A rare case of ectopic ACTH syndrome originating from malignant renal paraganglioma

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.

Adrenal venous sampling in a patient with adrenal Cushing syndrome / Uso del muestreo venoso adrenal en un paciente con un síndrome de Cushing adrenal

The primary bilateral macronodular adrenal hyperplasia or the independent adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause hypercortisolism, its diagnosis is challenging and there is no clear way to decide the best therapeutic approach. Adrenal venous sampling is commonly used to distinguish the source of hormonal production in patients with primary hyperaldosteronism. It could be a useful tool in this context because it might provide information to guide the treatment. We report the case of a patient with ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with some modifications radically modified the treatment and allowed the diagnosis of a macronodular adrenal hyperplasia.

La hiperplasia macro nodular bilateral o hiperplasia adrenal nodular bilateral independiente de la hormona adrenocorticotrópica es una de las causas menos frecuentes de hipercortisolismo, su diagnóstico supone un reto y no se tiene claridad de cuál es la mejor aproximación terapéutica. El muestreo venoso adrenal que frecuentemente se utiliza para hacer la distinción del sitio de producción hormonal en el hiperaldosteronismo primario podría ser una herramienta útil en este contexto ya que podría brindar información que pudiera guiar el tratamiento. Presentamos el caso de una paciente con síndrome de Cushing ACTH independiente en quien el uso del muestreo venoso adrenal con algunas modificaciones cambio de manera radical el tratamiento y permitió confirmar una hiperplasia adrenal macro nodular.

Nested stromal epithelial tumor of liver presenting with cushing syndrome: A rare case report.

Nested stromal and epithelial tumor of the liver is an extremely rare pediatric hepatic tumor. To the best of our knowledge, about 25 cases have been reported in the English literature so far, few of which accompanied with Cushing syndrome. Herein we report our experience with an 8-year-old boy presented with Cushing's syndrome because of ectopic ACTH production by this tumor.

Cellular and molecular abnormalities of a macronodular adrenal hyperplasia causing beta-blocker-sensitive Cushing's syndrome

Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia (AIMAH) can be associated with abnormal responses of aberrantly expressed adrenocortical receptors. This study aimed to characterize in vitro the pathophysiology of hypercortisolism in a b-blocker-sensitive Cushing's syndrome due to AIMAH. Cortisol secretion profile under aberrant receptors stimulation revealed hyperresponsiveness to salbutamol (beta2-adrenoceptor agonist), cisapride (5-HT4 receptor agonist), and vasopressin in AIMAH cultured cells, but not in normal adrenocortical cells. By RT-PCR, AIMAH tissues revealed beta2-adrenoceptor overexpression rather than ectopical expression. MC2R expression was similar in both AIMAH and normal adrenocortical tissues. Curiously, cortisol levels of AIMAH cells under basal condition were 15-fold higher than those of control cells and were not responsive to ACTH. Analysis of culture medium from AIMAH cells could detect the presence of ACTH, which was immunohistochemically confirmed. Finally, the present study of AIMAH cells has identified: a) cortisol hyperresponsiveness to catecholamines, 5-HT4 and vasopressin in vitro, in agreement with clinical screening tests; b) abnormal expression of beta2-adrenoceptors in some areas of the hyperplastic adrenal tissue; c) autocrine loop of ACTH production. Altogether, the demonstration of aberrant responses to hormonal receptors and autocrine hormone production in the same tissue supports the assumption of multiple molecular alterations in adrenal macronodular hyperplasia.

A síndrome de Cushing secundária à hiperplasia adrenal macronodular independente de ACTH (AIMAH) pode estar associada com respostas anômalas a estímulos sobre receptores hormonais expressos de maneira aberrante no córtex adrenal. O objetivo deste trabalho foi caracterizar a fisiopatologia do hipercortisolismo in vitro na síndrome de Cushing responsiva a beta-bloqueadores decorrente de AIMAH. Em cultura de células, a secreção de cortisol apresentou resposta aumentada ao salbutamol (agonista beta2-adrenérgico), à cisaprida (agonista de receptor 5-HT4) e à vasopressina, na AIMAH mas não no córtex adrenal normal. O estudo de receptores aberrantes por RT-PCR demonstrou que o gene do receptor beta2-adrenérgico estava superexpresso (e não expresso ectopicamente) nos fragmentos da AIMAH quando comparado ao tecido normal. A expressão de MC2R foi semelhante em ambos. Curiosamente, o nível basal de secreção de cortisol pelas células da AIMAH foi 15 vezes superior às células normais, não havendo resposta das células AIMAH ao estímulo com ACTH. A análise do meio de cultura das células AIMAH revelou a presença de ACTH, que foi confirmada por estudo imuno-histoquímico. Em suma, este estudo demonstrou: a) aumento dos níveis de cortisol in vitro em resposta a catecolaminas, 5-HT4 e vasopressina, correspondendo aos resultados dos testes clínicos para pesquisa de receptores aberrantes; b) expressão anormal de receptores beta2-adrenérgicos em algumas áreas de hiperplasia; c) produção autócrina de ACTH. Estes resultados envolvendo ativação de receptores aberrantes e estímulo hormonal autócrino no mesmo tecido favorecem a hipótese da existência de alterações moleculares múltiplas na hiperplasia adrenal macronodular.

