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.

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.

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.

[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.

Huge Hematoma as First Manifestation of Adrenocortical Carcinoma: A Case Report.

BACKGROUND Adrenocortical carcinoma (ACC) is a rare malignancy associated with unfavorable prognosis. It is mainly diagnosed in the fifth or sixth decade of life. Symptoms of ACC are associated with hormonal activity, presence of metastases, and size of the tumor. The treatment and prognosis depend on the stage of the disease assessed with the ENSAT staging system. CASE REPORT A 38-year-old White man was admitted to our department from the city hospital due to a huge hematoma of the right adrenal gland (130×100 mm). On admission, the patient's condition was stable, and no active bleeding or other complications were present. Therefore, initially, conservative treatment was performed. The control CT scan showed reduction of the hematoma (90×80 mm). Due to the unknown character of the tumor and the sudden onset of bleeding, the patient was prepared for elective surgery according to the phaeochromocytoma surgery protocol. Following preparation, the patient underwent right-sided adrenalectomy. In the postoperative histopathological examination, adrenocortical carcinoma was diagnosed, which allowed the patient to receive appropriate oncological treatment. CONCLUSIONS There is currently no clear algorithm for the management of adrenal hemorrhage. A hemodynamically unstable patient requires urgent surgical treatment. Patients in good general condition should be prepared for early elective surgery.

Adrenocortical carcinoma with venous tumor invasion: is there a role for mini-invasive surgery?

OBJECTIVE: This study aims to investigate early oncologic outcomes in patients with adrenocortical carcinoma (ACC) with venous invasion (VI) treated using both open and mini-invasive approaches. PATIENTS AND MATERIALS: We conducted a retrospective analysis of 4 international referral center databases, including all the patients undergoing adrenalectomy for ACC with VI from January 2007 to March 2020. According to CT scan or MRI, the tumor thrombus was classified into four levels: (1) adrenal vein invasion; (2) renal vein invasion; (3) infra-hepatic Inferior vena cava (IVC); and (4) retro-hepatic IVC. In addition, we divided our patients into patients who had undergone open surgery and mini-invasive surgery. RESULTS: We identified 20 patients with a median follow-up of 12 months. The median tumor size was 110mm. ENSAT stage was II in 4 patients, III in 13 patients, and IV in 3 patients. Tumor thrombus extended in the adrenal vein (n=5), renal vein (n=1), infra-hepatic IVC (n=9), or into the retro-hepatic IVC (n=5). Ten patients were treated with a mini-invasive approach. The patient treated with an open approach reported a more aggressive disease. The two groups did not differ in surgical margins, surgical time, blood losses, complications, and length of stay. The prognosis resulted worse in the patient undergoing open. Kaplan-Meier analysis indicated a difference in OS for the patients stratified by ENSAT stage (Log-rank p=0.011); we also reported a difference in DFS for patients stratified for thrombus extension (p=0.004) and ENSAT stage (p<0.001). CONCLUSION: The DFS of patients with VI from ACC is influenced by the staging and the extension of the venous invasion; the staging influences the OS. The mini-invasive approach seems feasible in selected patients; however, further studies investigating the oncological outcomes are needed. A mini-invasive approach for adrenal tumors with venous invasion is an explorable option in very selected patients.

FLCN-Driven Functional Adrenal Cortical Carcinoma with High Mitotic Tumor Grade: Extending the Endocrine Manifestations of Birt-Hogg-Dubé Syndrome.

