Publications by authors named "Daniela Pasquali"

55 Publications

Erectile Dysfunction and Decreased Libido in Klinefelter Syndrome: A Prevalence Meta-Analysis and Meta-Regression Study.

J Sex Med 2021 06 20;18(6):1053-1064. Epub 2021 May 20.

Endocrinology Unit, Medical Department, Azienda Usl Bologna Maggiore-Bellaria Hospital, Bologna, Italy.

Background: Only few studies have assessed sexual dysfunction in men with Klinefelter syndrome (KS).

Aim: To define pooled prevalence estimates and correlates of erectile dysfunction (ED) and decreased libido (DL) in KS.

Methods: A thorough search of Medline, Embase and Web of Science was performed to identify suitable studies. Quality of the articles was scored using the Assessment Tool for Prevalence Studies. Data were combined using random effect models and the between-studies heterogeneity was assessed by the Cochrane's Q and I. The sources of heterogeneity were investigated by meta-regression and sub-group analyses. Funnel plot, Begg's rank correlation and trim-and-fill test were used to assess publication bias.

Main Outcome Measure: The pooled prevalence of ED and DL in KS as well as 95% confidence intervals (CIs) were estimated from the proportion of cases of sexual dysfunction and the sample size. Variables that could affect the estimates were identified by linear meta-regression models.

Results: Sixteen studies included collectively gave information about ED and DL in 482 and 368 KS men, respectively, resulting in a pooled prevalence of 28% (95% CI: 19%-36%) for ED and 51% (95% CI: 36%-66%) for DL, with a large heterogeneity. The trim-and-fill adjustment for publication bias produced a negligible effect on the pooled estimates. At the meta-regression analyses, a higher prevalence of ED was significantly associated with an older age but not with lower testosterone levels. In series with a mean age >35 years, the ED prevalence estimate increased up to 38% (95% CI: 31%-44%) with no heterogeneity (I=0.0%, P=0.6). On the contrary, the prevalence of DL increased significantly as testosterone levels decreased, without a significant relationship with age.

Clinical Implications: While DL would largely reflect an androgen deficiency, in older men with KS, erectile function should be assessed irrespective of testosterone levels.

Strength & Limitations: This is the first meta-analysis defining pooled prevalence estimates and correlates of ED and DL in KS. Nevertheless, caution is required when interpreting results, due to the high risk of bias in many studies, as well as the dearth of data about psychosocial and/or psychosexological variables and age at the diagnosis.

Conclusions: ED and DL represent common clinical complaints in KS. While the prevalence of ED would increase with age, DL gets more common as serum testosterone decreases. Further studies are warranted to elucidate the pathogenetic mechanism(s) underlying the age-dependent increase in the prevalence of ED, apparently unrelated to the androgenic status. A Barbonetti, S D'Andrea, W Vena, et al. Erectile Dysfunction and Decreased Libido in Klinefelter Syndrome: A Prevalence Meta-Analysis and Meta-Regression Study. J Sex Med 2021;18:1054-1064.
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http://dx.doi.org/10.1016/j.jsxm.2021.03.078DOI Listing
June 2021

Diagnostic issues faced by a rare disease healthcare network during Covid-19 outbreak: data from the Campania Rare Disease Registry.

J Public Health (Oxf) 2021 05 13. Epub 2021 May 13.

Centro di Coordinamento Malattie Rare, Regione Campania Naples 80131, Italy.

Background: The aims of this study were: to investigate the capacity of the rare disease healthcare network in Campania to diagnose patients with rare diseases during the outbreak of Covid-19; and to shed light on problematic diagnoses during this period.

Methods: To describe the impact of the Covid-19 pandemic on the diagnosis of patients with rare diseases, a retrospective analysis of the Campania Region Rare Disease Registry was performed. A tailored questionnaire was sent to rare disease experts to investigate major issues during the emergency period.

Results: Prevalence of new diagnoses of rare disease in March and April 2020 was significantly lower than in 2019 (117 versus 317, P < 0.001 and 37 versus 349, P < 0.001, respectively) and 2018 (117 versus 389, P < 0.001 and 37 versus 282, P < 0.001, respectively). Eighty-two among 98 rare disease experts completed the questionnaire. Diagnostic success (95%), access to diagnosis (80%) and follow-up (72%), lack of Personal Protective Equipment (60%), lack of Covid-19 guidelines (50%) and the need for home therapy (78%) were the most important issues raised during Covid-19 outbreak.

Conclusions: This study describes the effects of the Covid-19 outbreak on the diagnosis of rare disease in a single Italian region and investigates potential issues of diagnosis and management during this period.
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http://dx.doi.org/10.1093/pubmed/fdab137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194710PMC
May 2021

Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multicentre nation-wide cohort.

Haematologica 2021 Jan 7. Epub 2021 Jan 7.

Department of Women, Child and General and Specialized Surgery, University " Luigi Vanvitelli", via Luigi De Crecchio n. 4, 80138, Naples.

Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusion-dependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX).We developed a multicentre follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95%CI=6.3-13.1). Multiple Cox regression analysis identified 3 key predictors: age showed a positive log-linear effect (adjusted HR for 50% increase=1.2, 95%CI=1.1-1.3, P=0.005), the serum concentration of thyrotropin (TSH) showed a positive linear effect (adjusted HR for 1 mIU/L increase=1.3, 95%CI=1.1-1.4, P.
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http://dx.doi.org/10.3324/haematol.2020.272419DOI Listing
January 2021

The Human Microbiota in Endocrinology: Implications for Pathophysiology, Treatment, and Prognosis in Thyroid Diseases.

Front Endocrinol (Lausanne) 2020 4;11:586529. Epub 2020 Dec 4.

Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

The human microbiota is an integral component in the maintenance of health and of the immune system. Microbiome-wide association studies have found numerous diseases associated to dysbiosis. Studies are needed to move beyond correlations and begin to address causation. Autoimmune thyroid diseases (ATD) are one of the most common organ-specific autoimmune disorders with an increasing prevalence, higher than 5% worldwide. Most frequent manifestations of ATD are Hashimoto's thyroiditis and Graves' disease. The exact etiology of ATD remains unknown. Until now it is not clear whether bacterial infections can trigger ATD or modulate the efficacy of treatment and prognosis. The aim of our review is to characterize the microbiota and in ATD and to evaluate the impact of dysbiosis on treatment and prognosis. Moreover, variation of gut microbiome has been associated with thyroid cancer and benign nodules. Here we will characterize the microbioma in benign thyroid nodules, and papillary thyroid cancer to evaluate their implications in the pathophysiology and progression.
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http://dx.doi.org/10.3389/fendo.2020.586529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746874PMC
May 2021

Patients with adrenal insufficiency have cardiovascular features associated with hypovolemia.

