Neuroendocrine tumours are frequently malignant and have often reached an advanced stage by the t... more Neuroendocrine tumours are frequently malignant and have often reached an advanced stage by the time of diagnosis when they are inoperable, accompanied by severe symptoms, sometimes of an endocrine nature. Current therapeutic procedures include surgery, embolisation of hepatic metastases, local radiotherapy, biotherapy and chemotherapy. Over the years somatostatin analogs, of which octreotide is the first form, have become increasingly important in the treatment of patients with neuroendocrine tumours. A major step forward in analog treatment is represented by the development of slow-release formulas which do not require multiple daily injections and reduce the onset of resistance. The treatment of neuroendocrine tumours in the future will be based on the increased use of somatostatin analogs alone or in association with interferon or chemotherapy, and will also include surgery, radiometabolic therapy and targeted irradiation of the tumour.
To investigate cardiac effects of excess and deficiency of growth hormone (GH) 20 acromegalic sub... more To investigate cardiac effects of excess and deficiency of growth hormone (GH) 20 acromegalic subjects and 11 adult patients with GH deficiency were studied by means of a non invasive method, the Doppler echocardiography. The results obtained in the group of patients were compared with those of 2 groups of 20 and 12 normal subjects, respectively, age and sex matched. The age of the acromegalic patients ranged from 20 to 62 years. Nineteen patients were considered to have active acromegaly at the time of the study. Mean duration of disease since treatment was 12 +/- 5 years (range 5 to 24 years). The age of GH deficient adults ranged from 21 to 33 years. All these patients have been treated with extractive GH over 9 years and the therapy withdrawal was performed at least 3 years before entering the study. In the acromegalic patient group, a subgroup including 9 patients with mild to moderate hypertension was considered. All subjects gave informed consent and the study protocol was approved by the Ethical Committee of the Medical School of Naples. Right ventricular free wall thickness resulted significantly increased in acromegalic patients (8 +/- 2 versus 4 +/- 1 mm; p < 0.001). Left ventricular mass index was augmented both in the whole group and in the subgroup of normotensive acromegalics as compared with normals (134 +/- 33 and 115 +/- 20 versus 80 +/- 18 g.m-2; p < 0.01). Ejection phase indices were normal in patient group, while impaired left and right ventricular diastolic filling was found.(ABSTRACT TRUNCATED AT 250 WORDS)
Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor of the th... more Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor of the thyroid gland. An algorithm for the diagnosis and treatment of SETTLE has yet to be established. The aim of this study was to identify all case reports of SETTLE and to compare the clinical-pathological features and therapy of the cases identified. We performed a PubMed search for case reports of SETTLE in English published up to November 2014 in which &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;SETTLE&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Spindle epithelial tumor with thymus-like differentiation&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; were keywords. We identified 35 articles for a total of 42 cases. We found that SETTLE usually occurs in children and adolescents as an asymptomatic neck mass. Thyroid function tests and tumor markers are invariably within normal range in all patients, and fine needle aspiration biopsy is rarely diagnostic for SETTLE. All 42 patients had undergone thyroidectomy. After surgical resection, chemotherapy (adjuvant or first/second-line treatment) and/or radiotherapy were administered to control tumor growth in cases with metastatic involvement. Although SETTLE presents a low-grade malignancy, it can metastasize to lymph nodes, the mediastinum, lung, vertebrae, and kidney even many years after the initial diagnosis. SETTLE may have a good prognosis if appropriately treated at initial presentation and if patients undergo long-term monitoring with regular clinical and morphological evaluations.
The Journal of Clinical Endocrinology and Metabolism, Sep 1, 1993
The aim of this study was to investigate the effects of a 6-month octreotide treatment on cardiac... more The aim of this study was to investigate the effects of a 6-month octreotide treatment on cardiac mass and function by means of Doppler echocardiography in 11 normotensive patients affected with active acromegaly. The GH and insulin-like growth factor-I levels were normalized during octreotide therapy from 34 +/- 6.5 and 767.4 +/- 72.4 micrograms/L to 4.6 +/- 0.9 and 235 +/- 10.3 micrograms/L, respectively (P &lt; 0.001; mean +/- SEM). After the 6-month treatment, we observed a significant decrease in the left ventricular mass index from 138 +/- 11 to 116 +/- 13 g/m2 (P &lt; 0.001) and in the mean wall thickness/internal end-diastolic radius ratio from 0.47 +/- 0.1 to 0.44 +/- 0.1 (P &lt; 0.001). No significant differences were found in systolic function indices, whereas diastolic filling indices improved over the course of the therapy; the isovolumic relaxation time decreased from 115 +/- 6 to 100 +/- 6 ms (P &lt; 0.05), tricuspid late diastolic filling velocities decreased from 41 +/- 3 to 36 +/- 2 cm/s (P &lt; 0.03), and tricuspid deceleration time decreased from 280 +/- 28 to 198 +/- 15 ms (P &lt; 0.005); the ratio of early to late peak velocity of the right ventricular filling significantly increased from 1 +/- 0.01 to 1.3 +/- 0.1 (P &lt; 0.03). A significant correlation was detected between left ventricular mass regression and increase in the early to late peak velocity ratio of the left ventricular filling (r = 0.62; P &lt; 0.05). The results of this study show an improvement in cardiac structural and functional abnormalities during chronic treatment with octreotide, thus supporting the hypothesis of a specific heart disease secondary to high circulating GH levels.
