The effect of adjuvant mitotane therapy of the adrenocortical carcinoma on the endometrium and its clinical consequences in menstruating women. Literature review and authors' own experiences.

Adrenocortical carcinoma (ACC) is a malignant tumour that originates from the adrenal cortex. It is a highly aggressive cancer characterised by a poor prognosis with an annual incidence estimated to be up to 2 cases per million. In the adult population, ACC is diagnosed typically between 40 and 50 years of age, more often in women. Complete surgical resection of the tumour is the primary treatment method for ACC. Unfortunately, despite properly performed adrenalectomy, regional recurrences or distant metastases are detected in up to 90% of the patients. For that reason, adjuvant therapy is recommended. Mitotane is the most effective adrenal-specific agent used in adjuvant and palliative therapy. Two menstruating patients, after adrenalectomy due to ACC, during adjuvant mitotane therapy, have been included in the study. The study aimed to assess the effect of mitotane therapy on the endometrium and its clinical consequences, based on the analysis of these two cases and a review of the literature. It seems that menorrhagia may be expected during adjuvant mitotane therapy of ACC in menstruating women. Heavy uterine bleeding during menstruation may appear several months after the beginning of therapy. The likely mechanism for heavy menstrual bleeding is complex. Menorrhagia can occur due to the toxic effect of mitotane in the form of a haemorrhagic diathesis, while long-term treatment (over ten months) can lead to relative hypoestrogenism resulting in endometrial hyperplasia. Clinical signs of hypoestrogenism during mitotane treatment, have been described (including pre-puberty girls) and should be considered as a side-effect of the therapy. Menorrhagia may lead to severe anaemia, so this should be considered when planning mitotane treatment. Continuous gestagen therapy is helpful in the treatment of the above disorders. After over 60 years of experience with mitotane usage, knowledge about it is still insufficient, and further studies are required.

Adrenocortical Cancer in the Real World: A Comprehensive Analysis of Clinical Features and Management from the Turkish Oncology Group (TOG).

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis. MATERIALS AND METHODS: A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan-Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses. RESULTS: The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses. CONCLUSION: ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.

Fluorodeoxyglucose (FDG) Uptake in the Remnant Adrenal Gland Mimicking Tumor Recurrence in a Patient With Adrenocortical Carcinoma After Treatment With Mitotane.

Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Its diagnosis requires clinical suspicion and confirmation through laboratory and imaging studies, including computed tomography (CT), magnetic resonance imaging (MRI), and abdominal ultrasound, as well as histological confirmation. Positron emission tomography (PET) is useful for distinguishing between benign and malignant lesions and for evaluating tumor recurrences or metastases. A case is described in which the uptake of fluorodeoxyglucose (18F-FDG) in a remnant adrenal gland could be misinterpreted as tumoral pathology. The article presents the case of a patient with ACC who, after treatment, showed increased FDG uptake in the remnant adrenal gland, which disappeared after discontinuation of treatment with mitotane. Possible explanations for this increase in FDG uptake are discussed, including the action of mitotane. In summary, it is highlighted that FDG uptake in remnant adrenal glands in patients treated with mitotane does not always indicate tumor recurrence or adrenal hypertrophy.

International consensus on mitotane treatment in pediatric patients with adrenal cortical tumors: indications, therapy, and management of adverse effects.

OBJECTIVE: Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects. METHODS: A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements. RESULTS: We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required. CONCLUSIONS: The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.

Safe long-term therapy of Cushing's syndrome over 37 years with mitotane.

While suggested, surgery is not always possible as a first-line treatment of Cushing's Disease (CD). In such cases, patients require medical therapy in order to prevent complications resulting from hypercortisolism. Although there has been a wide expansion in pharmacological options in recent years, mitotane was the agent of choice for treating hypercortisolism decades ago. Due to the introduction of other therapies, long-term experience with mitotane remains limited. Here, we report the case of a woman with CD who was treated with mitotane for 37 years. During the treatment period, biochemical and clinical disease control was achieved and the patient had two uncomplicated pregnancies. Drug-related side effects remained moderate and could be controlled by several dose adjustments. Our case highlights the ability of mitotane to allow an effective control of hypercortisolism and to represent a safe treatment option in special situations where CD requires an alternative therapeutic approach. Furthermore, we provide a literature review of the long-term use of mitotane and reported cases of pregnancy in the context of mitotane therapy.

