Ectopic adrenocorticotropic hormone syndrome originating from retroperitoneal paraganglioma: one case report and literature review / 中国医师杂志

Objective:To present the clinical characteristics and treatment on patients with ectopic adrenocorticotropic hormone(ACTH) syndrome (EAS) caused by the retroperitoneal paraganglioma.Methods:The clinical data of a case of EAS caused by retroperitoneal paraganglioma were analyzed retrospectively, and the related literature at home and abroad was reviewed.Results:The 53-year-old female patient was admitted to endocrinology department due to a fifteen-year history of hypertension, accompanied by fatigue for three months, headache and dizziness for one month. The laboratory data demonstrated severe hypokalemia, high level of serum and urinary cortisol, while the ACTH level remained unsuppressed. The 24 h urinary vanillyl mandelic acid (VMA) and serum free methoxyepinephrine (MNs) level were elevated. The abdominal computed tomographic scan suggested a retroperitoneal mass next to the abdominal aorta. After the retroperitoneal tumor resection was performed, immunohistochemical staining of the tumor revealed Syn (+ ), CgA (+ ), ACTH (focal + ). By the retrospective analysis of 22 similar cases from 16 papers and the case summarized above, we found that most patients with EAS caused by the paraganglioma could demonstrate the typical clinical features of Cushing′s syndrome, while lack of the manifestation of paraganglioma. Therefore, preoperative preparations for paraganglioma were usually neglected.Conclusions:Ectopic ACTH syndrome (EAS) originating from paraganglioma is very rare. To improve the diagnosis rate, examination for catecholamine, MNs and 24 h urinary VMA before surgery in patients with EAS is suggested. Considering surgical resection as the optimal treatment, comprehensive preoperative preparations for both paraganglioma and Cushing′s syndrome are significant. A genetic test for pheochromocytoma/ paraganglioma and lifelong postoperative follow-up are also recommend.

Adrenocorticotropic Hormone-Secreting Esthesioneuroblastoma with Ectopic Cushing's Syndrome

Esthesioneuroblastoma as a source of ectopic Cushing's syndrome is rare, and to the best of our knowledge, only 20 cases have been reported worldwide. A 46-year-old healthy man visited a local clinic for general weakness and hyposmia, and underwent examination with serial endocrinological workup and brain imaging. ⁶⁸Gallium-DOTA-TOC positron emission tomography scan was helpful where diagnosis of sellar MRI and inferior petrosal sinus sampling were discordant. Combined transcranial and endoscopic endonasal approach surgery was performed, and a diagnosis of esthesioneuroblastoma was given.

A case of ectopic adrenocorticotropic hormone syndrome caused by paraganglioma mimic dermatomyositis / 中华风湿病学杂志

Objective@#To improve the recognition of ectopic adrenocorticotropic hormone syndrome.@*Methods@#The diagnosis and treatment of a 43 years old female patient with multiorgan involvement mimic dermatomyositis was analyzed and discussed.@*Results@#The patient presented with fatigue, edema, skin pigmentation, neuropsychiatric abnormalities, hypertension, hypokalemia, hyperglycemia and other systemic involvement, was finally diagnosed with ectopic adrenocorticotropic hormone syndrome caused by paraganglioma of the anterior mediastinum. After surgical removal of the tumor, her clinical symptoms immediately relieved, meanwhile related hormone levels returned to normal.@*Conclusion@#Although paraganglioma-induced ectopic adrenocorticotropic hormone syndrome is rare in clinical practice, more attention should be paid to this specific situation.

A case of ectopic adrenocor ticotropic hormone syndrome caused by paraganglioma mimic dermatomyositis / 中华风湿病学杂志

Objective To improve the recognition of ectopic adrenocorticotropic hormone syndrome.Methods The diagnosis and treatment of a 43 years old female patient with multiorgan involvement mimic dermatomyositis was analyzed and discussed.Results The patient presented with fatigue,edema,skin pigmentation,neuropsychiatric abnormalities,hypertension,hypokalemia,hyperglycemia and other systemic involvement,was finally diagnosed with ectopic adrenocorticotropic hormone syndrome caused by paragang-lioma of the anterior mediastinum.After surgical removal of the tumor,her clinical symptoms immediately relieved,meanwhile related hormone levels returned to normal.Conclusion Although paraganglioma-induced ectopic adrenocorticotropic hormone syndrome is rare in clinical practice,more attention should be paid to this specific situation.

