Castleman disease, or angiofollicular lymph node hyperplasia, and POEMS (Polyneuropathy, Organomegaly, Endocrino-pathy, Monoclonal gammopathy, and Skin changes), are associated and can lead to a clinical conundrum. The physician caring for a patient with Castleman disease should be alert to the development of multiple endocrine deficiencies, including primary hypogonadism, diabetes mellitus, hypothyroidism, and adrenal insufficiency. Avoidance of treating hypothyroidism alone when there is concomitant subclinical adrenal insufficiency is important, to avoid precipitating an adrenal crisis. A better outcome may result from earlier recognition of the endocrinopathies of this syndrome. This article describes a patient with Castleman disease in whom the features of POEMS unfolded over the ensuing years.