ACTH-Producing Tumor of the Pituitary Gland

Nelson, Don H.; Meakin, J. W.; Dealy, James B.; Matson, Donald D.; Emerson, Kendall; Thorn, George W.

doi:10.1056/nejm195807242590403

Cited by 307 publications

(92 citation statements)

References 9 publications

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“…90 There is a 21% median rate of Nelson's syndrome (pituitary adenoma progression with progressive elevation of ACTH due to lack of cortisol negative feedback) after bilateral adrenalectomy. 67,68,90 Early data suggest the incidence and severity of Nelson's syndrome is minimized by precedent postoperative (after pituitary surgery) radiation. 48, 63 Nelson's syndrome can be treated by observation (for stable small tumors), tumor resection, tumor/sella radiation, and/or pharmacotherapy.…”

Section: Adrenalectomymentioning

confidence: 99%

Cushing's disease: pathobiology, diagnosis, and management

Lonser

Nieman

Oldfield

2017

JNS

150

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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Section: Adrenalectomymentioning

confidence: 99%

Cushing's disease: pathobiology, diagnosis, and management

Lonser

Nieman

Oldfield

2017

JNS

150

114

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“…She presented with visual field defects, skin hyperpigmentation, raised plasma ACTH and a large sellar mass shown on skull X-ray (1). The sellar mass was a pituitary corticotrophinoma, and its surgical removal led to symptom resolution (1).…”

Section: Introductionmentioning

confidence: 99%

Nelson's syndrome

Barber

Adams²,

Ansorge³

et al. 2010

European Journal of Endocrinology

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Nelson's syndrome is a potentially life-threatening condition that does not infrequently develop following total bilateral adrenalectomy (TBA) for the treatment of Cushing's disease. In this review article, we discuss some controversial aspects of Nelson's syndrome including diagnosis, predictive factors, aetiology, pathology and management based on data from the existing literature and the experience of our own tertiary centre. Definitive diagnostic criteria for Nelson's syndrome are lacking. We argue in favour of a new set of criteria. We propose that Nelson's syndrome should be diagnosed in any patient with prior TBA for the treatment of Cushing's disease and with at least one of the following criteria: i) an expanding pituitary mass lesion compared with pre-TBA images; ii) an elevated 0800 h plasma level of ACTH (O500 ng/l) in addition to progressive elevations of ACTH (a rise of O30%) on at least three consecutive occasions. Regarding predictive factors for the development of Nelson's syndrome post TBA, current evidence favours the presence of residual pituitary tumour on magnetic resonance imaging (MRI) post transsphenoidal surgery (TSS); an aggressive subtype of corticotrophinoma (based on MRI growth rapidity and histology of TSS samples); lack of prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels in year 1 post TBA. Finally, more studies are needed to assess the efficacy of therapeutic strategies in Nelson's syndrome, including the alkylating agent, temozolomide, which holds promise as a novel and effective therapeutic agent in the treatment of associated aggressive corticotroph tumours. It is timely to review these controversies and to suggest guidelines for future audit.

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“…N ELSON AND COLLEAGUES made the original description of a pituitary macroadenoma and high plasma ACTH, in a patient with Cushing's syndrome who had undergone bilateral adrenalectomy, in 1958 (1). Since that time there have been numerous similar case reports and series (2-8).…”

Section: History and Definitionmentioning

confidence: 96%

Nelson's Syndrome

Munir

Newell‐Price

2007

Arq Bras Endocrinol Metab

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Nelson's syndrome is a potentially severe complication of bilateral adrenalectomy performed in the treatment of Cushing's disease, and its management remains difficult. Of all of the features of Nelson's syndrome, the one that causes most concern is the development of a locally aggressive pituitary tumour, which, unusually for pituitary disease, may occasionally cause death from the tumour itself. This feature is especially pertinent given the increasing use in Cushing's disease of laparoscopic bilateral adrenal surgery as a highly effective treatment modality to control cortisol-excess. Despite numerous studies and reports, there is no formal consensus of what defines Nelson's syndrome. Thus, some will define Nelson's syndrome according to the classical description with an evolving pituitary mass after bilateral adrenalectomy, whereas others will rely on increasing plasma ACTH levels, even in the absence of a clear pituitary mass lesion on MRI. These factors need to be borne in mind when considering the reports of Nelson's syndrome, as there is great heterogeneity, and it is likely that overall the modern 'Nelson's syndrome' represents a different disease entity from that of the last century. In the present paper, clinical and epidemiological features of Nelson's syndrome, as well as its treatment modalities, are reviewed.

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ACTH-Producing Tumor of the Pituitary Gland

Cited by 307 publications

References 9 publications

Cushing's disease: pathobiology, diagnosis, and management

Cushing's disease: pathobiology, diagnosis, and management

Nelson's syndrome

Nelson's Syndrome

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