scholarly journals SUN-938 Rare Case of Ectopic Cushing Syndrome Caused by ACTH Secreting Thymic Neuroendocrine Tumor in a Patient with Multiple Endocrine Neoplasia Type 1

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yamuna Gorantla ◽  
Jorge Soria Moncada ◽  
Juan Sarmiento ◽  
Ambika Amblee ◽  
Malini Ganesh
Keyword(s):  
Neuroendocrine Tumor ◽  
Poor Prognosis ◽  
Rare Case ◽  
Cushing Syndrome ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Multiple Tumors ◽  
Men 1 ◽  
Acth Secreting

Abstract Introduction Cushing syndrome (CS) represents an uncommon manifestation of MEN1 and can be caused by both ACTH dependent or independent etiologies. Among them, ectopic ACTH secretion from a Thymic neuroendocrine tumor (TNET) in MEN1 is rare, with very few cases reported so far in literature. We report a case of Ectopic Cushing syndrome (ECS) in a MEN1 patient (pt) with multiple tumors, secondary to ACTH-secreting TNET. Case description: A 44 year old male presented to our institution for nausea, vomiting, dizziness. He had initial workup which revealed multiple tumors (papillary thyroid cancer, thymic mass, parathyroid adenomas, bilateral adrenal nodules, macroprolactinoma, peripancreatic nodules). Given concern for MEN 1, genetic testing was performed which was confirmative. Hormonal workup at this time for adrenal nodules was negative including low dose dexamethasone suppression test(DST). The immobile thymic mass was found to be poorly differentiated NET on biopsy with Ki-67 >50% with vascular invasion and adhesions to lung/chest wall on VATS, not amenable to surgery. The pt declined chemotherapy and radiotherapy due to poor social support. Six months later, he presented with complaints of shortness of breath, proximal muscle weakness, anasarca. Evaluation revealed AM cortisol >60 ug/dL(range 6.7-22), high-dose DST Cortisol >60 ug/dL, 24hr urine free cortisol: 8511mcg (range 4-50) and ACTH level: 278pg/mL(range 6-50) confirming ACTH-dependent CS. Special stains from the previous TNET biopsy demonstrated positive staining for ACTH confirming ectopic ACTH secretion. Ketoconazole and chemotherapy with Etoposide and Carboplatin was started, however he clinically deteriorated and expired a few weeks after diagnosed of ECS. Discussion: TNET in MEN 1 is rare, with a prevalence of 3-8%. TNET are unusual neoplasms that account for 2% to 7% of all mediastinal tumors. TNET in MEN1 rarely secrete functional hormones with very few reported Ectopic ACTH secretion. MEN1 associated ECS from TNET is an aggressive disease with local invasion of adjacent mediastinal structures or metastasis being common, resulting in poor prognosis as demonstrated in few case reports including our case. Radical surgery of involved adjacent structures and adjuvant local RT can provide local disease control. Conclusion: Our pt is a rare case of ECS from TNET in MEN1 with poor prognosis. A special feature of this case is that the patient had initial negative evaluation for hypercortisolemia, however 6 months later he presented with signs and symptoms of severe hypercortisolism, with evaluation confirming transformation into ACTH producing TNET. This conversion is very rarely found in literature and adds to the unique presentation of the case.

scholarly journals The value of corticotropin-releasing hormone (CRH) test for differential diagnosis of Cushing’s syndrome

2007 ◽  
Vol 135 (1-2) ◽  
pp. 31-37 ◽  
Author(s):  
Zorana Penezic ◽  
Milos Zarkovic ◽  
Svetlana Vujovic ◽  
Miomira Ivovic ◽  
Biljana Beleslin ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Roc Curve ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Test Sensitivity ◽  
Basal Cortisol ◽  
Area Under Roc Curve ◽  
Curve Method ◽  
Acth Secreting

