal hyperplasia. J Pediatr. 1999;135:71-5.
33. Kurtaran A, Traub T, Shapiro B. Scintigraphic imaging of the adrenal glands. Eur J Radiol. 2002;41:123-30.
34. Hempenstall LE, Kwok M, Siriwardana AR, Wang G, Desai D, Gleeson J. Testicular masses in congenital adrenal hyperplasia: using 123I-MIBG scintigraphy to support the diagnosis of tes- ticular adrenal rest tumors. J Clin Urol. 2018;13:122-4.
35. de Eyer JL, de Paz Oliveira AP, Porto LC, Dekermacher S. Tes- ticular adrenal rest tumors-epidemiology, diagnosis and treat- ment. J Pediatr Urol. 2024;20:77-87.
36. Auer MK, Nordenström A, Lajic S, Reisch N. Congenital adrenal hyperplasia. Lancet. 2023;401:227-44.
37. Fushimi Y, Taoka T, Naganawa S. From pituitary adenoma to PitNET: it is time to discuss PitNET/pituitary adenoma. Jpn J Radiol. 2023;41:787-8.
38. Bonneville J-F. Cushing disease. In: Bonneville J-F, Bonneville F, Cattin F, Nagi S, editors. MRI of the pituitary gland. Cham: Springer International Publishing; 2016. p. 107-11.
39. Miki Y, Matsuo M, Nishizawa S, Kuroda Y, Keyaki A, Makita Y, et al. Pituitary adenomas and normal pituitary tissue: enhance- ment patterns on gadopentetate-enhanced MR imaging. Radiol- ogy. 1990;177:35-8.
40. Varrassi M, Cobianchi Bellisari F, Bruno F, Palumbo P, Natella R, Maggialetti N, et al. High-resolution magnetic resonance imaging at 3T of pituitary gland: advantages and pitfalls. Gland Surg. 2019;8:S208-15.
41. Tsukamoto T, Miki Y. Imaging of pituitary tumors: an update with the 5th WHO Classifications-part 2. Neoplasms other than PitNET and tumor-mimicking lesions. Jpn J Radiol. 2023;41:808-29.
42. Yamamoto A, Oba H, Furui S. Influence of age and sex on signal intensities of the posterior lobe of the pituitary gland on T1-weighted images from 3 T MRI. Jpn J Radiol. 2013;31:186-91.
43. Chen S, Chen K, Lu L, Zhang X, Tong A, Pan H, et al. The effects of sampling lateralization on bilateral inferior petrosal sinus sampling and desmopressin stimulation test for pediatric Cushing’s disease. Endocrine. 2019;63:582-91.
44. Bonelli FS, Huston J 3rd, Carpenter PC, Erickson D, Young WF Jr, Meyer FB. Adrenocorticotropic hormone-dependent Cushing’s syndrome: sensitivity and specificity of inferior pet- rosal sinus sampling. AJNR Am J Neuroradiol. 2000;21:690-6.
45. Zampetti B, Grossrubatscher E, Dalino Ciaramella P, Boccardi E, Loli P. Bilateral inferior petrosal sinus sampling. Endocr Connect. 2016;5:R12-25.
46. Tritos NA, Biller BM, Swearingen B. Management of cushing disease. Nat Rev Endocrinol. 2011;7:279-89.
47. Kakade HR, Kasaliwal R, Jagtap VS, Bukan A, Budyal SR, Khare S, et al. Ectopic ACTH-secreting syndrome: a single- center experience. Endocr Pract. 2013;19:1007-14.
48. Ilias I, Torpy DJ, Pacak K, Mullen N, Wesley RA, Nieman LK. Cushing’s syndrome due to ectopic corticotropin secretion: twenty years’ experience at the National Institutes of Health. J Clin Endocrinol Metab. 2005;90:4955-62.
49. Paleń-Tytko JE, Przybylik-Mazurek EM, Rzepka EJ, Pach DM, Sowa-Staszczak AS, Gilis-Januszewska A, et al. Ectopic ACTH syndrome of different origin-Diagnostic approach and clinical outcome. Experience of one Clinical Centre. PLoS ONE. 2020;15:e0242679.
50. Wagner-Bartak NA, Baiomy A, Habra MA, Mukhi SV, Morani AC, Korivi BR, et al. Cushing syndrome: diagnostic workup and imaging features, with clinical and pathologic correlation. AJR Am J Roentgenol. 2017;209:19-32.
