79 results on '"Mormando M"'
Search Results
2. Clinical cure vs a novel trifecta system for evaluating long-term outcomes of minimally-invasive partial or total adrenalectomy for unilateral primary aldosteronism: results of a multicentric series
- Author
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Anceschi, U., primary, Mormando, M., additional, Fiori, C., additional, Carrara, A., additional, Zappalà, O., additional, De Concilio, B., additional, Brassetti, A., additional, Bove, A.M., additional, Misuraca, L., additional, Tuderti, G., additional, Mastroianni, R., additional, Ferriero, M.C., additional, Appetecchia, M., additional, Tirone, G., additional, Porpiglia, F., additional, Celia, A., additional, Gallucci, M., additional, Guaglianone, S., additional, and Simone, G., additional
- Published
- 2022
- Full Text
- View/download PDF
3. Arthropathy in acromegaly: a questionnaire-based estimation of motor disability and its relation with quality of life and work productivity
- Author
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Fatti, L, Cangiano, B, Vitale, G, Persani, L, Mantovani, G, Sala, E, Arosio, M, Maffei, P, Dassie, F, Mormando, M, Giampietro, A, Tanda, L, Masiello, E, Nazzari, E, Ferone, D, Corbetta, S, Passeri, E, Guaraldi, F, Grottoli, S, Cannavo, S, Torre, M, Soranna, D, Zambon, A, Cavagnini, F, Scacchi, M, Fatti L. M., Cangiano B., Vitale G., Persani L., Mantovani G., Sala E., Arosio M., Maffei P., Dassie F., Mormando M., Giampietro A., Tanda L., Masiello E. R., Nazzari E., Ferone D., Corbetta S., Passeri E., Guaraldi F., Grottoli S., Cannavo S., Torre M. L. T., Soranna D., Zambon A., Cavagnini F., Scacchi M., Fatti, L, Cangiano, B, Vitale, G, Persani, L, Mantovani, G, Sala, E, Arosio, M, Maffei, P, Dassie, F, Mormando, M, Giampietro, A, Tanda, L, Masiello, E, Nazzari, E, Ferone, D, Corbetta, S, Passeri, E, Guaraldi, F, Grottoli, S, Cannavo, S, Torre, M, Soranna, D, Zambon, A, Cavagnini, F, Scacchi, M, Fatti L. M., Cangiano B., Vitale G., Persani L., Mantovani G., Sala E., Arosio M., Maffei P., Dassie F., Mormando M., Giampietro A., Tanda L., Masiello E. R., Nazzari E., Ferone D., Corbetta S., Passeri E., Guaraldi F., Grottoli S., Cannavo S., Torre M. L. T., Soranna D., Zambon A., Cavagnini F., and Scacchi M.
- Abstract
Purpose: Arthropathy is a common and disabling complication of acromegaly. Since in this condition radiological findings rarely correspond to functional impairment, we elected to quantify in a large cohort of acromegalic patients: the degree of motor disability compared with data from general population, the impact of joint involvement on quality of life and work productivity, and to look for associated factors. Methods: In 211 acromegalic patients, 131 with controlled disease and 80 with active disease, eight validated scales were used to evaluate the (i) prevalence and distribution of arthropathy, (ii) degree of motor disability and joint symptoms (VAS, AIMS symptoms and WOMAC), (iii) quality of life (AcroQoL and PASQ) and work capability (WPAI:GH) as consequences of joint complications. Results: Using the WOMAC questionnaire, for which population based normative values are available, a significantly higher prevalence and severity of motor disability was detected in acromegalics compared to the general population from literature. The results provided by the different questionnaires turned out to be highly concordant. All measures of motor disability correlated both with impaired quality of life and motor disability and were worse in females and in patients with higher BMI. Conclusions: The questionnaires VAS, AIMS symptoms, and WOMAC (this latter both as a whole and with its functionality subscale), with their scores, proved to be the most adequate tools to evaluate motor disability and its consequences on both quality of life and work productivity in acromegaly. Female gender and higher BMI are associated with worse articular symptoms.
- Published
- 2019
4. The TIS score for the prediction of long-term clinical outcomes after minimally-invasive partial and total adrenalectomy for unilateral primary aldosteronism: Results of a multicentric series
- Author
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Anceschi, U., primary, Mormando, M., additional, Fiori, C., additional, Zappalà, O., additional, De Concilio, B., additional, Brassetti, A., additional, Carrara, A., additional, Ferriero, M.C., additional, Tuderti, G., additional, Misuraca, L., additional, Bove, A.M., additional, Mastroianni, R., additional, Appetecchia, M., additional, Tirone, G., additional, Porpiglia, F., additional, Celia, A., additional, Gallucci, M., additional, and Simone, G., additional
- Published
- 2021
- Full Text
- View/download PDF
5. Surgical quality, antihypertensive therapy and electrolyte balance: A novel trifecta for evaluating outcomes of unilateral primary aldosteronism
- Author
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Anceschi, U., primary, Mormando, M., additional, Fiori, C., additional, Zappalà, O., additional, De Concilio, B., additional, Brassetti, A., additional, Carrara, A., additional, Ferriero, M.C., additional, Tuderti, G., additional, Misuraca, L., additional, Bove, A.M., additional, Mastroianni, R., additional, Appetecchia, M., additional, Tirone, G., additional, Porpiglia, F., additional, Celia, A., additional, Gallucci, M., additional, and Simone, G., additional
- Published
- 2021
- Full Text
- View/download PDF
6. How gender influence the health state? A cross sectional study in an endocrine setting
- Author
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Lauretta R, Appetecchia M, Barnabei A, Chiefari A, Terrenato I, Mormando M, Puliani G, and Bianchini M
- Subjects
Cross-sectional study ,Environmental health ,Endocrine system ,Psychology - Abstract
Background: Gender medicine focuses on how gender differences affect health status and diseases development and how they influence health services access and attitude to screening programmes. Endocrine diseases are influenced by many gender-related issues, some of which have not been sufficiently investigated. The aim of this study was to evaluate gender difference in determinants of health (as lifestyle, level of education, area of origin, distance from hospital) and how these elements could influence diseases prevalence in an endocrine outpatients setting, with a special focus on oncological disease. Methods: We performed a cross-sectional study enrolling patients referring for the first time to our Oncological Endocrinology Unit, between January 2019 to December 2019. Results: We enrolled 1107 consecutive patients. Mean age was 56.8 ± 15.0 years (77% females). The main reasons for referral were thyroid and bone diseases. We found a gender difference in some disease prevalences: malignant endocrine diseases and iatrogenic thyroid diseases were more frequent in males, while other thyroid disorders, adrenal and metabolic diseases and cancer treatment induced bone loss were higher in females. The frequency of oncological comorbidities was higher in females. No difference was found in the propensity to travel long distances to reach the hospital. In our population, women had a higher socio-cultural level and followed healthier lifestyle. In fact, alcohol and tobacco consumption was lower in females and women had lower BMI. The percentage of smokers or ex-smokers was higher in patients with any malignancy compared to patients with benign endocrine diseases. Conclusions: the study showed the importance of considering gender as a determinant of health, able to influence also lifestyle and habits, and as an element to keep in consideration to promote a healthier lifestyle and a targeted endocrine screening especially in oncological setting.
- Published
- 2020
7. The treatment of neuroendocrine tumors with long-acting somatostatin analogs: A single center experience with lanreotide autogel
- Author
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Bianchi, A., De Marinis, L., Fusco, A., Lugli, F., Tartaglione, L., Milardi, D., Mormando, M., Lassandro, A. P., Paragliola, R., Rota, C. A., Della Casa, S., Corsello, S. M., Brizi, M. G., and Pontecorvi, A.
- Published
- 2011
- Full Text
- View/download PDF
8. Vertebral Fractures in Patients With Acromegaly: A 3-Year Prospective Study
- Author
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Mazziotti, G., Bianchi, A., Porcelli, T., Mormando, M., Maffezzoni, F., Cristiano, A., Giampietro, A., De Marinis, L., and Giustina, A.
- Published
- 2013
9. The Treatment of Neuroendocrine Tumours (NETs) with Long-Acting Somatostatin Analogues: Preliminary Data in a Single Centre Experience with Lanreotide Autogel.
- Author
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Bianchi, A, primary, Fusco, A, additional, Milardi, D, additional, Lugli, F, additional, Tartaglione, L, additional, Mormando, M, additional, Lassandro, AP, additional, Paragliola, RM, additional, Rota, CA, additional, Casa, S Della, additional, Corsello, M, additional, Pontecorvi, A, additional, and De Marinis, L, additional
- Published
- 2010
- Full Text
- View/download PDF
10. SC181 - Clinical cure vs a novel trifecta system for evaluating long-term outcomes of minimally-invasive partial or total adrenalectomy for unilateral primary aldosteronism: results of a multicentric series
- Author
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Anceschi, U., Mormando, M., Fiori, C., Carrara, A., Zappalà, O., De Concilio, B., Brassetti, A., Bove, A.M., Misuraca, L., Tuderti, G., Mastroianni, R., Ferriero, M.C., Appetecchia, M., Tirone, G., Porpiglia, F., Celia, A., Gallucci, M., Guaglianone, S., and Simone, G.
- Published
- 2022
- Full Text
- View/download PDF
11. Prevalence of morphometric vertebral fractures in 'difficult' patients with acromegaly with different biochemical outcomes after multimodal treatment.
- Author
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Chiloiro, Sabrina, Mormando, M, Bianchi, Antonio, Giampietro, Antonella, Milardi, Domenico, Bima, C, Grande, Giuseppe, Formenti, Am, Mazziotti, G, Pontecorvi, Alfredo, Giustina, Andrea, De Marinis Grasso, Laura, Chiloiro S (ORCID:0000-0001-9241-2392), Bianchi A, Giampietro A, Milardi D, Grande G, Pontecorvi A (ORCID:0000-0003-0570-6865), Giustina A, De Marinis Laura (ORCID:0000-0001-9916-0669), Chiloiro, Sabrina, Mormando, M, Bianchi, Antonio, Giampietro, Antonella, Milardi, Domenico, Bima, C, Grande, Giuseppe, Formenti, Am, Mazziotti, G, Pontecorvi, Alfredo, Giustina, Andrea, De Marinis Grasso, Laura, Chiloiro S (ORCID:0000-0001-9241-2392), Bianchi A, Giampietro A, Milardi D, Grande G, Pontecorvi A (ORCID:0000-0003-0570-6865), Giustina A, and De Marinis Laura (ORCID:0000-0001-9916-0669)
- Abstract
Introduction: Skeletal fragility with high risk of vertebral fractures is an emerging complication of acromegaly in close relationship with duration of active disease. The aim of this cross-sectional study was to evaluate the prevalence and determinants of vertebral fractures in males and females with a history of long-standing active acromegaly undergoing treatment with Pegvisomant. Subjects and methods: Thirty-eight patients (25 females, 13 males) with acromegaly under Pegvisomant therapy were evaluated for vertebral fractures and bone mineral density at lumbar spine and femoral neck. Gonadal status, serum IGF1 levels and growth hormone receptor genotype were also assessed. Results: Vertebral fractures were detected in 12 patients (31.6%). Fractured patients had longer duration of active disease (p = 0.01) with higher frequency of active acromegaly (p = 0.04), received higher dose of Pegvisomant (p = 0.008), and were more frequently hypogonadic (p = 0.02) as compared to patients who did not fracture. Stratifying the patients for gender, vertebral fractures were significantly associated with Pegvisomant dose (p = 0.02) and untreated hypogonadism (p = 0.02) in males and with activity of disease (p = 0.03), serum insulin-like growth factor-I values (p = 0.01) and d3GHR polymorphism (p = 0.005) in females. No significant association was found between vertebral fractures and bone mineral density at either skeletal site. Conclusion: Vertebral fractures are a frequent complication of long-standing active acromegaly. When patients are treated with Pegvisomant, vertebral fractures may occur in close relationship with active acromegaly and coexistent untreated hypogonadism.
