Republished: Clinicopathological correlates of adrenal Cushing's syndrome

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.

Simultaneous pituitary and adrenal adenomas in a patient with non ACTH dependent Cushing syndrome; a case report with literature review

“…Cushing's syndrome is a serious and well-known medical condition that results from persistent exposure of the body to excessive glucocorticoids, either from endogenous or, most frequently, exogenous sources [9] . The average age of diagnosis is 41.4 years, with a female-to-male ratio of 3:1 [10] .…”

“…All patients with CS should have a high-resolution pituitary MRI with a gadolinium-based contrast agent to prove the existence or absence of a pituitary lesion and to identify the source of ACTH between pituitary adenomas and ectopic lesions [24] . Adrenal CT scan is the imaging modality of choice for preoperatively localizing and subtyping adrenocortical lesions in ACTH-independent Cushing's syndrome [9] . MRI of the pituitary gland of the current case showed a microadenoma and a CT scan of the adrenals showed left adrenal adenoma.…”

ACTH-independent Cushing’s syndrome due to ectopic endocrinologically functional adrenal tissue caused by a GNAS heterozygous mutation: a rare case of McCune–Albright syndrome accompanied by central amenorrhea and hypothyroidism: a case report and literature review

“…The most crucial and novel finding is that we detected for the first time the GNAS mutation, encoding the Gsa subunit that mediates GPCR signalling, from this endocrinologically functional ectopic tumor. GNAS mutation causes the constitutive activation of adenylyl cyclase, which activates cAMP-dependent protein kinase A (PKA), leading to the hyperproduction of cortisol through the acceleration of the cAMP response element-binding protein CREB (20). Indeed, the GNAS mutation was detected in 16.9% out of 65 cases of ACTH-independent Cushing's syndrome (21), suggesting that this mutation is one of the causal molecular pathogeneses for cortisol-producing adrenocortical adenoma.…”

The Demonstration of Tumor Heterogeneity using 2DE Proteomic Approach

“…30 Cushing sendromlu vakaların %45'ini adrenokor-tikal adenomların, %35'ini ise adrenokortikal karsinomların oluşturduğu bildirilmiştir. 31 Literatürde adrenokortikal adenom ve adronokortikal kanser dokuları, 15,32,33 idrar örnekleri [34][35][36][37] ve hücre hatları [38][39][40][41] ve HCO 3 'ün taşınması gibi birçok başka fizyolojik sürece katılır. 43,44 Önceki bir çalışmada CAH1'in endometriyal kanserlerde erken evrede aşağı regüle edilirken ileri evrede yukarı regüle edildiği görülmüştür.…”