Alfredo Pontecorvi | Università Cattolica del Sacro Cuore (Catholic University of the Sacred Heart) (original) (raw)
Papers by Alfredo Pontecorvi
Journal of Clinical Investigation, 2009
The identification of biomarkers that distinguish between aggressive and indolent forms of prosta... more The identification of biomarkers that distinguish between aggressive and indolent forms of prostate cancer (PCa) is crucial for diagnosis and treatment. In this study, we used cultured cells derived from prostate tissue from patients with PCa to define a molecular mechanism underlying the most aggressive form of PCa that involves the functional activation of eNOS and HIFs in association with estrogen receptor β (ERβ). Cells from patients with poor prognosis exhibited a constitutively hypoxic phenotype and increased NO production. Upon estrogen treatment, formation of ERβ/eNOS, ERβ/HIF-1α, or ERβ/HIF-2α combinatorial complexes led to chromatin remodeling and transcriptional induction of prognostic genes. Tissue microarray analysis, using an independent cohort of patients, established a hierarchical predictive power for these proteins, with expression of eNOS plus ERβ and nuclear eNOS plus HIF-2α being the most relevant indicators of adverse clinical outcome. Genetic or pharmacologic modulation of eNOS expression and activity resulted in reciprocal conversion of the transcriptional signature in cells from patients with bad or good outcome, respectively, highlighting the relevance of eNOS in PCa progression. Our work has considerable clinical relevance, since it may enable the earlier diagnosis of aggressive PCa through routine biopsy assessment of eNOS, ERβ, and HIF-2α expression. Furthermore, proposing eNOS as a therapeutic target fosters innovative therapies for PCa with NO inhibitors, which are employed in preclinical trials in non-oncological diseases.
Journal of thyroid research, 2014
Objectives.Parathyroid involvement by thyroid cancer (TC) has not been frequently investigated in... more Objectives.Parathyroid involvement by thyroid cancer (TC) has not been frequently investigated in thyroidectomy-based studies. We aimed to detect cases of parathyroid invasion by TC in a large series of thyroidectomies and to review the literature on this topic. Study Design. A 10-yr period database research was made from the files of the Section of Pathology of two Italian University Hospitals. Out of 22,310 thyroidectomies, 10 patients with parathyroid involvement by TC were found. Results. The 10 patients, 7 females and 3 males, aged 55 ± 14 years (range 34-76, median 56) had papillary thyroid carcinoma and accounted for 0.4% of subjects affected by all TCs and submitted to thyroidectomy. The tumor invaded perithyroid soft tissues in 6 patients and central neck (level VI) lymph nodes in 3. Parathyroid involvement by TC occurred by infiltration in 6 cases, extension through an intervening pseudocapsule in 1, and both patterns in 3. All patients are alive and disease free at 5.6 ± ...
Minerva endocrinologica, 2013
The aim of this paper was to examine the efficacy and the safety of intraorbital administration o... more The aim of this paper was to examine the efficacy and the safety of intraorbital administration of the monoclonal anti-CD20 antibody rituximab (RTX) to treat patients affected by thyroid-associated orbitopathy (TAO) unresponsive to conventional therapy. Five patients with active moderately-severe TAO unresponsive to systemic glucocorticoids were studied. After a complete ophthalmological examination, disease activity and severity were assessed by the clinical activity score (CAS) and the NO SPECS scoring system. Computed tomography scans were performed in all patients. Patients were treated with intraorbital injection of RTX 10 mg once a week for one month repeated once one month apart. The patients were followed every three months until 18 months. In all patients treated with RTX, CAS was significantly reduced (p< 0,005), inactive phase of TAO was reached in four out of five patients. No patients experienced major side effects, minor side effects were reported in two patients. I...
Journal of endocrinological investigation, 2013
Patients with autonomously functioning thyroid nodules (AFTN) may not have an abnormal TSH value,... more Patients with autonomously functioning thyroid nodules (AFTN) may not have an abnormal TSH value, particularly in iodine-deficient areas. To verify the accuracy of TSH as screening test in detecting AFTN and to evaluate ultrasonographic features of thyroid nodules which have resulted autonomously functioning at thyroid scintigraphy (TS). Seventy-eight patients with nodular goiter, no marker of autoimmunity and at least one AFTN at TS were selected and divided in: Group 1 (no.=25) with TSH>0.35 IU/l, and Group 2 (no.=53) with TSH≤0.35 IU/l. In Group1 the mean nodule diameter was 19.8±9.4 mm; 12 nodules were isoechoic, 2 hyperechoic, and 11 hypoechoic. Vascular pattern was type I in 4, type II in 6 and type III in 15 nodules. In Group 2 the mean nodule diameter was 28.6±14.2 mm; 27 nodules were isoechoic, 9 hyperechoic and 17 hypoechoic. Vascular pattern was type I in 14, type II in 15 and type III in 24 nodules. In our study TSH alone was not able to identify AFTN in 32% of the pa...