The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinoma.

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex. Whilst surgery is the preferred treatment, adjunctive therapy with mitotane may be offered post-surgically to minimise the risk of recurrence or, in the absence of surgery, to attenuate progression. Aim: The objective was to evaluate the effects of mitotane treatment on serum protein concentrations in patients treated for ACC with mitotane therapy and compare this to patients with other adrenal neoplasms and a normal pregnant cohort. Methods: Serum cortisol, thyroid function tests, adrenocorticotrophic hormone (ACTH), cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG), gonadotrophins and androgens were measured on plasma and serum samples. Thirty-five patients with ACC were included, and mitotane levels were noted to be sub-/supra-therapeutic. Data were tested for normality, reported as mean ± s.d., and compared to other two cohorts using paired-sample t-test with a 5% P-value for significance and a 95% CI. Results: Patients on mitotane therapy had a higher mean serum CBG concentration compared to the adrenal neoplasm group (sub-therapeutic: 79.5 (95% CI: 33.6, 125.4 nmol/L), therapeutic: 85.3 (95% CI: 37.1-133.6 nmol/L), supra-therapeutic: 75.7 (95% CI: -19.3, 170.6 nmol/L) and adrenal neoplasm: 25.5 (95% CI: 17.5, 33.5 nmol/L). Negative correlations between serum cortisol and CBG concentration were demonstrated within the supra-therapeutic plasma mitotane and adrenal neoplasm groups. Conclusion: Patients with ACC and therapeutic plasma mitotane concentrations had higher serum CBG concentrations compared to those with adrenal neoplasms or pregnant women, and higher serum cortisol. Whilst there was no direct correlation with cortisol and mitotane level, the negative correlation of cortisol with CBG may suggest that the direct effect of mitotane in increasing cortisol may also reflect that mitotane has a direct adrenolytic effect.

Effect of mitotane in patients with ectopic adrenocorticotropic hormone syndrome caused by advanced pancreatic neuroendocrine tumors: a case series and review of the literature.

Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare condition caused by pancreatic neuroendocrine tumors (p-NETs). The severe hypercortisolemia that characterizes EAS is associated with a poor prognosis and survival. Mitotane is the only adrenolytic drug approved by the Food and Drug Administration and is often used to treat adrenocortical carcinoma. Combination therapy with mitotane and other adrenal steroidogenesis inhibitors is common for patients with Cushing's syndrome (CS). Here, we describe three patients who developed EAS secondary to the liver metastasis of p-NETs. All three rapidly developed hypercortisolemia but no typical features of CS. They underwent anti-tumor and mitotane therapy, which rapidly reduced their blood cortisol concentrations and ameliorated their symptoms. Their hypercortisolemia was controlled long term using a low dose of mitotane. The principal adverse effects were a slight loss of appetite and occasional dizziness, and there were no severe adverse effects. Importantly, even when the tumor progressed, the patients' circulating cortisol concentrations remained within the normal range. In summary, the present case series suggests that mitotane could be used to treat hypercortisolemia in patients with EAS caused by advanced p-NETs, in the absence of significant adverse effects.

Recovery of adrenal function after stopping mitotane in patients with adrenocortical carcinoma.

