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1.
Front Endocrinol (Lausanne) ; 15: 1399930, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948516

RESUMEN

Ectopic ACTH syndrome (EAS) remains one of the most demanding diagnostic and therapeutic challenges for endocrinologists. Thymic neuroendocrine tumors account for 5%-10% of all EAS cases. We report a unique case of a 31-year-old woman with severe EAS caused by primary metastatic combined large-cell neuroendocrine carcinoma and atypical carcinoid of the thymus. The patient presented with severe hypercortisolemia, which was successfully controlled with continuous etomidate infusion. Complex imaging initially failed to detect thymic lesion; however, it revealed a large, inhomogeneous, metabolically active left adrenal mass infiltrating the diaphragm, suspected of primary disease origin. The patient underwent unilateral adrenalectomy, which resulted in hypercortisolemia resolve. The pathology report showed an adenoma with adrenal infarction and necrosis. The thymic tumor was eventually revealed a few weeks later on follow-up imaging studies. Due to local invasion and rapid progression, only partial resection of the thymic tumor was possible, and the patient was started on radio- and chemotherapy.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Carcinoma Neuroendocrino , Síndrome de Cushing , Neoplasias del Timo , Humanos , Femenino , Adulto , Neoplasias del Timo/complicaciones , Neoplasias del Timo/patología , Neoplasias del Timo/cirugía , Síndrome de Cushing/etiología , Síndrome de Cushing/patología , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/secundario , Carcinoma Neuroendocrino/complicaciones , Carcinoma Neuroendocrino/cirugía , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/secundario , Neoplasias de las Glándulas Suprarrenales/patología , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de ACTH Ectópico/patología , Síndrome de ACTH Ectópico/etiología , Adrenalectomía , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/complicaciones
2.
Probl Endokrinol (Mosk) ; 70(3): 55-66, 2023 Nov 02.
Artículo en Ruso | MEDLINE | ID: mdl-39069773

RESUMEN

Endogenous hypercorticism (EH) is a severe symptom complex caused by hypercortisolemia; according to the etiology, ACTH-dependent and ACTH-independent variants are distinguished, which, according to the literature, occur in 70-80% and 20-30% of cases, respectively. A rare cause of ACTH-dependent endogenous hypercorticism is ACTH-ectopic syndrome (ACTH-ES) (about 15-20% of cases). ACTH-ES is a syndrome of adrenocorticotropic hormone (ACTH) hyperproduction by neuroendocrine tumors of extrahypophyseal origin. Various tumors can secrete ACTH: bronchopulmonary carcinoid, small cell lung cancer, less frequently, thymus carcinoid, islet cell tumors and pancreatic carcinoid, medullary thyroid cancer, carcinoid tumors of the intestine, ovaries, as well as pheochromocytoma (PCC).This publication presents a clinical case of rarely detected paraneoplastic ACTH production by pheochromocytoma. The patient had clinical manifestations of hypercorticism, therefore, she applied to the Russian National Research Center of Endocrinology of the Ministry of Health of Russia. During the examination Cushing's syndrome (CS) was confirmed, multispiral computed tomography (MSCT) of the abdominal cavity revealed a voluminous formation of the left adrenal gland. Additional examination recorded a multiple increase in urinary catecholamine levels. Subsequently, the patient underwent left-sided adrenalectomy. The diagnosis of pheochromocytoma was confirmed morphologically, immunohistochemical study demonstrated intensive expression of chromogranin A and ACTH by tumor cells.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Feocromocitoma , Humanos , Feocromocitoma/complicaciones , Feocromocitoma/patología , Feocromocitoma/metabolismo , Femenino , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/metabolismo , Síndrome de Cushing/etiología , Síndrome de Cushing/patología , Hormona Adrenocorticotrópica/sangre , Hormona Adrenocorticotrópica/metabolismo , Adulto , Síndrome de ACTH Ectópico/etiología , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de ACTH Ectópico/patología , Persona de Mediana Edad
3.
BMC Surg ; 22(1): 383, 2022 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-36348311