The Journal of Clinical Endocrinology & Metabolism, 2020
Purpose This work aimed to evaluate genotype-phenotype associations in individuals carrying germl... more Purpose This work aimed to evaluate genotype-phenotype associations in individuals carrying germline variants of transmembrane protein 127 gene (TMEM127), a poorly known gene that confers susceptibility to pheochromocytoma (PHEO) and paraganglioma (PGL). Design Data were collected from a registry of probands with TMEM127 variants, published reports, and public databases. Main Outcome Analysis Clinical, genetic, and functional associations were determined. Results The cohort comprised 110 index patients (111 variants) with a mean age of 45 years (range, 21-84 years). Females were predominant (76 vs 34, P < .001). Most patients had PHEO (n = 94; 85.5%), although PGL (n = 10; 9%) and renal cell carcinoma (RCC, n = 6; 5.4%) were also detected, either alone or in combination with PHEO. One-third of the cases had multiple tumors, and known family history was reported in 15.4%. Metastatic PHEO/PGL was rare (2.8%). Epinephrine alone, or combined with norepinephrine, accounted for 82% of ...
The aim of follow-up of differentiated thyroid carcinoma (CTD) is the assessment of remission, an... more The aim of follow-up of differentiated thyroid carcinoma (CTD) is the assessment of remission, and, in further steps, the early recognition of patients who develop a recurrence. Tools for the follow-up of CTD include the assessment of thyroglobulin and imaging procedures. Thyroglobulin (Tg) is a strong marker of persistent or recurrent disease, but it must be known that Tg antibodies may give falsely low Tg concentration. TSH stimulation, mainly by the mean of recombinant human TSH, improves the sensitivity of Tg determination. New highly sensitive assays may preclude the need for TSH stimulation, at least in some situations. In the last decades, (131)iodine whole body scan gave place to neck ultrasonography (US) as the most performing imaging procedure in the follow-up of CTD. Criteria to identify cervical lymph node suspect of metastasis have been described, and standardized procedures proposed. Finally, the proof of tumoral invasion is brought by cytological analysis of fine needle biopsies of suspicious lymph nodes. (18)FDG PET is a valuable tool for diagnosis and prognosis in metastatic patients, especially with negative (131)I WBS. Initial response to therapy, assessed by Tg determination and neck US, allows re-stratification of the risk of relapse. According to this "reassessed risk", adapted rhythms and modalities of follow-up have been recently proposed.
The Journal of Clinical Endocrinology & Metabolism, 2019
Context General rates of over- and underreplacement in levothyroxine (LT4) users with primary hyp... more Context General rates of over- and underreplacement in levothyroxine (LT4) users with primary hypothyroidism are variably high. No information on LT4 adequacy exists in obesity. Objective We explored rates and factors relating to LT4 adequacy in obese patients with primary hypothyroidism. Setting Tertiary care center. Design Among 4954 consecutive obese patients admitted between 2011 and 2014, 691 hypothyroid patients receiving LT4 therapy and 691 body mass index (BMI)-, age-, and sex-matched euthyroid controls underwent analysis of thyroid function, glucolipid profile, body composition, and indirect calorimetry. LT4 users were classified into low TSH (<0.27 mU/L), euthyroid (0.27 to 4.2 mU/L), and high TSH (>4.2 mU/L). Results LT4 users constituted 13.9% of the incident population. TSH was low in 7.5%, high in 17.2%, and normal in 75.2% of LT4 users. Overtreatment decreased with aging and more LT4 users ≥65 years of age had normal TSH than those <65 years of age (P < 0....
TO THE EDITOR: In his review of linezolid, Moellering (1) appro- priately calls for clinical tria... more TO THE EDITOR: In his review of linezolid, Moellering (1) appro- priately calls for clinical trials comparing the efficacy and safety of linezolid with those of other new drugs active against resistant gram- positive organisms, including quinupristin-dalfopristin (currently li- censed) and ...
