Nelson's Syndrome

Munir, Alia; Newell‐Price, John

doi:10.1590/s0004-27302007000800026

Cited by 14 publications

(19 citation statements)

References 47 publications

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“…Factors that were found to be significantly associated with a higher risk of developing corticotroph tumor progression included the duration of CD, the baseline plasma ACTH levels in the year after the bilateral adrenalectomy, and the rate of increase in plasma ACTH levels after surgery (432). The evidence raised from the evaluation of corticotroph tumor progression and the history of NS suggest that the crucial point in the prevention of this complication is a close clinical and radiological follow-up, with recommendations to perform a pituitary MRI 3-6 months after a bilateral adrenalectomy and then yearly (432,433).…”

Section: Nelson Syndrome or Corticotroph Tumor Progressionmentioning

confidence: 99%

“…When there is evidence of limited tumor progression without an anatomical damage, observation and repeated imaging are an acceptable strategy (433)(434)(435). Pituitary surgery should be the first-line treatment, particularly in case of compression of the optic apparatus (436 -438), with success rates ranging from 10 to 70% (122, 436 -440).…”

Section: Nelson Syndrome or Corticotroph Tumor Progressionmentioning

confidence: 99%

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The Treatment of Cushing's Disease

et al. 2015

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Cushing's disease (CD), or pituitary-dependent Cushing's syndrome, is a severe endocrine disease caused by a corticotroph pituitary tumor and associated with increased morbidity and mortality. The first-line treatment for CD is pituitary surgery, which is followed by disease remission in around 78% and relapse in around 13% of patients during the 10-year period after surgery, so that nearly one third of patients experience in the long-term a failure of surgery and require an additional second-line treatment. Patients with persistent or recurrent CD require additional treatments, including pituitary radiotherapy, adrenal surgery, and/or medical therapy. Pituitary radiotherapy is effective in controlling cortisol excess in a large percentage of patients, but it is associated with a considerable risk of hypopituitarism. Adrenal surgery is followed by a rapid and definitive control of cortisol excess in nearly all patients, but it induces adrenal insufficiency. Medical therapy has recently acquired a more important role compared to the past, due to the recent employment of novel compounds able to control cortisol secretion or action. Currently, medical therapy is used as a presurgical treatment, particularly for severe disease; or as postsurgical treatment, in cases of failure or incomplete surgical tumor resection; or as bridging therapy before, during, and after radiotherapy while waiting for disease control; or, in selected cases, as primary therapy, mainly when surgery is not an option. The adrenal-directed drug ketoconazole is the most commonly used drug, mainly because of its rapid action, whereas the glucocorticoid receptor antagonist, mifepristone, is highly effective in controlling clinical comorbidities, mainly glucose intolerance, thus being a useful treatment for CD when it is associated with diabetes mellitus. Pituitary-directed drugs have the advantage of acting at the site responsible for CD, the pituitary tumor. Among this group of drugs, the dopamine agonist cabergoline and the somatostatin analog pasireotide result in disease remission in a consistent subgroup of patients with CD. Recently, pasireotide has been approved for the treatment of CD when surgery has failed or when surgery is not an option, and mifepristone has been approved for the treatment of Cushing's syndrome when associated with impairment of glucose metabolism in case of the lack of a surgical indication. Recent experience suggests that the combination of different drugs may be able to control cortisol excess in a great majority of patients with CD.

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Section: Nelson Syndrome or Corticotroph Tumor Progressionmentioning

confidence: 99%

Section: Nelson Syndrome or Corticotroph Tumor Progressionmentioning

confidence: 99%

The Treatment of Cushing's Disease

et al. 2015

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“…Surprisingly, ACTH secretion followed a more orderly sequence in Nelson's syndrome compared with Cushing's disease and diurnal variation was maintained (27). The timing of collection of the blood sample for ACTH measurement in relation to the last steroid dose is important: the blood sample should be taken at 0800 h, 20 h following the last dose of glucocorticoid and before the morning dose of glucocorticoid (28). Plasma ACTH is sometimes also measured 2 h following the morning dose of glucocorticoid.…”

Section: Clinical Biochemical and Radiological Featuresmentioning

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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“…This syndrome is characterized by marked excessive ACTH secretion (demonstrated either laboratorially or by skin hyperpigmentation) and/or a documented enlarging pituitary tumor. Presently, no precise and uniform definition has been established for NS [1]. Each author uses an arbitrarily defined threshold of plasma ACTH concentration or even the skin hyperpigmentation for detection of ACTH excess.…”

Section: Introductionmentioning

confidence: 99%

“…The pituitary tumor of a NS patient can display a relentless growth capable of invading bone and other adjacent structures, generating mass effect intracranially, compromising neuro-ophthalmic or neurologic functions or even causing death by the tumor [1]. The mechanism underlying such an aggressive behavior in opposition to a generally more limited growth of pituitary adenoma in CD patients is unknown.…”

Section: Introductionmentioning

confidence: 99%

Possible role of a radiation-induced p53 mutation in a Nelson’s syndrome patient with a fatal outcome

et al. 2009

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Nelson's syndrome (NS) is characterized by the appearance and/or progression of ACTH-secreting pituitary macroadenomas in patients who had previously undergone bilateral adrenalectomy for the treatment of Cushing's disease. Such corticotroph macroadenomas respond poorly to currently available therapeutic options which include surgery, radiotherapy and chemotherapy. P53 protein accumulation may be detected by immunohistochemistry in pituitary corticotroph adenomas and it has been suggested that it might be causally related to tumor development. Wild type P53 protein plays an important role in the cellular response to ionizing radiation and other DNA damaging agents and is mutated in many human tumors. In this study we report an adult male patient with NS who underwent both transsphenoidal and transcranial pituitary surgeries, conventional and stereotaxic radiotherapy and brachytherapy. Despite of the efforts to control tumor mass and growth, this macroadenoma displayed relentless growth and aggressive behavior. DNA extracted from the first two surgical samples, as well as DNA from peripheral blood leukocytes disclosed normal p53 sequence. DNA extracted from tumor samples obtained at surgeries performed after pituitary irradiation carried a somatic heterozygous mutation, consisting of a deletion of four cytosines between nucleotides 12,144-12,149 in exon 4 of the p53 gene. This frameshift mutation creates a stop codon in exon 4 excluding the expression of a functional protein from the defective allele. These data demonstrate a possible association between the P53 protein loss of function induced by radiotherapy and the aggressive course of the disease in this patient.

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Nelson's Syndrome

Cited by 14 publications

References 47 publications

The Treatment of Cushing's Disease

The Treatment of Cushing's Disease

Nelson's syndrome

Possible role of a radiation-induced p53 mutation in a Nelson’s syndrome patient with a fatal outcome

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