Adrenal infections update: how radiologists can contribute to patient care

Abstract

Adrenal infections are considered clinically important but often go unrecognized, with a significant number of cases only diagnosed post-mortem. The limited evidence regarding imaging findings in the literature emphasizes the need to detect and diagnose these infections early in disease course to improve patient outcomes. A range of microorganisms, including fungi, viruses, parasites, and bacteria, can directly or indirectly affect the morphology and function of the adrenal glands. When evaluating a patient with adrenal infection, several immunological and hormonal factors should be considered, such as the status of the hypothalamic-pituitary-adreno cortical axis and the serum cortisol level. Moreover, certain microorganisms specifically target one of the zones of the adrenal glands or vascular supply, resulting in distinct imaging manifestations. The purpose of this article is to describe the fundamental clinical features and imaging manifestations associated with adrenal infections, enabling radiologists to make informed interpretations and contribute to accurate diagnostic assessments.

Highlights:

• Radiologists’ awareness and comprehension of adrenal infection characteristics facilitate early detection, prompt treatment, and better patient outcomes.

• The adrenal vascular-rich configuration, coupled with increased cortisol levels from zona fasciculata, creates an ideal microenvironment for the reservoir and replication of microorganisms.

• The radiological hallmark of adrenalitis is thickening with fat stranding, usually bilateral in histoplasmosis and tuberculosis and unilateral/variable in COVID-19, bacterial, HIV, and cytomegalovirus infections.

Introduction

Adrenal infections are an important entity in clinical practice; however, they often go unrecognized.¹ In more industrialized nations, approximately 10% of cases of Addison’s disease are related to infections, although there are limited data on the frequency of microorganisms responsible for adrenal insufficiency.² In contrast, in less economically developed regions, infectious aetiologies are the most frequent cause of adrenal dysfunction, with Mycobacterium tuberculosis as the leading infective organism.^1,3 Immunocompromised individuals are more susceptible to the development of primary or disseminated adrenal infections, with opportunistic organisms being particularly prevalent in this population.^1,4

The manifestation of adrenal gland infections depends on the interaction between the organism and the host. It is important to remember that the adrenals are part of the hypothalamus-pituitary-adrenal axis, and the endocrine interactions within this axis should be considered when assessing adrenal dysfunction. Therefore, a high level of clinical suspicion, along with laboratory findings and imaging features, should be evaluated and interpreted together to facilitate a timely diagnosis.

A variety of infectious agents can affect the adrenal gland, with most cases being described through case reports. These include viruses, with cytomegalovirus being the most commonly identified, bacteria often associated with sepsis, and various fungi such as Cryptococcus, Coccidioides, and Histoplasma (Table 1).^1,5

Table 1.

Cross-sectional imaging hallmarks and key clinical features of the most common adrenal infections.

Microorganism	Cross-sectional hallmarks	Key clinical features
Bacterial
General	Variable adrenal involvement Abscess formation may be evident Associated with haemorrhage/adrenal Insufficiency	Disseminated infection in a patient with fever, leukocytosis, and abdominal pain No history of primary malignancy
Mycobacterium tuberculosis	Bilateral adrenal thickening (active infection) Calcification and atrophy (healing changes/previous infection)	Could be asymptomatic even after years. Increased corticosteroid dose replacement in patients with rifampin Reversible adrenal thickening Antituberculosis treatment may not be effective in recovery of adrenal function after insufficiency
Viral
HIV	Variable degree of necrosis, fibrosis, haemorrhage Can be associated with neoplastic involvement of the adrenals	Adrenals are the most common endocrine organ involved Frequently associated with opportunistic infections (CMV)
SARS COVID-19	Variable degree of adrenal thickening necrosis, haemorrhage High attenuation/enhancing rim surrounding the infarcted parenchyma (capsular sign) may be present	Not infrequent adrenal involvement (33%-42.9%) Hypercoagulable state Adrenal insufficiency can be the result of viral hypophysitis
Fungal
Histoplasma capsulatum	Bilateral adrenal thickening (active infection) Variable adrenal infarction/necrosis Calcification and atrophy (healing changes/previous infection)	Usually in the setting of systemic infection Be aware of endemic areas
Paracoccidioides brasiliensis	Bilateral adrenal thickening Variable adrenal infarction	Suggest early antifungal therapy to increase adrenal function preservation
Parasitic
Echinococcuus spp	Adrenal cystic lesions ranging from simple cysts to more complex structures with internal septations, mural/septal calcifications and daughter cysts	Uncommon adrenal involvement Previous lung/liver infection before adrenal manifestations

The purpose of this article is to describe the fundamental clinical features and imaging manifestations associated with adrenal infections, enabling radiologists to make informed interpretations and contribute to accurate diagnostic assessments.