Neuroendocrine tumours are frequently malignant and have often reached an advanced stage by the t... more Neuroendocrine tumours are frequently malignant and have often reached an advanced stage by the time of diagnosis when they are inoperable, accompanied by severe symptoms, sometimes of an endocrine nature. Current therapeutic procedures include surgery, embolisation of hepatic metastases, local radiotherapy, biotherapy and chemotherapy. Over the years somatostatin analogs, of which octreotide is the first form, have become increasingly important in the treatment of patients with neuroendocrine tumours. A major step forward in analog treatment is represented by the development of slow-release formulas which do not require multiple daily injections and reduce the onset of resistance. The treatment of neuroendocrine tumours in the future will be based on the increased use of somatostatin analogs alone or in association with interferon or chemotherapy, and will also include surgery, radiometabolic therapy and targeted irradiation of the tumour.
To investigate cardiac effects of excess and deficiency of growth hormone (GH) 20 acromegalic sub... more To investigate cardiac effects of excess and deficiency of growth hormone (GH) 20 acromegalic subjects and 11 adult patients with GH deficiency were studied by means of a non invasive method, the Doppler echocardiography. The results obtained in the group of patients were compared with those of 2 groups of 20 and 12 normal subjects, respectively, age and sex matched. The age of the acromegalic patients ranged from 20 to 62 years. Nineteen patients were considered to have active acromegaly at the time of the study. Mean duration of disease since treatment was 12 +/- 5 years (range 5 to 24 years). The age of GH deficient adults ranged from 21 to 33 years. All these patients have been treated with extractive GH over 9 years and the therapy withdrawal was performed at least 3 years before entering the study. In the acromegalic patient group, a subgroup including 9 patients with mild to moderate hypertension was considered. All subjects gave informed consent and the study protocol was approved by the Ethical Committee of the Medical School of Naples. Right ventricular free wall thickness resulted significantly increased in acromegalic patients (8 +/- 2 versus 4 +/- 1 mm; p < 0.001). Left ventricular mass index was augmented both in the whole group and in the subgroup of normotensive acromegalics as compared with normals (134 +/- 33 and 115 +/- 20 versus 80 +/- 18 g.m-2; p < 0.01). Ejection phase indices were normal in patient group, while impaired left and right ventricular diastolic filling was found.(ABSTRACT TRUNCATED AT 250 WORDS)
Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor of the th... more Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor of the thyroid gland. An algorithm for the diagnosis and treatment of SETTLE has yet to be established. The aim of this study was to identify all case reports of SETTLE and to compare the clinical-pathological features and therapy of the cases identified. We performed a PubMed search for case reports of SETTLE in English published up to November 2014 in which &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;SETTLE&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Spindle epithelial tumor with thymus-like differentiation&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; were keywords. We identified 35 articles for a total of 42 cases. We found that SETTLE usually occurs in children and adolescents as an asymptomatic neck mass. Thyroid function tests and tumor markers are invariably within normal range in all patients, and fine needle aspiration biopsy is rarely diagnostic for SETTLE. All 42 patients had undergone thyroidectomy. After surgical resection, chemotherapy (adjuvant or first/second-line treatment) and/or radiotherapy were administered to control tumor growth in cases with metastatic involvement. Although SETTLE presents a low-grade malignancy, it can metastasize to lymph nodes, the mediastinum, lung, vertebrae, and kidney even many years after the initial diagnosis. SETTLE may have a good prognosis if appropriately treated at initial presentation and if patients undergo long-term monitoring with regular clinical and morphological evaluations.
The Journal of Clinical Endocrinology and Metabolism, Sep 1, 1993
The aim of this study was to investigate the effects of a 6-month octreotide treatment on cardiac... more The aim of this study was to investigate the effects of a 6-month octreotide treatment on cardiac mass and function by means of Doppler echocardiography in 11 normotensive patients affected with active acromegaly. The GH and insulin-like growth factor-I levels were normalized during octreotide therapy from 34 +/- 6.5 and 767.4 +/- 72.4 micrograms/L to 4.6 +/- 0.9 and 235 +/- 10.3 micrograms/L, respectively (P &lt; 0.001; mean +/- SEM). After the 6-month treatment, we observed a significant decrease in the left ventricular mass index from 138 +/- 11 to 116 +/- 13 g/m2 (P &lt; 0.001) and in the mean wall thickness/internal end-diastolic radius ratio from 0.47 +/- 0.1 to 0.44 +/- 0.1 (P &lt; 0.001). No significant differences were found in systolic function indices, whereas diastolic filling indices improved over the course of the therapy; the isovolumic relaxation time decreased from 115 +/- 6 to 100 +/- 6 ms (P &lt; 0.05), tricuspid late diastolic filling velocities decreased from 41 +/- 3 to 36 +/- 2 cm/s (P &lt; 0.03), and tricuspid deceleration time decreased from 280 +/- 28 to 198 +/- 15 ms (P &lt; 0.005); the ratio of early to late peak velocity of the right ventricular filling significantly increased from 1 +/- 0.01 to 1.3 +/- 0.1 (P &lt; 0.03). A significant correlation was detected between left ventricular mass regression and increase in the early to late peak velocity ratio of the left ventricular filling (r = 0.62; P &lt; 0.05). The results of this study show an improvement in cardiac structural and functional abnormalities during chronic treatment with octreotide, thus supporting the hypothesis of a specific heart disease secondary to high circulating GH levels.
