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Introduction: The differential diagnosis between Cushing's disease (CD) and ectopic ACTH syndrome (EAS) is complex, and bilateral inferior petrosal sinus sampling (BIPSS) is considered the gold-standard test. However, BIPSS with corticotropin-releasing hormone (CRH) stimulation is rarely available. Objective: This retrospective cohort study aimed to assess the accuracy of the inferior petrosal sinus to peripheral ACTH gradient (IPS:P) before and after desmopressin stimulation for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS), applying different cutoff values. Methods: A total of 50 patients (48 with CD and 2 with EAS) who underwent BIPSS were included in this study. The sensitivity and specificity of IPS:P in BIPSS before and after desmopressin stimulation were evaluated. Various cutoff values for IPS:P were examined to determine their diagnostic accuracy. Results: Using the traditional IPS:P cutoff, the sensitivity was 85.1% before stimulation, 89.6% after stimulation, and a combined sensitivity of 91.7%. Applying cutoff values of IPS:P >1.4 before and >2.8 after stimulation, the sensitivity was 87.2% and 89.6%, respectively, with a combined sensitivity of 91.7%. Receiver operating characteristic (ROC) curve analysis determined optimal cutoff values of 1.2 before stimulation and 1.57 after stimulation, resulting in a sensitivity of 93.6% and 93.8%, respectively, with a combined sensitivity of 97.9%. Specificity remained at 100% throughout all analyses. Among the 43 patients who responded positively to stimulation, 42 (97.7%) did so within the first three minutes, and all 43 (100%) did so within the first five minutes. None of the assessed clinical variables predicted the ACTH response to stimulation in BIPSS with statistical significance. Discussion: ACTH stimulation with desmopressin during BIPSS improves the accuracy of IPS:P, making it a valuable tool for investigating ACTH-dependent Cushing's syndrome. Considering the low risk of complications, we recommend the use of desmopressin stimulation during BIPSS for the differential diagnosis of ACTH-dependent CS.
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Síndrome de ACTH Ectópico , Síndrome de Cushing , Hipersecreção Hipofisária de ACTH , Humanos , Síndrome de ACTH Ectópico/diagnóstico , Hormônio Adrenocorticotrópico/metabolismo , Síndrome de Cushing/diagnóstico , Desamino Arginina Vasopressina/farmacologia , Amostragem do Seio Petroso , Hipersecreção Hipofisária de ACTH/diagnóstico , Estudos RetrospectivosRESUMO
A 13-year-old Labrador retriever was diagnosed with Cushing's syndrome (CS) caused by primary bilateral nodular adrenocortical hyperplasia with adrenocorticotropic hormone (ACTH) expression. The pituitary origin of CS was ruled out by suppression of plasma ACTH concentration and absence of a proliferative lesion on histological evaluation of the pituitary gland using periodic acid-Schiff (PAS) staining, reticulin staining, and immunostaining for ACTH. A pheochromocytoma also was found at necropsy examination. On histological evaluation of both adrenal glands, at the junction of the fascicular and glomerular zones, multiple cell clusters distributed in both hyperplastic adrenal cortices expressed ACTH, whereas the pheochromocytoma cells did not. These results indicate that a disease similar to primary bilateral macronodular adrenocortical hyperplasia in humans also occurs in dogs, with intra-adrenocortical expression of ACTH, glucocorticoids excess, and clinical signs of CS. Therefore, the term ACTH-independent could be inappropriate in some cases of bilateral adrenocortical hyperplasia and suppressed plasma ACTH concentration in dogs.