Adrenal cortical carcinoma is an aggressive and rare malignancy of steroidogenic cells of the adrenal gland. Most adult adrenal cortical carcinomas are sporadic, but a small fraction may be associated with inherited tumor syndromes, such as Li-Fraumeni, multiple endocrine neoplasia 1, Lynch syndrome, and Beckwith-Wiedemann syndrome, as well as isolated case reports of non-syndromic manifestations occurring in the context of other pathogenic germline variants. Birt-Hogg-Dubé (BHD) is a rare autosomal dominant syndrome caused by germline pathogenic variants in the FLCN gene. BHD syndrome causes a constellation of symptoms, including cutaneous manifestations, pulmonary cysts and pneumothorax, and risk of renal tumors. With the exception of a single case of adrenal cortical carcinoma, very few reports on the occurrence of adrenal cortical neoplasia in patients with BHD syndrome have been described. However, information on variant allele fraction in the tumor was not available in the index case, which precludes any mechanism supporting loss of heterozygosity. Here we present a case of an adult-onset adrenal cortical carcinoma in a 50-year-old female, found to harbor a germline likely pathogenic variant in the FLCN gene, denoted as c.694C > T (p.Gln232Ter). Genetic testing on the tumor revealed the same FLCN variant at an allele fraction of 83%, suggesting a contributory role to the pathogenesis of the adrenal cortical carcinoma. This case further supports the expansion of the clinical presentation and tumor spectrum of BHD syndrome and the need to consider germline FLCN testing in the clinical genetic workup of patients with adrenal cortical carcinomas.

Adrenal Cortical Carcinoma and Additional Rare Pathologic Findings in Multi-Organs in a Birt-Hogg-Dubé Syndrome Patient: With an Emphasis on the Molecular Characteristics of Adrenal Cortical Carcinoma.

Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disorder caused by germline alterations in the FLCN gene. We report a 38-year-old man with BHD syndrome presenting with multiple rare pathologic findings involving various organs, including adrenal cortical carcinoma (ACC). Initially, he presented with severe cholestatic jaundice and was found to have a 25 cm left adrenal mass with radiologic evidence of lung metastases, which was diagnosed as ACC on resection. Concurrently, pigmented, bile-stained granular casts were present within the kidney and diffuse cholestasis of the liver consistent with Stauffer syndrome was identified. Subsequent staging workup detected a 1.2 cm tubulovillous adenoma in the distal ascending colon and an incidental 1.2 cm thyroid nodule. Germline genetic testing revealed a pathogenic FLCN c.1285dup. Targeted DNA next generation sequencing of ACC revealed FLCN c.1285dup, IDH2 c.5332C>T, PRKAR1A c.1074del, and PDGFRB c.3282C>A and concurrent transcriptomic analysis demonstrated VEGFA overexpression. Fourteen months after resection, follow-up computerized tomography (CT) identified the progression of lung metastases and chemotherapy with etoposide doxorubicin and cisplatin was initiated. Here, we report the first ACC with the molecular characteristics in a BHD syndrome patient, although 5 adrenal lesions, including ACC, adenomas or neoplasm with malignant potential due to higher Ki67 labelling index, have been reported in the literature and no somatic analysis in these tumors were performed. Despite the rarity, our case potentially expands the tumor spectrum of BHD patients, helps to solidify possible association with adrenal cortical tumors and reiterates the value of genetic counseling in patients with ACC.

Avascular Necrosis of Femur as a Complication of Cushing's Syndrome Due to Adrenocortical Carcinoma.

A wide range of clinical presentations for Cushing's syndrome has been described in the literature. Avascular necrosis of femur is a well-recognized complication of excessive glucocorticoid administration, but its occurrence due to endogenous hypercortisolism is rare. We present the case of a 47-year-old male who presented to us with severe low backache, hypertension, uncontrolled diabetes, and other signs and symptoms of Cushing's syndrome. Hormonal evaluation confirmed hypercortisolism, and a contrast-enhanced computed tomography of the abdomen localized the lesion in the left adrenal gland. Assessment of the severe low back ache-the main symptom for which the patient came to us-by magnetic resonance imaging of the spine and pelvis revealed avascular necrosis of bilateral femoral heads. Resection of the left adrenal gland revealed an adrenocortical carcinoma. To the best of our knowledge, this is only the second case where an adrenocortical cancer leading to hypercortisolism is the cause of avascular necrosis of hip.

Adrenocortical Carcinoma With Cushing's Syndrome and Extensive Tumor Thrombosis of the Inferior Vena Cava in a 30-Year-Old Filipino Female.

