184 results on '"Di Dalmazi, G."'
Search Results
2. Artificial intelligence in endocrinology: a comprehensive review
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Giorgini, F., Di Dalmazi, G., and Diciotti, S.
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- 2024
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3. Shortage of hCRH for the diagnosis of endogenous CS: the end of an era or the beginning of a new journey?
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Ceccato, F. and Di Dalmazi, G.
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- 2023
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4. New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study
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Gambineri, A., Scarano, E., Rucci, P., Perri, A., Tamburrino, F., Altieri, P., Corzani, F., Cecchetti, C., Dionese, P., Belardinelli, E., Ibarra-Gasparini, D., Menabò, S., Vicennati, V., Repaci, A., di Dalmazi, G., Pelusi, C., Zavatta, G., Virdi, A., Neri, I., Fanelli, F., Mazzanti, L., and Pagotto, U.
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- 2022
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5. Computerized tomography texture analysis of pheochromocytoma: relationship with hormonal and histopathological data
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De Leo, A., Vara, G., Paccapelo, A., Balacchi, C., Vicennati, V., Tucci, L., Pagotto, U., Selva, S., Ricci, C., Alberici, L., Minni, F., Nanni, C., Ambrosi, F., Santini, D., Golfieri, R., Di Dalmazi, G., and Mosconi, C.
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- 2022
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6. 34P Impact of environmental pollution on adrenocortical carcinoma in Italy
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Puglisi, S., primary, Calabrese, A., additional, Ferraù, F., additional, Laganà, M., additional, Grisanti, S., additional, Ceccato, F., additional, Scaroni, C., additional, Di Dalmazi, G., additional, Stigliano, A., additional, Altieri, B., additional, Canu, L., additional, Luconi, M., additional, Loli, P., additional, De Martino, M.C., additional, Arvat, E., additional, Palmieri, S., additional, Basile, V., additional, Berruti, A., additional, Cannavò, S., additional, and Terzolo, M., additional
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- 2024
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7. Artificial intelligence in endocrinology: a comprehensive review
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Giorgini, F., primary, Di Dalmazi, G., additional, and Diciotti, S., additional
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- 2023
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8. Steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency in a population of PCOS with suspicious levels of 17OH-progesterone
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Oriolo, C., Fanelli, F., Castelli, S., Mezzullo, M., Altieri, P., Corzani, F., Pelusi, C., Repaci, A., Di Dalmazi, G., Vicennati, V., Baldazzi, L., Menabò, S., Dormi, A., Nardi, E., Brillanti, G., Pasquali, R., Pagotto, U., and Gambineri, A.
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- 2020
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9. Radiologically defined lipid-poor adrenal adenomas: histopathological characteristics
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De Leo, A., Mosconi, C., Zavatta, G., Tucci, L., Nanni, C., Selva, S., Balacchi, C., Ceccarelli, C., Santini, D., Pantaleo, M. A., Minni, F., Fanti, S., Golfieri, R., Pagotto, U., Vicennati, V., and Di Dalmazi, G.
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- 2020
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10. Thyroid dysfunctions secondary to cancer immunotherapy
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Chalan, P., Di Dalmazi, G., Pani, F., De Remigis, A., Corsello, A., and Caturegli, P.
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- 2018
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11. Obituary: Renato Pasquali (1946–2019)
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Gambineri, A., Di Dalmazi, G., Fanelli, F., Altieri, P., Repaci, A., Garelli, S., Ribichini, D., Pelusi, C., Vicennati, V., and Pagotto, U.
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- 2020
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12. Radiologically defined lipid-poor adrenal adenomas: histopathological characteristics
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De Leo, A., Mosconi, C., Zavatta, G., Tucci, L., Nanni, C., Selva, S., Balacchi, C., Ceccarelli, C., Santini, D., Pantaleo, M. A., Minni, F., Fanti, S., Golfieri, R., Pagotto, U., Vicennati, V., and Di Dalmazi, G.
- Abstract
Background: Adrenal lipid-poor adenomas (LPA) are defined by high unenhanced density (≥ 10 HU), and absolute and relative contrast medium washout > 60% and > 40%, respectively, at computerized tomography (CT). To date, no thorough histopathological characterization has been performed in those frequent lesions (one-third of adrenal adenomas). Our aim was to analyze the histopathological characteristics of adrenal LPA. Methods: Patients with LPA (n= 57) were selected among consecutive subjects referred for an adrenal incidentaloma or ACTH-independent Cushing syndrome. FluoroDeoxyGlucose-Positron Emission Tomography (FDG-PET) was performed in 37 patients. In patients treated by adrenalectomy (n= 17), Weiss score and Lin–Weiss–Bisceglia score (in tumors composed entirely or predominantly of oncocytes) were calculated. Results: Radiological parameters did not differ among patients with ACTH-independent Cushing syndrome (n= 6) and those with adrenal incidentalomas associated with primary aldosteronism (n= 2), autonomous cortisol secretion (n= 14), or non-functioning (n= 35). Patients treated by adrenalectomy had larger tumors (28.9 ± 11.2 vs17.3 ± 8.4 mm,P< 0.001), higher CT unenhanced density (29.1 ± 11.0 vs23.1 ± 9.0 HU, P= 0.043), and FDG-PET adrenal uptake (9.0 ± 6.4 vs4.4 ± 2.3 SUV, P= 0.003) than non-operated ones. Oncocytic features > 75% of the tumor were detected in 12/17 cases (70.6%). Five of those showed borderline-malignant histopathological characteristics by Lin–Weiss–Bisceglia score. Among remaining non-oncocytic tumors, 1/5 had a Weiss score ≥ 3. Overall, 6/17 tumors (35.3%) had borderline-malignant potential. Radiological parameters were similar between patients with benign and borderline-malignant tumors. Conclusions: Adrenal LPA are a heterogeneous group of tumors, mostly composed of oncocytomas. Up to 1/3 of those tumors may have a borderline-malignant potential at histopathology.
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- 2024
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13. Steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency in a population of PCOS with suspicious levels of 17OH-progesterone
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Oriolo, C., Fanelli, F., Castelli, S., Mezzullo, M., Altieri, P., Corzani, F., Pelusi, C., Repaci, A., Di Dalmazi, G., Vicennati, V., Baldazzi, L., Menabò, S., Dormi, A., Nardi, E., Brillanti, G., Pasquali, R., Pagotto, U., and Gambineri, A.
- Abstract
Objective: We aimed at defining the most effective routine immunoassay- or liquid chromatography-tandem mass spectrometry (LC–MS/MS)-determined steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency (21-NCAH) in a PCOS-like population before genotyping. Methods: Seventy PCOS-like patients in reproductive age with immunoassay-determined follicular 17OH-progesterone (17OHP) ≥ 2.00 ng/mL underwent CYP21A2gene analysis and
1–24 ACTH test. Serum steroids were measured by immunoassays at baseline and 60 min after ACTH stimulation; basal steroid profile was measured by LC–MS/MS. Results: Genotyping revealed 23 21-NCAH, 15 single allele heterozygous CYP21A2mutations (21-HTZ) and 32 PCOS patients displaying similar clinical and metabolic features. Immunoassays revealed higher baseline 17OHP and testosterone, and after ACTH stimulation, higher 17OHP (17OHP60 ) and lower cortisol, whereas LC–MS/MS revealed higher 17OHP (17OHPLC-MS/MS ), progesterone and 21-deoxycortisol and lower corticosterone in 21-NCAH compared with both 21-HTZ and PCOS patients. Steroid thresholds best discriminating 21-NCAH from 21-HTZ and PCOS were estimated, and their diagnostic accuracy in identifying 21-NCAH from PCOS was established by ROC analysis. The highest accuracy was observed for 21-deoxycortisol ≥ 0.087 ng/mL, showing 100% sensitivity, while the combination of 17OHPLC-MS/MS ≥ 1.79 ng/mL and corticosterone ≤ 8.76 ng/mL, as well as the combination of ACTH-stimulated 17OHP ≥ 6.77 ng/mL and cortisol ≤ 240 ng/mL by immunoassay, showed 100% specificity. Conclusions: LC–MS/MS measurement of basal follicular 21-deoxycortisol, 17OHP and corticosterone seems the most convenient method for diagnosing 21-NCAH in a population of PCOS with a positive first level screening, providing high accuracy and reducing the need for ACTH stimulation test.- Published
- 2024
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14. Empagliflozin, metformin and insulin degludec, during pregnancy: a case report
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Formoso, G., Ginestra, F., Di Dalmazi, G., and Consoli, A.
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- 2018
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15. Corticotroph tumor progression after bilateral adrenalectomy (Nelson's syndrome): systematic review and expert consensus recommendations
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Reincke, M, Albani, A, Assie, G, Bancos, I, Brue, T, Buchfelder, M, Chabre, O, Ceccato, F, Daniele, A, Detomas, M, Di Dalmazi, G, Elenkova, A, Findling, J, Grossman, AB, Gomez-Sanchez, CE, Heaney, AP, Honegger, J, Karavitaki, N, Lacroix, A, Laws, E R, Losa, M, Murakami, M, Newell-Price, J, Giraldi, FP, Perez-Rivas, LG, Pivonello, R, Rainey, WE, Sbiera, S, Schopohl, J, Stratakis, CA, Theodoropoulou, M, van Rossum, Liesbeth, Valassi, E, Zacharieva, S, Rubinstein, G, Ritzel, K, Reincke, M, Albani, A, Assie, G, Bancos, I, Brue, T, Buchfelder, M, Chabre, O, Ceccato, F, Daniele, A, Detomas, M, Di Dalmazi, G, Elenkova, A, Findling, J, Grossman, AB, Gomez-Sanchez, CE, Heaney, AP, Honegger, J, Karavitaki, N, Lacroix, A, Laws, E R, Losa, M, Murakami, M, Newell-Price, J, Giraldi, FP, Perez-Rivas, LG, Pivonello, R, Rainey, WE, Sbiera, S, Schopohl, J, Stratakis, CA, Theodoropoulou, M, van Rossum, Liesbeth, Valassi, E, Zacharieva, S, Rubinstein, G, and Ritzel, K
- Abstract
Background: Corticotroph tumor progression (CTP) leading to Nelson’s syndrome (NS) is a severe and difficult-to-treat complication subsequent to bilateral adrenalectomy (BADX) for Cushing’s disease. Its characteristics are not well described, and consensus recommendations for diagnosis and treatment are missing. Methods: A systematic literature search was performed focusing on clinical studies and case series (≥5 patients). Definition, cumulative incidence, treatment and long-term outcomes of CTP/NS after BADX were analyzed using descriptive statistics. The results were presented and discussed at an interdisciplinary consensus workshop attended by international pituitary experts in Munich on October 28, 2018. Results: Data covered definition and cumulative incidence (34 studies, 1275 patients), surgical outcome (12 studies, 187 patients), outcome of radiation therapy (21 studies, 273 patients), and medical therapy (15 studies, 72 patients). Conclusions: We endorse the definition of CTP-BADX/NS as radiological progression or new detection of a pituitary tumor on thin-section MRI. We recommend surveillance by MRI after 3 months and every 12 months for the first 3 years after BADX. Subsequently, we suggest clinical evaluation every 12 months and MRI at increasing intervals every 2–4 years (depending on ACTH and clinical parameters). We recommend pituitary surgery as first-line therapy in patients with CTP-BADX/NS. Surgery should be performed before extrasellar expansion of the tumor to obtain complete and long-term remission.
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- 2021
16. Chirurgie des incidentalomes surrénaliens unilateraux responsables de MACS : résultats de l’etude Chiracic sur l’hypertension
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Tabarin, A., Espiard, S., Deutschbein, T., Mouly, C., Di Dalmazi, G., Reznik, Y., Young, J., Desailloud, R., Goichot, B., Amar, L., Drui, D., Bertherat, J., Lefebvre, H., Strasburger, C., Castinetti, F., Laboureau-Soares, S., Mercky-Fraty, M., Galioot, A., Vantyghem, M.C., Fassnacht-Capeller, M., and Gosse, P.