Surgery treatment of ectopic adrenocorticotrophic hormone syndrome / 北京大学学报(医学版)

Objective: To investigation the diagnosis and treatment of ectopic adrenocorticotrophic hormone (ACTH) syndrome.Methods: The clinical characters of 57 cases of ecotopic ACTH syndrome from Jan.1996 to Dec.2016 were collected and analyzed.The 57 cases included 32 males and 25 females.The age ranged from 11 to 68 years (average 32 years).ACTH levels significantly increased from 16.5 to 365.6 pmol/L, with average 77.6 pmol/L (normal range <10.1 pmol/L).The pituitary MRI did not found lesions.The CT showed that their bilateral adrenal glands diffused small nodular changes or nodular hyperplasia.The 57 cases were divided into 3 groups according to different treatment options.In the study, 25 ectopic ACTH syndrome cases (44%) were group A, without identified source of ectopic hormone, were treated with bilateral or unilateral adrenalectomy due to the severity of the disease and difficulty of operation.Group B was composed of 16 cases (28%) diagnosed as ectopic ACTH syndrome by finding ectopic ACTH tumors and surgical resection.Group C included 16 cases (28%) with nonsurgical therapy.Different treatment results and prognosis were analyzed.Results: In the study, 40 cases of the 57 had been followed up for 6 months to 10 years.In group A, of the 25 cases with bilateral or unilateral adrenalectomy, 4 died of diabetes and severe pulmonary infection, 18 survived, and 3 were lost to the follow-up, and the survival rate was 81% (18/22).In group B, of the 16 cases with radical tumor resection, 5 died of tumor recurrence 0.5-6.0 years after operation, 3 survived, and 8 were lost to the follow-up, and the survival rate was 37.5% (3/8).In group C, of the 16 non-operation patients, 4 with radiotherapy and chemotherapy died of metastases, diabetes or pulmonary infection, 6 with chemotherapy died of pulmonary infection within 1 year and the others were lost to the follow-up, and the survival rate was 0.Conclusion: Ectopic ACTH syndrome is difficult to treat.Adrenalectomy is effective for the management of ectopic ACTH syndrome, especially for those patients with severe Cushing''s syndrome, but the primary tumor can not be located.

Síndrome de Cushing ectópico: revisión de la literatura / Ectopic Cushing Syndrome: A literature review

El síndrome de Cushing es una enfermedad muy rara pero asociada a una morbimortalidad significativa. Se clasifica como dependiente de la hormona adrenocorticotrópica (ACTH: tumores hipofisiarios y ectópicos) o independiente de ACTH (lesiones de origen adrenal). En la mayoría de los casos, las lesiones responsables del síndrome corresponden a tumores hipofisiarios, seguida de lesiones adrenales y por último de tumores ectópicos (5-15% de todos los casos). En este artículo se hará una revisión de los aspectos epidemiológicos, clínicos, diagnósticos y terapéuticos más importantes de los tumores ectópicos causantes del síndrome de Cushing.

Cushing's syndrome is a very rare disease associated with significant morbidity and mortality. It is classified as adrenocorticotropic hormone (ACTH) dependent (Pituitary and ectopic tumors) or ACTH independent (lesions of adrenal origin). In most cases, pituitary tumors are responsible for the Cushing's syndrome, followed by adrenal lesions and finally by ectopic tumors (5-15% of all cases). This article describes the most important epidemiological, clinical, diagnostic and therapeutic aspects of ectopic tumors causing Cushing's syndrome.

Ectopic ACTH syndrome caused by pulmonary carcinoid tumor mimicking long-standing sclerosing hemangioma

No abstract available.

The value of X-ray guided desmopressin stimulated bilateral inferior petrosal sinus sampling in diagnosing the recurrence of ACTH dependent Cushing disease or ineffectiveness of surgery or radiotherapy / 中华放射学杂志