RESUMEN

BACKGROUND: Bronchopulmonary carcinoids (BPCs) are rare malignancies but are known to be one of the most common causes of the ectopic adrenocorticotropic hormone (ACTH) syndrome. Surgery is the mainstay of therapy and one key question considering surgical treatment is the impact of local lymph node metastases. We sought to determine the risk factors and prognosis of LN metastases in resected carcinoid patients. METHODS: Data of 42 patients of BPCs with lymph node metastasis who received radical surgery in Peking Union Medical College Hospital (PUMCH) from Jan 2000 to Dec 2021 were retrospectively analysed. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves. Independent prognostic factors were assessed by COX hazard proportion model. RESULTS: It was indicated that in patients received radical surgery with local lymph node positive of BPCs, the 5-year OS and PFS rate was 74.5%, 68.3%, respectively. Multivariate Cox regression indicated that ectopic ACTH syndrome (EAS) could predict significantly to a better OS and PFS. In the subgroup analysis, the age, tumor size, Ki-67 index, histology and postoperative chemotherapy in patients with EAS had significantly differences with those without EAS. CONCLUSIONS: Our study certified R0 resection with lymphadenectomy was effective in patients with lymph nodal positive. The ectopic ACTH syndrome was a protective factor for a better prognosis, which could provide clear evidence for operations.


Asunto(s)
Síndrome de ACTH Ectópico , Tumor Carcinoide , Humanos , Metástasis Linfática , Estudios Retrospectivos , Síndrome de ACTH Ectópico/patología , Síndrome de ACTH Ectópico/cirugía , Pronóstico , Tumor Carcinoide/complicaciones , Tumor Carcinoide/cirugía , Tumor Carcinoide/patología , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Estadificación de Neoplasias
4.
Endocr J ; 69(3): 243-251, 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-34629336

RESUMEN

Pancreatic neuroendocrine tumors (P-NETs) secreting ectopic adrenocorticotropic hormones (ACTH) are rare and often delayed in diagnosis due to their atypical clinical characteristics. Here, we describe a case of P-NET in the pancreatic tail. The tumor had metastasized to the liver and secreted gastrin and ACTH. A 60-year-old female patient was diagnosed with gastrinoma in the pancreatic tail with liver metastases in 2015. After 3 months, the patient presented refractory hypokalemia and thyroid dysfunction. The final diagnosis was P-NET with ectopic ACTH syndrome (EAS). After cytoreductive surgery and the use of long-acting somatostatin analogs, plasma potassium levels and thyroid function were effectively corrected. Although Sandostatin LAR® Depot and proton pump inhibitors (PPIs) were used throughout the follow-up period, the tumor relapsed 4 years later. After aggressive treatment, including right hepatectomy, microwave coagulation of the left liver, and cholecystectomy, the tumor returned 4 months later. Finally, the patient underwent three hepatic artery embolizations and 12 courses of CAPTEM regimen chemotherapy. The markers of disease were almost maintained in the normal ranges until now. We have followed up on this case for more than 5 years. A timely and comprehensive examination of hormones and immunohistochemistry is essential. The prognosis of P-NET is poor. Regular long-term follow-up and the application of combined therapies are helpful to control the disease and improve the prognosis.


Asunto(s)
Síndrome de ACTH Ectópico , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de ACTH Ectópico/etiología , Síndrome de ACTH Ectópico/patología , Hormona Adrenocorticotrópica , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/terapia , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia
5.
Elife ; 102021 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-34905486

RESUMEN

Ectopic Cushing's syndrome due to ectopic ACTH&CRH-secreting by pheochromocytoma is extremely rare and can be fatal if not properly diagnosed. It remains unclear whether a unique cell type is responsible for multiple hormones secreting. In this work, we performed single-cell RNA sequencing to three different anatomic tumor tissues and one peritumoral tissue based on a rare case with ectopic ACTH&CRH-secreting pheochromocytoma. And in addition to that, three adrenal tumor specimens from common pheochromocytoma and adrenocortical adenomas were also involved in the comparison of tumor cellular heterogeneity. A total of 16 cell types in the tumor microenvironment were identified by unbiased cell clustering of single-cell transcriptomic profiles from all specimens. Notably, we identified a novel multi-functionally chromaffin-like cell type with high expression of both POMC (the precursor of ACTH) and CRH, called ACTH+&CRH + pheochromocyte. We hypothesized that the molecular mechanism of the rare case harbor Cushing's syndrome is due to the identified novel tumor cell type, that is, the secretion of ACTH had a direct effect on the adrenal gland to produce cortisol, while the secretion of CRH can indirectly stimulate the secretion of ACTH from the anterior pituitary. Besides, a new potential marker (GAL) co-expressed with ACTH and CRH might be involved in the regulation of ACTH secretion. The immunohistochemistry results confirmed its multi-functionally chromaffin-like properties with positive staining for CRH, POMC, ACTH, GAL, TH, and CgA. Our findings also proved to some extent the heterogeneity of endothelial and immune microenvironment in different adrenal tumor subtypes.