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Síndrome de Cushing , Doenças do Cão , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Hormônio Adrenocorticotrópico/metabolismo , Animais , Síndrome de Cushing/patologia , Síndrome de Cushing/veterinária , Doenças do Cão/patologia , Cães , Hidrocortisona , Hiperplasia/patologia , Hiperplasia/veterinária , HipófiseRESUMO
OBJECTIVE: The aim was to describe the clinical features of patients with ectopic Cushing syndrome (ECS) from Colombia and compare these findings with other series to provide the best management for these patients. METHODS: Records of patients with ECS from 1986 to 2017 were retrospectively reviewed; patients with a diagnosis of adrenal or pituitary Cushing syndrome (CS) were excluded. RESULTS: Fourteen patients with ECS were analyzed in this study. The mean age was 54.4 (SD 17.1) years, and the female to male ratio was 1.33:1. Regarding the etiology of ECS, four patients had lung carcinoids (28.6%), three had small-cell lung carcinoma (21.4%), three had pancreatic neuroendocrine tumors (21.4%), one had medullary thyroid cancer (7.1%), one had non-metastatic pheochromocytoma (7.1%), one had metastatic thymoma (7.1%) and one patient had an occult source of ACTH (7.1%). The most common clinical features at presentation were moon-face, muscle weakness, diabetes mellitus and hypertension. Hyperpigmentation was present in 36% of patients, and 12 patients had hypokalemia with a mean value of 2.3 mEq/L (SD 0.71). The median basal cortisol, 24-hour urinary free cortisol (UFC) and ACTH were 30.5 ug/dL (IQR 21-59 ug/dL), 2,600 ug/24 h (IQR 253-6,487 ug/24 h) and 91 pg/mL (IQR 31.9-141.9), respectively. Thirteen patients (92.8%) had the site of the primary lesion identified. Six patients had undergone a surgical intervention to address the primary tumor. Resection was curative in 28.5% of patients. Death occurred in 57.1% of patients, and the median overall survival was 27 months. Intrathoracic tumors had the most aggressive behavior. CONCLUSION: ECS is a rare disease; however, it is associated with high morbidity and mortality. A rapid intervention supported by an interdisciplinary group is required to improve overall survival and quality of life.
Assuntos
Síndrome de ACTH Ectópico , Síndrome de Cushing , Síndrome de ACTH Ectópico/diagnóstico , Colômbia , Síndrome de Cushing/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos RetrospectivosRESUMO
ABSTRACT Objective The aim was to describe the clinical features of patients with ectopic Cushing syndrome (ECS) from Colombia and compare these findings with other series to provide the best management for these patients. Materials and methods Records of patients with ECS from 1986 to 2017 were retrospectively reviewed; patients with a diagnosis of adrenal or pituitary Cushing syndrome (CS) were excluded. Results Fourteen patients with ECS were analyzed in this study. The mean age was 54.4 (SD 17.1) years, and the female to male ratio was 1.33:1. Regarding the etiology of ECS, four patients had lung carcinoids (28.6%), three had small-cell lung carcinoma (21.4%), three had pancreatic neuroendocrine tumors (21.4%), one had medullary thyroid cancer (7.1%), one had non-metastatic pheochromocytoma (7.1%), one had metastatic thymoma (7.1%) and one patient had an occult source of ACTH (7.1%). The most common clinical features at presentation were moon-face, muscle weakness, diabetes mellitus and hypertension. Hyperpigmentation was present in 36% of patients, and 12 patients had hypokalemia with a mean value of 2.3 mEq/L (SD 0.71). The median basal cortisol, 24-hour urinary free cortisol (UFC) and ACTH were 30.5 ug/dL (IQR 21-59 ug/dL), 2,600 ug/24 h (IQR 253-6,487 ug/24 h) and 91 pg/mL (IQR 31.9-141.9), respectively. Thirteen patients (92.8%) had the site of the primary lesion identified. Six patients had undergone a surgical intervention to address the primary tumor. Resection was curative in 28.5% of patients. Death occurred in 57.1% of patients, and the median overall survival was 27 months. Intrathoracic tumors had the most aggressive behavior. Conclusions ECS is a rare disease; however, it is associated with high morbidity and mortality. A rapid intervention supported by an interdisciplinary group is required to improve overall survival and quality of life