Imaging techniques in the assessment of adrenal infections

The widespread utilization of CT, particularly in critically ill patients, has established it as the primary diagnostic tool for assessing the adrenal gland in patients with suspected infection.⁶ This imaging technique allows for precise delineation of the gland and comprehensive evaluation of the extent of involvement. Furthermore, CT enables the detection of potential complications, including bleeding or abscess formation. Its ability to provide detailed anatomical information and visualize pathological changes in the adrenal gland makes CT an invaluable modality in diagnosing and managing adrenal infections.

The limited visibility of the adrenal glands on ultrasound renders this modality less optimal for comprehensive imaging assessment. However, it can still serve as a helpful adjunct in specific clinical situations for prompt evaluation and initial detection of certain adrenal pathologies. For example, ultrasound can provide real-time visualization and aid in the identification of adrenal haematomas or collections during bedside examinations.⁷ Ultrasound can also be utilized for biopsy and drainage guidance.

MRI can offer valuable insights in the nonemergent assessment of adrenal infections. Because it provides detailed anatomical information and excellent tissue characterization, MRI is particularly useful to evaluate the presence of underlying soft tissue lesions or enhancing abnormalities within the adrenal gland. Additionally, MRI can play a significant role in determining the age of a haematoma in patients presenting with adrenal haemorrhage, assisting clinicians in determining the acute or chronic nature of the haemorrhage, and aiding in patient management decisions and prognostic assessment.⁸

¹⁸Fluoride fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET/CT) is overall a valuable imaging tool for the evaluation of infection since it can identify and localize areas of augmented glucose metabolism which, in the appropriate clinical context, can represent infected tissues due to their increased metabolic activity.⁹ Nevertheless, there is limited evidence regarding its specific use in adrenal infections, and it is not commonly employed in clinical practice.

The normal adrenal gland can show physiological FDG uptake, which is usually mild with average maximum standardized uptake values (SUVmax) between 0.83 and 0.95.¹⁰ Infections such as CMV, tuberculosis, histoplasmosis, or fungal infection often exhibit increased FDG uptake, characterized by SUVmax values surpassing 2.5. Abnormal uptake may be diffuse or peripheral with central photopenia representing necrotic changes.^11,12 However, such uptake patterns lack specificity, as both benign conditions (eg, adrenal hyperplasia, and adenomas) and malignant tumours (eg, lymphoma, pheochromocytoma, adrenocortical carcinoma, and metastasis) may also display increased FDG uptake, with variable SUVmax values.^11,13 Notably, when using an SUVmax threshold of 3.1, FDG PET/CT has demonstrated sensitivity and specificity of 98.5% and 92%, respectively, in discriminating between benign and malignant adrenal lesions.¹⁴

In summary, differentiating benign entities, including infection, from malignancy on PET/CT is challenging, leading to the limited routine recommendation of this modality for the adrenal infection work up. It remains crucial to integrate PET/CT findings with the patient’s medical history, clinical presentation, laboratory tests, and additional imaging studies for accurate diagnosis and management.

Bacterial adrenalitis

Bacteria contribute to adrenal damage through direct colonization of adrenal tissue and through the disruption of biochemical and endocrinological host responses due to the release of endotoxins, exotoxins, and the activation of proinflammatory cytokines.¹⁵ In the acute stages, there is often an upregulation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in an increase in adrenocorticotrophic hormone (ACTH). This hormonal imbalance sets the stage for adrenal haemorrhage predisposition.¹ Bacterial sepsis and pyogenic infections pose a particular risk for bilateral adrenal haemorrhage, potentially leading to adrenal insufficiency, known as Waterhouse-Friderichsen Syndrome.^16,17 Several bacteria have been associated with this syndrome, including group A streptococcal infections, Neisseria meningitidis, Haemophilus Influenza, and pneumococcus, among others.^2,16,18

On CT, adrenal inflammation (adrenalitis) is characterized by either unilateral or bilateral adrenal enlargement with effacement of the adrenal borders and adjacent fat stranding (Figure 1). In addition, adrenal haemorrhage typically presents as a round or oval lesion with varying degrees of attenuation depending on the stage of haemorrhage. In the acute bleeding phase, the lesion is predominantly homogeneously hyperdense, whereas it becomes more heterogeneous during the subacute stage.^7,8 This can be associated with haziness along its margins and fat stranding.⁶

Figure 1.