Endocrine 2020 11 19;70(2):412-420. Epub 2020 Aug 19.

Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

Context: Patients with adrenal insufficiency (AI) have excess mortality and morbidity, mainly due to cardiovascular (CV) diseases. The mechanisms for this is unclear.

Objective: To assess CV structure and function in AI patients on conventional replacement therapy and after switching to once-daily, modified-release hydrocortisone (OD-HC) in comparison with healthy matched controls.

Methods: This was a retrospective analysis of 17 adult AI patients (11 with primary AI, 6 with secondary AI) on stable replacement with cortisone acetate [median (minimum, maximum) 33.5 (12.5-50) mg] and, if needed, fludrocortisone [0.1 (0.05-0.2) mg], and 17 healthy matched controls. Ten patients were switched to an equivalent dose of OD-HC. Data from echocardiography, 24 h Holter-ECG and 24 h blood pressure monitoring were collected at baseline and 6 months after the switch to OD-HC.

Results: At baseline, AI patients had smaller left ventricular diastolic diameter (47.1 ± 4.2 vs. 51.6 ± 2.3 mm; P = 0.001) and left atrial diameter (34.9 ± 4.7 vs. 38.2 ± 2.6 cm; P = 0.018), and a higher ejection fraction (62.5 ± 6.9% vs. 56.0 ± 4.7%; P = 0.003) than controls. AI patients had lower nocturnal systolic and diastolic blood pressure than controls (108 ± 15 mmHg vs. 117 ± 8 mmHg; P = 0.038 and 65 ± 9 mmHg vs. 73 ± 7 mmHg; P = 0.008, respectively). After the switch to OD-HC, nocturnal diastolic blood pressure normalised. No significant changes were observed in echocardiographic and Holter-ECG parameters following the switch.

Conclusions: AI patients on conventional treatment display cardiovascular abnormalities that could be related to hypovolemia. Switch to OD-HC seems to have beneficial effect on blood pressure profile, but no effect on cardiovascular structure and function.
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http://dx.doi.org/10.1007/s12020-020-02458-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581570PMC
November 2020

Patients with chronic autoimmune thyroiditis are not at higher risk for developing clinically overt thyroid cancer: a 10-year follow-up study.

Eur J Endocrinol 2020 Sep;183(3):317-323

Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy.

Objective: The association between chronic autoimmune thyroiditis (CAT) and differentiated thyroid cancer (DTC) remains controversial. The incidence of DTC increases when screening procedures are implemented, as typically occurs in CAT patients being routinely submitted to thyroid ultrasound (US). The aim of this study was to longitudinally evaluate the long-term development of DTC in patients with CAT.

Design And Methods: A retrospective longitudinal cohort study was designed. For the study, 510 patients with chronic autoimmune thyroiditis (CAT) with a 10-year follow-up were enrolled. Patients were divided in two groups according to the presence (CAT+ NOD+; n = 115) or absence (CAT+ NOD-; n = 395) of co-existent nodules at diagnosis. The main outcome measures were appearance of new thyroid-nodules and development of DTC during follow-up.

Results: During a 10-year median follow-up period, new thyroid-nodules were detected in 34/115 (29.5%) patients in the CAT+ NOD+ group and in 41/395 (10.3%) in the CAT+ NOD- group (P < 0.001). Logistic regression analysis showed that thyroid-volume at diagnosis and belonging to the CAT+ NOD+ group significantly predicted the appearance of a new thyroid nodule during follow-up, independently of baseline age and sex. Among the 75 patients experiencing the appearance of a new nodule, 27 (39%) met the criteria for fine-needle-aspiration-cytology (FNAC). A benign cytological diagnosis was rendered in all cases.

Conclusions: In our series of CAT patients, the appearance of new thyroid-nodules was frequent, but none of them were found to be malignant. The presence of CAT appears to be associated with a negligible risk of developing clinically overt DTC.
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http://dx.doi.org/10.1530/EJE-20-0350DOI Listing
September 2020

Combined effects of growth hormone and testosterone replacement treatment in heart failure.

ESC Heart Fail 2019 12 7;6(6):1216-1221. Epub 2019 Nov 7.

Department of Translational Medical Sciences, Division of Internal Medicine & Metabolism & Rehabilitation, Federico II University, Naples, Italy.

Aims: Although preliminary studies have demonstrated safety and effectiveness of single replacement therapy for growth hormone deficiency or testosterone deficiency in heart failure (HF), no data are available regarding the combined treatment with both GH and T in this setting. Thus, the aim of the present hypothesis generating pilot study was to evaluate the effectiveness and safety of multiple hormonal replacement therapies in chronic HF.

Methods And Results: Five stable HF with reduced ejection fraction patients, with a concomitant diagnosis of growth hormone deficiency and testosterone deficiency, on top of guideline-based HF treatment underwent 1 year of GH replacement therapy by subcutaneous injections of somatotropin at a dose of 0.012 mg/kg every second day. After 12 months, a T replacement treatment was added at a dosage of 1000 mg every 3 months. Each patient underwent a complete M-mode, two-dimensional, and Doppler echocardiographic examination, and an incremental symptom-limited cardiopulmonary exercise test on a bicycle ergometer at baseline (BL), after 1 year of GH treatment (V1), and after 1 year of combined GH + T treatments (V2). One-year of GH treatment resulted in a significant improvement in left ventricular ejection fraction (+5.4%, P < 0.01), New York Heart Association functional class (P < 0.05), and peak oxygen consumption (VO peak) (+19.3%, P < 0.01), and in a significant reduction in NT-proBNP levels (-35.1%, P < 0.01). Notably, one additional year of combined GH and T replacement therapy induced a further increase in VO peak (+27.7%, final delta change + 52.44%, P < 0.01), as well as a significant improvement in muscular strength, as assessed by handgrip dynamometry (+17.5%, final delta change + 25.8%, P < 0.01). These beneficial effects were paralleled with an improvement of the overall clinical status (as assessed by New York Heart Association class). Of note, neither adverse effects nor cardiovascular events were reported during the follow-up period.

Conclusions: Our preliminary data suggest for the first time that combined replacement therapy with GH and T could be considered safe and therapeutic in HF patients with multiple hormone deficiencies, supporting the hypothesis that multiple hormone deficiencies syndrome can be considered as a novel and promising therapeutic target in HF. Further studies with a more robust design and larger population are needed.
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http://dx.doi.org/10.1002/ehf2.12520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989300PMC
December 2019

Selenium supplementation in patients with subclinical hypothyroidism affected by autoimmune thyroiditis: Results of the SETI study.

