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 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 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 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 The role of corticotrophin-releasing hormone in the diagnosis of Cushing’s syndrome

2006 ◽  
Vol 155 (suppl_1) ◽  
pp. S93-S98 ◽  
Author(s):  
C J Peters ◽  
H L Storr ◽  
A B Grossman ◽  
M O Savage
Keyword(s):  
Cushing’S Syndrome ◽  
Peak Plasma ◽  
Cushing's Syndrome ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Principal Role ◽  
Releasing Hormone ◽  
Paediatric Patients

Background: Corticotrophin-releasing hormone (CRH) was identified by Vale and co-workers in 1981 and has since been used extensively in the diagnosis of ACTH-dependent Cushing’s syndrome (CS). It was hoped that the CRH test would discriminate between pituitary and ectopic ACTH secretion. In adults, a rise from basal to peak plasma cortisol of ≥20% and ACTH of ≥50% is consistent with Cushing’s disease (CD). Methods: Twenty-seven paediatric patients, with CD (mean age ± s.d. 13.1 ± 3.2; range 6.4–17.8 years) were investigated in our centre between 1982 and 2005. Results: During the CRH test, all patients showed an increase in cortisol of >20% (range 106–554%). In one patient with ectopic ACTH syndrome, there was no increase in cortisol after CRH. In six paediatric patients with CS due to primary adrenal hyperplasia, no patient showed an increase in cortisol after CRH of >1%. Conclusions: A further suggested use of CRH is to increase the sensitivity of the central to peripheral and interpetrosal ratios of ACTH during inferior petrosal sinus catheterisation (IPSS). Bilateral IPSS with human CRH (hCRH) has been performed in our unit in 21 children with CD, as part of the preoperative preparation prior to transsphenoidal surgery (TSS). Its principal role was to identify the site of the microadenoma. Sixteen of 21 patients (76%) who underwent IPSS with hCRH were cured following TSS. In our view, the CRH test is of value during IPSS by clarifying the position of the microadenoma and in this way contributed to the overall outcome of TSS in paediatric patients with CD.

scholarly journals Rapid control of ectopic Cushing’s syndrome during the COVID-19 pandemic in a patient with chronic hypokalaemia

2021 ◽  
Vol 2021 ◽  
Author(s):  
Ziadoon Faisal ◽  
Miguel Debono
Keyword(s):  
Type 2 Diabetes ◽  
Case Report ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Alternative Methods ◽  
Ectopic Acth Syndrome ◽  
High Dose ◽  
List Type ◽  
Ectopic Acth

Summary In this case report, we describe the management of a patient who was admitted with an ectopic ACTH syndrome during the COVID pandemic with new-onset type 2 diabetes, neutrophilia and unexplained hypokalaemia. These three findings when combined should alert physicians to the potential presence of Cushing’s syndrome (CS). On admission, a quick diagnosis of CS was made based on clinical and biochemical features and the patient was treated urgently using high dose oral metyrapone thus allowing delays in surgery and rapidly improving the patient’s clinical condition. This resulted in the treatment of hyperglycaemia, hypokalaemia and hypertension reducing cardiovascular risk and likely risk for infection. Observing COVID-19 pandemic international guidelines to treat patients with CS has shown to be effective and offers endocrinologists an option to manage these patients adequately in difficult times. Learning points This case report highlights the importance of having a low threshold for suspicion and investigation for Cushing’s syndrome in a patient with neutrophilia and hypokalaemia, recently diagnosed with type 2 diabetes especially in someone with catabolic features of the disease irrespective of losing weight. It also supports the use of alternative methods of approaching the diagnosis and treatment of Cushing’s syndrome during a pandemic as indicated by international protocols designed specifically for managing this condition during Covid-19.

Long-term morphological, hormonal, and clinical follow-up in a single unit on 118 patients with adrenal incidentalomas

2010 ◽  
Vol 162 (4) ◽  
pp. 779-785 ◽  
Author(s):  
R Giordano ◽  
E Marinazzo ◽  
R Berardelli ◽  
A Picu ◽  
M Maccario ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cumulative Risk ◽  
Cushing's Syndrome ◽  
Endocrine Function ◽  
Adrenal Incidentalomas ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Significant Clinical Improvement

ObjectiveTo evaluate long-term morphological, functional, and clinical outcome in adrenal incidentalomas.Design and methodsA total of 118 patients (77 F and 47 M; age 62.3±1.0 years) with adrenal incidentalomas were evaluated at baseline and followed-up for median 3 years (range 1–10 years) by clinical, biochemical, hormonal, and morphological evaluation. Among them, six patients with diagnosis of subclinical Cushing's syndrome (SCS) underwent surgery.ResultsAt entry, 86% (n=102) of tumors were nonfunctioning (NF) and 14% (n=16) showed SCS. Comparing NF with SCS patients, a significantly higher percentage of dyslipidemia was found in the group of SCS patients (50 vs 23%,P=0.033). During follow-up, adrenal function remained normal in all NF patients, none of them developed subclinical or overt endocrine disease. The cumulative risk of mass enlargement was globally low (25%), but progressive up to 8 years. SCS was confirmed in all patients, and none of them shifted to overt Cushing's syndrome. The cumulative risk of developing metabolic–cardiovascular abnormalities was globally low (22%), but progressive up to 8 years and new diseases were recorded in the group of NF patients only (three patients with dyslipidemia, four with impaired fasting glucose/impaired glucose tolerance, and three with diabetes mellitus). SCS patients who underwent surgery did not show any significant clinical improvement.ConclusionsThe risk of mass enlargement, hormonal, and metabolic impairment over time is globally low. Conservative management seems to be appropriate, but further prospective studies are needed to establish the long-term outcome of such patients, especially for metabolic status, cardiovascular risk profile and their relationship with endocrine function.

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