OBJECTIVE: Mitotane is the standard therapy of adrenocortical carcinoma (ACC) due to its relative selectivity of its cytotoxic effects toward adrenocortical cells. Therefore, it virtually always leads to adrenal insufficiency. Frequency and characteristics of hypothalamic-pituitary-adrenal axis recovery after discontinuation are ill-defined. METHODS: This was a retrospective study of patients with ACC adjuvantly treated with mitotane for ≥12 months who were disease-free at mitotane stop and had a minimum follow-up ≥1 year. Primary endpoint was adrenal recovery. Cox regression analyses were used to identify predictive factors. Moreover, mitotane plasma elimination rate and hormonal changes after mitotane stop were investigated. RESULTS: Fifty-six patients (36 women) treated with mitotane for a median time of 25 months and an average daily dose of 2.8 g were included. Median time after discontinuation until mitotane levels dropped below 5 and 2 mg/L, and the detection limit was 152 days (interquartile range: 114-202), 280 days (192-370), and 395 days (227-546), respectively. Full adrenal recovery was documented in 32 (57%) patients after a median time of 26 months (95% confidence interval [CI] = 19.6-32.4). In 4 patients (7.1%), adrenal insufficiency persisted >5 years after discontinuation. Mitotane peak ≥ 27 mg/L significantly correlated with longer time to adrenal recovery (hazard ratio [HR] = 0.2, 95% CI = 0.1-0.8, P = .03). Twenty-seven of 38 patients (71%) followed in reference centers achieved adrenal recovery compared with only 5/18 (28%) followed up in non-reference centers (HR = 4.51, 95% CI = 1.71-11.89, P = .002). Other investigated factors were not associated with adrenal function after discontinuation. CONCLUSIONS: Our study demonstrates that adrenal recovery occurs in most patients after stopping mitotane, particularly when followed up in specialized centers, but not in all. Elimination time of mitotane after treatment discontinuation is very long but individually quite variable.

Impact of EDP-M on survival of patients with metastatic adrenocortical carcinoma: A population-based study.

INTRODUCTION: Historically, stage IV adrenocortical carcinoma (mACC) has a poor prognosis with a median overall survival (OS) of only 5 months. Based on the FIRM-ACT trial published in 2012, guidelines now advise first line systemic treatment with etoposide, cisplatin, doxorubicin and mitotane (EDP-M). The effect of EDP-M on patient survival in clinical practice in the Netherlands is unknown. METHODS: The data of all patients with mACC (2005-2020) were obtained from the Netherlands comprehensive cancer organization (IKNL). The effect of EDP-M on patient survival was assessed using Kaplan-Meier analysis and multivariate Cox regression analysis including clinical, therapy and tumor characteristics. RESULTS: In total 167 patients with mACC were included. For patients diagnosed from 2014 onwards, EDP-M (in 22 patients (22%)) lead to a numerically but not statistically significant improved OS compared to those not receiving EDP-M (11.8 vs 5.6 months, p = 0.525). For systemic treatments, patients treated with mitotane only had the best 5-year OS (11.4%, p = 0.006) regardless of year of diagnosis. In multivariate Cox regression analysis EPD-M was not associated with OS; palliative adrenalectomy (HR: 0.26, p = <.001) and local treatment of metastases (HR: 0.35, p = 0.001) were associated with a better OS and a primary tumor Ki-67 index > 20% (HR: 2.67, p = 0.003) with a worse OS from 2014 onwards. Patients diagnosed before 2014 had a significantly poorer OS compared to from 2014 onwards (5-yr: 4.5 vs 8.4%, OS: 6.8 vs 8.3 months, p = 0.032). CONCLUSION: OS for mACC in the Netherlands has improved in the last decade. Receiving EDP-M did not significantly improve OS for patients with mACC. The use of multimodality treatment including palliative adrenalectomy, mitotane and local treatment of (oligo-)metastases in appropriately selected patients has improved the OS for mACC patients since 2014.

Albumin/Mitotane Interaction Affects Drug Activity in Adrenocortical Carcinoma Cells: Smoke and Mirrors on Mitotane Effect with Possible Implications for Patients' Management.