The Journal of Clinical Endocrinology & Metabolism, 2020
Purpose This work aimed to evaluate genotype-phenotype associations in individuals carrying germl... more Purpose This work aimed to evaluate genotype-phenotype associations in individuals carrying germline variants of transmembrane protein 127 gene (TMEM127), a poorly known gene that confers susceptibility to pheochromocytoma (PHEO) and paraganglioma (PGL). Design Data were collected from a registry of probands with TMEM127 variants, published reports, and public databases. Main Outcome Analysis Clinical, genetic, and functional associations were determined. Results The cohort comprised 110 index patients (111 variants) with a mean age of 45 years (range, 21-84 years). Females were predominant (76 vs 34, P < .001). Most patients had PHEO (n = 94; 85.5%), although PGL (n = 10; 9%) and renal cell carcinoma (RCC, n = 6; 5.4%) were also detected, either alone or in combination with PHEO. One-third of the cases had multiple tumors, and known family history was reported in 15.4%. Metastatic PHEO/PGL was rare (2.8%). Epinephrine alone, or combined with norepinephrine, accounted for 82% of ...
The aim of follow-up of differentiated thyroid carcinoma (CTD) is the assessment of remission, an... more The aim of follow-up of differentiated thyroid carcinoma (CTD) is the assessment of remission, and, in further steps, the early recognition of patients who develop a recurrence. Tools for the follow-up of CTD include the assessment of thyroglobulin and imaging procedures. Thyroglobulin (Tg) is a strong marker of persistent or recurrent disease, but it must be known that Tg antibodies may give falsely low Tg concentration. TSH stimulation, mainly by the mean of recombinant human TSH, improves the sensitivity of Tg determination. New highly sensitive assays may preclude the need for TSH stimulation, at least in some situations. In the last decades, (131)iodine whole body scan gave place to neck ultrasonography (US) as the most performing imaging procedure in the follow-up of CTD. Criteria to identify cervical lymph node suspect of metastasis have been described, and standardized procedures proposed. Finally, the proof of tumoral invasion is brought by cytological analysis of fine needle biopsies of suspicious lymph nodes. (18)FDG PET is a valuable tool for diagnosis and prognosis in metastatic patients, especially with negative (131)I WBS. Initial response to therapy, assessed by Tg determination and neck US, allows re-stratification of the risk of relapse. According to this "reassessed risk", adapted rhythms and modalities of follow-up have been recently proposed.
The Journal of Clinical Endocrinology & Metabolism, 2019
Context General rates of over- and underreplacement in levothyroxine (LT4) users with primary hyp... more Context General rates of over- and underreplacement in levothyroxine (LT4) users with primary hypothyroidism are variably high. No information on LT4 adequacy exists in obesity. Objective We explored rates and factors relating to LT4 adequacy in obese patients with primary hypothyroidism. Setting Tertiary care center. Design Among 4954 consecutive obese patients admitted between 2011 and 2014, 691 hypothyroid patients receiving LT4 therapy and 691 body mass index (BMI)-, age-, and sex-matched euthyroid controls underwent analysis of thyroid function, glucolipid profile, body composition, and indirect calorimetry. LT4 users were classified into low TSH (<0.27 mU/L), euthyroid (0.27 to 4.2 mU/L), and high TSH (>4.2 mU/L). Results LT4 users constituted 13.9% of the incident population. TSH was low in 7.5%, high in 17.2%, and normal in 75.2% of LT4 users. Overtreatment decreased with aging and more LT4 users ≥65 years of age had normal TSH than those <65 years of age (P < 0....
TO THE EDITOR: In his review of linezolid, Moellering (1) appro- priately calls for clinical tria... more TO THE EDITOR: In his review of linezolid, Moellering (1) appro- priately calls for clinical trials comparing the efficacy and safety of linezolid with those of other new drugs active against resistant gram- positive organisms, including quinupristin-dalfopristin (currently li- censed) and ...
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Papers by Bernadette Biondi