scholarly journals Olfactory neuroblastoma (esthesioneuroblastoma) presenting as ectopic ACTH syndrome: always follow your nose

2019 ◽  
Vol 2019 ◽  
Author(s):  
Karen Decaestecker ◽  
Veerle Wijtvliet ◽  
Peter Coremans ◽  
Nike Van Doninck
Keyword(s):  
Pituitary Gland ◽  
Cushing’S Syndrome ◽  
Olfactory Neuroblastoma ◽  
Cushing's Syndrome ◽  
Ectopic Acth Syndrome ◽  
Tumour Mass ◽  
List Type ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Late Night

Summary ACTH-dependent hypercortisolism is caused by an ectopic ACTH syndrome (EAS) in 20% of cases. We report a rare cause of EAS in a 41-year-old woman, presenting with clinical features of Cushing’s syndrome which developed over several months. Biochemical tests revealed hypokalemic metabolic alkalosis and high morning cortisol and ACTH levels. Further testing, including 24-hour urine analysis, late-night saliva and low-dose dexamethasone suppression test, confirmed hypercortisolism. An MRI of the pituitary gland was normal. Inferior petrosal sinus sampling (IPSS) revealed inconsistent results, with a raised basal gradient but no rise after CRH stimulation. Additional PET-CT showed intense metabolic activity in the left nasal vault. Biopsy of this lesion revealed an unsuspected cause of Cushing’s syndrome: an olfactory neuroblastoma (ONB) with positive immunostaining for ACTH. Our patient underwent transnasal resection of the tumour mass, followed by adjuvant radiotherapy. Normalisation of cortisol and ACTH levels was seen immediately after surgery. Hydrocortisone substitution was started to prevent withdrawal symptoms. As the hypothalamic–pituitary–axis slowly recovered, daily hydrocortisone doses were tapered and stopped 4 months after surgery. Clinical Cushing’s stigmata improved gradually. Learning points: Ectopic ACTH syndrome can originate from tumours outside the thoracoabdominal region, like the sinonasal cavity. The diagnostic accuracy of IPSS is not 100%: both false positives and false negatives may occur and might be due to a sinonasal tumour with ectopic ACTH secretion. Olfactory neuroblastoma (syn. esthesioneuroblastoma), named because of its sensory (olfactory) and neuroectodermal origin in the upper nasal cavity, is a rare malignant neoplasm. It should not be confused with neuroblastoma, a tumour of the sympathetic nervous system typically occurring in children. If one criticises MRI of the pituitary gland because of ACTH-dependent hypercortisolism, one should take a close look at the sinonasal field as well.

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.

scholarly journals Cushing’s Syndrome: Important Issues in Diagnosis and Management

2006 ◽  
Vol 91 (10) ◽  
pp. 3746-3753 ◽  
Author(s):  
James W. Findling ◽  
Hershel Raff
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Evidence Synthesis ◽  
Somatostatin Receptor ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Late Night ◽  
Recent Monograph

Abstract Context: The diagnosis, differential diagnosis, and treatment of Cushing’s syndrome are challenging problems in clinical endocrinology. We focus on critical questions addressing screening for Cushing’s syndrome, differentiation of Cushing’s subtypes, and treatment options. Evidence Acquisition: Ovid’s MEDLINE (1996 through April 2006) was used to search the general literature. We also relied on previously published reviews and a recent monograph and cite a mix of primary articles and recent reviews. Evidence Synthesis: Although this article represents our opinion, it draws heavily on a recent consensus statement from experts in the field and a recent monograph on Cushing’s syndrome. Conclusions: We concluded that: 1) measurement of late-night or bedtime salivary cortisol is a useful approach to screen for Cushing’s syndrome; 2) measurement of suppressed plasma ACTH by immunometric assay is useful to differentiate ACTH-dependent and -independent Cushing’s syndrome; 3) inferior petrosal sinus sampling for ACTH should be performed in patients with ACTH-dependent hypercortisolism in whom a pituitary magnetic resonance imaging is normal or equivocal (in the absence of a pituitary ACTH gradient, prolactin levels should be measured to confirm the integrity of venous sampling); 4) computed tomography of the chest and abdomen and somatostatin receptor scintigraphy should be performed in patients with the occult ectopic ACTH syndrome; and 5) patients with Cushing’s disease should be referred to a neurosurgeon with extensive experience operating on corticotroph microadenomas. Bilateral laparoscopic adrenalectomy should be considered in patients with Cushing’s disease who fail therapies directed at the pituitary.