Introduction: Diagnosis and differential diagnosis of Cushing?s syndrome (CS) remain considerable challenge in endocrinology. For more than 20 years, CRH has been widely used as differential diagnostic test. Following the CRH administration, the majority of patients with ACTH secreting pituitary adenoma show a significant rise of plasma cortisol and ACTH, whereas those with ectopic ACTH secretion characteristically do not. Objective The aim of our study was to assess the value of CRF test for differential diagnosis of CS using the ROC (receiver operating characteristic) curve method. Method A total of 30 patients with CS verified by pathological examination and postoperative testing were evaluated. CRH test was performed within diagnostic procedures. ACTH secreting pituitary adenoma was found in 18, ectopic ACTH secretion in 3 and cortisol secreting adrenal adenoma in 9 of all patients with CS. Cortisol and ACTH were determined -15, 0, 15, 30, 45, 60, 90 and 120 min. after i.v. administration of 100?g of ovine CRH. Cortisol and ACTH were determined by commercial RIA. Statistical data processing was done by ROC curve analysis. Due to small number, the patients with ectopic ACTH secretion were excluded from test evaluation by ROC curve method. Results In evaluated subgroups, basal cortisol was (1147.3?464.3 vs. 1589.8?296.3 vs. 839.2?405.6 nmol/L); maximal stimulated cortisol (1680.3?735.5 vs. 1749.0?386.6 vs. 906.1?335.0 nmol/L); and maximal increase as a percent of basal cortisol (49.1?36.9 vs. 9.0?7.6 vs. 16.7?37.3 %). Consequently, basal ACTH was (100.9 ?85.0 vs. 138.0?123.7 vs. 4.8?4.3 pg/mL) and maximal stimulated ACTH (203.8 ?160.1 vs. 288.0?189.5 vs. 7.4?9.2 pg/mL). For cortisol, determination area under ROC curve was 0.815?0.083 (CI 95% 0.652-0.978). For cortisol increase cut-off level of 20%, test sensitivity was 83%, with specificity of 78%. For ACTH, determination area under ROC curve was 0.637?0.142 (CI 95% 0.359-0.916). For ACTH increase cut-off level of 30%, test sensitivity was 70%, with specificity of 57%. Conclusion Determination of cortisol and ACTH levels in CRH test remains reliable tool in differential diagnosis of Cushing?s syndrome.

scholarly journals SAT-118 Rapid Decompensation from Complications of Severe Hypercortisolism in an Unusual Presentation of an Ectopic ACTH-Secreting Neuroendocrine Tumor

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Amit Kartar Singh Sumal ◽  
Charles Liao ◽  
Julie Chen
Keyword(s):  
Neuroendocrine Tumor ◽  
Cushing’S Syndrome ◽  
Cushing Syndrome ◽  
Pulseless Electrical Activity ◽  
Cushing's Syndrome ◽  
Bilateral Adrenalectomy ◽  
Unknown Primary ◽  
Who Grade ◽  
Ectopic Acth ◽  
Acth Secreting

Abstract Background: Ectopic Cushing’s syndrome from an ACTH-secreting neuroendocrine tumor (NET) is a rare condition whose onset and disease progression is often more aggressive than other forms of Cushing’s syndrome due to complications from severe hypercortisolism. Clinical Case: A 75-year old woman presented with profound proximal muscle weakness, severe hypokalemia, Cushingoid features, and biopsy-proven Candida esophagitis. Initial testing was consistent with ACTH-dependent Cushing syndrome: elevated 24 hour urinary cortisol excretion (1,310.54 mcg/24h; n <50 mcg/24h), abnormal 1 mg dexamethasone suppression test (68.3 ug/dL), and elevated ACTH level (200 pg/mL; n: 7.2–63.3 pg/mL). MRI was negative for a pituitary lesion but abdominal CT revealed an 8.8 cm liver mass with biopsy consistent with a well-differentiated neuroendocrine tumor, WHO Grade 2. Subsequent 68Ga-DOTATATE-PET/CT noted DOTATATE uptake in the liver lesion, a 0.9 cm right pulmonary nodule, and the pancreatic tail without CT correlate. Initially, the patient was prescribed mifepristone and spironolactone for hypokalemia. Given her NET of unknown primary, metastatic disease, and immunocompromised state due to hypercortisolism, the patient was not a candidate for surgical resection of her NET but was instead referred for bilateral adrenalectomy. However, she rapidly decompensated from complications of her hypercortisolism prior to surgery. Her weakness progressed to immobility, and she developed acute psychosis manifested as agitation and mutism. The patient was immediately admitted to the hospital where she developed new-onset atrial flutter and myelosuppression requiring multiple transfusions. She underwent urgent bilateral adrenalectomy, but despite surgery, her post-operative course was complicated by hypoxemic respiratory failure and shock. The patient shortly thereafter expired from pulseless electrical activity arrest. Conclusion: This atypical case of an ectopic ACTH-secreting NET highlights the life-threatening complications associated with severe hypercortisolism, including: opportunistic infection, severe metabolic abnormalities, psychosis, myopathy, and critical illness that can incite myelosuppression and unstable arrhythmias. These patients can quickly deteriorate and are at high risk for mortality. Early diagnosis and swift reversal of their hypercortisolism with bilateral adrenalectomy are oftentimes needed to prevent these potentially fatal complications.

scholarly journals MON-178 Cyclical Cushing’s Syndrome in 12 Patients with Ectopic ACTH Secretion

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Anna Zenno ◽  
Raven McGlotten ◽  
Atil Kargi ◽  
Lynnette Nieman
Keyword(s):  
Medical Treatment ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Inferior Petrosal Sinus ◽  
Acth Secretion ◽  
Diagnostic Challenge ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Inferior Petrosal Sinus Sampling ◽  
Acth Secreting

