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Current Medical Imaging Apr 2023Extra-adrenal non-functional adrenocortical carcinoma (ACC)is an extremely rare tumor with only eight cases having been reported at different localizations.
BACKGROUND
Extra-adrenal non-functional adrenocortical carcinoma (ACC)is an extremely rare tumor with only eight cases having been reported at different localizations.
CASE PRESENTATION
A 60-year-old woman was presented to our hospital with abdominal pain. Magnetic resonance imaging revealed a solitary mass abutting the wall of the small bowel. She underwent resection of the mass, and the results of histopathology and immunohistochemistry were consistent with ACC.
CONCLUSION
We report the first occurrence of non-functional adrenocortical carcinoma in the wall of the small bowel in the literature. Magnetic resonance examination is sensitive enough to indicate the accurate location of the tumor and is of great help to clinical operation.
PubMed: 37070449
DOI: 10.2174/1573405620666230417085102 -
BMC Urology Apr 2023Adrenal incidentalomas are radiologically discovered tumors that represent a variety of pathologies, with the diagnosis clinched only on surgical pathology. These tumors...
BACKGROUND
Adrenal incidentalomas are radiologically discovered tumors that represent a variety of pathologies, with the diagnosis clinched only on surgical pathology. These tumors may be clinically monitored, but triggers for surgery include size > 4 cm, concerning features on radiology, or hormonally functioning. Adrenal oncocytic neoplasms (AONs) are notably rare and typically nonfunctional tumors that are discovered as incidentalomas and exist on a spectrum of malignant potential.
CASE PRESENTATION
We discovered an exceptionally large (15 cm in the greatest dimension) incidentaloma in a 73-year-old man with left back pain and he was treated with robotic-assisted adrenalectomy. Surgical pathology was consistent with AON of borderline uncertain malignant potential; adjuvant mitotane and radiation were omitted based on shared decision-making.
CONCLUSION
Large AONs are rare, usually benign tumors that can be safely treated with robotic-assisted adrenalectomy. Surgical pathology is the crux of diagnosis and post-operative management, as it informs both the initiation of adjuvant therapy and the stringency of post-operative surveillance.
Topics: Male; Humans; Aged; Adrenal Gland Neoplasms; Adrenalectomy; Robotics; Adenoma, Oxyphilic; Incidental Findings
PubMed: 37061691
DOI: 10.1186/s12894-023-01238-1 -
International Journal of Molecular... Apr 2023Adrenocortical cancer (ACC) is a rare malignancy with a dismal prognosis. The treatment includes mitotane and EDP chemotherapy (etoposide, doxorubicin, and cisplatin)....
BACKGROUND
Adrenocortical cancer (ACC) is a rare malignancy with a dismal prognosis. The treatment includes mitotane and EDP chemotherapy (etoposide, doxorubicin, and cisplatin). However, new therapeutic approaches for advanced ACC are needed, particularly targeting the metastatic process. Here, we deepen the role of progesterone as a new potential drug for ACC, in line with its antitumoral effect in other cancers.
METHODS
NCI-H295R, MUC-1, and TVBF-7 cell lines were used and xenografted in zebrafish embryos. Migration and invasion were studied using transwell assays, and MMP2 activity was studied using zymography. Apoptosis and cell cycle were analyzed by flow cytometry.
RESULTS
Progesterone significantly reduced xenograft tumor area and metastases formation in embryos injected with metastatic lines, MUC-1 and TVBF-7. These results were confirmed in vitro, where the reduction of invasion was mediated, at least in part, by the decrease in MMP2 levels. Progesterone exerted a long-lasting effect in metastatic cells. Progesterone caused apoptosis in NCI-H295R and MUC-1, inducing changes in the cell-cycle distribution, while autophagy was predominantly activated in TVBF-7 cells.
CONCLUSION
Our results give support to the role of progesterone in ACC. The involvement of its analog (megestrol acetate) in reducing ACC progression in ACC patients undergoing EDP-M therapy is now under investigation in the PESETA phase II clinical study.
Topics: Animals; Humans; Adrenocortical Carcinoma; Progesterone; Matrix Metalloproteinase 2; Zebrafish; Cell Line, Tumor; Adrenal Cortex Neoplasms
PubMed: 37047801
DOI: 10.3390/ijms24076829 -
Frontiers in Endocrinology 2023Adult pure androgen-secreting adrenal tumors (PASATs) are extremely rare, and their characteristics are largely unknown.
