Alberto Angeli

Prevalence of adrenal incidentaloma in a contemporary computerized tomography series

Adrenal incidentalomas, defined as masses discovered incidentally during imaging investigation of non-adrenal disorders, have become a rather common finding in clinical practice. The prevalence is not well characterized and varies among studies. The aim of the present study was to perform a prospective evaluation of the prevalence of adrenal incidentalomas among subjects undergoing computerized tomography (CT) scan of the chest in a screening program of lung cancer (Tic TAC study) in Piedmont, a region of Northwestern Italy. This evaluation included 520 subjects (382 males and 138 females, aged between 55–82 yr), referred to our hospital from April to December 2001. Twenty-three patients with adrenal masses were identified: 21 adrenal adenomas, 1 myelolipoma, and 1 metastasis of lung cancer. Therefore, the overall prevalence of adrenal lesions was 4.4%, and that of benign adrenal masses was 4.2%. This prevalence is higher than those found in previous CT scan series reported in the literature, probably because of the use of high-resolution CT scanning technology. Another factor that influenced our results is that subject age is skewed towards the decades characterized by a greater occurrence of adrenal masses. The outcome of this study confirms that we are presently able to identify incidentally discovered adrenal masses more often than in early years and that the prevalence of adrenal incidentalomas on CT images is approaching that of autopsy series. The present study provides a reliable estimate of the prevalence of adrenal incidentaloma with currently used CT scanners. Notwithstanding that our subjects were at increased risk of lung cancer, the rate of adrenal metastases was low. We think that the present results can be generalized even if we may disclose the lack of histological diagnosis.

Glucocorticoid-induced osteoporosis: an update

Glucocorticoid-induced osteoporosis occurs in two phases: a rapid, early phase in which bone mineral density is reduced, possibly as a result of excessive bone resorption, and a slower, progressive phase in which bone mineral density declines because of impaired bone formation. Although the indirect effects of glucocorticoids on bone are evident, their direct effects on osteoblasts, osteoclasts and osteocytes are primarily operative in the pathogenesis of glucocorticoid-induced osteoporosis. The management of patients exposed to glucocorticoids includes general health measures, sufficient calcium and vitamin D, and reducing the therapeutic regimen to the minimal effective dose. The gold standard in the pharmacological treatment of glucocorticoid-induced osteoporosis in postmenopausal women involves the use of bisphosphonates, which should be started soon after beginning chronic glucocorticoid therapy. Anabolic and alternative therapeutic strategies are currently under investigation in glucocorticoid-induced osteoporosis.

Changes in Bone Mineral Density, Lean Body Mass and Fat Content as Measured by Dual Energy X-Ray Absorptiometry in Patients With Prostate Cancer Without Apparent Bone Metastases Given Androgen Deprivation Therapy

PURPOSE We characterize the consequences of androgen deprivation therapy on body composition in elderly men. MATERIALS AND METHODS Using a dual energy x-ray absorptiometry instrument, we determined the changes in bone mineral density, bone mineral content, fat body mass and lean body mass in 35 patients with prostate cancer without bone metastases who received luteinizing hormone releasing hormone analogue for 12 months. RESULTS At baseline conditions 46% of cases were classified as osteopenic and 14% as osteoporotic at the lumbar spine and 40% were osteopenic and 4% osteoporotic at the hip. Androgen deprivation significantly decreased bone mineral density either at the lumbar spine (mean gm./cm.2 [SD] 1.00 [0.194], 0.986 [0.172] and 0.977 [0.182] at baseline, and 6 and 12 months, respectively, p <0.002) or the hip (0.929 [0.136], 0.926 [0.144] and 0.923 [0.138], p <0.03). A more than 2% decrease in bone mineral density was found at the lumbar spine in 19 men (54.3%) and at the hip in 15 (42.9%). Bone mineral content paralleled the bone mineral density pattern. Lean body mass decreased (mean gm. [SD] 50,287 [6,656], 49,296 [6,554] and 49,327 [6,345], p <0.003), whereas fat body mass consistently increased (18,115 [6,209], 20,724 [6,029] and 21,604 [5,923] p <0.001). CONCLUSIONS Serial bone densitometry evaluation during androgen deprivation therapy may allow the detection of patients with prostate cancer at risk for osteoporotic fractures, that is those with osteopenia or osteoporosis at baseline and fast bone loss. The change in body composition may predispose patients to accidental falls, thus increasing the risk of bone fracture.