- Abstract
Les incidentalomes corticosurrénaliens (ICS) responsables d’hypercortisolisme modéré et autonome (MACS) sont associés à une morbidité et mortalité cardiovasculaires accrues par rapport aux ICS non fonctionnels. La causalité du MACS et le bénéfice de l’exérèse des ICS demeure incertaine du fait des imperfections méthodologiques des études publiées.
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- 2024
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17. Metabolic syndrome in narcolepsy-cataplexy: P22
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POLI, F., PLAZZI, G., DI DALMAZI, G., and PAGOTTO, U.
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- 2008
18. Long-term outcome of primary bilateral macronodular adrenocortical hyperplasia after unilateral adrenalectomy
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Martin Reincke, Jérôme Bertherat, German Rubinstein, Andrea Osswald, Di Dalmazi G, Stephanie Zopp, Timo Deutschbein, Katrin Ritzel, Marcus Quinkler, Felix Beuschlein, University of Zurich, and Reincke, Martin
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medicine.medical_specialty ,1303 Biochemistry ,business.industry ,Urology ,10265 Clinic for Endocrinology and Diabetology ,610 Medicine & health ,1308 Clinical Biochemistry ,2704 Biochemistry (medical) ,Outcome (game theory) ,Unilateral adrenalectomy ,Term (time) ,1310 Endocrinology ,2712 Endocrinology, Diabetes and Metabolism ,medicine ,business ,Adrenocortical hyperplasia - Published
- 2019
19. AN ITALIAN SURVEY OF COMPLIANCE WITH MAJOR GUIDELINES FOR L-THYROXINE OF PRIMARY HYPOTHYROIDISM.
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Vezzani, S, Giannetta, E, Altieri, B, Barbonetti, A, Bellastella, G, Certo, R, Cignarelli, A, Cinti, F, D'Andrea, S, Di Dalmazi, G, Frara, S, Garelli, S, Giuffrida, G, Maiorino, Mi, Mele, C, Mezza, T, Pani, Mg, Samà, Mt, Satta, C, Santi, D., Altieri B, Cinti F (ORCID:0000-0001-5170-7055), Mezza T (ORCID:0000-0001-5407-9576), Vezzani, S, Giannetta, E, Altieri, B, Barbonetti, A, Bellastella, G, Certo, R, Cignarelli, A, Cinti, F, D'Andrea, S, Di Dalmazi, G, Frara, S, Garelli, S, Giuffrida, G, Maiorino, Mi, Mele, C, Mezza, T, Pani, Mg, Samà, Mt, Satta, C, Santi, D., Altieri B, Cinti F (ORCID:0000-0001-5170-7055), and Mezza T (ORCID:0000-0001-5407-9576)
- Abstract
OBJECTIVE: The adherence by endocrinologists to guideline regarding levothyroxine (LT4) therapy and the compliance of patients may impact the management of hypothyroidism. The aim of this study was to compare the adherence of Italian endocrinologists to the ATA/AACE and ETA guidelines on the management of newly diagnosed primary hypothyroidism and to validate the Italian version of the Morisky-Green Medical Adherence Scale-8 (MMAS-8) questionnaire as applied to the evaluation of the adherence of patients with hypothyroidism to LT4 treatment. METHODS: This was an observational, longitudinal, multicenter, cohort study, involving 12 Italian Units of Endocrinology. RESULTS: The study enrolled 1,039 consecutive outpatients (mean age 48 years; 855 women, 184 men). The concordance of Italian endocrinologists with American Association of Clinical Endocrinologists/American Thyroid Association (AACE/ATA) and European Thyroid Association (ETA) recommendations was comparable (77.1% and 71.7%) and increased (86.7 and 88.6%) after the recommendations on LT4 dose were excluded, considering only the remaining recommendations on diagnosis, therapy, and follow-up. The MMAS-8 was filled out by 293 patients. The mean score was 6.71 with 23.9% low (score <6), 38.6% medium (6 to <8), 37.5% highly (= 8) adherers; the internal validation coefficient was 0.613. Highly adherent patients were not more likely to have good control of hypothyroidism compared with either medium (69% versus 72%, P = .878) or low (69% versus 43%, P = .861) adherers. CONCLUSION: Clinical management of hypothyroidism in Italy demonstrated an observance of international guidelines by Italian endocrinologists. Validation of the Italian version of the MMAS-8 questionnaire provides clinicians with a reliable and simple tool for assessing the adherence of patients to LT4 treatment. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; EDIPO = Endotrial
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- 2018
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20. Thyroid dysfunctions secondary to cancer immunotherapy
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Chalan, P., primary, Di Dalmazi, G., additional, Pani, F., additional, De Remigis, A., additional, Corsello, A., additional, and Caturegli, P., additional
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- 2017
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21. Recurrent somatic mutations in Ying Yang 1 (YY1) are found in a subgroup of sporadic insulinomas
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Lichtenauer, U, primary, Di Dalmazi, G, additional, Slater, E, additional, Wieland, T, additional, Kuebart, A, additional, Schmittfull, A, additional, Schwarzmayr, T, additional, Diener, S, additional, Reincke, M, additional, Meitinger, T, additional, Schott, M, additional, Fassnacht, M, additional, Bartsch, DK, additional, Strom, TM, additional, and Beuschlein, F, additional
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- 2015
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22. Adrenal function after adrenalectomy for subclinical and overt Cushing's syndrome: A systematic review of the literature
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Di Dalmazi, G, primary and Reincke, M, additional
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- 2014
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23. Body mass index-independent metabolic alterations in narcolepsy with cataplexy.
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Poli F, Plazzi G, Di Dalmazi G, Ribichini D, Vicennati V, Pizza F, Mignot E, Montagna P, Pasquali R, and Pagotto U
- Published
- 2009
24. Sleep quality and sex-related factors in adult patients with immune-mediated diabetes: a large cross-sectional study
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Claudio Bongiorno, Simona Moscatiello, Michele Baldari, Enrico Saudelli, Stefano Zucchini, Giulio Maltoni, Danilo Ribichini, Alessia Bruco, Valentina Lo Preiato, Gilberto Laffi, Uberto Pagotto, Guido Di Dalmazi, Bongiorno C., Moscatiello S., Baldari M., Saudelli E., Zucchini S., Maltoni G., Ribichini D., Bruco A., Lo Preiato V., Laffi G., Pagotto U., and Di Dalmazi G.
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Endocrinology ,Type 1 diabetes ,Endocrinology, Diabetes and Metabolism ,Pittsburgh Sleep Quality Index ,Internal Medicine ,Autoimmune diabete ,Sex ,General Medicine ,Sleep quality ,Sleep - Abstract
Aim To analyze sleep quality and its relationships with clinical and biochemical features in a large cohort of adults with autoimmune diabetes. Methods We administered to 553 patients with autoimmune diabetes the questionnaires: Pittsburgh Sleep Quality Index (PSQI), diabetes distress scale, diabetes-related quality of life and diabetes treatment satisfaction questionnaire. We excluded patients with missing HbA1c ± 4 months from PSQI administration or incorrect PSQI compilation (n = 110). Results Altered sleep quality was recorded in 142/443 subjects (32%), insufficient total sleep time in 177/443 (40%). The altered sleep quality group had higher HbA1c (median 56 mmol/mol [interquartile range-IQR 49–62] vs 59 [IQR 52–68]; P P 53 mmol/mol (74.6% vs 62.8%; P = 0.014). Diabetes duration (P = 0.63), type of insulin delivery (P = 0.48) and glucose monitoring (P = 0.35) were uninfluential. Patients with altered sleep quality showed higher prevalence of autoimmune (42 vs 28%; P = 0.005) and mental diseases (12 vs 4%; P = 0.002); there were greater emotional distress, and lower quality of life and treatment satisfaction (P Conclusion One-third of the patients with autoimmune diabetes showed altered sleep quality, which associates with worse glycemic control, and autoimmune and mental disorders, with sex-specific differences.
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- 2023
25. Development and validation of a preoperative 'difficulty score' for laparoscopic transabdominal adrenalectomy: a multicenter retrospective study
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Alessandro M. Paganini, Andrea Balla, Carlo Ingaldi, Guido A. M. Tiberio, Giovanni Casole, Silvia Quaresima, Riccardo Casadei, Claudio Ricci, Zeno Ballarini, Marie Sophie Alfano, Guido Di Dalmazi, Laura Alberici, Giovanni Lezoche, Francesco Minni, Monica Ortenzi, Saverio Selva, Pietro Ursi, Mario Guerrieri, Alberici L., Paganini A.M., Ricci C., Balla A., Ballarini Z., Ortenzi M., Casole G., Quaresima S., Di Dalmazi G., Ursi P., Alfano M.S., Selva S., Casadei R., Ingaldi C., Lezoche G., Guerrieri M., Minni F., and Tiberio G.A.M.
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medicine.medical_specialty ,medicine.medical_treatment ,Operative Time ,Population ,Adrenal Gland Neoplasms ,Laparoscopic adrenalectomy ,Difficulty score ,Logistic regression ,Cohort Studies ,Postoperative Complications ,Internal medicine ,laparoscopic adrenalectomy ,postoperative complications ,Humans ,Medicine ,education ,Retrospective Studies ,education.field_of_study ,business.industry ,Adrenalectomy ,Area under the curve ,Retrospective cohort study ,Odds ratio ,Cohort ,Laparoscopy ,Surgery ,business ,Abdominal surgery - Abstract
Background A difficulty score for laparoscopic adrenalectomy (LA) is lacking in the literature. A retrospective cohort study was designed to develop a preoperative “difficulty score” for LA. Methods A multicenter study was conducted involving four Italian tertiary centers for adrenal disease. The population was randomly divided into two subsets: training group and validation one. A multicenter study was undertaken, including 964 patients. Patient, adrenal lesion, surgeon’s characteristics, and the type of procedure were studied as potential predictors of target events. The operative time (pOT), conversion rate (cLA), or both were used as indicators of the difficulty in three multivariate models. All models were developed in a training cohort (70% of the sample) and validated using 30% of patients. For all models, the ability to predict complicated postoperative course was reported describing the area under the curve (AUCs). Logistic regression, reporting odds ratio (OR) with p-value, was used. Results In model A, gender (OR 2.04, p = 0.001), BMI (OR 1.07, p = 0.002), previous surgery (OR 1.29, p = 0.048), site (OR 21.8, p p = 0.002), cumulative sum of procedures (OR 0.99, p p p = 0.015) increased the pOT. In model B, ASA (OR 2.86, p = 0.001), lesion size (OR 1.20, p = 0.005), and extended resection (OR 8.85, p = 0.007) increased the cLA risk. Model C had similar results to model A. All scores obtained predicted the target events in validation cohort (OR 1.99, p p = 0.007; OR 1.70, p Conclusion A difficulty score based on both pOT and cLA (Model C) was developed using 70% of the sample. The score was validated using a second cohort. Finally, the score was tested, and its results are able to predict a complicated postoperative course.
- Published
- 2021
26. The changing face of drug-induced adrenal insufficiency in the food and drug administration adverse event reporting system
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Emanuel Raschi, Michele Fusaroli, Francesco Massari, Veronica Mollica, Andrea Repaci, Andrea Ardizzoni, Elisabetta Poluzzi, Uberto Pagotto, Guido Di Dalmazi, Raschi E., Fusaroli M., Massari F., Mollica V., Repaci A., Ardizzoni A., Poluzzi E., Pagotto U., and Di Dalmazi G.