BACKGROUND
Adult pure androgen-secreting adrenal tumors (PASATs) are extremely rare, and their characteristics are largely unknown.
METHODS
A rare case of adult bilateral PASATs was reported, and a systematic literature review of adult PASATs was conducted to summarize the characteristics of PASATs.
RESULTS
In total, 48 studies, including 40 case reports and 8 articles, were identified in this review. Analysis based on data of 42 patients (including current case and 41 patients from 40 case reports) showed that average age was 40.48 ± 15.80 years (range of 18-76). The incidence of adult PASAT peaked at 21-30 years old, while that of malignant PASAT peaked at 41-50 years old. Most PASAT patients were female (40/42, 95.23%), and hirsutism was the most common symptom (37/39, 94.87%). Testosterone (T) was the most commonly elevated androgen (36/42, 85.71%), and 26 of 32 tested patients presented increased dehydroepiandrosterone sulfate (DS) levels. In malignancy cases, disease duration was significantly decreased (1.96 vs. 4.51 years, P=0.025), and tumor diameter was significantly increased (8.9 vs. 4.9 cm, p=0.011). Moreover, the androgen levels, namely, T/upper normal range limit (UNRL) (11.94 vs. 4.943, P=0.770) and DS/UNRL (16.5 vs. 5.28, P=0.625), were higher in patients with malignancy. In total, 5 out of 7 patients showed an increase in DS or T in the human chorionic gonadotropin (HCG) stimulation test. Overall, 41 out of 42 patients (including current case) underwent adrenal surgery, and recurrence, metastasis, or death was reported in 5 out of 11 malignant patients even with adjuvant or rescue mitotane chemotherapy.
CONCLUSION
Adult PASAT, which is predominant in women, is characterized by virilism and menstrual dysfunction, especially hirsutism. Elevated T and DS may contribute to the diagnosis of adult PASAT, and HCG stimulation test might also be of help in diagnosis. Patients with malignant PASAT have a shorter disease duration, larger tumor sizes and relatively higher androgen levels. Surgery is recommended for all local PASATs, and Malignancy of PASAT should be fully considered due to the high risk of malignancy, poor prognosis and limited effective approaches.
Topics: Adult; Humans; Female; Adolescent; Young Adult; Middle Aged; Aged; Male; Androgens; Hirsutism; Adrenal Gland Neoplasms; Testosterone; Virilism
PubMed: 37033242
DOI: 10.3389/fendo.2023.1138114 -
The Journal of Clinical Endocrinology... Sep 2023Because of the rarity of adrenocortical cancer (ACC), only a few population-based studies are available, and they reported limited details in the characterization of...
CONTEXT
Because of the rarity of adrenocortical cancer (ACC), only a few population-based studies are available, and they reported limited details in the characterization of patients and their treatment.
OBJECTIVE
To describe in a nationwide cohort the presentation of patients with ACC, treatment strategies, and potential prognostic factors.
METHODS
Retrospective analysis of 512 patients with ACC, diagnosed in 12 referral centers in Italy from January 1990 to June 2018.
RESULTS
ACC diagnosed as incidentalomas accounted for overall 38.1% of cases, with a frequency that increases with age and with less aggressive pathological features than symptomatic tumors. Women (60.2%) were younger than men and had smaller tumors, which more frequently secreted hormones. Surgery was mainly done with an open approach (72%), and after surgical resection, 62.7% of patients started adjuvant mitotane therapy. Recurrence after tumor resection occurred in 56.2% of patients. In patients with localized disease, cortisol secretion, ENSAT stage III, Ki67%, and Weiss score were associated with an increased risk of recurrence, whereas margin-free resection, open surgery, and adjuvant mitotane treatment were associated with reduced risk. Death occurred in 38.1% of patients and recurrence-free survival (RFS) predicted overall survival (OS). In localized disease, age, cortisol secretion, Ki67%, ENSAT stage III, and recurrence were associated with increased risk of mortality. ACCs presenting as adrenal incidentalomas showed prolonged RFS and OS.
CONCLUSION
Our study shows that ACC is a sex-related disease and demonstrates that an incidental presentation is associated with a better outcome. Given the correlation between RFS and OS, RFS may be used as a surrogate endpoint in clinical studies.