Minerva endocrinologica, 2011
The scientific community is very interested in the biological aspects of gender disorders and sex... more The scientific community is very interested in the biological aspects of gender disorders and sexual orientation. There are different levels to define an individual's sex: chromosomal, gonadic, and phenotypic sex. Concerning the psychological sex, men and women are different by virtue of their own gender identity, which means they recognize themselves as belonging to a determinate sex. They are different also as a result of their own role identity, a set of behaviors, tendencies, and cognitive and emotional attitudes, commonly defined as "male" and "female". Transsexuality is a disorder characterized by the development of a gender identity opposed to phenotypic sex, whereas homosexuality is not a disturbance of gender identity but only of sexual attraction, expressing sexual orientation towards people of the same sex. We started from a critical review of literature on genetic and hormonal mechanisms involved in sexual differentiation. We re-examined the neuro...
Journal of endocrinological investigation, 2011
The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lan... more The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32-87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6-50 months). Fourteen patients (60.9%) showed flushing ...
Journal of endocrinological investigation, 2008
Fertility outcomes in hypopituitaric women are about half of those reported in isolated hypogonad... more Fertility outcomes in hypopituitaric women are about half of those reported in isolated hypogonadotropic hypogonadism; GH deficiency (GHD) is a major contributor to poor pregnancy rate. GH seems to play a physiological role in the control of male sexual maturation and adult reproductive functions. In males, GH regulates gonadal differentiation, steroidogenesis, and gametogenesis, as well as gonadotropin secretion and responsiveness. In females, GH has a role not only as a modulator on gonadotropins, mediated by the property of IGF-I to amplify the action of both LH and FSH on granulosa, but also, through a direct GH action, on follicular maturation. GH treatment seems to play an important role in the sensibilization of ovary responsivity and uterine morpholgy in GHD patients. Since GH, directly or indirectly via IGF-I, regulates reproductive functions at all levels of the hyophyseal-pituitary-gonadal, it should always be tested as a possible cause of unexplained infertility.
Thyroid : official journal of the American Thyroid Association, 1998
Fine-needle aspiration biopsy (FNAB) is an accurate, slightly invasive, and safe method for the p... more Fine-needle aspiration biopsy (FNAB) is an accurate, slightly invasive, and safe method for the preoperative diagnosis of thyroid nodules. Recently, ultrasound guidance has been suggested as a valuable aid to enhance FNAB diagnostic performance. In this study, we have compared diagnostic accuracy of conventional FNAB (C-FNAB) versus sonography-guided FNAB (SG-FNAB) on a large sample population of 9683 patients with thyroid nodules. Over a 15-year period, 4986 patients were investigated by C-FNAB and 4697 underwent SG-FNAB. A valid cytological diagnosis was obtained in 85.9% of C-FNAB and in 91.5% of SG-FNAB cases, allowing detection of thyroid cancer in 1.6% and 2.1% of patients, respectively. The indeterminate pattern of follicular neoplasia was observed in 238 C-FNAB (5%) and in 272 (5.4%) SG-FNAB nodules. Specimens were cytologically inadequate in 433 C-FNAB (8.7%), but only in 167 SG-FNAB cases (3.5%). A total of 535 C-FNAB and 540 SG-FNAB nodules underwent surgery. False-negati...
Il Giornale di chirurgia
The surgical approach of adrenal masses requires a careful preoperative and postoperative managem... more The surgical approach of adrenal masses requires a careful preoperative and postoperative management. In order to avoid iatrogenic hypocortisolism, Cushing patients have to be treated, before adrenal surgery and then every eight hours, with hydrocortisone 100 mg iv. The therapy should be gradually reduced to 10-20 mg/die by mouth for six-twelve months. In primary hyperaldosteronism the target of medical treatment is to control blood pressure and serum potassium values as well as to normalize the circulating aldosterone levels or to obtain mineralocorticoid receptor blockade. Epleronone and spironolactone are the most common used drugs. Spironolactone has long been the drug of choice while epleronone represents a newer more expensive alternative with fewer side effects. Postoperative management generally does not require steroid replacement therapy. The management of pheochromocytoma requires a careful medical preparation for surgery: in fact, the surgical removal of a pheochromocyto...
Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases, 2013
Osteoporosis in men is less frequent than in women and is more often due to an underlying cause, ... more Osteoporosis in men is less frequent than in women and is more often due to an underlying cause, such as nutritional deficiencies or lifestyle factors, endocrinological or systemic affections, long-term specific therapies. The growing attention on male osteoporosis is mainly explained by the increasing use of some drugs producing bone loss as frequent side effect, like gonadotropin-releasing hormone (GnRH) agonists for prostate cancer, immunosuppressive agents, or glucocorticoids. Glucocorticoids are largely used for the cure of lots of haematological, rheumatological, dermatological, pneumological, and other systemic diseases. It is well known glucocorticoid-induced osteoporosis (GIOP) develops rapidly at prednisone > 5mg/d or equivalent levels but recurrence is recently also observed in patients receiving low dose and intermittent therapy. However, the possible side effects of corticosteroids at low dose on bone are not completely understood and rightly prevented. We present th...
Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases, 2013
It is largely recognized that Growth Hormone (GH) plays an important role in linear growth during... more It is largely recognized that Growth Hormone (GH) plays an important role in linear growth during childhood and subsequent completion of appropriate height in early adulthood. It has also significant influence on a variety of metabolic activities, as well as the cardiovascular system and quality of life (QoL) in adults. GH is involved in the attainment of optimal Bone Mineral Density (BMD), the most important predictor of osteoporotic fractures, during the transition from paediatric to adult age. The time interval between paediatric and adult age is a critical period of life to clinically assess persistence of GHD in patients affected by childhood onset GHD (COGHD) and determine the need for continuing treatment with recombinant human Growth Hormone (rhGH) even in the face of closure of epiphyseal growth plates. It has been reported GHD is associated with higher fracture's risk in COGHD patients and GH therapy should minimize, if not prevent, osteoporosis in adulthood. We report...
HORMONES, 2010
Zoledronic acid is a newly FDA-approved bisphosphonate for the treatment of hypercalcemia of mali... more Zoledronic acid is a newly FDA-approved bisphosphonate for the treatment of hypercalcemia of malignancy. Although the safety and efficacy of this drug in treating hypercalcemia associated with hyperparathyroidism have not yet been established in clinically controlled trials, its off-label use is not uncommon. We describe a patient with primary hyperparathyroidism treated with zoledronic acid who developed severe postoperative hypocalcemia. A 64-yr-old woman was admitted with severe hypercalcemia. She was treated with rehydration, calcitonin, methylprednisolone, furosemide as well as 4 mg/day of zoledronic acid for two consecutive days. Primary hyperparathyroidism caused by a right inferior parathyroid lesion was diagnosed. While awaiting surgery, she continued furosemide, methylprednisolone and hydration: after one week, serum calcium had fallen to such a low level that a short-term calcium carbonate supplementation was required. Three weeks after admission, the patient underwent selective right inferior parathyroidectomy, followed by reduction of PTH. During the postoperative period the patient presented severe hypocalcemia resistant to the usual treatment. Serum calcium levels returned to normal three months after surgery. The severity of hypocalcemia and the resistance to conventional treatments suggest that the effect of hungry bone syndrome could be worse in patients treated with bisphosphonates in the preoperative phase.
Thyroid, 2014
The current approach for calculating the starting dose of levothyroxine (LT4) after total thyroid... more The current approach for calculating the starting dose of levothyroxine (LT4) after total thyroidectomy is based on the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s body weight (BW). The aim of the study was to identify the major predictive factors of LT4 requirement and to elaborate a new method to improve the accuracy of the LT4 starting dose after total thyroidectomy. The study consists of two parts. The first part consisted of the retrospective identification of 92 adult patients (retrospective cohort) who had undergone a total thyroidectomy for benign disease and who had begun LT4 treatment at a dose of 1.6 μg/kg/day. Adjustments to optimize the LT4 dose were then performed at the post-surgery follow-up on the basis of serum thyrotropin (TSH) levels. The results of this retrospective analysis were used to formulate a nomogram for a proper calculation of the LT4 starting dose that was then used prospectively in the second part of the study on 31 consecutive patients (prospective cohort). At the first follow-up, 37 (40%) patients from the retrospective cohort were euthyroid. Univariate analysis indicated significant correlations between the optimal dose of LT4 and BW, body mass index (BMI), age, preoperative mean corpuscular volume, and free triiodothyronine (fT3). The optimal dose of LT4, analyzed for BMI and age, showed an inverse relationship with these two parameters, and ranged from 1.4 to 1.8 μg/kg/day. In the prospective cohort, the use of an age- and BMI-related nomogram improved the prediction of the optimal LT4 starting dose, with 68% of patients being euthyroid at the first follow-up compared to 41% of patients reported to have reached euthyroid state using the best strategy proposed in the literature. This study confirms that BW is not the only variable for predicting LT4 requirement, as it decreases with the increase in age and BMI, probably due to the relative decrease of lean body mass. A new correlation between optimal dose and presurgical levels of fT3 and mean corpuscular volume was observed. We propose an easy and more efficient method of calculating LT4 starting dose after total thyroidectomy for benign disease.
Case Reports in Endocrinology, 2014
Cushing&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more Cushing&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (CD) is the most common cause of endogenous Cushing&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome in children and adolescents and represents a rare cause of short stature. A 14-year-old boy came to our attention for progressive weight gain and short stature. At examination, height was 140 cm (3rd centile) and weight was 37.7 kg (10th centile). Tanner stage was G2, PH 3, testis 3 mL. Hypothyroidism and growth hormone deficiency were excluded. A marked increase of urinary free cortisol, a nonsuppressible serum cortisol after Liddle 1 test, and an elevated ACTH value confirmed the diagnosis of ACTH dependent Cushing&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome. Pituitary magnetic resonance imaging (MRI) showed a left microadenoma and a right focal area of lesser enhancement. Therefore, bilateral inferior petrosal sinus sampling (BIPSS) with CRH stimulation was performed to obtain an accurate preoperative localization of the adenoma: the interpetrosal sinus ACTH gradient indicated lateralization of ACTH secretion to the left side. The patient underwent transsphenoidal surgery with selective microadenomectomy, with an immediate ACTH decline in the postoperative phase. Histology confirmed the diagnosis of corticotrophic pituitary adenoma. Glucocorticoid replacement therapy was instituted. Clinical examination demonstrated a rapid catch-up growth (10th centile), with a normalization of body mass index and an adequate pubertal development.
