scholarly journals The Dexamethasone-CRH Stimulation Test: A Single-Center Experience

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A97-A97
Author(s):  
Leen Wehbeh ◽  
Ula Abed Alwahab ◽  
Alexandra Mikhael ◽  
Georgiana Dobri ◽  
Laurence Kennedy ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Cortisol Level ◽  
Additional Case ◽  
Stimulation Test ◽  
Ectopic Acth Syndrome ◽  
Case Detection ◽  
Cushing Disease ◽  
Ectopic Acth ◽  
Significant Difference

Abstract Background: The diagnostic value of adding a Corticotropin Releasing Hormone (CRH) Stimulation Test to the 2-day Low Dose Dexamethasone Suppression Test (Dex-CRH Test) has been debated in the literature. We hypothesized that adding CRH to LDDST would provide additional case detection in patients suspected of having Cushing’s disease (CD). Methods: We identified 118 patients who underwent the Dex-CRH test to evaluate ACTH-dependent CS from a prospectively maintained pituitary database over 12 years. Seven patients were excluded (2 lost to follow up, 2 were on Dilantin with no available Dexamethasone (Dex) level, 2 had cyclic CD, and 1 suspected noncompliance with Dex intake). Three patients with ectopic ACTH Syndrome had very high cortisol levels after both LDDST and Dex-CRH tests. The remaining 108 patients are the subjects of this analysis. Patients were instructed to take 8 doses of Dex 0.5 mg PO every 6 hours starting at noon with the last dose of Dex taken at 6 AM. Ovine CRH injection (1 µg/kg, max 100 mcg) was given IV 2 hours afterwards. Cortisol was measured 2 hours after the last Dex dose prior to and 15 minutes after CRH administration. CD diagnosis was made based on positive ACTH staining on pituitary pathology and/or development of hypocortisolism postoperatively. Patients with no Cushing disease (NCD) are the group of patients in whom CD diagnosis could not be confirmed after a minimum follow up of 30 months. Results: Among 108 patients who underwent Dex-CRH test, 66 had CD and 42 had NCD. The female sex ratio, and median (range) for each of age, BMI, and follow-up duration in months were as follows with no statistically significant difference between the two groups: CD: 83%, 40 (15–82), 34 (30–42) and 63 (24–102). NCD: 88%, 40 (20–71), 37 (31–43) and 52 (30–67). Among 66 patients with CD, 5 patients (7.6%) had a cortisol level ≤ 1.4 µg/dl after LDDST but were appropriately classified as CD with a cortisol level >1.4 µg/dL at 15-min post CRH stimulation. In contrast, 3/42 patients (7.1%) in NCD had an abnormal Dex-CRH test. In only one of these three patients the LDDST was normal (cortisol post-Dex was 1.4 µg/dL and increased to 3.1 µg/dL 15-min post CRH). A cortisol cut-off value of > 1.4 µg/dL at 15 min during Dex-CRH test provided a sensitivity of 100%, specificity of 93%, and diagnostic accuracy of 97% to diagnose CD. When patients without a Dex level were excluded from the analysis (n=74), the sensitivity did not change but specificity and accuracy of Dex-CRH test further increased to 97% and 99%, respectively. Conclusion: The CRH test addition to the 2-day LDDST provided additional case detection in 5/66 (7.6%) of patients with CD. It resulted in one additional false-positive case compared to LDDST. Measurement of Dex level provided improved diagnostic accuracy of DEX-CRH test.

Usefulness of composite methionine–positron emission tomography/3.0-tesla magnetic resonance imaging to detect the localization and extent of early-stage Cushing adenoma

2010 ◽  
Vol 112 (4) ◽  
pp. 750-755 ◽  
Author(s):  
Hidetoshi Ikeda ◽  
Takehiko Abe ◽  
Kazuo Watanabe
Keyword(s):  
Mr Imaging ◽  
Diagnostic Accuracy ◽  
Fdg Pet ◽  
Early Stage ◽  
False Negative ◽  
Mr Images ◽  
Cushing Disease ◽  
Significant Difference ◽  
3.0 T ◽  
Met Pet