Forty two-year-old woman presenting with systemic meticillin-sensitive Staphylococcus aureus (MSSA) bacteraemia with abdominal pain and hypotension. (A, B) Axial portal venous CT shows enlargement of the bilateral adrenal glands (arrows) with associated ill-defined margins and mild stranding of the adjacent fat (arrowheads) predominantly involving the left adrenal. (C) Axial portal venous CT performed a year before shows slightly thickened adrenals with no significant margin distortion (short arrow). Overall findings are representative of acute/active adrenalitis.

MRI can provide valuable information regarding the age of the bleed and the presence of occult lesions, as mentioned earlier. In the acute stage of haemorrhage (within 7 days of onset), the lesion appears isointense or mildly hypointense on T1-weighted images and hypointense on T2-weighted images due to the presence of intracellular deoxyhemoglobin. Subsequently, the oxidation of haemoglobin leads to the formation of free methaemoglobin in the subacute stage (occurring between 7 days and 7 weeks after onset). This results in hyperintense signal on both T1-weighted and T2-weighted images, initially at the periphery and gradually progressing from the periphery towards the centre of the lesion (Figure 2). In the chronic stage (usually around seven weeks after onset), the haemorrhage or haematoma demonstrates low signal intensity on both T1-weighted and T2-weighted images due to hemosiderin deposition and development of a fibrous capsule^3,6,8 (Figure 2). Over time, haemorrhagic collections tend to decrease in size until complete resolution, although in some cases, they may persist and even calcify.^19,20

Figure 2.

Sixty four-year-old woman with history of systemic bacteraemia and upper abdominal discomfort. (A) Axial portal venous CT shows an oval shaped soft tissue lesion replacing the right adrenal (arrow) with mild stranding of the periadrenal fat (short arrow), felt to represent a subacute bleed. In addition, a well circumscribed left adrenal nodule was identified (arrowhead) incompletely characterized in the single-phase examination. Follow-up elective MRI was performed for reassessment and further characterization. (B) Axial T2W fat sat image shows interval decrease in size of the right adrenal lesion with linear, dark appearance (arrow); homogeneous, low signal intensity left adrenal nodule also noted (arrowhead). (C, D) Axial T1W in-phase (IP) and opposed-phase (OP) dual echo GRE images show a linear hypointensity in the normal sized right adrenal (arrow in C) and signal loss in the left sided adrenal nodule on OP T1W when compared to IP T1W (arrowheads). (E) Coronal T2W image shows corresponding marked hypointensity at the site of the previously suspected haematoma (arrow) and almost homogeneous low signal in the left adrenal nodule (arrowhead). Overall findings are in keeping with a smaller right sided, likely calcified old haematoma and a left sided lipid rich adrenal adenoma.

Adrenal abscess

Adrenal abscesses are considered rare, and most of the available documentation comes from case reports.^21–23 When a cystic lesion is observed in the adrenal gland during cross-sectional imaging, the possibility of adrenal infection should be considered, especially in the clinical setting of disseminated infection. Adrenal abscess as a primary source of infection is infrequent and likely results as consequence of haematogenous spread from another source.²⁴ Distinguishing an abscess from adrenal metastasis, necrotic adrenal tumour, or a complex adrenal cyst can be challenging.²¹ Therefore, the clinical context plays a vital role in guiding the diagnosis, particularly in a patient presenting with fever, leukocytosis, and abdominal pain but lacking a history of primary malignancy.

On CT, abscesses present as hypodense lesions with either a unilocular or multilocular configuration. These lesions typically exhibit peripheral enhancement and fat stranding in the adjacent tissue (Figure 3).³

Figure 3.

