scholarly journals Etomidate infusion at low doses is an effective and safe treatment for severe Cushing’s syndrome outside intensive care

2020 ◽  
Vol 183 (2) ◽  
pp. 161-167
Author(s):  
Stefan M Constantinescu ◽  
Natacha Driessens ◽  
Aurélie Lefebvre ◽  
Raluca M Furnica ◽  
Bernard Corvilain ◽  
...  
Keyword(s):  
Intensive Care ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Low Doses ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Frequent Monitoring ◽  
Cortisol Levels ◽  
Medical Wards

Introduction Intravenous etomidate infusion is effective to rapidly lower cortisol levels in severe Cushing’s syndrome (CS) in the intensive care unit (ICU). Recently, etomidate treatment has also been proposed at lower doses in non-ICU wards, but it is not yet clear how this approach compares to ICU treatment. Methods We compared data from patients with severe CS treated with high starting doses of etomidate (median: 0.30 mg/kg BW/day) in ICU or with lower starting doses (median: 0.025 mg/kg BW/day) in non-ICU medical wards. Results Fourteen patients were included, among which ten were treated with low starting doses (LD) and four with high starting doses etomidate (HD). All patients had severe and complicated CS related to adrenal carcinoma (n = 8) or ectopic ACTH secretion (n = 6). Etomidate was effective in reducing cortisol levels below 500 nmol/L in a median of 1 day in the HD group compared to 3 days in the LD group (P = 0.013). However, all patients of the HD group had etomidate-induced cortisol insufficiency and needed frequent monitoring, while no patient from the LD group required hydrocortisone supplementation. No patient in either group died from complications of CS or etomidate treatment, but final outcome was poor as six patients in the LD group and all four patients in the HD group died from their cancer during follow-up. Conclusion Our study suggests that, for patients with severe CS who do not require intensive organ-supporting therapy, the use of very low doses of etomidate in medical wards should be considered.

scholarly journals ACTH-Producing Thymic Carcinoid: A Rare Cause of Cushing’s Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A990-A990
Author(s):  
Lisette Patricia Rodriguez ◽  
Wende Michele Kozlow
Keyword(s):  
Cushing’S Syndrome ◽  
Mediastinal Mass ◽  
Cushing's Syndrome ◽  
Anterior Mediastinal Mass ◽  
Thymic Carcinoid ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
History Of

Abstract Background: Thymic carcinoids are rare neoplasms that account for less than 5% of all thymic tumors. Approximately 25% of these tumors will result in Cushing’s syndrome due to ectopic ACTH secretion. These tumors can also be associated with MEN1 syndrome. This is a case report of a patient with history of macroprolactinoma now presenting with Cushing’s syndrome due to ectopic ACTH production from a thymic carcinoid tumor. Clinical Case: This is a 57 year old male with history of pituitary macroprolactinoma diagnosed in 2011, now status post transsphenoidal resection and external beam radiation therapy, with persistent hyperprolactinemia on cabergoline, who presented to our clinic for a routine follow up visit. Patient had already developed secondary hypogonadism and secondary hypothyroidism as a consequence of treatment for the macroprolactinoma. He complained of worsening fatigue and weight gain ongoing for several months. Laboratory studies revealed an hemoglobin A1c of 8.3% (nl < 5.7%), TSH 0.24 MIU/L (0.4-4.5 MIU/L), free T4 1.2 ng/dL (0.8-1.8 ng/dL), 8 AM cortisol 31.4 mcg/dL (4-22 mcg/dL), ACTH 185 pg/mL (6-50 pg/dL), prolactin 29.6 ng/mL (2-18 ng/mL), IGF-1 88 ng/mL (50-317 ng/mL). Follow up labs confirmed cushings syndrome: cortisol AM-DST 36.4 mcg/dL (< 2 mcg/dL), free urinary cortisol 291.9 mcg/24h (2-50 mcg/24h). Pituitary MRI showed empty sella turcica. Cortisol after an 8 mg DST 32.5 mcg/dL (< 5 mcg/dL). CT chest, abdomen and pelvis revealed an heterogeneously enhancing solid anterior mediastinal mass measuring 4.9 x 3.1 x 4.3 cm. Whole body OctreoScan showed a markedly hyperintense large mass adjacent to the right heart border measuring 47 x 32 mm. He was referred to cardiothoracic surgery and underwent a right video-assisted thoracic surgery with resection of the anterior mediastinal mass. Pathology revealed a thymic well-differentiated neuroendocrine tumor with strong cytoplasmic staining for ACTH. It was also positive for OSCAR, Cam5.2, synaptophysin, CD56, and S100. Ki67 stain was positive in fewer than 1% of tumor cells. Final diagnosis was carcinoid tumor. Conclusion: Cushing’s syndrome secondary to ectopic ACTH secretion from a thymic carcinoid is rare. The presence of two MEN1-associated tumors in this patient, macroprolactinoma and thymic carcinoid, is highly suggestive of a clinical diagnosis of MEN 1.

