Primary Generalized Glucocorticoid Resistance and Hypersensitivity Syndromes: A 2021 Update

Glucocorticoids are the final products of the neuroendocrine hypothalamic–pituitary—adrenal axis, and play an important role in the stress response to re-establish homeostasis when it is threatened, or perceived as threatened. These steroid hormones have pleiotropic actions through binding to their cognate receptor, the human glucocorticoid receptor, which functions as a ligand-bound transcription factor inducing or repressing the expression of a large number of target genes. To achieve homeostasis, glucocorticoid signaling should have an optimal effect on all tissues. Indeed, any inappropriate glucocorticoid effect in terms of quantity or quality has been associated with pathologic conditions, which are characterized by short-term or long-lasting detrimental effects. Two such conditions, the primary generalized glucocorticoid resistance and hypersensitivity syndromes, are discussed in this review article. Undoubtedly, the tremendous progress of structural, molecular, and cellular biology, in association with the continued progress of biotechnology, has led to a better and more in-depth understanding of these rare endocrinologic conditions, as well as more effective therapeutic management.