Long-term outcome after bilateral adrenalectomy in Cushing's disease with focus on Nelson's syndrome

ABSTRACT Objective We analyzed the clinical, biochemical, and imaging findings of adrenalectomized patients with Cushing's disease (CD) in order to compare the characteristics of those who developed Nelson's syndrome (NS) versus those who did not develop this complication (NNS), aiming to identify possible predictive factors for its occurrence. Subjects and methods We performed a retrospective review of the clinical records of a group of patients with CD who underwent TBA between 1974 and 2011. Results Out of 179 patients with CD, 13 (7.3%) underwent TBA. NS occurred in 6 of them (46%) after a mean of 24 months from the total bilateral adrenalectomy (TBA). Age at diagnosis, duration of Cushing's syndrome (CS) until TBA, and steroid replacement doses were similar in both groups. Initial urinary cortisol levels (24-hour urinary free cortisol [UFC]) were significantly higher in the NS group than in the NNS group (p = 0.009). Four patients in the NS group and three of those in the NNS group received radiotherapy before TBA (p = 0.26). Three patients in the NS group presented residual tumors before TBA, compared with none in the NNS group (p = 0.04). At 1 year after TBA, the median ACTH level was 476 ng/L (240-1500 ng/L) in the NS group and 81 ng/L (48-330 ng/L) in the NNS group (p = 0.0007). Conclusion In conclusion, a residual tumor before TBA, higher 24-hour UFC at diagnosis, and increasing ACTH levels within 1 year after TBA emerged as predictive factors of development of NS.

Incidence of Nelson's syndrome and residual adrenocortical function in patients of Cushing's disease after bilateral adrenalectomy.

Eighteen patients of Cushing's Disease, who had undergone bilateral "total" adrenalectomy 2 to 10 years back, were evaluated for residual adrenocortical function and for any evidence of Nelson's Syndrome. Surprisingly, all patients were discovered to have measurable plasma cortisol, albeit in the subnormal range. The standard criteria for accepting "completeness of adrenalectomy" were fulfilled in 16 patients. It was possible to wean one patient off replacement therapy. Thus, the dose of replacement steroids needs to be regulated according to the blood steroid levels in order to avoid unnecessary hypercortisolism. Radiological evidence of pituitary tumor diagnosed Nelson's Syndrome in 2 patients. Nelson's Syndrome was further suspected in 8 others who showed pigmentation. One of these had an enlarged sella and an erosion of the dorsum sellae, but had a normal CT scan. Another patient had evidence of incidental pituitary pathology (incidentaloma) which resolved spontaneously. Contrast enhanced CT scans of the sella are necessary for early detection of Nelson's Syndrome.

Síndrome de nelson: de uma consegüencia par uma convergência com a doença de cushing / Nelson syndrome: a consequence for a convergence with a cushing disease

Em 1958, a descriçao original da síndrome de nelson, incluia a presença de um tumor hipofisário secretor de ACTH, após o tratamento da doença de Cushing pela adrenalectomia bilaterial. Entretanto, hoje, reconhece-se que uma adenoma hipofisário está presente em cerca de 90 por cento dos casos de doença de Cushing, antes de qualquer tratamento. O objetivo desta revisao foi atualizar o conceito e os critérios diagnósticos da síndorme de Nelson. A etiopatogenia dos tumores corticotróficos e a resistência aumentada à retroalimentaçao negativa dos glicoforticóides nao estao totalmente esclarecidas. Embora os tumores da síndrome de Nelson sejam mais agressivos, aparentemente nao existem diferenças de natureza genética ou de processamento dos peptídeos derivados da POMC, entre os adenomas oriundos da doença de Cushing ou da síndrome de Nelson. Os limites biológicos se superpoem. Porém, é de interêsse prático o estabelecimento dos limites e critérios diagnóticos entre a doença de Cushing pós-adrenaloctomia e a síndrome de Nelson, principalmente para determinar a ocasiao da reexploraçao cirúrgica da hipófise. A primeira tem tumores geralmente nao visualizados, menores que 5mm e níveis plasmáticos de ACTH geralmente menores que 1000pg/ml. Na segunda, so níveis de ACTH sao iguais ou maiores que 1000 pg/ml, aos 12 meses pós-adrenalectomia, aumentando rapidamente para 2000 pg/ml ou mais, após o 2§ ano e apresentando-se, através do CT, como tumores em crescimento e iguais ou maiores que 8 mm. A evoluçao científico-tecnológica levou a uma convergência dos conceitos e dos limites diagnósticos entre a síndrome de Nelson e a doença de Cushing. (Arq Bras Endocrinol Metab 1994; 38/1:47-51).