Distant Metastases From Childhood Differentiated Thyroid Carcinoma: Clinical Course and Mutational Landscape.

CONTEXT: Distant metastases (DM) from childhood differentiated thyroid carcinoma (DTC) are uncommon and published studies are limited. OBJECTIVE: This work aimed to describe the outcomes of patients with DM from childhood DTC and to evaluate the molecular landscape of these tumors. METHODS: A retrospective study was conducted at a tertiary cancer center including patients with pediatric DTC (diagnosed at age ≤ 18 years from 1946 to 2019) and DM. RESULTS: We identified 148 patients; 144 (97%) had papillary thyroid carcinoma (PTC) and 104 (70%) were female. Median age at DTC diagnosis was 13.4 years (interquartile range [IQR], 9.9-15.9 years). Evaluable individuals received a median of 2 (IQR, 1-3) radioactive iodine (RAI) treatments at a median cumulative administered activity of 238.0 mCi (IQR, 147.5-351.0 mCi). The oncogenic driver was determined in 64 of 69 PTC samples: RET fusion (38/64; 59%), NTRK1/3 fusions (18/64; 28%), and the BRAF V600E mutation (8/64; 13%). At last evaluation, 93% had persistent disease. The median overall and disease-specific survival after DTC diagnosis were 50.7 and 52.8 years, respectively. Eight (5%) PTC patients died of disease after a median of 30.7 years (IQR, 20.6-37.6 years). CONCLUSION: Childhood DTC with DM persists in most patients despite multiple courses of RAI, but disease-specific death is uncommon, typically occurring decades after diagnosis. Fusion genes are highly prevalent in PTC, and all identified molecular alterations have appropriate targeted therapies. Future studies should focus on expanding genotype-phenotype correlations, determining how to integrate molecularly targeted therapy into treatment paradigms, and relying less on repeated courses of RAI to achieve cure in patients with DM from childhood DTC.

Preexisting adrenal masses in patients with adrenocortical carcinoma: clinical and radiological factors contributing to delayed diagnosis.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy that is usually large (>5 cm) at time of diagnosis. Delayed diagnosis significantly worsens survival. We describe adrenal gland morphology prior to ACC diagnosis and discern potential causes of delayed diagnosis. ACC patients seen at The University of Texas MD Anderson Cancer Center between 1998 and 2014 who had cross-sectional body imaging ≥3 months prior to their diagnosis. We conducted a detailed review of clinical and radiological features in these patients prior to ACC diagnosis. Of 439 patients with ACC, 25 had imaging preceding ACC diagnosis (5 with normal adrenal glands and 20 with preexisting masses). On the first available images, the median mass size was 2.8 cm (range 0-9) with median precontrast density of 36 Hounsfield units (range 17-43) and became 9 cm (range 1-18) at the time of ACC diagnosis. The median interval between first available image and ACC diagnosis was 20 months (range 3-89). In the 5 patients whose initial images showed normal adrenal glands, the time between the last normal scan and ACC diagnosis ranged from 5 to 36 months. The most common reason for delayed ACC diagnosis was the presumed benign status of the preexisting mass (n = 13, 65 %). Radiologically suspicious adrenal masses can precede ACC diagnosis and have variable growth patterns. ACC can also develop de novo within a few months in a radiologically documented normal adrenal gland. The presumed benignancy of preexisting masses based on size is the main reason for delayed ACC diagnosis.

Adrenal ganglioneuroma: features and outcomes of 27 cases at a referral cancer centre.

