Vitam Horm. 2026;132:1-55. doi: 10.1016/bs.vh.2026.04.001. Epub 2026 May 15.
ABSTRACT
Cushing's syndrome (CS) presents with a constellation of features reflecting chronic glucocorticoid excess. Hallmarks-central adiposity with thin extremities, dorsocervical and supraclavicular fat pads, round facies with plethora, wide violaceous striae, skin fragility, acne or hirsutism, and proximal myopathy-often coexist with systemic complications that drive morbidity and mortality. Phenotype and evolution vary by etiology: Cushing's disease typically evolves insidiously and may cycle, whereas ectopic ACTH secretion often presents abruptly with severe hypercortisolism, hypokalemic metabolic alkalosis, profound protein catabolism, and heightened infection risk. Adrenal forms range from overt CS to mild autonomous cortisol secretion, with attenuated stigmata yet meaningful cardiometabolic burden. Age and sex modulate expression: children frequently show growth deceleration with weight gain; older adults exhibit sarcopenic obesity, osteoporosis, and cardiovascular disease; men may develop hypogonadism, and women menstrual dysfunction. The comorbidity spectrum spans hypertension, insulin resistance, atherogenic dyslipidemia, and hepatic steatosis; venous thromboembolism due to a prothrombotic milieu; skeletal fragility with vertebral fractures; immune dysregulation predisposing to serious infections; and neuropsychiatric and cognitive sequelae that impair quality of life and can persist after biochemical remission. This chapter synthesizes contemporary evidence to (i) highlight red-flag patterns that shorten diagnostic latency; (ii) link pathophysiologic axes to multisystem complications; and (iii) offer practical screening and initial management clues for high-risk populations (e.g., refractory hypertension, difficult-to-control diabetes), to reduce the long-term health burden of hypercortisolism.
PMID:42236005 | DOI:10.1016/bs.vh.2026.04.001