Endocrinol Diabetes Nutr (Engl Ed) 2020 Jan 10;67(1):28-35. Epub 2019 Jun 10.

Endocrine and Metabolic Unit, Department of Medical and Surgical Sciences, University of Brescia, Italy. Electronic address:

Objective: The purpose of this prospective study was to assess the effects of selenium supplementation on TSH and interferon-γ inducible chemokines (CXCL9, CXCL10 and CXCL11) levels in patients with subclinical hypothyroidism due to Hashimoto's thyroiditis.

Patients And Methods: Patients with subclinical hypothyroidism due to Hashimoto thyroiditis were prospectively enrolled in the SETI study. They received 83mcg of selenomethionine/day orally in a soft gel capsule for 4 months with water after a meal. No further treatment was given. All patients were measured thyroid hormone, TPOAb, CXCL9, CXCL10, CXCL11, iodine, and selenium levels at baseline and at study end.

Results: 50 patients (43/7 female/male, median age 43.9±11.8 years) were enrolled, of which five withdrew from the study. At the end of the study, euthyroidism was restored in 22/45 (48.9%) participants (responders), while 23 patients remained hypothyroid (non-responders). There were no significant changes in TPOAb, CXCL9, CXCL10, CXCL11, and iodine levels from baseline to the end of the study in both responders and non-responders. TSH levels were re-tested six months after selenomethionine withdrawal: 83.3% of responding patients remained euthyroid, while only 14.2% of non-responders became euthyroid.

Conclusions: The SETI study shows that short-course supplementation with selenomethionine is associated to a normalization of serum TSH levels which is maintained 6 months after selenium withdrawal in 50% of patients with subclinical hypothyroidism due to chronic autoimmune thyroiditis. This TSH-lowering effect of selenium supplementation is unlikely to be related to changes in humoral markers of autoimmunity and/or circulating CXCL9.
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http://dx.doi.org/10.1016/j.endinu.2019.03.018DOI Listing
January 2020

Evalutation of the perceived quality in the Orthopedics/Traumatology Unit at Carlo Poma Hospital in Mantova.

Acta Biomed 2019 03 28;90(4-S):63-73. Epub 2019 Mar 28.

ASST Carlo Poma Mantova.

The background and the aim of the work: The Department of Orthopedics and Traumatology of the "Carlo Poma" Hospital (Social Territorial Health Authority of Mantova), has pointed out in 2017, through the questionnaires survey over the citizens satisfaction, an appreciation decrease compared to the previous years. The obtained data were not sufficiently explanatory of the reasons for that kind of deterioration and also not enough specific to define possible corrective measures. The aim of this work was to identify the patients' perception regarding the hospitalization phases (from booking to follow up), taking into account five kind of operations and pathologies: 1st knee, shoulder and tibio-talar arthroscopy; 2nd hip and knee prosthesis; 3rd upper limb traumatology; 4th lower limb traumatology and 5th orthogeriatrics.

Methods: The research is based on 29 narrations resulted from orthopedic patients between 30 and 80 days after the time of discharge.

Results: The phases of care path which get the highest level of satisfaction are those concerning the operation and the outpatient visit followed by rehabilitation and assistive continuation. The most negative phase was the discharge but, also the needs assistance respond, the reception, the microclimate and the pre-operative medical assessment resulted contradictory. At the same time the three most significant areas of improvement were: the organization (critical for upper limb traumatology, arthroscopy and prosthetics); the health features (critical for the lower limb, orthogeriatrics and traumatology) and medical information (the most critical issues were those concerning the upper limb traumatology while the less were the orthogeriatrics ones).

Conclusion: Use the narration to go into the orthopedic patient needs and perceptions allows to activate appropriate and customized organizational and professional changes in order to answer adequatly to the patient's needs to limit litigation and defence medicine expences.
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http://dx.doi.org/10.23750/abm.v90i4-S.8245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625557PMC
March 2019

Management of cardiovascular complications in Klinefelter syndrome patients.

Expert Rev Endocrinol Metab 2019 03 22;14(2):145-152. Epub 2019 Feb 22.

a Department of Medical, Surgical, Neurologic , Metabolic and Aging Sciences, University of Campania "L. Vanvitelli" Naples , Naples , Italy.

Introduction: Klinefelter syndrome (KS), also known as 47, XXY, shows increased mortality when compared with mortality rates among the general population. Cardiovascular, hemostatic, metabolic diseases are implicated. Moreover, cardiac congenital anomalies in KS can contribute to the increase in mortality.

Areas Covered: In this study, we have systematically reviewed the relationships between KS and the cardiovascular system and the management of cardiovascular complication. In summary, patients with KS display increased cardiovascular risk profile, characterized by increased prevalence of metabolic alterations including dyslipidemia, diabetes mellitus (DM), and abnormalities in biomarkers of cardiovascular disease. KS subjects are characterized by subclinical abnormalities in endothelial function and in left ventricular (LV) systolic and diastolic function, which - when associated with chronotropic incompetence - may negatively influence cardiopulmonary performance. Moreover, KS patients appear to be at a higher risk for cardiovascular disease, due to thromboembolic events with high prevalence of recurrent venous ulcers, venous insufficiency, recurrent venous and arterial thromboembolism leading to deep venous thrombosis or pulmonary embolism.

Expert Opinion: Considering the unequivocal finding of increased mortality of KS patients, we suggest a periodic cardiovascular follow up in specialized centers with multidisciplinary care teams that comprise endocrinologists and cardiologists dedicated to KS syndrome.
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http://dx.doi.org/10.1080/17446651.2019.1584036DOI Listing
March 2019

Neuropsychiatric Aspects in Men with Klinefelter Syndrome.

Endocr Metab Immune Disord Drug Targets 2019 ;19(2):109-115

Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, Interdisciplinary Department of Medicine, University of Bari, School of Medicine, Policlinico, Bari, Italy.

Background And Objective: Klinefelter Syndrome (KS) is the most common sex chromosome aneuploidy (47, XXY) and cause of male hypergonadotropic hypogonadism. It is characterized by an extreme clinical heterogeneity in presentation, including infertility, hypogonadism, language delay, metabolic comorbidities, and neurocognitive and psychiatric disorders. Since testosterone is known to have organizational, neurotrophic and neuroprotective effects on brain, the condition of primary hypogonadism could play a role. Moreover, given that KS subjects have an additional X, genes on the extra-chromosome could also exert a significant impact. The aim of this narrative review is to analyze the available literature on the relationship between KS and neuropsychiatric disorders.

Methods: To extend to the best of published literature on the topic, appropriate keywords and MeSH terms were identified and searched in Pubmed. Finally, references of original articles and reviews were examined.