BACKGROUND: Adrenal ganglioneuroma (AGN) is a rare neurogenic tumour that can mimic other adrenal neoplasms. Limited information, mostly derived from small cases series, is available for AGN. METHODS: A retrospective review for AGNs seen at a tertiary referral centre describing important features to distinguish AGN from other adrenal neoplasms. RESULTS: Of 53 ganglioneuromas, 27 were AGNs. Median age was 31 years (range, 1·7-64 years) and median tumour size was 8 cm (range, 1·5-20 cm). Seventeen AGNs (63%) were detected incidentally and nine patients (33%) presented with abdominal/back discomfort. Catecholamine levels, available for 21 patients, were normal. On computed tomography (CT), most AGNs were homogenous and well circumscribed with a median density of 32·5 Hounsfield units (HU) on unenhanced CT; 40 HU on postcontrast venous phase; and 66·5 HU on delayed postcontrast phase. On magnetic resonance imaging (MRI), AGNs had hypo-intense signal on T1-weighted images with heterogeneous hyperintense signal on T2-weighted images. In four patients, there was no tumour growth during median follow-up of 48 months (range, 21-60 months). One patient had malignant peripheral nerve sheath tumour arising from AGN. Thirteen patients with resected AGN had no recurrence during a median follow-up of 50 months (range, 2-135 months). CONCLUSIONS: We herein describe the largest AGN series reported to date. Isolated AGNs do not produce catecholamines and have CT imaging characteristics that can help in distinguishing them from other adrenal and para-adrenal neoplasms. The natural history of AGNs is usually benign, although local extra-adrenal extension or malignant transformation can rarely occur.

Mitotane-induced hyperlipidemia: a retrospective cohort study.

Limited data are available about mitotane-nduced hyperlipidemia. We retrospectively analyzed lipid data in 38 patients with adrenocortical carcinoma (ACC) who received mitotane therapy with emphasis on HDL cholesterol (HDL-c) and clinical predictors of lipid changes. At baseline, the mean levels of HDL-c, LDL-c, and triglycerides were 53.3 mg/dL, 114.4 mg/dL, and 149 mg/dL, respectively. HDL-c, LDL-c, and triglyceride concentrations significantly increased with mitotane therapy to a mean HDL peak (HDL-P) of 86.3 mg/dL (P < 0.001), a mean LDL peak of 160.1 mg/dL (P < 0.001), and a mean triglyceride peak (Tg-P) of 216.7 mg/dL (P = 0.042). HDL-P positively correlated with mitotane concentration (r = 0.52, P < 0.001), while LDL-P levels and Tg-P did not. Gender, body mass index, cortisol overproduction, baseline levels of HDL-c, and triglyceride did not predict change in HDL-c. Similar changes were noticed in subgroup analysis after excluding patients who were using lipid-lowering agents. In conclusion, in ACC patients, mitotane caused significant increases in HDL-c that may counteract the deleterious atherosclerotic effects of LDL-c and Tg rise. Understanding the mechanism of HDL change may lead to the discovery of novel HDL-c-elevating drugs.

Adrenocortical carcinoma: clinical outcomes and prognosis of 330 patients at a tertiary care center.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Herein, we describe the clinical features and outcomes for a large series of ACC patients. DESIGN AND METHODS: Retrospective review of ACC patients seen at The University of Texas MD Anderson Cancer Center from 1998 through 2011. RESULTS: A total of 330 patients with median age at diagnosis of 48.5 years; 12 (3.6%) patients were under 18 years. Hormonally functioning tumors represented 41.8% (n=138) of all cases. Surgical resection for the primary tumor was done in 275 (83.3%) patients (45 at MD Anderson (16.4%)). For those who had surgical resection, the median local-recurrence-free time was 1.04 years. Factors associated with local recurrence included positive surgical margins (P=0.007) and advanced disease stage (P=0.026). Median overall survival time for all patients was 3.21 years. Median survival times were 24.1, 6.08, 3.47, and 0.89 years for stages I, II, III, and IV respectively. In multivariable analysis, older age, functioning tumors, and higher disease stage remained significant prognostic factors associated with poor survival. CONCLUSION: ACC prognosis remains poor with the use of currently available treatments. Older age, functioning tumors, and incomplete resections are clinical factors associated with poor survival. Surgical expertise is important to achieve complete resections and to improve outcome.

Impact and timing of bilateral adrenalectomy for refractory adrenocorticotropic hormone-dependent Cushing's syndrome.