Asunto(s)
Síndrome de ACTH Ectópico/diagnóstico , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Feocromocitoma/diagnóstico , Transcriptoma , Síndrome de ACTH Ectópico/metabolismo , Síndrome de ACTH Ectópico/patología , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/patología , Hormona Adrenocorticotrópica/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Perfilación de la Expresión Génica , Feocromocitoma/metabolismo , Feocromocitoma/patología , Análisis de la Célula Individual
6.
Am J Surg ; 221(2): 460-464, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32921404

RESUMEN

BACKGROUND: Endogenous Cushing syndrome (CS) can be caused by ectopic corticotropin-producing tumors of known (EK) and unknown origin (EU). Bilateral adrenalectomy (BA) can be used as definite treatment of hypercortisolism in such cases. This study compared patients undergoing BA for CS secondary to EK vs EU. METHODS: Retrospective review (1995-2017) of patients undergoing BA due to EK or EU. We analyzed demographic characteristics, laboratory values, intraoperative variables, surgical outcomes, and survival. RESULTS: 48 patients (26 EU, 22 EK) were identified. Serum cortisol and ACTH concentrations were similar. 92% of BA for EU were performed minimally invasively vs 77% for EK, P = 0.22. Complications occurred in 19% of EU and 4.5% EK, P = 0.2. Mean survival was 4.3 years for EU and 4.0 years for EK without difference in all-cause mortality P = 0.63. CONCLUSION: BA cure rate was 100% for CS in EU and EK. Morbidity, long term and all-cause mortality differences were not statistically significant between EK and EU.


Asunto(s)
Síndrome de ACTH Ectópico/cirugía , Adrenalectomía/efectos adversos , Neoplasias Primarias Desconocidas/cirugía , Complicaciones Posoperatorias/epidemiología , Síndrome de ACTH Ectópico/sangre , Síndrome de ACTH Ectópico/mortalidad , Síndrome de ACTH Ectópico/patología , Adrenalectomía/estadística & datos numéricos , Hormona Adrenocorticotrópica/sangre , Hormona Adrenocorticotrópica/metabolismo , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/sangre , Neoplasias Primarias Desconocidas/mortalidad , Neoplasias Primarias Desconocidas/patología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del Tratamiento
7.
Artículo en Inglés | MEDLINE | ID: mdl-32903471

RESUMEN

Ectopic ACTH-secretion causing Cushing's syndrome is unusual and its diagnosis is frequently challenging. The presence of high-molecular-weight precursors throughout pro-opiomelanocortin (POMC) translation by these tumors is often not reported. We present the case of a 49-year-old woman with a 3-month history of proximal muscular weakness, skin pigmentation, and weight loss. Upon initial evaluation, she had a full moon face, hirsutism, and a buffalo hump. Laboratory workup showed hyperglycemia, hypokalemia and metabolic alkalosis. ACTH, plasma cortisol, and urinary free cortisol levels were quite elevated. Serum cortisol levels were not suppressed on dexamethasone suppression testing. An octreo-SPECT scan showed enhanced nucleotide uptake in the liver and pancreas. Transendoscopic ultrasound-guided biopsy confirmed the diagnosis of a pancreatic ACTH-secreting neuroendocrine tumor (NET). Surgical excision of both pancreatic and liver lesions was carried out. Western blot analysis of the tumor and metastases revealed the presence of a high-molecular-weight precursor possibly POMC (at 30 kDa) but not ACTH (normally 4.5 kDa). ACTH-precursor secretion is more frequent in ectopic ACTH-secreting tumors compared with other causes of Cushing's syndrome. Hence, the measurement of such ACTH precursors warrants further evaluation, especially in the context of ACTH-dependent hypercortisolism.


