Adrenal Infections: An Underrecognized Cause of Primary Adrenal Insufficiency

Adrenal infections are an underrecognized but clinically significant cause of primary adrenal insufficiency (PAI).

This review proposes a diagnostic algorithm for the evaluation of suspected cases.

The most common causative pathogens are Mycobacterium tuberculosis and Histoplasma capsulatum; however, bacterial infections and viral pathogens such as cytomegalovirus (CMV) and SARS-CoV-2 (COVID-19) have also been reported. These infections, particularly in tuberculosis and histoplasmosis, can induce granulomatous inflammation, tissue necrosis, and destruction of the adrenal glands, leading to systemic symptoms and hormonal deficiency. The prevalence of adrenal insufficiency varies widely, ranging from 14% to 100%, depending on the study population and diagnostic criteria. Affected patients may present across a broad clinical spectrum, from chronic adrenal insufficiency to adrenal crisis, and some patients may be identified incidentally through imaging performed for unrelated indications. Computed tomography is the primary imaging modality for diagnosing adrenal infection, typically demonstrating bilateral adrenal lesions characterized by hypodensity with central necrosis, peripheral rim enhancement, and calcification. In contrast, during the late phase, the adrenal glands progressively decrease in size and may become atrophic, particularly in tuberculosis, and often with persistent calcifications. Tissue biopsy with histopathological examination and culture remains the definitive diagnostic tool to confirm the infectious etiology.

Early recognition is essential, as management requires two complementary approaches: 1. antimicrobial therapy directed at the causative pathogen, and 2. hormonal replacement in patients with established adrenal insufficiency and longitudinal hormonal surveillance in those with preserved adrenal reserve at initial presentation.