Adrenal granulomatous disease is the involvement of adrenal glands by infectious or systemic inflammatory processes characterized by granulomatous inflammation. The most common causes are tuberculosis (Mycobacterium tuberculosis) and histoplasmosis (Histoplasma capsulatum), while sarcoidosis, blastomycosis, coccidioidomycosis, and cryptococcosis can also produce adrenal granulomas. Bilateral involvement is common, and progressive destruction of adrenal glands in chronic cases can lead to adrenal insufficiency (Addison's disease) — more than 90% of both glands must be destroyed for adrenal insufficiency to develop. On imaging, acute phase shows bilateral adrenal enlargement, subacute phase shows heterogeneous enhancement, and chronic phase demonstrates bilateral adrenal atrophy and calcification pattern. Tuberculosis-related adrenal calcification is the most common cause of Addison's disease in developing countries.
Age Range
20-70
Peak Age
45
Gender
Male predominant
Prevalence
Rare
The pathogenesis of adrenal granulomatous disease varies by etiology but the common mechanism is granuloma formation. In tuberculosis, Mycobacterium tuberculosis reaches the adrenal glands via hematogenous spread — adrenal glands are susceptible to hematogenous infection due to rich blood supply. Mycobacterium lipid-rich cell wall components (mycolic acids) trigger macrophage activation → epithelioid histiocytes and Langhans giant cells form caseating granulomas. Caseation necrosis manifests on imaging as central low-density/low-signal areas. In the chronic phase, caseous necrotic material calcifies — calcification is dystrophic type representing mineralization of necrotic tissue within granulomas; appears as coarse or fine calcifications on CT. In histoplasmosis, a similar mechanism operates; Histoplasma evades macrophage phagocytosis by replicating intracellularly and triggers granuloma formation. In sarcoidosis, the etiology is unknown but CD4+ T cells and macrophages form non-caseating granulomas — the absence of caseation provides different signal pattern on MRI. Granulomatous inflammation destroys adrenal cortex and medulla → cortisol, aldosterone, and adrenal androgen production decreases → Addison's disease.
The presence of coarse or fine calcifications in bilateral adrenal glands on non-contrast CT is near-pathognomonic for sequelae of prior granulomatous infection (tuberculosis or histoplasmosis). This finding is diagnostic especially when evaluated in endemic areas and with clinical Addison's disease.
On non-contrast CT, different findings are observed depending on disease stage. Acute/subacute phase: bilateral adrenal enlargement, diffuse or nodular, symmetric or asymmetric. Adrenal gland thickness >10 mm. Central low density (caseation necrosis) surrounded by soft tissue density. Chronic phase: bilateral adrenal atrophy (shrunken, irregular-contoured glands) with coarse or fine calcifications. Calcification pattern may be diffuse or punctate. Calcification rate in tuberculosis can reach 50%.
Report Sentence
Bilateral adrenal gland enlargement/atrophy with calcifications is observed; granulomatous disease (tuberculosis/histoplasmosis) should be primarily considered in the clinical and epidemiological context.
On contrast-enhanced CT, peripheral rim enhancement with central low density is observed in the active granulomatous phase. This ring-enhancement pattern reflects the contrast between active granulomatous tissue at the periphery (hypervascular inflammation) and central avascular necrosis. Enhancement may be smooth or irregular. Enhancement is more prominent in the subacute phase. In the chronic calcified phase, enhancement is minimal or absent.
Report Sentence
Peripheral rim enhancement with central low density is observed in bilateral adrenal glands; consistent with active granulomatous infection (tuberculosis).
On T2-weighted MRI, adrenal masses show heterogeneous signal. Caseous necrosis areas may exhibit variable T2 signal — intermediate signal if protein content is high, high signal if liquefied necrosis. Peripheral granulomatous tissue shows intermediate-to-low T2 signal. Fibrotic areas show low T2 signal. Calcifications cause signal loss on all sequences. In sarcoidosis, the T2 signal pattern differs due to absence of caseation — more homogeneous low-to-intermediate signal is observed.
Report Sentence
Masses with heterogeneous signal on T2-weighted images containing central necrotic areas are observed in bilateral adrenal glands; consistent with granulomatous disease.
Diffusion restriction is observed on DWI in the active granulomatous phase — ADC values are low (typically 0.8-1.2 × 10⁻³ mm²/s). This finding reflects dense inflammatory cell infiltration within granulomas and viscous protein-lipid material in caseous necrosis. In the chronic fibrotic/calcified phase, diffusion restriction decreases or disappears. DWI is useful in distinguishing active infection from chronic sequelae.
Report Sentence
Diffusion restriction is observed on DWI in bilateral adrenal lesions; consistent with active granulomatous inflammation.