Objective To investigate the value of X-ray guided desmopressin (DDAVP) stimulated bilateral inferior petrosal sinus sampling (IPSS) in diagnosing the recurrence of ACTH dependent Cushing disease or ineffectiveness after surgery or radiotherapy. Methods Retrospective analyses of patients with recurrent ACTH dependent Cushing disease (31 cases) or ineffective (3 cases) treatment after surgery or radiotherapy from January 2013 to October 2014 in our hospital was conducted. Bilateral inferior petrosal sinus angiography showed the same side of the cavernous sinus to prove successful intubation. The cases with discontinuous of the inferior petrosal sinus and cavernous sinus were excluded by this study. Finally, there were 34 cases of the patients in this study. Diagnosis was based on the ratio of ACTH level in IPS to peripheral vein after desmopressin test.The gradient≥2 at baseline or gradient≥3 after desmopressin test suggested the sources were in the pituitary. Diagnosis was confirmed by gold standard to investigate the value of X-ray guided desmopressin (DDAVP) stimulated bilateral IPSS. Results The IPS gradient≥2 at baseline or gradient≥3 after desmopressin test suggested the sources were in the pituitary in 30 patients. A total of 22 (22/30) patients underwent surgery with a final diagnosis of ACTH adenoma. The symptoms were obviously relieved in 8 (8/30) cases after sellar area gamma knife treatment and lesions were confirmed in the pituitary. IPS gradient<2 at baseline or gradient<3 after desmopressin test was found in 4 cases. One case (1/4) was found to have for ACTH adenoma after pituitary surgery. The other 3 cases (3/4) were confirmed to have lung carcinoid and clinical symptom alleviated after surgery. The sensitivity of desmopressin stimulated IPSS was 96.8%, the specificity was 100%, and the accuracy was 97.1%. Conclusion Desmopressin stimulated IPSS is an effective diagnostic procedure in diagnosing ACTH dependent Cushing disease recurrence or ineffectiveness after surgery or radiotherapy.

Adrenocorticotropic hormone (ACTH)-producing pheochromocytoma presented as Cushing syndrome and complicated by invasive aspergillosis / 영남의대학술지

Adrenocorticotropic hormone (ACTH)-producing pheochromocytoma has been rarely reported, whereas only a few cases of Cushing syndrome accompanied by opportunistic infections have been reported. We experienced a patient with pheochromocytoma with ectopic Cushing syndrome complicated by invasive aspergillosis. A 35-year-old woman presented with typical Cushingoid features. Her basal plasma cortisol, ACTH, and 24-hour urine free cortisol levels were significantly high, and 24-hour urine metanephrine and catecholamine levels were slightly elevated. The endogeneous cortisol secretion was not suppressed by either low- or high-dose dexamethasone. Abdominal computed tomography (CT) revealed a heterogeneous enhancing mass measuring approximately 2.5 cm in size in the left adrenal gland. No definitive mass lesion was observed on sellar magnetic resonance imaging. On fluorine-18 fluorodeoxyglucose positron emission tomography/CT, a hypermetabolic nodule was observed in the left upper lung. Thus, we performed a percutaneous needle biopsy, which revealed inflammation, not malignancy. Thereafter, we performed a laparoscopic left adrenalectomy, and its pathologic finding was a pheochromocytoma with positive immunohistostaining for ACTH. After surgery, the biochemistry was normalized, but the clinical course was fatal despite intensive care because of the invasive aspergillosis that included the lungs, retina, and central nervous system.

A Case of Ectopic Adrenocorticotropic Hormone Syndrome in Small Cell Lung Cancer / 결핵및호흡기질환

Small cell lung cancer (SCLC), which originated from neuroendocrine tissue, can develop into paraneoplastic endocrine syndromes, such as Cushing syndrome, because of an inappropriate secretion of ectopic adrenocorticotropic hormone (ACTH). This paraneoplastic syndrome is known to be a poor prognostic factor in SCLC. The reason for poor survival may be because of a higher risk of infection associated with hypercortisolemia. Therefore, early detection and appropriate treatment for this syndrome is necessary. But the diagnosis is challenging and the source of ACTH production can be difficult to identify. We report a 69-year-old male patient who had severe hypokalemia, metabolic alkalosis, and hypertension as manifestations of an ACTH-secreting small cell carcinoma of the lung. He was treated with ketoconazole and spironolactone to control the ACTH dependent Cushing syndrome. He survived for 15 months after chemotherapy, which is unusual considering the poor outcome of the ectopic ATH syndrome associated with SCLC.

Secreción ectópica de ACTH: Presentación infrecuente de un estesioneuroblastoma / An Infrequent Presentation of Esthesioneuroblastoma with Ectopic ACTH Syndrome