Asunto(s)
Síndrome de ACTH Ectópico/etiología , Hormona Adrenocorticotrópica/sangre , Tumores Neuroendocrinos/complicaciones , Neoplasias Pancreáticas/complicaciones , Síndrome de ACTH Ectópico/sangre , Síndrome de ACTH Ectópico/patología , Femenino , Humanos , Persona de Mediana Edad , Tumores Neuroendocrinos/sangre , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/secundario
8.
J Clin Endocrinol Metab ; 105(11)2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32785672

RESUMEN

OBJECTIVE: Pancreatic neuroendocrine tumors (pNETs) causing ectopic adrenal corticotropic hormone (ACTH) syndrome (EAS) are rare and aggressive with little known information. We aimed to elucidate the clinical features and molecular mechanisms of pNETs with EAS by methylation analysis. METHODS: Seven patients with ectopic ACTH-secreting pNETs who were diagnosed at Shanghai Clinical Endocrine and Metabolic Diseases Center and Pancreatic Disease Center in Ruijin Hospital between 2001 and 2019 were enrolled. Twenty patients with ectopic ACTH-secreting thymic neuroendocrine tumors (TNETs) and 7 with nonfunctional pNETs (nf-pNETs) were also enrolled as controls. We collected clinical data and measured POMC promoter CpG methylation. RESULTS: All 7 patients had elevated ACTH and urinary free cortisol (UFC) levels with positive ACTH staining in the pancreas and were diagnosed with ectopic ACTH-secreting pNET. Of the 7 patients, 6 underwent surgery and 1 underwent transarterial embolization (TAE). Two patients were free of disease after surgery; 2 died within 90 days after surgery; and 3 had metastases and died within 1 year. Compared with ACTH-secreting TNETs, ACTH-secreting pNETs had similar clinical and biochemical features but a significantly poorer prognosis. POMC promoter CpG methylation was significantly lower in ACTH-secreting pNETs than in nf-pNETs and normal pancreas. CONCLUSIONS: ACTH-secreting pNETs are aggressive and fatal. Surgery is definitively curative for patients with resectable primary tumors without metastasis. Pro-opiomelanocortin (POMC) promoter hypomethylation caused pNETs to produce ACTH. This study further supplements the genetic features of ACTH-secreting NETs.


Asunto(s)
Síndrome de ACTH Ectópico/metabolismo , Hormona Adrenocorticotrópica/metabolismo , Tumores Neuroendocrinos/metabolismo , Neoplasias Pancreáticas/metabolismo , Síndrome de ACTH Ectópico/etiología , Síndrome de ACTH Ectópico/patología , Síndrome de ACTH Ectópico/cirugía , Adulto , Metilación de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/cirugía , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Proopiomelanocortina/genética , Proopiomelanocortina/metabolismo , Regiones Promotoras Genéticas , Resultado del Tratamiento , Adulto Joven
9.
J Endocrinol Invest ; 43(9): 1197-1204, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32062826

RESUMEN

BACKGROUND: Adrenal lipid-poor adenomas (LPA) are defined by high unenhanced density (≥ 10 HU), and absolute and relative contrast medium washout > 60% and > 40%, respectively, at computerized tomography (CT). To date, no thorough histopathological characterization has been performed in those frequent lesions (one-third of adrenal adenomas). Our aim was to analyze the histopathological characteristics of adrenal LPA. METHODS: Patients with LPA (n = 57) were selected among consecutive subjects referred for an adrenal incidentaloma or ACTH-independent Cushing syndrome. FluoroDeoxyGlucose-Positron Emission Tomography (FDG-PET) was performed in 37 patients. In patients treated by adrenalectomy (n = 17), Weiss score and Lin-Weiss-Bisceglia score (in tumors composed entirely or predominantly of oncocytes) were calculated. RESULTS: Radiological parameters did not differ among patients with ACTH-independent Cushing syndrome (n = 6) and those with adrenal incidentalomas associated with primary aldosteronism (n = 2), autonomous cortisol secretion (n = 14), or non-functioning (n = 35). Patients treated by adrenalectomy had larger tumors (28.9 ± 11.2 vs 17.3 ± 8.4 mm, P < 0.001), higher CT unenhanced density (29.1 ± 11.0 vs 23.1 ± 9.0 HU, P = 0.043), and FDG-PET adrenal uptake (9.0 ± 6.4 vs 4.4 ± 2.3 SUV, P = 0.003) than non-operated ones. Oncocytic features > 75% of the tumor were detected in 12/17 cases (70.6%). Five of those showed borderline-malignant histopathological characteristics by Lin-Weiss-Bisceglia score. Among remaining non-oncocytic tumors, 1/5 had a Weiss score ≥ 3. Overall, 6/17 tumors (35.3%) had borderline-malignant potential. Radiological parameters were similar between patients with benign and borderline-malignant tumors. CONCLUSIONS: Adrenal LPA are a heterogeneous group of tumors, mostly composed of oncocytomas. Up to 1/3 of those tumors may have a borderline-malignant potential at histopathology.