INTRODUCTION: In patients with refractory adrenocorticotropic hormone-dependent Cushing's syndrome,we evaluated steroidogenesis inhibition (SI) and bilateral adrenalectomy (BA) to predict which patients might benefit most from each treatment modality. METHODS: Clinical data from patients treated 1970-2012 were reviewed retrospectively by treatment group (SI or SI+BA). Validated severity scales were used to calculate metabolic (M) score (hypokalemia, hyperglycemia, hypertension, proximal muscle weakness) and adverse events (AE) score (thrombosis, fracture, infection). RESULTS: A total of 65 patients (16 pituitary, 49 ectopic) were treated with SI+BA (n = 21,32%) or SI alone (n = 44,68%). Presenting M scores and source of adrenocorticotropic hormone excess (ectopic versus pituitary) were similar. Both groups improved metabolically after treatment. Over one-third of AEs in the SI+BA group occurred within 12 months of presentation. Half (n = 24, 55%) of the patients treated with SI died (median survival, 24.0 months). Steroid excess contributed to 71% of complications. Six SI+BA patients died (29%), including all 3 patients with recurrent Cushing's syndrome after BA. Minor perioperative complications occurred in 7 patients (33%). CONCLUSION: Posttreatment M and AE scores improved for all patients and 70% of AEs occurred in SI+BA patients within 12 months of presentation, emphasizing the importance of early operative intervention. These data argue for the safety and efficacy of early BA in selected patients with uncontrollable Cushing's syndrome.

A retrospective cohort analysis of the efficacy of adjuvant radiotherapy after primary surgical resection in patients with adrenocortical carcinoma.

CONTEXT: Adrenocortical carcinoma (ACC) is a rare malignancy with high recurrence and mortality rates. The role of adjuvant radiation therapy (RT) to improve outcome remains unclear. OBJECTIVE: The aim of this study was to evaluate the impact of adjuvant RT on overall survival and recurrence rates of ACC patients. DESIGN: We conducted a retrospective cohort study of select ACC patients who were seen at The University of Texas MD Anderson Cancer Center (MDACC) between 1998 and 2011. All patients in this study underwent primary tumor resection and received adjuvant RT within 3 months of primary surgical resection prior to referral to the MDACC. We compared patients who had surgery and adjuvant RT with patients who had surgery alone. RESULTS: Baseline characteristics and adjuvant mitotane use were not significantly different between the adjuvant RT group (n = 16) and the non-RT group (n = 32). Local recurrence occurred in seven patients (43.8%) who received RT and 10 patients (31.3%) in the control group. At 5 yr, the estimated local recurrence-free rate (95% confidence interval) was 53% (32-87%) in the RT group and 67% (52-86%) in the non-RT group (P = 0.53). The distributions of time to distant recurrence and recurrence-free survival were not significantly different between the two groups. Using a multivariate Cox proportional hazards model for overall survival, the hazard ratio for RT use was 1.593 (95% confidence interval, 0.707-3.589; P = 0.26) after adjusting for stage and adjuvant mitotane therapy. CONCLUSIONS: ACC has high rates of recurrence. In our study, RT did not improve clinical outcomes in patients who received their initial care in the community. We believe there is a need for a collaborative, multicenter, prospective randomized trial to evaluate the role of adjuvant treatments (both mitotane and RT) to assess their impact on recurrence patterns and survival.

The noninvestigational use of tyrosine kinase inhibitors in thyroid cancer: establishing a standard for patient safety and monitoring.

CONTEXT: The increasing use of tyrosine kinase inhibitor therapy outside of the context of the clinical trial for treatment of advanced thyroid cancer has highlighted the need for a systematic approach to the clinical application of these agents in order to improve patient safety and monitoring promote consistency among providers, and ensure compliance with both institutional and industry standards. EVIDENCE: We reviewed professional thyroid cancer guidelines, the National Comprehensive Cancer Network task force reports, American Society of Clinical Oncology safety standards, review articles, and clinical trials published within the past 10 yr and also included relevant older studies. CONCLUSIONS: Review of available published data and the collective experience prescribing tyrosine kinase inhibitors at The University of Texas MD Anderson Cancer Center have highlighted the need for a systematic, comprehensive, and uniform approach to managing these patients. This paper discusses the approach adopted by the Department of Endocrine Neoplasia at the MD Anderson Cancer Center and illustrates practice patterns, experience, and our standardized approach related to prescribing commercially available tyrosine kinase inhibitors outside of the context of a clinical trial for patients with advanced thyroid cancer.

