[Clinical treatment and prognosis of adrenocortical carcinoma with venous tumor thrombus].

OBJECTIVE: To analyze the clinicopathological features, prognostic value and surgical treatment experience in patients with adrenocortical carcinoma with venous tumor thrombus. METHODS: We collected relevant data of the patients with adrenocortical carcinoma who had undergone surgery in Peking University Third Hospital from 2018 to 2023. The patients were divided into venous tumor thrombus group and non-tumor thrombus group. The Wilcoxon rank sum test was used to compare the quantitative variables. The chi-squared test and Fisher's exact test were used to compare the categorical variables. The Kaplan-Meier method was used to estimate the survival rate. RESULTS: A total of 27 patients with adrenocortical carcinoma were included, of whom 11 cases (40.7%) had venous tumor thrombus. In the patients with venous tumor thrombus, 8 patients were female and 3 were male. The median age was 49 (36, 58) years. The median body mass index was 26.0 (24.1, 30.4) kg/m2. Seven patients presented with symptoms at their initial visit. Six patients had a history of hypertension. Elevated levels of cortisol were observed in 2 cases. Three tumors were found on the left side, while 8 were found on the right side. Median tumor diameter was 9.4 (6.5, 12.5) cm. On the left, there was a case of tumor thrombus limited to the central vein of the left adrenal gland without invasion into the left renal vein, and two cases of tumor thrombus growth extending into the inferior vena cava below the liver. One case of tumor thrombus on the right adrenal central vein did not invade the inferior vena cava. Four cases of tumor thrombus invaded the inferior vena cava below the liver and three cases extended to the posterior of the liver. Ten patients were in European Network for the Study of Adrenal Tumors (ENSAT) stage Ⅲ and one was in ENSAT stage Ⅳ. Open surgery was performed in 6 cases, laparoscopic surgery alone in 4 cases and robot-assisted laparoscopic surgery in 1 case. Two patients underwent ipsilateral kidney resection. Median operative time was 332 (261, 440) min. Median intraoperative bleeding was 900 (700, 2 200) mL. Median hospital stay was 9 (5, 10) days. Median survival time for the patients with tumor thrombus was 24.0 months and median time to recurrence was 7.0 months. The median survival and recurrence time of 16 patients without tumor thrombus were not reached. The patients with tumor thrombus had worse 3-year overall survival (OS) rate (40.9% vs. 71.4%; Log-rank, P=0.038) and 2-year recurrence-free survival (RFS) (9.1% vs.53.7%; Log-rank, P=0.015) rates compared with the patients with non-tumor thrombus. CONCLUSION: Patients with adrenocortical carcinoma with venous tumor thrombus have poor prognosis. Different adrenal tumor resections and venous tumor thrombus removal procedures based on different tumor thrombus locations are safe and effective in treating this disease.

Fully-automated CT derived body composition analysis reveals sarcopenia in functioning adrenocortical carcinomas.

Determination of body composition (the relative distribution of fat, muscle, and bone) has been used effectively to assess the risk of progression and overall clinical outcomes in different malignancies. Sarcopenia (loss of muscle mass) is especially associated with poor clinical outcomes in cancer. However, estimation of muscle mass through CT scan has been a cumbersome, manually intensive process requiring accurate contouring through dedicated personnel hours. Recently, fully automated technologies that can determine body composition in minutes have been developed and shown to be highly accurate in determining muscle, bone, and fat mass. We employed a fully automated technology, and analyzed images from a publicly available cancer imaging archive dataset (TCIA) and a tertiary academic center. The results show that adrenocortical carcinomas (ACC) have relatively sarcopenia compared to benign adrenal lesions. In addition, functional ACCs have accelerated sarcopenia compared to non-functional ACCs. Further longitudinal research might shed further light on the relationship between body component distribution and ACC prognosis, which will help us incorporate more nutritional strategies in cancer therapy.