Results: Both morphological and functional studies focusing on the brain showed that there were important differences in brain structure of KS subjects. Different psychiatric disorders such as Schizophrenia, autism, attention deficit hyperactivity disorder, depression and anxiety were frequently reported in KS patients according to a broad spectrum of phenotypes. T supplementation (TRT) was not able to improve the psychotic disorders in KS men with or without overt hypogonadism.

Conclusion: Although the risk of psychosis, depression and autism is increased in subjects with KS, no definitive evidence has been found in studies aiming at identifying the relationship between aneuploidy, T deficit and the risk of psychiatric and cognitive disorders in subjects affected by KS.
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http://dx.doi.org/10.2174/1871530318666180703160250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360906PMC
June 2019

Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives.

Endocrine 2018 08 23;61(2):194-203. Epub 2018 Mar 23.

Department of Translational Medical Sciences, Federico II University School of Medicine, Naples, Italy.

Purpose: Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. This review summarises the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population.

Methods: We searched PubMed, Web of Science, and Scopus for manuscripts published prior to November 2017 using key words "Klinefelter syndrome" AND "insulin resistance" OR "metabolic syndrome" OR "diabetes mellitus" OR "cardiovascular disease" OR "testosterone". Manuscripts were collated, studied and carried forward for discussion where appropriate.

Results: Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system.

Conclusion: Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS.
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http://dx.doi.org/10.1007/s12020-018-1584-6DOI Listing
August 2018

Single center experience with laparoscopic adrenalectomy on a large clinical series.

BMC Surg 2018 Jan 11;18(1). Epub 2018 Jan 11.

Endocrine Surgery Unit, University of Perugia, Piazza dell'Università, 06123, Perugia, Italy.

Background: Laparoscopic adrenalectomy is considered the gold standard technique for the treatment of benign small and medium size adrenal masses (<6 cm), due to low morbidity rate, short hospitalization and patient rapid recovery. The aim of our study is to analyse the feasibility and efficiency of this surgical approach in a broad spectrum of adrenal gland pathologies.

Methods: Pre-operative, intra-operative and post-operative data from 126 patients undergone laparoscopic adrenalectomy between January 2003 and December 2015 were retrospectively collected and reviewed. Diagnosis was obtained on the basis of clinical examination, laboratory values and imaging techniques. Doxazosin was preoperatively administered in case of pheochromocytoma while spironolactone and potassium were employed to treat Conn's disease. Laparoscopic adrenalectomies were all performed by the same surgeon (CG). First 30 procedures were considered as learning curve adrenalectomies.

Results: One hundred twenty-six patients were included in the study. Functioning tumors were diagnosed in 84 patients, 27 patients were affected by pheochromocytomas, 29 by Conn's disease, 28 by Cushing disease. Surgery mean operative time was 137.33 min (range 100-180) during the learning curve adrenalectomies and 96.5 min (range 75-110) in subsequent procedures. Mean blood loss was respectively 160.2 ml (range 60-280) and 90.5 ml (range 50-200) in the first 30 procedures and the subsequent ones. Only one conversion to open surgery occurred. No post-operative major complications were observed, while minor complications occurred in 8 patients (0,79%). In 83 out of 84 functioning neoplasms, laparoscopic adrenalectomy was effective in normalization of endocrine profile.

Conclusions: Laparoscopic adrenalectomy is a safe and feasible procedure, even for functioning masses and pheochromocytomas. A multidisciplinary team including endocrinologists, endocrine surgeons and anaesthesiologists, is recommended in the management of adrenal pathology, and adrenal surgery should be performed in referral high volume centers. A thirty-procedures learning curve is recommended to improve surgical outcomes.
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http://dx.doi.org/10.1186/s12893-017-0333-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765650PMC
January 2018

Primary Adrenal Insufficiency: Managing Mineralocorticoid Replacement Therapy.

J Clin Endocrinol Metab 2018 02;103(2):376-387

Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Context: Mineralocorticoid (MC) replacement therapy in patients with primary adrenal insufficiency (PAI) was introduced more than 60 years ago. Still, there are limited data on how MC substitution should be optimized, because MC dosing regimens have only been systematically investigated in a few studies. We review the management of current standard MC replacement therapy in PAI and its plausible impact on outcome.

Design: Using PubMed, we conducted a systematic review of the literature from 1939 to 2017, with the following keywords: adrenal insufficiency, MC deficiency, aldosterone, cardiovascular disease, hypertension, and heart failure.

Results: The current standard treatment consists of fludrocortisone (FC) given once daily in the morning, aiming at normotension, normokalemia, and plasma renin activity in the upper normal range. Available data suggest that patients with PAI may be underreplaced with FC as symptoms and signs indicating chronic MC underreplacement, such as salt craving and postural dizziness persist, in many treated patients with PAI. Data acquired from large registry-based studies show that glucocorticoid doses for replacement in PAI are higher than those estimated from endogenous production. Glucocorticoid overreplacement may reduce the need of MC replacement but may also be a consequence of inadequate MC replacement.

Conclusions: The commonly used MC replacement in PAI may not be adequate in some patients. Insufficient MC substitution may be responsible for poor cardiometabolic outcome and the failure to restore well-being adequately in patients with PAI. Well-designed studies oriented at optimizing MC replacement therapy are urgently needed.
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http://dx.doi.org/10.1210/jc.2017-01928DOI Listing
February 2018

Sexual function and sex hormones in breast cancer patients.

Endocrine 2018 06 14;60(3):510-515. Epub 2017 Nov 14.

Department of Medical, Neurological and Metabolic Sciences of Ageing, University of Campania "Luigi Vanvitelli", Naples, 80138, Italy.

Purpose: Breast cancer patients (BCP) are at risk of female sexual dysfunction (FSD). Our aim was to clarify the effects of treatment strategies, and steroid hormones levels on FSD.

Methods: We enrolled 136 BCP (46.9 ± 0.8 years), and 122 completed questionnaires. BCP were divided into four groups: 22 women with advanced breast cancer on neoadjuvant therapy (NAT), 48 on adjuvant therapy (AT), 30 taking hormonal therapy (HT) and 22 with metastatic cancer on first line chemotherapy (FLT). Fifty-eight healthy women (43 ± 2.8 years) were enrolled as controls. FSD was evaluated by FSFI, and sexual distress was assessed with FSDS-R. We have collected demographic data, laboratory values, and LH, FSH, total testosterone (T), and estradiol (E2) levels.