Durable effect of radioactive iodine in a patient with metastatic follicular thyroid carcinoma.

Objective. Thyroid cancer is the most common endocrine malignancy and fastest increasing of all cancers in both men and women in the United States. Traditionally, differentiated thyroid cancer (DTC) carries a good prognosis when diagnosed early, but increasingly patients are presenting with late-stage disease and bone metastasis which carries a poor prognosis. Treatment of DTC involves surgical resection followed by radioactive iodine (RAI), which conventionally is thought to reach maximal effectiveness between 6 and 12 months following treatment. We report a case and review the literature surrounding long-term effect of radioactive iodine treatment in metastatic thyroid carcinoma. Methods. Patient clinical encounter and the literature review. Results. We describe a 49-year-old woman with symptomatic metastatic follicular thyroid cancer (FTC) to the spine and radiographic evidence of spinal cord compression who was effectively treated with RAI. Her initial serum thyroglobulin (Tg) levels following total thyroidectomy were 1,343 ng/mL which dramatically dropped to less than 100 ng/mL following RAI. Forty-three months following treatment with RAI, she has experienced complete resolution of her symptoms and continues to maintain persistently low-thyroglobulin levels of less than 100 ng/mL. Conclusions. RAI is believed to reach peak efficacy within 6-12 months; however, little has been reported regarding the long-term duration of benefit. This case demonstrates that the benefits of RAI therapy may be enduring, even in patients with widely metastatic thyroid cancer. It suggests in clinically stable patients with declining thyroglobulin after treatment, that there may not be an immediate need for additional therapy as RAI treatment may provide lasting effects.

Tibolone increases bone mineral density but also relapse in breast cancer survivors: LIBERATE trial bone substudy.

INTRODUCTION: The Livial Intervention Following Breast Cancer: Efficacy, Recurrence and Tolerability Endpoints (LIBERATE: Clinical http://Trials.gov number NCT00408863), a randomized, placebo-controlled, double-blind trial that demonstrated that tibolone (Livial), a tissue-selective hormone-replacement therapy (HRT), increased breast cancer (BC) recurrence HR 1.40 (95% CI, 1.14 to 1.70; P = 0.001). A subgroup of women was entered into a study of bone mineral density (BMD). METHODS: Women with surgically excised primary BC (T1-3, N0-2, M-0) within the last 5 years, complaining of vasomotor symptoms, were assigned to tibolone, 2.5 mg daily, or placebo treatment for a maximum of 5 years. The BMD substudy enrolled 763 patients, using dual-energy X-ray absorptiometry (DXA) scanning at baseline and at 2 years. RESULTS: In the bone substudy, 699 of 763 women were eligible (345 allocated to tibolone, and 354, to placebo). After undergoing DXA scans, 300 (43%) women had normal BMD; 317 (45%), osteopenia; and 82 (11.7%), osteoporosis. Low body-mass index (P < 0.001), Asian race (P < 0.001), and late age at menarche (P < 0.04) predicted low bone mass at baseline. Tibolone increased BMD by 3.2% at the lumbar spine and 2.9% at the hip compared with placebo (both P < 0.001). The majority of fractures (55%) occurred in osteopenic patients. Women with normal BMD had increased recurrence with tibolone, 22 (15.6%) of 141 compared with placebo, 11 (6.9%) of 159 (P = 0.016), whereas no increased BC recurrence was seen in women with low BMD; 15 (7.4%) of 204 taking tibolone versus 13 (6.7%) of 195 taking placebo. CONCLUSIONS: Tibolone is contraindicated after BC treatment, as it increases BMD and BC recurrence. Risk of BC recurrence was elevated in BC women with normal BMD (compared with low) who took tibolone.

Cushing syndrome secondary to ectopic adrenocorticotropic hormone secretion: the University of Texas MD Anderson Cancer Center Experience.