Venous thromboembolism in adrenocortical carcinoma: a retrospective analysis.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of death in patients with cancer. Limited data exist about VTE in patients with adrenocortical carcinoma (ACC). The primary objective of this study was to identify the prevalence of VTE in a cohort of patients with ACC. Secondary objectives were to determine the impact of VTE events on overall survival (OS) and to describe the characteristics of VTE in patients with ACC. PATIENTS AND METHODS: We retrospectively reviewed data from 289 patients with ACC cared for at a major referral center from February 2010 to June 2022. RESULTS: VTE prevalence was 18.7% (54 events). Thirty patients (55.6%) had pulmonary embolism (PE); 12 patients (22.2%) had deep vein thrombosis (DVT); and 12 patients (22.2%) had both PE and DVT. VTE occurred after ACC diagnosis in 50 patients (92.6%) including 44 patients (88%) with stage 3 or 4 ACC. VTEs were CTCAE grade ≤2 in 32 cases (59.3%), grade 3 in 17 (31.5%), and grade 4 in 2 (3.7%). Thirteen patients (24%) died within 6 months after VTE diagnosis, although there was no statistically significant association between VTE and overall survival. CONCLUSION: Despite the potential to underestimate the prevalence of VTEs, we found a high frequency of VTE events in patients with ACC. A majority of VTEs occurred in the context of advanced ACC and we observed high short-term mortality. Further studies are needed to validate our findings and investigate mechanisms associated with VTE in ACC.

Mild autonomous cortisol secretion: pathophysiology, comorbidities and management approaches.

The majority of incidentally discovered adrenal tumours are benign adrenocortical adenomas and the prevalence of adrenocortical adenomas is around 1-7% on cross-sectional abdominal imaging. These can be non-functioning adrenal tumours or they can be associated with autonomous cortisol secretion on a spectrum that ranges from rare clinically overt adrenal Cushing syndrome to the much more prevalent mild autonomous cortisol secretion (MACS) without signs of Cushing syndrome. MACS is diagnosed (based on an abnormal overnight dexamethasone suppression test) in 20-50% of patients with adrenal adenomas. MACS is associated with cardiovascular morbidity, frailty, fragility fractures, decreased quality of life and increased mortality. Management of MACS should be individualized based on patient characteristics and includes adrenalectomy or conservative follow-up with treatment of associated comorbidities. Identifying patients with MACS who are most likely to benefit from adrenalectomy is challenging, as adrenalectomy results in improvement of cardiovascular morbidity in some, but not all, patients with MACS. Of note, diagnosis and management of patients with bilateral MACS is especially challenging. Current gaps in MACS clinical practice include a lack of specific biomarkers diagnostic of MACS-related health outcomes and a paucity of clinical trials demonstrating the efficacy of adrenalectomy on comorbidities associated with MACS. In addition, little evidence exists to demonstrate the efficacy and safety of long-term medical therapy in patients with MACS.

Case report: A rare combination of aldosterone-secreting adrenocortical carcinoma and papillary thyroid carcinoma with Graves' disease.

Adrenocortical carcinoma (ACC) is a rare malignancy originating in the adrenal glands, aldosterone-producing ACC, even rarer. Papillary thyroid carcinoma (PTC), by contrast, accounts for the majority of thyroid carcinomas. We herein describe the first reported case of a female with comorbidities of aldosterone-producing ACC, PTC, and Graves' Disease(GD). The patient achieved transient clinical remission following adrenalectomy. However, three months later, aldosterone-producing ACC lung metastases emerged. Subsequently, within another three-month interval, she developed thyroid eye disease(TED). The patient died roughly one year after the adrenal operation. Exome sequencing did not reveal associations between aldosterone-producing ACC, PTC, and GD, and the underlying concurrence mechanism has yet to be elucidated. Further research of similar cases are needed to confirm potential links between the three pathologies.

Rare Coexistence of Aldosterone-producing Adrenocortical Adenoma Confirmed by an Immunohistochemical Analysis of Steroidogenic Enzymes with Adrenal Ectopic Thyroid Tissue: A Case Report and Literature Review.

A 56-year-old man presented with a history of hypertension; clinically, the patient had primary aldosteronism (PA) and a 4-cm left adrenal tumor. The left adrenal glands, resected by adrenalectomy, also contained ectopic thyroid tissue (ETT). An immunohistochemical analysis of steroid-converting enzymes revealed an aldosterone-producing adenoma (APA). Among 19 previously reported cases of adrenal ETT, 4 had adrenal hormonal abnormalities, all of which were PA. This is the first case of adrenal ETT coexisting with APA, confirmed by steroid-converting enzyme expression. Further analyses using cumulative case data are required to clarify the correlation between adrenal ETT and APA.

Efficacy of metyrapone for symptoms of adrenocortical carcinoma.

Elevated cortisol by adrenocortical carcinoma leads to a variety of symptoms. We report on the efficacy of metyrapone in treatment of a variety of distressing symptoms caused by elevated cortisol in a patient who refused advanced treatment for adrenocortical carcinoma.

Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes.

