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Clinicopathological correlates of adrenal Cushing's syndrome
  1. Kai Duan1,2,
  2. Karen Gomez Hernandez3,4,
  3. Ozgur Mete1,2,4
  1. 1Department of Pathology, University Health Network, Toronto, Ontario, Canada
  2. 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada
  3. 3Department of Medicine, University Health Network, Toronto, Ontario, Canada
  4. 4Endocrine Oncology Site Group, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
  1. Correspondence to Dr Ozgur Mete, 200 Elizabeth Street, 11th floor, University Health Network, Department of Pathology, Toronto, Ontario, Canada M5G 2C4; ozgur.mete2{at}uhn.ca

Abstract

Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease.

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