51. Hasenmajer V, Sbardella E, Sciarra F, Minnetti M, Isidori AM, Venneri MA. The immune system in cushing’s syndrome. Trends Endocrinol Metab. 2020;31:655-69.
52. Diwaker C, Shah RK, Patil V, Jadhav S, Lila A, Bandgar T, et al. 68Ga-DOTATATE PET/CT of ectopic cushing syndrome due to appendicular carcinoid. Clin Nucl Med. 2019;44:881-2.
53. Wannachalee T, Turcu AF, Bancos I, Habra MA, Avram AM, Chuang HH, et al. The clinical impact of [(68) Ga]-DOTA- TATE PET/CT for the diagnosis and management of ectopic adrenocorticotropic hormone-secreting tumours. Clin Endo- crinol (Oxf). 2019;91:288-94.
54. Valizadeh M, Rahmani F, Nikoohemmat M, Ramezani Ahmadi A, Hosseinpanah F, Niroomand M, et al. Diagnostic accu- racy of the desmopressin stimulation test in the comprehen- sive assessment of ACTH-dependent cushing’s syndrome: a comparative analysis with BIPSS and TSS. Endocr Res. 2024;49:1-11.
55. Young J, Haissaguerre M, Viera-Pinto O, Chabre O, Baudin E, Tabarin A. MANAGEMENT OF ENDOCRINE DISEASE: Cushing’s syndrome due to ectopic ACTH secretion: an expert operational opinion. Eur J Endocrinol. 2020;182:R29-r58.
56. Inoue M, Okamura K, Kitaoka C, Kinoshita F, Namitome R, Nakamura U, et al. Metyrapone-responsive ectopic ACTH- secreting pheochromocytoma with a vicious cycle via a glu- cocorticoid-driven positive-feedback mechanism. Endocr J. 2018;65:755-67.
57. Mete O, Erickson LA, Juhlin CC, de Krijger RR, Sasano H, Volante M, et al. Overview of the 2022 WHO classification of adrenal cortical tumors. Endocr Pathol. 2022;33:155-96.
58. Mayo-Smith WW, Boland GW, Noto RB, Lee MJ. State-of-the- art adrenal imaging. Radiographics. 2001;21:995-1012.
59. Miller FH, Wang Y, McCarthy RJ, Yaghmai V, Merrick L, Larson A, et al. Utility of diffusion-weighted MRI in char- acterization of adrenal lesions. AJR Am J Roentgenol. 2010;194:W179-85.
60. Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO, et al. Treatment of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015;100:2807-31.
61. Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, et al. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalo- mas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2023;189:G1-g42.
62. Bui F, Macri C, Varotto L, Boscaro M, Mantero F. Adrenal scin- tigraphy in the morphological and functional evaluation of Cush- ing’s syndrome. Cardiology. 1985;72(Suppl 1):76-83.
63. Ricciato MP, Di Donna V, Perotti G, Pontecorvi A, Bellantone R, Corsello SM. The role of adrenal scintigraphy in the diagnosis of subclinical cushing’s syndrome and the prediction of post- surgical hypoadrenalism. World J Surg. 2014;38:1.
64. Fagour C, Bardet S, Rohmer V, Arimone Y, Lecomte P, Valli N, et al. Usefulness of adrenal scintigraphy in the follow-up of adrenocortical incidentalomas: a prospective multicenter study. Eur J Endocrinol. 2009;160:257-64.
65. Okada Y, Matsushita S, Yamaguchi K. Investigation of Cush- ing’s and subclinical Cushing’s syndromes using adrenocortical scintigraphy. Nucl Med Commun. 2021;42:619-24.
66. Mulatero P, Monticone S, Deinum J, Amar L, Prejbisz A, Zen- naro MC, et al. Genetics, prevalence, screening and confirmation of primary aldosteronism: a position statement and consensus of the working group on endocrine hypertension of the european society of hypertension. J Hypertens. 2020;38:1919-28.
67. Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. The management of primary aldosteron- ism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101:1889-916.
68. Yen RF, Wu VC, Liu KL, Cheng MF, Wu YW, Chueh SC, et al. 131I-6beta-iodomethyl-19-norcholesterol SPECT/CT for pri- mary aldosteronism patients with inconclusive adrenal venous sampling and CT results. J Nucl Med. 2009;50:1631-7.