BACKGROUND: Mitotane is the only drug approved for the treatment of adrenocortical carcinoma (ACC). Although it has been used for many years, its mechanism of action remains elusive. H295R cells are, in ACC, an essential tool to evaluate drug mechanisms, although they often lead to conflicting results. METHODS: Using different in vitro biomolecular technologies and biochemical/biophysical experiments, we evaluated how the presence of "confounding factors" in culture media and patient sera could reduce the pharmacological effect of mitotane and its metabolites. RESULTS: We discovered that albumin, the most abundant protein in the blood, was able to bind mitotane. This interaction altered the effect of the drug by blocking its biological activity. This blocking effect was independent of the albumin source or methodology used and altered the assessment of drug sensitivity of the cell lines. CONCLUSIONS: In conclusion, we have for the first time demonstrated that albumin does not only act as an inert drug carrier when mitotane or its metabolites are present. Indeed, our experiments clearly indicated that both albumin and human serum were able to suppress the pharmacological effect of mitotane in vitro. These experiments could represent a first step towards the individualization of mitotane treatment in this rare tumor.

A Case of Adrenocortical Carcinoma With a Favorable Tumor Control by Radiofrequency Ablation for Liver Metastasis.

A 57-year-old woman was diagnosed with adrenocortical carcinoma. Following the adrenalectomy, she underwent adjuvant radiation and mitotane therapy; however, liver metastases were observed. Repeated radiofrequency ablation (RFA) was performed for liver metastases. In addition, a multidisciplinary approach combining systemic chemotherapy, radiotherapy, and surgery was used for lung and distant lymph node metastases that arose during the course of treatment. Notably, 49 months have passed since the adrenalectomy and 36 months since the recurrence of the liver metastases, and the patient remains on multidisciplinary therapy. Thus, RFA for liver metastasis of adrenocortical carcinoma may be an effective component of a multidisciplinary treatment.

Durable response to pembrolizumab in microsatellite instability-high advanced adrenocortical carcinoma.

Introduction: Advanced adrenocortical carcinoma has a poor prognosis and is treated with chemotherapy that includes mitotane with etoposide, doxorubicin, and cisplatin as first-line therapy. However, second-line therapy has not been determined yet. Pembrolizumab has been approved for high microsatellite instability for which standard treatments have failed. Case presentation: Here, we present a patient with advanced adrenocortical carcinoma treated with complete surgical resection. 21 months later, he had local and metastatic recurrences. After four cycles of first-line therapy, we switched to pembrolizumab because microsatellite instability-high was detected in his tumor. He has received mitotane and pembrolizumab for 15 months, and this has exerted a radiographical response without severe adverse events. Conclusion: We presented a patient with microsatellite instability-high advanced adrenocortical carcinoma treated with pembrolizumab and mitotane.

Dual Aldosterone- and Cortisol-Secreting Adrenal Cortical Carcinoma: Pre- and Perioperative Evaluation and Management.

Adrenal cortical carcinoma (ACC) is a rare cancer (1-2/million) that presents with hormone overproduction in 60% of cases. Presentation of ACC with multiple hormone syndromes from different adrenal zones is rare. We present a case of dual-secreting ACC with hyperaldosteronism and cortisol excess. The previously healthy patient was noted to have new-onset hypertension and hypokalemia during a primary care visit. On hormonal evaluation, he was found to have evidence of hyperaldosteronism and adrenocorticotropic hormone (ACTH)-independent cortisol excess. Imaging revealed a 2.7 × 3.1 × 3.5 cm left adrenal mass with indeterminant computed tomography characteristics. He underwent laparoscopic adrenalectomy and required glucocorticoid replacement for adrenal insufficiency postoperatively. Pathology revealed stage T2N0M0 ACC. His hypokalemia resolved and glucocorticoids were stopped within a month. This case stresses the importance of routine screening for cortisol excess in all adrenal masses detected on imaging. Avoidance of postoperative adrenal insufficiency in patients with cortisol excess without overt Cushing syndrome is paramount.

Adrenocortical carcinoma: Diagnosis, prognostic classification and treatment of localized and advanced disease.

