Long-term quiescence of ectopic Cushing’s syndrome caused by pulmonary neuroendocrine tumor (typical carcinoid) and tumorlets: Spontaneous remission or therapeutic effect of bromocriptine?

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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Abstract #129 Detection and Management of Ectopic Cushing’s Syndrome in the Setting of a Metastatic Pancreatic Neuroendocrine Tumor

Endocrine Practice ◽

10.1016/s1530-891x(20)46473-0 ◽

2019 ◽

Vol 25 ◽

pp. 18-19

Author(s):

Radhika Chugh ◽

Diana Barb

Keyword(s):

Neuroendocrine Tumor ◽

Cushing’S Syndrome ◽

Pancreatic Neuroendocrine Tumor ◽

Cushing's Syndrome ◽

Ectopic Cushing’S Syndrome

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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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High Molecular Weight ACTH-Precursor Presence in a Metastatic Pancreatic Neuroendocrine Tumor Causing Severe Ectopic Cushing's Syndrome: A Case Report

Frontiers in Endocrinology ◽

10.3389/fendo.2020.00557 ◽

2020 ◽

Vol 11 ◽

Author(s):

Roopa Mehta ◽

César Ernesto Lam-Chung ◽

José Miguel Hinojosa-Amaya ◽

Paola Roldán-Sarmiento ◽

Maria Fernanda Guillen-Placencia ◽

...

Keyword(s):

Molecular Weight ◽

Case Report ◽

Neuroendocrine Tumor ◽

High Molecular Weight ◽

Cushing’S Syndrome ◽

Pancreatic Neuroendocrine Tumor ◽

Cushing's Syndrome ◽

Ectopic Cushing’S Syndrome

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.9.7870 ◽

2001 ◽

Vol 86 (9) ◽

pp. 4104-4108 ◽

Cited By ~ 1

Author(s):

Jonathan Krakoff ◽

Christian A. Koch ◽

Karim Anton Calis ◽

R. H. Alexander ◽

Lynnette K. Nieman

Keyword(s):

Propylene Glycol ◽

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Ectopic Cushing’S Syndrome ◽

Term Management

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Spontaneous remission of ectopic Cushing's syndrome due to pheochromocytoma: a case report

Acta Endocrinologica ◽

10.1530/eje.0.1350440 ◽

1996 ◽

Vol 135 (4) ◽

pp. 440-443 ◽

Cited By ~ 15

Author(s):

Keh-Chuan Loh ◽

Rekha Gupta ◽

Allan H Shlossberg

Keyword(s):

Case Report ◽

Cushing’S Syndrome ◽

Spontaneous Remission ◽

Cushing's Syndrome ◽

Young Female ◽

Cell Hyperplasia ◽

Ectopic Acth ◽

Ectopic Cushing’S Syndrome ◽

Ectopic Acth Production ◽

Biochemical Remission

Loh K-C, Gupta R, Shlossberg AH. Spontaneous remission of ectopic Cushing's syndrome due to pheochromocytoma: a case report. Eur J Endocrinol 1996;135:440–3. ISSN 0804–4643 A young female adult with Cushing's syndrome arising from ectopic production of corticotropin (ACTH) from an adrenal pheochromocytoma showed spontaneous clinical and biochemical remission of hypercortisolism after a brief period of ketoconazole administration. Despite continued remission of the hypercortisolism over the next 18 months, there was progressive catecholamine hypersecretion with significant morbidity as a result of the pheochromocytoma. Surgical resection of the left adrenal gland revealed a pheochromocytoma showing focal cytoplasmic immunostaining for ACTH and marked diffuse compact cell hyperplasia in the adrenocortical tissue. To our knowledge this is the first reported case of spontaneous clinical and biochemical remission of ectopic ACTH production from a pheochromocytoma. The pathogenesis of the remission remains unknown. Keh-Chuan Loh, Division of Endocrinology and Metabolism, Dalhousie University, 5303 Morris Street, Halifax, Nova Scotia B3J 1B6, Canada

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A rare case of an ACTH/CRH co-secreting midgut neuroendocrine tumor mimicking Cushing's disease

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-17-0058 ◽

2017 ◽

Vol 2017 ◽

Cited By ~ 2

Author(s):

Regina Streuli ◽

Ina Krull ◽

Michael Brändle ◽

Walter Kolb ◽

Günter Stalla ◽

...

Keyword(s):

Neuroendocrine Tumor ◽

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Rapid Development ◽

Cushing's Syndrome ◽

Cushing's Disease ◽

High Dose ◽

List Type ◽

Ectopic Acth ◽

Ectopic Cushing’S Syndrome

Summary Ectopic ACTH/CRH co-secreting tumors are a very rare cause of Cushing’s syndrome and only a few cases have been reported in the literature. Differentiating between Cushing’s disease and ectopic Cushing’s syndrome may be particularly difficult if predominant ectopic CRH secretion leads to pituitary corticotroph hyperplasia that may mimic Cushing’s disease during dynamic testing with both dexamethasone and CRH as well as bilateral inferior petrosal sinus sampling (BIPSS). We present the case of a 24-year-old man diagnosed with ACTH-dependent Cushing’s syndrome caused by an ACTH/CRH co-secreting midgut NET. Both high-dose dexamethasone testing and BIPSS suggested Cushing’s disease. However, the clinical presentation with a rather rapid onset of cushingoid features, hyperpigmentation and hypokalemia led to the consideration of ectopic ACTH/CRH-secretion and prompted a further workup. Computed tomography (CT) of the abdomen revealed a cecal mass which was identified as a predominantly CRH-secreting neuroendocrine tumor. To the best of our knowledge, this is the first reported case of an ACTH/CRH co-secreting tumor of the cecum presenting with biochemical features suggestive of Cushing’s disease. Learning points: The discrimination between a Cushing’s disease and ectopic Cushing’s syndrome is challenging and has many caveats. Ectopic ACTH/CRH co-secreting tumors are very rare. Dynamic tests as well as BIPSS may be compatible with Cushing’s disease in ectopic CRH-secretion. High levels of CRH may induce hyperplasia of the corticotroph cells in the pituitary. This could be the cause of a preserved pituitary response to dexamethasone and CRH. Clinical features of ACTH-dependent hypercortisolism with rapid development of Cushing’s syndrome, hyperpigmentation, high circulating levels of cortisol with associated hypokalemia, peripheral edema and proximal myopathy should be a warning flag of ectopic Cushing’s syndrome and lead to further investigations.

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