69. Volpe C, Enberg U, Sjögren A, Wahrenberg H, Jacobsson H, Törring O, et al. The role of adrenal scintigraphy in the preop- erative management of primary aldosteronism. Scand J Surg. 2008;97:248-53.
70. Sturgeon C, Shen WT, Clark OH, Duh Q-Y, Kebebew E. Risk assessment in 457 adrenal cortical carcinomas: how much does tumor size predict the likelihood of malignancy? J Am Coll Surg. 2006;202:423-30.
71. Kiseljak-Vassiliades K, Bancos I, Hamrahian A, Habra M, Vaidya A, Levine AC, et al. American association of clinical endocrinology disease state clinical review on the evaluation and management of adrenocortical carcinoma in an adult: a practical approach. Endocr Pract. 2020;26:1366-83.
72. Hodgson A, Pakbaz S, Mete O. A diagnostic approach to adreno- cortical tumors. Surg Pathol Clin. 2019;12:967-95.
73. Soler R, Rodríguez E, López MF, Marini M. MR imaging in inferior vena cava thrombosis. Eur J Radiol. 1995;19:101-7.
74. Kedra A, Dohan A, Gaujoux S, Sibony M, Jouinot A, Assié G, et al. Preoperative detection of liver involvement by right-sided adrenocortical carcinoma using CT and MRI. Cancers (Basel). 2021;13:1603.
75. Young WF Jr. Conventional imaging in adrenocortical carci- noma: update and perspectives. Horm Cancer. 2011;2:341-7.
76. Bharwani N, Rockall AG, Sahdev A, Gueorguiev M, Drake W, Grossman AB, et al. Adrenocortical carcinoma: the range of appearances on CT and MRI. AJR Am J Roentgenol. 2011;196:W706-14.
77. Schaafsma M, Berends AMA, Links TP, Brouwers AH, Ker- stens MN. The diagnostic value of 18F-FDG PET/CT scan in characterizing adrenal tumors. J Clin Endocrinol Metab. 2023;108:2435-45.
78. Libè R, Fratticci A, Bertherat J. Adrenocortical cancer: patho- physiology and clinical management. Endocr Relat Cancer. 2007;14:13-28.
79. Kamai T, Murakami S, Arai K, Ishida K, Kijima T. Association of Nrf2 expression and mutation with Weiss and Helsinki scores in adrenocortical carcinoma. Cancer Sci. 2022;113:2368-77.
80. Pennanen M, Heiskanen I, Sane T, Remes S, Mustonen H, Haglund C, et al. Helsinki score-a novel model for predic- tion of metastases in adrenocortical carcinomas. Hum Pathol. 2015;46:404-10.
81. Gust L, Taieb D, Beliard A, Barlier A, Morange I, de Micco C, et al. Preoperative 18F-FDG uptake is strongly correlated with malignancy, Weiss score, and molecular markers of aggressive- ness in adrenal cortical tumors. World J Surg. 2012;36:1406-10.
82. Daher M, Varghese J, Gruschkus SK, Jimenez C, Waguespack SG, Bedrose S, et al. Temporal trends in outcomes in patients with adrenocortical carcinoma: a multidisciplinary referral- center experience. J Clin Endocrinol Metab. 2022;107:1239-46.
83. Ahmed AA, Thomas AJ, Ganeshan DM, Blair KJ, Lall C, Lee JT, et al. Adrenal cortical carcinoma: pathology, genomics, progno- sis, imaging features, and mimics with impact on management. Abdom Radiol (NY). 2020;45:945-63.
84. Neumann HPH, Young WF Jr, Eng C. Pheochromocytoma and paraganglioma. N Engl J Med. 2019;381:552-65.
85. Fonseca E, Ponte M, Yamauchi FI, Baroni RH. The light bulb sign in pheochromocytoma. Abdom Radiol (NY). 2017;42:2779.
86. Sahdev A, Sohaib A, Monson JP, Grossman AB, Chew SL, Reznek RH. CT and MR imaging of unusual locations of extra- adrenal paragangliomas (pheochromocytomas). Eur Radiol. 2005;15:85-92.