scholarly journals DIAGNOSIS OF ENDOCRINE DISEASE: The role of the desmopressin test in the diagnosis and follow-up of Cushing’s syndrome

2018 ◽  
Vol 178 (5) ◽  
pp. R201-R214 ◽  
Author(s):  
Dimitra Argyro Vassiliadi ◽  
Stylianos Tsagarakis
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Aberrant Expression ◽  
Ectopic Acth ◽  
Long Term Outcome ◽  
Ectopic Acth Secretion ◽  
Paradoxical Response

Desmopressin is a vasopressin analogue selective for type 2 vasopressin receptors that mediate renal water retention. In contrast to the native hormone arginine vasopressin, a well-known ACTH secretagogue, desmopressin, exerts minimal or no activity on ACTH excretion. However, in a substantial proportion of patients with ACTH-dependent Cushing’s syndrome (CS), desmopressin elicits an ACTH and cortisol response, which contrasts with the minimal responses obtained in healthy subjects. The mechanism underlying this paradoxical response involves upregulation of vasopressin type 3 and/or the aberrant expression of type 2 receptors by neoplastic ACTH-producing cells. This makes desmopressin administration a suitable test enabling the distinction between neoplastic from functional (formerly termed ‘pseudo-Cushing syndrome’) ACTH-dependent cortisol excess. Several studies have now established an adjunctive role of desmopressin in the initial diagnostic workup of CS. Despite some early data indicating that this test may also have a role in distinguishing between Cushing’s disease (CD) and ectopic ACTH secretion, subsequent studies failed to confirm this observation. The ability of the paradoxical response to desmopressin to depict the presence of neoplastic ACTH-secreting cells was also exploited in the follow-up of patients with CD undergoing surgery. Loss of the desmopressin response, performed in the early postoperative period, was a good predictor for a favorable long-term outcome. Moreover, during follow-up, reappearance of desmopressin paradoxical response was an early indicator for recurrence. In conclusion, the desmopressin test is a valid tool in both the diagnosis and follow-up of patients with CD and should be more widely applied in the workup of these patients.

scholarly journals Vandetanib induces a marked anti-tumor effect and amelioration of ectopic Cushing’s syndrome in a medullary thyroid carcinoma patient

2016 ◽  
Vol 2016 ◽  
Author(s):  
Hashem Bseiso ◽  
Naama Lev-Cohain ◽  
David J Gross ◽  
Simona Grozinsky-Glasberg
Keyword(s):  
Cushing’S Syndrome ◽  
Tumor Size ◽  
Cushing's Syndrome ◽  
Whole Body ◽  
List Type ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Ectopic Cushing’S Syndrome ◽  
Free Cortisol