Acute bacterial adrenal abscess in a 78 y/o man presenting with E. coli bacteraemia. (A) Axial portal venous phase CT shows a 3.8 × 3.0 cm peripherally enhancing collection along the lateral limb of the left adrenal gland (arrow) associated to small amount of fluid and thickening of the left anterior renal fascia (arrowhead). (B) Corresponding coronal reformat shows the bilobed morphology of the collection with a hypodense component within the adrenal (arrowhead). (C) Axial T2W image of an MRI performed 10 days apart shows a similar sized thick wall collection (arrow). (D) Axial T1W image shows a punctate hyperintense component suggestive of high proteinaceous/haemorrhagic contents within the collection (arrowhead). (E) Portal venous phase postcontrast T1W image demonstrating rim enhancement (arrow). (F) Coronal subtracted T1W image shows no enhancement of the internal components.

On MRI, adrenal abscesses generally demonstrate variable or predominantly high signal intensity on T2-weighted images, while demonstrating predominantly low signal intensity on T1-weighted images. The degree of signal intensity can depend on the quantity of high proteinaceous content within the abscess. Additionally, restricted diffusion may be observed in certain cases (Figure 4).³

Figure 4.

Sixty eight-year-old man post renal transplant with disseminated Nocardia infection presenting with a left sided adrenal abscess. (A) Axial T2W image shows a thick-walled collection almost replacing the adrenal parenchyma with central hyperintense component (arrowhead). (B) Axial T1W fat sat pre contrast image shows corresponding variable signal intensity within the collection with a small marginal anterior hyperintense focus (arrowhead), favoured to represent haemorrhagic/high proteinaceous contents. (C) Axial T1w GRE MR image after contrast in the late arterial phase shows peripheral enhancement (arrowhead). (D) Axial high b-value DWI MRI image shows corresponding hyperintensity (arrowhead). (E) Axial ADC map MRI shows marked low signal in the collection (arrowhead) in keeping with restricted diffusion. (F) Axial high resolution chest CT shows concomitant airspace disease/consolidation in the right lower lobe (arrow) and bilateral pleural effusions (asterisks). (G) Axial T1w GRE MR image after contrast shows an additional peripherally enhancing collection involving the right cerebellar hemisphere (arrow). (H) Axial high b-value DWI MRI image shows marked hyperintensity within the posterior aspect of the collection (arrowhead). (I) Axial ADC map MRI shows marked low signal in the collection (arrowhead) in keeping with restricted diffusion.

Immunocompromised individuals are more susceptible to developing disseminated infections including Nocardia organisms. These infections can present as multiloculated adrenal lesions in patients with disseminated disease, which commonly affects the lungs and central nervous system (Figure 4).^22,23

Tuberculosis and adrenal BCG granulomatosis

M. tuberculosis stands as the primary bacteria responsible for adrenal destruction.^1,25 The extent of parenchymal involvement dictates the impairment of adrenal function, with over 90% gland destruction required before hormone insufficiency becomes apparent^2,25 and therefore, asymptomatic infection is not uncommon with clinical manifestations not apparent even after years.² Notably, during the early phases of involvement, additional factors such as dehydration or recent surgeries must be considered in contributing to the unmasking of adrenocortical insufficiency.²⁶

It is crucial to highlight that antituberculous treatment, particularly involving rifampicin, necessitates vigilance due to hepatic enzyme induction and increased cortisol metabolism, elevating the risk of precipitating adrenal insufficiency.²⁷

While the return of adrenal function has been proposed as a marker of successful treatment,^28,29 it is essential to recognize that when the infection results in adrenal insufficiency, antituberculous treatment does not directly contribute to the re-establishment of adrenal function.²

Imaging manifestations of tuberculous involvement of the adrenal glands varies based on the severity and duration of infection. In the setting of active tuberculosis, particularly in pulmonary cases, the adrenals often display thickening and increased size, usually in a bilateral fashion (Figure 5).^1,2,29 This phenomenon is attributed to two distinct pathophysiological mechanisms. The first involves the primary infection of the adrenal parenchyma by the bacillus, while the second results from the activation of the hypothalamus-pituitary-adrenal axis in response to stress induced by Mycobacterium.^25,29 Bilateral enlargement of the glands associated with preserved shape suggests the latter. Conversely, atrophic and calcified glands are indicative of remote or inactive infection.^1,2

Figure 5.