- Published
- 2018
12. Effects of pegvisomant and somatostatin receptor ligands on incidence of vertebral fractures in patients with acromegaly.
- Author
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Chiloiro, S, Mazziotti, G, Giampietro, A, Bianchi, A, Frara, S, Mormando, M, Pontecorvi, A, Giustina, A, De Marinis Grasso, Laura, Chiloiro S (ORCID:0000-0001-9241-2392), Giampietro A, Bianchi A, Pontecorvi A (ORCID:0000-0003-0570-6865), Giustina A, De Marinis Laura (ORCID:0000-0001-9916-0669), Chiloiro, S, Mazziotti, G, Giampietro, A, Bianchi, A, Frara, S, Mormando, M, Pontecorvi, A, Giustina, A, De Marinis Grasso, Laura, Chiloiro S (ORCID:0000-0001-9241-2392), Giampietro A, Bianchi A, Pontecorvi A (ORCID:0000-0003-0570-6865), Giustina A, and De Marinis Laura (ORCID:0000-0001-9916-0669)
- Abstract
Purpose: Acromegalic osteopathy is an emerging complication of acromegaly characterized by increase in bone turnover, deterioration in bone microarchitecture and high risk of vertebral fractures (VFs). Somatostatin receptor ligands (SRLs) and pegvisomant (PegV) are used for treatment of acromegaly and there is evidence that both drugs may exert direct effects on peripheral targets regardless of biochemical control of disease. However, whether or not SRLs and PegV may directly influence skeletal health its is unknown. Methods: In this longitudinal study, we evaluated the incidence of radiological VFs in 83 patients (48 females, 35 males; median age 47 years, range 18-80 years) who were treated with SRLs alone (42 cases), PegV alone (6 cases) or in combination with SRLs (35 cases) for median period of 82 months (range 36-126). PegV was given when acromegaly was not controlled by SRLs alone. Results: During the follow-up, 29 patients (34.9%) developed incident VFs. In patients receiving PegV due to active disease during SRL therapy, incidence of VFs decreased significantly from 43.9 to 26.8% (p = 0.039). When acromegaly was controlled by PegV, the incidence of VFs was slightly but not significantly lower as compared to that observed in patients with biochemical control of disease by SRLs (10.0 vs. 26.7%; p = 0.09). In the multivariate logistic regression analysis, incident VFs were independently predicted by pre-existing VFs (odds ratio 61.0; p = 0.009), duration of active acromegaly (odds ratio 1.01; p = 0.05) and mean serum IGF-I during the follow-up (odds ratio 5.26; p = 0.03), regardless of the therapeutic regimen (odds ratio 1.05; p = 0.94). Conclusions: PegV and SRLs had comparable effects on VF risk in acromegaly. The activity of disease was the main determinant of VFs independently of the drug used to control acromegaly.
- Published
- 2018
13. A0625 - Clinical cure vs. a novel trifecta system for evaluating long-term outcomes of minimally-invasive partial or total adrenalectomy for unilateral primary aldosteronism: Results of a multicentric series.
- Author
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Anceschi, U., Mormando, M., Fiori, C., Zappalà, O., De Concilio, B., Brassetti, A., Tuderti, G., Ferriero, M.C., Misuraca, L., Bove, A.M., Mastroianni, R., Carrara, A., Appetecchia, M., Porpiglia, F., Celia, A., Gallucci, M., Tirone, G., and Simone, G.
- Subjects
- *
ADRENALECTOMY , *HYPERALDOSTERONISM - Published
- 2022
- Full Text
- View/download PDF
14. GH receptor isoforms and skeletal fragility in acromegaly
- Author
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Mormando M, Nasto LA, Bianchi A, Mazziotti G, Giampietro A, Pola E, Pontecorvi A, Giustina A, De Marinis L., Mormando, M, Nasto, La, Bianchi, A, Mazziotti, G, Giampietro, A, Pola, E, Pontecorvi, A, Giustina, A, and De Marinis, L.
- Subjects
hormones, hormone substitutes, and hormone antagonists - Abstract
OBJECTIVE: Acromegaly is associated with an increased prevalence of vertebral fractures (VFs) in close relationship with GH hypersecretion. Two isoforms of the GH receptor (GHR) have been identified; the two isoforms differ or not by the expression of the protein fragment encoded by exon 3 of the GHR gene. Deletion of the exon 3 may influence the functional properties of the GHR and affect fracture risk in acromegalic patients. DESIGN: A cross-sectional study was designed to investigate the association between the d3-GHR isoform and the prevalence of VFs in patients with acromegaly. METHODS: In this study, 109 acromegalic patients were included (M/F, 48/61): 73 with controlled/cured acromegaly and 36 with active disease. GHR genotype was assessed in each patient. All patients were evaluated for VFs and bone mineral density at lumbar spine and hip. Serum IGF1 levels and bone metabolism markers were measured. A multivariate analysis was performed to establish risk factors for VFs in our population. RESULTS: d3-GHR carriers showed an increased prevalence of VFs when compared with patients expressing full-length GHR (35/55 vs 12/54; P
- Published
- 2014
15. Arthropathy in acromegaly: a questionnaire-based estimation of motor disability and its relation with quality of life and work productivity.
- Author
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Fatti, L. M., Cangiano, B., Vitale, G., Persani, L., Mantovani, G., Sala, E., Arosio, M., Maffei, P., Dassie, F., Mormando, M., Giampietro, A., Tanda, L., Masiello, E. R., Nazzari, E., Ferone, D., Corbetta, S., Passeri, E., Guaraldi, F., Grottoli, S., and Cannavò, S.
- Abstract
Purpose: Arthropathy is a common and disabling complication of acromegaly. Since in this condition radiological findings rarely correspond to functional impairment, we elected to quantify in a large cohort of acromegalic patients: the degree of motor disability compared with data from general population, the impact of joint involvement on quality of life and work productivity, and to look for associated factors. Methods: In 211 acromegalic patients, 131 with controlled disease and 80 with active disease, eight validated scales were used to evaluate the (i) prevalence and distribution of arthropathy, (ii) degree of motor disability and joint symptoms (VAS, AIMS symptoms and WOMAC), (iii) quality of life (AcroQoL and PASQ) and work capability (WPAI:GH) as consequences of joint complications. Results: Using the WOMAC questionnaire, for which population based normative values are available, a significantly higher prevalence and severity of motor disability was detected in acromegalics compared to the general population from literature. The results provided by the different questionnaires turned out to be highly concordant. All measures of motor disability correlated both with impaired quality of life and motor disability and were worse in females and in patients with higher BMI. Conclusions: The questionnaires VAS, AIMS symptoms, and WOMAC (this latter both as a whole and with its functionality subscale), with their scores, proved to be the most adequate tools to evaluate motor disability and its consequences on both quality of life and work productivity in acromegaly. Female gender and higher BMI are associated with worse articular symptoms. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
16. Severe spinal deformity and multiple vertebral collapses in juvenile Cushing Syndrome: a case report
- Author
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Pola E, Rossi B, Mormando M, La, Nasto, Colangelo D, Sd, Casa, Ld, Marinis, Aulisa L, Pola, E, Rossi, B, Mormando, M, Nasto, La, Colangelo, D, Casa, Sd, Marinis, Ld, and Aulisa, L
- Abstract
Cushing's Syndrome (CS) is rare in adolescence but the pathological effects of excessive circulating glucocorticoids concentration on bone during the developmental age still represent a challenge for orthopedists. Only few reports describe the gravity of early developed damages of spine in young affected by CS. A 18-years-old woman suffering from Cushing's Disease presented after many years treatment of the primary disease referring severe back pain and worsening back deformity. Radiological investigations showed vertebral collapses a devastating thoraco-lumbar scoliosis of 80° Cobb. Lumbar dual X-ray absorptiometry Z-score values were very low and consistent with severe osteoporosis. The patient was treated with bracing, antiresorptive therapy, calcium and vitamin D supplementation, and followed-up with imaging investigations to screen for further fractures. The bone mineral density will be monitored until its normalization will allow to plane surgical treatment in case of progression of spinal deformity and collapses. Early diagnosis and treatment of hypercortisolism, periodical clinical and radiographic follow-up, and treatment for the bone damage are mandatory to prevent the devastating sequelae of secondary osteoporosis.
- Published
- 2012
17. Clinical predictors of vertebral osteoporotic fractures in post-menopausal women: a cross-sectional analysis
- Author
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Luigi Aurelio NASTO, Fusco, A., Colangelo, D., Mormando, M., Di Giacomo, G., Rossi, B., Marinis, L., Logroscino, C. A., Pola, E., Nasto, La, Fusco, A, Colangelo, D, Mormando, M, Di Giacomo, G, Rossi, B, De Marinis, L, Logroscino, Ca, and Pola, E
- Subjects
Aged, 80 and over ,Postmenopause ,Cross-Sectional Studies ,Logistic Models ,Bone Density ,Humans ,Spinal Fractures ,Female ,Middle Aged ,Osteoporotic Fractures ,Aged ,Retrospective Studies - Abstract
BACKGROUND: Osteoporosis is a very common bone disorder and accounts for 1.4 million vertebral compression fractures (VCFs) per year, mostly in post-menopausal women. AIM: The aim of this study was to develop a risk scoring system to identify and gauge the risk of osteoporotic VCFs in post-menopausal women.Materials and Methods: We conducted a retrospective cross-sectional study on 477 post-menopausal women consecutively visited at our institution. We studied 15 different clinical variables, i.e. age, body mass index (BMI), weight, L1-L4 lumbar T-Score, L1-L4 lumbar Z-Score, L1-L4 lumbar bone mineral density (BMD), femoral neck T-Score, femoral neck Z-Score, femoral neck BMD, smoking habit, alcohol consumption, 25-OH-vitamin D, total alkaline phosphatase, bone alkaline phosphatase, and L4 vertebral volume. Study population was split in a derivation and a validation cohort. A logistic regression model was used to develop a predictive score of osteoporotic VCFs in the derivation cohort, finally the performance of the score was tested in the validation cohort. RESULTS: Age, L1-L4 lumbar T-Score, femoral neck T-Score, L4 vertebral volume, and smoking habit were found to be predictors of VCFs. To each variable a score from 0 to +12 was assigned to the magnitude of regression coefficient. A score ≥ 22 identified VCFs with a sensitivity of 87%/89% and a specificity of 87%/90% in the derivation and validation cohorts, respectively. CONCLUSIONS: Our findings indicate that a simple score derived from clinical history and routine diagnostic workout can be usefully employed to gauge the risk of fragility VCFs in post-menopausal women.