Topics: Male; Humans; Female; Mitotane; Adrenocortical Carcinoma; Cohort Studies; Adrenal Gland Neoplasms; Retrospective Studies; Hydrocortisone; Ki-67 Antigen; Adrenal Cortex Neoplasms
PubMed: 37022947
DOI: 10.1210/clinem/dgad199 -
Frontiers in Endocrinology 2023The prognosis of adrenocortical carcinoma (ACC) is poor but highly variable. The present study aimed to characterize patients with ACC at a single center in Taiwan and...
BACKGROUND
The prognosis of adrenocortical carcinoma (ACC) is poor but highly variable. The present study aimed to characterize patients with ACC at a single center in Taiwan and to determine the prognostic predictors of overall and progression-free survival.
METHODS
Medical records of patients, who were diagnosed with ACC at Taipei Veterans General Hospital between January 1992 and June 2021, were reviewed. Patient demographics, tumor characteristics, and subsequent treatment were analyzed with regard to overall survival and progression-free survival using Kaplan-Meier methods and a Cox regression model.
RESULTS
Sixty-seven patients were included. Females (65.7%) were more susceptible to ACC, with a younger onset and active hormonal secretion. One-half of the patients exhibited distant metastases at the time of diagnosis. The European Network for the Study of Adrenal Tumours (ENSAT) stage (hazard ratio [HR] 3.60 [95% confidence interval (CI) 1.25-10.38]; p=0.018), large vessel invasion (HR 5.19 [95% CI 1.75-15.37]; p=0.003), and mitotane use (HR 0.27 [95% CI 0.11-0.70]; p=0.007) were significantly associated with overall survival (OS). There was no single factor independently associated with progression-free survival.
CONCLUSION
ENSAT stage had a substantial impact on overall survival though there was no difference in OS between patients with stage II and stage III ACC. Large vessel invasion portended poor prognosis and influenced OS significantly. Moreover, mitotane only improved clinical outcomes of patients with stage IV disease.
Topics: Female; Humans; Adrenocortical Carcinoma; Prognosis; Mitotane; Adrenal Cortex Neoplasms; Neoplasm Recurrence, Local
PubMed: 36967802
DOI: 10.3389/fendo.2023.1134643 -
Expert Opinion on Pharmacotherapy Apr 2023Untreated Cushing's syndrome (CS) is associated with significant morbidity and mortality. Cortisol normalization is a key goal to treatment. Pituitary surgery remains...
INTRODUCTION
Untreated Cushing's syndrome (CS) is associated with significant morbidity and mortality. Cortisol normalization is a key goal to treatment. Pituitary surgery remains the first-line approach for Cushing's disease, but sometimes it is impracticable, unsuccessful, or complicated by recurrence. Medical therapy has been historically considered a palliative. However, in the latest years, interest on this topic has grown due to both the availability of new drugs and the reevaluation of the old, commonly used drugs in clinical practice.
AREAS COVERED
In this article, we will discuss the current options and future directions of medical therapy for CS, aiming at fitting best patients' features. An extensive literature search regarding already approved and investigational principles was conducted (PubMed, ClinicalTrials.gov. Available drugs include inhibitors of ACTH secretion, steroidogenesis inhibitors, and glucocorticoid receptor antagonists; drugs acting at different levels can be also combined in uncontrolled patients.
EXPERT OPINION
Since there is still no standardized pharmacological approach and the superiority of one drug over another has not been established yet in the absence of comparative studies, each time clinicians' choices should be patient-tailored. Age, gender, tumor features, severity of hypercortisolism, comorbidities/complications, rapidity of action, side effects, drug-drug interactions, contraindications, availability, patients' preferences, and costs should be all considered.
Topics: Humans; Pituitary ACTH Hypersecretion; Cushing Syndrome
PubMed: 36927238
DOI: 10.1080/14656566.2023.2192349 -
Surgical Oncology Clinics of North... Apr 2023Adjuvant and neoadjuvant chemotherapy in the treatment of adrenocortical carcinoma (ACC) is limited by few existing trials, most of which are retrospective. The drug... (Review)
Review
Adjuvant and neoadjuvant chemotherapy in the treatment of adrenocortical carcinoma (ACC) is limited by few existing trials, most of which are retrospective. The drug mitotane has been used for the treatment of ACC, although existing guidelines only support its use in high risk of recurrence. The first phase 3 trial involving systemic chemotherapy for ACC supports the use of etoposide, doxorubicin, cisplatin, and mitotane for combination therapy. No significant breakthrough has been discovered thus far in of targeted and immunotherapies. Neoadjuvant chemotherapy is only used to allow for complete surgical resection because complete excision is the definitive treatment of ACC.