Asunto(s)
Adenoma/diagnóstico , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de ACTH Ectópico/etiología , Síndrome de ACTH Ectópico/metabolismo , Síndrome de ACTH Ectópico/patología , Adenoma/metabolismo , Adenoma/patología , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/patología , Hormona Adrenocorticotrópica/metabolismo , Adulto , Anciano , Biopsia , Estudios de Cohortes , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiología , Síndrome de Cushing/metabolismo , Síndrome de Cushing/patología , Femenino , Fluorodesoxiglucosa F18 , Humanos , Italia , Metabolismo de los Lípidos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
10.
Hormones (Athens) ; 19(3): 351-360, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31950464

RESUMEN

PURPOSE: Ectopic Cushing's syndrome (ECS) caused by an ACTH secreting neuroendocrine neoplasm (NEN) is a rare and challenging condition. We aimed to detect predictive and prognostic parameters for ECS patients identified from a retrospective, comprehensive cohort of NENs treated at a tertiary referral center. METHODS: Medical records of 886 patients with NENs were reviewed. We identified 51 patients with ECS (33 females/18 men); mean age 52 ± 15 years (SD). Clinical parameters including symptoms, biochemical markers, and survival were extracted and further analyzed. RESULTS: The primary tumor was located in the thorax (n = 28) or pancreas (n = 15) or was of unknown primary origin (n = 8). In 30 patients, tumor and ECS were diagnosed simultaneously. In 12 patients, the NEN diagnosis preceded ECS development, with a median time of 43.5 months (range: 9-96), and 10 of these showed radiological tumor progression at ECS diagnosis. Twenty-one patients had multiple hormone secretion, which correlated with shorter overall survival (OS), p = 0.012 (HR 2.4 (95% CI 1.2-4.9)), as did high morning cortisol, p = 0.037 (HR 2.3 (1.0-5.2)), higher tumor grade, p = 0.044 (HR 2.3 (1.0-5.1)), and diabetes, p = 0.050 (HR 2.4 (1.0-6.0)). CONCLUSIONS: Multiple hormone secretion, high morning cortisol, higher tumor grade, and diabetes were correlated with shorter OS. Development of ECS in patients with a non-functioning NEN may indicate tumor progression. Multiple hormone secretion should be considered as a bad prognostic sign in ECS patients and should lead to intensified clinical management.


Asunto(s)
Síndrome de ACTH Ectópico/diagnóstico , Hormona Adrenocorticotrópica/sangre , Síndrome de Cushing/sangre , Síndrome de Cushing/diagnóstico , Hidrocortisona/sangre , Tumores Neuroendocrinos/diagnóstico , Síndrome de ACTH Ectópico/complicaciones , Síndrome de ACTH Ectópico/patología , Adulto , Anciano , Síndrome de Cushing/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/patología , Pronóstico , Estudios Retrospectivos , Centros de Atención Terciaria
11.
J Pediatr Hematol Oncol ; 42(7): e668-e669, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-31343485

RESUMEN

Ectopic adrenocorticotropic hormone syndrome is a paraneoplastic phenomenon rarely seen in pediatrics and rarely described in Ewing sarcoma. We report a 15-year-old boy with abdominal Ewing sarcoma and clinical and laboratory findings of ectopic adrenocorticotropic hormone syndrome that promptly resolved with treatment of the tumor.