- Published
- 2012
18. Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study.
- Author
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Iacovazzo, D, Carlsen, E, Lugli, F, Chiloiro, S, Piacentini, S, Bianchi, A, Giampietro, A, Mormando, M, Clear, AJ, Doglietto, F, Anile, C, Maira, G, LAURIOLA, LIBERO, Rindi, G, Roncaroli, F, Pontecorvi, A, Korbonits, M, De Marinis, L, Iacovazzo, D, Carlsen, E, Lugli, F, Chiloiro, S, Piacentini, S, Bianchi, A, Giampietro, A, Mormando, M, Clear, AJ, Doglietto, F, Anile, C, Maira, G, LAURIOLA, LIBERO, Rindi, G, Roncaroli, F, Pontecorvi, A, Korbonits, M, and De Marinis, L
- Published
- 2016
19. Understanding the effect of acromegaly on the human skeleton.
- Author
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Bima, C, Chiloiro, Sabrina, Mormando, M, Piacentini, Serena, Bracaccia, E, Giampietro, Antonella, Tartaglione, Linda, Bianchi, Antonio, De Marinis Grasso, Laura, Chiloiro S (ORCID:0000-0001-9241-2392), Piacentini S, Giampietro A, Tartaglione L, Bianchi A, De Marinis Laura (ORCID:0000-0001-9916-0669), Bima, C, Chiloiro, Sabrina, Mormando, M, Piacentini, Serena, Bracaccia, E, Giampietro, Antonella, Tartaglione, Linda, Bianchi, Antonio, De Marinis Grasso, Laura, Chiloiro S (ORCID:0000-0001-9241-2392), Piacentini S, Giampietro A, Tartaglione L, Bianchi A, and De Marinis Laura (ORCID:0000-0001-9916-0669)
- Abstract
Acromegaly, caused in most cases by Growth Hormone (GH)-secreting pituitary adenomas, is characterized by increased skeletal growth and enlargement of the soft tissue, because GH and its effector Insulin-like Growth factor-1 are important regulators of bone homeostasis and have a central role in the longitudinal bone growth and maintenance of bone mass. Areas covered: Despite the anabolic effect of these hormones is well known, as a result of the stimulation of bone turnover and especially of bone formation, many acromegalic patients are suffering from a form of secondary osteoporosis with increased risk of fractures. Expert commentary: In this review, we summarize the pathophysiology, diagnosis, clinical picture, disease course and management of skeletal complications of acromegaly, focusing in particular on secondary osteoporosis and fracture risk in acromegaly.
- Published
- 2016
20. Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone-deficient patients.
- Author
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Mormando, M, Chiloiro, Sabrina, Bianchi, Antonio, Giampietro, Antonella, Angelini, F, Tartaglione, Linda, Nasto, L, Milardi, Domenico, Formenti, Am, Giustina, Andrea, De Marinis Grasso, Laura, Chiloiro S (ORCID:0000-0001-9241-2392), Bianchi A, Giampietro A, Tartaglione L, Milardi D, Giustina A, De Marinis Laura (ORCID:0000-0001-9916-0669), Mormando, M, Chiloiro, Sabrina, Bianchi, Antonio, Giampietro, Antonella, Angelini, F, Tartaglione, Linda, Nasto, L, Milardi, Domenico, Formenti, Am, Giustina, Andrea, De Marinis Grasso, Laura, Chiloiro S (ORCID:0000-0001-9241-2392), Bianchi A, Giampietro A, Tartaglione L, Milardi D, Giustina A, and De Marinis Laura (ORCID:0000-0001-9916-0669)
- Abstract
Introduction: Growth hormone deficiency is considered the most important factor determining skeletal fragility in hypopituitary patients. Osteoblasts and chondrocytes express growth hormone (GH) receptor. Two GH receptor isoforms (GHRi) have been identified: they differ for the presence/absence of a protein fragment encoded by exon 3 of GHR gene. Consequently, three genotypes were identified: carriers of both the full-length proteins (flfl-GHR), carriers of one full-length protein and one deleted protein (fld3-GHR) and carriers of both deleted proteins (d3d3-GHR). This polymorphism confers a higher sensitivity to endogenous GH and to recombinant human GH (rhGH); its effect on bone metabolism and skeletal fragility is unknown. The aim of this article was to investigate the role of GHRi in predicting skeletal fragility in adult-onset GHD (AO-GHD) patients. Subjects and methods: A cross-sectional study was conducted to investigate the association between the d3-GHR isoform and the prevalence of morphometric vertebral fractures (VFs) in AO-GHD. Ninety-three AO-GHD were enrolled. Forty-nine patients carried flfl-GHRi (52·7%), and 44 patients (47·3%) carried at least one allele of the d3-GHR isoform. Thirty-two VFs were documented. Fifty-seven patients underwent rhGH replacement therapy. Results: Median age was significantly higher in fractured patients as compared to nonfractured ones; d3-carrier patients showed a lower VF risk as compared to flfl-GHRi (OR: 0·37, 95% IC: 0·24-0·55, P < 0·0001). This finding was also confirmed in AO-GHD undergoing rhGH replacement therapy. Conclusion: This study suggests that d3-GHR may protect AO-GHD particularly when treated with rhGH from the risk of VFs.
- Published
- 2016
21. Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone-deficient patients
- Author
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Mormando, M., primary, Chiloiro, S., additional, Bianchi, A., additional, Giampietro, A., additional, Angelini, F., additional, Tartaglione, L., additional, Nasto, L., additional, Milardi, D., additional, Formenti, A.M., additional, Giustina, A., additional, and De Marinis, L., additional
- Published
- 2016
- Full Text
- View/download PDF
22. Understanding the effect of acromegaly on the human skeleton
- Author
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Bima, C., primary, Chiloiro, S., additional, Mormando, M., additional, Piacentini, S., additional, Bracaccia, E., additional, Giampietro, A., additional, Tartaglione, L., additional, Bianchi, A., additional, and De Marinis, L., additional
- Published
- 2016
- Full Text
- View/download PDF
23. Prevalence of morphometric vertebral fractures in “difficult” patients with acromegaly with different biochemical outcomes after multimodal treatment.
- Author
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Chiloiro, S., Mormando, M., Bianchi, A., Giampietro, A., Milardi, D., Bima, C., Grande, G., Formenti, A. M., Mazziotti, G., Pontecorvi, A., Giustina, A., and De Marinis, L.
- Abstract
Introduction: Skeletal fragility with high risk of vertebral fractures is an emerging complication of acromegaly in close relationship with duration of active disease. The aim of this cross-sectional study was to evaluate the prevalence and determinants of vertebral fractures in males and females with a history of long-standing active acromegaly undergoing treatment with Pegvisomant.Subjects and methods: Thirty-eight patients (25 females, 13 males) with acromegaly under Pegvisomant therapy were evaluated for vertebral fractures and bone mineral density at lumbar spine and femoral neck. Gonadal status, serum IGF1 levels and growth hormone receptor genotype were also assessed.Results: Vertebral fractures were detected in 12 patients (31.6%). Fractured patients had longer duration of active disease (
p = 0.01) with higher frequency of active acromegaly (p = 0.04), received higher dose of Pegvisomant (p = 0.008), and were more frequently hypogonadic (p = 0.02) as compared to patients who did not fracture. Stratifying the patients for gender, vertebral fractures were significantly associated with Pegvisomant dose (p = 0.02) and untreated hypogonadism (p = 0.02) in males and with activity of disease (p = 0.03), serum insulin-like growth factor-I values (p = 0.01) andd3GHR polymorphism (p = 0.005) in females. No significant association was found between vertebral fractures and bone mineral density at either skeletal site.Conclusion: Vertebral fractures are a frequent complication of long-standing active acromegaly. When patients are treated with Pegvisomant, vertebral fractures may occur in close relationship with active acromegaly and coexistent untreated hypogonadism. [ABSTRACT FROM AUTHOR]- Published
- 2018
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- View/download PDF
24. Association between l-thyroxine treatment, GH deficiency, and radiological vertebral fractures in patients with adult-onset hypopituitarism
- Author
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Mazziotti, G, primary, Mormando, M, additional, Cristiano, A, additional, Bianchi, A, additional, Porcelli, T, additional, Giampietro, A, additional, Maffezzoni, F, additional, Serra, V, additional, De Marinis, L, additional, and Giustina, A, additional
- Published
- 2014
- Full Text
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25. A Rare Case of Malignant Granular Cell Tumor of the Colon Incidentally Detected by (18) F-FDG Positron Emission Tomography/Computed Tomography
- Author
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Treglia, G, Mormando, M, Iacovazzo, D, Caldarella, Carmelo, Muoio, B, Bianchi, A, Ricci, Riccardo, Ricci, Riccardo (ORCID:0000-0002-9089-5084), Treglia, G, Mormando, M, Iacovazzo, D, Caldarella, Carmelo, Muoio, B, Bianchi, A, Ricci, Riccardo, and Ricci, Riccardo (ORCID:0000-0002-9089-5084)
- Abstract
We report an unusual case of malignant granular cell tumor (GCT) of the colon incidentally detected by Fluorine-18-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in a 54-year-old female patient with history of pulmonary adenocarcinoma. 18F-FDG-PET/CT showed an area of increased radiopharmaceutical uptake, corresponding to a 3 cm nodule in the caecum. Based on PET/CT findings, the patient underwent endoscopic resection of the colonic lesion. Histology demonstrated the presence of a malignant GCT of the colon.
- Published
- 2013
26. Risk of vertebral fractures in osteoporotic women: definition of a clinically relevant scale of risk
- Author
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Fusco, A., primary, Pola, E., additional, Mormando, M., additional, Colangelo, D., additional, Nasto, L.A., additional, Bianchi, A., additional, Logroscino, C.A., additional, and De Marinis, L., additional
- Published
- 2010
- Full Text
- View/download PDF
27. Clinical predictors of vertebral osteoporotic fractures in post-menopausal women: a cross-sectional analysis.
- Author
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NASTO, L. A., FUSCO, A., COLANGELO, D., MORMANDO, M., DI GIACOMO, G., ROSSI, B., DE MARINIS, L., LOGROSCINO, C. A., and POLA, E.