Introducción: El estesioneuroblastoma es un tumor derivado de los neuroblastos del epitelio respiratorio neuroectodérmico. Representa entre el 3 al 6 % de los tumores intranasales. La secreción ectópica de Hormona Adrenocorticotrofina (ACTH) es la causa del 10 al 20 % de Síndrome de Cushing dependiente de ACTH, siendo el estesioneuroblastoma una rara causa de secreción ectópica de ACTH. Presentación del caso: Paciente de sexo femenino de 63 años que consulta por mareos, náuseas, debilidad muscular, y rinorrea de dos años de evolución tratada con corticoides tópicos en forma prolongada. Al examen físico mostraba fenotipo Cushing característico. El laboratorio confirmó valores de ACTH veinte veces por encima de los rangos normales. En IRM cerebral se evidencia lesión expansiva en región etmoidal con compromiso de órbita y base de cráneo. Se resuelve tratamiento quirúrgico ante la necesidad de descompresión tumoral y tratamiento médico para hipercortisolismo en el período pre y posquirúrgico. La anatomía patológica informó proliferación neoplásica maligna de origen neurogénico y las pruebas inmunohistoquímicas confirmaron positividad para ACTH. Comentario: El Síndrome de Cushing por secreción ectópica de ACTH a partir de estesioneuroblastoma es muy poco frecuente, reportándose solo once casos a la fecha en la literatura médica indexada. El tratamiento es complejo y requiere de equipo interdisciplinario. Rev Argent Endocrinol Metab 51:192-196, 2014 Los autores declaran no poseer conflictos de interés.

Introduction: Esthesioneuroblastoma is a tumor originating from the neuroblasts in the neuroectodermal olfactory epithelium. It accounts for 3 % to 6 % of nasal tumors. Adrenocorticotropic hormone (ACTH) ectopic secretion is the cause for 10 % to 20 % of ACTH-dependent Cushing Syndrome cases. Esthesioneuroblastoma constitutes a rare cause of ectopic ACTH secretion. Case presentation: A 63 year-old female patient presented with dizziness, nausea, muscle weakness, and rhinorrhea of two-year duration under long-term treatment with topical corticosteroids. On physical examination, she showed typical Cushingoid phenotype. Brain MRI revealed an expanding lesion in the ethmoid area involving the orbit and the cranial base. Sub­maxillary metastasis was also detected. Lab tests confirmed ACTH values 20-fold above normal. The patient underwent treatment for hypercortisolism prior to surgery. Surgical treatment was prompted by the need to decompress the tumor. Comment: Esthesioneuroblastoma is a rare tumor. Although approximately 1,000 cases have been published in the last 20 years, only eleven of them were due to ACTH secretion. Treatment is complex and requires an interdisciplinary team. Rev Argent Endocrinol Metab 51:192-196, 2014 No financial conflicts of interest exist.

Síndrome de Cushing secundario a carcinoma medular de tiroides: descripción de un caso y revisión de la literatura / Cushing syndrome secondary to a medullary thyroid carcinoma: report of a case and review of the literature

Se describe el caso de una paciente evaluada a los 29 años por un tumor tiroideo, clasificado inicialmente como un carcinoma insular de tiroides; presentaba gran compromiso tumoral en cuello, mediastino y pulmones. Tres años después de recibir tratamiento específico para su neoplasia tiroidea, desarrolló un síndrome de Cushing y lesiones hepáticas sugestivas de metástasis del tumor primario. Al revisar la patología se encontró, en lo que inicialmente se había clasificado como un carcinoma insular, un carcinoma medular de tiroides productor de hormona adrenocorticotrópica (ACTH). Con base en este caso, se presenta una revisión de la literatura médica sobre el tema.

Cushing syndrome secondary to a medullary thyroid carcinoma: report of a case and review of the literature We report the case of a 29-year old female who was evaluated because of a thyroid tumor. The initial pathological classification was an insular thyroid carcinoma. There was strong involvement in the neck, mediastinum and lungs. Three years after receiving specific therapy for her thyroid neoplasia, she developed a Cushing syndrome and liver lesions suggestive of metastases from the primary tumor. A review of the previous pathological material revealed a medullary thyroid carcinoma producing ACTH, instead of the insular carcinoma. Based on this case a review of the literature is presented.

Medullary Thyroid Carcinoma with Ectopic Adrenocorticotropic Hormone Syndrome

Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.

Cushing's Syndrome Caused by an ACTH-Producing Neuroendocrine Carcinoma of the Gallbladder / 대한내과학회지

Neuroendocrine tumors of the gallbladder are rare, and typically found incidentally after a cholecystectomy. Few data are available on adrenocorticotrophic hormone (ACTH)-producing neuroendocrine tumors originating specifically from the gallbladder. We experienced the case of a patient with a gallbladder mass who presented with Cushing's syndrome, who was subsequently diagnosed as an ACTH-producing neuroendocrine carcinoma of the gallbladder. Despite being rare, hormone-producing neuroendocrine tumors should be part of the differential diagnosis in patients with Cushing's syndrome.