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United State ,Drug-Related Side Effects and Adverse Reactions ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,immune checkpoint inhibitor ,Biochemistry ,checkpoint ,Endocrinology ,Antineoplastic Agents, Immunological ,Retrospective Studie ,cancer ,Adverse Drug Reaction Reporting Systems ,Humans ,Retrospective Studies ,withdrawal ,United States Food and Drug Administration ,FAERS ,iatrogenic ,Biochemistry (medical) ,Antibodies, Monoclonal ,United States ,drug-induced ,glucocorticoid ,Adverse Drug Reaction Reporting System ,FDA ,Human ,Adrenal Insufficiency - Abstract
Context Adrenal insufficiency (AI) is a life-threatening condition complicating heterogeneous disorders across various disciplines, with challenging diagnosis and a notable drug-induced component. Objective This work aimed to describe the spectrum of drug-induced AI through adverse drug event reports received by the US Food and Drug Administration (FDA). Methods A retrospective disproportionality analysis reporting trends of drug-induced AI was conducted on the FDA Adverse Event Reporting System (FAERS) (> 15 000 000 reports since 2004). AE reports were extracted from FAERS over the past 2 decades. Interventions included cases containing any of the preferred terms in the Medical Dictionary for Regulatory Activities describing AI, and signals of disproportionate reporting for drugs recorded in 10 or more cases as primary suspect. Results We identified 8496 cases of AI: 97.5% serious, 41.1% requiring hospitalization. AI showed an exponential increase throughout the years, with 5282 (62.2%) cases in 2015 to 2020. We identified 56 compounds associated with substantial disproportionality: glucocorticoids (N = 1971), monoclonal antibodies (N = 1644, of which N = 1330 were associated with immune checkpoint inhibitors—ICIs), hormone therapy (N = 291), anti-infectives (N = 252), drugs for hypercortisolism or adrenocortical cancer diagnosis/treatment (N = 169), and protein kinase inhibitors (N = 138). Cases of AI by glucocorticoids were stable in each 5-year period (22%-27%), whereas those by monoclonal antibodies, largely ICIs, peaked from 13% in 2010 to 2015 to 33% in 2015 to 2020. Conclusion We provide a comprehensive insight into the evolution of drug-induced AI, highlighting the heterogeneous spectrum of culprit drug classes and the emerging increased reporting of ICIs. We claim for the urgent identification of predictive factors for drug-induced AI, and the establishment of screening and educational protocols for patients and caregivers.
- Published
- 2022
27. New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study
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A. Gambineri, E. Scarano, P. Rucci, A. Perri, F. Tamburrino, P. Altieri, F. Corzani, C. Cecchetti, P. Dionese, E. Belardinelli, D. Ibarra-Gasparini, S. Menabò, V. Vicennati, A. Repaci, G. di Dalmazi, C. Pelusi, G. Zavatta, A. Virdi, I. Neri, F. Fanelli, L. Mazzanti, U. Pagotto, Gambineri, A, Scarano, E, Rucci, P, Perri, A, Tamburrino, F, Altieri, P, Corzani, F, Cecchetti, C, Dionese, P, Belardinelli, E, Ibarra-Gasparini, D, Menabò, S, Vicennati, V, Repaci, A, di Dalmazi, G, Pelusi, C, Zavatta, G, Virdi, A, Neri, I, Fanelli, F, Mazzanti, L, and Pagotto, U
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Adult ,Endocrinology, Diabetes and Metabolism ,Osteoporosi ,Turner Syndrome ,Cardiovascular event ,Type 2 diabete ,Autoimmune Diseases ,Cohort Studies ,Young Adult ,Endocrinology ,Diabetes Mellitus, Type 2 ,Neoplasms ,Neoplasm ,Humans ,Cohort Studie ,Cancer ,Human - Abstract
Purpose Many questions concerning Turner syndrome (TS) remain unresolved, such as the long-term complications and, therefore, the optimal care setting for adults. The primary aim of this long-term cohort study was to estimate the incidence of comorbid conditions along the life course. Methods A total of 160 Italian patients with TS diagnosed from 1967 to 2010 were regularly and structurally monitored from the diagnosis to December 2019 at the University Hospital of Bologna using a structured multidisciplinary monitoring protocol. Results The study cohort was followed up for a median of 27 years (IQR 12–42). Autoimmune diseases were the comorbid condition with the highest incidence (61.2%), followed by osteoporosis and hypertension (23.8%), type 2 diabetes (16.2%) and tumours (15.1%). Median age of onset ranged from 22 years for autoimmune diseases to 39 years for type 2 diabetes. Malignant tumours were the most prominent type of neoplasm, with a cumulative incidence of 11.9%. Papillary thyroid carcinoma was the most common form of cancer, followed by skin cancer and cancer of the central nervous system. Only one major cardiovascular event (acute aortic dissection) was observed during follow-up. No cases of ischaemic heart disease, heart failure, stroke or death were recorded. Conclusions This cohort study confirms the need for continuous, structured and multidisciplinary lifelong monitoring of TS, thus ensuring the early diagnosis of important comorbid conditions, including cancer, and their appropriate and timely treatment. In addition, these data highlight the need for the increased surveillance of specific types of cancer in TS, including thyroid carcinoma.
- Published
- 2022
28. Impact of age, body weight and metabolic risk factors on steroid reference intervals in men
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Uberto Pagotto, Margherita Baccini, Alessia Fazzini, Flaminia Fanelli, Marco Mezzullo, Alessandra Gambineri, Carla Pelusi, Valentina Vicennati, Guido Di Dalmazi, Andrea Repaci, Mezzullo M., Di Dalmazi G., Fazzini A., Baccini M., Repaci A., Gambineri A., Vicennati V., Pelusi C., Pagotto U., and Fanelli F.
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Male ,Hydrocortisone ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Body Mass Index ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Risk Factors ,Tandem Mass Spectrometry ,Corticosterone ,Age Factor ,Multivariate Analysi ,Testosterone ,2. Zero hunger ,17-alpha-Hydroxyprogesterone ,Age Factors ,Dihydrotestosterone ,General Medicine ,030220 oncology & carcinogenesis ,Human ,medicine.drug ,medicine.medical_specialty ,Cortodoxone ,Dehydroepiandrosterone ,030209 endocrinology & metabolism ,Estrone ,03 medical and health sciences ,Insulin resistance ,Internal medicine ,medicine ,Humans ,Obesity ,Cross-Sectional Studie ,business.industry ,Risk Factor ,Insulin ,Body Weight ,Androstenedione ,Overweight ,medicine.disease ,Cross-Sectional Studies ,chemistry ,Multivariate Analysis ,business ,Chromatography, Liquid - Abstract
Objective To evaluate the independent impact of age, obesity and metabolic risk factors on 13 circulating steroid levels; to generate reference intervals for adult men. Design Cross-sectional study. Methods Three hundred and fifteen adults, drug-free and apparently healthy men underwent clinical and biochemical evaluation. Thirteen steroids were measured by LC-MS/MS and compared among men with increasing BMI. Moreover, the independent impact of age, BMI and metabolic parameters on steroid levels was estimated. Upper and lower reference limits were generated in steroid-specific reference sub-cohorts and compared with dysmetabolic sub-cohorts. Results We observed lower steroid precursors and testosterone and increase in estrone levels in men with higher BMI ranges. By multivariate analysis, 17-hydroxyprogesterone and dihydrotestosterone decreased with BMI, while cortisol decreased with waist circumference. Estrone increased with BMI and systolic blood pressure. Testosterone decreased with worsening insulin resistance. 17-hydroxypregnenolone and corticosterone decreased with increasing total/HDL-cholesterol ratio. Age-related reference intervals were estimated for 17-hydroxypregnenolone, DHEA, 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol, cortisol and androstenedione, while age-independent reference intervals were estimated for progesterone, 11-deoxycorticosterone, testosterone, dihydrotestosterone, estrone and estradiol. Testosterone lower limit was 2.29 nmol/L lower (P = 0.007) in insulin resistant vs insulin sensitive men. Furthermore, the upper limits for dihydrotestosterone (−0.34 nmol/L, P = 0.045), cortisol (−87 nmol/L, P = 0.045–0.002) and corticosterone (−10.1 nmol/L, P = 0.048–0.016) were lower in overweight/obese, in abdominal obese and in dyslipidaemic subjects compared to reference sub-cohorts, respectively. Conclusions Obesity and mild unmedicated metabolic risk factors alter the circulating steroid profile and bias the estimation of reference limits for testosterone, dihydrotestosterone, cortisol and corticosterone. Applying age-dependent reference intervals is mandatory for steroid precursors and corticosteroids.
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- 2020
29. Computerized tomography texture analysis of pheochromocytoma: relationship with hormonal and histopathological data
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A. De Leo, G. Vara, A. Paccapelo, C. Balacchi, V. Vicennati, L. Tucci, U. Pagotto, S. Selva, C. Ricci, L. Alberici, F. Minni, C. Nanni, F. Ambrosi, D. Santini, R. Golfieri, G. Di Dalmazi, C. Mosconi, De Leo, A, Vara, G, Paccapelo, A, Balacchi, C, Vicennati, V, Tucci, L, Pagotto, U, Selva, S, Ricci, C, Alberici, L, Minni, F, Nanni, C, Ambrosi, F, Santini, D, Golfieri, R, Di Dalmazi, G, and Mosconi, C
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Endocrinology, Diabetes and Metabolism ,Adrenal Gland Neoplasms ,Pheochromocytoma ,Adrenal Gland Neoplasm ,Paraganglioma ,Endocrinology ,Pheocromocytoma ,Retrospective Studie ,Humans ,Adrenal ,Radiomic ,Tomography, X-Ray Computed ,Computed tomography ,Texture analysi ,Metanephrine ,Retrospective Studies ,Human - Abstract
Objectives Pheochromocytomas are rare tumors which can present with heterogeneous secretion profiles, clinical manifestations, and radiologic appearance. Under a histopathological point of view, they can be characterized as more or less aggressive with the Pheochromocytoma of the Adrenal gland Scaled Score (PASS) and the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) score. The aim of this study is to analyze the texture analysis characteristics of pheochromocytoma and identify whether the texture analysis can yield information aiding in the diagnosis and the characterization of those tumors. Methods Radiological, biochemical, and histopathological data regarding 30 consecutive patients with histologically confirmed pheochromocytoma were analyzed. Images obtained in the unenhanced, late arterial, venous, and delayed phases were used for the texture analysis. Results Urinary epinephrine and metanephrine levels showed a significant correlation (R2 = 0.946; R2 = 699) in the multivariate linear model with texture features, as well as Ki-67 (R2 = 0.397), PASS score (R2 = 0.182), GAPP score (R2 = 0.705), and cellularity showed a significant correlation (R2 = 0.389). The cluster analysis based on radiomic features resulted in 2 clusters, with significative differences in terms of systolic and diastolic blood pressure values at the time of diagnosis (p = 0.025), GAPP score (4 vs 6, p = 0.05), histological pattern (1–2, p = 0.039), and comedonecrosis (0% vs 50%, p = 0.013). Conclusion In conclusion, our study provides the proof of concept for the use of texture analysis on contrast-enhanced CT images as a noninvasive, quantitative tool for helping in the characterization of the clinical, biochemical, and histopathological features of pheochromocytoma.
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- 2022
30. Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System
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Emanuel Raschi, Michele Fusaroli, Valentina Giunchi, Andrea Repaci, Carla Pelusi, Veronica Mollica, Francesco Massari, Andrea Ardizzoni, Elisabetta Poluzzi, Uberto Pagotto, Guido Di Dalmazi, Raschi E., Fusaroli M., Giunchi V., Repaci A., Pelusi C., Mollica V., Massari F., Ardizzoni A., Poluzzi E., Pagotto U., and Di Dalmazi G.