Asunto(s)
Síndrome de ACTH Ectópico/patología , Neoplasias Abdominales/complicaciones , Neoplasias Óseas/complicaciones , Sarcoma de Ewing/complicaciones , Síndrome de ACTH Ectópico/etiología , Síndrome de ACTH Ectópico/terapia , Neoplasias Abdominales/patología , Adolescente , Hormona Adrenocorticotrópica/metabolismo , Neoplasias Óseas/patología , Humanos , Masculino , Pronóstico , Sarcoma de Ewing/patología
14.
Biomed Res Int ; 2019: 9721781, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31001560

RESUMEN

Previous studies have linked systemic glucocorticoid use with intestinal perforation. However, the association between intestinal perforation and endogenous hypercortisolism has not been well described, with only 14 previously published case reports. In this study, we investigated if intestinal perforation occurred more frequently in patients with ectopic ACTH syndrome and in those with a greater than 10-fold elevation of 24-hour urinary free cortisol level. Of 110 patients with ACTH-dependent Cushing's syndrome followed in two clinics in Canada, six cases with intestinal perforation were identified over 15 years. Age of patients ranged from 52 to 72, five females and one male, four with Cushing's disease and two with ectopic ACTH production, one from a pancreatic neuroendocrine tumor and one from medullary carcinoma of the thyroid. Five had diverticular perforation and one had intestinal perforation from a stercoral ulcer. All cases had their lower intestinal perforation when the cortisol production was high, and one patient had diverticular perforation 15 months prior to the diagnosis of Cushing's disease. As in previously reported cases, most had hypokalemia and abdominal pain with minimal or no peritoneal symptoms and this occurred during the active phase of Cushing's syndrome. Whereas all previously reported cases occurred in patients with 24-hour urinary free cortisol levels greater than 10-fold the upper limit of normal when measured and 11 of 14 patients had ectopic ACTH production, only one of our patients had this degree of hypercortisolism and four of our six patients had Cushing's disease. Similar to exogenous steroid use, patients with endogenous hypercortisolism also have a higher risk of intestinal, in particular diverticular, perforation and should be monitored closely for its occurrence with a low threshold for investigation and surgical intervention. Elective colonoscopy probably should be deferred until Cushing's syndrome is under control.


Asunto(s)
Síndrome de ACTH Ectópico , Hormona Adrenocorticotrópica/sangre , Síndrome de Cushing , Hidrocortisona/orina , Perforación Intestinal , Síndrome de ACTH Ectópico/sangre , Síndrome de ACTH Ectópico/patología , Síndrome de ACTH Ectópico/orina , Anciano , Carcinoma Neuroendocrino/sangre , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/orina , Síndrome de Cushing/sangre , Síndrome de Cushing/fisiopatología , Síndrome de Cushing/orina , Femenino , Humanos , Perforación Intestinal/sangre , Perforación Intestinal/patología , Perforación Intestinal/orina , Masculino , Persona de Mediana Edad , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/orina
15.
Endocr J ; 66(6): 547-554, 2019 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-30918166

RESUMEN

Ectopic ACTH syndrome (EAS) due to a prostate small cell carcinoma (SCC) is very rare with only 26 cases reported to date and has a poor prognosis. We here describe another case of this disorder that was clinically typical based on prior reports as it showed hypercortisolemia and severe hypokalemia with multiple metastasis. However, our current case of prostate SCC causing EAS is the first to display negative immunostaining for ACTH despite detectable POMC mRNA expression in the primary lesion. ACTH immunonegativity is thought to be associated with a more aggressive disease course and a poorer prognosis although there are few studies of the underlying mechanisms. We explored two possibilities for this finding in our current patient: aberrant POMC processing prevented immunodetection with an anti-ACTH antibody; and the ACTH content per cell was below the threshold for immunodetection due to its rapid secretion or low synthesis. The aberrant processing theory was thought to be less likely because of immunonegative findings even using anti-POMC/ACTH antibodies. As the plasma ACTH levels in our patient were comparable with those reported for previous immunopositive prostate EAS cases, we speculated that the depletion of ACTH may be caused not only by rapid secretion but also by low production levels as a sign of de-differentiation. De-differentiation may therefore explain the mechanism underlying the negative correlation between immunoreactivity for ACTH in EAS and disease aggressiveness. We believe that our present findings will be of use in future prospective studies aimed at confirming the mechanism of immunonegativity.