Assuntos
Humanos , Masculino , Feminino , Síndrome de ACTH Ectópico , Síndrome de Cushing/etiologia , Qualidade de Vida , Estudos Retrospectivos , Colômbia , Pessoa de Meia-IdadeRESUMO
ABSTRACT Objective To analyze the morphological and functional characteristics of primary macronodular adrenal hyperplasia (PMAH) nodules carrying or not carrying ARMC5 mutations and the consequences of the presence of mutations in terms of the pattern of macronodule composition and functional state. Subjects and methods The analyses were performed by hematoxylin-eosin staining, immunohistochemistry, microdissection of spongiocyte tissue and RT-qPCR of histological sections from 16 patients diagnosed with PMAH with germline (5) or germline/somatic mutations (5) and without mutations (6) in the ARMC5 gene. Results Hyperplastic nodules were predominantly composed of spongiocytes in mutated and nonmutated sections. ARMC5 mRNA expression in spongiocytes was higher in ARMC5-mutated nodules than in ARMC5-nonmutated nodules, and homogenous ARMC5 protein distribution was observed. The presence of arginine-vasopressin receptor (AVP1AR) and ectopic ACTH production were observed in both cell populations regardless of ARMC5 mutations; the numbers of serotonin receptor (5HT4R)- and proliferating cell nuclear antigen (PCNA)-positive cells were higher in macronodules carrying ARMC5 mutations than in those without mutations. Conclusions Our results suggest that the presence of ARMC5 mutations does not interfere with the pattern of distribution of spongiocytes and compact cells or with the presence of AVP1AR, gastric-inhibitory polypeptide receptor (GIPR) and ectopic ACTH. Nevertheless, the higher numbers of PCNA-positive cells in mutated nodules than in nonmutated nodules suggest that mutated ARMC5 can be related to higher proliferation rates in these cells. In conclusion, our results provide more information about the crosstalk among abnormal GPCRs, ectopic ACTH in steroidogenesis and the ARMC5 gene, which may be relevant in understanding the pathogenesis and diagnosis of patients with PMAH.
Assuntos
Humanos , Proteínas do Domínio Armadillo/genética , Serotonina , Antígeno Nuclear de Célula em Proliferação , Receptores 5-HT4 de Serotonina , MutaçãoRESUMO
Cushing's syndrome caused by an ectopic tumour secreting adrenocorticotropic hormone (ACTH) is not common. Furthermore, an ACTH-secreting panreatic neoplasm is extremely rare. We present a 27-year old female patient suffering from a pancreatic neuroendocrine tumour (p-NET) with extensive pelvic metastases, which could secrete ACTH and cause Cushing's syndrome. The postoperative pathologic examinations of this patient prompted pancreatic poorly differentiated neuroendocrine tumour with extensive metastases of bilateral ovarian, uterus and pelvic peritoneum. The immunohistochemical staining of her tumour tissues was positive for Chromogranin A, Synaptophysin and ACTH. The main aim of this article is to share the experience of her diagnosis and treatment and to review the relevant literature, with an emphasis on discussing the possible transfer modes. Moreover, we strongly suggest that a careful examination of pelvic cavity during the follow-up of patients diagnosed as ACTH-secreting p-NET should also be carried out.
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Se presenta el caso de un paciente varón de 32 años, derivado a nuestro servicio para evaluación de cuadro de 8 meses de evolución caracterizado por edema y rubicundez facial, obesidad central, edema en miembros inferiores e hipertensión arterial, compatible con síndrome de Cushing clínico. Aportaba estudios previos con cortisol séríco 29,8 y 33 Ag/dl (determinaciones realizadas con un mes de diferencia), ACTH 72,8 pg/ml, cortisol salival 2,1 Ag/dl, cortisol libre urinario (CLU) 993,4 Ag/24 hs. Los estudios imagenológicos (ecografía doppler renal, TAC de abdomen y pelvis c/contraste oral y e.v., TAC de cráneo s/contraste y RMI de cráneo c/contraste e.v.) no aportaron datos relevantes. Se confirmó