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.

scholarly journals A case of severe ectopic ACTH syndrome from an occult primary – diagnostic and management dilemmas

2015 ◽  
Vol 2015 ◽  
Author(s):  
Harish Venugopal ◽  
Katherine Griffin ◽  
Saima Amer
Keyword(s):  
Cushing’S Syndrome ◽  
Primary Tumour ◽  
Cushing's Syndrome ◽  
Bilateral Adrenalectomy ◽  
Ectopic Acth Syndrome ◽  
High Dose ◽  
List Type ◽  
Ectopic Acth ◽  
Alcohol Ablation ◽  
Life Threatening

Summary Resection of primary tumour is the management of choice in patients with ectopic ACTH syndrome. However, tumours may remain unidentified or occult in spite of extensive efforts at trying to locate them. This can, therefore, pose a major management issue as uncontrolled hypercortisolaemia can lead to life-threatening infections. We present the case of a 66-year-old gentleman with ectopic ACTH syndrome from an occult primary tumour with multiple significant complications from hypercortisolaemia. Ectopic nature of his ACTH-dependent Cushing's syndrome was confirmed by non-suppression with high-dose dexamethasone suppression test and bilateral inferior petrosal sinus sampling. The primary ectopic source remained unidentified in spite of extensive anatomical and functional imaging studies, including CT scans and Dotatate-PET scan. Medical adrenolytic treatment at maximum tolerated doses failed to control his hypercortisolaemia, which led to recurrent intra-abdominal and pelvic abscesses, requiring multiple surgical interventions. Laparoscopic bilateral adrenalectomy was considered but decided against given concerns of technical difficulties due to recurrent intra-abdominal infections and his moribund state. Eventually, alcohol ablation of adrenal glands by retrograde adrenal vein approach was attempted, which resulted in biochemical remission of Cushing's syndrome. Our case emphasizes the importance of aggressive management of hypercortisolaemia in order to reduce the associated morbidity and mortality and also demonstrates that techniques like percutaneous adrenal ablation using a retrograde venous approach may be extremely helpful in patients who are otherwise unable to undergo bilateral adrenalectomy. Learning points Evaluation and management of patients with ectopic ACTH syndrome from an unidentified primary tumour can be very challenging. Persisting hypercortisolaemia in this setting can lead to debilitating and even life-threatening complications and hence needs to be managed aggressively. Bilateral adrenalectomy should be considered when medical treatment is ineffective or poorly tolerated. Percutaneous adrenal ablation may be considered in patients who are otherwise unable to undergo bilateral adrenalectomy.

scholarly journals Severe Cushing’s syndrome and bilateral pulmonary nodules: beyond ectopic ACTH

2017 ◽  
Vol 2017 ◽  
Author(s):  
Carlos Tavares Bello ◽  
Emma van der Poest Clement ◽  
Richard Feelders
Keyword(s):  
Cushing’S Syndrome ◽  
Prolonged Exposure ◽  
Opportunistic Infections ◽  
Cushing's Syndrome ◽  
List Type ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Thrombotic Risk ◽  
Ectopic Acth Secretion ◽  
Increased Risk

Summary Cushing’s syndrome is a rare disease that results from prolonged exposure to supraphysiological levels of glucocorticoids. Severe and rapidly progressive cases are often, but not exclusively, attributable to ectopic ACTH secretion. Extreme hypercortisolism usually has florid metabolic consequences and is associated with an increased infectious and thrombotic risk. The authors report on a case of a 51-year-old male that presented with severe Cushing’s syndrome secondary to an ACTH-secreting pituitary macroadenoma, whose diagnostic workup was affected by concurrent subclinical multifocal pulmonary infectious nodules. The case is noteworthy for the atypically severe presentation of Cushing’s disease, and it should remind the clinician of the possible infectious and thrombotic complications associated with Cushing’s syndrome. Learning points: Severe Cushing’s syndrome is not always caused by ectopic ACTH secretion. Hypercortisolism is a state of immunosuppression, being associated with an increased risk for opportunistic infections. Infectious pulmonary infiltrates may lead to imaging diagnostic dilemmas when investigating a suspected ectopic ACTH secretion. Cushing’s syndrome carries an increased thromboembolic risk that may even persist after successful surgical management. Antibiotic and venous thromboembolism prophylaxis should be considered in every patient with severe Cushing’s syndrome.