CONTEXT: Clinical implications of unilateral primary aldosteronism (PA) histopathology remain to be determined in various ethnic populations. OBJECTIVE: We examined the histopathology of unilateral PA using CYP11B2 immunostaining in relation to clinical phenotypes and postsurgical outcomes. METHODS: Patients consecutively operated for unilateral PA from 2010 to 2020 at 3 tertiary hospitals in South Korea were retrospectively enrolled. Adrenals with solitary aldosterone-producing adenomas and/or dominant aldosterone-producing nodules were classified as the classical and the others as the nonclassical groups. The classical group was subdivided into mixed or solitary group according to whether other aldosterone-producing lesions coexist or not. RESULTS: Of the 240 cases, 124 were solitary, 86 mixed, and 30 nonclassical. Baseline serum potassium concentration was lower in the solitary group than the mixed or nonclassical group. Plasma aldosterone concentration after saline loading was the highest in the solitary group (median 31.65 ng/dL), followed by the mixed group (median 25.40 ng/dL), and the lowest in the nonclassical group (median 14.20 ng/dL). Solitary and mixed groups showed higher lateralization indices and lower contralateral indices than the nonclassical group. The contralateral index was lower in the solitary group than the mixed group. At 6 to 12 months after adrenalectomy, fewer antihypertensive medications were required for the solitary and mixed groups than the nonclassical group. CONCLUSION: The solitary group, followed by the mixed group, was associated with more severe hyperaldosteronism and more suppressed aldosterone production from the contralateral side than the nonclassical group. Histopathologic phenotypes were related to the clinical manifestations and may suggest postoperative prognosis.

Case Report: Adrenocortical carcinoma in children-symptoms, diagnosis, and treatment.

Adrenocortical carcinomas are extremely rare in the paediatric population. Most of them are hormone-secretive lesions; therefore, they should be taken into consideration in a child with signs of precocious puberty and/or Cushing's syndrome symptoms. Nonetheless, differentiation from benign adrenal tumours is necessary. We report a rare case of adrenocortical carcinoma in a girl and a literature review using the PubMed database. A four-year-old girl presented with rapidly progressing precocious puberty and signs of Cushing's syndrome. Imaging of the abdomen revealed a large heterogeneous solid mass. Histopathologic evaluation confirmed adrenocortical carcinoma with high mitotic activity, atypical mitoses, pleomorphism, necrosis, and vascular invasion. After tumourectomy, a decrease of previously elevated hormonal blood parameters was observed. Genetic tests confirmed Li Fraumeni syndrome. Adrenocortical carcinoma should be suspected in children with premature pubarche and signs of Cushing's syndrome. Diagnosis must be based on clinical presentation, hormonal tests, imaging, and histopathological evaluation. Complete surgical resection of the tumour is the gold standard. Oncological treatment in children is not yet well-studied and should be individually considered, especially in advanced, inoperable carcinomas with metastases. Genetic investigations are useful for determining the prognosis in patients and their siblings.

[Comparison of coagulation function between adrenocorticotropic hormone independent Cushing syndrome and nonfunctional adrenal adenoma and its influence factors].

OBJECTIVE: To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS). METHODS: In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups. RESULTS: In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001; (29.22±3.39) s vs. (31.86±3.63) s, P < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher (P < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% vs. 3.5%, P < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% vs. 6.6%, P=0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (r=-0.315, P < 0.001) and APTT (r=-0.410, P < 0.001), and positively associated with FDP (r=0.303, P < 0.001) and D-dimer levels (r=0.258, P < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients (P < 0.05). CONCLUSION: ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.

Right Adrenocortical Carcinoma Coexisting With Left Adrenal Sarcomatoid Carcinoma on FDG PET/CT.

ABSTRACT: Bilateral adrenal glands synchronously involved by different types of pathologies are uncommon. An 80-year-old man underwent FDG PET/CT to evaluate bilateral adrenal masses, which were initially discovered by ultrasonography and confirmed by MRI. The images demonstrated elevated FDG activity in both lesions, which were subsequently diagnosed as concurrent right adrenocortical carcinoma and left adrenal sarcomatoid carcinoma respectively by histopathological examination.

Adrenal tumors treated by adrenalectomy following spontaneous rupture carry an overall favorable prognosis: retrospective evaluation of outcomes in 59 dogs and 3 cats (2000-2021).