Asunto(s)
Síndrome de ACTH Ectópico/etiología , Carcinoma de Células Pequeñas/complicaciones , Próstata/metabolismo , Neoplasias de la Próstata/complicaciones , Síndrome de ACTH Ectópico/metabolismo , Síndrome de ACTH Ectópico/patología , Hormona Adrenocorticotrópica/sangre , Anciano , Carcinoma de Células Pequeñas/metabolismo , Carcinoma de Células Pequeñas/patología , Humanos , Masculino , Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología
17.
Endocr J ; 65(12): 1161-1169, 2018 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-30232300

RESUMEN

Ectopic ACTH syndrome (EAS) is a potentially fatal endocrine disease that results from a variety of neuroendocrine tumors (NETs), such as small cell lung cancer (SCLC) and bronchial typical carcinoid. Typical carcinoid is usually slow growing, not associated with plasma progastrin releasing peptide (ProGRP) elevation. Here, we report a 47-year-old female smoker with progressive typical carcinoid and plasma ProGRP elevation. Several types of Cushingoid features were found on physical examination. In addition, laboratory examination showed elevated plasma ACTH and serum cortisol levels. These findings indicated ACTH-dependent Cushing's syndrome. Moreover, the serum cortisol level was not suppressed by overnight high-dose dexamethasone treatment, suggesting the presence of an extra-pituitary tumor. Contrast-enhanced brain MRI revealed no pituitary adenoma, which also supported the idea that EAS occurred in the present case. Strikingly, chest computed tomographic (CT) scan showed a single 18-mm peripheral nodule in the right middle lobe of the lung. Tumor marker analysis revealed an elevation in plasma ProGRP. These data suggested a possibility that SCLC secreted ACTH and caused EAS in this patient. Of note, the plasma ACTH level was increased (1.7 fold) in l-desamino-8-D-arginine vasopressin (DDAVP) test, also suggesting the specific clinical feature in this case. After additional imaging examinations, we performed surgical resection with the suspicion of limited SCLC. As a result, pathological examination revealed a vasopressin receptor Ib (V1b) receptor-negative bronchial typical carcinoid with ACTH production and mediastinal lymphatic metastasis. In summary, we present a case of EAS caused by progressive bronchial typical carcinoid with plasma ProGRP elevation. We propose a novel subtype of lung typical carcinoid.


Asunto(s)
Síndrome de ACTH Ectópico/etiología , Neoplasias de los Bronquios/complicaciones , Tumor Carcinoide/complicaciones , Fragmentos de Péptidos/sangre , Síndrome de ACTH Ectópico/sangre , Síndrome de ACTH Ectópico/patología , Hormona Adrenocorticotrópica/sangre , Neoplasias de los Bronquios/sangre , Neoplasias de los Bronquios/patología , Tumor Carcinoide/sangre , Tumor Carcinoide/patología , Desamino Arginina Vasopresina , Femenino , Humanos , Hidrocortisona/sangre , Metástasis Linfática/patología , Persona de Mediana Edad , Proteínas Recombinantes/sangre
19.
J Postgrad Med ; 64(1): 47-49, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28862247

RESUMEN

Ectopic adrenocorticotropic hormone (ACTH) syndrome is an uncommon disorder and comprises about 15% of all patients with Cushing's syndrome (CS). Duodenal carcinoids are rare, indolent tumors usually associated with a benign progression. We hereby report a rare case of CS resulting from ectopic ACTH secretion from a duodenal neuroendocrine tumor (NET) presenting with liver metastasis. A 37-year-old female presented with abdominal discomfort and dyspepsia of 1-month duration. Ultrasound abdomen suggested a well-defined hypoechoic lesion in the left lobe of the liver, suggestive of neoplasia. On clinical examination, she had Cushingoid features and persistent hypokalemia. Midnight ACTH and cortisol levels were grossly elevated at 1027 pg/ml (n < 46 pg/ml) and 87.56 µg/dl (n < 7.5 µg/ml), respectively. Both overnight and high-dose dexamethasone suppression test confirmed nonsuppressed cortisol levels - 86.04 and 84.42 µg/dl (n < 1.8 µg/ml), respectively. Magnetic resonance imaging brain showed a structurally normal pituitary gland. Computed tomography scan of the abdomen revealed hepatic lesion with bilateral adrenal enlargement. A diagnosis of ectopic ACTH-dependent CS was made. Intraoperatively, a duodenal lesion of 0.5 cm × 0.5 cm was identified alongside an 8 cm × 6 cm exophytic lesion in segment IV of the liver. Frozen section of the duodenal lesion was positive for NET. She underwent a Whipple's surgery, cholecystectomy, and left hepatic lobectomy. Postoperatively, she showed clinical and biochemical remission. Herewith, we report the third case of duodenal carcinoid tumor presenting as ectopic ACTH syndrome and the first with liver metastasis.