Results: BCP showed a prevalence of FSD of 69%, total FSFI score was 17. FSDS-R was 8.3. FSD had a prevalence of 72 % in NAT, 65% in AT, 77% in metastatic BCP under FLT, 67% in HT, compared with a prevalence of 20% in controls. BCP showed lower E2 than normal values, as well as T. LH and FSH were significantly elevated than normal values. Total FSFI score was positively correlated with T in 122 BCP, no significant correlation was found between E2 and FSFI. Significant differences were found between NAT and HT in lubrication, pain domains and total FSDS-R score, AT and HT in pain domain, AT and NAT in lubrication domain.

Conclusions: BCP are at high risk of developing FSD both for treatment choice and hormonal status, but they have not sexually related personal distress.
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http://dx.doi.org/10.1007/s12020-017-1470-7DOI Listing
June 2018

Genetics of medullary thyroid cancer: An overview.

Int J Surg 2017 May;41 Suppl 1:S2-S6

Department of Neurological, Metabolic and Geriatric Science, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address:

Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or absence of hyperparathyroidism, pheocromocytoma and characteristic clinical features. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC, but there are many other mutational patterns involved. In MEN2A, Codon 634 in exon 11 (Cys634Arg), corresponding to a cysteine in the extracellular cysteine-rich domain, is the most commonly altered codon. Many other mutations include codons 611, 618, 620. In the genetical testing of RET mutations in MTCs, Next-Generation Sequencing (NGS) is taking an increasingly important role. One of the most important benefit is the comprehensive analysis of molecular alterations in MTC, which allows rapidly to select patients with different risk levels. There is a difference in miRNA expression pathway between sporadic and hereditary MTCs. Among sporadic cases, expression of miR-127 was significantly lower in those who harbor somatic RET mutations than those with wild-type RET. CDKN1B mutations are associated with many clinical pictures of cancers, such as MEN4. V109G polymorphism is associated with sporadic MTCs negative for RET mutations, and might influence the clinical course of the patients affected by MTC. Although surgery (i.e. total thyroidectomy with neck lymph node dissection) is the elective treatment for MTCs, about 80% of patients have distant metastases at diagnosis and in this cases surgery is not enough and an additional treatment is needed. Interesting results come from two large phase III clinical trials with two targeted tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib.

Conclusions: New genetical testings and therapeutical approaches open new perspectives in MTC management.
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http://dx.doi.org/10.1016/j.ijsu.2017.02.064DOI Listing
May 2017

Sperm recovery and ICSI outcomes in Klinefelter syndrome: a systematic review and meta-analysis.

Hum Reprod Update 2017 05;23(3):265-275

Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy.

Background: Specific factors underlying successful surgical sperm retrieval rates (SRR) or pregnancy rates (PR) after testicular sperm extraction (TESE) in adult patients with Klinefelter syndrome (KS) have not been completely clarified.

Objective And Rationale: The aim of this review was to meta-analyse the currently available data from subjects with KS regarding SRRs as the primary outcome. In addition, when available, PRs and live birth rates (LBRs) after the ICSI technique were also investigated as secondary outcomes.

Search Methods: An extensive Medline, Embase and Cochrane search was performed. All trials reporting SRR for conventional-TESE (cTESE) or micro-TESE (mTESE) and its specific determinants without any arbitrary restriction were included.

Outcomes: Out of 139 studies, 37 trials were included in the study, enrolling a total of 1248 patients with a mean age of 30.9 ± 5.6 years. The majority of the studies (n = 18) applied mTESE, 13 applied cTESE and in one case testicular sperm aspiration (TESA) was used. Additionally, four studies used a mixed approach and in one study, the method applied for sperm retrieval was not specified. Overall, a SRR per TESE cycle of 44[39;48]% was detected. Similar results were observed when mTESE was compared to cTESE (SRR 43[35;50]% vs 45[38;52]% for cTESE vs micro-TESE, respectively; Q = 0.20, P = 0.65). Meta-regression analysis showed that none of the parameters tested, including age, testis volume and FSH, LH and testosterone (T) levels at enrollment, affected the final SRR. Similarly, no difference was observed when a bilateral procedure was compared to a unilateral approach. No sufficient data were available to evaluate the effect of previous T treatment on SRR. Information on fertility outcome after ICSI was available for 29 studies. Overall a total of 218 biochemical pregnancies after 410 ICSI cycles were observed (PR = 43[36;50]%). Similar results were observed when LBR was analyzed (LBR = 43[34;53]%). Similar to what was observed for SRR, no influence of KS age, mean testis volume, LH, FSH or total T levels on either PR and LBR was observed. No sufficient data were available to test the effect of the women's age or other female fertility problems on PR and LBR. Finally, no difference in PR or LBR was observed when the use of fresh sperm was compared to the utilization of cryopreserved sperm.

Wider Implications: The present data suggest that performing TESE/micro-TESE in subjects with KS results in SRRs of close to 50%, and then PRs and LBRs of close to 50%, with the results being independent of any clinical or biochemical parameters tested.
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http://dx.doi.org/10.1093/humupd/dmx008DOI Listing
May 2017

Role of prophylactic central compartment lymph node dissection in clinically N0 differentiated thyroid cancer patients: analysis of risk factors and review of modern trends.

World J Surg Oncol 2016 May 17;14:149. Epub 2016 May 17.

Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy.

In the last years, especially thanks to a large diffusion of ultrasound-guided FNBs, a surprising increased incidence of differentiated thyroid cancer (DTC), "small" tumors and microcarcinomas have been reported in the international series. This led endocrinologists and surgeons to search for "tailored" and "less aggressive" therapeutic protocols avoiding risky morbidity and useless "overtreatment". Considering the most recent guidelines of referral endocrine societies, we analyzed the role of routine or so-called prophylactic central compartment lymph node dissection (RCLD), also considering its benefits and risks. Literature data showed that the debate is still open and the surgeons are divided between proponents and opponents of its use. Even if lymph node metastases are commonly observed, and in up to 90% of DTC cases micrometastases are reported, the impact of lymphatic involvement on long-term survival is subject to intensive research and the best indications of lymph node dissection are still controversial. Identification of prognostic factors for central compartment metastases could assist surgeons in determining whether to perform RLCD. Considering available evidence, a general agreement to definitely reserve RCLD to "high-risk" cases was observed. More clinical researches, in order to identify risk factors of meaningful predictive power and prospective long-term randomized trials, should be useful to validate this selective approach.
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http://dx.doi.org/10.1186/s12957-016-0879-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869299PMC
May 2016

Klinefelter syndrome, cardiovascular system, and thromboembolic disease: review of literature and clinical perspectives.

Eur J Endocrinol 2016 Jul 5;175(1):R27-40. Epub 2016 Feb 5.