bioquímicamente el síndrome de Cushing dependiente de ACTH: cortisol sérico (8 hs) 34,8 Ag/dl, ACTH (8 hs) 72 pg/ml, cortisol libre urinario 828 Ag/24 hs. El test de Nugent no mostró freno. El test de Liddle (8 mg oral dexametasona 23 hs) produjo un descenso del cortisol plasmático de solo 21%. La función tiroidea, las gonadotrofinas y la prolactina séricas eran normales. La radiografía de tórax mostró mediastino ensanchado e imagen nodular parahiliar basal derecha; esto se confirmó por TAC. La formación nodular medía 20 x 13mm, era de bordes lisos y aspecto inespecífico. Se exploró quirúrgicamente esta lesión, con diagnóstico intraoperatorio de población linfoide de pequeño tamaño. Se realizó nodulectomía por toracotomía con la sospecha de lesión linfoproliferativa. El diagnóstico anatomopatológico definitivo: tumor neuroendócrino bien diferenciado ... (AU)
The case of a male patient aged 32, referred to our service for evaluation of 8-month history of facial redness and edema,central obesity, lower limb edema and arterial hypertension consistent with clinical Cushing syndrome is presented. He hadprevious studies showing serum cortisol 29.8 and 33 mg/dl (determinations performed one month apart), ACTH 72.8 pg/ml, salivary cortisol 2.1 Ag/dl, urinary free cortisol (UFC) 993.4 Ag/24 h. Imaging studies (renal ultrasound doppler, CTof the abdomen and pelvis with oral and iv contrast, skull CT without contrast and skull RMI with iv contrast) did notprovide relevant data. Serum cortisol (8 hours) 34.8 Ag/dl, ACTH (8 h) 72 pg/ml, urinary free cortisol 828 Ag/24 h: anACTH-dependent CushingÆs syndrome was biochemically confirmed. NugentÆs test was negative. Overnight LiddleÆs test (8mg oral dexamethasone 23 h) resulted in a modest decrease (21%) in plasma cortisol. Thyroid function, serum gonadotropinsand prolactin were normal. The chest radiograph showed widened mediastinum and a right basal parahilar nodularimage; this was confirmed by CT. The nodule measured 20 x 13 mm, it had smooth edges and nonspecific appearance. Thislesion was explored surgically, with intraoperative diagnosis of small lymphoid population. Lumpectomy was performed bythoracotomy The final pathological diagnosis was well-differentiated neuroendocrine tumo...(AU)
Assuntos
Humanos , Masculino , Adulto , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/terapia , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/terapia , Síndrome de ACTH Ectópico , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapiaRESUMO
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.
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Se presenta el caso de un paciente varón de 32 años, derivado a nuestro servicio para evaluación de cuadro de 8 meses de evolución caracterizado por edema y rubicundez facial, obesidad central, edema en miembros inferiores e hipertensión arterial, compatible con síndrome de Cushing clínico. Aportaba estudios previos con cortisol séríco 29,8 y 33 µg/dl (determinaciones realizadas con un mes de diferencia), ACTH 72,8 pg/ml, cortisol salival 2,1 µg/dl, cortisol libre urinario (CLU) 993,4 µg/24 hs. Los estudios imagenológicos (ecografía doppler renal, TAC de abdomen y pelvis c/contraste oral y e.v., TAC de cráneo s/contraste y RMI de cráneo c/contraste e.v.) no aportaron datos relevantes. Se confirmó bioquímicamente el síndrome de Cushing dependiente de ACTH: cortisol sérico (8 hs) 34,8 µg/dl, ACTH (8 hs) 72 pg/ml, cortisol libre urinario 828 µg/24 hs. El test de Nugent no mostró freno. El test de Liddle (8 mg oral dexametasona 23 hs) produjo un descenso del cortisol plasmático de solo 21%. La función tiroidea, las gonadotrofinas y la prolactina séricas eran normales. La radiografía de tórax mostró mediastino ensanchado e imagen nodular parahiliar basal derecha; esto se confirmó por TAC. La formación nodular medía 20 x 13mm, era de bordes lisos y aspecto inespecífico. Se exploró quirúrgicamente esta lesión, con diagnóstico intraoperatorio de población linfoide de pequeño tamaño. Se realizó nodulectomía por toracotomía con la sospecha de lesión linfoproliferativa. El diagnóstico anatomopatológico definitivo: tumor neuroendócrino bien diferenciado ...