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Cancer Research ,VEGFR ,adrenal insufficiency ,pharmacovigilance ,disproportionality analysis ,FAERS ,Oncology ,disproportionality analysi - Abstract
Background: We described clinical features of adrenal insufficiency (AI) reported with tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Reports of AI recorded in FAERS (January 2004–March 2022) were identified through the high-level term “adrenal cortical hypofunctions”. Demographic and clinical features were inspected, and disproportionality signals were detected through the Reporting Odds Ratio (ROR) and Information Component (IC) with relevant 95% confidence/credibility interval (CI), using different comparators and adjusting the ROR for co-reported corticosteroids and immune checkpoint inhibitors (ICIs). Results: Out of 147,153 reports with VEGFR-TKIs, 314 cases of AI were retained, mostly of which were serious (97.1%; hospitalization recorded in 44.9%). In a combination regimen with ICIs (43% of cases), VEGFR-TKIs were discontinued in 52.2% of the cases (26% as monotherapy). The median time to onset was 72 days (IQR = 14–201; calculated for 189 cases). A robust disproportionality signal emerged, also in comparison with other anticancer drugs (ROR = 2.71, 95%CI = 2.42–3.04; IC = 0.25, 95%CI = 0.07–0.39). Cabozantinib, sunitinib and axitinib generated robust disproportionality even after ROR adjustment. Conclusions: We call pharmacologists, internists, oncologists and endocrinologists to raise awareness of serious AI with VEGFR-TKIs, and to develop dedicated guidelines, especially for combination regimens with immunotherapy.
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- 2022
31. DNA Methylation of steroidogenic enzymes in benign adrenocortical tumors: New insights in aldosterone-producing Adenomas
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Guido Di Dalmazi, Valentina Vicennati, Uberto Pagotto, Francesca Ambrosi, Beatrice Rubin, Valeria Maffeis, Francesco Fallo, Sofia Asioli, Luca Morandi, Donatella Santini, Catia Pilon, Ambrogio Fassina, Antonio De Leo, Di Dalmazi G., Morandi L., Rubin B., Pilon C., Asioli S., Vicennati V., De Leo A., Ambrosi F., Santini D., Pagotto U., Maffeis V., Fassina A., and Fallo F.
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Male ,0301 basic medicine ,steroidogenesis ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Biochemistry ,law.invention ,Cohort Studies ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,law ,Gonadal Steroid Hormones ,Aldosterone ,Polymerase chain reaction ,Adrenal cortex ,Chemistry ,APCC ,Methylation ,Middle Aged ,Enzymes ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,CYP17A1 ,030220 oncology & carcinogenesis ,Adrenocortical Adenoma ,DNA methylation ,Female ,Metabolic Networks and Pathways ,Adult ,Cortisol secretion ,medicine.medical_specialty ,Biology ,Gene Expression Regulation, Enzymologic ,03 medical and health sciences ,Steroidogenic enzymes ,Internal medicine ,medicine ,Humans ,Aged ,Biochemistry (medical) ,DNA Methylation ,APA ,Adrenal Cortex Neoplasms ,CYP11B2 ,CYP11B1 ,Cross-Sectional Studies ,030104 developmental biology ,HSD3B1 ,HSD3B2 ,Cancer research ,Steroidogenesis ,methylation - Abstract
Context DNA methylation has been identified among putative regulatory mechanisms for CYP11B2 expression in primary aldosteronism. Objective The objective of this work is to investigate DNA methylation and expression of genes encoding steroidogenic enzymes in benign adrenocortical tumors. Design and Setting This cross-sectional study took place at university hospitals. Patients We collected fresh-frozen tissues from patients with benign adrenocortical adenomas (n = 48) (nonfunctioning n = 9, autonomous cortisol secretion n = 9, Cushing syndrome n = 17, aldosterone-producing [APA] n = 13) and adrenal cortex adjacent to APA (n = 12). We collected formalin-fixed, paraffin-embedded (FFPE) specimens of paired APA and concurrent aldosterone-producing cell clusters (APCCs) (n = 6). Intervention DNA methylation levels were evaluated by quantitative bisulfite next-generation sequencing in fresh-frozen tissues (CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD3B1, HSD3B2, NR5A1, STAR, and TSPO) and FFPE APA/APCC paired samples (CYP11B2). CYP11B1, CYP11B2, CYP17, CYP21, and STAR gene expressions were examined by quantitative real-time polymerase chain reaction. Main Outcome Measure The main outcome measure was DNA methylation. Results CYP11B2 methylation levels were significantly lower in APA than in other adrenal tissues (P < .001). Methylation levels of the remaining genes were comparable among groups. Overall, CYP11B2 expression and DNA methylation were negatively correlated (ρ = –0.379; P = .003). In FFPE-paired APA/APCC samples, CYP11B2 methylation level was significantly lower in APA than in concurrent APCCs (P = .028). Conclusions DNA methylation plays a regulatory role for CYP11B2 expression and may contribute to aldosterone hypersecretion in APA. Lower CYP11B2 methylation levels in APA than in APCCs may suggest an APCC-to-APA switch via progressive CYP11B2 demethylation. Conversely, DNA methylation seems not to be relevant in regulating the expression of genes encoding steroidogenic enzymes other than CYP11B2.
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- 2021
32. Identifying New Potential Biomarkers in Adrenocortical Tumors Based on mRNA Expression Data Using Machine Learning
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Marquardt, André, Landwehr, Laura-Sophie, Ronchi, Cristina L., Dalmazi, Guido di, Riester, Anna, Kollmannsberger, Philip, Altieri, Barbara, Fassnacht, Martin, Sbiera, Silviu, Marquardt A., Landwehr L.-S., Ronchi C.L., Di Dalmazi G., Riester A., Kollmannsberger P., Altieri B., Fassnacht M., and Sbiera S.
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machine learning ,nervous system ,In silico analysi ,bioinformatic clustering ,adrenocortical carcinoma ,in silico analysis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,biomarker prediction ,ddc:610 ,behavioral disciplines and activities ,psychological phenomena and processes ,RC254-282 ,Article - Abstract
Simple Summary Using a visual-based clustering method on the TCGA RNA sequencing data of a large adrenocortical carcinoma (ACC) cohort, we were able to classify these tumors in two distinct clusters largely overlapping with previously identified ones. As previously shown, the identified clusters also correlated with patient survival. Applying the visual clustering method to a second dataset also including benign adrenocortical samples additionally revealed that one of the ACC clusters is more closely located to the benign samples, providing a possible explanation for the better survival of this ACC cluster. Furthermore, the subsequent use of machine learning identified new possible biomarker genes with prognostic potential for this rare disease, that are significantly differentially expressed in the different survival clusters and should be further evaluated. Abstract Adrenocortical carcinoma (ACC) is a rare disease, associated with poor survival. Several “multiple-omics” studies characterizing ACC on a molecular level identified two different clusters correlating with patient survival (C1A and C1B). We here used the publicly available transcriptome data from the TCGA-ACC dataset (n = 79), applying machine learning (ML) methods to classify the ACC based on expression pattern in an unbiased manner. UMAP (uniform manifold approximation and projection)-based clustering resulted in two distinct groups, ACC-UMAP1 and ACC-UMAP2, that largely overlap with clusters C1B and C1A, respectively. However, subsequent use of random-forest-based learning revealed a set of new possible marker genes showing significant differential expression in the described clusters (e.g., SOAT1, EIF2A1). For validation purposes, we used a secondary dataset based on a previous study from our group, consisting of 4 normal adrenal glands and 52 benign and 7 malignant tumor samples. The results largely confirmed those obtained for the TCGA-ACC cohort. In addition, the ENSAT dataset showed a correlation between benign adrenocortical tumors and the good prognosis ACC cluster ACC-UMAP1/C1B. In conclusion, the use of ML approaches re-identified and redefined known prognostic ACC subgroups. On the other hand, the subsequent use of random-forest-based learning identified new possible prognostic marker genes for ACC.
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- 2021
33. Association Between Aldosterone and Parathyroid Hormone Levels in Patients With Adrenocortical Tumors
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Rita Golfieri, Valentina Vicennati, Claudio Borghi, Guido Di Dalmazi, Caterina Balacchi, Paola Altieri, Cristina Mosconi, Carla Pelusi, Jennifer Malandra, Eugenio Roberto Cosentino, Uberto Pagotto, Ilaria Di Cintio, Guido Zavatta, Zavatta G., Di Dalmazi G., Altieri P., Pelusi C., Golfieri R., Mosconi C., Balacchi C., Borghi C., Cosentino E.R., Di Cintio I., Malandra J., Pagotto U., and Vicennati V.
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Parathyroid hormone ,Adrenal Cortex Neoplasm ,hyperparathyroidism ,chemistry.chemical_compound ,Endocrinology ,Primary aldosteronism ,Mineralocorticoid receptor ,Retrospective Studie ,Internal medicine ,Hyperaldosteronism ,medicine ,Vitamin D and neurology ,Humans ,Vitamin D ,Aldosterone ,Retrospective Studies ,primary hyperaldosteronism ,Hyperparathyroidism ,Aldosterone-to-renin ratio ,business.industry ,Adrenalectomy ,General Medicine ,medicine.disease ,Adrenal Cortex Neoplasms ,chemistry ,Parathyroid Hormone ,adrenocortical tumor ,Calcium ,business ,hormones, hormone substitutes, and hormone antagonists ,Human - Abstract
Objective: Patients with primary aldosteronism (PA) can present with high PTH levels and negative calcium balance, with some studies speculating that aldosterone could directly stimulate PTH secretion. Either adrenalectomy or mineralocorticoid receptor blockers could reduce PTH levels in patients with PA. The aim of this study was to assess the relationship between aldosterone levels and parathyroid hormone (PTH)-vitamin D-calcium axis in a cohort of patients with PA, compared with patients with nonsecreting adrenocortical tumors in conditions of vitamin D sufficiency. Methods: We enrolled a series of 243 patients retrospectively, of whom 66 had PA and 177 had nonsecreting adrenal tumors, and selected those with full mineral metabolism evaluation and 25(OH) vitamin D levels >20 ng/mL at the time of initial endocrine screening. The final cohort was composed of 26 patients with PA and 39 patients, used as controls, with nonsecreting adrenal tumors. The relationships between aldosterone, PTH levels, and biochemistries of mineral metabolism were assessed. Results: Aldosterone was positively associated with PTH levels (r = 0.260, P < .05) in the whole cohort and in the PA cohort alone (r = 0.450; P = .02). In the multivariate analysis, both aldosterone concentrations and urinary calcium excretion were significantly related to PTH levels, with no effect of 25(OH) vitamin D or other parameters of bone metabolism. Conclusion: PTH level is associated with aldosterone, probably independent of 25(OH) vitamin D levels and urinary calcium. Whether aldosterone interacts directly with the parathyroid glands remains to be established.
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- 2021
34. Long-Term Outcome of Primary Bilateral Macronodular Adrenocortical Hyperplasia After Unilateral Adrenalectomy
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Felix Beuschlein, Martin Reincke, Stephanie Zopp, Guido Di Dalmazi, Jérôme Bertherat, German Rubinstein, Andrea Osswald, Timo Deutschbein, Katrin Ritzel, Marcus Quinkler, Osswald A., Quinkler M., Di Dalmazi G., Deutschbein T., Rubinstein G., Ritzel K., Zopp S., Bertherat J., Beuschlein F., and Reincke M.