Endocrine, 2014
The aim of the study was to compare, in a randomized prospective study, the efficacy and safety o... more The aim of the study was to compare, in a randomized prospective study, the efficacy and safety of intraorbital administration of low doses of RTX versus intravenous glucocorticoids (GCs) to treat patients affected by moderately severe thyroid-associated active orbitopathy. Twenty patients with active, moderately severe TAO, whose mean age was 56.7 years±10.2 SD participated in the study. Patients were randomly selected and treated with intraorbital injections of RTX or with i.v. GCs. Disease activity and severity were assessed by the Clinical Activity Score (CAS) and the NOSPECS. Computed tomography or magnetic resonance scans were performed in all patients. In the RTX group, full blood cell count and flow cytometric analysis on peripheral blood lymphocytes were done. The patients were followed for 20 months. In both groups, CAS and NOSPECS indexes were significantly reduced (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.005). In particular, CAS reduction was evident since the first follow-up with both treatments. Proptosis decreased significantly only in group B and diplopia showed no significant changes during follow-up times in both groups. Neither of the treatments affected the peripheral TRab. In group A, 5 weeks after the first injection, the CD20+ peripheral lymphocytes value was nearly zero. One patient treated with rituximab progressed to severe TAO (optic neuropathy) following the second injection so the treatment was discontinued. The data confirm the therapeutic efficacy of RTX in active TAO, even in low doses and locally administered. The efficacy on the inflammatory component of the disease is comparable to that of steroids and seems to be related with the reduction of peripheral CD20+ lymphocytes. Caution should be given to an accurate patient selection.
European Journal of Endocrinology, 1984
Sixty-two patients affected with subacute thyroiditis (SAT) were followed for a mean period of 14... more Sixty-two patients affected with subacute thyroiditis (SAT) were followed for a mean period of 14 months (range 1-40), by monitoring thyroid hormone levels in basal condition, pituitary TSH reserve, antithyroglobulin (TgAb) and antimicrosomal antibodies ( MsAb ), in order to study the natural course of the disease and to characterize its intermediate phase. In the first phase the mean serum iodothyronine levels were within normal limits, nevertheless elevated T3 and T4 levels were detected in 34 (54%) and 20 (32%) patients, respectively. The next phase was characterized by normal serum iodothyronine levels; TRH stimulation test, however, showed a significant increase of pituitary TSH reserve in 35 (56%) patients. All parameters reverted gradually towards normal in all but 3 patients, who showed overt permanent hypothyroidism. TgAb and MsAb were positive in the early stage in 15 (24%) and 40 (64%) patients, respectively, disappearing at the end of the follow-up period in all but one patient; this particular patient belonged to the group of 3 patients affected with permanent hypothyroidism. Our data indicate that the onset of SAT is characterized by transient hyperthyroidism and that transient subclinical hypothyroidism characterizes the next phase. TRH stimulation test is required for the diagnosis of the latter and for the identification of the few who develop permanent hypothyroidism.
JNCI Journal of the National Cancer Institute, 2014
Although indolent, MPC may be locally aggressive with recurrent disease. The pathogenesis and dia... more Although indolent, MPC may be locally aggressive with recurrent disease. The pathogenesis and diagnostic biomarkers of MPC are poorly understood. We discovered that 15% of benign MPCs (thyroid, skin; 3 of 20 samples) harbored BRAF WT/V600E ; 33.3% (1 of 3 samples) of BRAF WT/V600E -MPCs were multifocal/infiltrative/recurrent.
Frontiers in Endocrinology, 2014
Objective:Thyroid-related emergencies are caused by overt dysfunction of the gland which are so s... more Objective:Thyroid-related emergencies are caused by overt dysfunction of the gland which are so severe that require admission to intensive care units (ICU) frequently. Nonetheless, in the ICU setting, it is crucial to differentiate patients with non-thyroidal illness and alterations in thyroid function tests from those with intrinsic thyroid disease. This review presents and discusses the main etiopathogenetical and clinical aspects of hypothyroid coma (HC) and thyrotoxic storm (TS), including therapeutic strategy flow-charts. Furthermore, a special chapter is dedicated to the approach to massive goiter, which represents a surgical thyroid emergency.
Background. Infertility is both a clinical and a public problem, affecting the life of the couple... more Background. Infertility is both a clinical and a public problem, affecting the life of the couple, the healthcare services, and social environment. Standard semen analysis is the surrogate measure of male fertility in clinical practice. Objective. To provide information about the relationship between semen parameters and spontaneous conception. Methods. We evaluated retrospectively 453 pregnancies that occurred among 2935 infertile couples evaluated at an infertility clinic of a tertiary-care university hospital, between 2004 and 2009. Results. Normal semen analysis was present only in 158 patients; 295 subfertile patients showed alterations in at least one seminal parameter. A reduction in all seminal parameters was observed in 41 patients. Etiological causes of male infertility were identified in 314 patients. Conclusion. Our data highlights the possibility of a spontaneous conception with semen parameters below WHO reference values. Therefore, we support the importance of defining reference values on a population of fertile men. Finally, we analyzed the related ethical issues.
