ACTH Dependent Cushing’s Syndrome: A 72-Hour Trial of Octreotide will Identify Patients with Pituitary Dependent and Ectopic ACTH Overproduction

Aims:To determine whether the use of an octreotide suppression test will reliably distinguish pituitary from ectopic ACTH overproduction. Somatostatin receptors are expressed in NETs, but are downgraded in the pituitary as the result of hypercortisolaemia. Octreotide should therefore lower ACTH and cortisol levels in patients with NETs but not in patients with Cushing’s disease and pituitary tumors. Methodology:A cross sectional study was performed in 13 patents with ACTH dependent Cushing’s (8 women, 5 men) with ages ranging between 21 to 40 years were studied. Serum cortisol concentrations were measured at 0800 hrs before and during the administration of. Octreotide at a dosage of 100 mcg subcutaneously every 8 hours for 72 hours.Results:The serum cortisol concentrations returned to normal in 4 patients who were later documented to have ectopic disease, two with typical bronchial carcinoids and two with pancreatic NETs and metastatic disease. The other 9 patients had no suppression in serum cortisol concentrations and were documented later to have pituitary tumours.Conclusion:These results indicate that a short trial of octreotide will identify patients with ectopic disease as evidenced by a fall inserum cortisol levels whereas in those with Cushing’s disease and pituitary tumours serum cortisol levels remains unchanged. Recommendation: We recommend all patients with ACTH dependent Cushing’s syndrome have an octreotidesuppression test, even if the MRI shows an adenoma, so as to exclude the possibility of a pituitary incidentaloma in a patient with ectopic disease, or false localization from IPSS to the pituitary gland due to ectopic CRH secretion

Diagnóstico y tratamiento de tumores neuroendocrinos productores de ACTH

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.

The value of bilateral inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome / 中华内分泌代谢杂志

Objective To evaluate the values of bilateral inferior petrosal sinus sampling ( BIPSS),high dosage dexamethasone suppression test (HDDST) and pituitary image in the differential diagnosis of ACTH-dependent Cushing's syndrome. Methods Totally 87 patients with confirmed pathological diagnosis were recruited in the study.All received the procedure of BLPSS,HDDST,and pituitary MRI with dynamic enhancement.The diagnostic performances of three differential diagnosis methods in ACTH-dependent Cushing's syndrome were evaluated.Results Seventy-eight patients were diagnosed as cases of pituitary ACTH adenoma,and the remaining 9 were confirmed cases of ectopic ACTH syndrome due to the thymic carcinoid.The sensitivity and specificity of HDDST,pituitary MRI,and BIPSS for the diagnosis of ACTH-dependent Cushing's syndrome were 82.1％ and 100％,79.5％ and 44.4％,92.3％ and 100％,respectively.In Cushing's disease,the diagnostic accuracy was 83.9％ with HDDST,77.0％with pituitary MRI,and93.1％ with BIPSS.In those patients with Cushing's disease,the coincidence of lateralization was 83.9％ with BIPSS and 64.5％ with MRII.Conclusion BIPSS was better than the other two methods in differential diagnosis of ACTH-dependent Cushing's syndrome.Compared with the pituitary MRI,the concordant rate of BIPSS in lateralization of the tumor is higher,and it is more reliable.