Subclinical Cushing's syndrome in adrenal incidentaloma

Some patients with incidentally discovered adrenal adenomas display autonomous cortisol secretion not fully restrained by pituitary feedback, a condition that may be defined as subclinical Cushings syndrome. We have evaluated the presence of subclinical Cushings syndrome and its natural history in a cohort of patients with incidentally discovered adrenal adenomas.

INCIDENCE OF SKELETAL COMPLICATIONS IN PATIENTS WITH BONE METASTATIC PROSTATE CANCER AND HORMONE REFRACTORY DISEASE: PREDICTIVE ROLE OF BONE RESORPTION AND FORMATION MARKERS EVALUATED AT BASELINE

PURPOSE We evaluated the incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease. We also assessed the predictive role of bone turnover markers determined at baseline. MATERIALS AND METHODS A total of 112 patients were consecutively enrolled in our study from July 1990 to July 1998 and followed until death or the last followup. Bone pain, disease extent in bone, serum prostate specific antigen, hemoglobin, and a panel of bone formation and resorption markers were assessed at baseline before any second line treatment. RESULTS Skeletal complications in 34 patients (30.3%, estimated yearly incidence 12.3%) involved vertebral deformity or collapse requiring spinal orthosis in 20 (17.9%), spinal cord compression in 7 (6.2%), pathological bone fracture in 10 (8.9%), symptomatic hypercalcemia in 1 (0.9%) and symptomatic hypocalcemia in 1 (0.9%). Median time to the evidence of the initial skeletal complication was 9.5 months. These adverse events did not influence overall survival. At baseline patients with eventual skeletal complications had greater bone pain (p = 0.02), a heavier tumor load in bone (p = 0.005), lower performance status (p = 0.05), and higher serum alkaline phosphatase (p <0.02) and urinary deoxypyridoline (p <0.05) than their counterparts. Multivariate analysis revealed that only urinary deoxypyridinoline was independently associated with the onset of these events (p <0.02). The scatterplot of urinary deoxypyridinoline values in patients with and without skeletal complications enabled us to detect a cutoff of 38 pM./mM. for predicting 51% of skeletal events with only an 8% false-positive rate. CONCLUSIONS Skeletal complications are common in patients with prostate cancer and hormone refractory disease. Bone loss is the major cause of onset. Baseline deoxypyridinoline at the cutoff point noted had moderate sensitivity but high specificity for predicting these adverse skeletal events.

Adrenal Incidentaloma: An Overview of Clinical and Epidemiological Data from the National Italian Study Group

BACKGROUND The incidental discovery of an adrenal mass raises the problem of distinguishing the frequent benign masses from the infrequent malignant ones that require surgery. At present, univocal guidelines to approach this problem are not available. The aim of the present study was to perform a multicentric retrospective analysis of adrenal masses incidentally discovered (adrenal incidentalomas). PATIENTS AND METHODS Hospital records of adrenal incidentalomas diagnosed over a 15-year period in 29 surgical and medical centers in Italy were scrutinized. Collected cases were 1,013, and 887 were analyzed. RESULTS The majority of patients were in the 5th and 6th decade and females were predominantly affected. The frequency of adrenocortical cancer was 12% among operated patients (316 cases). The tumor diameter was highly correlated with the risk of malignancy, as well as the CT characteristics such as density, shape and margins. The frequency of pheochromocytoma was 10% among operated patients. CONCLUSIONS The occurrence of incidentally discovered adrenocortical carcinomas and pheochromocytomas is not rare. Evaluation of the mass size and CT characteristics are simple and effective methods to differentiate malignant lesions. Biochemical screening for pheochromocytoma is mandatory before surgery.

Circulating neuroendocrine markers in patients with prostate carcinoma.