Adrenocortical carcinoma (ACC) is a rare and aggressive neoplasm with poor prognosis. We report a case of a 30-year-old female who presented with profound classic features of an adrenocorticotrophic hormone (ACTH)-independent Cushing's syndrome (CS) and a large adrenal mass with massive venous tumor thrombosis of the entire inferior vena cava (IVC), left renal and adrenal veins confirmed by imaging. Adrenal biopsy histopathology and immunohistochemistry confirmed ACC. Systemic palliative chemotherapy was administered. This rare case presents a unique and atypical presentation of an extensive tumor thrombosis of IVC. With the advanced stage at diagnosis, aggressive nature and poor prognosis of the disease, there is still a need to determine viable therapeutic options for metastatic ACC associated with venous invasion.

Genetic Dissection of Primary Aldosteronism in a Patient With MEN1 and Ipsilateral Adrenocortical Carcinoma and Adenoma.

BACKGROUND: Adrenal tumors are found in up to 40% of patients with multiple endocrine neoplasia type 1 (MEN1). However, adrenocortical carcinomas (ACC) and primary aldosteronism (PA) are rare in MEN1. CASE: A 48-year-old woman known to have primary hyperparathyroidism and hypertension with hypokalemia was referred for a right complex 8-cm adrenal mass with a 38.1 SUVmax uptake on 18F-FDG PET/CT. PA was confirmed by saline suppression test (aldosterone 1948 pmol/L-1675 pmol/L; normal range [N]: <165 post saline infusion) and suppressed renin levels (<5 ng/L; N: 5-20). Catecholamines, androgens, 24-hour urinary cortisol, and pituitary panel were normal. A right open adrenalectomy revealed a concomitant 4-cm oncocytic ACC and a 2.3-cm adrenocortical adenoma. Immunohistochemistry showed high expression of aldosterone synthase protein in the adenoma but not in the ACC, supporting excess aldosterone production by the adenoma. GENETIC ANALYSIS: After genetic counseling, the patient underwent genetic analysis of leucocyte and tumoral DNA. Sequencing of MEN1 revealed a heterozygous germline pathogenic variant in MEN1 (c.1556delC, p.Pro519Leufs*40). The wild-type MEN1 allele was lost in the tumoral DNA of both the resected adenoma and carcinoma. Sequencing analysis of driver genes in PA revealed a somatic pathogenic variant in exon 2 of the KCNJ5 gene (c.451G>A, p.Gly151Arg) only in the aldosteronoma. CONCLUSION: To our knowledge, we describe the first case of adrenal collision tumors in a patient carrying a germline pathogenic variant of the MEN1 gene associated with MEN1 loss of heterozygosity in both oncocytic ACC and adenoma and a somatic KCNJ5 pathogenic variant leading to aldosterone-producing adenoma. This case gives new insights on adrenal tumorigenesis in MEN1 patients.

Lived experience of people with adrenocortical carcinoma and associated adrenal insufficiency.

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare cancer with an annual incidence of 0.7-2 cases per million population and 5-year survival of 31.2%. Adrenal insufficiency (AI) is a common and life shortening complication of ACC, and little is understood about how it impacts on patients' experience. OBJECTIVE: To understand patients' lived experience of the condition, its treatment, care process, impact of AI on ACC wellbeing, self-care needs and support. METHODS: Systematic review of MEDLINE, EMBASES, CINAHL, PsycINFO and Open Grey for studies published until February 2021. All research designs were included. The findings underwent a thematic analysis and narrative synthesis. Studies quality was assessed using mixed method assessment tools. RESULTS: A total of 2837 citations were identified; 15 titles with cohort, cross-sectional, case series and case report study designs met the inclusion criteria involving 479 participants with adrenal insufficiency secondary to adrenocortical carcinoma (AI/ACC). Quantitative research identified impacts of disease and treatment on survivorship, the burden of living with AI/ACC, toxicity of therapies, supporting self-care and AI management. These impact factors included adjuvant therapies involved and their toxicities, caregivers/family supports, healthcare and structure support in place, specialist skill and knowledge provided by healthcare professional on ACC management. No qualitative patient experiences evidence was identified. CONCLUSION: ACC appears to have high impact on patients' wellbeing including the challenges with self-care and managing AI. Evidence is needed to understand patient experience from a qualitative perspective.