Journal of Clinical Investigation, 2009
The identification of biomarkers that distinguish between aggressive and indolent forms of prosta... more The identification of biomarkers that distinguish between aggressive and indolent forms of prostate cancer (PCa) is crucial for diagnosis and treatment. In this study, we used cultured cells derived from prostate tissue from patients with PCa to define a molecular mechanism underlying the most aggressive form of PCa that involves the functional activation of eNOS and HIFs in association with estrogen receptor β (ERβ). Cells from patients with poor prognosis exhibited a constitutively hypoxic phenotype and increased NO production. Upon estrogen treatment, formation of ERβ/eNOS, ERβ/HIF-1α, or ERβ/HIF-2α combinatorial complexes led to chromatin remodeling and transcriptional induction of prognostic genes. Tissue microarray analysis, using an independent cohort of patients, established a hierarchical predictive power for these proteins, with expression of eNOS plus ERβ and nuclear eNOS plus HIF-2α being the most relevant indicators of adverse clinical outcome. Genetic or pharmacologic modulation of eNOS expression and activity resulted in reciprocal conversion of the transcriptional signature in cells from patients with bad or good outcome, respectively, highlighting the relevance of eNOS in PCa progression. Our work has considerable clinical relevance, since it may enable the earlier diagnosis of aggressive PCa through routine biopsy assessment of eNOS, ERβ, and HIF-2α expression. Furthermore, proposing eNOS as a therapeutic target fosters innovative therapies for PCa with NO inhibitors, which are employed in preclinical trials in non-oncological diseases.
Journal of thyroid research, 2014
Objectives.Parathyroid involvement by thyroid cancer (TC) has not been frequently investigated in... more Objectives.Parathyroid involvement by thyroid cancer (TC) has not been frequently investigated in thyroidectomy-based studies. We aimed to detect cases of parathyroid invasion by TC in a large series of thyroidectomies and to review the literature on this topic. Study Design. A 10-yr period database research was made from the files of the Section of Pathology of two Italian University Hospitals. Out of 22,310 thyroidectomies, 10 patients with parathyroid involvement by TC were found. Results. The 10 patients, 7 females and 3 males, aged 55 ± 14 years (range 34-76, median 56) had papillary thyroid carcinoma and accounted for 0.4% of subjects affected by all TCs and submitted to thyroidectomy. The tumor invaded perithyroid soft tissues in 6 patients and central neck (level VI) lymph nodes in 3. Parathyroid involvement by TC occurred by infiltration in 6 cases, extension through an intervening pseudocapsule in 1, and both patterns in 3. All patients are alive and disease free at 5.6 ± ...
Minerva endocrinologica, 2013
The aim of this paper was to examine the efficacy and the safety of intraorbital administration o... more The aim of this paper was to examine the efficacy and the safety of intraorbital administration of the monoclonal anti-CD20 antibody rituximab (RTX) to treat patients affected by thyroid-associated orbitopathy (TAO) unresponsive to conventional therapy. Five patients with active moderately-severe TAO unresponsive to systemic glucocorticoids were studied. After a complete ophthalmological examination, disease activity and severity were assessed by the clinical activity score (CAS) and the NO SPECS scoring system. Computed tomography scans were performed in all patients. Patients were treated with intraorbital injection of RTX 10 mg once a week for one month repeated once one month apart. The patients were followed every three months until 18 months. In all patients treated with RTX, CAS was significantly reduced (p< 0,005), inactive phase of TAO was reached in four out of five patients. No patients experienced major side effects, minor side effects were reported in two patients. I...
Journal of endocrinological investigation, 2013
Patients with autonomously functioning thyroid nodules (AFTN) may not have an abnormal TSH value,... more Patients with autonomously functioning thyroid nodules (AFTN) may not have an abnormal TSH value, particularly in iodine-deficient areas. To verify the accuracy of TSH as screening test in detecting AFTN and to evaluate ultrasonographic features of thyroid nodules which have resulted autonomously functioning at thyroid scintigraphy (TS). Seventy-eight patients with nodular goiter, no marker of autoimmunity and at least one AFTN at TS were selected and divided in: Group 1 (no.=25) with TSH>0.35 IU/l, and Group 2 (no.=53) with TSH≤0.35 IU/l. In Group1 the mean nodule diameter was 19.8±9.4 mm; 12 nodules were isoechoic, 2 hyperechoic, and 11 hypoechoic. Vascular pattern was type I in 4, type II in 6 and type III in 15 nodules. In Group 2 the mean nodule diameter was 28.6±14.2 mm; 27 nodules were isoechoic, 9 hyperechoic and 17 hypoechoic. Vascular pattern was type I in 14, type II in 15 and type III in 24 nodules. In our study TSH alone was not able to identify AFTN in 32% of the pa...