Adrenocortical carcinoma (ACC) is a rare cancer with an estimated incidence of 0.7 to 2.0 cases per 1 million population per year in the United States. It is an aggressive cancer originating in the cortex of the adrenal gland with a poor prognosis. The 5-year survival rate is less than 15% among patients with metastatic disease. In this article, we review the epidemiology and pathogenesis of ACC, the diagnostic procedures, the prognostic classification of ACC, and the treatment options from localized and resectable forms to advanced disease detailing recent therapeutic developments such as immunotherapy and molecularly targeted therapy.

Neurological adverse events of mitotane in adrenocortical carcinoma: results of a pilot study.

Introduction: Mitotane, the only drug approved by the Food and Drug Administration (FDA) for the treatment of adrenocortical carcinoma, is associated with several side effects including neurotoxicity. The aim of our study is to investigate the relationship between mitotane plasma levels and neurological toxicity. Methods: We have considered five patients affected by adrenocortical carcinoma treated with mitotane. The neurological assessment included a neurological examination, an electroencephalogram, event-related potentials (P300), and a neuropsychological assessment. All of the patients were first considered at the onset of symptoms of neurotoxicity or when mitotanemia levels were above 18 mg/L, for the second time at mitotanemia normalization and subsequently at its further increase, or in case of persistent neurological abnormalities, some months after normalization. Results: At the first neurotoxicity, four patients showed impaired neurological examination, electroencephalogram, and P300; three patients had impaired neuropsychological assessment; one patient, only P300. At mitotanemia normalization, the neurological examination became normal in all patients and electroencephalogram normalized in one patient, improved in another one, continuing to be altered in the other three. P300 latency and neuropsychological assessment normalized in two patients and persisted altered in the patient experiencing long-term mitotane toxicity. At the third evaluation, in the patient with prolonged mitotane toxicity, the normal mitotanemia in the previous 9 months restored P300 and improved the electroencephalogram but not the neuropsychological assessment. In the two patients experiencing a further rise of mitotanemia, neurological examination was normal but P300 and electroencephalogram were altered. Conclusion: The results of our study highlighted the presence of neurophysiological and neuropsychological abnormalities associated with mitotane values above 18 mg/L.

Metastatic Adrenocortical Carcinoma With Chromothripsis: A Case Report and Literature Review.

Metastatic adrenocortical carcinoma (ACC) often has a poor outcome, with a five-year survival of less than 25%. We report a rare case of metastatic ACC with a myxoid variant with chromothripsis. We review the histologic variants of ACC, including myxoid type, molecular drivers, and current and investigational therapies for adrenocortical carcinoma. We also discuss the mechanism of chromothripsis, chromothripsis in ACC tumorigenesis, and propose potential therapies targeting chromothripsis.

Outcome of immunotherapy in adrenocortical carcinoma: a retrospective cohort study.

OBJECTIVE: Clinical trials with immune checkpoint inhibitors (ICI) in adrenocortical carcinoma (ACC) have yielded contradictory results. We aimed to evaluate treatment response and safety of ICI in ACC in a real-life setting. DESIGN: Retrospective cohort study of 54 patients with advanced ACC receiving ICI as compassionate use at 6 German reference centres between 2016 and 2022. METHODS: Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAE) were assessed. RESULTS: In 52 patients surviving at least 4 weeks after initiation of ICI, ORR was 13.5% (6-26) and DCR was 24% (16-41). PFS was 3.0 months (95% CI, 2.3-3.7). In all patients, median OS was 10.4 months (3.8-17). 17 TRAE occurred in 15 patients, which was associated with a longer PFS of 5.5 (1.9-9.2) vs 2.5 (2.0-3.0) months (HR 0.29, 95% CI, 0.13-0.66, P = 0.001) and OS of 28.2 (9.5-46.8) vs 7.0 (4.1-10.2) months (HR 0.34, 95% CI, 0.12-0.93). Positive tissue staining for programmed cell death ligand 1 (PD-L1) was associated with a longer PFS of 3.2 (2.6-3.8) vs 2.3 (1.6-3.0, P < 0.05) months. Adjusted for concomitant mitotane use, treatment with nivolumab was associated with lower risk of progression (HR 0.36, 0.15-0.90) and death (HR 0.20, 0.06-0.72) compared to pembrolizumab. CONCLUSIONS: In the real-life setting, we observe a response comparable to other second-line therapies and an acceptable safety profile in ACC patients receiving different ICI. The relevance of PD-L1 as a marker of response and the potentially more favourable outcome in nivolumab-treated patients require confirmation.