Object Fifty to eighty percent of Cushing disease is diagnosed by typical endocrine responses. Recently, the number of diagnoses of Cushing disease without typical Cushing syndrome has been increasing; therefore, improving ways to determine the localization of the adenoma and making an early diagnosis is important. This study was undertaken to determine the present diagnostic accuracy for Cushing microadenoma and to compare the differences in diagnostic accuracy between MR imaging and PET/MR imaging. Methods During the past 3 years the authors analyzed the diagnostic accuracy in a series of 35 patients with Cushing adenoma that was verified by surgical pituitary exploration. All 35 cases of Cushing disease, including 20 cases of “overt” and 15 cases of “preclinical” Cushing disease, were studied. Superconductive MR images (1.5 or 3.0 T) and composite images from FDG-PET or methionine (MET)–PET and 3.0-T MR imaging were compared with the localization of adenomas verified by surgery. Results The diagnostic accuracy of superconductive MR imaging for detecting the localization of Cushing microadenoma was only 40%. The causes of unsatisfactory results for superconductive MR imaging were false-negative results (10 cases), false-positive results (6 cases), and instances of double pituitary adenomas (3 cases). In contrast, the accuracy of microadenoma localization using MET-PET/3.0-T MR imaging was 100% and that of FDG-PET/3.0-T MR imaging was 73%. Moreover, the adenoma location was better delineated on MET-PET/MR images than on FDG-PET/MR images. There was no significant difference in maximum standard uptake value of adenomas evaluated by MET-PET between preclinical Cushing disease and overt Cushing disease. Conclusions Composite MET-PET/3.0-T MR imaging is useful for the improvement of the delineation of Cushing microadenoma and offers high-quality detectability for early-stage Cushing adenoma.

scholarly journals Cushing's syndrome associated with a nested stromal epithelial tumor of the liver: hormonal, immunohistochemical, and molecular studies

2009 ◽  
Vol 161 (5) ◽  
pp. 805-810 ◽  
Author(s):  
Anne Rod ◽  
Manuela Voicu ◽  
Laurence Chiche ◽  
Céline Bazille ◽  
Hervé Mittre ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Malignant Tumors ◽  
Cushing's Syndrome ◽  
Good Prognosis ◽  
University Hospital ◽  
Ectopic Acth Syndrome ◽  
Epithelial Tumor ◽  
Ectopic Acth ◽  
Normal Human

ContextEctopic ACTH syndrome (EAS) is principally associated with aggressive malignant tumors but also with neuroendocrine tumors of good prognosis. Recently, rare nonhepatocytic nested stromal and epithelial tumors (NSET) were characterized by their possible association with Cushing's syndrome of which biochemical and physiopathological features were still incompletely studied.ObjectiveTo describe the clinical and hormonal characteristics of an EAS originating from a liver NSET and further understand the mechanism of cortisol overproduction.Design and settingThis is a clinical case report from the Endocrinology Department of Caen University Hospital, France.Patient and interventionA 17-year-old female patient was found to have a large liver NSET with mild Cushingoid clinical features and intense biological hypercortisolism but moderate ACTH secretion. Resection of the tumor was curative with a 30-month follow-up.ResultsThe epithelial component of the tumor coexpressed ACTH mildly, corticotropin-releasing hormone (CRH) strongly, and 11β-hydroxysteroid dehydrogenase at a level comparable with normal human hepatocytes.ConclusionsLiver NSET is a new cause of EAS, which may evoke hypercortisolism by multiple biochemical pathways.

scholarly journals 223 Long Term Follow-up of Patients With Suspected Early Chronic Pancreatitis to Determine the Diagnostic Accuracy of the Secretin Pancreatic Stimulation Test

2012 ◽  
Vol 142 (5) ◽  
pp. S-55
Author(s):  
Gyanprakash A. Ketwaroo ◽  
Alphonso Brown ◽  
Benjamin E. Young ◽  
Rakhi Kheraj ◽  
Steven D. Freedman ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Diagnostic Accuracy ◽  
Stimulation Test ◽  
Long Term Follow Up

scholarly journals Cushing's syndrome due to ectopic ACTH production by a nasal paraganglioma