- Abstract
BACKGROUND: Osteoporosis is a very common bone disorder and accounts for 1.4 million vertebral compression fractures (VCFs) per year,mostly in post-menopausal women. AIM: The aim of this study was to develop a risk scoring system to identify and gauge the risk of osteoporotic VCFs in post-menopausal women. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study on 477 post-menopausal women consecutively visited at our institution.We studied 15 different clinical variables, i.e. age, body mass index (BMI), weight, L1-L4 lumbar T-Score, L1-L4 lumbar ZScore, L1-L4 lumbar bone mineral density (BMD), femoral neck T-Score, femoral neck ZScore, femoral neck BMD, smoking habit, alcohol consumption, 25-OH-vitamin D, total alkaline phosphatase, bone alkaline phosphatase, and L4 vertebral volume. Study population was split in a derivation and a validation cohort. A logistic regression model was used to develop a predictive score of osteoporotic VCFs in the derivation cohort, finally the performance of the score was tested in the validation cohort. RESULTS: Age, L1-L4 lumbar T-Score, femoral neck T-Score, L4 vertebral volume, and smoking habit were found to be predictors of VCFs.To each variable a score from 0 to +12 was assigned to the magnitude of regression coefficient. A score ≤ 22 identified VCFs with a sensitivity of 87%/89% and a specificity of 87%/90% in the derivation and validation cohorts, respectively. CONCLUSIONS: Our findings indicate that a simple score derived from clinical history and routine diagnostic workout can be usefully employed to gauge the risk of fragility VCFs in postmenopausal women. [ABSTRACT FROM AUTHOR]
- Published
- 2012
28. Insulin Autoimmune Syndrome Mimicking Insulinoma: A Challenging Diagnosis.
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Lugli, F., Iacovazzo, D., Fusco, A., Bianchi, A., Chiloiro, S., Mormando, M., Tartaglione, L., Piacentini, S., Giaccari, A., and De Marinis, L.
- Subjects
AUTOIMMUNE diseases ,HYPOGLYCEMIA ,AUTOANTIBODIES ,INSULINOMA ,DIFFERENTIAL diagnosis ,INSULIN - Abstract
Introduction: Insulin autoimmune syndrome (IAS) is a rare condition characterized by hypoglycemia due to autoantibodies against endogenous insulin. It is correlated, in approximately 50% of cases, to specific drugs intake. Hypoglycemia occurs typically during the late post-prandial period. Aim(s): We report two cases of IAS patients who came to our attention because of recurrent and severe hypoglycemia. Materials and methods: Case 1: A 29-year-old female, affected by Graves disease and treated with methimazole, was evaluated in 2006 because of recurrent hypoglycemia. Insulinemia was > 1000 µUI/ml. Fasting test was negative as well as abdomen MRI. After total thyroidectomy glycemic and insulin levels normalized. Case 2: A 45-year-old female came to our attention in 2011 because of recurrent post-prandial hypoglycemia. Insulinemia was >1000 µUI/ml. An OGTT revealed late reactive hypoglycemia, while fasting test was normal as well as EUS. Dosing of insulin antibodies was 658 U/ml (<0.4). With an adequate diet and acarbose treatment the symptoms improved. Results: In these two cases, inappropriately high levels of insulin were associated with late post-prandial hypoglycemia, with no evidence of pancreatic lesions and negative fasting tests. Conclusion: In the evaluation of patients with hypoglycemia and inappropriate secretion of insulin, IAS should be considered in the differential diagnosis, especially in patients with late post-prandial hypoglycemia with a history of specific drugs intake and negative imaging. [ABSTRACT FROM AUTHOR]
- Published
- 2012
29. Arthropathy in acromegaly: a questionnaire-based estimation of motor disability and its relation with quality of life and work productivity
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M. L. Torre, Massimo Scacchi, Luca Persani, S. Cannavò, Davide Soranna, Biagio Cangiano, Elena Nazzari, Pietro Maffei, Elena Passeri, Maura Arosio, F. Cavagnini, Sabrina Corbetta, Diego Ferone, Elisa Sala, Letizia Maria Fatti, Francesca Dassie, Giovanni Vitale, Giovanna Mantovani, Silvia Grottoli, Federica Guaraldi, E. R. Masiello, Marilda Mormando, Antonella Giampietro, Antonella Zambon, L. Tanda, Fatti, L, Cangiano, B, Vitale, G, Persani, L, Mantovani, G, Sala, E, Arosio, M, Maffei, P, Dassie, F, Mormando, M, Giampietro, A, Tanda, L, Masiello, E, Nazzari, E, Ferone, D, Corbetta, S, Passeri, E, Guaraldi, F, Grottoli, S, Cannavo, S, Torre, M, Soranna, D, Zambon, A, Cavagnini, F, and Scacchi, M
- Subjects
Adult ,Male ,medicine.medical_specialty ,WOMAC ,Cross-sectional study ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Population ,030209 endocrinology & metabolism ,Osteoarthritis ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Endocrinology ,Quality of life ,Surveys and Questionnaires ,Arthropathy ,Acromegaly ,Articular impairment ,Complication ,Gender ,Rehabilitation ,Aged ,Aged, 80 and over ,Cross-Sectional Studies ,Female ,Humans ,Joint Diseases ,Middle Aged ,Quality of Life ,Acromegaly, Articular impairment, Complication ,Gender, Osteoarthritis, Rehabilitation ,medicine ,80 and over ,Young adult ,education ,education.field_of_study ,business.industry ,medicine.disease ,Diabetes and Metabolism ,Physical therapy ,Osteoarthriti ,business ,030217 neurology & neurosurgery - Abstract
Purpose: Arthropathy is a common and disabling complication of acromegaly. Since in this condition radiological findings rarely correspond to functional impairment, we elected to quantify in a large cohort of acromegalic patients: the degree of motor disability compared with data from general population, the impact of joint involvement on quality of life and work productivity, and to look for associated factors. Methods: In 211 acromegalic patients, 131 with controlled disease and 80 with active disease, eight validated scales were used to evaluate the (i) prevalence and distribution of arthropathy, (ii) degree of motor disability and joint symptoms (VAS, AIMS symptoms and WOMAC), (iii) quality of life (AcroQoL and PASQ) and work capability (WPAI:GH) as consequences of joint complications. Results: Using the WOMAC questionnaire, for which population based normative values are available, a significantly higher prevalence and severity of motor disability was detected in acromegalics compared to the general population from literature. The results provided by the different questionnaires turned out to be highly concordant. All measures of motor disability correlated both with impaired quality of life and motor disability and were worse in females and in patients with higher BMI. Conclusions: The questionnaires VAS, AIMS symptoms, and WOMAC (this latter both as a whole and with its functionality subscale), with their scores, proved to be the most adequate tools to evaluate motor disability and its consequences on both quality of life and work productivity in acromegaly. Female gender and higher BMI are associated with worse articular symptoms.
- Published
- 2019
30. Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone-deficient patients
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Domenico Milardi, Luigi Aurelio Nasto, Sabrina Chiloiro, Antonio Bianchi, Marilda Mormando, L. De Marinis, Linda Tartaglione, Antonella Giampietro, Andrea Giustina, Anna Maria Formenti, Flavia Angelini, Mormando, M, Chiloiro, S, Bianchi, A, Giampietro, A, Angelini, F, Tartaglione, L, Nasto, L, Milardi, D, Formenti, Am, Giustina, A, De Marinis, L, Giustina, Andrea, and De Marinis, L.
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Adult ,Male ,0301 basic medicine ,Gene isoform ,medicine.medical_specialty ,Genotype ,Hormone Replacement Therapy ,Fracture risk ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Growth hormone receptor ,Biology ,Bone remodeling ,Growth hormone deficiency ,Fractures, Bone ,Young Adult ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,Humans ,Protein Isoforms ,Allele ,AO-GHD ,Receptor ,Growth hormone deficit ,Aged ,Polymorphism, Genetic ,Human Growth Hormone ,Settore MED/13 - ENDOCRINOLOGIA ,Receptors, Somatotropin ,Middle Aged ,medicine.disease ,Recombinant Proteins ,Cross-Sectional Studies ,030104 developmental biology ,Female ,Growth hormon receptor isoform ,Gene Deletion - Abstract
SummaryIntroduction Growth hormone deficiency is considered the most important factor determining skeletal fragility in hypopituitary patients. Osteoblasts and chondrocytes express growth hormone (GH) receptor. Two GH receptor isoforms (GHRi) have been identified: they differ for the presence/absence of a protein fragment encoded by exon 3 of GHR gene. Consequently, three genotypes were identified: carriers of both the full-length proteins (flfl-GHR), carriers of one full-length protein and one deleted protein (fld3-GHR) and carriers of both deleted proteins (d3d3-GHR). This polymorphism confers a higher sensitivity to endogenous GH and to recombinant human GH (rhGH); its effect on bone metabolism and skeletal fragility is unknown. The aim of this article was to investigate the role of GHRi in predicting skeletal fragility in adult-onset GHD (AO-GHD) patients. Subjects and methods A cross-sectional study was conducted to investigate the association between the d3-GHR isoform and the prevalence of morphometric vertebral fractures (VFs) in AO-GHD. Ninety-three AO-GHD were enrolled. Forty-nine patients carried flfl-GHRi (52·7%), and 44 patients (47·3%) carried at least one allele of the d3-GHR isoform. Thirty-two VFs were documented. Fifty-seven patients underwent rhGH replacement therapy. Results Median age was significantly higher in fractured patients as compared to nonfractured ones; d3-carrier patients showed a lower VF risk as compared to flfl-GHRi (OR: 0·37, 95% IC: 0·24–0·55, P < 0·0001). This finding was also confirmed in AO-GHD undergoing rhGH replacement therapy. Conclusion This study suggests that d3-GHR may protect AO-GHD particularly when treated with rhGH from the risk of VFs.