87. Djuric-Stefanovic A, Toncev J, Mijovic K. “Salt-and-pepper” sign. Abdom Radiol (NY). 2024;49:2552-3.
88. Elsayes KM, Menias CO, Siegel CL, Narra VR, Kanaan Y, Hus- sain HK. Magnetic resonance characterization of pheochromocy- tomas in the abdomen and pelvis: imaging findings in 18 surgi- cally proven cases. J Comput Assist Tomogr. 2010;34:548-53.
89. Ota Y, Naganawa S, Kurokawa R, Bapuraj JR, Capizzano A, Kim J, et al. Assessment of MR imaging and CT in differentiat- ing hereditary and nonhereditary paragangliomas. AJNR Am J Neuroradiol. 2021;42:1320-6.
90. Ota Y, Liao E, Capizzano AA, Kurokawa R, Bapuraj JR, Syed F, et al. Diagnostic role of diffusion-weighted and dynamic con- trast-enhanced perfusion MR imaging in paragangliomas and schwannomas in the head and neck. AJNR Am J Neuroradiol. 2021;42:1839-46.
91. Rufini V, Treglia G, Castaldi P, Perotti G, Giordano A. Com- parison of metaiodobenzylguanidine scintigraphy with positron emission tomography in the diagnostic work-up of pheochromo- cytoma and paraganglioma: a systematic review. Q J Nucl Med Mol Imaging. 2013;57:122-33.
92. Jacobson AF, Deng H, Lombard J, Lessig HJ, Black RR. 123I-meta-iodobenzylguanidine scintigraphy for the detection of neuroblastoma and pheochromocytoma: results of a meta- analysis. J Clin Endocrinol Metab. 2010;95:2596-606.
93. Chang CA, Pattison DA, Tothill RW, Kong G, Akhurst TJ, Hicks RJ, et al. (68)Ga-DOTATATE and (18)F-FDG PET/CT in para- ganglioma and pheochromocytoma: utility, patterns and hetero- geneity. Cancer Imaging. 2016;16:22.
94. Fonte JS, Robles JF, Chen CC, Reynolds J, Whatley M, Ling A, et al. False-negative 123I-MIBG SPECT is most commonly found in SDHB-related pheochromocytoma or paraganglioma with high frequency to develop metastatic disease. Endocr Relat Cancer. 2012;19:83-93.
95. Taïeb D, Hicks RJ, Hindié E, Guillet BA, Avram A, Ghedini P, et al. European association of nuclear medicine practice guideline/society of nuclear medicine and molecular imaging procedure standard 2019 for radionuclide imaging of phaeochro- mocytoma and paraganglioma. Eur J Nucl Med Mol Imaging. 2019;46:2112-37.
96. Rao D, van Berkel A, Piscaer I, Young WF, Gruber L, Deutsch- bein T, et al. Impact of 123I-MIBG scintigraphy on clinical decision-making in pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2019;104:3812-20.
97. Carrasquillo JA, Chen CC, Jha A, Pacak K, Pryma DA, Lin FI. Systemic radiopharmaceutical therapy of pheochromocytoma and paraganglioma. J Nucl Med. 2021;62:1192-9.
98. Kayano D, Kinuya S. Current consensus on I-131 MIBG therapy. Nucl Med Mol Imaging. 2018;52:254-65.
99. Pryma DA, Chin BB, Noto RB, Dillon JS, Perkins S, Solnes L, et al. Efficacy and safety of high-specific-activity (131)I-MIBG therapy in patients with advanced pheochromocytoma or para- ganglioma. J Nucl Med. 2019;60:623-30.
100. van Hulsteijn LT, Niemeijer ND, Dekkers OM, Corssmit EP. (131)I-MIBG therapy for malignant paraganglioma and
phaeochromocytoma: systematic review and meta-analysis. Clin Endocrinol (Oxf). 2014;80:487-501.
101. Louis CU, Shohet JM. Neuroblastoma: molecular pathogenesis and therapy. Annu Rev Med. 2015;66:49-63.
102. Brisse HJ, McCarville MB, Granata C, Krug KB, Wootton- Gorges SL, Kanegawa K, et al. Guidelines for imaging and staging of neuroblastic tumors: consensus report from the International Neuroblastoma Risk Group Project. Radiology. 2011;261:243-57.