Summary A 55-year-old woman diagnosed with sporadic MTC underwent total thyroidectomy 20 years ago. After the first surgery, elevated calcitonin levels in parallel with local disease persistence were noted and therefore she underwent repeated neck dissections. During follow-up, multiple foci of metastatic disease were noted in the neck and mediastinal lymph nodes, lungs and bones; however, the disease had an indolent course for a number of years, in parallel with a calcitonin doubling time of more than two years and without significant symptoms. During a routine follow-up visit 2 years ago, findings suggestive of Cushing’s syndrome were observed on physical examination. The biochemical evaluation demonstrated markedly elevated serum calcitonin level, in parallel with lack of cortisol suppression after an overnight 1 mg dexamethasone suppression test, lack of cortisol and ACTH suppression after high-dose IV dexamethasone 8 mg, elevated plasma ACTH up to 79 pg/mL (normal <46 pg/mL) and elevated 24-h urinary free cortisol up to 501 µg/24 h (normal 9–90 µg/24 h). After a negative pituitary MRI, she underwent IPSS, which was compatible with EAS. Whole-body CT demonstrated progressive disease at most of the tumor sites. Treatment with vandetanib at a dosage of 200 mg/day was commenced. The patient showed a significant, rapid and consistent clinical improvement already after two months of treatment, in parallel with biochemical improvement, whereas a decrease in tumor size was demonstrated on follow-up CT. Learning points: Ectopic Cushing’s syndrome due to ectopic ACTH secretion (EAS) by MTC is an uncommon and a poor prognostic event, being associated with significant morbidity and mortality. We demonstrate that vandetanib is effective in controlling the signs and symptoms related to the EAS in patients with advanced progressive MTC. We demonstrate that vandetanib is effective in decreasing tumor size and in inducing tumor control.

scholarly journals Case Report: A Challenging Localization of a Pulmonary Ectopic ACTH-Secreting Tumor in a Patient With Severe Cushing’s Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Andreea Liliana Serban ◽  
Lorenzo Rosso ◽  
Paolo Mendogni ◽  
Arianna Cremaschi ◽  
Rita Indirli ◽  
...  
Keyword(s):  
Ct Scan ◽  
Rectal Carcinoma ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Pet Ct ◽  
The Right ◽  
Acth Secreting

BackgroundEctopic adrenocorticotropic syndrome (EAS) is a rare cause of endogenous ACTH-dependent Cushing’s syndrome, usually associated with severe hypercortisolism as well as comorbidities. Tumor detection is still a challenge and often requires several imaging procedures. In this report, we describe a case of an ectopic ACTH secretion with a misleading localization of the responsible tumor due to a concomitant rectal carcinoma.Case presentationA 49-year-old man was referred to our Endocrinology Unit due to suspicion of Cushing’s syndrome. His medical history included metastatic rectal adenocarcinoma, diagnosed 5 years ago and treated with adjuvant chemotherapy, radiotherapy and surgical resection. During follow-up, a thoracic computed tomography scan revealed two pulmonary nodules located in the superior and middle lobes of the right lung with a diameter of 5 and 10 mm, respectively. However, these nodules remained radiologically stable thereafter and were not considered relevant. All biochemical tests were suggestive of EAS (basal ACTH levels: 88.2 ng/L, nv 0–46; basal cortisol levels: 44.2 µg/dl, nv 4.8–19.5; negative response to CRH test and high dose dexamethasone suppression test) and radiological localization of the ectopic ACTH-secreting tumor was scheduled. The CT scan revealed a dimensional increase of the right superior lung nodule (from 5 to 12 mm). [68Ga]-DOTA-TOC PET/CT scan was negative, while [18F]-FDG-PET/CT showed a tracer accumulation in the superior nodule. After a multidisciplinary consultation, the patient underwent thoracic surgery that started with two atypical wedge resections of nodules. Frozen section analyses showed a neuroendocrine tumor on the right middle lobe nodule and a metastatic colorectal adenocarcinoma on the superior lesion. Then, a right superior nodulectomy and a right middle lobectomy with mediastinal lymphadenectomy were performed. The final histopathological examination confirmed a typical carcinoid tumor, strongly positive for ACTH. A post-surgical follow-up showed a persistent remission of Cushing’s syndrome.ConclusionsThe present report describes a case of severe hypercortisolism due to EAS not detected by functional imaging methods, in which the localization of ACTH ectopic origin was puzzled by a concomitant metastatic rectal carcinoma. The multidisciplinary approach was crucial for the management of this rare disease.