Circulating neuroendocrine markers were measured in patients with prostate carcinoma (PC), prostatic intraepithelial neoplasia (PIN), and benign prostatic hypertrophy (BPH) with the goal to: 1) evaluate the differences in the expression of these markers in patients with benign, premalignant, and primary or metastatic PC; 2) evaluate their prognostic significance; 3) compare values in patients with hormone‐naive and hormone‐refractory disease; and 4) assess changes after androgen deprivation or chemotherapy.

Inhibition by cortisol of human natural killer (NK) cell activity.

The effects of cortisol on the natural killer (NK) activity of human peripheral blood mononuclear (PBM) cells were studied in vitro using a direct 4-h 51Cr-release assay and K 562 cell line as a target. Preincubation for 20 h of PBM cells drawn from healthy donors with 1 X 10(-8) to 1 X 10(-5) M cortisol resulted in a significant decrease of NK cell activity. The magnitude of the suppression was directly related to the steroid concentration and inversely related to the number of effector cells. Cortisol was able to minimize the enhancement of NK cytotoxicity obtainable in the presence of immune interferon (IFN-gamma). A significantly higher suppression was achieved after sequential exposure of PBM cells to cortisol and equimolar levels of prostaglandin E2 (PgE2). The concomitant incubation with theophylline and isobutyl-methylxanthine failed to enhance the cortisol-induced suppression, whereas PgE2-dependent inhibition significantly increased after exposure of PBM cells to methyl-xanthines. The inhibitory effect of cortisol was partially or totally prevented by the concomitant incubation with equimolar amounts of 11-deoxycortisol and RU 486 but not of progesterone. Treatment of NK effectors with a monoclonal anti-human corticosteroid-binding globulin (CBG) antibody produced an enhancement of the spontaneous NK activity and a partial suppression of cortisol-mediated effects. Our results suggest that endogenous glucocorticoids play a role in the regulation of NK cell-mediated cytotoxicity. Since the effect of cortisol was additive to that of PgE2 and was not changed by phosphodiesterase inhibitors, it is conceivable that the hormone acts at a level different from the adenylate cyclase-phosphodiesterase system. Data obtained with the use of antiglucocorticoids and the anti-CBG antibody are compatible with a role both of high-affinity glucocorticoid receptors and of CBG in mediating cortisol action on the human NK cell activity.

Mitotane associated with etoposide, doxorubicin, and cisplatin in the treatment of advanced adrenocortical carcinoma

The use of either mitotane or chemotherapy in the treatment of advanced adrenocortical carcinoma (ACC) has led to scanty and controversial results. The recent finding that mitotane is able to reverse in vitro multidrug resistance has provided a rational basis for combining this agent with cytotoxic drugs. The association of mitotane with etoposide, doxorubicin, and cisplatin (EDP) in the treatment of patients with advanced, inoperable ACC was tested in an Italian multicenter Phase II trial.

The overtraining syndrome in athletes: A stress-related disorder

Physical exercise is a type of allostatic load for several endocrine systems, notably the hypothalamic-pituitary-adrenal (HPA) axis. Athletes undergoing a strenuous training schedule can develop a significant decrease in performance associated with systemic symptoms or signs: the overtraining syndrome (OTS). This is a stress-related condition that consists of alteration of physiological functions and adaptation to performance, impairment of psychological processing, immunological dysfunction and biochemical abnormalities. Universally agreed diagnostic criteria for OTS are lacking. The pituitary-adrenal response to a standardized exercise test is usually reduced in overtrained athletes. This HPA dysfunction could reflect the exhaustion stage of Selye’s general adaptation syndrome. The most attractive hypothesis that accounts for the observed neuro-endocrine-immune dysregulation is the Smith’s cytokine hypothesis of OTS. It assumes that physical training can produce muscle and skeletal trauma, thus generating a local inflammatory reaction. With the excessive repetition of the training stimulus the local inflammation can generate a systemic inflammatory response. The main actors of these processes are the cytokines, polypeptides that modulate HPA function in and outside the brain at nearly every level of activity. It is hoped that future research will focus on endogenous risk factors for morbidities related to the neuro-endocrine-immune adaptation to exercise.