Minerva endocrinologica, 2011
The scientific community is very interested in the biological aspects of gender disorders and sex... more The scientific community is very interested in the biological aspects of gender disorders and sexual orientation. There are different levels to define an individual's sex: chromosomal, gonadic, and phenotypic sex. Concerning the psychological sex, men and women are different by virtue of their own gender identity, which means they recognize themselves as belonging to a determinate sex. They are different also as a result of their own role identity, a set of behaviors, tendencies, and cognitive and emotional attitudes, commonly defined as "male" and "female". Transsexuality is a disorder characterized by the development of a gender identity opposed to phenotypic sex, whereas homosexuality is not a disturbance of gender identity but only of sexual attraction, expressing sexual orientation towards people of the same sex. We started from a critical review of literature on genetic and hormonal mechanisms involved in sexual differentiation. We re-examined the neuro...
Journal of endocrinological investigation, 2011
The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lan... more The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32-87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6-50 months). Fourteen patients (60.9%) showed flushing ...
Journal of endocrinological investigation, 2008
Fertility outcomes in hypopituitaric women are about half of those reported in isolated hypogonad... more Fertility outcomes in hypopituitaric women are about half of those reported in isolated hypogonadotropic hypogonadism; GH deficiency (GHD) is a major contributor to poor pregnancy rate. GH seems to play a physiological role in the control of male sexual maturation and adult reproductive functions. In males, GH regulates gonadal differentiation, steroidogenesis, and gametogenesis, as well as gonadotropin secretion and responsiveness. In females, GH has a role not only as a modulator on gonadotropins, mediated by the property of IGF-I to amplify the action of both LH and FSH on granulosa, but also, through a direct GH action, on follicular maturation. GH treatment seems to play an important role in the sensibilization of ovary responsivity and uterine morpholgy in GHD patients. Since GH, directly or indirectly via IGF-I, regulates reproductive functions at all levels of the hyophyseal-pituitary-gonadal, it should always be tested as a possible cause of unexplained infertility.
Thyroid : official journal of the American Thyroid Association, 1998
Fine-needle aspiration biopsy (FNAB) is an accurate, slightly invasive, and safe method for the p... more Fine-needle aspiration biopsy (FNAB) is an accurate, slightly invasive, and safe method for the preoperative diagnosis of thyroid nodules. Recently, ultrasound guidance has been suggested as a valuable aid to enhance FNAB diagnostic performance. In this study, we have compared diagnostic accuracy of conventional FNAB (C-FNAB) versus sonography-guided FNAB (SG-FNAB) on a large sample population of 9683 patients with thyroid nodules. Over a 15-year period, 4986 patients were investigated by C-FNAB and 4697 underwent SG-FNAB. A valid cytological diagnosis was obtained in 85.9% of C-FNAB and in 91.5% of SG-FNAB cases, allowing detection of thyroid cancer in 1.6% and 2.1% of patients, respectively. The indeterminate pattern of follicular neoplasia was observed in 238 C-FNAB (5%) and in 272 (5.4%) SG-FNAB nodules. Specimens were cytologically inadequate in 433 C-FNAB (8.7%), but only in 167 SG-FNAB cases (3.5%). A total of 535 C-FNAB and 540 SG-FNAB nodules underwent surgery. False-negati...
Il Giornale di chirurgia
The surgical approach of adrenal masses requires a careful preoperative and postoperative managem... more The surgical approach of adrenal masses requires a careful preoperative and postoperative management. In order to avoid iatrogenic hypocortisolism, Cushing patients have to be treated, before adrenal surgery and then every eight hours, with hydrocortisone 100 mg iv. The therapy should be gradually reduced to 10-20 mg/die by mouth for six-twelve months. In primary hyperaldosteronism the target of medical treatment is to control blood pressure and serum potassium values as well as to normalize the circulating aldosterone levels or to obtain mineralocorticoid receptor blockade. Epleronone and spironolactone are the most common used drugs. Spironolactone has long been the drug of choice while epleronone represents a newer more expensive alternative with fewer side effects. Postoperative management generally does not require steroid replacement therapy. The management of pheochromocytoma requires a careful medical preparation for surgery: in fact, the surgical removal of a pheochromocyto...
Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases, 2013
Osteoporosis in men is less frequent than in women and is more often due to an underlying cause, ... more Osteoporosis in men is less frequent than in women and is more often due to an underlying cause, such as nutritional deficiencies or lifestyle factors, endocrinological or systemic affections, long-term specific therapies. The growing attention on male osteoporosis is mainly explained by the increasing use of some drugs producing bone loss as frequent side effect, like gonadotropin-releasing hormone (GnRH) agonists for prostate cancer, immunosuppressive agents, or glucocorticoids. Glucocorticoids are largely used for the cure of lots of haematological, rheumatological, dermatological, pneumological, and other systemic diseases. It is well known glucocorticoid-induced osteoporosis (GIOP) develops rapidly at prednisone > 5mg/d or equivalent levels but recurrence is recently also observed in patients receiving low dose and intermittent therapy. However, the possible side effects of corticosteroids at low dose on bone are not completely understood and rightly prevented. We present th...
Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases, 2013
It is largely recognized that Growth Hormone (GH) plays an important role in linear growth during... more It is largely recognized that Growth Hormone (GH) plays an important role in linear growth during childhood and subsequent completion of appropriate height in early adulthood. It has also significant influence on a variety of metabolic activities, as well as the cardiovascular system and quality of life (QoL) in adults. GH is involved in the attainment of optimal Bone Mineral Density (BMD), the most important predictor of osteoporotic fractures, during the transition from paediatric to adult age. The time interval between paediatric and adult age is a critical period of life to clinically assess persistence of GHD in patients affected by childhood onset GHD (COGHD) and determine the need for continuing treatment with recombinant human Growth Hormone (rhGH) even in the face of closure of epiphyseal growth plates. It has been reported GHD is associated with higher fracture's risk in COGHD patients and GH therapy should minimize, if not prevent, osteoporosis in adulthood. We report...
HORMONES, 2010
Zoledronic acid is a newly FDA-approved bisphosphonate for the treatment of hypercalcemia of mali... more Zoledronic acid is a newly FDA-approved bisphosphonate for the treatment of hypercalcemia of malignancy. Although the safety and efficacy of this drug in treating hypercalcemia associated with hyperparathyroidism have not yet been established in clinically controlled trials, its off-label use is not uncommon. We describe a patient with primary hyperparathyroidism treated with zoledronic acid who developed severe postoperative hypocalcemia. A 64-yr-old woman was admitted with severe hypercalcemia. She was treated with rehydration, calcitonin, methylprednisolone, furosemide as well as 4 mg/day of zoledronic acid for two consecutive days. Primary hyperparathyroidism caused by a right inferior parathyroid lesion was diagnosed. While awaiting surgery, she continued furosemide, methylprednisolone and hydration: after one week, serum calcium had fallen to such a low level that a short-term calcium carbonate supplementation was required. Three weeks after admission, the patient underwent selective right inferior parathyroidectomy, followed by reduction of PTH. During the postoperative period the patient presented severe hypocalcemia resistant to the usual treatment. Serum calcium levels returned to normal three months after surgery. The severity of hypocalcemia and the resistance to conventional treatments suggest that the effect of hungry bone syndrome could be worse in patients treated with bisphosphonates in the preoperative phase.
Thyroid, 2014
The current approach for calculating the starting dose of levothyroxine (LT4) after total thyroid... more The current approach for calculating the starting dose of levothyroxine (LT4) after total thyroidectomy is based on the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s body weight (BW). The aim of the study was to identify the major predictive factors of LT4 requirement and to elaborate a new method to improve the accuracy of the LT4 starting dose after total thyroidectomy. The study consists of two parts. The first part consisted of the retrospective identification of 92 adult patients (retrospective cohort) who had undergone a total thyroidectomy for benign disease and who had begun LT4 treatment at a dose of 1.6 μg/kg/day. Adjustments to optimize the LT4 dose were then performed at the post-surgery follow-up on the basis of serum thyrotropin (TSH) levels. The results of this retrospective analysis were used to formulate a nomogram for a proper calculation of the LT4 starting dose that was then used prospectively in the second part of the study on 31 consecutive patients (prospective cohort). At the first follow-up, 37 (40%) patients from the retrospective cohort were euthyroid. Univariate analysis indicated significant correlations between the optimal dose of LT4 and BW, body mass index (BMI), age, preoperative mean corpuscular volume, and free triiodothyronine (fT3). The optimal dose of LT4, analyzed for BMI and age, showed an inverse relationship with these two parameters, and ranged from 1.4 to 1.8 μg/kg/day. In the prospective cohort, the use of an age- and BMI-related nomogram improved the prediction of the optimal LT4 starting dose, with 68% of patients being euthyroid at the first follow-up compared to 41% of patients reported to have reached euthyroid state using the best strategy proposed in the literature. This study confirms that BW is not the only variable for predicting LT4 requirement, as it decreases with the increase in age and BMI, probably due to the relative decrease of lean body mass. A new correlation between optimal dose and presurgical levels of fT3 and mean corpuscular volume was observed. We propose an easy and more efficient method of calculating LT4 starting dose after total thyroidectomy for benign disease.
Case Reports in Endocrinology, 2014
Cushing&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more Cushing&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (CD) is the most common cause of endogenous Cushing&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome in children and adolescents and represents a rare cause of short stature. A 14-year-old boy came to our attention for progressive weight gain and short stature. At examination, height was 140 cm (3rd centile) and weight was 37.7 kg (10th centile). Tanner stage was G2, PH 3, testis 3 mL. Hypothyroidism and growth hormone deficiency were excluded. A marked increase of urinary free cortisol, a nonsuppressible serum cortisol after Liddle 1 test, and an elevated ACTH value confirmed the diagnosis of ACTH dependent Cushing&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome. Pituitary magnetic resonance imaging (MRI) showed a left microadenoma and a right focal area of lesser enhancement. Therefore, bilateral inferior petrosal sinus sampling (BIPSS) with CRH stimulation was performed to obtain an accurate preoperative localization of the adenoma: the interpetrosal sinus ACTH gradient indicated lateralization of ACTH secretion to the left side. The patient underwent transsphenoidal surgery with selective microadenomectomy, with an immediate ACTH decline in the postoperative phase. Histology confirmed the diagnosis of corticotrophic pituitary adenoma. Glucocorticoid replacement therapy was instituted. Clinical examination demonstrated a rapid catch-up growth (10th centile), with a normalization of body mass index and an adequate pubertal development.