- Published
- 2016
31. Prevalence of morphometric vertebral fractures in 'difficult' patients with acromegaly with different biochemical outcomes after multimodal treatment
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Giuseppe Grande, Anna Maria Formenti, Chiara Bima, Sabrina Chiloiro, Antonio Bianchi, Antonella Giampietro, Alfredo Pontecorvi, L. De Marinis, Domenico Milardi, Marilda Mormando, Gherardo Mazziotti, Andrea Giustina, Chiloiro, S., Mormando, M., Bianchi, A., Giampietro, A., Milardi, D., Bima, C., Grande, G., Formenti, A. M., Mazziotti, G., Pontecorvi, A., Giustina, Andrea, and De Marinis, L.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Pegvisomant ,030209 endocrinology & metabolism ,Growth hormone receptor ,Disease ,Growth hormone receptor isoforms ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Absorptiometry, Photon ,Bone Density ,Growth hormone receptor isoform ,Diabetes mellitus ,Acromegaly ,medicine ,Prevalence ,Humans ,Bone ,Femoral neck ,Aged ,Bone mineral ,Lumbar Vertebrae ,business.industry ,Femur Neck ,Human Growth Hormone ,Settore MED/13 - ENDOCRINOLOGIA ,Middle Aged ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Fracture ,Cross-Sectional Studies ,030220 oncology & carcinogenesis ,Spinal Fractures ,Female ,business ,Complication ,medicine.drug - Abstract
Introduction: Skeletal fragility with high risk of vertebral fractures is an emerging complication of acromegaly in close relationship with duration of active disease. The aim of this cross-sectional study was to evaluate the prevalence and determinants of vertebral fractures in males and females with a history of long-standing active acromegaly undergoing treatment with Pegvisomant. Subjects and methods: Thirty-eight patients (25 females, 13 males) with acromegaly under Pegvisomant therapy were evaluated for vertebral fractures and bone mineral density at lumbar spine and femoral neck. Gonadal status, serum IGF1 levels and growth hormone receptor genotype were also assessed. Results: Vertebral fractures were detected in 12 patients (31.6%). Fractured patients had longer duration of active disease (p = 0.01) with higher frequency of active acromegaly (p = 0.04), received higher dose of Pegvisomant (p = 0.008), and were more frequently hypogonadic (p = 0.02) as compared to patients who did not fracture. Stratifying the patients for gender, vertebral fractures were significantly associated with Pegvisomant dose (p = 0.02) and untreated hypogonadism (p = 0.02) in males and with activity of disease (p = 0.03), serum insulin-like growth factor-I values (p = 0.01) and d3GHR polymorphism (p = 0.005) in females. No significant association was found between vertebral fractures and bone mineral density at either skeletal site. Conclusion: Vertebral fractures are a frequent complication of long-standing active acromegaly. When patients are treated with Pegvisomant, vertebral fractures may occur in close relationship with active acromegaly and coexistent untreated hypogonadism.
- Published
- 2017
32. Long-term effects of the combination of pegvisomant with somatostatin analogs (SSA) on glucose homeostasis in non-diabetic patients with active acromegaly partially resistant to SSA
- Author
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Vincenzo Cimino, Antonio Bianchi, L. Tilaro, Alessandra Fusco, Alfredo Pontecorvi, Marilda Mormando, Laura De Marinis, Gherardo Mazziotti, Andrea Giustina, DE MARINIS, L, Bianchi, A, Fusco, A, Cimino, V, Mormando, M, Tilaro, L, Mazziotti, G, Pontecorvi, A, and Giustina, Andrea
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Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Drug Resistance ,Carbohydrate metabolism ,non-diabetic patients ,Hormone Antagonists ,Endocrinology ,Insulin resistance ,stomatognathic system ,Internal medicine ,Glucose Intolerance ,Acromegaly ,medicine ,glucose homeostasis ,Homeostasis ,Humans ,Glucose homeostasis ,Longitudinal Studies ,Insulin-Like Growth Factor I ,Glycemic ,Human Growth Hormone ,business.industry ,Insulin ,Settore MED/13 - ENDOCRINOLOGIA ,Glucose Tolerance Test ,Middle Aged ,medicine.disease ,Long-Term Care ,stomatognathic diseases ,Somatostatin ,somatostatin analogs (SSA) ,Pegvisomant ,Drug Therapy, Combination ,Female ,business ,medicine.drug - Abstract
Several recent studies have reported beneficial effects of pegvisomant monotherapy on glucose homeostasis for acromegalic patients resistant to somatostatin analogs (SSA). The aim of our longitudinal study was to test whether these beneficial effects on glucose homeostasis would also occur during combined pegvisomant + SSA treatment amongst partially SSA-resistant acromegalic patients. Ten non-diabetic, partially SSA-resistant acromegalic patients underwent a 12-month SSA+pegvisomant treatment after SSA-only therapy. Glucose homeostasis was evaluated at disease diagnosis, at the end of the SSA treatment and after 6 and 12 months of combined SSA+pegvisomant treatment. The addition of pegvisomant treatment was accompanied by a significant improvement in insulin and glycemic responses to the oral glucose tolerance test, without any significant changes in fasting plasma glucose, glycosylated haemoglobin, homeostatic model assessment-derived insulin resistance index and homeostatic model assessment-derived beta-cell function. Moreover, the number of patients with glucose intolerance did not significantly change during the 12-month combined treatment, notwithstanding the significant decrease in serum IGF-1 values. Therefore, our findings suggest that the combined pegvisomant and SSA treatment may not be able to restore normal clinical and biochemical glycometabolic features occurring in acromegalic patients resistant to SSA, while a slight but significant improvement in some biochemical features may be expected.
- Published
- 2007
33. ASSOCIATION BETWEEN L-THYROXINE TREATMENT, GH DEFICIENCY, AND RADIOLOGICAL VERTEBRAL FRACTURES IN PATIENTS WITH ADULT-ONSET HYPOPITUITARISM
- Author
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V Serra, Andrea Giustina, Filippo Maffezzoni, Antonella Giampietro, T Porcelli, Marilda Mormando, A Cristiano, Antonio Bianchi, G. Mazziotti, L. De Marinis, Mazziotti, G, Mormando, M, Cristiano, A, Bianchi, A, Porcelli, T, Giampietro, A, Maffezzoni, F, Serra, V, De Marinis, L, and Giustina, Andrea
- Subjects
Adult ,Male ,medicine.medical_specialty ,Hormone Replacement Therapy ,Cross-sectional study ,Endocrinology, Diabetes and Metabolism ,Hypopituitarism ,Young Adult ,Endocrinology ,Internal medicine ,Prevalence ,Central hypothyroidism ,Humans ,Medicine ,In patient ,Age of Onset ,Young adult ,Aged ,Human Growth Hormone ,business.industry ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Radiography ,Thyroxine ,Cross-Sectional Studies ,Radiological weapon ,Spinal Fractures ,Female ,Age of onset ,business - Abstract
ObjectiveIn this study, we aimed at evaluating the association between radiological vertebral fractures and levo-thyroxine (l-T4) replacement doses in adult patients with hypopituitarism.DesignCross-sectional study.MethodsWe studied 74 adult hypopituitary patients (males, 43; females, 31; mean age, 57 years; and range, 23–79) with central hypothyroidism treated with l-T4 (median daily dose: 1.1 μg/kg). All patients also had severe GH deficiency (GHD) and 38 of them were replaced with recombinant GH. Vertebral fractures were assessed by a quantitative morphometric analysis performed on thoracic and lumbar spine lateral X-ray.ResultsRadiological vertebral fractures were found in 23 patients (31.1%) in association with untreated GHD (P=0.02), higher serum free T4 levels (P=0.03), a higher daily dose of l-T4 (P=0.005), and a longer duration of hypopituitarism (P=0.05). When GHD was treated, the prevalence of vertebral fractures was more frequent (P=0.03) in patients receiving high l-T4 doses (third tertile: >1.35 μg/kg per day) as compared with patients who were treated with lower drug doses (first tertile: l-T4 daily doses. Multivariate analysis showed that untreated GHD (odds ratio: 4.27, 95% CI 1.27–14.33; P=0.01) and the daily dose of l-T4 (odds ratio: 4.01, 95% CI 1.16–14.39; P=0.03) maintained a significant and independent association with vertebral fractures in patients with central hypothyroidism.ConclusionsOur data suggest for the first time that a relative overtreatment with l-T4 may influence the fracture risk in some patients with hypopituitarism.
- Published
- 2014
34. Vertebral fractures in males with prolactinoma
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Gherardo Mazziotti, Andrea Giustina, Laura De Marinis, Tatiana Mancini, Teresa Porcelli, Marilda Mormando, C Mejia, Antonio Bianchi, Ernesto De Menis, Mazziotti, G, Porcelli, T, Mormando, M, De Menis, E, Bianchi, A, Mejia, C, Mancini, T, De Marinis, L, and Giustina, Andrea
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adenoma ,Bone density ,Endocrinology, Diabetes and Metabolism ,males ,Urology ,Lumbar vertebrae ,Bone remodeling ,Absorptiometry, Photon ,Endocrinology ,Bone Density ,Pituitary adenoma ,Cabergoline ,Humans ,Medicine ,Pituitary Neoplasms ,Testosterone ,vertebral fractures ,Prolactinoma ,Aged ,Bone mineral ,Lumbar Vertebrae ,business.industry ,Hypogonadism ,Settore MED/13 - ENDOCRINOLOGIA ,Middle Aged ,medicine.disease ,Surgery ,Hyperprolactinemia ,medicine.anatomical_structure ,prolactinoma ,Osteoporosis ,Spinal Fractures ,business ,medicine.drug - Abstract
Data on osteoporotic fractures in hyperprolactinemia are limited. An increased prevalence of radiological vertebral fractures was recently observed in women with prolactin (PRL)-secreting adenoma, whereas it is unknown whether this observation may reflect a more general increased risk of fractures in this disease and whether the prevalence of fractures in males is affected by gonadal status. Thirty-two males (median age 47 years, range: 22-79) with PRL-secreting pituitary adenoma (10 with microadenoma and 22 with macroadenoma) and 64 control males, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 12 patients with PRL-secreting adenoma (37.5%) and in 5 controls (7.8%, P < 0.001). Fractured patients had lower BMD T-score (P = 0.007) and longer duration of disease (P < 0.001) as compared to patients who did not fracture. Fractures occurred more frequently (P = 0.03) in patients with untreated hyperprolactinemia versus patients treated with cabergoline whose frequency of vertebral fractures was still higher than control subjects. The prevalence of vertebral fractures was not significantly different between eugonadal and hypogonadal patients (33.3% vs. 38.5%; P = 0.8). Moreover, no significant (P = 0.4) difference in serum testosterone values was found between fractured and not fractured males. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in men with PRL-secreting adenoma. These findings would also suggest that PRL excess may produce negative skeletal effects independently of hypogonadism.
