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Background: Up to 70% of adrenal masses detected in patients affected by extra-adrenal malignancy are metastatic lesions. Therefore, detection of an adrenal mass in patients with active or previous malignancy requires a careful differential diagnostic workup. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) is increasingly being used to determine the malignant potential of adrenal lesions. Clinical case: We report the case of a 64-year-old man who had a single adrenal metastasis due to non-small-cell lung carcinoma developing on a pre-existing benign adrenal lesion. This metastasis occurred in a phase of perceived oncological remission and was detected thanks to 18F-FDG-PET/CT showing a focal adrenal uptake. Contrast-enhanced computed tomography (CT), performed as part of oncological follow-up, and MRI with chemical shift sequences did not lead to the correct diagnosis. The patient underwent laparoscopic adrenalectomy and the pathological evaluation confirmed a lung carcinoma metastasis. Conclusion: The present case highlights the peculiarity of the follow-up of adrenal masses in cancer patients and the primary role of 18F-FDG-PET/CT in the management of such patients.

Adjuvant treatment with mitotane is commonly used after resection of adrenocortical carcinoma; however, treatment remains controversial, particularly if risk of recurrence is not high. We aimed to assess the efficacy and safety of adjuvant mitotane compared with surveillance alone following complete tumour resection in patients with adrenocortical carcinoma considered to be at low to intermediate risk of recurrence.

The association between cortisol secretion and mortality in patients with adrenal incidentalomas is controversial. We aimed to assess all-cause mortality, prevalence of comorbidities, and occurrence of cardiovascular events in uniformly stratified patients with adrenal incidentalomas and cortisol autonomy (defined as non-suppressible serum cortisol on dexamethasone suppression testing).

Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC.

Background: Non-osteoporotic patients with endocrine-sensitive breast cancer are oftentreated with denosumab only during the anti-aromatase treatment, and when the anti-aromatasetherapy is discontinued, no antiresorptive drug is prescribed. This case report clearly shows howeven a patient with a low risk of fractures could have multiple rebound vertebral fractures afterdenosumab discontinuation. Case Presentation: We report the case of a 60-year-old woman who suffered from multiple vertebralfractures only seven months after discontinuation of denosumab that had been administered toprevent bone loss related to three years of aromatase inhibitors as adjuvant therapy for breast cancer.No antiresorptive therapy was prescribed at the time of denosumab discontinuation, assumingthat the patient had a low absolute risk of fracture after the withdrawal of the aromatase inhibitor. Conclusion: This case underlines the relative irrelevance of bone mineral density and clinical algorithmsin predicting the risk of rebound-associated vertebral fractures after denosumab discontinuationand the strong recommendation to always switch to another antiresorptive therapy (such aszoledronic acid) immediately at the time of denosumab discontinuation.

Metyrapone has been approved for the treatment of patients with Cushing’s syndrome (CS), but only few retrospective clinical studies are available. The aim of our study was the prospective assessment of metyrapone as pre-operative treatment.Before adrenalectomy, seven patients with ACTH-independent CS due to adrenal adenoma were prospectively treated with metyrapone for 3 months in three tertiary academic centers, with endocrine work-up and clinical evaluation at screening and at predefined evaluation time points (Days 14, 31, 48, 65, 82).In all patients, UFC levels decreased up to normal range from baseline to Day 82 (609 (188–1476) vs 69 (28–152) nmol/24 h, P< 0.02), with a reduction of serum and salivary cortisol levels, and no significant increase of plasma ACTH and serum DHEAS levels. Clinical improvement was reported on quality of life (+16.7 (+4.2; +52.00) points, P< 0.04) and pressure control (systolic pressure, −25 (−52; −10) mmHg, P< 0.01; diastolic pressure, −16 (−50; +2 mmHg), P< 0.03). No significant change in weight, electrolytes, glycemic and lipid profile was reported. Although in women a significant increase of testosterone and androstenedione was reported, no worsening of clinical hyperandrogenism was observed. All drug-related adverse events (nausea, fatigue, low grade fever, edema of lower limbs and facial rash) were grade 1 or 2 and generally transient.This prospective pilot study demonstrated that metyrapone is effective in normalizing biochemical and clinical parameters in patients with CS due to adrenal adenoma before surgical intervention, with minimal side effects.

Acute porphyrias are metabolic disorders of heme biosynthesis characterized by acute life-threatening attacks. The diagnosis is often missed since clinical presentation is aspecific mimicking other medical and surgical conditions. Variegate porphyria (VP) is an autosomal dominant inherited disease with incomplete penetrance due to decreased activity of the Protoporphyrinogen Oxydase (PPOX) gene; most VP mutations are family specific. We report the case of a 40 year-old woman who presented many times to the emergency department complaining of unexplained abdominal pain and laboratory investigations showed repeatedly hyponatremia. Syndrome of inappropriate antidiuresis (SIAD) was confirmed and measurement of urine porphobilinogen and delta-aminolevulinic acid disclosed the diagnosis of acute porphyria. The genetic analysis of PPOX gene was performed. The entire coding sequence and exon/intron boundaries of PPOX gene were amplified in 5 different Polymerase Chain Reaction (PCR) fragments. In silico prediction of the pathogenicity of the mutation was determined by using different tools, Polyphen2, SNPs&GO, SNPs3D. The genetic analysis of PPOX gene revealed a novel missense variant c.1376 G > A (p.Cys459Tyr) in heterozygous state. The same variant was later found in one of her cousins with skin lesions and other three younger asymptomatic relatives. We provided evidence that this novel mutation is likely to be pathogenetic. Our case highlights the importance of considering VP in the differential diagnosis of SIAD and underlines the role of genetic screening in the management of such patients. The finding of a novel mutation of PPOX gene in our index case has allowed to recognize an affected family.