2013 ◽  
Vol 2013 ◽  
Author(s):  
F Serra ◽  
S Duarte ◽  
S Abreu ◽  
C Marques ◽  
J Cassis ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Microscopic Analysis ◽  
Cushing's Syndrome ◽  
Ectopic Acth Syndrome ◽  
List Type ◽  
Rare Tumour ◽  
Ectopic Acth ◽  
Ectopic Acth Production ◽  
The Right

Summary Ectopic secretion of ACTH is an infrequent cause of Cushing's syndrome. We report a case of ectopic ACTH syndrome caused by a nasal paraganglioma, a 68-year-old female with clinical features of Cushing's syndrome, serious hypokalaemia and a right paranasal sinus' lesion. Cranial magnetic resonance image showed a 46-mm mass on the right paranasal sinuses. Endocrinological investigation confirmed the diagnosis of ectopic ACTH production. Resection of the tumour normalised ACTH and cortisol secretion. The tumour was found to be a paraganglioma through microscopic analysis. On follow-up 3 months later, the patient showed nearly complete clinical recovery. Ectopic ACTH syndrome due to nasal paraganglioma is extremely uncommon, as only two other cases have been discussed in the literature. Learning points Ectopic Cushing's syndrome accounts for 10% of Cushing's syndrome etiologies. Most paraganglioma of the head and neck are not hormonally active. Nasal paraganglioma, especially ACTH producing, is a very rare tumour.

CLINICAL HETEROGENEITY OF ECTOPIC ACTH SYNDROME: A LONG-TERM FOLLOW-UP STUDY

2020 ◽  
Vol 26 (12) ◽  
pp. 1435-1441
Author(s):  
Ana Laura Espinosa-de-los-Monteros ◽  
Claudia Ramírez-Rentería ◽  
Moisés Mercado
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Cushing Syndrome ◽  
Neuroendocrine Neoplasm ◽  
Ectopic Acth Syndrome ◽  
Tumor Type ◽  
Ectopic Acth ◽  
Long Term Outcome ◽  
Free Cortisol

Objective: Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a heterogeneous condition caused by neuroendocrine neoplasms (NENs) located in the lungs, thymus, or pancreas. Our purpose was to evaluate the long-term outcome of these patients. Methods: Retrospective study at a referral center. The charts of 164 patients with Cushing syndrome, followed at our center from 1993 to 2019, were analyzed. Results: EAS was found in 16 patients (9.75%, 9 women, mean age 36.01 years) who had been followed for a median of 72 months. The source of EAS was a NEN in 10 patients (8 bronchial and 2 thymic carcinoid tumors) and a mixed corticomedullary tumor, consisting of a pheochromocytoma and an adrenocortical carcinoma in 1 patient. In 2 of the 6 patients initially considered to have occult EAS, the source of the ACTH excess became apparent after adrenalectomy, whereas in the remaining 4 (25%) patients, it has remained occult. Of the 11 patients in whom resection of the NEN was attempted, 10 patients achieved an early remission (91%), but 4 (25%) of these patients had a recurrence during follow-up (biochemically and clinically silent in 2 patients). Three patients died (18.75%): the young woman with the mixed corticomedullary tumor, a man with a thymic NEN that evolved into a neuroendocrine (NE) carcinoma after 11 years of follow-up, and a woman with a bronchial NEN. Conclusion: The course of EAS varies according to tumor type and grade. Some patients have a protracted course, whereas others may evolve into neuroendocrine carcinomas. Abbreviations: ACTH = adrenocorticotropic hormone; CS = Cushing syndrome; CT = computed tomography; CV = coefficient of variation; EAS = ectopic ACTH syndrome; IQR = interquartile range; NEN = neuroendocrine neoplasm; SCCL = small cell carcinoma of the lung; TSS = transsphenoidal surgery; UFC = urinary free cortisol

scholarly journals Clinical and laboratory characteristics and results of treatment of patients with ACTH-producing neuroendocrine tumors of various localization

2021 ◽  
Vol 93 (10) ◽  
pp. 1171-1178
Author(s):  
Olga O. Golounina ◽  
Zhanna E. Belaya ◽  
Liudmila Ya. Rozhinskaya ◽  
Evgeniya I. Marova ◽  
Michail Yu. Pikunov ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Fatal Outcome ◽  
Distant Metastases ◽  
Multiple Organ ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Results Of Treatment ◽  
Single Center Study ◽  
Pancreatic Net