Síndrome de Cushing / Cushing Syndrome

Paciente masculino de 38 anos notou aumento do peso (principalmente com acúmulo de gordura abdominal) e fraqueza muscular, de início há cerca de 2 anos. Nesse período, observou também aumento de volume da face, acne no dorso, perda de pêlos nas pernas e queda de cabelos, além do aparecimento de estrias violáceas no abdômen. Há 1 ano foi diagnosticada hipertensão arterial sistêmica e diabetes melito

Síndrome de Cushing associada à hiperplasia macronodular das adrenais: apresentaçäo de um caso e revisäo da literatura / Cushing's syndrome associated with macronodular adrenal hyperplasia: report of a case and literature review

O objetivo dessa apresentaçäo é discutir a Síndrome de Cushing secundária à hiperplasia macronodular primária das adrenais. Inicialmente, será apresentado um caso clínico e, em seguida, seräo discutidos a apresentaçäo clínica, laboratorial, radiológica e histológica, e os possíveis mecanismos patogenéticos envolvidos no desenvolvimento dessa patologia.

A clinico-pathological study of Cushing's syndrome at the University Hospital of the West Indies and a review of the literature

Cushing's syndrome is an uncommon but important disease. Twenty-one confirmed cases of spontaneous Cushing's syndrome were documented at the University Hospital of the West Indies over a 21-year period. They were predominantly young females (F:M ratio of 17:4; mean age 25 years and 3 months). The commonest presenting symptoms were amenorrhoea (41) and obesity (19). Common clinical features were cushingnoid features (95), hypertension (76) and hirsutism (82). Twenty-nine per cent had frank hyperglycaemia. Cushing's syndrome was due to Cushing's disease in 10 cases, adrenal adenoma in 3 and adrenal carcinoma in 2 cases. In 4 cases with presumed adrenal hyperplasia, the histology was either unavailable or was not consistent with the diagnosis. Two cases appear now to have had the ectopic ACTH Syndrome. Adrenalectomy was the commonest treatment offered. There were no intra-operative or post-operative deaths but recurrence was common after subtotal adrenalectomy in Cushing's disease. Twenty-seven per cent of the patients developed Nelson's syndrome, which was fatal in 50. Long-term hormone replacement therapy was unnecessary after surgery for adrenal adenomas. Treatment of Cushing's syndrome was well tolerated by the patients.

Hipercortisolismo: supresión persistente con la prueba de dexametasona 8 MG / Hypercortisolism: persistent elimination with the dexamethasone 8 MG of sample

Un hombre de 26 años de edad había presentado aumento de 10 Kg de peso durante 1993 con episodios de cefalea bitemporal y nerviosismo hasta noviembre cuando tuvo una primoconvulsión tónico-clónica generalizada. Se demostró Obesidad, Hipertensión, Hiperglicemia, Acidosis Metabólica descompensada, Cortisol plasmático un límite superior sin variación circadiana y cortisol urinario elevado, mayor de 100 mcg en 24 horas. No suprimió con Dexametasona 2 mg pero si con dexametasona 8 mg. Posterior a la prueba de supresión desaparecieron los síntomas, signos y hallazgos de laboratorio. Todos los estudios de imagenología fueron negativos. En 4 años de seguimiento el cortisol urinario no ha superado los 63 mcg/día

Hypertension secondary to adrenal tumors ten years experience

We have presented our ten years experience in the surgical management of adrenal tumors. Patients presenting with hypertension (9) are normotensive following the removal of the offending adrenal tumor. One patient had an extra-adrenal pheochromocytoma, one had a huge organized adrenal hematoma and one patient has a non-functional tumor. The diagnosis and management of endocrine tumors is a challenge to the clinician

ACTH secreting pituitary microadenomas disclosed only by gadolinium DTPA enhanced MRI

Objetivo. Valorar la utilidad del Gd-DTPA y evidenciar aquellos microadenomas de la glándula hipófisis que no han sido demostrados por IRM sin su empleo en pacientes con enfermedad de Cushing. Método: se practicó a seis pacientes RM con y sin gadolinio para hacer evidente la tumoración, y los hallazgos fueron correlacionados con cirugía y confirmados por estudios inmunohistoquímico e histológico de la pieza quirúrgica. Resultados. En todos los casos postadministración del medio, en la RM se demostró una imagen hipodensa circunscrita que correspondía en forma precisa con la localización y extensión del tejido adenimatoso encontrado duarante la cirugía. La extirpación selectiva del microadenoma no tuvo éxito en la mejoría clínica y bioquímica en dos de los seis pacientes. Dichos casos no presentaron imagen residual hipodensa en la RM con Gd-DTPA en el postoperatorio. Conclusiones. Los resultados suguieren que la IRM con Gd-DTPA es un método útil para detectar microadenomas hipofisiarios no demostrables por IRM sin el medio de contraste; sin embargo, las alteraciones del tejido hipofisiario pueden extenderse más allá de la imagen anormal.

Hepatocholangiome et Cushing paraneoplasique

A case of paraneoplasic cushing's syndrome, the rarest a etiology of which is reported and correlated in our analysis to habitual a etiologies such as bronchogenic carcinoma thymic or pancreatic which could be a causative factor in such syndrome. To our knowledge and after meticulous study of medical litterature, the observation we present is the only case of hepatic cholangioma associated with paraneoplasic cushing's syndrome