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medicine.medical_specialty ,Adenoma ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,030209 endocrinology & metabolism ,Context (language use) ,Biochemistry ,03 medical and health sciences ,Cushing syndrome ,0302 clinical medicine ,Endocrinology ,Quality of life ,Internal medicine ,medicine ,business.industry ,PBMAH, primary bilateral macronodular adrenocortical hyperplasia, adrenalectomy, adrenal Cushing’s syndrome, hypercortisolism ,Adrenalectomy ,Biochemistry (medical) ,Adrenal crisis ,Retrospective cohort study ,Hyperplasia ,medicine.disease ,Surgery ,030220 oncology & carcinogenesis ,medicine.symptom ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Context Unilateral adrenalectomy has been proposed in selected patients with primary bilateral macronodular adrenocortical hyperplasia (PBMAH), but its long-term outcome is unclear. Objective The aim of this study was to analyze long-term clinical and biochemical outcomes of unilateral adrenalectomy vs bilateral adrenalectomy in patients with PBMAH in comparison with the outcome of cortisol-producing adenoma (CPA) treated with unilateral adrenalectomy. Design Retrospective observational study in three German and one Italian academic tertiary care center. Patients and methods Twenty-five patients with PBMAH after unilateral adrenalectomy (unilat-ADX-PBMAH), nine patients with PBMAH and bilateral adrenalectomy (bilat-ADX-PBMAH), and 39 patients with CPA and unilateral adrenalectomy (unilat-ADX-CPA) were included. Results Baseline clinical and biochemical parameters were comparable in patients with unilat-ADX-PBMAH, bilat-ADX-PBMAH, and unilat-ADX-CPA. Directly after surgery, 84% of the patients with unilat-ADX-PBMAH experienced initial remission of Cushing syndrome (CS). In contrast, at last follow-up (median, 50 months), 32% of the patients with unilat-ADX-PBMAH were biochemically controlled compared with nearly all patients in the other two groups (P = 0.000). Adrenalectomy of the contralateral side had to be performed in 12% of the initial patients with unilat-ADX-PBMAH. Three of 20 patients with unilat-ADX-PBMAH (15%) died during follow-up, presumably of CS-related causes; no deaths occurred in the other two groups (P = 0.008). Deaths occurred exclusively in patients who were not biochemically controlled after unilateral ADX. Conclusions Our data suggest that unilateral adrenalectomy of patients with PBMAH leads to clinical remission and a lower incidence of adrenal crisis but in less sufficient biochemical control of hypercortisolism, potentially leading to higher mortality.
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- 2019
35. Somatic PRKACA Mutations: Association With Transition From Pituitary-Dependent to Adrenal-Dependent Cushing Syndrome
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Kerstin Bathon, Guido Di Dalmazi, Ad R. M. M. Hermus, Henri J L M Timmers, Giorgio Arnaldi, Felix Beuschlein, Davide Calebiro, Marina Scarpelli, Martin Reincke, Benno Küsters, Di Dalmazi G., Timmers H.J.L.M., Arnaldi G., Kusters B., Scarpelli M., Bathon K., Calebiro D., Beuschlein F., Hermus A., and Reincke M.
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Adult ,0301 basic medicine ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Clinical Biochemistry ,030209 endocrinology & metabolism ,Context (language use) ,Biochemistry ,03 medical and health sciences ,Cushing syndrome ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Adrenal Glands ,medicine ,Humans ,Missense mutation ,Pituitary ACTH Hypersecretion ,Cushing Syndrome ,Cushing´s disease, PRKACA, PKA, macronodular hyperplasia, transition ,Cyclic AMP-Dependent Protein Kinase Catalytic Subunits ,Adrenal cortex ,business.industry ,Biochemistry (medical) ,Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16] ,Cushing's disease ,Hyperplasia ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,medicine.disease ,Cushing Disease ,PRKACA ,Cross-Sectional Studies ,030104 developmental biology ,medicine.anatomical_structure ,Female ,business - Abstract
ContextProlonged adrenal stimulation by corticotropin, as in long-standing Cushing disease (CD), leads to diffuse to nodular hyperplasia. Adrenal functional autonomy has been described in a subset of patients with CD, leading to the hypothesis of transition from ACTH-dependent to ACTH-independent hypercortisolism.ObjectiveWith the consideration that the catalytic α subunit of protein kinase A (PKA; PRKACA) somatic mutations are the most common finding in adrenal adenomas associated with ACTH-independent Cushing syndrome, our aim was to analyze PRKACA mutations in adrenals of patients with persistent/long-standing CD.DesignCross-sectional.SettingUniversity hospital.PatientsTwo patients with long-standing CD and suspicion of coexistence of autonomous adrenal hyperfunction, according to pre and postoperative evaluations, were selected for this study, following an intensive literature search and patient-chart reviewing.InterventionClinical data were analyzed. DNA was extracted from adrenal tissue for PRKACA sequencing. PKA activity was assayed.Main Outcome MeasurePRKACA somatic mutations.ResultsBoth patients showed mutations of PRKACA in the macronodule in the context of micronodular adrenal hyperplasia. One patient harbored the previously described p.Leu206Arg substitution, whereas a p.Ser213Arg missense variation was detected in the adrenal nodule of the second patient. No mutations were detected in the adjacent adrenal cortex of the second patient. In silico analysis predicts that p.Ser213Arg can interfere with the interaction between the regulatory and catalytic subunits of PKA.ConclusionsOur study shows that PRKACA somatic mutations can be found in adrenal nodules of patients with CD. These genetic alterations could represent a possible mechanism underlying adrenal nodule formation and autonomous cortisol hyperproduction in a subgroup of patients with long-standing CD.
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- 2019
36. Corticotroph tumor progression after bilateral adrenalectomy (Nelson’s syndrome): systematic review and expert consensus recommendations
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Luis G. Perez-Rivas, Atanaska Elenkova, Martin Reincke, Marily Theodoropoulou, German Rubinstein, Elisabeth F.C. van Rossum, Olivier Chabre, Ashley B. Grossman, Mario Detomas, Niki Karavitaki, Katrin Ritzel, André Lacroix, Irina Bancos, Elena Valassi, Thierry Brue, Marco Losa, Edward R. Laws, Jochen Schopohl, Masanori Murakami, Andrea Daniele, Juergen Honegger, Adriana Albani, Sabina Zacharieva, Michael Buchfelder, Constantine A. Stratakis, Rosario Pivonello, Guillaume Assié, Anthony P. Heaney, Francesca Pecori Giraldi, Celso E. Gomez-Sanchez, Filippo Ceccato, William E. Rainey, John Newell-Price, Guido Di Dalmazi, James W. Findling, Silviu Sbiera, Ludwig-Maximilians-Universität München (LMU), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mayo Clinic [Rochester], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Marseille Maladies Rares (MarMaRa), Aix Marseille Université (AMU), Service d'endocrinologie, diabète, maladies métaboliques [Hôpital de la Conception - APHM], Universitätsklinikum Erlangen [Erlangen], Centre Hospitalier Universitaire [Grenoble] (CHU), Università degli Studi di Padova = University of Padua (Unipd), University of Würzburg = Universität Würzburg, University of Bologna/Università di Bologna, Medical University of Sofia [Bulgarie], Medical College of Wisconsin [Milwaukee] (MCW), Queen Mary University of London (QMUL), University of Mississippi Medical Center (UMMC), School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), University of Tübingen, University of Birmingham [Birmingham], Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, University Hospitals Birmingham [Birmingham, Royaume-Uni], Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Harvard Medical School [Boston] (HMS), IRCCS San Raffaele Scientific Institute [Milan, Italie], Tokyo Medical and Dental University [Japan] (TMDU), University of Sheffield [Sheffield], Università degli Studi di Milano = University of Milan (UNIMI), University of Naples Federico II = Università degli studi di Napoli Federico II, University of Michigan [Ann Arbor], University of Michigan System, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital de la Santa Creu i Sant Pau, Gall, Valérie, Internal Medicine, Reincke, M., Albani, A., Assie, G., Bancos, I., Brue, T., Buchfelder, M., Chabre, O., Ceccato, F., Daniele, A., Detomas, M., Dalmazi, G. D., Elenkova, A., Findling, J., Grossman, A. B., Gomez-Sanchez, C. E., Heaney, A. P., Honegger, J., Karavitaki, N., Lacroix, A., Laws, E. R., Losa, M., Murakami, M., Newell-Price, J., Giraldi, F. P., Perez-Rivas, L. G., Pivonello, R., Rainey, W. E., Sbiera, S., Schopohl, J., Stratakis, C. A., Theodoropoulou, M., van Rossum, E. F. C., Valassi, E., Zacharieva, S., Rubinstein, G., Ritzel, K., Reincke M., Albani A., Assie G., Bancos I., Brue T., Buchfelder M., Chabre O., Ceccato F., Daniele A., Detomas M., Di Dalmazi G., Elenkova A., Findling J., Grossman A.B., Gomez-Sanchez C.E., Heaney A.P., Honegger J., Karavitaki N., Lacroix A., Laws E.R., Losa M., Murakami M., Newell-Price J., Giraldi F.P., Perez-Rivas L.G., Pivonello R., Rainey W.E., Sbiera S., Schopohl J., Stratakis C.A., Theodoropoulou M., van Rossum E.F.C., Valassi E., Zacharieva S., Rubinstein G., and Ritzel K.
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Adenoma ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,030209 endocrinology & metabolism ,Radiosurgery ,Article ,Nelson Syndrome ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Humans ,Cumulative incidence ,[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,business.industry ,Pituitary tumors ,Nelson's syndrome ,Adrenalectomy ,General Medicine ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,medicine.disease ,Radiation therapy ,[SDV] Life Sciences [q-bio] ,ACTH-Secreting Pituitary Adenoma ,Tumor progression ,030220 oncology & carcinogenesis ,Radiological weapon ,Disease Progression ,Radiology ,business ,Complication ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Human - Abstract
Background Corticotroph tumor progression (CTP) leading to Nelson’s syndrome (NS) is a severe and difficult-to-treat complication subsequent to bilateral adrenalectomy (BADX) for Cushing’s disease. Its characteristics are not well described, and consensus recommendations for diagnosis and treatment are missing. Methods A systematic literature search was performed focusing on clinical studies and case series (≥5 patients). Definition, cumulative incidence, treatment and long-term outcomes of CTP/NS after BADX were analyzed using descriptive statistics. The results were presented and discussed at an interdisciplinary consensus workshop attended by international pituitary experts in Munich on October 28, 2018. Results Data covered definition and cumulative incidence (34 studies, 1275 patients), surgical outcome (12 studies, 187 patients), outcome of radiation therapy (21 studies, 273 patients), and medical therapy (15 studies, 72 patients). Conclusions We endorse the definition of CTP-BADX/NS as radiological progression or new detection of a pituitary tumor on thin-section MRI. We recommend surveillance by MRI after 3 months and every 12 months for the first 3 years after BADX. Subsequently, we suggest clinical evaluation every 12 months and MRI at increasing intervals every 2–4 years (depending on ACTH and clinical parameters). We recommend pituitary surgery as first-line therapy in patients with CTP-BADX/NS. Surgery should be performed before extrasellar expansion of the tumor to obtain complete and long-term remission. Conventional radiotherapy or stereotactic radiosurgery should be utilized as second-line treatment for remnant tumor tissue showing extrasellar extension
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- 2021
37. The learning curve for the second generation of laparoscopic surgeons: lesson learned from a large series of laparoscopic adrenalectomies
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Uberto Pagotto, Saverio Selva, Claudio Ricci, Valentina Vicennati, Riccardo Casadei, Laura Alberici, Guido Di Dalmazi, Carlo Ingaldi, Francesco Minni, Riccardo Turrini, Alberici L., Ricci C., Ingaldi C., Casadei R., Turrini R., Di Dalmazi G., Vicennati V., Pagotto U., Selva S., and Minni F.