scholarly journals Occult Carcinoid Causes Cushing’s Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A594-A595
Author(s):  
Sabrina Meftali ◽  
Rebecca Unterborn ◽  
Amanda Gifford ◽  
Bankim Bhatt
Keyword(s):  
Weight Gain ◽  
Carcinoid Tumor ◽  
Neuroendocrine Tumors ◽  
Cushing’S Syndrome ◽  
Pulmonary Nodule ◽  
Cushing's Syndrome ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Ectopic Cushing’S Syndrome

Abstract Introduction: Lung neuroendocrine tumors (NETs) are a common cause of ectopic ACTH-secretion. Only 3% of NETs cause Cushing’s syndrome1; the majority are small and may be radiographically occult. Additionally, the responses to dexamethasone, metyrapone, and oCRF can be indistinguishable from that observed in pituitary Cushing’s disease2. These challenges lead to misdiagnosis and unnecessary procedures. Case Description: 45-year-old male presented for resection of right-sided pulmonary carcinoid tumor. He was diagnosed with Cushing’s syndrome in 2011 when he experienced uncontrolled hypertension and excessive weight gain with elevations in cortisol and ACTH levels. He underwent transsphenoidal pituitary resection in May 2011 for a possible pituitary microadenoma. Post-operative worsening hypertension, weight gain, and striae led to bilateral adrenalectomy in November 2011, complicated by retroperitoneal hemorrhage and resuscitation-induced pulmonary edema. On chest CT in early 2012, an 8 mm incidental right pulmonary nodule was documented. 8 years later, chest imaging for mild COVID-19 infection again revealed a right-sided pulmonary nodule. He underwent CT-guided biopsy of the nodule in July 2020 with pathology demonstrating carcinoid histology. Right lower lobectomy was performed. Pre-operative ACTH was 1673 pg/mL (normal: 10-60 pg/mL) and post-operative ACTH was 16 pg/mL. The resected tumor stained positive for ACTH, confirming that carcinoid tumor was the source of Cushing’s for the past decade. Conclusion: The diagnosis of ectopic Cushing’s syndrome can be elusive, leading to surgeries with significant morbidity, as seen in our patient. In one retrospective review, 14% of patients with Cushing’s had transsphenoidal resection before they were diagnosed with an ectopic source3. Ectopic Cushing’s syndrome can be a challenging diagnosis to make and a multidisciplinary approach with close collaboration between endocrinologist, radiologist, surgeon and pathologist may increase the diagnosis accuracy. Citations: 1Kamp, K, Alwani, R A, Korpershoek, E, Franssen, G., de Herder, W W, & Feelders, R A. (2016). Prevalence and clinical features of the ectopic ACTH syndrome in patients with gastroenteropancreatic and thoracic neuroendocrine tumors, European Journal of Endocrinology, 174(3), 271-280. Retrieved Jan 15, 2021, from https://eje.bioscientifica.com/view/journals/eje/174/3/271.xml 2Malchoff CD, Orth DN, Abboud C, Carney JA, Pairolero PC, Carey RM. Ectopic ACTH syndrome caused by a bronchial carcinoid tumor responsive to dexamethasone, metyrapone, and corticotropin-releasing factor. The American Journal of Medicine. 1988;84(4):760-764. doi:10.1016/0002-9343(88)90116-7 3Ioannis Ilias, David J. Torpy, Karel Pacak, Nancy Mullen, Robert A. Wesley, Lynnette K. Nieman,Cushing’s Syndrome Due to Ectopic Corticotropin Secretion: Twenty Years’ Experience at theNational Institutes of Health, The Journal of Clinical Endocrinology & Metabolism, Volume 90, Issue8, 1 August 2005, Pages 4955–4962, https://doi.org/10.1210/jc.2004-2527

