Outcome of Bilateral Adrenalectomy in Cushing's Syndrome: A Systematic Review

Ritzel, Katrin; Beuschlein, Felix; Mickisch, Anne; Oßwald, Andrea; Schneider, Holger; Schopohl, Jochen; Reincke, Martín

doi:10.1210/jc.2013-1470

Cited by 173 publications

(128 citation statements)

References 67 publications

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“…Mortality associated with bilateral adrenalectomy has been estimated at 9% and is most frequently due to stroke and myocardial infarction. 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.…”

Section: Adrenalectomymentioning

confidence: 99%

“…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%

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Cushing's disease: pathobiology, diagnosis, and management

Lonser

Nieman

Oldfield

2017

JNS

147

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%

Section: Adrenalectomymentioning

confidence: 99%

Cushing's disease: pathobiology, diagnosis, and management

Lonser

Nieman

Oldfield

2017

JNS

147

114

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“…The risk of CD recurrence can reach 25%, 3 years after surgery (Patil et al 2008). Second and third line therapies such as a second pituitary surgery (Patil et al 2008, Fleseriu 2012, pituitary irradiation (conventional and/or stereotactic) (Estrada et al 1997, Tritos et al 2011 and bilateral adrenalectomy (Young & Thompson 2005, Assie et al 2007, Chow et al 2008, Ritzel et al 2013) have been utilized with variable results and specific complications.…”

Section: Overview Of CD Therapymentioning

confidence: 99%

Treatment of Cushing's disease: a mechanistic update

Cuevas‐Ramos¹,

Fleseriu²

2014

Journal of Endocrinology

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Cushing's disease (CD) is characterized by an ACTH-producing anterior corticotrope pituitary adenoma. If hypothalamus-pituitary-adrenal (HPA) axis physiology is disrupted, ACTH secretion increases, which in turn stimulates adrenocortical steroidogenesis and cortisol production. Medical treatment plays an important role for patients with persistent disease after surgery, for those in whom surgery is not feasible, or while awaiting effects of radiation. Multiple drugs, with different mechanisms of action and variable efficacy and tolerability for controlling the deleterious effects of chronic glucocorticoid excess, are available. The molecular basis and clinical data for centrally acting drugs, adrenal steroidogenesis inhibitors, and glucocorticoid receptor antagonists are reviewed, as are potential novel molecules and future possible targets for CD treatment. Although progress has been made in the understanding of specific corticotrope adenoma receptor physiology and recent clinical studies have detected improved effects with a combined medical therapy approach, there is a clear need for a more efficacious and better-tolerated medical therapy for patients with CD. A better understanding of the molecular mechanisms in CD and of HPA axis physiology should advance the development of new drugs in the future.

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“…Reisch et al (27) studied the incidence in adult patients with congenital adrenal hyperplasia and reported a frequency of 5.7 crises/100 patient years. More recently, Ritzel et al (28) have investigated patients after bilateral adrenalectomy for Cushing's syndrome and found 9.3 crises/100 patient years. The largest analysis thus far was conducted via a postal survey by the UK Addison's disease Self Help Group in 841 patients from the UK, Canada, Australia, and New Zealand indicating an incidence of eight crises per 100 patient years (29).…”

Section: Introductionmentioning

confidence: 99%

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Adrenal crisis

Allolio

2015

European Journal of Endocrinology

189

230

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Adrenal crisis is a life-threatening emergency contributing to the excess mortality of patients with adrenal insufficiency. Studies in patients on chronic replacement therapy for adrenal insufficiency have revealed an incidence of 5-10 adrenal crises/100 patient years and suggested a mortality rate from adrenal crisis of 0.5/100 patient years. Patients with adrenal crisis typically present with profoundly impaired well-being, hypotension, nausea and vomiting, and fever responding well to parenteral hydrocortisone administration. Infections are the major precipitating causes of adrenal crisis. Lack of increased cortisol concentrations during infection enhances pro-inflammatory cytokine release and sensitivity to the toxic effects of these cytokines (e.g. tumour necrosis factor alpha). Furthermore, pro-inflammatory cytokines may impair glucocorticoid receptor function aggravating glucocorticoid deficiency. Treatment of adrenal crisis is simple and highly effective consisting of i.v. hydrocortisone (initial bolus of 100 mg followed by 200 mg over 24 h as continuous infusion) and 0.9% saline (1000 ml within the first hour). Prevention of adrenal crisis requires appropriate hydrocortisone dose adjustments to stressful medical procedures (e.g. major surgery) and other stressful events (e.g. infection). Patient education is a key for such dose adjustments but current education concepts are not sufficiently effective. Thus, improved education strategies are needed. Every patient should carry an emergency card and should be provided with an emergency kit for parenteral hydrocortisone self-administration. A hydrocortisone pen would hold a great potential to lower the current barriers to hydrocortisone self-injection. Improved patient education and measures to facilitate parenteral hydrocortisone self-administration in impending crisis are expected to significantly reduce morbidity and mortality from adrenal crisis.

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Outcome of Bilateral Adrenalectomy in Cushing's Syndrome: A Systematic Review

Abstract: BADx is relatively safe and provides adequate success. Excess mortality within the first year after surgery suggests that intensive clinical care for patients after BADx is warranted.

Cited by 173 publications

References 67 publications

Cushing's disease: pathobiology, diagnosis, and management

Cushing's disease: pathobiology, diagnosis, and management

Treatment of Cushing's disease: a mechanistic update

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Adrenal crisis

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