Use of a Parenteral Propylene Glycol-Containing Etomidate Preparation for the Long-Term Management of Ectopic Cushing's Syndrome

ObjectiveOur aim was to review short- and long-term outcomes of patients treated with bilateral adrenalectomy (BADx) in ACTH-dependent Cushing's syndrome.MethodsWe reviewed the literature and analysed our experience with 53 patients treated with BADx since 1990 in our institution.ResultsBADx 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.ConclusionBADx is a relatively safe and highly effective treatment, and it provides adequate control of long-term co-morbidities associated with hypercortisolism.

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Surviving ectopic Cushing’s syndrome: quality of life, cardiovascular and metabolic outcomes in comparison to Cushing’s disease during long-term follow-up

Acta Endocrinologica ◽

10.1530/eje-18-0212 ◽

2018 ◽

Vol 179 (2) ◽

pp. 109-116 ◽

Cited By ~ 11

Author(s):

Andrea Osswald ◽

Timo Deutschbein ◽

Christina M Berr ◽

Eva Plomer ◽

Anne Mickisch ◽

...

Keyword(s):

Quality Of Life ◽

Cushing’S Syndrome ◽

Psychiatric Morbidity ◽

Serum Cortisol ◽

Cushing's Syndrome ◽

Ectopic Cushing’S Syndrome ◽

Cortisol Levels

Objective Aim of our study was to analyze long-term outcome of patients with the ectopic Cushing’s syndrome (ECS) compared to patients with Cushing’s disease (CD) regarding cardiovascular, metabolic, musculoskeletal and psychiatric comorbidities. Design Cross-sectional study in patients with ECS and CD in two German academic tertiary care centers. Methods Standardized clinical follow-up examination was performed including health-related quality of life (QoL) in 21 ECS patients in long-term remission (≥18 months since successful surgery). Fifty-nine patients with CD in remission served as controls. Results Time from first symptoms to diagnosis of Cushing’s syndrome (CS) was shorter in ECS than in CD (8.5 (IQR: 30.3) vs 25 (IQR: 39.0) months, P = 0.050). ECS patients had lower self-reported psychiatric morbidity compared to CD (19% vs 43%, P = 0.050) at follow-up. Moreover, female ECS patients reported favorable scores for QoL in the SF-36 questionnaire (mental health: 92 (IQR: 30) vs 64 (IQR: 32) in CD, P = 0.010) and a Cushing-specific QoL questionnaire (73 (IQR: 18) vs 59 (IQR: 36) in CD, P = 0.030). In a pooled analysis of ECS and CD patients, QoL correlated with time from first symptoms until diagnosis of CS, but not with urinary free cortisol levels or serum cortisol after dexamethasone at the time of diagnosis. Long-term outcomes regarding hypertension, metabolic parameters, bone mineral density and grip strength were comparable in ECS and CD. Conclusions Our data support the concept that time of exposure to glucocorticoid excess appears to be a better predictor than peak serum cortisol levels at the time of diagnosis regarding long-term psychiatric morbidity and QoL.

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Prospective Study of the Clinical Course, Prognostic Factors, Causes of Death, and Survival in Patients With Long-Standing Zollinger-Ellison Syndrome

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.2.615 ◽

1999 ◽

Vol 17 (2) ◽

pp. 615-615 ◽

Cited By ~ 258

Author(s):

Fang Yu ◽

David J. Venzon ◽

Jose Serrano ◽

Stephan U. Goebel ◽

John L. Doppman ◽

...

Keyword(s):

Prognostic Factors ◽

Liver Metastases ◽

Bone Metastases ◽

Cushing’S Syndrome ◽

Clinical Course ◽

Cushing's Syndrome ◽

Ectopic Cushing’S Syndrome ◽

Zollinger Ellison Syndrome ◽

Large Primary

PURPOSE: The long-term clinical course of unselected patients with gastrinomas as well as other functional pancreatic endocrine tumors (PETs) in whom the excess-hormone state is controlled is largely unknown. To address this issue, patients with gastrinomas were assessed. PATIENTS AND METHODS: Two hundred twelve patients with Zollinger-Ellison syndrome (ZES) were prospectively studied. All had controlled acid hypersecretion and were assessed yearly, with a mean follow-up period of 13.8 ± 0.6 years (range, 0.1 to 31 years). Annual assessments of possible factors that might affect prognosis or treatment approaches were performed, such as those for tumor size and location; the presence, location, and extent of metastases; and the occurrence of ectopic Cushing's syndrome or another PET syndrome. Deaths were categorized as ZES-related or non–ZES-related and classified into different causes. RESULTS: Thirty-one percent of patients died, all of non–acid-related causes. One half died of a ZES-related cause; they differed from those who died of non–ZES deaths by having a large primary tumor, more frequently a pancreatic tumor; lymph node, liver, or bone metastases; ectopic Cushing's syndrome; or higher gastrin levels. The extent of liver metastases correlated with survival rate. The presence of liver metastases alone only moderately decreased survival time; however, the additional development of bone metastases or ectopic Cushing's syndrome markedly decreased survival rate. CONCLUSIONS: In ZES, gastrinoma growth is now the main single determinant of long-term survival, with one half of patients dying a gastrinoma-related death and none an acid-related death. Large primary tumors that are pancreatic in location, the development of liver metastases, (especially if associated with bone metastases or Cushing's syndrome), and the extent of liver metastases are all important prognostic factors. The identification of these factors allows the recognition of subgroups that can be used to tailor antitumor treatment approaches.

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MANAGEMENT OF ENDOCRINE DISEASE: Cushing's syndrome: a structured short- and long-term management plan for patients in remission

Acta Endocrinologica ◽

10.1530/eje-13-0534 ◽

2013 ◽

Vol 169 (5) ◽

pp. R139-R152 ◽

Cited By ~ 29

Author(s):

Oskar Ragnarsson ◽

Gudmundur Johannsson

Keyword(s):

Cushing’S Syndrome ◽

Management Plan ◽

Postoperative Management ◽

Cushing's Syndrome ◽

Postoperative Phase ◽

Related Quality ◽

Long Term Follow Up ◽

Health Related ◽

Term Management

One hundred years have passed since Harvey Williams Cushing presented the first patient with the syndrome that bears his name. In patients with Cushing's syndrome (CS), body composition and lipid, carbohydrate and protein metabolism are dramatically affected and psychopathology and cognitive dysfunction are frequently observed. Untreated patients with CS have a grave prognosis with an estimated 5-year survival of only 50%. Remission can be achieved by surgery, radiotherapy and sometimes with medical therapy. Recent data indicate that the adverse metabolic consequences of CS are present for years after successful treatment. In addition, recent studies have demonstrated that health-related quality of life and cognitive function are impaired in patients with CS in long-term remission. The focus of specialised care should therefore be not only on the diagnostic work-up and the early postoperative management but also on the long-term follow-up. In this paper, we review the long-term consequences in patients with CS in remission with focus on the neuropsychological effects and discuss the importance of these findings for long-term management. We also discuss three different phases in the postoperative management of surgically-treated patients with CS, each phase distinguished by specific challenges: the immediate postoperative phase, the glucocorticoid dose tapering phase and the long-term management. The focus of the long-term specialised care should be to identify cognitive impairments and psychiatric disorders, evaluate cardiovascular risk, follow pituitary function and detect possible recurrence of CS.

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