Seventy one-year-old previously healthy man referred for further management of hypercalcemia, hyponatremia, bilateral adrenal masses, spinal mass, and a cerebellar mass. Initial concern for malignancy. He pursed biopsy of adrenal gland showing a necrotizing, granulomatous process concerning for tuberculosis. He then presented with adrenal insufficiency and was started on antituberculous treatment and steroid replacement therapy with gradual improvement of symptomatology. (A) Coronal reformat of a CT in the portal venous phase shows bilateral adrenal enlargement with lobulated contours and haziness of the periadrenal fat (arrowheads). (B) Axial portal venous CT shows corresponding bilateral adrenal enlargement typically seen in tuberculous adrenalitis (arrows). Case courtesy of Dr. Michael Corwin – University of California, Davis.

Viral adrenalitis

The HIV stands as the most frequent virus associated with adrenal gland impairment or dysfunction, making the adrenal gland the most common endocrine organ involved.^30,31 In patients with AIDS, the affected gland often exhibits manifestations such as necrosis, fibrosis, haemorrhage, or replacement by neoplastic disease.³² These alterations can arise from direct involvement by the HIV virus, an increased susceptibility to opportunistic infections (eg, cytomegalovirus), or as a consequence of associated neoplasms such as Kaposi sarcoma and non-Hodgkin’s lymphoma.¹

As with other infections, HIV can also lead to adrenal insufficiency, which is thought to be the consequence of co-infection by opportunistic organisms, the presence of anti-adrenal cell antibodies, and peripheral cortisol resistance.^33,34 Cytomegalovirus is the most commonly associated opportunistic pathogen linked with HIV, causing a mixed inflammatory infiltrate involving the cortex-medulla junction³² and is considered to be the leading causes of adrenal insufficiency due to bilateral adrenal destruction.^35,36 Mechanisms of injury include endothelial cell damage with consequent thrombosis, progressing to ischaemic necrosis. Infarct-like coagulative necrosis mainly affects the medulla but also the cortex.³⁷

Dedicated cross-sectional adrenal imaging is typically reserved for cases with clinical suspicion of adrenal insufficiency, particularly when investigating an infiltrative process that may include the adrenal glands. Findings are generally non-specific for diagnosing a viral infection and can include thickening of the gland with surrounding oedema, as illustrated in Figure 6.⁸ It is important to note that not all patients with infiltrative disease exhibit radiographically enlarged adrenals.³⁸

Figure 6.

Sixty two-year-old man with history of human immunodeficiency virus (HIV) infection. (A) Axial portal venous CT shows bilateral adrenal enlargement predominantly on the left side (arrowheads). A subcentimeter calcified focus is also seen in the left adrenal, likely reflecting a sequela from prior active infection (arrow). (B) Corresponding coronal CT reformat shows diffusely thickened left adrenal gland (arrowhead) with no significant stranding of the adjacent fat.

Adrenal involvement in patients with SARS COVID-19 infection

The SARS-CoV-2 virus, responsible for COVID-19 disease, can infect various organs and systems beyond the lungs, including the adrenal glands. While the exact incidence is not well-defined, adrenal involvement has been reported in numerous case reports, series, and post-mortem studies. These studies have found macroscopic or microscopic adrenal involvement in approximately 33%-42.9% of patients.^39–41

Several potential mechanisms have been proposed to explain adrenal involvement in COVID-19. Firstly, the virus may directly invade the adrenal glands through ACE2 receptors expressed in these organs, leading to focal inflammation (adrenalitis), necrosis, and haemorrhage. Secondly, the hypercoagulable state associated with cytokine storm may contribute to the formation of microthrombi and subsequent infarction. Thirdly, endothelial damage caused by an exaggerated systemic inflammatory response can result in small vessel vasculitis or endothelitis affecting not only the adrenal parenchyma but also the surrounding periadrenal fat.^42,43

In addition to the aforementioned mechanisms, adrenal insufficiency or dysfunction can arise from viral hypophysitis or impaired function of endogenous ACTH. This can be induced by high secretion of TNF-α or by specific viral aminoacids that resemble human ACTH.^40,41 The interplay of these various factors contributes to the complex involvement of the adrenal glands in COVID-19, highlighting the multi-faceted nature of the disease’s impact on the endocrine system.