The case of a male patient aged 32, referred to our service for evaluation of 8-month history of facial redness and edema,central obesity, lower limb edema and arterial hypertension consistent with clinical Cushing syndrome is presented. He hadprevious studies showing serum cortisol 29.8 and 33 mg/dl (determinations performed one month apart), ACTH 72.8 pg/ml, salivary cortisol 2.1 µg/dl, urinary free cortisol (UFC) 993.4 µg/24 h. Imaging studies (renal ultrasound doppler, CTof the abdomen and pelvis with oral and iv contrast, skull CT without contrast and skull RMI with iv contrast) did notprovide relevant data. Serum cortisol (8 hours) 34.8 µg/dl, ACTH (8 h) 72 pg/ml, urinary free cortisol 828 µg/24 h: anACTH-dependent Cushings syndrome was biochemically confirmed. Nugents test was negative. Overnight Liddles test (8mg oral dexamethasone 23 h) resulted in a modest decrease (21%) in plasma cortisol. Thyroid function, serum gonadotropinsand prolactin were normal. The chest radiograph showed widened mediastinum and a right basal parahilar nodularimage; this was confirmed by CT. The nodule measured 20 x 13 mm, it had smooth edges and nonspecific appearance. Thislesion was explored surgically, with intraoperative diagnosis of small lymphoid population. Lumpectomy was performed bythoracotomy The final pathological diagnosis was well-differentiated neuroendocrine tumo...
Assuntos
Humanos , Masculino , Adulto , Hipersecreção Hipofisária de ACTH , Hipersecreção Hipofisária de ACTH , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/terapia , Síndrome de ACTH Ectópico , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapiaRESUMO
La secreción ectópica de corticotropina (ACTH) es responsable de aproximadamente 10 a 20% de los casos de síndrome de Cushing. Constituye un síndrome paraneoplásico clásico que puede estar asociado a una gran variedad de tumores heterogéneos, debido a sus múltiples localizaciones y comportamiento biológico que va desde lesiones benignas hasta lesiones agresivas. El diagnóstico del síndrome de Cushing involucra 3 pasos: 1. Confirmación del hipercortisolismo, 2. Determinación de su dependencia de hipersecreción de ACTH y 3. Discriminación entre lesión hipofisaria o ectópica. En esta revisión, enfocaremos los aspectos actuales que involucran el diagnóstico bioquímico, la localización del tumor, basándose en técnicas elementales como la radiografía, tomografía computarizada y resonancia magnética, así como otras técnicas entre las que figuran el cintilograma con octreotido y la tomografía por emisión de positrones, que en la actualidad han demostrado ventajas en cuanto a su sensibilidad, en combinación con las pruebas bioquímicas e imagenológicas básicas. Finalmente, abordaremos las opciones terapéuticas, considerando que la remoción selectiva del tumor está asociada con una alta probabilidad de cura; en su defecto, cabe considerar el uso de fármacos, como los análogos de la somatostatina para control del hipercortisolismo.
Ectopic corticotropin (ACTH) secretion is responsible for approximately 10 to 20% of cases of Cushing´s syndrome. It is a classic paraneoplasic syndrome which may be heterogeneous due to variety tumors, multiple locations and different biological behavior, ranging from benign to aggressive lesions. The diagnosis of CS involves 3 steps: 1. Confirmation of hypercortisolism, 2. Determination of its dependence to ACTH hypersecretion and 3. Discrimination between pituitary and ectopic lesion. In this review, we will focus on the biochemical diagnosis, the utility of various imaging modalities for the detection of the lesion, such as radiography, computed tomography, magnetic resonance imaging; functional imaging including Scitilography with octreotide and positron emission tomography and its contribution in terms of sensitivity. Finally, we will discuss therapeutic options, specially the role of medical treatment, with emphasis on somatostatin analogues for the management of residual disease.