103. Lonergan GJ, Schwab CM, Suarez ES, Carlson CL. Neuroblas- toma, ganglioneuroblastoma, and ganglioneuroma: radiologic- pathologic correlation. Radiographics. 2002;22:911-34.
104. Dumba M, Jawad N, McHugh K. Neuroblastoma and nephroblas- toma: a radiological review. Cancer Imaging. 2015;15:5.
105. Xu Y, Wang J, Peng Y, Zeng J. CT characteristics of primary ret- roperitoneal neoplasms in children. Eur J Radiol. 2010;75:321-8.
106. Kembhavi SA, Shah S, Rangarajan V, Qureshi S, Popat P, Kurkure P. Imaging in neuroblastoma: an update. Indian J Radiol Imaging. 2015;25:129-36.
107. Aslan M, Aslan A, Arıöz Habibi H, Kalyoncu Uçar A, Özmen E, Bakan S, et al. Diffusion-weighted MRI for differentiating Wilms tumor from neuroblastoma. Diagn Interv Radiol. 2017;23:403-6.
108. Bleeker G, Tytgat GA, Adam JA, Caron HN, Kremer LC, Hooft L, et al. 123I-MIBG scintigraphy and 18F-FDG-PET imaging for diagnosing neuroblastoma. Cochrane Database Syst Rev. 2015;2015:Cd009263.
109. Liu S, Yin W, Lin Y, Huang S, Xue S, Sun G, et al. Metastasis pattern and prognosis in children with neuroblastoma. World J Surg Oncol. 2023;21:130.
110. Orr KE, McHugh K. The new international neuroblastoma response criteria. Pediatr Radiol. 2019;49:1433-40.
111. Monclair T, Brodeur GM, Ambros PF, Brisse HJ, Cecchetto G, Holmes K, et al. The international neuroblastoma risk group (INRG) staging system: an INRG task force report. J Clin Oncol. 2009;27:298-303.
112. Irwin MS, Naranjo A, Zhang FF, Cohn SL, London WB, Gastier- Foster JM, et al. Revised neuroblastoma risk classification sys- tem: a report from the children’s oncology group. J Clin Oncol. 2021;39:3229-41.
113. Geoerger B, Hero B, Harms D, Grebe J, Scheidhauer K, Berthold F. Metabolic activity and clinical features of primary ganglioneu- romas. Cancer. 2001;91:1905-13.
114. Iacobone M, Torresan F, Citton M, Schiavone D, Viel G, Favia G. Adrenal ganglioneuroma: the padua endocrine surgery unit experience. Int J Surg. 2017;41(Suppl 1):S103-8.
115. Alexander N, Sullivan K, Shaikh F, Irwin MS. Characteristics and management of ganglioneuroma and ganglioneuroblastoma- intermixed in children and adolescents. Pediatr Blood Cancer. 2018;65: e26964.
116. Bteich F, Larmure O, Stella I, Klein O, Joud A. Spinal gangli- oneuroma: a rare and challenging tumor in the pediatric popula- tion. Childs Nerv Syst. 2024;40:4301-7.
117. Luo L, Zheng X, Tao KZ, Zhang J, Tang YY, Han FG. Imaging analysis of ganglioneuroma and quantitative analysis of paraspi- nal ganglioneuroma. Med Sci Monit. 2019;25:5263-71.
118. Ichikawa T, Ohtomo K, Araki T, Fujimoto H, Nemoto K, Nanbu A, et al. Ganglioneuroma: computed tomography and magnetic resonance features. Br J Radiol. 1996;69:114-21.
119. Zhang Y, Nishimura H, Kato S, Fujimoto K, Ohkuma K, Kojima K, et al. MRI of ganglioneuroma: histologic correlation study. J Comput Assist Tomogr. 2001;25:617-23.
120. Fendler WP, Melzer HI, Walz C, von Schweinitz D, Coppen- rath E, Schmid I, et al. High 123I-MIBG uptake in neuroblastic tumors indicates unfavourable histopathology. Eur J Nucl Med Mol Imaging. 2013;40:1701-10.
121. Melzer HI, Coppenrath E, Schmid I, Albert MH, von Schwein- itz D, Tudball C, et al. 123I-MIBG scintigraphy/SPECT versus 18F-FDG PET in paediatric neuroblastoma. Eur J Nucl Med Mol Imaging. 2011;38:1648-58.