Abstract Background: Cyclical Cushing’s syndrome (CCS) is characterized by alternating periods of endogenous hypercortisolism and eucortisolism. A literature survey of 60 adult patients with CCS found 15 to have ectopic ACTH secretion (EAS) (1). The duration and frequency of hypercortisolemia are unpredictable, creating a diagnostic challenge. Objective: Describe biochemical and clinical characteristics of patients with CCS due to occult or histologically proven ectopic ACTH-secreting neuroendocrine tumor (NET). Methods: We conducted a retrospective medical record review of 12 adults with EAS admitted to our institution. Inclusion required 1) evidence of ectopic ACTH tumor from biochemical testing (CRH stimulation, 8 mg dexamethasone suppression [DST], and/or inferior petrosal sinus sampling [IPSS]) or pathology results and 2) cycles of hypercortisolism (Hi-F) to eucortisolism (Eu-F) off medical treatment. Results: Average age on admission was 61 (46-79) years; 58% were women. All 12 had biochemical evidence of ACTH-dependent Hi-F. IPSS results suggested EAS in 9 patients, 8 of whom had Hi-F for more than two months, and 1 whose cycles occurred every 5 - 7 days. IPSS was consistent with Cushing’s disease (CD) in 2 patients after Hi-F of only 6 -7 weeks and one with Eu-F on admission, estimated duration < 4 weeks. DST suggested EAS in 9 patients, and CD in the one with recent Eu-F. CRH was consistent with EAS in 10 patients, but suggested CD in 2 with marginal increases in ACTH (34.5%, 38%) but not cortisol. 7 patients had ACTH-secreting tumor on pathology (5 pulmonary, 1 pancreas, 1 appendix NET), and 5 had occult presumed EAS. Time from one Hi-F episode to the next ranged from 1 week to 6 years with Hi-F duration of 3 days to 5 years. 24-hour urine free cortisol (UFC) levels were 17 - 301 times the upper reference range (RR) during Hi-F periods. During Eu-F, lowest UFCs were within RR in 9 patients and subnormal in 3. Hypokalemia occurred in 11 patients with Hi-F; increasing values paralleled movement to Eu-F. Conclusion: Patients with possible ectopic ACTH-secretion and CCS may pose a diagnostic challenge: clinical and biochemical evidence of hypercortisolemia may not be present, depending on the timing and/or duration of hypercortisolism. Furthermore, test results may inappropriately suggest Cushing’s disease if performed after less than 8 weeks of hypercortisolism, or with recent eucortisolism. Thus, weekly UFC measurement may facilitate diagnosis of cyclical Cushing’s syndrome and determine appropriate timing of dynamic testing such as inferior petrosal sinus sampling. Potassium may be a useful marker to determine when medical treatment can be tapered or stopped. 1. Meinardi JR, et al. Eur J Endocrinol. 157:245, 2007.

scholarly journals SUN-385 A Rare Case of Ectopic ACTH Secretion by Pancreatic Adenocarcinoma

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Le Angela ◽  
Robert Arashahi ◽  
Mahmood Shahlapour ◽  
Manal Zabad ◽  
Mohamad Horani
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Rare Case ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion

scholarly journals A rare case of Cushing's syndrome caused by 'cyclical' ectopic ACTH secretion

2014 ◽  
Author(s):  
Preeshila Behary ◽  
Raghunath Kadiyala ◽  
Agnieszka Falinska ◽  
Hannah Beckwith ◽  
James Jackson ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Rare Case ◽  
Cushing's Syndrome ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion

scholarly journals A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing’s syndrome

2016 ◽  
Vol 2016 ◽  
Author(s):  
M J Trott ◽  
G Farah ◽  
V J Stokes ◽  
L M Wang ◽  
A B Grossman
Keyword(s):  
Cushing’S Syndrome ◽  
Neuroendocrine Tumours ◽  
Neuroendocrine Tumour ◽  
Cushing's Syndrome ◽  
Young Female ◽  
Diagnostic Workup ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Men 1

Summary We present a case of a young female patient with a rare cause of relapsing and remitting Cushing’s syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing’s syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms ‘relapsing and remitting’ in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing’s syndrome with thymic neuroendocrine tumours (NETs), although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking. Learning points Ectopic corticotrophin (ACTH) secretion should always be considered in the diagnostic workup of young patients with Cushing’s syndrome There is a small but growing body of literature describing the correlation between ectopic ACTH secretion and thymic neuroendocrine tumours (NETs) The possibility of a MEN-1 syndrome should be considered in all patients with thymic NETs, and we note the observational association with male gender and cigarette smoking in this cohort An exception to these associations is the finding of relatively high incidence of thymic NETs among female non-smoking MEN-1 patients in the Japanese compared with Western populations The relapsing and remitting course of our patient’s symptoms is noteworthy, given the paucity of this finding among other published cases

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