On FDG PET-CT, increased FDG uptake is observed in bilateral adrenal glands in the active granulomatous phase (SUVmax generally 3-8). This uptake reflects increased glucose metabolism of active inflammatory cells (particularly macrophages). FDG uptake may be confused with malignancy — differential diagnosis from bilateral adrenal metastasis is particularly important. In the chronic calcified phase, FDG uptake is minimal or absent. Decrease in FDG uptake after treatment indicates treatment response.
Report Sentence
Increased FDG uptake is observed in bilateral adrenal glands on FDG PET-CT; consistent with active granulomatous infection, though bilateral adrenal metastasis should be excluded in the differential diagnosis.
On chemical shift MRI (opposed-phase), no signal drop is observed in adrenal granulomatous masses. This indicates absence of intracellular lipid and is important in differentiating from lipid-rich adenoma. Granulomatous tissue consists of cellular inflammatory infiltrate without lipid content; caseous necrotic material may carry lipid components but does not provide sufficient water-fat mixing at voxel level.
Report Sentence
No signal drop is observed on opposed-phase chemical shift MRI in adrenal lesions; absence of intracellular lipid does not support adenoma diagnosis.
Criteria
Mycobacterium tuberculosis infection. Caseating granulomas characteristic. PPD/Quantiferon positivity, pulmonary or other organ TB findings supportive.
Distinct Features
Most common cause. Bilateral involvement very frequent. Caseous necrosis prominent. High calcification rate in chronic phase (50%). Highest risk of Addison's disease in this group. Pulmonary TB may accompany.
Criteria
Histoplasma capsulatum infection. Ohio and Mississippi River valley endemic region. Granulomas may caseate. Histoplasma antigen/antibody test positive.
Distinct Features
Common especially in endemic areas of USA. Pulmonary + adrenal involvement combination typical. Calcification as frequent as tuberculosis. Liver and spleen calcified granulomas may accompany. Disseminated form in immunosuppressed patients.
Criteria
Adrenal involvement in patient with sarcoidosis diagnosis. Non-caseating granulomas. Elevated serum ACE, bilateral hilar lymphadenopathy supportive. Pulmonary, ocular, cutaneous involvement may accompany.
Distinct Features
Adrenal involvement rare in sarcoidosis (5%). Calcification rarer than tuberculosis and histoplasmosis. Rim enhancement less prominent due to non-caseating granulomas. Addison's disease very rare in sarcoidosis. Bilateral hilar LAP + adrenal enlargement combination characteristic.
Distinguishing Feature
Adrenal metastasis generally with known primary malignancy history. Calcification rare in metastasis (except post-treatment). Metastasis usually irregularly bordered, heterogeneously enhancing mass. Rim enhancement + central necrosis and chronic calcification pattern more typical in granulomatous disease.
Distinguishing Feature
Adrenal lymphoma shows homogeneous low T2 signal and homogeneous enhancement. Calcification very rare in lymphoma. Lymphoma symptoms (B symptoms) more prominent than Addison's disease. Lymphoma shows more pronounced and homogeneous diffusion restriction on DWI.
Distinguishing Feature
Adrenal hemorrhage shows T1 hyperintense signal (methemoglobin). No enhancement (avascular hematoma). Size decrease over time. Calcification may occur in hemorrhage sequelae but usually unilateral. Clinical context of anticoagulation, trauma, or sepsis history is guiding.
Distinguishing Feature
Lipid-poor adenoma is usually unilateral, small (<4 cm), homogeneous mass. Washout analysis (absolute >60%) supports adenoma. Calcification very rare in adenoma. Adenoma usually not bilateral. The bilateral involvement, rim enhancement, and calcification pattern of granulomatous disease are not seen in adenoma.
Urgency
urgentManagement
medicalBiopsy
NeededFollow-up
3-monthAdrenal granulomatous disease requires urgent evaluation for diagnosis and treatment of the underlying infection. Anti-TB treatment should be initiated if tuberculosis is suspected, and morning cortisol and ACTH levels should be checked for adrenal insufficiency. Lifelong corticosteroid replacement is needed if Addison's disease is identified. Biopsy is indicated when malignancy-infection distinction cannot be made — CT-guided percutaneous biopsy or EUS-FNA can be performed. Treatment response is monitored with imaging and biochemical parameters. In the calcified chronic phase, treatment is generally not needed but replacement continues if Addison's disease is present.
In the presence of bilateral adrenal calcification, granulomatous disease (TB/histoplasmosis) should be strongly considered. Adrenal insufficiency may develop requiring cortisol replacement therapy. AFB culture and PCR should be evaluated for TB diagnosis.