Imaging findings of adrenal infarction have been reported in 23% of cases in the largest series, with bilateral involvement observed in up to 88% of patients.⁴³ Typical tomographic findings of acute adrenalitis and infarction include enlarged or thickened adrenal glands, with low attenuation and lack of enhancement. Periadrenal fat stranding is often seen, and sporadically, a high attenuation or enhancing rim surrounding the infarcted parenchyma, known as the “capsular sign,” may be present (Figure 7).^40,43 Patients may also present with adrenal and periadrenal haemorrhagic collections of variable sizes and appearances, depending on the time of onset as shown in Figure 8.

Figure 7.

Sixty three-year-old woman with shortness of breath and upper abdominal pain. PCR confirmed COVID-19 infection. (A) Axial portal venous CT shows thickening of the right adrenal gland with associated decreased enhancement. High attenuation/enhancing rim noted along its medial margin (arrow). (B) Coronal CT reformat shows corresponding findings predominantly involving the medial limb (arrowhead). (C) Axial portal venous CT shows thickening and hypoenhancement of the left adrenal lateral limb. “Capsular sign” with peripheral enhancing rim also identified (arrowhead). Associated mild periadrenal fat stranding (arrow). (D) Coronal CT reformat at the level of the left adrenal gland shows differential hypoenhancement of the lateral limb (arrow). Findings consistent with bilateral adrenal infarction in the context of active COVID-19 infection. No clinical features of adrenal insufficiency, with morning cortisol within normal limits.

Figure 8.

Acute right adrenal haematoma in a 68-year-old man with history of COVID-19 pneumonia and right upper quadrant abdominal pain. (A) Axial unenhanced CT shows a 4.9 cm oval shaped predominantly hyperdense focal lesion almost replacing the right adrenal gland (arrow), likely in keeping with acute adrenal haematoma. (B). Axial portal venous CT shows no enhancing components within the lesion. Mild stranding of the periadrenal fat noted (arrowhead). (C) Coronal unenhanced reformat shows the mostly hyperdense haematoma with some heterogeneous/hypodense areas along its cranial aspect (arrowhead). (D) axial contrast enhanced CT at the level of the lung bases demonstrates bilateral ground-glass changes and patchy consolidation in keeping with known COVID pneumonia.

Fungal infections

Fungal infections of the adrenal glands are uncommon, but typically occur in the context of disseminated systemic infections, affecting both immunocompetent and immunocompromised patients, particularly those with impaired cell-mediated immunity. The common factor being impairment of activation of phagocytes and T-lymphocyte functions.¹

The responsible pathogens vary based on geographic areas and the prevalence of microorganisms. Histoplasmosis is seen throughout the world, but in the United States Ohio and Mississippi River Valleys are considered endemic areas. Histoplasmosis usually manifests as a pulmonary infection, with most cases resolving without sequelae. However, adrenal involvement should be suspected when bilateral adrenal enlargement is observed on cross-sectional imaging, surpassing the anticipated degree for hyperplasia, and accompanied by noticeable bulging of the adrenal contours (Figure 9).⁴⁴ The relatively high cortisol concentration in the zona fasciculata makes it more sensitive for Histoplasma involvement. Vascular involvement, mainly of extracapsular vessels, leads to extensive infarction and caseation,⁴⁵ visible as central areas of low attenuation on CT.⁴⁴ On MR, these areas may demonstrate variable signal on T1 or restricted diffusion, depending on the degree of high proteinaceous content.³ Adrenal calcifications are not frequently observed during acute episode but more with the latter period.⁴⁶

Figure 9.

Seventy one-year-old woman with history of pulmonary histoplasmosis. (A) Posterior/anterior chest radiograph demonstrating a well circumscribed radiopaque left parahilar lesion (arrow). (B) Axial contrast enhanced chest confirmed a calcified granuloma in the superior segment of the left lower lobe (arrowhead). (C and D) Axial portal venous CT shows bilateral adrenal enlargement, likely in keeping with Histoplasma related adrenalitis (arrows). Case courtesy of Dr. Benjamin Carney – University of California, Davis.