122. Bancos I, Prete A. Approach to the patient with adrenal inciden- taloma. J Clin Endocrinol Metab. 2021;106:3331-53.
123. Song JH, Chaudhry FS, Mayo-Smith WW. The incidental inde- terminate adrenal mass on CT (> 10 H) in patients without cancer: is further imaging necessary? Follow-up of 321 con- secutive indeterminate adrenal masses. AJR Am J Roentgenol. 2007;189:1119-23.
124. Kenney PJ, Wagner BJ, Rao P, Heffess CS. Myelolipoma: CT and pathologic features. Radiology. 1998;208:87-95.
125. Fowler MR, Williams RB, Alba JM, Byrd CR. Extra-adrenal myelolipomas compared with extramedullary hematopoietic tumors: a case of presacral myelolipoma. Am J Surg Pathol. 1982;6:363-74.
126. Decmann Á, Perge P, Tóth M, Igaz P. Adrenal myelolipoma: a comprehensive review. Endocrine. 2018;59:7-15.
127. Schieda N, Siegelman ES. Update on CT and MRI of adrenal nodules. AJR Am J Roentgenol. 2017;208:1206-17.
128. Schieda N, Al Dandan O, Kielar AZ, Flood TA, McInnes MD, Siegelman ES. Pitfalls of adrenal imaging with chemical shift MRI. Clin Radiol. 2014;69:1186-97.
129. Hamidi O, Raman R, Lazik N, Iniguez-Ariza N, Mckenzie TJ, Lyden ML, et al. Clinical course of adrenal myelolipoma: a long-term longitudinal follow-up study. Clin Endocrinol (Oxf). 2020;93:11-8.
130. Rao P, Kenney PJ, Wagner BJ, Davidson AJ. Imaging and patho- logic features of myelolipoma. Radiographics. 1997;17:1373-85.
131. Cao J, Huang X, Cui N, Wang X, You C, Ni X, et al. Surgi- cal management and outcome of Extra-adrenal myelolipomas at unusual locations: a report of 11 cases in a single center. J Bone Oncol. 2022;35: 100438.
132. Littrell LA, Carter JM, Broski SM, Wenger DE. Extra-adrenal myelolipoma and extramedullary hematopoiesis: imaging fea- tures of two similar benign fat-containing presacral masses that may mimic liposarcoma. Eur J Radiol. 2017;93:185-94.
133. Craig WD, Fanburg-Smith JC, Henry LR, Guerrero R, Barton JH. Fat-containing lesions of the retroperitoneum: radiologic- pathologic correlation. Radiographics. 2009;29:261-90.
134. Lee JJ, Dickson BC, Sreeharsha B, Gladdy RA, Thipphavong S. Presacral myelolipoma: diagnosis on imaging with path- ologic and clinical correlation. AJR Am J Roentgenol. 2016;207:470-81.
135. Mozos A, Ye H, Chuang WY, Chu JS, Huang WT, Chen HK, et al. Most primary adrenal lymphomas are diffuse large B-cell lymphomas with non-germinal center B-cell phenotype, BCL6 gene rearrangement and poor prognosis. Mod Pathol. 2009;22:1210-7.
136. Wang Y, Ren Y, Ma L, Li J, Zhu Y, Zhao L, et al. Clinical fea- tures of 50 patients with primary adrenal lymphoma. Front Endo- crinol (Lausanne). 2020;11:595.
137. Rong-ju S. CT and MR imaging findings of primary adrenal lymphoma. J Med Imaging, 2015.
138. Huang W, Chao F, Li L, Gao Y, Qiu Y, Wang W, et al. Predictive value of clinical characteristics and baseline (18)F-FDG PET/CT quantization parameters in primary adrenal diffuse large B-cell lymphoma: a preliminary study. Quant Imaging Med Surg. 2023;13:8571-86. https://doi.org/10.21037/qims-23-803.
139. Satou A, Nakamura S. EBV-positive B-cell lymphomas and lymphoproliferative disorders: review from the perspec- tive of immune escape and immunodeficiency. Cancer Med. 2021;10:6777-85.
140. Tokuyama K, Okada F, Sato H, Matsumoto S, Matsumoto A, Haruno A, et al. Computed tomography findings in Epstein-Barr
virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly: comparison with EBV-negative DLBCL. Br J Radiol. 2017;90:20160879.