Effect of Mitotane on Male Gonadal Function.

BACKGROUND: Clinical evidence has shown frequent hypogonadism following mitotane (MTT) treatment in male patients with adrenocortical carcinoma. This study aimed to evaluate the impact of MTT on male gonadal function. METHODS: Morphological analysis of testes and testosterone assays were performed on adult CD1 MTT-treated and untreated mice. The expression of key genes involved in interstitial and tubular compartments was studied by real-time PCR. Moreover, quantitative and qualitative analysis of spermatozoa was performed. RESULTS: Several degrees of damage to the testes and a significant testosterone reduction in MTT-treated mice were observed. A significant decline in 3ßHsd1 and Insl3 mRNA expression in the interstitial compartment confirmed an impairment of androgen production. Fsh-R mRNA expression was unaffected by MTT, proving that Sertoli cells are not the drug's primary target. Sperm concentrations were significantly lower in MTT-treated animals. Moreover, the drug caused a significant increase in the percentage of spermatozoa with abnormal chromatin structures. CONCLUSION: MTT negatively affects the male reproductive system, including changes in the morphology of testicular tissue and reductions in sperm concentration and quality.

Prominent 18F-FDG Uptake in the Adrenal Gland after Contralateral Adrenalectomy in a Known Case of Adrenocortical Oncocytic Carcinoma.

Adrenocortical carcinoma (ACC) is a rare type of cancer that is associated with a high rate of recurrence and poor prognosis. The main diagnostic approaches to adrenocortical cancer include CT scan, MRI and the promising role of 18F-FDG PET/CT. The main therapeutic approaches include radical surgery of local disease and recurrences, as well as adjuvant mitotane therapy. The evaluation of adrenocortical carcinoma (ACC) could be difficult by using 18F-FDG PET/CT in view of the significant association between the 18F-FDG uptake and ACC. At the same time, not all adrenal glands with 18F-FDG uptake are considered to be malignant, so awareness of these various findings is substantial for ACC management, especially with limited data regarding the role of 18F-FDG PET/CT in ACC post-operative settings. This report discusses the case of a 47-year-old man with a history of left adrenocortical carcinoma who underwent adrenalectomy and received adjuvant mitotane therapy. 9 months after the surgery, a follow-up 18F-FDG PET/CT scan showed that the 18F-FDG uptake was prominent in the right adrenal gland without corresponding abnormal CT scan findings.

Long-term partial response in a patient with liver metastasis of primary adrenocortical carcinoma with adjuvant mitotane plus transcatheter arterial chemoembolization and microwave ablation: a case report.

Adrenocortical carcinoma (ACC) is a rare, heterogeneous, and aggressive malignancy with a generally poor prognosis. Surgical resection is the optimal treatment plan. After surgery, both mitotane treatment or the etoposide-doxorubicin-cisplatin (EDP) protocol plus mitotane chemotherapy have a certain effect, but there is still an extremely high possibility of recurrence and metastasis. The liver is one of the most common metastatic targets. Therefore, techniques such as transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA) for liver tumors can be attempted in a specific group of patients. We present the case of a 44-year-old female patient with primary ACC, who was diagnosed with liver metastasis 6 years after resection. During mitotane treatment, we performed four courses of TACE and two MWA procedures in accordance with her clinical condition. The patient has maintained the partial response status and has currently returned to normal life to date. This case illustrates the value of the practical application of mitotane plus TACE and MWA treatment.