- Subjects
medicine.medical_specialty ,Multivariate analysis ,education ,Operative Time ,Laparoscopic adrenalectomy ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Surgeons ,business.industry ,General surgery ,Large series ,Retrospective cohort study ,Adrenalectomy ,Stepwise regression ,Learning curve ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Surgery ,Laparoscopy ,business ,Body mass index ,Learning Curve ,Abdominal surgery - Abstract
Background: Laparoscopic adrenalectomy has a well-demonstrated learning curve in the first generation of laparoscopic surgeons. Data about the second generation of laparoscopic surgeons are lacking. Methods: In this retrospective observational study, data from patients undergoing laparoscopic adrenalectomy from 2000 to 2019 in a high-volume center were collected and analyzed. The cumulative sum of procedures of each surgeon and the operating time were evaluated. A multivariate analysis with backward stepwise logistic regression was carried out to define which factors influenced the operative time. Three surgeons performed the analyzed procedures: a senior surgeon who began his laparoscopic activity without receiving specific training or supervision and two young surgeons, who performed their procedures under the guidance of the “senior” experienced surgeon. The first 38 procedures of the three surgeons were then compared. Results: A total of 244 laparoscopic adrenalectomies were performed. Age, clinical diagnosis, side of the lesion, body mass index, comorbidities, Charlson index, American Society of Anaesthesiologists (ASA) score, and lower abdominal surgery were found to have no significant relationship with the operative time (p > 0.05). Gender, symptoms, previous upper abdominal surgery, size of the lesion, and cumulative sum of procedures were independent predictors of operative time. In the comparison between different surgeons, operative time resulted significantly longer for the senior (165min; 140–180) than for the two junior surgeons (137.5min; 115–160; p = 0.003 and 130min; 120–170; p = 0.001). Conclusions: The presence of a mentor in operative theater and specific training programs could be useful during the learning period. The cumulative sum of procedures related to the operative time represents a good parameter to measure the acquired expertise of a surgeon.
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- 2020
38. Obituary: Renato Pasquali (1946-2019)
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Andrea Repaci, Valentina Vicennati, Uberto Pagotto, Alessandra Gambineri, C. Pelusi, Paola Altieri, Flaminia Fanelli, Danilo Ribichini, G. Di Dalmazi, Silvia Garelli, Gambineri, A, Di Dalmazi, G, Fanelli, F, Altieri, P, Repaci, A, Garelli, S, Ribichini, D, Pelusi, C, Vicennati, V, and Pagotto, U
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Philosophy ,obituary ,Obituary ,Humanities - Abstract
n.a.
- Published
- 2020
39. Radiologically defined lipid-poor adrenal adenomas: histopathological characteristics
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Stefano Fanti, Donatella Santini, Valentina Vicennati, Francesco Minni, Caterina Balacchi, Cristina Mosconi, Saverio Selva, G. Di Dalmazi, Cristina Nanni, Uberto Pagotto, A. De Leo, Lorenzo Tucci, Guido Zavatta, Maria Abbondanza Pantaleo, Claudio Ceccarelli, Rita Golfieri, De Leo A., Mosconi C., Zavatta G., Tucci L., Nanni C., Selva S., Balacchi C., Ceccarelli C., Santini D., Pantaleo M.A., Minni F., Fanti S., Golfieri R., Pagotto U., Vicennati V., and Di Dalmazi G.
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Cortisol secretion ,Adenoma ,Adult ,Male ,medicine.medical_specialty ,Adrenal tumor ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Biopsy ,Adrenal Gland Neoplasms ,030209 endocrinology & metabolism ,Lipid-poor adenoma ,Gastroenterology ,Cohort Studies ,03 medical and health sciences ,Cushing syndrome ,0302 clinical medicine ,Endocrinology ,Primary aldosteronism ,Adrenocorticotropic Hormone ,Fluorodeoxyglucose F18 ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,In patient ,Borderline-malignant ,Cushing Syndrome ,Aged ,Retrospective Studies ,Adrenal oncocytoma ,Heterogeneous group ,drenal oncocytoma ,business.industry ,Adrenalectomy ,Middle Aged ,medicine.disease ,Lipid Metabolism ,Prognosis ,Contrast medium ,ACTH Syndrome, Ectopic ,Italy ,030220 oncology & carcinogenesis ,Positron-Emission Tomography ,Histopathology ,Female ,business ,Tomography, X-Ray Computed - Abstract
Background: Adrenal lipid-poor adenomas (LPA) are defined by high unenhanced density (≥ 10 HU), and absolute and relative contrast medium washout > 60% and > 40%, respectively, at computerized tomography (CT). To date, no thorough histopathological characterization has been performed in those frequent lesions (one-third of adrenal adenomas). Our aim was to analyze the histopathological characteristics of adrenal LPA. Methods: Patients with LPA (n = 57) were selected among consecutive subjects referred for an adrenal incidentaloma or ACTH-independent Cushing syndrome. FluoroDeoxyGlucose-Positron Emission Tomography (FDG-PET) was performed in 37 patients. In patients treated by adrenalectomy (n = 17), Weiss score and Lin–Weiss–Bisceglia score (in tumors composed entirely or predominantly of oncocytes) were calculated. Results: Radiological parameters did not differ among patients with ACTH-independent Cushing syndrome (n = 6) and those with adrenal incidentalomas associated with primary aldosteronism (n = 2), autonomous cortisol secretion (n = 14), or non-functioning (n = 35). Patients treated by adrenalectomy had larger tumors (28.9 ± 11.2 vs 17.3 ± 8.4mm, P < 0.001), higher CT unenhanced density (29.1 ± 11.0 vs 23.1 ± 9.0 HU, P = 0.043), and FDG-PET adrenal uptake (9.0 ± 6.4 vs 4.4 ± 2.3 SUV, P = 0.003) than non-operated ones. Oncocytic features > 75% of the tumor were detected in 12/17 cases (70.6%). Five of those showed borderline-malignant histopathological characteristics by Lin–Weiss–Bisceglia score. Among remaining non-oncocytic tumors, 1/5 had a Weiss score ≥ 3. Overall, 6/17 tumors (35.3%) had borderline-malignant potential. Radiological parameters were similar between patients with benign and borderline-malignant tumors. Conclusions: Adrenal LPA are a heterogeneous group of tumors, mostly composed of oncocytomas. Up to 1/3 of those tumors may have a borderline-malignant potential at histopathology.
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- 2020
40. Steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency in a population of PCOS with suspicious levels of 17OH-progesterone
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S Castelli, Flaminia Fanelli, G. Di Dalmazi, Alessandra Gambineri, Valentina Vicennati, Lilia Baldazzi, G Brillanti, Uberto Pagotto, Andrea Repaci, Paola Altieri, Soara Menabo, C. Pelusi, Renato Pasquali, Marco Mezzullo, Elena Nardi, A Dormi, Francesca Corzani, Claudia Oriolo, Oriolo C., Fanelli F., Castelli S., Mezzullo M., Altieri P., Corzani F., Pelusi C., Repaci A., Di Dalmazi G., Vicennati V., Baldazzi L., Menabo S., Dormi A., Nardi E., Brillanti G., Pasquali R., Pagotto U., and Gambineri A.
- Subjects
Adult ,medicine.medical_specialty ,Adolescent ,Genotyping Techniques ,Endocrinology, Diabetes and Metabolism ,Population ,DNA Mutational Analysis ,Steroid profiling ,CYP21A2 genotyping ,ACTH test ,Cohort Studies ,Diagnostic Techniques, Endocrine ,Basal (phylogenetics) ,chemistry.chemical_compound ,Young Adult ,Endocrinology ,Corticosterone ,Tandem Mass Spectrometry ,Internal medicine ,Follicular phase ,Medicine ,Humans ,Testosterone ,education ,education.field_of_study ,medicine.diagnostic_test ,biology ,Adrenal Hyperplasia, Congenital ,business.industry ,17-alpha-Hydroxyprogesterone ,ACTH stimulation test ,21-Hydroxylase ,Reproducibility of Results ,Hyperplasia ,Non-classic adrenal hyperplasia due to 21-hydroxylase deficiency ,medicine.disease ,1–24 ,chemistry ,biology.protein ,Female ,Steroids ,Steroid 21-Hydroxylase ,business ,Biomarkers ,Blood Chemical Analysis ,Chromatography, Liquid ,Polycystic Ovary Syndrome - Abstract
Objective: We aimed at defining the most effective routine immunoassay- or liquid chromatography-tandem mass spectrometry (LC–MS/MS)-determined steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency (21-NCAH) in a PCOS-like population before genotyping. Methods: Seventy PCOS-like patients in reproductive age with immunoassay-determined follicular 17OH-progesterone (17OHP) ≥ 2.00 ng/mL underwent CYP21A2 gene analysis and 1–24ACTH test. Serum steroids were measured by immunoassays at baseline and 60 min after ACTH stimulation; basal steroid profile was measured by LC–MS/MS. Results: Genotyping revealed 23 21-NCAH, 15 single allele heterozygous CYP21A2 mutations (21-HTZ) and 32 PCOS patients displaying similar clinical and metabolic features. Immunoassays revealed higher baseline 17OHP and testosterone, and after ACTH stimulation, higher 17OHP (17OHP60) and lower cortisol, whereas LC–MS/MS revealed higher 17OHP (17OHPLC-MS/MS), progesterone and 21-deoxycortisol and lower corticosterone in 21-NCAH compared with both 21-HTZ and PCOS patients. Steroid thresholds best discriminating 21-NCAH from 21-HTZ and PCOS were estimated, and their diagnostic accuracy in identifying 21-NCAH from PCOS was established by ROC analysis. The highest accuracy was observed for 21-deoxycortisol ≥ 0.087 ng/mL, showing 100% sensitivity, while the combination of 17OHPLC-MS/MS ≥ 1.79 ng/mL and corticosterone ≤ 8.76 ng/mL, as well as the combination of ACTH-stimulated 17OHP ≥ 6.77 ng/mL and cortisol ≤ 240 ng/mL by immunoassay, showed 100% specificity. Conclusions: LC–MS/MS measurement of basal follicular 21-deoxycortisol, 17OHP and corticosterone seems the most convenient method for diagnosing 21-NCAH in a population of PCOS with a positive first level screening, providing high accuracy and reducing the need for ACTH stimulation test.
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- 2019
41. Female and male serum reference intervals for challenging sex and precursor steroids by liquid chromatography - tandem mass spectrometry
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Alessandra Gambineri, Uberto Pagotto, Flaminia Fanelli, Marco Mezzullo, Carla Pelusi, Andrea Repaci, Guido Di Dalmazi, Alessia Fazzini, Mezzullo M., Pelusi C., Fazzini A., Repaci A., Di Dalmazi G., Gambineri A., Pagotto U., and Fanelli F.