scholarly journals Cushing's storm secondary to a rare case of ectopic ACTH secreting metastatic breast cancer

2015 ◽  
Vol 2015 ◽  
Author(s):  
Maura Bucciarelli ◽  
Ya-Yu Lee ◽  
Vasudev Magaji
Keyword(s):  
Breast Cancer ◽  
Intensive Care ◽  
Metastatic Breast Cancer ◽  
Cushing’S Syndrome ◽  
Metastatic Breast ◽  
Cushing's Syndrome ◽  
List Type ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Acth Secreting

Summary Ectopic ACTH secretion from breast cancer is extremely rare. We report a case of a 30-year-old woman with a history of breast cancer, who presented with psychosis and paranoid behaviour. CT of the head showed white matter disease consistent with posterior reversible encephalopathy syndrome (PRES). Despite using mifepristone with multiple antihypertensives including lisinopril, spironolactone and metoprolol, she was hypertensive. Transaminitis did not allow mifepristone dose escalation and ketoconazole utilization. Etomidate infusion at a non-sedating dose in the intensive care unit controlled her hypertension and cortisol levels. She was transitioned to metyrapone and spironolactone. She was discharged from the hospital on metyrapone with spironolactone and underwent chemotherapy. She died 9 months later after she rapidly redeveloped Cushing's syndrome and had progressive metastatic breast cancer involving multiple bones, liver and lungs causing respiratory failure. Learning points Cushing's syndrome from ectopic ACTH secreting breast cancer is extremely rare. Cushing's syndrome causing psychosis could be multifactorial including hypercortisolism and PRES. Etomidate at non-sedating doses in intensive care setting can be effective to reduce cortisol production followed by transition to oral metyrapone.

scholarly journals Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Carlotta Pozza ◽  
Chiara Graziadio ◽  
Elisa Giannetta ◽  
Andrea Lenzi ◽  
Andrea M. Isidori
Keyword(s):  
Cushing’S Syndrome ◽  
Somatostatin Receptor ◽  
Cushing's Syndrome ◽  
Chemotherapeutic Agents ◽  
Peroxisome Proliferator ◽  
Significant Activity ◽  
Ectopic Acth ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ectopic Acth Secretion ◽  
Free Cortisol

Cushing’s syndrome (CS) is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing’s disease, CD) or an ectopic source (ectopic ACTH secretion, EAS). The remaining causes (20%) are ACTH independent. As soon as the diagnosis is established, the therapeutic goal is the removal of the tumor. Whenever surgery is not curative, management of patients with CS requires a major effort to control hypercortisolemia and associated symptoms. A multidisciplinary approach that includes endocrinologists, neurosurgeons, oncologists, and radiotherapists should be adopted. This paper will focus on traditional and novel medical therapy for aggressive ACTH-dependent CS. Several drugs are able to reduce cortisol levels. Their mechanism of action involves blocking adrenal steroidogenesis (ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidate) or inhibiting the peripheral action of cortisol through blocking its receptors (mifepristone “RU-486”). Other drugs include centrally acting agents (dopamine agonists, somatostatin receptor agonists, retinoic acid, peroxisome proliferator-activated receptorγ“PPAR-γ” ligands) and novel chemotherapeutic agents (temozolomide and tyrosine kinase inhibitors) which have a significant activity against aggressive pituitary or ectopic tumors.

Sign in / Sign up

Export Citation Format

Share Document