141. Majidi F, Martino S, Kondakci M, Antke C, Haase M, Chortis V, et al. Clinical spectrum of primary adrenal lymphoma: results of a multicenter cohort study. Eur J Endocrinol. 2020; 183:453-62.
142. Rashidi A, Fisher SI. Primary adrenal lymphoma: a systematic review. Ann Hematol. 2013;92:1583-93.
143. Kandathil A, Wong KK, Wale DJ, Zatelli MC, Maffione AM, Gross MD, et al. Metabolic and anatomic characteristics of benign and malignant adrenal masses on positron emission tomography/computed tomography: a review of literature. Endo- crine. 2015;49:6-26.
144. Maciel J, Cavaco D, Fraga D, Donato S, Simões H, Sousa R, et al. Adrenal findings in FDG-PET: analysis of a cohort of 1021 patients from a cancer center. Hormones (Athens). 2023;22:131-8.
145. Ozcan Kara P, Kara T, Kara Gedik G, Kara F, Sahin O, Ceylan Gunay E, et al. The role of fluorodeoxyglucose-positron emission tomography/computed tomography in differentiating between benign and malignant adrenal lesions. Nucl Med Commun. 2011;32:106-12.
146. Jiang H, Li A, Liao S, Ke S, Ji Z, Tian M, et al. Simultaneous adrenal tuberculosis and renal oncocytoma mimicking malignant masses incidentally detected by (18)F-FDG PET/CT in a patient with lymphoma. Eur J Nucl Med Mol Imaging. 2022;49:777-8.
147. Teng Q, Fan B, Wang Y, Wen S, Wang H, Liu T, et al. Pri- mary adrenal tuberculosis infection in patients with Behcet’s disease presenting as isolated adrenal metastasis by (18)F-FDG PET/CT: a rare case report and literature review. Gland Surg. 2021;10:3431-42.
148. Badawy M, Gaballah AH, Ganeshan D, Abdelalziz A, Remer EM, Alsabbagh M, et al. Adrenal hemorrhage and hemorrhagic masses; diagnostic workup and imaging findings. Br J Radiol. 2021;94:20210753.
149. Adem PV, Montgomery CP, Husain AN, Koogler TK, Aran- gelovich V, Humilier M, et al. Staphylococcus aureus sepsis and the Waterhouse-Friderichsen syndrome in children. N Engl J Med. 2005;353:1245-51.
150. Dong A, Cui Y, Wang Y, Zuo C, Bai Y. (18)F-FDG PET/CT of adrenal lesions. AJR Am J Roentgenol. 2014;203:245-52.
151. Kurokawa R, Gonoi W, Yokota H, Isshiki S, Ohira K, Mizuno H, et al. Computed tomography findings of early-stage TAFRO syndrome and associated adrenal abnormalities. Eur Radiol. 2020;30:5588-98.
152. Leyendecker P, Ritter S, Riou M, Wackenthaler A, Meziani F, Roy C, et al. Acute adrenal infarction as an incidental CT finding and a potential prognosis factor in severe SARS-CoV-2 infec- tion: a retrospective cohort analysis on 219 patients. Eur Radiol. 2021;31:895-900.
153. Buxi TB, Vohra RB, Byotra SP, Mukherji S, Daniel M. CT in adrenal enlargement due to tuberculosis: a review of literature with five new cases. Clin Imaging. 1992;16:102-8.
154. Zhang XC, Yang ZG, Li Y, Min PQ, Guo YK, Deng YP, et al. Addison’s disease due to adrenal tuberculosis: MRI features. Abdom Imaging. 2008;33:689-94.
155. Parmar H, Shah J, Patkar D, Varma R. Intramedullary tuberculo- mas. MR findings in seven patients. Acta Radiol. 2000;41:572-7.
156. Hoshino Y, Nagata Y, Gatanaga H, Hosono O, Morimoto C, Tachikawa N, et al. Cytomegalovirus (CMV) retinitis and CMV antigenemia as a clue to impaired adrenocortical function in patients with AIDS. AIDS. 1997;11:1719-24.
157. Park JS, Ben-David M, Mckenzie C, Sandroussi C. Cytomeg- alovirus adrenalitis mimicking adrenal metastasis in an immu- nocompetent patient. J Surg Case Rep. 2022;2022:rjac122.
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