Aim. To study the clinical, biochemical characteristics, treatment results and follow-up of patients with ectopic ACTH syndrome EAS (ACTH adrenocorticotropic hormone ). Materials and methods. A retrospective, observational, single-center study of 130 patients with EAS. Demographic information of patients, medical history, results of laboratory and instrumental investigations at the pre- and postoperative stages and follow-up of EAS were analyzed. Results. The mean age at the diagnosis ranged from 12 to 74 years (Me 40 years [28; 54]). The duration of the disease from the onset of symptoms to the verification of the diagnosis varied from 2 to 168 months (Me 17.5 months [7; 46]). Eighty-one (62,3%) patients had bronchopulmonary NET, 9 thymic carcinoid, 7 pancreatic NET, 5 pheochromocytoma, 1 cecum NET, 1 appendix carcinoid tumor, 1 medullary thyroid cancer and 25 (19.2%) had an occult source of ACTH. The median follow-up period of patients was 27 months [9.75; 61.0] with a maximum follow-up of 372 months. Currently, primary tumor was removed in 82 (63.1%) patients, bilateral adrenalectomy was performed in 23 (18%) patients, in 16 of them there was an occult source of ACTH-producing NET and in 7 patients in order to control hypercortisolism after non-successful surgical treatment. Regional and distant metastases were revealed in 25 (19.2%) patients. At the time of the last observation 59 (72%) patients were exhibited a full recovery, 12 (14.6%) had relapse of the disease and 26 (20%) died from multiple organ failure (n=18), pulmonary embolism (n=4), surgical complications (n=2), disseminated intravascular coagulation syndrome (n=1) or COVID-19 (n=1). Conclusion. In our cohort of patients bronchopulmonary NET are the most frequent cause of EAS (62.3%). Surgical treatment leads to remission of hypercortisolism in 72% cases; the proportion of relapse (14.6%) and fatal outcome (20%) remains frequent in EAS.

scholarly journals SUN-919 Ectopic ACTH Syndrome: An Aggressive Presentation Due to Metastatic Liver Cancer of Unknown Primary

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ivan Alexander Serrano ◽  
Sara Ahmad ◽  
Ramona Dadu ◽  
Paul Graham ◽  
Steven Weitzman
Keyword(s):  
Liver Cancer ◽  
Cortisol Level ◽  
Metastatic Cancer ◽  
Performance Status ◽  
Bilateral Adrenalectomy ◽  
Ectopic Acth Syndrome ◽  
Unknown Primary ◽  
Ectopic Acth ◽  
Morning Cortisol ◽  
Metastatic Liver

Abstract Background: Ectopic Cushing’s Syndrome is a rare but often aggressive condition caused by ACTH-hypersecretion from non-pituitary tumors. In patients with metastatic cancer, as well as those with occult tumors, the diagnosis and management can be extremely challenging. Clinical Case: A 25-year old woman recently diagnosed with poorly differentiated metastatic liver carcinoma of unknown primary was admitted for lower extremity edema and worsening fatigue for the preceding month. Since being diagnosed with liver cancer, she developed uncontrolled hypertension, persistent severe hypokalemia and facial “puffiness”. Physical exam was remarkable for moon facies and truncal obesity but no evidence of striae. An overnight 1-mg dexamethasone suppression test resulted in an elevated morning cortisol level of 93.4 mcg/dL and elevated ACTH of 299 pg/mL. A 24-hour urine cortisol was significantly elevated at 4,448 mcg/24 hours. These findings were consistent with hypercortisolism due to hypersecretion of ACTH. An MRI of the sella revealed no pituitary abnormality. A high-dose dexamethasone suppresion test (single 8 mg dose) was performed and her morning cortisol level remained elevated at 98.6 mcg/dL, consistent with ectopic ACTH secretion. She was treated for the underlying malignancy with carboplatin and paclitaxel. After a thorough discussion of therapeutic options, she was prescribed Ketoconazole with the plan to medically control the hypercortisolism potentially followed by bilateral adrenalectomy. Ketoconazole was up-titrated and Spironolactone was added resulting in significant improvement of hypokalemia and hypertension. Unfortunately, one week after discharge she was re-admitted due to worsening performance status, watery diarrhea and abdominal pain. A serum cortisol level was elevated at 124 mcg/dL and Metyrapone was added to her regimen. Unfortunately, her performance status continued to decline due to progression of cancer and uncontrolled hypercortisolism. As a result, she was deemed a poor surgical candidate for bilateral adrenalectomy. The patient’s condition rapidly deteriorated and she developed malignant ascites as well as altered mental status. In accordance with her wishes, a DNR order was placed and she passed away shortly thereafter. Conclusion: Ectopic ACTH-syndrome is the etiology of 10–20% of cases of Cushing’s syndrome. Clinical presentation is often sudden and rapidly progressive. Severe hypertension and hypokalemia are seen more commonly than in Cushing’s disease. Cases secondary to occult tumors or metastatic cancer can be particularly challenging to treat when it is not possible to eliminate the source of ACTH hypersecretion via surgical or medical treatment. In patients such as this, early bilateral adrenalectomy should be considered after starting medical therapy in order to reduce morbidity and mortality due to hypercortisolism.

