Bone Evaluation by High-Resolution Peripheral Quantitative Computed Tomography in Patients With Adrenal Incidentaloma.

CONTEXT: Data regarding high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with adrenal incidentaloma (AI) are unknown. PURPOSE: To evaluate the areal bone mineral density (aBMD), microstructure, and fractures in patients with nonfunctioning AI (NFAI) and autonomous cortisol secretion (ACS). METHODS: We evaluated 45 patients with NFAI (1 mg dexamethasone suppression test [DST] ≤1.8 µg/dL) and 30 patients with ACS (1 mg DST 1.9-5.0 µg/dL). aBMD was measured using dual-energy X-ray absorptiometry; vertebral fracture by spine X-ray; and bone geometry, volumetric bone mineral density (vBMD), and microstructure by HR-pQCT. RESULTS: Patients with ACS showed lower aBMD values at the spine, femoral neck, and radius 33% than those with NFAI. Osteoporosis was frequent in both groups: NFAI (64.9%) and ACS (75%). Parameters at the distal radius by HR-pQCT were decreased in patients with ACS compared to those with NFAI: trabecular vBMD (Tb.vBMD, P = 0.03), inner zone of the trabecular region (Inn.Tb.vBMD, P = 0.01), the bone volume/tissue volume ratio (BV/TV, P = 0.03) and trabecular thickness (P = 0.04). As consequence, a higher ratio of the outer zone of the trabecular region/inner zone vBMD (Meta/Inn.vBMD, P = 0.003) was observed. A correlation between the cortisol levels after 1 mg DST and Meta/Inn.vBMD ratio was found (r = 0.29; P = 0.01). The fracture frequency was 73.7% in patients with ACS vs 55.6% in patients with NFAI (P = 0.24). CONCLUSION: Our findings point to an association between trabecular bone microarchitectural derangement at the distal radius and ACS. Our data suggest that AI have a negative impact on bone when assessed by HR-pQCT, probably associated to subclinical hypercortisolism.

Is there a role for epithelial-mesenchymal transition in adrenocortical tumors?

PURPOSE: Epithelial-mesenchymal transition (EMT) is a biological dynamic process by which epithelial cells lose their epithelial phenotype and acquire mesenchymal invasive and migratory characteristics. This has been postulated as an essential step during cancer progression and metastasis. Although this is well described in other tumors, the role of EMT in adrenocortical tumors (ACT) has yet to be addressed. METHODS: The aim of this study was to evaluate the expression of EMT markers e-cadherin, vimentin, and fibronectin, along with EMT-transcription factors (EMT-TFs), TWIST1, SIP1, and SNAIL in 24 adrenocortical carcinoma (ACC), 19 adrenocortical adenomas (ACA), 27 childhood-onset adrenocortical tumors (CAT), and 12 normal adrenal glands. The association of EMT and EMT-TFs with clinical outcomes and pathology features were also evaluated. RESULTS: Cytoplasmic vimentin expression was increased among CAT samples when compared to ACC, ACA, and normal adrenal samples (p < 0.001). There was no difference in e-cadherin and fibronectin expression observed between groups. Nuclear and cytoplasmic expression of TWIST1 and SIP1 was stronger in CAT and ACC vs. ACA and normal tissue samples (all, p < 0.05). ACT, regardless of classification, exhibited increased SNAIL expression when compared to normal tissue (p < 0.05). A significant correlation was observed between vimentin and TWIST1 (r s = 0.44, p < 0.001); SIP1 (r s = 0.51, p < 0.001); and SNAIL (r s = 0.23, p < 0.05). TWIST1 and SIP1 expressions demonstrated a significant correlation (r s = 0.56, p < 0.001). High SIP1 expression was associated with a lower survival rate among ACC cases (p < 0.05). CONCLUSIONS: Vimentin, TWIST1, and SIP1 expressions are increased in aggressive ACT. Therefore, EMT may play a relevant role in adrenal tumorigenesis.

Recurrence and mortality prognostic factors in childhood adrenocortical tumors: Analysis from the Brazilian National Institute of Cancer experience.

Prognostic markers that can help identifying precocious risk of unfavorable outcomes in patients with childhood adrenocortical tumors (ACTs) are still unclear. This observational and retrospective study aimed to identify clinical and pathology prognostic factors of recurrence and death in a tertiary cancer center population. Clinical, pathology, demographic, staging, and therapy data from patients with childhood ACT (median age: 3.6 years) treated at the Brazilian National Institute of Cancer between 1997 and 2015 were assessed. Univariate and bivariate analyses were used to study the association of clinical and pathology characteristics with recurrence and mortality. Recurrence and disease-related mortality were the main outcomes. Twenty-seven patients were included. Complete tumor resection was performed in 21 cases. The median tumor size was 8.2 cm. Mitotane was the most common adjuvant/palliative therapy (n = 13). Recurrence occurred in 6 patients, after a median time of 7.2 months, and was more common among those with larger tumors (P =.008), higher Weiss score (P =.001), and microscopic tumoral necrosis (P =.002). Ten patients died from the disease. Older age (P =.04), larger tumor size (P =.002), metastatic disease (P =.003), previous recurrence (P =.003), incomplete resection (P =.002), intraoperative tumor spillage (P =.005), higher Weiss score (P =.03), microscopic necrosis (P =.005), and capsular invasion (P =.02) were all associated with increased death risk. Even though complete tumor resection was performed in most cases, a considerable number of cases of childhood ACT resulted in recurrence and death. Early identification of unfavorable outcomes is essential to determine ideal therapy and appropriate surveillance.