- Published
- 2011
35. High prevalence of radiological vertebral fractures in women with prolactin-secreting pituitary adenomas
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Laura De Marinis, Antonio Bianchi, Teresa Porcelli, Tatiana Mancini, Gherardo Mazziotti, Marilda Mormando, Pier Paolo Vescovi, Mauro Doga, Ernesto De Menis, Andrea Giustina, Mazziotti, G, Mancini, T, Mormando, M, De Menis, E, Bianchi, A, Doga, M, Porcelli, T, Vescovi, Pp, De Marinis, L, and Giustina, Andrea
- Subjects
Bone density ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Pituitary neoplasm ,Gastroenterology ,spine radiography ,Endocrinology ,Absorptiometry, Photon ,Bone Density ,80 and over ,Prevalence ,Aged, 80 and over ,dual energy X ray absorptiometry ,Lumbar Vertebrae ,medicine.diagnostic_test ,morphometrics ,lumbar spine ,article ,Middle Aged ,Photon ,postmenopause ,prolactin blood level ,medicine.anatomical_structure ,priority journal ,cabergoline ,Spinal Fractures ,Female ,Adult ,medicine.medical_specialty ,prolactin ,Adenoma ,premenopause ,Lumbar vertebrae ,Young Adult ,Pituitary adenoma ,hyperprolactinemia ,Internal medicine ,microadenoma ,medicine ,cross-sectional study ,Humans ,controlled study ,Pituitary Neoplasms ,Prolactinoma ,human ,Absorptiometry ,Dual-energy X-ray absorptiometry ,Aged ,business.industry ,disease association ,Settore MED/13 - ENDOCRINOLOGIA ,vertebra fracture ,medicine.disease ,somatomedin C ,major clinical study ,Surgery ,Cross-Sectional Studies ,protein blood level ,disease duration ,business ,somatomedin C, adult ,aged ,bone density ,female ,prevalence ,prolactinoma ,vertebra fracture, Absorptiometry, Photon - Abstract
Hyperprolactinemia may cause bone loss but data on fractures are scanty. The aim of this study was to evaluate the prevalence of vertebral fractures in women with prolactin (PRL)-secreting adenoma. In this cross-sectional study, 78 women (median age 45.5 years, range: 20-81) with PRL-secreting pituitary adenoma (66 with microadenoma and 12 with macroadenoma) and 156 control subjects, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 25 patients with PRL-secreting adenoma (32.6%) and in 20 controls (12.8%, P < 0.001). Fractured patients were significantly older (P < 0.001) and had lower BMD T-score (P < 0.001), longer duration of disease (P < 0.001), higher serum PRL (P = 0.004) and lower serum IGF-I (P < 0.001) values as compared to patients who did not fracture. The prevalence of vertebral fractures was significantly (P < 0.001) higher in post-menopausal women with PRL-secreting adenoma as compared to pre-menopausal patients. Fractures occurred more frequently (P = 0.01) in patients with untreated hyperprolactinemia versus patients treated with cabergoline. Logistic regression analysis demonstrated that duration of disease maintained a significant correlation with vertebral fractures (odds ratio 1.16, C.I. 95% 1.02-1.33) even after correction for age, menopausal status, treatment with cabergoline, BMD, serum IGF-I and serum PRL values. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in women with PRL-secreting adenoma.
- Published
- 2011
36. The Role of Inositols in Endocrine and Neuroendocrine Tumors.
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Mormando M, Puliani G, Bianchini M, Lauretta R, and Appetecchia M
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- Humans, Endocrine Gland Neoplasms metabolism, Endocrine Gland Neoplasms drug therapy, Animals, Oxidative Stress, Neuroendocrine Tumors metabolism, Neuroendocrine Tumors drug therapy, Inositol metabolism, Inositol therapeutic use
- Abstract
Inositols have demonstrated a role in cancer prevention and treatment in many kinds of neoplasms. Their molecular mechanisms vary from the regulation of survival and proliferative pathways to the modulation of immunity and oxidative stress. The dysregulation of many pathways and mechanisms regulated by inositols has been demonstrated in endocrine and neuroendocrine tumors but the role of inositol supplementation in this context has not been clarified. The aim of this review is to summarize the molecular basis of the possible role of inositols in endocrine and neuroendocrine tumors, proposing it as an adjuvant therapy.
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- 2024
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- View/download PDF
37. Neurological adverse events of mitotane in adrenocortical carcinoma: results of a pilot study.
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Mormando M, Galiè E, Bianchini M, Lauretta R, Puliani G, Tanzilli A, Anceschi U, Simone G, Petreri G, Graziano G, Pace A, and Appetecchia M
- Abstract
Introduction: Mitotane, the only drug approved by the Food and Drug Administration (FDA) for the treatment of adrenocortical carcinoma, is associated with several side effects including neurotoxicity. The aim of our study is to investigate the relationship between mitotane plasma levels and neurological toxicity., Methods: We have considered five patients affected by adrenocortical carcinoma treated with mitotane. The neurological assessment included a neurological examination, an electroencephalogram, event-related potentials (P300), and a neuropsychological assessment. All of the patients were first considered at the onset of symptoms of neurotoxicity or when mitotanemia levels were above 18 mg/L, for the second time at mitotanemia normalization and subsequently at its further increase, or in case of persistent neurological abnormalities, some months after normalization., Results: At the first neurotoxicity, four patients showed impaired neurological examination, electroencephalogram, and P300; three patients had impaired neuropsychological assessment; one patient, only P300. At mitotanemia normalization, the neurological examination became normal in all patients and electroencephalogram normalized in one patient, improved in another one, continuing to be altered in the other three. P300 latency and neuropsychological assessment normalized in two patients and persisted altered in the patient experiencing long-term mitotane toxicity. At the third evaluation, in the patient with prolonged mitotane toxicity, the normal mitotanemia in the previous 9 months restored P300 and improved the electroencephalogram but not the neuropsychological assessment. In the two patients experiencing a further rise of mitotanemia, neurological examination was normal but P300 and electroencephalogram were altered., Conclusion: The results of our study highlighted the presence of neurophysiological and neuropsychological abnormalities associated with mitotane values above 18 mg/L., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mormando, Galiè, Bianchini, Lauretta, Puliani, Tanzilli, Anceschi, Simone, Petreri, Graziano, Pace and Appetecchia.)
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- 2023
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38. The Therapeutic Intensity Score as Predictor of Clinical Outcomes after Total and Partial Adrenalectomy for Unilateral Primary Aldosteronism: Results of a Multicentric Series.
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Anceschi U, Mormando M, Flammia RS, Fiori C, Zappalà O, De Concilio B, Brassetti A, Carrara A, Ferriero MC, Tuderti G, Misuraca L, Prata F, Tufano A, Bove AM, Mastroianni R, Appetecchia M, Tirone G, Porpiglia F, Celia A, and Simone G
- Abstract
Background: To evaluate the ability of therapeutic intensity score (TIS) in predicting the clinical outcomes of partial (PA) and total adrenalectomy (TA) for UPA., Methods: Between 2011 and 2022, a four-center adrenalectomy dataset was queried for "unilateral adrenal mass" and "UPA" (n = 90). Preoperative TIS of each antihypertensive medication were individually calculated and merged to create a single, cumulative variable. Probability of complete clinical, partial, and absent pooled success rates according to TIS were assessed for the overall cohort by Kaplan-Meier. Cox analyses were used to identify predictors of complete clinical and partial/absent success, respectively. For all analyses, a two-sided p < 0.05 was considered significant., Results: At a median follow-up of 42 months (IQR 27-54) complete partial, and absent clinical success were observed in 60%, 17.7%, and 22.3%, respectively. On Kaplan-Meier analysis, TIS < 1 predicted higher complete success rates ( p < 0.001), while TIS ≥ 1 was predictor of either partial and absent clinical success ( p = 0.008). On multivariable analysis, TIS < 1 (HR 0.25; 95% CI 0.11-0.57; p = 0.001) and adenoma size (HR 1.11; 95% CI 1-1.23; p = 0.0049) were independent predictors of complete clinical success, while TIS ≥ 1 (HR 2.84; 95% CI 1.32-6.1; p = 0.007) was the only independent predictor of absent clinical success., Conclusions: TIS score and adenoma size may help to identify patients who are likely to be at risk of persistent hypertension after surgery.
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- 2023
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39. Syndrome of Inappropriate Antidiuresis and Diabetes Insipidus as Two Sides of the Same Coin in Hypothalamic Lymphoma: A Case Report.
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Marilda M, Rosa L, Stefano T, Marta B, Alfonsina C, Fiammetta N, Giulia P, and Marialuisa A
- Subjects
- Female, Humans, Middle Aged, Deamino Arginine Vasopressin, Sodium, Electrolytes, Hyponatremia complications, Hyponatremia diagnosis, Diabetes Insipidus complications, Diabetes Insipidus diagnosis, Lymphoma complications, Lymphoma diagnosis, Lymphoma therapy, Inappropriate ADH Syndrome complications, Inappropriate ADH Syndrome diagnosis, Diabetes Mellitus
- Abstract
Background: Hypothalamic-pituitary region lymphoma is rare and diabetes insipidus (DI) represents one of the most common endocrine manifestations. We report the first case of hypothalamic lymphoma associated with both the syndrome of inappropriate antidiuresis (SIAD) and DI., Case Presentation: A 64-year-old woman with a history of stage IV large B-cell non-Hodgkin lymphoma, underwent atypical right lung resection for pulmonary nodules. A few days after surgery, the patient presented severe normovolemic hyponatremia and serum hypo-osmolarity, therefore, we suspected a paraneoplastic syndrome (SIAD) related to the lung neoplasm, histologically diagnosed as typical carcinoid. The brain magnetic resonance imaging (MRI) showed a 9 mm lesion in the hypothalamic region that significantly increased one month later with the onset of neurological symptoms. A trans-sphenoidal biopsy showed localization of the large B-cell lymphoma. After surgery, the patient presented with polyuria and polydipsia, so desmopressin therapy was started. In the following days, serum osmolarity and sodium fluctuated between normal and low values, then DI was excluded, and SIAD became more likely. Desmopressin therapy was discontinued and hyponatremia was treated with sodium infusion. Hypothalamic lymphoma was treated with chemotherapy and radiotherapy with substantial shrinkage. The hyponatremia persisted during anticancer treatments and improved only after radiotherapy, confirming paraneoplastic SIAD., Conclusion: Lymphomas of the hypothalamic region can cause electrolyte imbalance for various causes. The differential diagnosis between SIAD, DI and impaired thirst centers may not be straightforward and the electrolyte disorders must be evaluated step by step in all different stages of the disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2023
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40. New Insights in PRRT: Lessons From 2021.