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Objetivo: discutir las dificultades en el diagnóstico y manejo terapéutico de un caso poco frecuente de Síndrome de Cushing (SC). Caso Clínico: se reporta el caso de un paciente femenino, de 24 años, con hipercortisolismo y patrón bioquímico sugestivo de SC dependiente de corticotropina (ACTH). Estudios imagenológicos mostraron agrandamiento de la glándula hipófisis, extensión supraselar y una lesión lateral izquierda, sugestiva de microadenoma. Sometida a cirugía transesfenoidal en dos oportunidades, sin obtenerse la remisión del cuadro. Tomografía computarizada (TC) de tórax demostró la presencia de nódulo pulmonar único izquierdo, hipercaptante en el gammagrama con octreotido. Fue removido quirúrgicamente en forma satisfactoria produciéndose un abrupto descenso en los niveles de ACTH y cortisol pero nuevamente se incrementaron 24 horas después, permaneciendo elevados desde entonces. La inmunohistoquímica fue positiva para ACTH y cromogranina; el estudio anatomapatológico reportó tumor carcinoide típico sin invasión a ganglios linfáticos; sin embargo, la evolución clínica sugirió enfermedad residual. Se inició tratamiento con análogos de somatostatina (octreotido), el cual se ha mantenido por once meses, obteniéndose mejoría significativa del cuadro clínico y control parcial del hipercortisolismo. TC de tórax y gammagrama con octreotido recientemente practicados, revelaron pequeño foco, el cual correspondió a adenopatía mediastinal derecha. Se plantea la hipótesis de que el tumor producía simultáneamente ACTH y hormona liberadora de corticotropina (CRH, por sus siglas en inglés), explicándose de esta manera la hiperplasia hipofisaria. Conclusión: En pacientes con SC dependiente de ACTH hay que tener presente la existencia de incidentalomas que pueden confundir el diagnóstico. Considerar que la hiperplasia hipofisaria puede ser secundaria a una fuente ectópica productora de CRH y aunque en este caso no pudo realizarse inmunohistoquímica para CRH en las células tumorales, es posible suponer que dichas células secretaban conjuntamente CRH y ACTH lo cual explica la hiperplasia hipofisaria.
Objective: to discuss the diagnostic and therapeutic difficulties of a rare case of Cushing´s syndrome. Case Report: we describe a case of a 24-year-old female patient who developed symptoms compatible with hypercortisolism; the biochemical pattern was suggestive of ACTH dependent Cushin´s Syndrome. Imaging studies showed pituitary enlargement with suprasellar extension and a lesion suggestive microadenoma on the left side. Transsphenoidal surgery was performed in two occasions without remission. Subsequent explorations showed the presence of a single left lung nodule, positive to octreoscan. It was successfully operated and, a sharp decline on ACTH and cortisol levels was seen immediately after operation, increasing again 24 hours later and, remained elevated since then. Inmunohistochemestry studies were positive for ACTH and chromogranin and although the pathology was compatible with typical carcinoid, and no lymph node invasion was seen, the clinical evolution suggested the presence of residual disease. Treatment with somatostatin analogues (Octreotide) was started and has being maintained for eleven months, up to the present. A significant improvement of the clinical picture and partial control of the hypercortisolism has being obtained. Chest CT and octreoscan recently performed, revealed small focus, which corresponded to a right mediastinal adenopathy. We hypothesize that the tumor was simulta-neously producing ACTH and CRH, explaining in this way the pituitary hyperplasia. Conclusion: In patients with ACTH dependent Cushing the existence of incidentalomas could confuse the diagnosis and should be ruled out. Pituitary hyperplasia might be secondary to an ectopic CRH source. Although in our case immunohistochemostry for CRH was not performed, we assume that tumor cells secreted both, CRH and ACTH, explaining the pituitary hyperplasia.
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Twelve percent of Cushing syndromes (CS) are caused by ectopic ACTH secretion. We report two cases of the condition. A 57 years old woman with an ectopic CS caused by a bronchial carcinoid tumor. After the tumor excision, the patient had a favorable evolution. A 63 years old woman consulting for cough, dyspnea and weight loss causes by a small cell lung cancer. The patient presented hyperglycemia, hypokalemia and metabolic alcalosis. The laboratory showed a severe hypercortisolism with elevated ACTH levels. The metabolic condition did not subside after the first course of chemotherapy and the patient died due to an infectious complication...
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Humanos , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Pequenas , Neoplasias Pulmonares , Síndrome de ACTH Ectópico/etiologia , Síndrome de Cushing/etiologiaRESUMO
Ectopic ACTH production occurs in about 10 percent of all cases of Cushing's syndrome, and about 25 percent of cases of ACTH-dependent Cushing's syndrome. Diverse tumor types are able to produce ACTH ectopically, including small cell lung carcinoma. Ectopic ACTH secretion by malignant neoplasm has been reported to have earlier and more aggressive metabolic effects. We report a 59-year-old male patient with severe hypertension, metabolic alkalosis and hypokalemia as the first clinical manifestations of an ACTH-secreting small cell lung carcinoma, although the typical phenotypic features of Cushing's syndrome were not present. Ectopic Cushing's syndrome should always be ruled out in patients with severe hypertension and hypokalemia.