Adrenocortical carcinoma (ACC) is a rare and aggressive tumor. ACC may be associated with different syndromes of hormone excess, most frequently Cushing’s syndrome with or without hypersecretion of androgens. Recent data suggest that cortisol excess is a negative prognostic factor in advanced and localized ACC. Surgery with radical intent, when feasible, is the most effective treatment for ACC with hypercortisolism. Mitotane is the medical treatment of choice, both postoperatively and in inoperable or metastatic cases. Because of its slow onset of action, combination with other antisecretory agents (ie, metyrapone) is helpful to achieve more rapid and effective control of hypercortisolism.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with overall poor prognosis. The Ki67 labeling index (LI) has a major prognostic role in localized ACC after complete resection, but its estimates may suffer from considerable intra- and interobserver variability. VAV2 overexpression induced by increased Steroidogenic Factor-1 dosage is an essential factor driving ACC tumor cell invasion.

Background: Adrenocortical carcinoma (ACC) is an extremely rare aggressive disease. Few data are available on the efficacy of systemic antineoplastic treatments (mitotane and cytotoxic therapy) in the treatment of advanced disease. Objective/methods: this paper will review the existing treatment strategies and new perspectives in the management of ACC patients. Results/conclusion: An ongoing randomized international trial aims to define the best combination chemotherapy plus mitotane regimen. Based on the results of a case control study, mitotane is being explored as adjuvant therapy. Genetic and biological studies have identified molecular targets for specific targeted drugs such as IGF receptor inhibitors and antiangiogenetic drugs. Phase II trials are exploring the activity of these drugs either alone or in combination with chemotherapy.

In this “talking chapter” bell hooks reveals, through dialogue about her thoughts and experiences related to college teaching and learning, a profound and robust perspective on what could be called “deep” faculty development. Topics include engaged pedagogy, therapeutic conversations, spiritual practice, difference, conflict, and love.

Objective: The long-term outcome of non-functioning pituitary adenoma (NFPA) patients is not clearly established, probably due to the low annual incidence and prolonged natural history of these rare tumors. The aim of this study was to evaluate clinical data at presentation and long-term post-surgery and radiotherapy outcome in a cohort of patients with NFPA.Design and methods: A computerized database was developed using Access 2000 software (Microsoft Corporation, 1999). Retrospective registration of 295 NFPA patients was performed in seven Endocrinological Centers of North West Italy. Data were analyzed by STATA software.Results: The main presenting symptoms were visual defects (67.8%) and headache (41.4%) and the most frequent pituitary deficit was hypogonadism (43.3%), since almost all tumors were macroadenomas (96.5%). Surgery was the first choice treatment (98% of patients) and total debulking was achieved in 35.5%. Radiotherapy was performed as adjuvant therapy after surgery in 41% of patients. At the follow-up, recurrence occurred in 19.2% of patients without post-surgical residual tumor after 7.5 ± 2.6 years, regrowth in 58.4% of patients with post-surgical remnant after 5.3 ± 4.0 years and residue enlargement in 18.4% of patients post-surgically treated with radiotherapy after 8.1 ± 7.3 years.Conclusions: Our database indicates that the goal of a definitive surgical cure has been achieved during the last decade in a low percentage of patients with NFPA. This tumor database may help to reduce the delay between symptom onset and diagnosis, to assess prognostic parameters for the follow-up of patients with different risk of recurrence and to define the efficacy and safety of different treatments and their association with mortality/morbidity.

Objective: It is presently unclear whether the accuracy of midnight serum cortisol (F24) in the diagnosis of Cushing’s syndrome (CS) may be replicated under usual conditions of clinical care. The aim of the present study was to assess retrospectively the effectiveness of F24 for confirming the diagnosis in a consecutive series of 106 patients, in 78 of whom a definitive diagnosis of CS was made.Design and methods: We have compared the results of F24, urinary free cortisol (UFC) and the overnight 1 mg dexamethasone suppression test (DST) with the definitive clinical diagnosis. Receiver operating characteristic (ROC) analysis has been performed to define the best cutoff values, the sensitivity (Se) and the specificity (Sp) of the tests.Results: The best cutoff value for F24 was 8.3 μg/dl (Se 91.8%; Sp 96.4%). The best cutoff value for the DST was 4.0 μg/dl (Se 89.2%; Sp 90.9%). The best cutoff value for UFC was 238 μg/24 h (Se 73.2%; Sp 96.3%). The area under the curve of F24 was significantly greater than that of UFC, both in the overall series (P= 0.004) and in the subgroup of patients with mild CS (P= 0.02). The differences were analyzed by means of the two-tailed students’s t-test. With the thresholds generated by the ROC analysis, UFC would have failed to achieve the correct diagnosis in a significantly higher percentage of cases than F24 (20.4% vs 7.9%; P= 0.01). The difference was analyzed by means of the chi-squared test with Yates correction.Conclusions: The present results show that F24 has excellent effectiveness in the diagnostic procedures for CS in stressed conditions (patients studied in a hospital ward in a nonsleeping state). The test appears to be accurate also for patients with mild hypercortisolism.