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Puliani G, Chiefari A, Mormando M, Bianchini M, Lauretta R, and Appetecchia M
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- Adult, Humans, Positron-Emission Tomography, Prognosis, Radionuclide Imaging, Radiopharmaceuticals therapeutic use, Somatostatin therapeutic use, Neuroendocrine Tumors pathology
- Abstract
Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs has been used for over two decades for the treatment of well-differentiated neuroendocrine tumors (NETs), and the publication of the NETTER-1 trials has further strengthened its clinical use. However, many aspects of this treatment are still under discussion. The purpose of this review is to collect and discuss the new available evidence, published in 2021, on the use of
177 Lu-Oxodotreotide (DOTATATE) or90 Y-Edotreotide (DOTATOC) in adult patients with NETs focusing on the following hot topics: 1) PRRT use in new clinical settings, broaden its indications; 2) the short- and long-term safety; and 3) the identification of prognostic and predictive factors. The review suggests a possible future increase of PRRT applications, using it in other NETs, as a neoadjuvant treatment, or for rechallenge. Regarding safety, available studies, even those with long follow-up, supported the low rates of adverse events, even though 1.8% of treated patients developed a second malignancy. Finally, there is a lack of prognostic and predictive factors for PRRT, with the exception of the crucial role of nuclear imaging for both patient selection and treatment response estimation., Competing Interests: MA does consultancy and has received research grants from Bayer, Eisai, and Eli-Lilly. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Puliani, Chiefari, Mormando, Bianchini, Lauretta and Appetecchia.)- Published
- 2022
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41. Surgical Quality, Antihypertensive Therapy, and Electrolyte Balance: A Novel Trifecta to Assess Long-Term Outcomes of Adrenal Surgery for Unilateral Primary Aldosteronism.
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Anceschi U, Mormando M, Fiori C, Zappalà O, De Concilio B, Brassetti A, Carrara A, Ferriero MC, Tuderti G, Misuraca L, Bove AM, Mastroianni R, Chiefari A, Appetecchia M, Tirone G, Porpiglia F, Celia A, Gallucci M, and Simone G
- Abstract
Background: To propose a trifecta that summarizes endpoints and predicts their maintenance after adrenalectomy ( n = 90) for unilateral primary aldosteronism (UPA)., Methods: Trifecta was defined as coexistence of: ≥50% antihypertensive therapeutic intensity score reduction (∆TIS), no hypokalemia at 3 months, and no Clavien grade 2-5. Logistic regression was used to identify predictors of trifecta. Probability of clinical, biochemical, and simultaneous success according to trifecta were assessed by Kaplan-Meier. Cox regression was used to identify predictors of long-term clinical, biochemical, and simultaneous success. For all analyses, a two-sided p < 0.05 was considered significant., Results: Simultaneous success rate was 50%. On multivariable analysis, TIS was an independent predictor of trifecta achievement (HR 3.28; 95% CI 1.07-10.9; p = 0.03). At Kaplan-Meier, trifecta predicted higher success for all endpoints (each p < 0.03). On multivariable Cox analysis, adenoma size (AS) ≥6 cm and trifecta were independent predictors of biochemical (AS: HR 2.87; 95% CI 1.53-5.36; trifecta: HR 2.1; 95% CI 1.13-3.90; each p < 0.02) and simultaneous success (AS: HR 3.81; 95% CI 1.68-8.65; trifecta: HR 4.29; 95% CI 2.08-8.86; each p < 0.01), while trifecta was an independent predictor of complete clinical success (HR 2.84; 95% CI 1.45-5.58; p < 0.01)., Conclusions: Trifecta and AS are independent predictors of either long-term complete clinical, biochemical, or combined success after adrenalectomy for UPA.
- Published
- 2022
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42. Clinical cure vs a novel trifecta system for evaluating long-term outcomes of minimally-invasive partial or total adrenalectomy for unilateral primary aldosteronism: results of a multicentric series.
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Anceschi U, Tufano A, Flammia RS, Mormando M, Fiori C, Zappalà O, De Concilio B, Carrara A, Maria Consiglia F, Tuderti G, Brassetti A, Misuraca L, Bove AM, Mastroianni R, Appetecchia M, Tirone G, Porpiglia F, Celia A, Gallucci M, and Simone G
- Abstract
Introduction: Several predictive scores to evaluate outcomes of adrenal surgery for unilateral primary aldosteronism (UPA), have been conceived. We compared a novel trifecta that summarizes outcomes of adrenal surgery for UPA with the clinical cure proposed by Vorselaars., Material and Methods: Between March 2011 and January 2022, a multi-institutional dataset was queried for UPA. Baseline, perioperative and functional data were collected. Clinical and biochemical complete and partial success rates according to Primary Aldosteronism Surgical Outcome (PASO) criteria were assessed for the overall cohort. Clinical cure was defined either as normotension without antihypertensive medications or normotension with lower or equal use of antihypertensive medications. Trifecta was defined as the coexistence of ≥50% antihypertensive therapeutic intensity score (TIS) reduction (ΔTIS), no electrolyte impairment at 3-months and no Clavien-Dindo (2-5) complications. Cox regression analyses were used to identify predictors of long-term clinical and biochemical success. For all analyses, a two-sided p <0.05 was considered significant., Results: Baseline, perioperative and functional outcomes were analyzed. Out of 90 patients, at a median follow-up of 42 months (IQR 27-54) a complete and partial clinical success was observed in 60% and 17.7% of cases while a complete and partial biochemical success was achieved in 83.3% and 12.3% of cases, respectively. Overall trifecta and clinical cure rates were 21.1% and 58.9%, respectively. On multivariable Cox regression analysis, trifecta achievement (HR 2.87; 95% CI 1.45-5.58; p = 0.02) was the only independent predictor of complete clinical success at long-term follow-up., Conclusions: Despite its complex estimation and more restrictive criteria, trifecta but not clinical cure allows to independently predict composite PASO endpoints on the long run., Competing Interests: The authors declare no conflicts of interest., (Copyright by Polish Urological Association.)
- Published
- 2022
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43. Metabolic and Endocrine Toxicities of Mitotane: A Systematic Review.
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Bianchini M, Puliani G, Chiefari A, Mormando M, Lauretta R, and Appetecchia M
- Abstract
Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this systematic review is to collect the available evidence on the side effects of mitotane on the endocrine and metabolic systems in both children and adults affected by adrenal carcinoma. Sixteen articles on 493 patients were included. Among the adrenal insufficiency, which is an expected side effect of mitotane, 24.5% of patients increased glucocorticoid replacement therapy. Mineralocorticoid insufficiency usually occurred late in treatment in 36.8% of patients. Thyroid dysfunction is characterized by a decrease in FT4, which occurs within 3-6 months of treatment in 45.4% of patients, while TSH seems to not be a reliable marker. Dyslipidemia is characterized by an increase in both LDL-c and HDL-c (54.2%). Few studies have found evidence of hypertriglyceridemia. In males, gynecomastia and hypogonadism can occur after 3-6 months of treatment (38.4% and 35.6%, respectively), while in pre-menopausal women, mitotane can cause ovarian cysts and, less frequently, menstrual disorders. Most of these side effects appear to be reversible after mitotane discontinuation. We finally suggest an algorithm that could guide metabolic and endocrine safety assessments in patients treated with mitotane for ACC.
- Published
- 2021
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44. Inositols Depletion and Resistance: Principal Mechanisms and Therapeutic Strategies.
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Lepore E, Lauretta R, Bianchini M, Mormando M, Di Lorenzo C, and Unfer V
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- Animals, Biological Transport, Biosynthetic Pathways, Dietary Supplements, Gastrointestinal Absorption, Gastrointestinal Microbiome, Humans, Inositol administration & dosage, Kidney metabolism, Carbohydrate Metabolism, Inositol deficiency, Inositol metabolism
- Abstract
Inositols are natural molecules involved in several biochemical and metabolic functions in different organs and tissues. The term "inositols" refers to five natural stereoisomers, among which myo-Inositol (myo-Ins) is the most abundant one. Several mechanisms contribute to regulate cellular and tissue homeostasis of myo-Ins levels, including its endogenous synthesis and catabolism, transmembrane transport, intestinal adsorption and renal excretion. Alterations in these mechanisms can lead to a reduction of inositols levels, exposing patient to several pathological conditions, such as Polycystic Ovary Syndrome (PCOS), hypothyroidism, hormonal and metabolic imbalances, like weight gain, hyperinsulinemia, dyslipidemia, and metabolic syndrome. Indeed, myo-Ins is involved in different physiological processes as a key player in signal pathways, including reproductive, hormonal, and metabolic modulation. Genetic mutations in genes codifying for proteins of myo-Ins synthesis and transport, competitive processes with structurally similar molecules, and the administration of specific drugs that cause a central depletion of myo-Ins as a therapeutic outcome, can lead to a reduction of inositols levels. A deeper knowledge of the main mechanisms involved in cellular inositols depletion may add new insights for developing tailored therapeutic approaches and shaping the dosages and the route of administration, with the aim to develop efficacious and safe approaches counteracting inositols depletion-induced pathological events.
- Published
- 2021
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45. Case Report: Ipilimumab-Induced Panhypophysitis: An Infrequent Occurrence and Literature Review.
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Barnabei A, Carpano S, Chiefari A, Bianchini M, Lauretta R, Mormando M, Puliani G, Paoletti G, Appetecchia M, and Torino F
- Abstract
Background: Immune checkpoint inhibitors (ICIs), by unleashing the anticancer response of the immune system, can improve survival of patients affected by several malignancies, but may trigger a broad spectrum of adverse events, including autoimmune hypophysitis. ICI-related hypophysitis mainly manifests with anterior hypopituitarism, while the simultaneous involvement of both anterior and posterior pituitary (i.e., panhypophysitis) has rarely been described., Case Presentation: In June 2015, a 64-year-old man affected by liver metastases of a uveal melanoma was referred to us due to polyuria and polydipsia. Two months prior, he had started ipilimumab therapy (3 mg/kg iv every 21 days). The treatment was well-tolerated (only mild asthenia and diarrhea were reported). A few days before the fourth cycle, the patient complained of intense headaches, profound fatigue, nocturia, polyuria (up to 10 L urine/daily), and polydipsia. Laboratory tests were consistent with adrenal insufficiency, hypothyroidism, and transient central diabetes insipidus. The pituitary MRI showed an enlarged gland with microinfarcts, while the hypophyseal stalk was normal, and the neurohypophyseal 'bright signal' in T1 sequences was not detected. The treatment included dexamethasone (then cortisone acetate at replacement dose), desmopressin, and levothyroxine. Within the next five days, the symptoms resolved, and blood pressure, electrolytes, glucose, and urinalysis were stable within the normal ranges; desmopressin was discontinued while cortisone acetate and levothyroxine were maintained. The fourth ipilimumab dose was entirely administered in the absence of further side effects., Conclusion: As ICIs are increasingly used as anticancer agents, the damage to anterior and/or posterior pituitary can be progressively encountered by oncologists and endocrinologists in their clinical practice. Patients on ICIs and their caregivers should be informed about that risk and be empowered to alert the referring specialists early, at the onset of panhypopituitarism symptoms, including polyuria/polydipsia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Barnabei, Carpano, Chiefari, Bianchini, Lauretta, Mormando, Puliani, Paoletti, Appetecchia and Torino.)