Ectopic Adrenocorticotropic Hormone Syndrome Associated With Thymic Carcinoma in Old Age

A 70-year-old woman who developed a moon face was hospitalized. At admission, adrenocorticotropic hormone (ACTH) and serum cortisol levels were elevated. A high-dose dexamethasone suppression test demonstrated that cortisol secretion was uninhibited. Furthermore, chest computed tomography revealed an anterior mediastinal mass. On the basis of these results, ectopic ACTH syndrome was diagnosed and complete resection of the thymic tumor was performed. Histological examination revealed large cell neuroendocrine carcinoma of the thymus and positive immunoreactivity for ACTH. However, despite complete excision of the thymic tumor, ACTH and serum cortisol levels were high. Therefore, we investigated whether the lesion had recurred or metastasized; however, the results were inconclusive. Finally, laparoscopic bilateral adrenalectomy was performed to control the hypercortisolemia. After the surgery, the serum cortisol level was well-controlled and the general condition of the patient was good.

Approach to the patients with ectopic ACTH syndrome / 中华内分泌代谢杂志

Clinical features of 2 cases of ectopic ACTH syndrome with manifestation of severe hypercortisonism are described with the aim of exploring effective therapies.

Approach to the patient with ectopic ACTH syndrome caused by adrenal pheochromocytoma : diagnosis and treatment / 中华内分泌代谢杂志

Ectopic ACTH syndrome caused by adrenal pheochromocytoma is very rare.A case was herewith reported and the domestic and foreign literatures were reviewed.The correct diagnosis of the syndrome depends on clinical,biochemical,hormonal,radiographic,pathological investigations,as well as tumor immunohistochemistry for final comprehensive judgments.

Ectopic ACTH Syndrome and Severe Hypokalemia Associated with Suspicious Pancreatic Malignancy: A Case Report / 대한신장학회지

A 72-year-old woman had a 1-month history of general weakness. Previously, after rectal cancer was treated with a low anterior resection, 12 cycles of adjuvant chemotherapy with 5-fluorouracil plus leucovorin was undergone. Follow-up examination showed no evidence of recurrence. However, she suffered from general weakness attributable to hypokalemia, which was refractory to potassium replacement therapy. After further work-up of the hypokalemia, Cushing's syndrome and ectopic adrenocorticotropic hormone (ACTH) syndrome were diagnosed from the laboratory findings that included a markedly elevated level of 24-hour urine-free cortisol. Several imaging studies revealed masses of the pancreas and other organs, which was more likely to be pancreatic cancer. This case is interesting in that cancerous lesions were identified during work-up of hypokalemia.

The clinical features of ectopic ACTH syndrome: a report of 16 cases / 中华内科杂志

Objectives To improve the diagnostic and therapeutic ability of ectopic ACTH syndrome by analysing its clinical features.Methods Sixteen cases of ectopic ACTH syndrome diagnosed in Chinese PLA General Hospital from 2000 to 2009 were analyzed retrospectively.Results ( 1 ) The main causes of ectopic ACTH syndrome were lung tumor and thymic carcinoid;(2) Abnormal glucose metabolism, hypertension, hypokalemia and edema of both lower limbs were the most common clinical symptoms;(3) Laboratory examination showed a significant increase of serum cortisol, adrenocorticotropic hormone(ACTH) and 24 h urinary free cortisol (24hUFC) together with severe hypokalemia and alkalosis;(4) High dose dexamethasone suppressing test, corticotrophin-releasing hormone(CRH) stimulating test and petrosal sinus sampling were the most meaningful diagnostic methods;(5) Most of the primary lesions might be detected with chest film and CT;(6) Resection of the primary lesion was the treatment of first choice.Conclusion The diagnosis of ectopic ACTH syndrome is very hard.Resection of the primary lesion is the best treatment.

Analysis of glucose dysbolism in patients with ectopic ACTH syndrome / 中华内分泌代谢杂志

The characteristics of glucose dysbolism in ectopic ACTH syndrome (EAS) were investigated by analysing the clinical data of 117 patients with Cushing syndrome (CS). The patients with CS were divided into 3 groups : EAS group (n = 9) , Cushing's disease (CD) group (n = 67) and adrenocortical adenoma (AA) group (n =41). Retrospective analysis of the data covered the prevalence of secondary diabetes, blood glucose, HbAlc, blood potassium, and blood ACTH and 24 h urinary-free cortisol (UFC) levels. Compared with CD and AA groups, the prevalence of secondary diabetes and blood glucose level were higher in EAS group, while HbAlc level was lower. Blood glucose level in patients with ectopic ACTH syndrome decreased to normal after tumor removal.