Crooke's Changes In Cushing's Syndrome Depends on Degree of Hypercortisolism and Individual Susceptibility

Oldfield, Edward H.; Vance, Mary Lee; Louis, Robert G.; Pledger, Carrie L.; Jane, John A.; Lopes, Maria-Beatriz S.

doi:10.1210/jc.2015-2493

Cited by 34 publications

(21 citation statements)

References 6 publications

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“…These changes are known as Crooke’s hyaline changes, and their identification is of paramount importance. The presence of these changes is associated with the degree of hypercortisolism and individual susceptibility to it [300]. These changes involve the massive accumulation of perinuclear cytokeratin under the effect of excessive glucocorticoid levels.…”

Section: Pathological Characteristicsmentioning

confidence: 99%

“…Consequently, their presence can be used to confirm CS in patients in whom no signs of CS are noted during the surgical exploration of the pituitary. Conversely, approximately 20% of the patients with ACTH-positive pituitary tumor at surgery did not exhibit Crooke’s changes, thus, the absence of Crooke’s changes does not always establish the absence of CS [299,300]. Non-neoplastic increase in the number of adenohypophyseal corticotrophs, called corticotroph hyperplasia, in which the reticulin framework is intact but expanded, may be due to the reduced negative feedback effect of glucocorticoids or increased exposure to CRH.…”

Section: Pathological Characteristicsmentioning

confidence: 99%

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Cushing’s Disease

Nishioka

Yamada²

2019

JCM

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In patients with Cushing’s disease (CD), prompt diagnosis and treatment are essential for favorable long-term outcomes, although this remains a challenging task. The differential diagnosis of CD is still difficult in some patients, even with an organized stepwise diagnostic approach. Moreover, despite the use of high-resolution magnetic resonance imaging (MRI) combined with advanced fine sequences, some tumors remain invisible. Surgery, using various surgical approaches for safe maximum tumor removal, still remains the first-line treatment for most patients with CD. Persistent or recurrent CD after unsuccessful surgery requires further treatment, including repeat surgery, medical therapy, radiotherapy, or sometimes, bilateral adrenalectomy. These treatments have their own advantages and disadvantages. However, the most important thing is that this complex disease should be managed by a multidisciplinary team with collaborating experts. In addition, a personalized and individual-based approach is paramount to achieve high success rates while minimizing the occurrence of adverse events and improving the patients’ quality of life. Finally, the recent new insights into the pathophysiology of CD at the molecular level are highly anticipated to lead to the introduction of more accurate diagnostic tests and efficacious therapies for this devastating disease in the near future.

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Section: Pathological Characteristicsmentioning

confidence: 99%

Section: Pathological Characteristicsmentioning

confidence: 99%

Cushing’s Disease

Nishioka

Yamada²

2019

JCM

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“…These changes are histological changes known as Crooke's changes. 76 The presence of these changes is associated with the degree of hypercortisolism and individual susceptibility to them. The changes are never present in the absence of hypercortisolism.…”

Section: Pathologic Findingsmentioning

confidence: 99%

Cushing's disease: pathobiology, diagnosis, and management

Lonser

Nieman

Oldfield

2017

JNS

Self Cite

151

114

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Cushing's syndrome (CS) is caused by prolonged supraphysiological levels of circulating cortisol. Cushing's disease (CD) is the most common etiology (70%-80% of CS cases) of endogenous CS. It is caused by a pituitary adenoma that secretes adrenocorticotropic hormone (ACTH), which stimulates secretion of cortisol by the adrenal glands. If not effectively treated, CD is associated with hypertension, diabetes, obesity, osteoporosis, vascular disease, and shortened life span. Successful resection of a CD-associated ACTH-secreting pituitary adenoma results in immediate biochemical remission and preservation of pituitary function. Early identification of CD by clinical findings, endocrinological evaluation, and imaging studies is critical for diagnosis and effective surgical management. endocrinological and Clinical Features endocrinological Features Normal PhysiologyInsight into the normal and pathophysiological mechanisms of control of the hypothalamic-anterior pituitaryadrenal axis is critical to understanding the pathologic, diagnostic, and therapeutic features of CD (Fig. 1). 52 Under normal physiological conditions (circadian rhythm, where cortisol levels peak in early morning and nadir late at night), systemic inflammation (cytokine), or stress (physiological or psychological), corticotropin-releasing hormone (CRH; a 41-amino acid peptide) is released from the paraventricular hypothalamic nucleus via the median eminence. From the median eminence, CRH is transported in the hypophyseal portal venous system to the pituitary gland, where it binds to the CRH receptor-1 (CRH-R1) on pituitary corticotroph cells. CRH binding to CRH-R1 receptors activates adenylate cyclase and stimulates proopiomelanocortin (POMC) gene expression in the corticotroph cells.17,66 Proopiomelanocortin preprohormone is processed into ACTH (a 39-amino acid peptide) and b-lipotropin (a 93-amino acid peptide). Products of b-lipotropin include b-endorphin and a-lipotropin. ACTH is secreted into the systemic circulation and binds to receptors in the adrenal cortex, where it stimulates production and secretion of glucocorticoids, including cortisol. 83 Under normal conditions, circulating cortisol provides physiological control of this endocrine axis by its negative feedback inhibition on hypothalamic CRH and pituitary ACTH secretion. Cushing's disease (CD) is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma. The excessive secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol. The pathophysiological levels of cortisol are associated with hypertension, diabetes, obesity, and early death. Successful resection of the CD-associated ACTH-secreting pituitary adenoma is the treatment of choice and results in immediate biochemical remission with preservation of pituitary function. Accurate and early identification of CD is critical for effective surgical management and optimal prognosis. The authors review the cu...

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“…In a recent study, it was shown that depending on the degree of hypercortisolism, densely/sparsely corticotroph tumors show focal Crooke’s changes 67 . This suggests that Crooke’s cell adenomas have no specific genetic/epigenetic background but derive from densely/sparsely CAs at a high hypercortisolemic state.…”

Section: Progression Of Corticotroph Adenomasmentioning

confidence: 99%

Recent advances in understanding corticotroph pituitary tumor initiation and progression

2018

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Cushing’s disease is the most frequent form of hypercortisolism and is caused by hypophyseal corticotroph adenomas secreting excessive amounts of adrenocorticotropic hormone. Most of the tumors develop sporadically and only a limited number of corticotroph adenomas have been found to be associated with different neuroendocrine syndromes or with familial isolated pituitary adenomas. The pathogenic mechanisms of corticotroph adenomas are largely unknown, but the discovered aberrant chaperoning activity of heat shock protein 90 on the one hand and the presence of ubiquitin-specific protease 8 mutations on the other hand partially explained the causes of their development. Corticotroph tumors arise initially as benign microadenomas but with time form invasively growing aggressive macroadenomas which can switch to corticotroph carcinomas in extremely rare cases. The mechanisms through which corticotroph tumors escape from glucocorticoid negative feedback are still poorly understood, as are the processes that trigger the progression of benign corticotroph adenomas toward aggressive and malignant phenotypes. This review summarizes recent findings regarding initiation and progression of corticotroph pituitary tumors.

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Crooke's Changes In Cushing's Syndrome Depends on Degree of Hypercortisolism and Individual Susceptibility

Cited by 34 publications

References 6 publications

Cushing’s Disease

Cushing’s Disease

Cushing's disease: pathobiology, diagnosis, and management

Recent advances in understanding corticotroph pituitary tumor initiation and progression

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