Department of Translational Medical Sciences, University "Federico II"Naples, Italy

Klinefelter syndrome (KS) is the most frequently occurring sex chromosomal aberration in males, with an incidence of about 1 in 500-700 newborns. Data acquired from large registry-based studies revealed an increase in mortality rates among KS patients when compared with mortality rates among the general population. Among all causes of death, metabolic, cardiovascular, and hemostatic complication seem to play a pivotal role. KS is associated, as are other chromosomal pathologies and genetic diseases, with cardiac congenital anomalies that contribute to the increase in mortality. The aim of the current study was to systematically review the relationships between KS and the cardiovascular system and hemostatic balance. In summary, patients with KS display an increased cardiovascular risk profile, characterized by increased prevalence of metabolic abnormalities including Diabetes mellitus (DM), dyslipidemia, and alterations in biomarkers of cardiovascular disease. KS does not, however, appear to be associated with arterial hypertension. Moreover, KS patients are characterized by subclinical abnormalities in left ventricular (LV) systolic and diastolic function and endothelial function, which, when associated with chronotropic incompetence may led to reduced cardiopulmonary performance. KS patients appear to be at a higher risk for cardiovascular disease, attributing to an increased risk of thromboembolic events with a high prevalence of recurrent venous ulcers, venous insufficiency, recurrent venous and arterial thromboembolism with higher risk of deep venous thrombosis or pulmonary embolism. It appears that cardiovascular involvement in KS is mainly due to chromosomal abnormalities rather than solely on low serum testosterone levels. On the basis of evidence acquisition and authors' own experience, a flowchart addressing the management of cardiovascular function and prognosis of KS patients has been developed for clinical use.
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http://dx.doi.org/10.1530/EJE-15-1025DOI Listing
July 2016

Serum but not salivary cortisol levels are influenced by daily glycemic oscillations in type 2 diabetes.

Endocrine 2016 Jul 28;53(1):220-6. Epub 2015 Oct 28.

Endocrinology and Metabolic Diseases Unit, Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Piazza L. Miraglia 2, 80138, Naples, Italy.

Diurnal salivary and plasma cortisol variations are considered valid expression of circadian cortisol rhythmicity. The aim of this study was to assess the reliability of salivary and plasma cortisol and if glycemia and glycemic oscillations may interfere with their concentration. Forty-seven type 2 diabetic patients and 31 controls were studied for glycemic profile and diurnal salivary and plasma cortisol variations on two contemporary samples taken at 08:00 a.m.-11:00 p.m (Late Night, LN). Glucose variability was evaluated in diabetic patients by considering the standard deviation of blood glucose (BGSD) readings, by calculating the mean amplitude of glycemic excursions (MAGEs) and continuous overlapping net glycemic action (CONGA). A significant correlation between LN serum cortisol and morning fasting glycemia (r = 0.78; p = 0.004) was observed in T2DM group but not in the control group (r = 0.09; p = 0.74). While LN serum cortisol significantly correlated with CONGA in diabetic patients (r = 0.50; p < 0.001), LN salivary cortisol did not correlate with any indices of glucose variability. Moreover, a highly significant correlation between LN salivary and LN serum cortisol concentrations was found in control group (r = 0.80; p < 0.001) but not in diabetic patients (r = 0.07; p = 0.62). This study shows for the first time that LN salivary rather than plasma cortisol may give information on the dynamics of adrenal function of type 2 diabetic patients, as it is not significantly influenced by glycemic variations. However, our preliminary results need to be confirmed by further studies with more complete evaluations including many more patients.
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http://dx.doi.org/10.1007/s12020-015-0777-5DOI Listing
July 2016

A Gelatin-Thrombin Matrix Topical Hemostatic Agent (Floseal) in Combination With Harmonic Scalpel Is Effective in Patients Undergoing Total Thyroidectomy: A Prospective, Multicenter, Single-Blind, Randomized Controlled Trial.

Surg Innov 2016 Feb 3;23(1):23-9. Epub 2015 Aug 3.

Second University of Naples, Naples, Italy.

Background: Hemostasis during thyroidectomy is essential; however, the safest, most efficient, and most cost-effective way to achieve this is unclear. This randomized, multicenter, single-blind, prospective study evaluated the efficacy and safety of using different hemostatic approaches in patients undergoing total thyroidectomy.

Methods: Patients aged ≥18 to 70 years were randomized to Floseal + a harmonic scalpel (HS), Floseal alone, HS alone, or standard total thyroidectomy. Primary endpoint was 24-hour drain output. Secondary endpoints included surgery duration and complications.

Results: Two hundred and six patients were randomized to Floseal + HS (n = 52), Floseal alone (n = 54), HS alone (n = 50), and standard total thyroidectomy (n = 50). The 24-hour drain output was lower in the Floseal + HS group compared with standard thyroidectomy. Floseal + HS also had a shorter surgery time (P < .0001) versus the other 3 treatments.

Conclusion: Floseal + HS can be effective at reducing postsurgical drain output and provides a complementary hemostatic approach in patients undergoing total thyroidectomy.
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http://dx.doi.org/10.1177/1553350615596638DOI Listing
February 2016

Prognostic role of the CDNK1B V109G polymorphism in multiple endocrine neoplasia type 1.

J Cell Mol Med 2015 Jul 30;19(7):1735-41. Epub 2015 Mar 30.

CEINGE Advanced Biotechnologies, Naples, Italy.

CDKN1B encodes the cyclin-dependent kinase inhibitor p27/Kip1. CDKN1B mutations and polymorphisms are involved in tumorigenesis; specifically, the V109G single nucleotide polymorphism has been linked to different tumours with controversial results. Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome, characterized by the development of different types of neuroendocrine tumours and increased incidence of other malignancies. A clear genotype-phenotype correlation in MEN1 has not been established yet. In this study, we assessed whether the CDKN1B V109G polymorphism was associated with the development of aggressive tumours in 55 consecutive patients affected by MEN1. The polymorphism was investigated by PCR amplification of germline DNA followed by direct sequencing. Baseline and follow-up data of tumour types and their severity were collected and associated with the genetic data. MEN1-related aggressive and other malignant tumours of any origin were detected in 16.1% of wild-type and 33.3% of polymorphism allele-bearing patients (P = NS). The time interval between birth and the first aggressive tumour was significantly shorter in patients with the CDKN1B V109G polymorphism (median 46 years) than in those without (median not reached; P = 0.03). Similarly, shorter was the time interval between MEN1 diagnosis and age of the first aggressive tumour (P = 0.02). Overall survival could not be estimated as 96% patients were still alive at the time of the study. In conclusion, CDKN1B V109G polymorphism seems to play a role in the development of aggressive tumours in MEN1.
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http://dx.doi.org/10.1111/jcmm.12552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511370PMC
July 2015

Maternal hypothyroidism and subsequent neuropsychological outcome of the progeny: a family portrait.