A produção de ACTH ectópico ocorre em aproximadamente 10 por cento dos casos de síndrome de Cushing, e em aproximadamente 25 por cento dos casos de síndrome de Cushing dependentes de ACTH. Diversos tipos de tumores são capazes de produzir ACTH ectopicamente, incluindo carcinoma pulmonar de células pequenas. Relatórios indicam que a secreção de ACTH ectópico por neoplasma maligno causa efeitos metabólicos prematuros e mais agressivos. Apresentamos um paciente, 59 anos, com hipertensão grave, alcalose metabólica e hipocalemia, tendo estas como as primeiras manifestações clínicas de um carcinoma pulmonar de células pequenas com secreção de ACTH, embora as características fenótipas típicas da síndrome de Cushing não estavam presentes. A síndrome de Cushing ectópica deveria ser excluída sempre em pacientes com hipertensão grave e hipocalemia.
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Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de Cushing/diagnóstico , Hipertensão/diagnóstico , Hipopotassemia/diagnóstico , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Alcalose/diagnóstico , Evolução Fatal , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Hidrocortisona/urina , Hipertensão/metabolismo , Hipopotassemia/tratamento farmacológicoRESUMO
Once the diagnosis of Cushing's syndrome (CS) has been established, the main step is to differentiate between ACTH dependent and independent disease. In adults, 80 percent of CS is due to ACTH-dependent causes and 20 percent due to adrenal causes. ACTH-secreting neoplasms cause ACTH-dependent CS. These are usually anterior pituitary microadenomas, which result in the classic Cushing's disease. Non-pituitary ectopic sources of ACTH, such as a small-cell lung carcinoma or carcinoid tumours, are the source of the remainder of ACTH-dependent disease. In the majority of patients presenting with clinical and biochemical evidence of CS, modern non-invasive imaging can accurately and efficiently provide the cause and the nature of the underlying pathology. Imaging is essential for determining the source of ACTH in ectopic ACTH production, locating the pituitary tumours and distinguishing adrenal adenomas, carcinomas and hyperplasias. In our chapter we review the adrenal appearances in ACTH-dependent and ACTH-independent CS. We also include a discussion on the use of MRI and CT for the detection and management of pituitary ACTH secreting adenomas. CT of the chest, abdomen and pelvis with intravenous injection of contrast medium is the most sensitive imaging modality for the identification of the ectopic ACTH source and detecting adrenal pathology. MRI is used for characterising adrenal adenomas, problem solving in difficult cases and for detecting ACTH-secreting pituitary adenomas.
Uma vez estabelecido o diagnóstico da síndrome de Cushing (SC), o passo principal é diferenciar entre a doença ACTH-dependente e a independente. Em adultos, 80 por cento da SC é devida a causas ACTH-dependentes e 20 por cento a causas adrenais. Neoplasias secretoras de ACTH causam a SC ACTH-dependente: usualmente são microadenomas da hipófise anterior que resultam na clássica doença de Cushing. Fontes ectópicas (não hipofisárias) de ACTH, como o carcinoma pulmonar de células pequenas e tumores carcinóides, são a origem do restante da doença ACTH-dependente. Na maioria dos pacientes que se apresentam com evidências clínicas e bioquímicas da SC, técnicas modernas de imagem não invasivas podem apontar acurada e eficientemente a causa e a natureza da patologia subjacente. A imagem é essencial para a determinação da fonte de ACTH na produção ectópica desse hormônio, na localização de tumores hipofisários e na distinção entre adenomas, carcinomas e hiperplasias adrenais. Nesse artigo revisaremos a imagem adrenal na SC ACTH-dependente e independente. Incluiremos, também, uma discussão sobre o uso da RM e da TC na detecção e manejo dos adenomas hipofisários secretores de ACTH. TC de tórax, abdome e pelve, com a injeção intravenosa de meio de contraste, é a modalidade de imagem mais sensível para a identificação da fonte ectópica de ACTH e na detecção da patologia adrenal. A RM é empregada para a caracterização de adenomas adrenais, para a solução de problemas em casos difíceis e para a detecção de adenomas hipofisários secretores de ACTH.