THERAPY OF ENDOCRINE DISEASE: Outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence

Petersenn, Stephan; Beckers, Albert; Ferone, Diego; Lely, Aart van der; Bollerslev, Jens; Boscaro, Marco; Brue, Thierry; Bruzzi, Paolo; Casanueva, Felipe F.; Chanson, Philippe; Colao, Annamaria; Reincke, Martín; Stalla, Günter; Tsagarakis, Stelios

doi:10.1530/eje-14-0883

Cited by 132 publications

(121 citation statements)

References 59 publications

(65 reference statements)

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“…In a significant percentage of patients, hypercortisolism persists or recurs after a few years. Recurrence occurs in 3-47% of cases, with a median of 12% (8), and there are higher recurrence rates with longterm follow-up. The primary approach to ACTH-producing neuroendocrine tumours that cause ectopic Cushing's syndrome is resection or tumour debulking.…”

Section: Introductionmentioning

confidence: 99%

“…According to a meta-analysis by Petersenn et al (8), 31% of patients are in need of secondary treatment options, either because they are not controlled by a first pituitary surgery (22% of patients) or because they develop recurrence (9% of patients). Second-line therapeutic options consist of second transsphenoidal surgery, pituitary irradiation, medical therapy and BADx.…”

Section: Introductionmentioning

confidence: 99%

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A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing's syndrome

Reincke

Ritzel

Oßwald

et al. 2015

European Journal of Endocrinology

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Objective: Our aim was to review short-and long-term outcomes of patients treated with bilateral adrenalectomy (BADx) in ACTH-dependent Cushing's syndrome. Methods: We reviewed the literature and analysed our experience with 53 patients treated with BADx since 1990 in our institution. Results: BADx is considered if ACTH-dependent Cushing's syndrome is refractory to other treatment modalities. In Cushing's disease (CD), BADx is mainly used as an ultima ratio after transsphenoidal surgery and medical therapies have failed. In these cases, the time span between the first diagnosis of CD and treatment with BADx is relatively long (median 44 months). In ectopic Cushing's syndrome, the time from diagnosis to BADx is shorter (median 2 months), and BADx is often performed as an emergency procedure because of life-threatening complications of severe hypercortisolism. In both situations, BADx is relatively safe (median surgical morbidity 15%; median surgical mortality 3%) and provides excellent control of hypercortisolism; Cushing's-associated signs and symptoms are rapidly corrected, and co-morbidities are stabilised. In CD, the quality of life following BADx is rapidly improving, and long-term mortality is low. Specific long-term complications include the development of adrenal crisis and Nelson's syndrome. In ectopic Cushing's syndrome, long-term mortality is high but is mostly dependent on the prognosis of the underlying malignant neuroendocrine tumour. Conclusion: BADx is a relatively safe and highly effective treatment, and it provides adequate control of long-term co-morbidities associated with hypercortisolism.European Journal of Endocrinology (2015) 173, M23-M32 Invited Author's profile Prof. Martin Heinrich Reincke is Director of the Medizinische Klinik and Poliklinik IV, Ludwig-MaximiliansUniversität München, and Chair of the Department of Endocrinology and Diabetology. His research specialities include adrenal physiology and pathophysiology, endocrine hypertension, pituitary disease, mineralocorticoid and glucocorticoid action and stress research. Professor Reincke heads a research team that specifically explores the prevalence and relevance of Cushing's syndrome at the epidemiological, clinical, genetic and molecular levels. The research teams of his clinic have particular expertise in assay development and validation for endocrine disease and in the development of genetically manipulated animals as models for human adrenal disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing's syndrome

Reincke

Ritzel

Oßwald

et al. 2015

European Journal of Endocrinology

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“…Corticotroph adenomas are typically isolated tumors consisting of a monoclonal cell population in a pituitary of normal size (5,6,7). Selective transsphenoidal adenomectomy causes remission in 60-96% of patients (8,9).…”