Blastomyces dermatitidis is a global pathogen, with endemic regions in the eastern part of the United States. It exhibits a strong affinity for the adrenal glands, typically manifesting as adrenal enlargement and abscess formation (Figure 10). Like other fungal infections, the diagnosis is often delayed in regions with lower prevalence. Fortunately, blastomycosis is characterized by comparatively lower rates of adrenal insufficiency.^1,2

Figure 10.

Seventy nine-year-old woman with known right sided adrenal adenoma presenting with new superimposed abscess. (A) Axial portal venous CT shows a 5.0 cm peripherally enhancing lesion in the right adrenal with central hypodense, likely necrotic component (arrow). (B) Axial T2W image shows central multiloculated fluid component within the lesion (arrowhead). (C) Axial T1w GRE MR image after contrast in portal venous phase shows peripherally enhancing components (arrow) (D) Coronal T1W GRE MR image after contrast in portal venous phase shows peripheral enhancement with central hypoenhancing/necrotic components (asterisk). (E) Macroscopic appearance of the resection specimen revealed a dark tan-to-yellow cortical tumour (aldestoronoma) with extensive white, chalky, friable central component (asterisk). (F) Low power H&E-stained microscopic image shows the interface between the tumour and the central component containing necrotizing granulomas (dark arrow). (G) High power H&E-stained microscopic image shows extensive necrotizing granulomatous inflammation. (H) High power GMS-stained microscopic image reveals abundant budding yeast forms. Clinical laboratories showed aldosterone hypersecretion status. Subsequent antibody assessment demonstrated Blastomyces spp. Case courtesy of Dr. Robert Petrocelli - NYU Langone Health.

Other microorganisms are less commonly found in the United States or less often associated with adrenal involvement. Paracoccidioides brasiliensis is endemic in Latin America and paracoccidioidomycosis may be seen in association with recent travel or immigration. The fungus causes occlusion of the small adrenal vessels, leading to endovasculitis and the formation of granulomas. This typically results in bilateral adrenal involvement, with fungal emboli being responsible for significant glandular tissue loss.^2,47 Hence, initiating antifungal therapy in the early stages of the disease is crucial to improve the likelihood of preserving adrenal function.⁴⁸

Cryptococcosis, caused by Cryptococcus neoformans, is a rare infection in immunocompetent individuals. It primarily affects immunocompromised individuals, particularly those with AIDS, who may exhibit visceral dissemination, including bilateral adrenals,¹ presenting with caseating granulomas. Adrenal insufficiency remains uncommon and is contingent on the degree of extension of adrenal tissue involvement.⁴⁹ This rarity may be attributed to the fact that patients with extensive disease may succumb to cryptococcal meningitis before developing insufficiency. While Cryptococcus infection is still prevalent worldwide, especially in sub-Saharan Africa, the availability of antiretroviral therapy (ART) has significantly reduced fungal infections in individuals with advanced HIV/AIDS in the United States.

Parasitic infections

Host immunity, endemic regions, and the biology of microorganisms are critical considerations when suspecting parasitic involvement in the adrenal gland. Typically observed in the context of disseminated disease, adrenal parasitism is not commonly recognized as a primary source of infection. The existing body of evidence relies predominantly on case reports, reflecting the rarity of this condition.

Infections by Echinococcus spp, particularly in areas with inadequate veterinary control of animal husbandry, can lead to human infection through the ingestion of food or water contaminated with parasite eggs found in faeces.⁵⁰ Interaction with the host’s immune system results in the formation of cysts, which can manifest throughout the body, including the adrenals. Cross-sectional imaging reveals varying appearances of the cysts depending on the infection stage, ranging from simple cysts to more complex structures with internal septations, mural/septal calcifications, and daughter cysts^50,51 (see Figure 11). Given the infrequent occurrence of adrenal involvement, the presence of additional cysts in more common sites such as the liver and lungs become crucial for an accurate diagnosis. Notably, lung involvement tends to precede adrenal infection.^51,52

Figure 11.

Thirty nine-year-old man with history of remote echinococcal infection in his childhood, recently migrated to North America. Presents with history of unintentional weight loss and right flank pain. (A) Axial portal venous CT shows a lobulated 8.3 cm cystic lesion with multiple enhancing internal septations (arrows) and dystrophic calcifications along the anterior margin (arrowhead). (B) Coronal reformat at the level of the right adrenal better delineates the septations within the lesion, measuring up to 4 mm in thickness (arrowhead). (C) Sagittal reformat demonstrates the lesion inseparable from remnant right adrenal gland (arrow) and shows the full extent of the anterior calcifications (arrowhead). Surgical resection revealed a multicystic lesion with detached laminated membrane and occasional echinococcal protoscolices present in keeping with hydatid cyst.