Endocrine 2015 Dec 6;50(3):797-801. Epub 2015 Mar 6.

Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri I.R.C.C.S., Laboratory for Endocrine Disruptors, University of Pavia, Via S. Maugeri 10, 27100, Pavia, Italy.

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http://dx.doi.org/10.1007/s12020-015-0564-3DOI Listing
December 2015

Testicular parenchymal abnormalities in Klinefelter syndrome: a question of cancer? Examination of 40 consecutive patients.

Asian J Androl 2015 Jan-Feb;17(1):154-8

Department of Cardiothoracic and Respiratory Sciences, Endocrine Unit, Second University of Naples, Italy.

Klinefelter syndrome (KS) is a hypergonadotropic hypogonadism characterized by a 47, XXY karyotype. The risk of testicular cancer in KS is of interest in relation to theories about testicular cancer etiology generally; nevertheless it seems to be low. We evaluated the need for imaging and serum tumor markers for testicular cancer screening in KS. Participants were 40 consecutive KS patients, enrolled from December 2009 to January 2013. Lactate dehydrogenase (LDH), alpha-fetoprotein (AFP), and beta-human chorionic gonadotrophin subunit (β-HCG) serum levels assays and testicular ultrasound (US) with color Doppler, were carried out at study entry, after 6 months and every year for 3 years. Abdominal magnetic resonance (MR) was performed in KS when testicular US showed micro-calcifications, testicular nodules and cysts. Nearly 62% of the KS had regular testicular echotexture, 37.5% showed an irregular echotexture and 17.5% had micro-calcifications and cysts. Eighty seven percent of KS had a regular vascular pattern, 12.5% varicocele, 12.5% nodules <1 cm, but none had nodules >1 cm. MR ruled out the diagnosis of cancer in all KS with testicular micro calcifications, nodules and cysts. No significant variations in LDH, AFP, and β-HCG levels and in US pattern have been detected during follow-up. We compared serum tumor markers and US pattern between KS with and without cryptorchidism and no statistical differences were found. We did not find testicular cancer in KS, and testicular US, tumor markers and MR were, in selected cases, useful tools for correctly discriminating benign from malignant lesions.
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http://dx.doi.org/10.4103/1008-682X.128514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291860PMC
June 2016

Long-term outcomes of laparoscopic adrenalectomy for Cushing disease.

Int J Surg 2014 23;12 Suppl 1:S107-11. Epub 2014 May 23.

Department of Cardio-Thoracic and Respiratory Science, Endocrinology Unit, Second University of Naples, Italy.

Introduction: In the surgical management of the patients with Cushing syndrome (CS), minimal invasive adrenalectomy (MA) has become the procedure of choice to treat adrenal tumors with a benign appearance ≤6 cm in diameter. Authors evaluated medium- and long-term outcomes of laparoscopic adrenalectomy (LA) for CS or subclinical CS (sCS), performed for ten years in an endocrine surgery unit.

Methods: We retrospectively reviewed 21 consecutive patients undergone LA for CS or sCS from 2003 to 2013. Postoperative clinical and cardiovascular status modifications and surgical medium and long-term outcomes were analyzed.

Results: In each patient surgery determined a normalization of the hormonal profile. There was no mortality neither major post-operative complications. Mean operative time was higher during the learning curve, there was no conversion, and morbidity rate was 6.3%. Regression of the main clinical symptoms occurred slowly in twelve months.

Conclusions: LA is a safe, effective and well-tolerated procedure for the treatment of CS and sCS reducing arterial blood pressure, body weight and fasting glucose levels. Following the learning curve a morbidity rate similar to that reported in the MA series for other adrenal diseases is observed.
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http://dx.doi.org/10.1016/j.ijsu.2014.05.036DOI Listing
July 2015

Impact of prophylactic central compartment neck dissection on locoregional recurrence of differentiated thyroid cancer in clinically node-negative patients: a retrospective study of a large clinical series.

Surgery 2014 Jun 20;155(6):998-1005. Epub 2014 Feb 20.

Endocrine Surgery Unit, University of Perugia, Perugia, Italy.

Background: In clinically node-negative patients with differentiated thyroid cancer (DTC), indications for routine central lymph node dissection (RCLD) are the subject of intensive research, and surgeons are divided between the pros and cons of this surgery. To better define the role of neck dissection in the treatment of DTC, we analyzed retrospectively the results in three centers in Italy.

Methods: The clinical records of 752 clinically node-negative patients with DTC who underwent operative treatment between January 1998 and December 2005 in three endocrine surgery referral units were evaluated retrospectively. The complications and medium- and long-term outcomes of total thyroidectomy (TT) alone (performed in 390 patients: group A) and TT combined with bilateral RCLD (362 patients: group B) were analyzed and compared.

Results: The incidence of permanent hypoparathyroidism and permanent unilateral vocal folds was 1% and 0.8% in group A and 3.6% and 1.7% in the group B, respectively. Bilateral temporary recurrent nerve palsy was observed in one of the 362 patients in group B. After a follow-up of 9.5 ± 3.5 years (mean ± SD), the locoregional recurrence rate with positive cervical lymph nodes was not substantially significantly different between the two groups.

Conclusion: In our series, TT combined with bilateral RCLD was associated with a greater rate of transient and permanent complications. Similar incidences of locoregional recurrence were reported in the two groups of patients. Considering the recent trend toward routine central lymphadenectomy, further studies are needed to evaluate the benefits of these different approaches.
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http://dx.doi.org/10.1016/j.surg.2014.02.010DOI Listing
June 2014

Current concepts of pheochromocytoma.

Int J Surg 2014 12;12(5):469-74. Epub 2014 Apr 12.

Department of Cardio-Thoracic and Respiratory Science, Endocrinology Unit, Second University of Naples, Italy.

Pheochromocytoma (PCC), a rare neuroendocrine tumor, shows a prevalence ranging between 0.1% and 0.6% in individuals suffering from hypertension. To date, an increasing number of patients with hereditary forms or subclinical PCCs have been diagnosed. We reviewed the main controversies and the most recent updates, especially inheritance genetics and surgical management. According to the "rule of 10", in 1/10 patients with pheochromocytoma it is malignant, in 1/10 of cases the tumor is bilateral, in 1/10 extra-adrenal and in 1/10 familial. Surgical resection, the only curative treatment, carries a high risk of hypertensive crises due to massive catecholamine release. Alpha 1 blocker therapy, alone or in combination with beta blockers, calcium antagonists, and plasma volume expansion, is the most commonly used preoperative treatment protocol. Minimally invasive adrenalectomy (laparoscopic and retro-peritoneoscopic) allows earlier mobilization and recovery, reducing the risk of pulmonary infections and thromb-oembolic complications, and is associated with lower morbidity and mortality rates than traditional surgery; it is currently considered the gold standard for the treatment of adrenal tumors ≤6 cm in diameter and weighing < 100 g. Genetic testing will increasingly be the key factor in estimating the life-long risk for development of recurrent disease, contralateral disease or malignant dedifferentiation, thus influencing follow-up protocols.
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http://dx.doi.org/10.1016/j.ijsu.2014.04.001DOI Listing
March 2015

The role of surgery in the current management of differentiated thyroid cancer.