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0301 basic medicine ,Male ,17-hydroxypregnenolone ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Tandem mass spectrometry ,Biochemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Liquid chromatography–mass spectrometry ,Reference Values ,Tandem Mass Spectrometry ,estrogen ,Aged, 80 and over ,Estradiol ,Dihydrotestosterone ,Middle Aged ,3. Good health ,Menopause ,030220 oncology & carcinogenesis ,Molecular Medicine ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Estrone ,17-alpha-Hydroxypregnenolone ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Endocrine system ,Humans ,immunoassay ,LC-MS/MS ,Molecular Biology ,Aged ,business.industry ,Selected reaction monitoring ,Cell Biology ,medicine.disease ,030104 developmental biology ,chemistry ,reference intervals ,Estrogen ,business ,Chromatography, Liquid - Abstract
Measuring some sex and precursor steroids is still challenging even by liquid chromatography – tandem mass spectrometry (LC-MS/MS), and few normal values are available. We developed a LC-MS/MS method for estradiol, estrone, dihydrotestosterone and 17-hydroxypregnenolone measurement, compared it with direct immunoassays, and generated sex, age, menopausal and menstrual status specific reference intervals. Liquid-liquid extraction was optimized on 300 μL serum spiked with isotopic internal standards. A 2D-LC system allowed on-line purification and separation in 11 min run. Electrospray ionization was enhanced by ammonium fluoride. MS-detection was obtained by multiple reaction monitoring. Direct ECLIA for estradiol (n = 80) and RIA for estrone (n = 41) were compared with LC-MS/MS. Reference values were estimated in healthy, lean women in reproductive age (n = 118), menopausal women (n = 33) and men (n = 159). The assay showed satisfying imprecision, trueness, recovery and selectivity. Adequate functional sensitivity was achieved for measuring estrone (18.1 pmol/L) and 17-hydroxypregnenolone (117 pmol/L) in all subjects, and estradiol (35.9 pmol/L) and dihydrotestosterone (134 pmol/L) in women in reproductive age and men, but not in menopausal women. Compared with LC-MS/MS, immunoassays showed good agreement for estradiol but severe disagreement for estrone. Estrogens exhibited sex, menopausal and menstrual variations. Dihydrotestosterone and 17-hydroxypregnenolone depended on sex and menopause, the latter also declining with age in men. Strictly defined reference intervals in the adult female and male population were generated for challenging steroids such as estrogens, dihydrotestosterone and 17-hydroxypregnenolone by a novel LC-MS/MS method. Our achievement can be used to deepen the comprehension of several endocrine diseases.
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- 2019
42. Serum steroid profiling by mass spectrometry in adrenocortical tumors: diagnostic implications
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Flaminia Fanelli, Guido Di Dalmazi, Fanelli F., and Di Dalmazi G.
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Oncology ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Steroid ,Classification rate ,Endocrinology ,Primary aldosteronism ,Adrenal steroid ,Tandem Mass Spectrometry ,Internal medicine ,Hyperaldosteronism ,Internal Medicine ,medicine ,Adrenal disease ,Adrenocortical Carcinoma ,Humans ,In patient ,Cushing Syndrome ,mass spectrometry ,Nutrition and Dietetics ,business.industry ,medicine.disease ,Adrenal Cortex Neoplasms ,adrenocortical tumor ,Adrenocortical Adenoma ,Adrenal vein sampling ,Steroids ,serum steroid profiling ,business ,Biomarkers ,Blood Chemical Analysis ,Chromatography, Liquid - Abstract
Purpose of review Liquid chromatography-tandem mass spectrometry (LC-MS/MS), allowing the reliable measurement of large panels of steroids, opened a new era in the characterization of adrenal diseases. This review summarizes the most recent findings on serum steroid profile in benign adrenocortical tumors and provides a focus on the most promising analytical developments. Recent findings Recently developed LC-MS/MS assays included challenging compounds, providing new knowledge on adrenal steroid secretion. Pioneering studies highlighted the potential of incoming technologies in increasing measurement selectivity and implementing the steroidomic approach. In primary aldosteronism, several studies highlighted the signature of aldosterone-producing adenomas, mainly characterized by secretion of hybrid steroids. The combination of steroid panel and radiological data reached an agreement with adrenal vein sampling-based classification in more than 80% of the cases. The serum steroid profiling in patients with Cushing's syndrome, mainly characterized by reduced androgens and increased 11-dexoycorticosterone in adrenal hypercortisolism, showed a good discriminant power for patients' subtyping (90% correct classification rate). Finally, a selected panel of steroids, including 11-deoxycortisol as the main discriminant compound, was able to achieve a good separation of patients with and without adrenocortical carcinomas. Summary The constantly evolving serum steroid profiling by MS may improve the diagnosis of different types of adrenocortical tumors.
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- 2019
43. The Steroid Profile of Adrenal Incidentalomas: Subtyping Subjects With High Cardiovascular Risk
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Carla Pelusi, Flaminia Fanelli, Rita Golfieri, Claudio Borghi, Paola Altieri, Uberto Pagotto, Alessandra Gambineri, Guido Di Dalmazi, Guido Zavatta, Eugenio Roberto Cosentino, Renato Pasquali, Andrea Repaci, Caterina Balacchi, Marco Mezzullo, Cristina Mosconi, Silvia Ricci Bitti, Valentina Vicennati, Di Dalmazi G., Fanelli F., Zavatta G., Ricci Bitti S., Mezzullo M., Repaci A., Pelusi C., Gambineri A., Altieri P., Mosconi C., Balacchi C., Golfieri R., Cosentino E.R., Borghi C., Vicennati V., Pasquali R., and Pagotto U.
- Subjects
Cortisol secretion ,Male ,medicine.medical_specialty ,Adenoma ,Hydrocortisone ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Cortodoxone ,Adrenal Gland Neoplasms ,Dehydroepiandrosterone ,Biochemistry ,Gastroenterology ,Steroid ,chemistry.chemical_compound ,Endocrinology ,Corticosterone ,Risk Factors ,Tandem Mass Spectrometry ,Internal medicine ,medicine ,Humans ,Aged ,business.industry ,Biochemistry (medical) ,Hazard ratio ,Hyperplasia ,Middle Aged ,Adrenal Incidentalomas: Cardiovascular Risk ,medicine.disease ,chemistry ,Cardiovascular Diseases ,Female ,business ,Cohort study ,Chromatography, Liquid - Abstract
Context Steroid profiling by mass spectrometry has shown implications for diagnosis and subtyping of adrenal tumors. Objectives To investigate steroid profiles and their cardiovascular correlates in a large cohort of patients with nonsecreting (NS) adrenal incidentalomas and autonomous cortisol secretion (ACS). Design Cohort study. Setting University hospital. Patients Patients (n = 302) with incidentally discovered adrenal masses, divided into unilateral adenoma and hyperplasia with ACS (n = 46 and n = 52, respectively) and NS (n = 120 and n = 84, respectively). Post–dexamethasone suppression test (DST) cortisol 50 nmol/L defined NS and ACS, respectively. Intervention Analysis of 10-steroid panel by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and clinical data (mean follow-up 39 months). Main Outcome Measures Difference in baseline and post-DST steroid profiles between groups. Correlation with cardiovascular profile. Results Patients with unilateral adenomas and ACS showed higher cortisol, 11-deoxycortisol, and corticosterone and lower dehydroepiandrosterone than those with NS adenomas. Patients with ACS hyperplasia showed higher cortisol and lower androgens in women than those with NS. Patients with ACS had reduced suppression of post-DST cortisol, 11-deoxycortisol, and corticosterone, irrespective of adrenal morphology. Post-DST cortisol and corticosterone were associated with higher prevalence of severe/resistant hypertension. Patients with ACS unilateral adenomas showed higher incidence of worsening of hypertensive disease and novel cardiovascular events than those with NS, with post-DST cortisol [hazard ratio (HR) 1.02; 95% CI, 1.01 to 1.03; P < 0.001] and baseline corticosterone (HR 1.06; 95% CI, 1.01 to 1.12; P = 0.031) among the main predictors. Conclusions Patients with adrenal incidentalomas showed different steroid profiles, depending on functional status and adrenal morphology, with implications for their cardiovascular status.
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- 2019
44. Hyperandrogenism and Adrenocortical Tumors
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Guido Di Dalmazi and Di Dalmazi G.
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Pathogenesis ,medicine.medical_specialty ,business.industry ,Hyperandrogenism ,Epidemiology ,medicine ,Physiology ,Hyperandrogenism, Adrenocortical Tumors, adrenal gland, androgens ,Androstenedione ,medicine.disease ,business ,Testosterone ,Hormone - Abstract
Androgen-secreting tumors are a rare cause of hyperandrogenism of adrenal origin. Although these tumors are identified in less than 2% of patients, the prevalence of adrenocortical carcinomas is relevant (2/3 of the cases). Those tumors are associated with simultaneous elevation of several androgens, mainly androstenedione, DHEAS, and testosterone, in more than half of the patients, as measured either by immunoassay or mass spectrometry. Despite the recent advances on the pathogenesis of adrenocortical tumors, to date no driver molecular event have been identified in those tumors. This chapter provides a comprehensive review of all studies published in the last 20 years on androgen-secreting tumors, with focus on epidemiology, clinical presentation, and hormonal profile.
- Published
- 2019
45. Comparison of the effects of lockdown due to COVID-19 on glucose patterns among children, adolescents, and adults with type 1 diabetes: CGM study
- Author
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Andrea Pession, Uberto Pagotto, Simona Moscatiello, Gilberto Laffi, Lorenzo Tucci, Giulio Maltoni, Claudio Bongiorno, Guido Di Dalmazi, Valeria Di Natale, Stefano Zucchini, DI Dalmazi G., Maltoni G., Bongiorno C., Tucci L., DI Natale V., Moscatiello S., Laffi G., Pession A., Zucchini S., and Pagotto U.
- Subjects
Blood Glucose ,Male ,Research design ,Pediatrics ,Activities of daily living ,Endocrinology, Diabetes and Metabolism ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Insulin ,Child ,diabetes mellitu ,Middle Aged ,type 1 ,Italy ,diabetes mellitus ,Female ,Coronavirus Infections ,Human ,Adult ,Insulin pump ,medicine.medical_specialty ,Adolescent ,Coronavirus disease 2019 (COVID-19) ,Pneumonia, Viral ,Monitoring, Ambulatory ,Betacoronavirus ,Diabetes mellitus ,Blood Glucose Self-Monitoring ,medicine ,Humans ,Hypoglycemic Agents ,Pandemics ,Exercise ,Type 1 diabetes ,lcsh:RC648-665 ,Betacoronaviru ,Hypoglycemic Agent ,Pandemic ,SARS-CoV-2 ,Coronavirus Infection ,business.industry ,COVID-19 ,Emerging Technologies, Pharmacology and Therapeutics ,medicine.disease ,Diabetes Mellitus, Type 1 ,Metabolic control analysis ,Communicable Disease Control ,business ,Stress, Psychological - Abstract
IntroductionThe COVID-19 pandemic forced the Italian government to issue extremely restrictive measures on daily activities since 11 March 2020 (‘lockdown’), which may have influenced the metabolic control of type 1 diabetes mellitus (T1D). The aims of the study were to investigate continuous glucose monitoring (CGM) metrics in children and adults with T1D during lockdown and to identify their potentially related factors.Research design and methodsWe enrolled 130 consecutive patients with T1D (30 children (≤12 years), 24 teenagers (13–17 years), and 76 adults (≥18 years)) using either Dexcom or FreeStyle LibreCGM>70% during the study period, without hybrid closed-loop insulin pump. CGM metrics during the 20 days before and the 20 days after lockdown were calculated. By telephonic contact, we performed validated physical activity and perceived stress questionnaires.ResultsIn children, significantly lower glucose SD (SDglu) (p=0.029) and time below range (TBR)ConclusionIn patients with T1D during lockdown, CGM metrics mostly improved in children and adults, whereas it was unchanged in teenagers. In adults, age, physical activity, and perceived stress may be relevant contributing factors.
- Published
- 2020
46. Plasma Steroid Profiles in Subclinical Compared With Overt Adrenal Cushing Syndrome
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Felix Beuschlein, Katharina Langton, Guido Di Dalmazi, Matthias Gruber, Stefan R. Bornstein, Graeme Eisenhofer, Julia Fazel, Stephanie Zopp, Martin Reincke, Denise Kaden, Mirko Peitzsch, Martin Bidlingmaier, Jimmy Masjkur, Masjkur J., Gruber M., Peitzsch M., Kaden D., Di Dalmazi G., Bidlingmaier M., Zopp S., Langton K., Fazel J., Beuschlein F., Bornstein S.R., Reincke M., and Eisenhofer G.
