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.

Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease

OBJECTIVES: Patients with Cushing's disease exhibit wide phenotypic variability in the severity of obesity, diabetes and hypertension. In the general population, several glucocorticoid receptor genes (NR3C1) and HSD11B1 polymorphisms are associated with altered glucocorticoid sensitivity and/or metabolism, resulting in an increased or reduced risk of an adverse metabolic profile. Our aim was to analyze the association of NR3C1 and HSD11B1 gene variants with the severity of some clinical and hormonal features of Cushing's disease. METHODS: Sixty-four patients presenting with Cushing's disease were diagnosed based on adrenocorticotrophic hormone levels, high-dose dexamethasone suppression tests and/or inferior petrosal sinus sampling and magnetic resonance imaging. The A3669G, ER22/23EK, N363S BclI-NR3C1 and HSD11B1-rs12086634 variants were screened. RESULTS: The BclI, HSD11B1-rs12086634 and A3669G variants were found in 36%, 19.5% and 14% of alleles, respectively. The N363S and ER22/23EK polymorphisms were identified in heterozygosis once in only two patients (1.5% of alleles). There were no differences in the weight gain or prevalence of diabetes and hypertension in the patients carrying the abovementioned alleles compared to the wild-type carriers. Interestingly, the mean body mass index (BMI) of the BclI carriers was significantly higher than the non-carriers (34.4±7 kg/m2 vs. 29.6±4.7 kg/m2, respectively). None of the polymorphisms were associated with the basal adrenocorticotrophic hormone, FU levels or F level after dexamethasone suppression testing. CONCLUSION: Although Cushing's disease results from increased glucocorticoid secretion, we observed that interindividual variability in the peripheral glucocorticoid sensitivity, mediated by the glucocorticoid receptor, could modulate the obesity phenotype. .

Avaliação do eixo hipotálamo-hipófise adrenal no diagnóstico e na remissão da doença de Cushing / Assessment of the hypothalamic-pituitary-adrenal axis in Cushing's disease diagnosis and remission

A doença de Cushing (DC) permanece um desafio médico com muitas questões ainda não respondidas. O sucesso terapêutico dos pacientes com DC está ligado à correta investigação do diagnóstico síndrômico e etiológico, além da experiência e talento do neurocirurgião. A adenomectomia hipofisária transesfenoidal constitui-se no tratamento de escolha para a DC. A avaliação da remissão da doença no pós-operatório e da recorrência em longo prazo constitui um desafio ainda maior. Especial destaque deve ser dado para o cortisol sérico no pós-operatório como marcador de remissão. Adicionalmente, o uso de corticoide exógeno no pós-operatório apenas em vigência de insuficiência adrenal tem sido sugerido por alguns autores como requisito essencial para permitir a correta interpretação do cortisol sérico nesse cenário. Neste artigo, revisamos as formas de avaliação da atividade da DC e os marcadores de remissão e recidiva da DC após a realização da cirurgia transesfenoidal.

Cushing's disease (CD) remains a medical challenge, with many questions still unanswered. Successful treatment of CD patients is closely related to correct approach to syndromic and etiological diagnosis, besides the experience and talent of the neurosurgeon. Pituitary transsphenoidal adenomectomy is the treatment of choice for DC. Assessment of remission after surgery and recurrence in the long term is an even greater challenge. In this regard, special attention should be paid to the role of postoperative serum cortisol as a marker of CD remission. Additionally, the postoperative use of exogenous glucocorticoids only in cases of adrenal insufficiency has been suggested by some authors as an essential practice to enable the use of serum cortisol in this scenario. In this article, we review the forms of evaluation of DC activity, and markers of remission and relapse of CD after transsphenoidal surgery.