OBJECTIVE: To conduct a retrospective multi-institutional study reporting short- and long-term outcomes of adrenalectomy in patients presenting with acute hemorrhage secondary to spontaneous adrenal rupture. ANIMALS: 59 dogs and 3 cats. METHODS: Medical records of dogs and cats undergoing adrenalectomy between 2000 and 2021 for ruptured adrenal masses were reviewed. Data collected included clinical presentation, preoperative diagnostics, surgical report, anesthesia and hospitalization findings, histopathology, adjuvant treatments, and long-term outcome (recurrence, metastasis, and survival). RESULTS: Median time from hospital admission to surgery was 3 days, with 34% of surgeries being performed emergently (within 1 day of presentation). Need for intraoperative blood transfusion was significantly associated with emergent surgery and presence of active intraoperative hemorrhage. The short-term (≤ 14 days) complication and mortality rates were 42% and 21%, respectively. Negative prognostic factors for short-term survival included emergent surgery, intraoperative hypotension, and performing additional surgical procedures. Diagnoses included adrenocortical neoplasia (malignant [41%], benign [12%], and undetermined [5%]), pheochromocytoma (38%), a single case of adrenal fibrosis and hemorrhage (2%), and a single case of hemangiosarcoma (2%). Local recurrence and metastasis of adrenocortical carcinoma were confirmed in 1 and 3 cases, respectively. Overall median survival time was 574 days and 900 days when short-term mortality was censored. No significant relationship was found between histopathological diagnosis and survival. CLINICAL RELEVANCE: Adrenalectomy for ruptured adrenal gland masses was associated with similar short- and long-term outcomes as compared with previously reported nonruptured cases. If hemodynamic stability can be achieved, delaying surgery and limiting additional procedures appear indicated to optimize short-term survival.

Cortisol-Producing Adrenocortical Carcinoma Presenting with Hypertensive Emergency.

BACKGROUND Hypertensive crisis is a relatively common condition often due to uncontrolled essential hypertension, but also potentially driven by one of many possible secondary etiologies. In this report, we detail a case of new-onset resistant hypertension leading to hypertensive emergency complicated by myocardial infarction and congestive heart failure secondary to underlying cortisol-producing metastatic adrenocortical carcinoma. CASE REPORT A 57-year-old woman with no past medical history presented with generalized weakness and weight gain. Her blood pressure was 239/141 with a pulse of 117. Other vital signs were normal. A physical exam was notable for obesity and lower-extremity edema. Initial serum investigations were notable for leukocytosis, hypokalemia, metabolic alkalosis, and elevated troponin and BNP. An ECG showed anterolateral ST depression and left ventricular hypertrophy. A coronary angiogram revealed no coronary artery disease. Her ejection fraction was 25% by echocardiogram. Further investigation revealed severely elevated serum cortisol levels. CT scans were notable for left adrenal mass with evidence of hepatic, lung, and bone metastasis. A liver biopsy confirmed metastatic adrenocortical carcinoma. The patient was started on antihypertensives and a steroidogenesis inhibitor, with improvement in her blood pressure. She received palliative chemotherapy but later elected to pursue hospice care. CONCLUSIONS This report highlights the potential for underlying cortisol excess and adrenocortical carcinoma as a potential secondary etiology of resistant hypertension and hypertensive crisis. Due to the aggressive nature of this tumor, as demonstrated in this patient, a high index of suspicion and prompt attention are required for patients presenting with these clinical manifestations.

Primary Aldosteronism: Spatial Multiomics Mapping of Genotype-Dependent Heterogeneity and Tumor Expansion of Aldosterone-Producing Adenomas.

BACKGROUND: Primary aldosteronism is frequently caused by an adrenocortical aldosterone-producing adenoma (APA) carrying a somatic mutation that drives aldosterone overproduction. APAs with a mutation in KCNJ5 (APA-KCNJ5MUT) are characterized by heterogeneous CYP11B2 (aldosterone synthase) expression, a particular cellular composition and larger tumor diameter than those with wild-type KCNJ5 (APA-KCNJ5WT). We exploited these differences to decipher the roles of transcriptome and metabolome reprogramming in tumor pathogenesis. METHODS: Consecutive adrenal cryosections (7 APAs and 7 paired adjacent adrenal cortex) were analyzed by spatial transcriptomics (10x Genomics platform) and metabolomics (in situ matrix-assisted laser desorption/ionization mass spectrometry imaging) co-integrated with CYP11B2 immunohistochemistry. RESULTS: We identified intratumoral transcriptional heterogeneity that delineated functionally distinct biological pathways. Common transcriptomic signatures were established across all APA specimens which encompassed 2 distinct transcriptional profiles in CYP11B2-immunopositive regions (CYP11B2-type 1 or 2). The CYP11B2-type 1 signature was characterized by zona glomerulosa gene markers and was detected in both APA-KCNJ5MUT and APA-KCNJ5WT. The CYP11B2-type 2 signature displayed markers of the zona fasciculata or reticularis and predominated in APA-KCNJ5MUT. Metabolites that promote oxidative stress and cell death accumulated in APA-KCNJ5WT. In contrast, antioxidant metabolites were abundant in APA-KCNJ5MUT. Finally, APA-like cell subpopulations-negative for CYP11B2 gene expression-were identified in adrenocortical tissue adjacent to APAs suggesting the existence of tumor precursor states. CONCLUSIONS: Our findings provide insight into intra- and intertumoral transcriptional heterogeneity and support a role for prooxidant versus antioxidant systems in APA pathogenesis highlighting genotype-dependent capacities for tumor expansion.