Leishmaniasis can also present as cystic adrenal disease in both immunocompetent and immunocompromised individuals.¹ Visceral compromise typically arises from the reproduction of parasites within the phagocytes of the monocyte-macrophage system.⁵³ Like other infective agents, the increased steroid concentration within the adrenals renders them susceptible to parasite infestation.⁵⁴ While no specific imaging characteristics have been reported due to the low prevalence of adrenal involvement, the identification of a predominantly unilateral complex cystic lesion within an endemic area, especially in immunocompromised individuals, should raise suspicion of visceral/adrenal leishmaniasis. Although the presence of Trypanosoma cruzi (the causative microorganism of Chagas’s disease) has been noted within adrenal gland veins, serving as a potential reservoir,^55,56 definitive features of parenchymal invasion have not been described to our knowledge.

Radiologist role in adrenal infections

CT imaging plays a pivotal role in identifying infective sources in the abdomen, with radiologists needing to recognize specific features that suggest adrenal involvement.³ Although imaging features are often non-specific, radiologists can crucially guide clinical colleagues towards a potential diagnosis. For example, the appearance of thickening in single or bilateral adrenal glands, combined with ill-defined margins and surrounding fat stranding in a critically ill or septic patient, should raise the suspicion of an infective agent. Such presentations are unusual for adrenal hyperplasia, which typically does not show surrounding stranding, and differ from malignancy, which often exhibits nodular or irregular adrenal parenchyma replacement.^57,58 Additional signs like rim-enhancing collections or abscesses within the adrenal or in distant organs provide further evidence of infection. In cases of bilateral involvement, specific agents such as histoplasmosis and tuberculosis should be considered⁵⁹ (Table 1).

The clinical context, including laboratory values like elevated white blood cell counts and reactive markers such as C-reactive protein, can direct the medical team towards a specific aetiology, supported by blood cultures. For atypical cases, targeted antibodies or cultures from lesion biopsies might be necessary. Importantly, the radiologist can also flag potential infections in vulnerable patients, such as those who are immunosuppressed and display general non-specific findings, even when the aetiology is not definitively established by imaging alone. This proactive identification is crucial, particularly for patients at risk of developing adrenal insufficiency. Conversely, clinicians and laboratory results can help radiologists refine their differential diagnoses, enhancing collaborative diagnosis accuracy. In COVID-19 positive patients with adrenal infarction or haemorrhage, the potential for adrenal infective involvement should be underscored and monitored due to the increased risk of adrenal insufficiency.⁴⁰

Conclusion

Given the widespread use of cross-sectional imaging, particularly CT scans, in the acute clinical setting and amongst critically ill patients, radiologists play a fundamental role in assessing adrenal pathology. Although adrenal infectious involvement is uncommon, it should be considered in the differential diagnosis of patients with widespread inflammation, taking into account the host’s hormonal/immune status and the geographic region where certain infective agents are more prevalent. The vascular-rich configuration of the adrenal gland, coupled with increased cortisol levels from the zona fasciculata, creates an ideal microenvironment and may act as a reservoir for microorganisms and promote replication. These conditions can be unique to the adrenal gland and are not reproducible in other anatomical sites. Cross-sectional features of the presented microorganisms can overlap and therefore, correlation with clinical presentation, notion of contagion and microbiologic testing would be critical to obtain a more specific diagnosis. Adrenal thickening with associated stranding of the adjacent fat serves as the radiological hallmark of infective adrenalitis, typically bilateral in histoplasmosis and tuberculosis and unilateral/variable in COVID-19, bacterial, HIV, and cytomegalovirus infections. Destruction of the adrenal parenchyma results in loss of endocrine adrenal function, contributing to a high mortality rate. Early radiological identification and awareness by the clinical team are considered pivotal for prompt patient management and the preservation/recovery of endocrine function.

Funding

No funding was received for the manuscript.

Conflicts of interest

No relevant disclosures regarding the educational content included on the current review article.