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Cortisol secretion ,Male ,medicine.medical_specialty ,Hypothalamo-Hypophyseal System ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Dehydroepiandrosterone ,030209 endocrinology & metabolism ,Context (language use) ,Biochemistry ,Sensitivity and Specificity ,Severity of Illness Index ,Statistics, Nonparametric ,Hospitals, University ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Adrenocorticotropic Hormone ,Reference Values ,Tandem Mass Spectrometry ,Internal medicine ,Germany ,Severity of illness ,medicine ,Humans ,Subclinical Hypercortisolism, steroidomics ,Cushing Syndrome ,Dexamethasone ,030304 developmental biology ,Subclinical infection ,Retrospective Studies ,0303 health sciences ,business.industry ,Biochemistry (medical) ,Retrospective cohort study ,3. Good health ,Cross-Sectional Studies ,ROC Curve ,Multivariate Analysis ,Pregnenolone ,Female ,Steroids ,business ,Switzerland ,medicine.drug ,Chromatography, Liquid - Abstract
Context Diagnosis of subclinical adrenal hypercortisolism is based on several tests of the hypothalamic-pituitary-adrenal axis to establish mild alterations of cortisol secretion and dysregulated cortisol physiology. Objective We assessed whether plasma steroid profiles might assist diagnosis of subclinical Cushing syndrome (SC). Design Retrospective cross-sectional study. Setting Two tertiary medical centers. Patients Of 208 patients tested for hypercortisolism, disease was excluded in 152 and confirmed in 21 with overt adrenal Cushing syndrome (AC) compared to 35 with SC. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for reference. Main Outcome Measures A panel of 15 plasma steroids was measured by mass spectrometry, with classification by discriminant analysis. Results Patients with SC had lower plasma concentrations of dehydroepiandrosterone and dehydroepiandrosterone-sulfate than subjects without SC (P < 0.05). The largest increases (P < 0.001) in plasma steroids among patients with SC were observed for 11-deoxycortisol and 11-deoxycorticosterone. Nevertheless, concentrations of 11-deoxycorticosterone, 11-deoxycortisol, and pregnenolone in patients with AC were higher (P < 0.05) than in those with SC. Patients with SC or AC could be distinguished from subjects without disease using this combination of steroids as precisely as with use of measurements of serum cortisol after administration of dexamethasone. The steroid combination provided superior diagnostic performance compared with each of the other routine biochemical tests. Conclusion Distinct plasma steroid profiles in patients with SC may provide a simple and reliable screening method for establishing the diagnosis.
- Published
- 2018
47. Subclinical hypercortisolism: a state, a syndrome, or a disease?
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Guido Di Dalmazi, F Beuschlein, Martin Reincke, Renato Pasquali, Di Dalmazi, G, Pasquali, R, Beuschlein, F, and Reincke, M.
- Subjects
Cortisol secretion ,Hypothalamo-Hypophyseal System ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Adrenal Gland Neoplasms ,Pituitary-Adrenal System ,Disease ,Type 2 diabetes ,Cushing syndrome ,Endocrinology ,Cardiovascular Disease ,Diabetes mellitus ,Internal medicine ,Humans ,Medicine ,Cushing Syndrome ,Pathological ,Subclinical infection ,business.industry ,Incidence (epidemiology) ,General Medicine ,medicine.disease ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Obesity, Abdominal ,Asymptomatic Diseases ,Spinal Fractures ,business ,Osteoporotic Fractures - Abstract
Subclinical hypercortisolism (SH), defined as alterations of the hypothalamus–pituitary–adrenal axis in the absence of clinical signs or symptoms related to cortisol secretion, is a common finding in patients with adrenal incidentalomas. The clinical correlates of this pathological condition have become clearer over the last few years. The aim of this review is to summarize the co-morbidities and the clinical outcomes of patients with SH. According to the analysis of the results of the studies published within the last 15 years, hypertension and type 2 diabetes are a common finding in patients with SH, occurring roughly in 2/3 and 1/3 of the patients respectively. Moreover, several additional cardiovascular and metabolic complications, like endothelial damage, increased visceral fat accumulation and impaired lipid metabolism have been shown to increase the cardiovascular risk of those patients. Accordingly, recent independent reports investigating the natural history of the disease in a long-term follow-up setting have shown that patients with SH have a higher incidence of cardiovascular events and related mortality. Moreover, longitudinal studies have also shown increased incidence of osteoporotic vertebral fractures. Future research is needed to improve the diagnostic performance of hormonal tests, by assessment of the complete steroid profile with more accurate assays, and to define the efficacy of surgical vs medical treatment in a randomized-controlled setting.
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- 2015
48. Radiological formula for differentiating between secreting and non secreting adrenal adenomas
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Cristina Mosconi, Dimitris Papadopoulos, Rita Golfieri, Elena Casadio, Guido Di Dalmazi, Uberto Pagotto, Eleonora Rinaldi, Valentina Vicennati, Renato Pasquali, and Vicennati V, Casadio E, Pagotto U, Di Dalmazi G, Rinaldi E, Mosconi C, Papadopoulos D, Golfieri R, Renato Pasquali R.
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Pathology ,medicine.medical_specialty ,medicine.anatomical_structure ,business.industry ,Radiological weapon ,non secreting adrenal adenomas ,Medicine ,Abdomen ,business - Abstract
Poster: "ECR 2016 / B-1242 / Radiological formula for differentiating between secreting and non secreting adrenal adenomas " by: "C. Mosconi, V. Vicennati, D. Papadopoulos , R. Pasquali, R. Golfieri; Bologna/IT"
- Published
- 2016
49. Combined Aldosterone and Cortisol Secretion by Adrenal Incidentaloma
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Donatella Santini, Eleonora Rinaldi, Valentina Vicennati, Francesco Minni, Emanuela Giampalma, Rita Golfieri, Andrea Repaci, Renato Pasquali, Guido Di Dalmazi, Nicola Marrano, Vicennati V, Repaci A, di Dalmazi G, Rinaldi E, Golfieri R, Giampalma E, Minni F, Marrano N, Santini D, and Pasquali R.
- Subjects
Cortisol secretion ,medicine.medical_specialty ,Hydrocortisone ,adrenal incidentaloma, Cushing's syndrome, Conn's syndrome ,Adrenal Gland Neoplasms ,Plasma renin activity ,Pathology and Forensic Medicine ,chemistry.chemical_compound ,Internal medicine ,Hyperaldosteronism ,Adrenal insufficiency ,Humans ,Medicine ,Adrenal adenoma ,Obesity ,Aldosterone ,Cushing Syndrome ,Aged ,Metabolic Syndrome ,business.industry ,medicine.disease ,Conn's syndrome ,Endocrinology ,Diabetes Mellitus, Type 2 ,chemistry ,Female ,Surgery ,Anatomy ,business ,Glucocorticoid ,medicine.drug - Abstract
A 70-year-old woman was referred to the authors’ unit following hospitalization for cardiac failure, high urinary free cortisol concentrations and severe hypokaliemia. A computed tomography scan of the abdomen showed an adrenal adenoma. The 24-hour urinary free cortisol values were high and plasma cortisol levels failed to suppress following 1 mg dexamethasone test. Aldosterone to plasma renin activity ratio was also pathologic, confirmed by saline load. She showed no symptoms of glucocorticoid excess. She was diagnosed with combined primary hyperaldosteronism and Cushing’s syndrome. Cases of adrenal incidentalomas co-secreting cortisol and aldosterone are rare; they should be addressed in patients undergoing adrenal surgery for Conn’s syndrome to avoid adrenal insufficiency after removal of the tumor.
- Published
- 2011
50. Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing's syndrome: a 15-year retrospective study
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Uberto Pagotto, Emanuela Giampalma, Renato Pasquali, Eleonora Rinaldi, Rita Golfieri, Valentina Vicennati, Alexandro Paccapelo, Guido Di Dalmazi, Elena Casadio, Cristina Mosconi, Silvia Garelli, Di Dalmazi, G, Vicennati, V, Garelli, S, Casadio, E, Rinaldi, E, Giampalma, E, Mosconi, C, Golfieri, R, Paccapelo, A, Pagotto, U, and Pasquali, R
- Subjects
Cortisol secretion ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Adrenal Gland Neoplasms ,Gastroenterology ,Endocrinology ,Internal medicine ,Internal Medicine ,medicine ,Humans ,In patient ,Cushing Syndrome ,Subclinical infection ,Aged ,Retrospective Studies ,business.industry ,Intermediate phenotype ,Incidence (epidemiology) ,Hazard ratio ,Retrospective cohort study ,Middle Aged ,Adrenal Gland Neoplasms/complications* Adrenal Gland Neoplasms/mortality* Adrenal Gland Neoplasms/secretion Aged Cardiovascular Diseases/epidemiology* Cardiovascular Diseases/etiology* Cushing Syndrome/etiology* Female Follow-Up Studies Humans Male Middle Aged Phenotype Retrospective Studies ,Phenotype ,Cardiovascular Diseases ,Dexamethasone suppression test ,Female ,business ,Follow-Up Studies - Abstract
Summary Background Incidental discovery of adrenal masses has increased over the past few years. Mild alterations in cortisol secretion without clinical signs of overt hypercortisolism (subclinical Cushing's syndrome) are a common finding in patients with these tumours. Although metabolic alterations and increased cardiovascular risk have been noted in patients with subclinical Cushing's syndrome, incidence of cardiovascular events and mortality in the long term have not been assessed. We aimed to ascertain the frequency of new cardiovascular events and mortality in patients with non-secreting adrenal incidentalomas, tumours of intermediate phenotype, or those causing subclinical Cushing's syndrome. Methods From January, 1995, to September, 2010, consecutive outpatients with adrenal incidentalomas who were referred to the endocrinology unit of S Orsola-Malpighi Hospital, Bologna, Italy, were enrolled into our study. Individuals were assessed every 18–30 months for the first 5 years (mean follow-up 7·5 [SD 3·2] years, range 26 months to 15 years). Cortisol concentrations after the 1 mg dexamethasone suppression test (DST) were used to define non-secreting (+50 nmol/L) and intermediate phenotype (50–138 nmol/L) adrenal incidentalomas and subclinical Cushing's syndrome (+138 nmol/L). At the end of follow-up, patients were reclassified as having either unchanged or worsened secreting patterns from baseline. Findings 198 outpatients were assessed; at the end of follow-up, 114 patients had stable non-secreting adrenal incidentalomas, 61 had either a stable intermediate phenotype or subclinical Cushing's syndrome, and 23 had a pattern of secretion that had worsened. By comparison with patients with stable non-secreting adrenal incidentalomas, the incidence of cardiovascular events was higher in individuals with a stable intermediate phenotype or subclinical Cushing's syndrome (6·7% vs 16·7%; p=0·04) and in those with worsened secreting patterns (6·7% vs 28·4%; p=0·02). Cardiovascular events were associated independently with a change (from baseline to the end of follow-up) in cortisol concentrations post DST (hazard ratio 1·13, 95% CI 1·05–1·21; p=0·001). Survival rates for all-cause mortality were lower in patients with either stable intermediate phenotype adrenal incidentalomas or subclinical Cushing's syndrome compared with those with stable non-secreting masses (57·0% vs 91·2%; p=0·005). Factors associated with mortality were age (hazard ratio 1·06, 95% CI 1·01–1·12; p=0·03) and mean concentrations of cortisol post DST (1·10, 1·01–1·19; p=0·04). Compared with patients with stable non-secreting adrenal incidentalomas, unadjusted survival for cardiovascular-specific mortality was lower in patients with either a stable intermediate phenotype or subclinical Cushing's syndrome (97·5% vs 78·4%; p=0·02) and in those with worsened secreting patterns (97·5% vs 60·0%; p=0·01). Cancer mortality did not differ between groups. Interpretation Even when clinical signs of overt hypercortisolism are not present, patients with adrenal incidentalomas and mild hypercortisolism have an increased risk of cardiovascular events and mortality. Funding None.
- Published
- 2014
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