Cushing’s syndrome in infancy due to ectopic ACTH secretion by a sacro-coccygeal teratoma

2017 ◽  
Vol 30 (4) ◽  
Author(s):  
Marta Rydzewska ◽  
Maryna Krawczuk-Rybak ◽  
Adrianna Zajkowska ◽  
Natalia Jurczuk ◽  
Dariusz Polnik ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Current Control ◽  
Immature Teratoma ◽  
Ectopic Acth Syndrome ◽  
Normal Range ◽  
Antihypertensive Medications ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Currarino Syndrome

AbstractBackground:Adenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome in infancy is extremely rare. We describe the case of a sacro-coccygeal ectopic ACTH-secreting immature teratoma in an infant who also presented the triad of defects characteristic of Currarino syndrome.Case presentation:A girl was born with a large immature teratoma in the sacro-coccygeal region associated with anal atresia. At the age of 7 days, the concentration of α-fetoprotein (AFP) was above the age-specific normal range. Two non-radical surgical excisions of the tumour were performed. At the age of 7 months, she developed polyphagia, acne, hirsutism, hypertension and hypokalemia with elevated ACTH and absence of serum cortisol circadian rhythm. Immunostaining of tumour tissue showed ACTH-immunoreactive cells. Due to unsuccessful therapy with ketoconazole and resistance to antihypertensive medications [blood pressure (BP) 210/160 mmHg], metyrapone was administered, which controlled her ACTH and cortisol levels in the normal range. Following further removal of tumour bulk after three operations during the first year of life, there was a decrease of BP to normal values.Conclusions:A rare case of ectopic ACTH syndrome causing Cushing’s syndrome in infancy in the context of Currarino syndrome is reported. Radical surgery has resulted in excision of the tumour and current control of Cushing’s syndrome.

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 A rare cause of severe Cushing’s syndrome

2020 ◽  
Vol 2020 ◽  
Author(s):  
Shamaila Zaman ◽  
Bijal Patel ◽  
Paul Glynne ◽  
Mark Vanderpump ◽  
Ali Alsafi ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Primary Tumour ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
List Type ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Baseline Serum ◽  
Ectopic Acth Secretion ◽  
Alpha Blockade

Summary Ectopic adrenocorticotropic hormone (ACTH) production is an uncommon cause of Cushing’s syndrome and, rarely, the source can be a phaeochromocytoma. A 55-year-old man presented following an episode of presumed gastroenteritis with vomiting and general malaise. Further episodes of diarrhoea, joint pains and palpitations followed. On examination, he was hypertensive with no clinical features to suggest hypercortisolaemia. He was subsequently found to have raised plasma normetanephrines of 3.98 nmol/L (NR <0.71) and metanephrines of 0.69 nmol/L (NR <0.36). An adrenal CT showed a 3.8 cm right adrenal nodule, which was not MIBG-avid but was clinically and biochemically consistent with a phaeochromocytoma. He was started on alpha blockade and referred for right adrenalectomy. Four weeks later, on the day of admission for adrenalectomy, profound hypokalaemia was noted (serum potassium 2.0 mmol/L) with non-specific ST-segment ECG changes. He was also diagnosed with new-onset diabetes mellitus (capillary blood glucose of 28 mmol/L). He reported to have gained weight and his skin had become darker over the course of the last 4 weeks. Given these findings, he underwent overnight dexamethasone suppression testing, which showed a non-suppressed serum cortisol of 1099 nmol/L. Baseline serum ACTH was 273 ng/L. A preliminary diagnosis of ectopic ACTH secretion from the known right-sided phaeochromocytoma was made and he was started on metyrapone and insulin. Surgery was postponed for 4 weeks. Following uncomplicated laparoscopic adrenalectomy, the patient recovered with full resolution of symptoms. Learning points: Phaeochromocytomas are a rare source of ectopic ACTH secretion. A high clinical index of suspicion is therefore required to make the diagnosis. Ectopic ACTH secretion from a phaeochromocytoma can rapidly progress to severe Cushing’s syndrome, thus complicating tumour removal. Removal of the primary tumour often leads to full recovery. The limited literature suggests that the presence of ectopic Cushing’s syndrome does not appear to have any long-term prognostic implications.

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.

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