- Published
- 2020
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46. A Rare Case of Pituitary Melanoma Metastasis: A Dramatic and Prolonged Response to Dabrafenib-Trametinib Therapy.
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Mormando M, Puliani G, Barnabei A, Lauretta R, Bianchini M, Chiefari A, Russillo M, Cognetti F, Romano L, and Appetecchia M
- Subjects
- Adult, Humans, Imidazoles administration & dosage, Male, Melanoma genetics, Melanoma secondary, Mutation, Oximes administration & dosage, Pituitary Neoplasms genetics, Pituitary Neoplasms pathology, Prognosis, Proto-Oncogene Proteins B-raf genetics, Pyridones administration & dosage, Pyrimidinones administration & dosage, Skin Neoplasms genetics, Skin Neoplasms secondary, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Melanoma drug therapy, Pituitary Neoplasms drug therapy, Skin Neoplasms drug therapy
- Abstract
Introduction: Pituitary metastases (PM) are rare events and to date only very few cases of melanoma PM have been described in literature up to now. Case Presentation: We describe the clinical history of a 33-year-old male patient who underwent surgical excision of an inter-scapular melanoma in 2008. The subsequent follow-up was negative for ~10 years. In September 2018, due to the onset of a severe headache, the patient underwent a brain magnetic resonance imaging, which showed an expansive mass in the saddle and suprasellar region with a maximum diameter of 17 mm. Pituitary function tests and visual field were normal. Worsening of the headache and the appearance of a left eye ptosis led the patient to surgical removal of the lesion in October 2018. The histological examination unexpectedly showed metastasis of the melanoma. Post-operative hormonal assessment showed secondary hypothyroidism and hypoadrenalism, which were both promptly treated, and a mild hypogonadism. Three months after surgery, a sellar MRI showed a persistent, increased pituitary mass (3 cm of diameter); fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (
18 F-FDG PET/CT) detected an increased radiopharmaceutical uptake in the sellar region. Due to the persistence of the disease and the evidence of a BRAF V600E mutation, in February 2019, the patient underwent a combined treatment with dabrafenib (a BRAF inhibitor) and trametinib (mitogen-activated extracellular signal-regulate kinase inhibitor). Sellar MRI performed 6 months later showed no evidence of mass in the sellar region. The patient was in a good clinical condition and did not complain of headaches or other symptoms; there were no significant side-effects from the anticancer therapy. After 13 months of treatment, the patient showed no recurrence of the disease on morphological imaging. Anticancer therapy was confirmed, replacement therapies with hydrocortisone and levothyroxine continued and the pituitary-gonadal axis was restored. Conclusion: This is a very interesting case, both for the rarity of the pituitary melanoma metastasis and for the singular therapeutic course carried out by the patient. This is the first case of a pituitary melanoma metastasis with BRAF mutation, successfully treated with the combination of dabrafenib and trametinib after incomplete surgical removal., (Copyright © 2020 Mormando, Puliani, Barnabei, Lauretta, Bianchini, Chiefari, Russillo, Cognetti, Romano and Appetecchia.)- Published
- 2020
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47. Correction to: Effects of pegvisomant and somatostatin receptor ligands on incidence of vertebral fractures in patients with acromegaly.
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Chiloiro S, Mazziotti G, Giampietro A, Bianchi A, Frara S, Mormando M, Pontecorvi A, Giustina A, and De Marinis L
- Abstract
The original version of the article contained an error in the results section of the Abstract. The vertebral fractures (VFs) odds ratio is incorrectly published as 61.0 and the correct value is 6.10.
- Published
- 2018
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48. Effects of pegvisomant and somatostatin receptor ligands on incidence of vertebral fractures in patients with acromegaly.
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Chiloiro S, Mazziotti G, Giampietro A, Bianchi A, Frara S, Mormando M, Pontecorvi A, Giustina A, and De Marinis L
- Subjects
- Acromegaly metabolism, Adolescent, Adult, Aged, Aged, 80 and over, Bone Density drug effects, Female, Human Growth Hormone therapeutic use, Humans, Insulin-Like Growth Factor I metabolism, Logistic Models, Longitudinal Studies, Male, Middle Aged, Somatostatin therapeutic use, Young Adult, Acromegaly drug therapy, Human Growth Hormone analogs & derivatives, Receptors, Somatostatin metabolism
- Abstract
Purpose: Acromegalic osteopathy is an emerging complication of acromegaly characterized by increase in bone turnover, deterioration in bone microarchitecture and high risk of vertebral fractures (VFs). Somatostatin receptor ligands (SRLs) and pegvisomant (PegV) are used for treatment of acromegaly and there is evidence that both drugs may exert direct effects on peripheral targets regardless of biochemical control of disease. However, whether or not SRLs and PegV may directly influence skeletal health its is unknown., Methods: In this longitudinal study, we evaluated the incidence of radiological VFs in 83 patients (48 females, 35 males; median age 47 years, range 18-80 years) who were treated with SRLs alone (42 cases), PegV alone (6 cases) or in combination with SRLs (35 cases) for median period of 82 months (range 36-126). PegV was given when acromegaly was not controlled by SRLs alone., Results: During the follow-up, 29 patients (34.9%) developed incident VFs. In patients receiving PegV due to active disease during SRL therapy, incidence of VFs decreased significantly from 43.9 to 26.8% (p = 0.039). When acromegaly was controlled by PegV, the incidence of VFs was slightly but not significantly lower as compared to that observed in patients with biochemical control of disease by SRLs (10.0 vs. 26.7%; p = 0.09). In the multivariate logistic regression analysis, incident VFs were independently predicted by pre-existing VFs (odds ratio 61.0; p = 0.009), duration of active acromegaly (odds ratio 1.01; p = 0.05) and mean serum IGF-I during the follow-up (odds ratio 5.26; p = 0.03), regardless of the therapeutic regimen (odds ratio 1.05; p = 0.94)., Conclusions: PegV and SRLs had comparable effects on VF risk in acromegaly. The activity of disease was the main determinant of VFs independently of the drug used to control acromegaly.
- Published
- 2018
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49. An Overview of Diagnosis of Primary Autoimmune Hypophysitis in a Prospective Single-Center Experience.
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Chiloiro S, Tartaglione T, Angelini F, Bianchi A, Arena V, Giampietro A, Mormando M, Sciandra M, Laino ME, and De Marinis L
- Subjects
- Adult, Antibodies, Antinuclear metabolism, Antigens, Nuclear metabolism, Female, Humans, Male, Middle Aged, Neurologic Examination, Pituitary Gland diagnostic imaging, Prospective Studies, Retrospective Studies, Young Adult, Autoimmune Hypophysitis classification, Autoimmune Hypophysitis diagnosis
- Abstract
Background: Autoimmune hypophysitis is a rare disease with a natural progression that is not well known., Aim: To collect representative data on clinical features of autoimmune hypophysitis and better characterize the disease., Patients and Methods: A prospective single-center study was designed. Autoimmune hypophysitis-affected patients evaluated from 2011 at our tertiary care Pituitary Unit were enrolled. After ruling out other pituitary masses and secondary causes of hypophysitis, autoimmune hypophysitis was the diagnosis of exclusion. Autoimmune hypophysitis was classified as adenohypophysitis, panhypophysitis, and infundibuloneurohypophysitis according to clinical and neuroradiological findings., Results: A total of 21 patients met the inclusion criteria: 9 were diagnosed with adenohypophysitis, 4 with panhypophysitis, and 8 with infundibuloneurohypophysitis. The frequency of secondary hypoadrenalism was similar in adenohypophysitis, panhypophysitis, and infundibuloneurohypophysitis. Growth hormone deficit and secondary hypogonadism occurred more frequently in infundibuloneurohypophysitis than in adenohypophysitis and panhypophysitis (p = 0.009; p = 0.04). All cases of multiple pituitary secretion deficits occurred in cases of infundibuloneurohypophysitis (p = 0.04). No correlations between hypophysitis subtype and anti-pituitary and anti-hypothalamus autoantibodies were found. A higher frequency of extractable nuclear antigens (ENA) and anti-nuclear antibodies (ANA) was found in cases of panhypophysitis (OR 5.0, 95% CI 0.86-28.8, p < 0.001, and OR 1.8, 95% CI 1.1-3.2, p = 0.02, respectively) as compared to adenohypophysitis and infundibuloneurohypophysitis., Conclusion: Infundibuloneurohypophysitis should be taken into account in the etiological diagnosis of hypopituitarism, particularly if it is associated with diabetes insipidus and in cases of growth hormone deficit, secondary hypogonadism, or multiple hormone deficits. Contrast-enhanced MRI is crucial for the clinical and noninvasive diagnosis of hypophysitis. Screening for autoantibodies, particularly anti-ENA and anti-ANA, is strongly suggested in the clinical context of hypophysitis., (© 2016 S. Karger AG, Basel.)
- Published
- 2017
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50. Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study.
- Author
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Iacovazzo D, Carlsen E, Lugli F, Chiloiro S, Piacentini S, Bianchi A, Giampietro A, Mormando M, Clear AJ, Doglietto F, Anile C, Maira G, Lauriola L, Rindi G, Roncaroli F, Pontecorvi A, Korbonits M, and De Marinis L
- Subjects
- Adult, Drug Resistance, Female, Humans, Intracellular Signaling Peptides and Proteins, Ki-67 Antigen, Male, Middle Aged, Somatostatin administration & dosage, Somatostatin pharmacology, Treatment Outcome, Acromegaly drug therapy, Adenoma drug therapy, Growth Hormone-Secreting Pituitary Adenoma drug therapy, Receptors, Somatostatin metabolism, Somatostatin analogs & derivatives
- Abstract
Aim: To gather data regarding factors predicting responsiveness to pasireotide in acromegaly., Patients and Methods: SSTR2a, SSTR3, SSTR5, AIP, Ki-67 and the adenoma subtype were evaluated in somatotroph adenomas from 39 patients treated post-operatively with somatostatin analogues (SSAs). A standardized SSTR scoring system was applied (scores 0-3). All patients received first-generation SSAs, and 11 resistant patients were subsequently treated with pasireotide LAR., Results: None of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0-1) were responsive to first-generation SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (P=0.04). None of the patients with an SSTR5 score of 0-1 were responsive to pasireotide, as opposed to 5/7 cases with a score of 2 or 3 (P=0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; P=0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; P=0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0-1 44.4 vs 6.7%; P=0.006) while no difference was seen in SSTR5 (SSTR5 scores 0-1 33.3 vs 23.3%; P=0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; P=0.04)., Conclusion: The expression of SSTR5 might predict responsiveness to pasireotide in acromegaly. AIP deficient and sparsely granulated adenomas may benefit from pasireotide treatment. These results need to be confirmed in larger series of pasireotide-treated patients., (© 2016 European Society of Endocrinology.)
- Published
- 2016
- Full Text
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