Endocrine 2014 Nov 10;47(2):380-8. Epub 2014 Apr 10.

VII Division of General and Endocrine Surgery, Department of Anesthesiologic, Surgical and Emergency Sciences, School of Medicine, Second University of Naples, Via Sergio Pansini 5, 80131, Naples, Italy,

In the last decades, a surprising increased incidence of differentiated thyroid cancer (DTC), along with a precocious diagnosis of "small" tumors and microcarcinomas have been observed. In these cases, better oncological outcomes are expected, and a "tailored" and "less aggressive" multimodal therapeutic protocol should be considered, avoiding an unfavorable even if minimal morbidity following an "overtreatment." In order to better define the most suitable surgical approach, its benefits and risks, we discuss the role of surgery in the current management of DTCs in the light of data appeared in the literature. Even if lymph node metastases are commonly observed, and in up to 90 % of DTC cases micrometastases are reported, the impact of lymphatic involvement on long-term survival is still argument of intensive research, and indications and extension of lymph node dissection (LD) are still under debate. In particular, endocrine and neck surgeons are still divided between proponents and opponents of routine central LD (RCLD). Considering the available evidence, there is agreement about total thyroidectomy, therapeutic LD in clinically node-positive DTC patients, and RCLD in "high risk" cases. Nevertheless, indications to the best surgical treatment of clinically node-negative "low risk" patients are still subject of research. Considering on the one hand, the recent trend toward routine central lymphadenectomy, avoiding radioactive treatment, and on the other hand, the satisfactory results obtained reserving prophylactic LD to "high risk" patients, we think that further prospective randomized trials are needed to evaluate the best choice between the different surgical approaches.
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http://dx.doi.org/10.1007/s12020-014-0251-9DOI Listing
November 2014

Laparoscopic adrenal surgery: ten-year experience in a single institution.

BMC Surg 2013 8;13 Suppl 2:S5. Epub 2013 Oct 8.

Background: Minimal invasive adrenalectomy has become the procedure of choice to treat adrenal tumors with a benign appearance, ≤ 6 cm in diameter and weighing < 100 g. Authors evaluated medium- and long-term outcomes of laparoscopic adrenalectomy (LA), performed for ten years in a single endocrine surgery unit.

Methods: We retrospectively reviewed 88 consecutive patients undergone LA for lesions of adrenal glands from 2003 to 2013. The first 30 operations were considered part of the learning curve. Doxazosin was preoperatively administered in case of pheochromocytoma (PCC), while spironolactone and potassium were employed to treat Conn's disease. Perioperative cardiovascular status modifications and surgical and medium- and long-term results were analyzed.

Results: Forty nine (55.68%) functioning tumors, and one (1.13%) bilateral adrenal disease were identified. In 2 patients (2.27%) a supposed adrenal metastasis was postoperatively confirmed, while in no patients a diagnosis of incidental primitive malignancy was performed. There was no mortality or major post operative complication. The mean operative time was higher during the learning curve. Conversion and morbidity rates were respectively 1.13% and 5.7%. Intraoperative hypertensive crises (≥180/90 mmHg) were observed in 23.5% (4/17) of PCC patients and were treated pharmacologically with no aftermath. There was no influence of age, size and operative time on the occurrence of PCC intraoperative hypertensive episodes. Surgery determined a normalization of the endocrine profile. One single PCC persistence was observed, while in a Conn's patient, just undergone right LA, a left sparing adrenalectomy was performed for a contralateral metachronous aldosteronoma.

Conclusions: LA, a safe, effective and well tolerated procedure for the treatment of adrenal neoplasms ≤ 6 cm, is feasible for larger lesions, with a similar low morbidity rate. Operative time has improved along with the increase of the experience and of the technological development. Preoperative adrenergic blockade did not prevent PCC intraoperative hypertensive crises, but facilitated the control of the hemodynamic stability.
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http://dx.doi.org/10.1186/1471-2482-13-S2-S5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850966PMC
August 2014

Predictive value of nodal metastases on local recurrence in the management of differentiated thyroid cancer. Retrospective clinical study.

BMC Surg 2013 8;13 Suppl 2:S3. Epub 2013 Oct 8.

Background: The significance of nodal metastases, very common in papillary thyroid cancer, and the role of lymph node dissection in the neoplasm management, are still controversial. The impact of lymph node involvement on local recurrence and long-term survival remains subject of active research. With the aim to better analyze the predictive value of lymph node involvement on recurrence and survival, we investigated the clinico-pathological patterns of local relapse following total thyroidectomy associated with lymph node dissection, for clinical nodal metastases papillary thyroid cancer, in order to identify the preferred surgical treatment.

Methods: Clinical records, between January 2000 and December 2006, of 69 patients undergoing total thyroidectomy associated with selective lymph node dissection for clinical nodal metastases papillary thyroid cancer, were retrospectively evaluated. Radioiodine ablation, followed by Thyroid Stimulating Hormone suppression therapy was recommended in every case. In patients with loco regional lymph nodal recurrence, a repeated lymph node dissection was carried out. The data were compared with those following total thyroidectomy not associated with lymph node dissection in 210 papillary thyroid cancer patients without lymph node involvement, at preoperative ultrasonography and intra operative inspection.

Results: Incidence of permanent hypoparathyroidism (iPTH < 10 pg/ml) and permanent monolateral vocal fold paralysis were respectively 1.4 % (1/69) and 1.4% (1/69), similar to those reported after total thyroidectomy "alone". The rate of loco regional recurrence, with positive cervical lymph nodes, following 8 year follow-up, was 34.7% (24/69), higher than that reported in patients without nodal metastases (4.2%). A repeated lymph node dissection was carried out without significant complications.

Conclusions: Nodal metastases are a predictor of local recurrence, and a higher rate of lymph node involvement is expected after therapeutic lymph node dissection associated with total thyroidectomy. The prognostic significance of nodal metastases on long-term survival remains unclear, and more prospective randomized trials are requested to better evaluate the benefits of different therapeutic approaches.
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http://dx.doi.org/10.1186/1471-2482-13-S2-S3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851192PMC
August 2014
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