Peripheral precocious puberty in Li-Fraumeni syndrome: a case report and literature review of pure androgen-secreting adrenocortical tumors.

INTRODUCTION: Pure androgen-secreting adrenocortical tumors are a rare but important cause of peripheral precocious puberty. CASE PRESENTATION: Here, we report a pure androgen-secreting adrenocortical tumor in a 2.5-year-old boy presenting with penile enlargement, pubic hair, frequent erections, and rapid linear growth. We confirmed the diagnosis through laboratory tests, medical imaging, and histology. Furthermore, genetic testing detected a pathogenic germline variant in the TP53 gene, molecularly confirming underlying Li-Fraumeni syndrome. DISCUSSION: Only 15 well-documented cases of pure androgen-secreting adrenocortical tumors have been reported so far. No clinical or imaging signs were identified to differentiate adenomas from carcinomas, and no other cases of Li-Fraumeni syndrome were diagnosed in the four patients that underwent genetic testing. However, diagnosing Li-Fraumeni syndrome is important as it implies a need for intensive tumor surveillance and avoidance of ionizing radiation. CONCLUSION: In this article, we emphasize the need to screen for TP53 gene variants in children with androgen-producing adrenal adenomas and report an association with arterial hypertension.

[Comparison the characteristics of serum adrenocortical hormone profile in patients with adrenal cortical carcinoma and adrenal coritcal adenoma].

Objective: To compare the characteristics of serum adrenocortical hormone profiles detected by liquid chromatography tandem mass spectrometry in patients with adrenal cortical carcinoma and adrenal adenoma. Methods: A total of 23 patients with adrenal cortical carcinoma and 119 patients with adrenal cortical adenoma/hyperplasia who visited the Department of Endocrinology and/or the Department of Urology of Peking University First Hospital from January 2018 to June 2022 were analyzed retrospectively. The imaging characteristics and serum adrenal cortical hormone profiles detected by liquid chromatography tandem mass spectrometry were analyzed retrospectively. The independent related factors of adrenal cortical carcinoma were screened by univariate analysis and multivariate logistic regression analysis. Results: The age of patients with adrenal cortical carcinoma was 46 (35, 57) years, and 15 (65.2%) were female; The age of adrenal cortical adenoma patients was 49 (40, 58) years old, and 80 (67.2%) were female. There was no significant difference in age and gender between the two groups (all P values>0.05). The maximum tumor diameter M (Q1, Q3) of patients with adrenocortical carcinoma was 7.05 (5.45, 9.78) cm, which was larger than that of patients with adrenocortical adenoma [2.1 (1.6, 3.0) cm] (P<0.001). Compared with patients with adrenal adenoma, the androstenedione (AD) of patients with adrenal cortical carcinoma [4.056 9 (1.619 5, 7.907 9) nmol/L vs 1.517 5 (0.935 1, 2.582 1) nmol/L (P<0.001)] was significantly increased; 11-ketotestosterone/11-ketoandrostenedione [0.034 3 (0.020 6, 0.079 2) vs 0.041 0 (0.028 6, 0.061 5) (P=0.089)] and 11-ketoandrostenedione/11-hydroxyandrostenedione [0.013 0 (0.006 4, 0.086 7) vs 0.063 0 (0.018 2, 0.162 5) (P=0.042)] were significantly decreased. Multivariate analysis found that AD, the largest diameter of the tumor, 11-ketotestosterone/11-ketoandrostenedione and 11-ketoandrostenedione/11-hydroxyandrostenedi-one were related factors for adrenal cortical carcinoma, with OR values (95%CI) of 1.841 (1.093-3.100), 5.130 (2.332-11.285), 0.381 (0.167-0.867) and 0.000 (0.000-0.014), respectively, all P values <0.05. Conclusions: The larger diameter of adrenal cortical tumor and the higher the level of androstenedione are independent risk factors for adrenal cortical carcinoma. The reduction conversion of 11-hydroxyandrostenedione to 11-ketoandrostenedione and 11-ketoandrostenedione to 11-ketotestosterone were independently associated with adrenal cortical carcinoma.