Asunto(s)
Síndrome de ACTH Ectópico/patología , Hormona Liberadora de Corticotropina/metabolismo , Síndrome de Cushing/etiología , Neoplasias Duodenales/patología , Neoplasias Hepáticas/patología , Tumores Neuroendocrinos/patología , Síndrome de ACTH Ectópico/cirugía , Adulto , Colecistectomía , Neoplasias Duodenales/metabolismo , Neoplasias Duodenales/cirugía , Femenino , Humanos , Hígado/diagnóstico por imagen , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirugía , Metástasis de la Neoplasia , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/cirugía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Ultrasonografía
20.
Arch. endocrinol. metab. (Online) ; 61(3): 291-295, May-June 2017. tab, graf
Artículo en Inglés | LILACS | ID: biblio-887558

RESUMEN

SUMMARY Ectopic adrenocorticotropic hormone (ACTH) syndrome is characterized by hypercortisolism due to the hypersecretion of a non-pituitary ACTH-secreting tumor leading to Cushing's syndrome. Only a few cases have been reported previously as causing ectopic ACTH related to paraganglioma. Herein, we present a case of Cushing's syndrome, in who was proved to be attributable to an ACTH-secreting renal malignant paraganglioma. A 40-year-old woman presented with a five-month history of newly diagnosed hypertension and diabetes, weakness, hyperpigmentation, oligomenorrhea, hirsutism, and acneiform lesions. She showed cushingoid features, including moon face, facial hirsutism, facial and truncal acne, hyperpigmentation, and severe muscle weakness of the limbs. She did not have other findings such as striae, supraclavicular fat accumulation, and buffalo hump. Laboratory examination showed the presence of hypopotasemia, hyperglycemia, hyperthyroidism, and leukocytosis. The serum levels of ACTH, cortisol, and urine-free cortisol were markedly elevated. Results of an overnight 2-mg dexamethasone suppression test included a basal serum cortisol of 61.1 mcg/dL (normal range: 4.6-22.8 mcg/dL) and a cortisol value of 46.1 mcg/dL after dexamethasone administration. There was no suppression found after 2-day 8-mg dexamethasone administration. Magnetic resonance imaging (MRI) of the pituitary gland indicated two microadenomas. An abdominal MRI scan revealed horseshoe kidney, bilateral adrenal hyperplasia, and masses with dimensions of 35 x 31 mm in the left kidney. Inferior petrosal sinus sampling showed no evidence of a central-to-peripheral gradient of ACTH. A positron emission tomography/computed tomography scan showed intense increased activity in the lower pole of the left kidney. Left adrenalectomy and left partial nephrectomy were performed. The resected tumor was diagnosed as the ACTH-secreting paraganglioma in the pathological examination, which was confirmed by immunohistochemical studies with chromogranin A, synaptophysin, and ACTH. Only a few cases of paragangliomas as a cause of ectopic ACTH syndrome have been reported. To our knowledge, this is the first case of renal paraganglioma resulting in Cushing's syndrome due to ectopic ACTH hypersecretion.


Asunto(s)
Humanos , Femenino , Adulto , Paraganglioma/complicaciones , Paraganglioma/metabolismo , Síndrome de ACTH Ectópico/etiología , Síndrome de Cushing/etiología , Neoplasias Renales/complicaciones , Neoplasias Renales/metabolismo , Paraganglioma/patología , Hipófisis/patología , Síndrome de ACTH Ectópico/patología , Inmunohistoquímica , Síndrome de Cushing/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Renales/patología , Metástasis Linfática
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