Section: Introductionmentioning

confidence: 99%

Decoding the genetic basis of Cushing's disease: USP8 in the spotlight

Theodoropoulou

Reincke

Faßnacht

et al. 2015

European Journal of Endocrinology

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Cushing's disease (CD) arises from pituitary-dependent glucocorticoid excess due to an ACTH-secreting corticotroph tumor. Genetic hits in oncogenes and tumor suppressor genes that afflict other pituitary tumor subtypes are not found in corticotrophinomas. Recently, a somatic mutational hotspot was found in up to half of corticotrophinomas in the USP8 gene that encodes a protein that impairs the downregulation of the epidermal growth factor receptor (EGFR) and enables its constitutive signaling. EGF is an important regulator of corticotroph function and its receptor is highly expressed in Cushing's pituitary tumors, where it leads to increased ACTH synthesis in vitro and in vivo. The mutational hotspot found in corticotrophinomas hyper-activates USP8, enabling it to rescue EGFR from lysosomal degradation and ensure its stimulatory signaling. This review presents new developments in the study of the genetics of CD and focuses on the USP8-EGFR system as trigger and target of corticotroph tumorigenesis.

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“…Эндоскопическая трансна-зальная транссфеноидальная аденомэкто-мия является методом выбора в лечении БИК [3][4][5]. Несмотря на высокие показатели ремиссии -порядка 60-90% [6][7][8][9], частота рецидивов заболевания после первоначаль-но успешной (с развитием послеоперацион-ной ремиссии) трансназальной аденомэкто-мии варьирует от 10 до 65% [10][11][12][13]. Большая часть рецидивов возникает в первые 2-4 года после трансназальной аденомэктомии [14,15].…”

Section: обоснованиеunclassified

Factors affecting the probability of recurrence of the Cushing’s disease within 3 years after effective neurosurgical treatment

Nadezhdina

Юрьевна²,

Rebrova

et al. 2018

Endo Serg

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Background. Cushing’s disease (СD) is а severe neuroendocrine disease that can rapidly progress with the development of severe complications of hypercorticism requiring immediate treatment. The main method of treatment is a neurosurgical operation, the effectiveness of which at the present time can reach 80% or more, however, about a quarter of patients after successful neurosurgical treatment experience reccurence. Aim. The analysis of prognostic factors potentially affecting the occurrence of recurrence of CD after successful primary transnasal adenomectomy. Material and methods. A retrospective monocenter comparative study of treatment outcomes in 219 patients (32 men, 187 women) with confirmed diagnosis of Cushing's disease who underwent endoscopic transsphenoidal adenomectomy between 2007 and 2014 was performed. The inclusion criteria were: the absence of previous pathogenetic treatment for this disease and the development of remission of the disease in the early postoperative period. The duration of follow-up period was three years and more. We used methods of statistical comparison of groups, including survival analysis and ROC-analysis. Results. Within 3 years the remission was preserved in 172 patients, the recurrence of Cushing's disease developed in 47 patients (21.5% [16%; 28%]). The probability of CD recurrence was associated with morning levels of ACTH and cortisol and evening ACTH in the early postoperative period. As a result of the ROC-analysis for morning ACTH and cortisol, the optimal cutting points were 7 pg/ml and 123 nmol/l respectively. In patients with ACTH level less than 7 pg/ml, three years recurrence appeared to be 7%, 95% CI [3%, 14%], while at the level of ≥7 pg/ml recurrence was observed in 31% [23%, 40%] cases, RR 0.22 [0.09; 0.51], ОR – 0.16 [0.06; 0.43]. In patients with cortisol level below 123 nmol/l the recurrence developed in 13% [9%, 20%] of cases, while in patients with cortisol level ≥123 nmol/l, recurrence was equal to 45% [32%, 59%], RR 0.29 [0.18; 0.50], ОR – 0.19 [0.09; 0.39]. Conclusion. The development of adrenal insufficiency (a decrease in ACTH level less than 7 pg/ml and cortisol level less than 123 nmol/l) statistically significantly reduces the probability of the recurrence of CD within three years after surgery.

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THERAPY OF ENDOCRINE DISEASE: Outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence

Cited by 132 publications

References 59 publications

A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing's syndrome

A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing's syndrome

Decoding the genetic basis of Cushing's disease: USP8 in the spotlight

Factors affecting the probability of recurrence of the Cushing’s disease within 3 years after effective neurosurgical treatment

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