Iliac vein deep vein thrombosis as an atypical presentation of an adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare form of cancer with an annual incidence of two per million. The risk of venous thromboembolism increases sevenfold in patients with cancer. This case report describes an iliac vein deep vein thrombosis (DVT) as an atypical presentation of an ACC and highlights the value of further imaging investigation in patients with unprovoked DVTs.

Adrenal carcinoma as the first manifestation of a Li­Fraumeni syndrome in three paediatric patients.

Not required for clinical vignette.

68Ga-DOTANOC PET/CT in Multiple Endocrine Neoplasia 1 With Associated Adrenocortical Carcinoma.

ABSTRACT: Multiple endocrine neoplasia 1 (MEN1) syndrome is an autosomal dominant syndrome comprising a triad of pancreatic, pituitary, and parathyroid tumors. Adrenal cortical carcinoma occurs rarely in MEN1 syndrome. Here, we have presented a case of a 62-year-old woman with adrenal mass and elevated serum parathormone levels, who underwent 68Ga-DOTANOC PET/CT. 68Ga-DOTANOC PET/CT showed intense tracer concentration in the left adrenal mass and lesions in the liver, pancreas, and peritoneum. Biopsy of the peritoneal deposit revealed metastatic adrenocortical carcinoma, and further genetic testing showed MEN1 mutation.

A 2-Stage Surgical Approach for Adrenocortical Carcinoma With Intracardiac Extension.

Direct intracardiac extension of abdominal malignant diseases represents a rare but challenging situation. Removal of the intracardiac extension requires cardiopulmonary bypass with systemic anticoagulation, which could potentially increase the risk of bleeding if it is associated with liver resection. This report describes a 2-stage surgical approach for malignant disease with intracardiac extension in a high-risk patient. Atrial thrombectomy was performed first, followed by right portal vein embolization. Four months after the cardiac surgical procedure, the patient underwent right hepatectomy extended to segment 1, the right adrenal gland, and the retrohepatic inferior vena cava under venovenous bypass. The advantages and drawbacks of this approach are discussed.

Sarcopenia is Associated with Reduced Survival following Surgery for Adrenocortical Carcinoma.

AIM: Adrenocortical cancer (ACC) is an aggressive malignancy and robust prognostic factors remain unclear. The presence of sarcopenia has been shown to negatively impact survival for other malignancies, but has not been extensively analyzed in ACC. METHODS: Patients who underwent resection of their ACC between 2010 and 2020 were identified; therapeutic, operative, and outcome data were analyzed. Sarcopenia was assessed by calculation of the skeletal muscle index (SMI) and was defined as an SMI <52.4cm2/m2 for males and <38.5cm2/m2 for females. RESULTS: Data on 35 patients (18 F: 17 M; median age 54 [range: 18-86]) who had primary surgical treatment were analyzed. Median tumor size was 10 cm [range:3-15]. In eleven patients (31%), the tumor was hormonally active (cortisol = 8;23%). Seventeen patients (49%) were classified as having sarcopenia on their pre-operative CT scan. The Intraclass Correlation Coefficient (ICC) for intra- and inter-observer variability showed very good agreement (0.99 and 0.98). There was no difference in incidence of sarcopenia stratifying for sex, BMI, or tumor-size, but incidence was higher with increasing age (p < .05). Overall median survival was 36 months, with 1- and 3-year survival rates of 77% and 52%. The presence of sarcopenia was strongly associated with a shorter overall survival (HR = 3.21; [95%CI: 1.06-9.69];p = .03) on unadjusted analyses. Moreover, age, higher T-stage, and presence of capsular invasion were also associated with poorer survival on univariable analyses. CONCLUSION: The presence of sarcopenia in patients undergoing surgery for ACC could be a predictor of reduced overall survival, although replications of these analyses should be performed in similar, larger cohorts. Specifically, the influence of a patient's hormonal status on the manifestation of sarcopenia should be further defined.