Endocrine, 2014
The aim of the study was to compare, in a randomized prospective study, the efficacy and safety o... more The aim of the study was to compare, in a randomized prospective study, the efficacy and safety of intraorbital administration of low doses of RTX versus intravenous glucocorticoids (GCs) to treat patients affected by moderately severe thyroid-associated active orbitopathy. Twenty patients with active, moderately severe TAO, whose mean age was 56.7 years±10.2 SD participated in the study. Patients were randomly selected and treated with intraorbital injections of RTX or with i.v. GCs. Disease activity and severity were assessed by the Clinical Activity Score (CAS) and the NOSPECS. Computed tomography or magnetic resonance scans were performed in all patients. In the RTX group, full blood cell count and flow cytometric analysis on peripheral blood lymphocytes were done. The patients were followed for 20 months. In both groups, CAS and NOSPECS indexes were significantly reduced (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.005). In particular, CAS reduction was evident since the first follow-up with both treatments. Proptosis decreased significantly only in group B and diplopia showed no significant changes during follow-up times in both groups. Neither of the treatments affected the peripheral TRab. In group A, 5 weeks after the first injection, the CD20+ peripheral lymphocytes value was nearly zero. One patient treated with rituximab progressed to severe TAO (optic neuropathy) following the second injection so the treatment was discontinued. The data confirm the therapeutic efficacy of RTX in active TAO, even in low doses and locally administered. The efficacy on the inflammatory component of the disease is comparable to that of steroids and seems to be related with the reduction of peripheral CD20+ lymphocytes. Caution should be given to an accurate patient selection.
European Journal of Endocrinology, 1984
Sixty-two patients affected with subacute thyroiditis (SAT) were followed for a mean period of 14... more Sixty-two patients affected with subacute thyroiditis (SAT) were followed for a mean period of 14 months (range 1-40), by monitoring thyroid hormone levels in basal condition, pituitary TSH reserve, antithyroglobulin (TgAb) and antimicrosomal antibodies ( MsAb ), in order to study the natural course of the disease and to characterize its intermediate phase. In the first phase the mean serum iodothyronine levels were within normal limits, nevertheless elevated T3 and T4 levels were detected in 34 (54%) and 20 (32%) patients, respectively. The next phase was characterized by normal serum iodothyronine levels; TRH stimulation test, however, showed a significant increase of pituitary TSH reserve in 35 (56%) patients. All parameters reverted gradually towards normal in all but 3 patients, who showed overt permanent hypothyroidism. TgAb and MsAb were positive in the early stage in 15 (24%) and 40 (64%) patients, respectively, disappearing at the end of the follow-up period in all but one patient; this particular patient belonged to the group of 3 patients affected with permanent hypothyroidism. Our data indicate that the onset of SAT is characterized by transient hyperthyroidism and that transient subclinical hypothyroidism characterizes the next phase. TRH stimulation test is required for the diagnosis of the latter and for the identification of the few who develop permanent hypothyroidism.
JNCI Journal of the National Cancer Institute, 2014
Although indolent, MPC may be locally aggressive with recurrent disease. The pathogenesis and dia... more Although indolent, MPC may be locally aggressive with recurrent disease. The pathogenesis and diagnostic biomarkers of MPC are poorly understood. We discovered that 15% of benign MPCs (thyroid, skin; 3 of 20 samples) harbored BRAF WT/V600E ; 33.3% (1 of 3 samples) of BRAF WT/V600E -MPCs were multifocal/infiltrative/recurrent.
Frontiers in Endocrinology, 2014
Objective:Thyroid-related emergencies are caused by overt dysfunction of the gland which are so s... more Objective:Thyroid-related emergencies are caused by overt dysfunction of the gland which are so severe that require admission to intensive care units (ICU) frequently. Nonetheless, in the ICU setting, it is crucial to differentiate patients with non-thyroidal illness and alterations in thyroid function tests from those with intrinsic thyroid disease. This review presents and discusses the main etiopathogenetical and clinical aspects of hypothyroid coma (HC) and thyrotoxic storm (TS), including therapeutic strategy flow-charts. Furthermore, a special chapter is dedicated to the approach to massive goiter, which represents a surgical thyroid emergency.
Background. Infertility is both a clinical and a public problem, affecting the life of the couple... more Background. Infertility is both a clinical and a public problem, affecting the life of the couple, the healthcare services, and social environment. Standard semen analysis is the surrogate measure of male fertility in clinical practice. Objective. To provide information about the relationship between semen parameters and spontaneous conception. Methods. We evaluated retrospectively 453 pregnancies that occurred among 2935 infertile couples evaluated at an infertility clinic of a tertiary-care university hospital, between 2004 and 2009. Results. Normal semen analysis was present only in 158 patients; 295 subfertile patients showed alterations in at least one seminal parameter. A reduction in all seminal parameters was observed in 41 patients. Etiological causes of male infertility were identified in 314 patients. Conclusion. Our data highlights the possibility of a spontaneous conception with semen parameters below WHO reference values. Therefore, we support the importance of defining reference values on a population of fertile men. Finally, we analyzed the related ethical issues.