BACKGROUND: Cushing syndrome (CS) secondary to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) has been described in association with a variety of tumors. The current experience with this syndrome was based on a few case series and individual case reports. Limited data were available about the tumors associated with CS-EAS in a cancer center setting. In this report, the authors have described their experience with CS-EAS at The University of Texas MD Anderson Cancer Center to further enhance the current understanding and management of this syndrome. METHODS: This was a retrospective review of 43 patients with CS-EAS who were diagnosed between 1979 and 2009 at The University of Texas MD Anderson Cancer Center. RESULTS: Different neuroendocrine tumors were associated with CS-EAS. Twenty-one patients (48.9%) had tumors located in the chest cavity, with bronchial carcinoid and small cell lung cancer representing the 2 most common causes. The ACTH source remained occult in 4 patients (9.3%) despite extensive workup. Clinical presentation varied, and the classic features of CS were not evident in some patients. Death occurred in 27 patients (62.8%), and the median overall survival was 32.2 months. Major morbidities included new-onset or worsening hyperglycemia (77%), symptomatic venous thromboembolism (14%), and infections (23%). CONCLUSIONS: In patients with CS-EAS who attended a comprehensive cancer center, tumors originating in the chest cavity were the leading tumors associated with this syndrome. The authors suspect that CS-EAS is under reported because of the atypical presentation in some patients. Thus, they suggest careful evaluation of patients with neuroendocrine tumors to avoid missing coexisting CS-EAS.

Skeletal sequelae of cancer and cancer treatment.

INTRODUCTION: Survivors of cancer may experience lingering adverse skeletal effects such as osteoporosis and osteomalacia. Skeletal disorders are often associated with advancing age, but these effects can be exacerbated by exposure to cancer and its treatment. This review will explore the cancer and cancer treatment-related causes of skeletal disorders. METHODS: We performed a comprehensive search, using various Internet-based medical search engines such as PubMed, Medline Plus, Scopus, and Google Scholar, for published articles on the skeletal effects of cancer and cancer therapies. RESULTS: One-hundred-forty-two publications, including journal articles, books, and book chapters, met the inclusion criteria. They included case reports, literature reviews, systematic analyses, and cohort reports. Skeletal effects resulting from cancer and cancer therapies, including hypogonadism, androgen deprivation therapy, estrogen suppression, glucocorticoids/corticosteroids, methotrexate, megestrol acetate, platinum compounds, cyclophosphamide, doxorubicin, interferon-alpha, valproic acid, cyclosporine, vitamin A, NSAIDS, estramustine, ifosfamide, radiotherapy, and combined chemotherapeutic regimens, were identified and described. Skeletal effects of hyperparathyroidism, vitamin D deficiency, gastrectomy, hypophosphatemia, and hyperprolactinemia resulting from cancer therapies were also described. DISCUSSION/CONCLUSIONS: The publications researched during this review both highlight and emphasize the association between cancer therapies, including chemotherapy and radiotherapy, and skeletal dysfunction. IMPLICATIONS FOR CANCER SURVIVORS: These studies confirm that cancer survivors experience a more rapid acceleration of bone loss than their age-matched peers who were never diagnosed with cancer. Further studies are needed to better address the skeletal needs of cancer survivors.

Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial.