The Incidence of Adrenal Insufficiency in Myeloma Patients Receiving Pulse-Dose Dexamethasone

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5640-5640
Author(s):  
Aimaz Afrough ◽  
Amy Sidorski ◽  
Roberto Salvatori ◽  
Ivan Borrello
Keyword(s):  
Adrenal Insufficiency ◽  
Cortisol Level ◽  
Research Funding ◽  
Serum Cortisol ◽  
Stimulation Test ◽  
Serum Cortisol Level ◽  
Acth Stimulation Test ◽  
Acth Stimulation ◽  
Pulse Dose ◽  
Significant Difference

Abstract Introduction: Glucocorticoids (GC's) are major drugs in the treatment of multiple myeloma (MM). Chronic administration of supra-physiological doses of GC's suppresses the hypothalamus-pituitary-adrenal (HPA) axis and is associated with secondary adrenal insufficiency (AI). In MM, GC's are usually administered in weekly high dose pulses. Due to long GC-free periods in such therapy, GC-induced AI is not usually considered to be a consequence of GC therapy in MM (Krasner, AS. JAMA, 1999. 282(7): p. 671-6). Here we report on the incidence of AI in MM patients treated at our center with pulse-dose GC. Methods: This is a retrospective cross-sectional study of patients with MM treated with GC-based regimens. Patients were required to have at least a random serum cortisol or a standard 250 mcg ACTH stimulation test result available in their medical record during dexamethasone-based chemotherapy. Patients were excluded if they were on dexamethasone more than 1 day a week, were lost to follow-up, had prior use of synthetic progestational agents such as megestrol or had been on oral glucocorticoids for any other medical indication. Diagnosis of AI was established by a frankly low AM serum cortisol level (<3 ug/dL) or an inadequate cortisol response to ACTH stimulation test (Salvatori, R. JAMA, 2005. 294(19): p. 2481-8). Results: A total of 45 patients were included in this study with median age of 62 (range, 49-89). Fifteen (33.3%) of patients were diagnosed with AI. The median random cortisol level in AI group was 2.3 ug/dL (range, 0.3-7.4 ug/dL) compared to 9.9 ug/dL (range, 1.0-21.2 ug/dL) in the non-AI group. The median time between the last dexamethasone dose and the serum cortisol assay was 5 days (range, 1-21). The median number of GC-based chemotherapy cycles taken before diagnosis of AI was 15 (range, 2-60). The median cumulative dexamethasone consumption was 1280 mg (range, 180-5220 mg). There was no correlation between developing AI and dose or duration of dexamethasone treatment. We observed clinical trend between cumulative doses of ≥1500 mg (P= 0.055) or use of clarithromycin (P=0.079) and developing AI, without reaching a statistically significant difference. Conclusion: The rate of AI was 33% among patients with MM on weekly pulse-dose dexamethasone. As such, patients should be periodically evaluated for this to enable early detection and proper management. Disclosures Borrello: BMS: Honoraria, Research Funding; WindMIL Therapeutics: Equity Ownership, Patents & Royalties, Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau.

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