The idiopathic multicentric Castleman disease (CD)-TAFRO variant (iMCD-TAFRO) is a rare, clinically aggressive lymphoproliferative disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly. Associated with elevated inflammatory cytokines, iMCD-TAFRO can present severe systemic complications. Here, we report a previously healthy adolescent male presenting with severe systemic inflammation, diffuse lymphadenopathy, anasarca, renal impairment, and hepatosplenomegaly. His clinical course was complicated by suspected bilateral adrenal infarction leading to primary adrenal insufficiency (PAI) requiring glucocorticoid (GC) replacement and new-onset autoimmune thyroiditis (AIT) requiring thyroid hormone replacement, suggesting a broader autoimmune process. Diagnosis of iMCD-TAFRO was supported by a right iliac lymph node biopsy showing CD features. The patient was successfully treated with high-dose GC followed by targeted immunosuppressive therapy with siltuximab, an anti-interleukin-6 monoclonal antibody. This case highlights a rare presentation of iMCD-TAFRO syndrome in a pediatric patient with unique co-occurrence of 2 endocrinopathies; PAI and AIT. Prompt recognition of potential associated endocrinopathies and a multidisciplinary approach are critical for management and improved outcomes in this life-threatening condition.