BACKGROUND: Vasomotor symptoms and bone loss are complications frequently induced by adjuvant treatment for breast cancer. Tibolone prevents both side-effects, but its effect on cancer recurrence is unknown. The aim of this study was to show non-inferiority of tibolone to placebo regarding risk of recurrence in breast-cancer patients with climacteric complaints. METHODS: Between July 11, 2002, and Dec 20, 2004, women surgically treated for a histologically confirmed breast cancer (T(1-3)N(0-2)M(0)) with vasomotor symptoms were randomly assigned to either tibolone 2.5 mg daily or placebo at 245 centres in 31 countries. Randomisation was done by use of a centralised interactive voice response system, stratified by centre, with a block size of four. The primary endpoint was breast-cancer recurrence, including contralateral breast cancer, and was analysed in the intention-to-treat (ITT) and per-protocol populations; the margin for non-inferiority was set as a hazard ratio of 1.278. This study is registered with ClinicalTrials.gov, number NCT00408863. FINDINGS: Of the 3148 women randomised, 3098 were included in the ITT analysis (1556 in the tibolone group and 1542 in the placebo group). Mean age at randomisation was 52.7 years (SD 7.3) and mean time since surgery was 2.1 years (SD 1.3). 1792 of 3098 (58%) women were node positive and 2185 of 3098 (71%) were oestrogen-receptor positive. At study entry, 2068 of 3098 (67%) women used tamoxifen and 202 of 3098 (6.5%) women used aromatase inhibitors. The mean daily number of hot flushes was 6.4 (SD 5.1). After a median follow-up of 3.1 years (range 0.01-4.99), 237 of 1556 (15.2%) women on tibolone had a cancer recurrence, compared with 165 of 1542 (10.7%) on placebo (HR 1.40 [95% CI 1.14-1.70]; p=0.001). Results in the per-protocol population were similar (209 of 1254 [16.7%] women in the tibolone group had a recurrence vs 138 of 1213 [11.4%] women in the placebo group; HR 1.44 [95% CI 1.16-1.79]; p=0.0009). Tibolone was not different from placebo with regard to other safety outcomes, such as mortality (72 patients vs 63 patients, respectively), cardiovascular events (14 vs 10, respectively), or gynaecological cancers (10 vs 10, respectively). Vasomotor symptoms and bone-mineral density improved significantly with tibolone, compared with placebo. INTERPRETATION: Tibolone increases the risk of recurrence in breast cancer patients, while relieving vasomotor symptoms and preventing bone loss. FUNDING: Schering-Plough (formerly NV Organon, Oss, Netherlands).

Long term physical sequelae after adult-onset cancer.

INTRODUCTION: With two thirds of cancer patients living for at least 5 years, clinical research has increasingly focused on the long-term health of cancer survivors. Contrary to the amount of knowledge on long-term consequences observations on late effects after childhood cancer in adult-onset cancer are sparse. Only limited literature is available recommending guidelines for long-term follow-up of cancer patients and their implementation in the delivery of health care. METHODS: In this review we summarize updated knowledge on the most frequent physical long-term effects after adult-onset cancer, and we discuss how these findings can be implemented in life-long follow-up programs of cancer survivors. RESULTS: Second cancer, cardiovascular disorders and gonadal dysfunction are the most common physical late effects along with fatigue. Common age-related co-morbidity reduces physical function in long-term cancer survivors. CONCLUSIONS: Cancer survivors have to be informed about their risk of late effects, and how to prevent them by life style adjustments and, if indicated, regular health care visits. Studies on late effects after cancer treatment should be combined with translational research in order to improve our understanding of pathophysiological mechanisms of long-term effects. The effectiveness of therapeutic interventions for reduction of these treatment sequelae in long-term survivors need to be investigated in randomized trials. Guidelines for life-long follow-up of cancer survivors should be established and will form the first step is the design of an individual life-long cancer survivor care plan.

Systemic chemotherapy for adrenocortical carcinoma: comparative responses to conventional first-line therapies.

The objective of this study was to evaluate and compare the efficacies of conventional first-line chemotherapies for adrenocortical carcinoma. We reviewed the records of adult patients (> or =17 years) who had received first-line systemic chemotherapy with serial pretreatment and posttreatment radiologic staging studies in our institution between 1980 and 2000. Overall survival (OS) and time to progression (TTP) for different treatment groups were determined using the Kaplan-Meier method and were compared using the log-rank test. Univariate and multivariate models were fitted to different subsets of patients for OS and TTP and used to calculate hazard ratios (HRs) with 95% confidence intervals. We identified 224 patients with a diagnosis of adrenocortical carcinoma, 57 of whom met the inclusion criteria for further study. Chemotherapy groups included: mitotane (n=12), platinum and etoposide (n=16), mitotane with platinum and etoposide (n=11), mitotane and other cytotoxics (n=5), platinum and etoposide with other cytotoxics (n=3), and other miscellaneous cytotoxics (n=10). No statistically significant differences in OS (P=0.31) were noted among the treatment groups, but there was a statistically significant difference in TTP (P=0.02) favoring mitotane alone (TTP=6.24 months; 95% confidence interval, 3.58-32.13). Multivariate analysis was most notable for a significantly greater OS (HR=0.49, P=0.04) and TTP (HR=0.3, P=0.01) associated with peritoneal metastases. Our analysis revealed no clear advantage for any single agent or combination over any of the other conventional frontline chemotherapeutic choices for adrenocortical carcinoma. Novel agents are thus sorely needed in the treatment of this aggressive cancer.