Topics: Humans; Adrenocortical Carcinoma; Mitotane; Neoadjuvant Therapy; Adrenal Cortex Neoplasms; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant
PubMed: 36925185
DOI: 10.1016/j.soc.2022.10.005 -
American Journal of Cancer Research 2023Although N7-methylguanosine (m7G) is one of the most frequent RNA modifications, it has received little attention. Adrenocortical carcinoma (ACC) is a highly malignant...
Although N7-methylguanosine (m7G) is one of the most frequent RNA modifications, it has received little attention. Adrenocortical carcinoma (ACC) is a highly malignant and easily metastatic tumor, eagerly needing for novel therapeutic strategy. Herein, a novel m7G risk signature (METTL1, NCBP1, NUDT1 and NUDT5) was constructed using the Lasso regression analysis. It possessed highly prognostic value and could improve the predictive accuracy and clinical making-decision benefit of traditional prognostic model. Its prognostic value was also successfully validated in GSE19750 cohort. Through CIBERSORT, ESTIMATE, ssGSEA and GSEA analyzes, high-m7G risk score was found to be closely associated with increased enrichment of glycolysis and suppression of anti-cancer immune response. Therapeutic correlation of m7G risk signature was also investigated using tumor mutation burden, the expressions of immune checkpoints, TIDE score, IMvigor 210 cohort and TCGA cohort. m7G risk score was a potential biomarker for predicting the efficacy of ICBs and mitotane. Furthermore, we explored the biofunctions of METTL1 in ACC cells through a series of experimentations. Overexpression of METTL1 stimulated the proliferation, migration and invasion of H295R and SW13 cells. Immunofluorescence assays revealed that the infiltrating levels of CD8+ T cells was lower and that of macrophages was higher in clinical ACC samples with high METTL1 expression compared to that in low expression ones. Silencing METTL1 could significantly inhibited tumor growth in mouse xenograft model. Western blot assays showed that METTL1 positively regulated the expression of glycolysis rate-limiting enzyme HK1. Finally, miR-885-5p and CEBPB were predicted as the upstream regulators of METTL1 through data mining of the public databases. In conclusions, m7G regulatory genes well represented by METTL1 profoundly affected the prognosis, tumor immune, therapeutic outcomes, and malignant progression of ACC.
PubMed: 36895966
DOI: No ID Found -
The Journal of Clinical Endocrinology... Aug 2023Central hypothyroidism was described previously in mitotane-treated patients but data on its prevalence and time of occurrence are limited. (Review)
Review
CONTEXT
Central hypothyroidism was described previously in mitotane-treated patients but data on its prevalence and time of occurrence are limited.
OBJECTIVE
To better characterize thyroid hormone insufficiency in patients exposed to mitotane.
METHODS
We reviewed medical records of patients from 2 academic centers in Montreal (Canada) and Toulouse (France) with exposure to mitotane therapy for adrenocortical cancer between 1995 and 2020. We analyzed the thyroid function parameters during and after treatment.
RESULTS
In our cohort of 83 patients, 17 were excluded because of preexisting primary hypothyroidism or drug-induced hypothyroidism. During follow-up, 3/66 patients maintained a normal thyroid function and 63/66 developed central hypothyroidism. Among those 63 patients, 56 presented with an inappropriately normal or low TSH and 7 with a mildly elevated TSH. The onset of hypothyroidism was: <3 months in 33.3%, 3 to 6 months in 19.1%, 6 to 9 months in 14.3%, and 9 to 12 months in 9.5%. At least 14.3% of cases occurred after 12 months of exposure, and 6 patients had an undetermined time of occurrence. Over time, 27 patients stopped mitotane and partial (42.3%) or complete (23.1%) recovery from hypothyroidism was observed, mainly in the first 2 years after mitotane discontinuation.
CONCLUSION
Mitotane therapy is frequently associated with new onset of central hypothyroidism with a prevalence of 95.5%. Most cases occurred in the first year of treatment. Partial or full recovery of thyroid function occurs in 65.4% of cases. This study supports the importance of systematic monitoring of TSH and free T4 levels during and following discontinuation of mitotane therapy.
Topics: Humans; Mitotane; Prevalence; Antineoplastic Agents, Hormonal; Hypothyroidism; Adrenal Cortex Neoplasms; Thyrotropin; Adrenocortical Carcinoma
PubMed: 36856782
DOI: 10.1210/clinem/dgad115