Interferon-induced hypothyroidism causing reversible pituitary enlargement.

OBJECTIVE: To present the first reported case of interferon-induced hypothyroidism with radiographic confirmation of secondary pituitary hyperplasia. METHODS: We describe the case of a woman with recurrent malignant melanoma, outline the details of her endocrine work-up, and illustrate the serial findings on magnetic resonance imaging of the head. RESULTS: A 26-year-old woman underwent surgical excision of a melanoma of the left thigh and 10 years later had a second melanoma removed from her right knee. Metastatic work-up revealed evidence of tumor involvement in the cervical and mediastinal lymph nodes. After treatment with interferon for 1 year, persistent fatigue and menstrual irregularities led to the laboratory diagnosis of hypothyroidism, and magnetic resonance imaging revealed pituitary enlargement. Both her endocrinopathy and the pituitary hyperplasia resolved with discontinuation of the interferon treatment and with institution of thyroid replacement therapy. CONCLUSION: Clinicians should be aware of the potential adverse effects of interferon therapy to avoid inappropriate diagnosis of a pituitary adenoma or metastatic lesion in patients with cancer who are treated with interferon. In addition, screening for hypothyroidism should be performed in patients receiving interferon.

Response to mitotane predicts outcome in patients with recurrent adrenal cortical carcinoma.

BACKGROUND: Adrenal cortical carcinoma (ACC) is a rare disease in which recurrence after surgery is common. Mitotane is the primary systemic treatment for recurrent ACC; data are limited regarding the impact of mitotane on recurrent ACC. METHODS: We reviewed the records of all patients who underwent surgery for ACC evaluated at our institution from 1991 to 2006. RESULTS: The median disease-free survival for all 186 patients was 12 months and the median overall survival (OS) was 37 months. Higher stage at presentation (P = .002) and tumor cortisol production (P = .007) were associated with a worse OS. Mitotane was given to 67 evaluable patients with recurrent ACC. A response to mitotane was observed in 13 (19%) of the 67 patients. For patients with stable or responding disease to mitotane, the median OS from date of recurrence was 18 months, compared with 9 months (P = .01) for those who progressed. CONCLUSIONS: Patients with recurrent ACC who have stable or responding disease to mitotane have a more favorable prognosis than those who progress. Mitotane should be considered in most patients with recurrent ACC, including as preoperative therapy for those with recurrent disease considered for surgical resection.

Diagnostic challenges in adrenocortical carcinoma: recommendations for surveillance after surgical resection of selected adrenal nodules.

OBJECTIVE: To discuss challenges in the diagnosis of adrenocortical carcinoma and to suggest surveillance measures after removal of selected adrenal nodules. METHODS: We present the case of a 65-year-old man with worsening hypertension and new-onset hypokalemia attributed to primary hyperaldosteronism due to a 3-cm right adrenal nodule. RESULTS: A laparoscopic right adrenalectomy was performed, and the histologic diagnosis was a benign adenoma. The patient's hypertension and hypokalemia improved postoperatively but recurred 8 months later, and florid Cushing's syndrome developed. Magnetic resonance imaging showed an 8-cm mass in the right adrenal bed and multiple hepatic metastatic lesions. Fine-needle biopsy confirmed the presence of adrenocortical carcinoma. CONCLUSION: Despite a comprehensive biochemical, radiologic, and histologic assessment, the diagnosis of adrenocortical carcinoma can be missed. Particularly, we caution against undue reliance on the initial tumor size. We recommend that abdominal imaging be performed every 3 months for the first year and every 6 months for the second year after surgical removal of selected adrenal nodules.