Internal medicine
Internal medicine
Componenti
- Terzolo Massimo (Coordinatore)
- Reimondo Giuseppe
- Perotti Paola Carla Giuseppina
- Saba Laura
- Calabrese Anna
- Puglisi Soraya
- Vittoria Basile
- Anna Pia
Contatti
Settore ERC
Attività
RESEARCH ACTIVITY OF INTERNAL MEDICINE (P.I. M. TERZOLO)
The department of Internal Medicine is a tertiary referral center for patients with adrenal tumors that is deeply involved in clinical and translational research. The department is devoted to clinical research thanks to its large patient cohorts and a well-established network of national and international collaborations (particularly in the context of the European Network for the Study of Adrenal Tumors - ENSAT).
The department comprises a clinical study center and laboratories equipped for biochemical determinations, cell cultures and hormone assays. Moreover, state-of-the-art laboratory facilities for genomics, transcriptomics, and proteomics are available. The department was appointed as Center of Excellence for its clinical activity on patients with adrenocortical carcinoma or adrenal incidentalomas, and for research activity on adrenal tumors.
Professor Terzolo was co-chair of the panel of international experts that wrote the Guidelines of the European Society of Endocrinology for the management of patients with adrenocortical carcinoma (Fassnacht et al., European Journal of Endocrinology 2018; Fasssnacht et al., Annals of Oncology 2020).
We have contributed to the development of novel therapeutic modalities for patients with adrenocortical carcinoma with the aim of improving either their life expectancy and quality of life. This is an unmet clinical need because adrenocortical carcinoma is a rare but very aggressive endocrine cancer, with limited therapeutic strategies. We have demonstrated the beneficial effect of adjuvant mitotane in reducing risk of recurrence after radical surgery in patients with localized adrenocortical carcinoma in a seminal study that prompted use of post-operative adjuvant mitotane (Terzolo et al., New England Journal of Medicine 2007).
Recently, we have provided more evidence on the adjuvant concept with the publication of the results of the ADIUVO study (Terzolo et al., The Lancet Diabetes & Endocrinology 2023), an international, multicentric, investigator-initiated, randomized, clinical trial focusing on patients with low-intermediate risk of recurrence after radical extirpation of adrenocortical carcinoma. This study is the first randomized trial ever done in the adjuvant setting and showed that patient with low risk of recurrence have unexpectedly a rather good prognosis also with surveillance alone. Therefore, adjuvant mitotane treatment can be avoided in this subset of patients, and this provides the first step toward a personalized approach for patients with adrenocortical carcinoma. However, adjuvant mitotane remains recommended in patients with high risk of recurrence (Calabrese et al., European Journal of Endocrinology 2019).
In these years, our research group has investigated many aspects concerning the management of mitotane treatment, including dosing and drug level monitoring (Puglisi et al., Journal of Clinical Medicine 2019; Puglisi et al., Cancers 2020), management of toxicities (Basile & Puglisi et al., Cancers 2020) and the duration of treatment (Basile & Puglisi et al., Journal of Personalized Medicine 2021).
We have recently coordinated a multicentric study in Italy to describe in a nationwide cohort the presentation of patients with adrenocortical carcinoma, treatment strategies, and potential prognostic factors (Puglisi et al., The Journal of Clinical Endocrinology and Metabolism 2023), and we presented the experience of our center to support the use of locoregional treatments to treat recurrence (Calabrese et al., European Journal of Endocrinology 2023).
We did many collaborative studies with centers partaking in ENSAT, of which the most important was the publication of the outcome of the largest prospective trial on treatment of patients with advanced adrenocortical carcinoma (FIRMACT trial) (Fassnacht, Terzolo et al., New England Journal of Medicine 2012).
Moreover, we have contributed to the development of diagnostic and therapeutic strategies for adrenal tumors of incidental discovery, the so-called “adrenal incidentalomas”. These adrenal tumors are increasingly found in up to 7% of individuals undergoing radiologic imaging studies; therefore, a correct management is key for health care systems (Reimondo et al., The Journal of Clinical Endocrinology and Metabolism 2020). Although adrenal incidentalomas are usually benign tumors, they are able to secrete cortisol autonomously in up to 50% of patients. We contributed to characterize the possible clinical consequences of autonomous cortisol secretion, such as hypertension, obesity, dyslipidemia, osteoporosis, and diabetes.
In this context, we have coordinated a large, retrospective, international, cohort study including more than 3600 patients with adrenal adenomas, in which we found an overall association of autonomous cortisol secretion with all-cause mortality, demonstrating for the first time that the mortality risk varies by age and sex (Deutschbein & Reimondo et al., The Lancet Diabetes & Endocrinology 2022).
Professor Terzolo was part of the panel of international experts that wrote the first and second version of the Guidelines of the European Society of Endocrinology for the management of patients with adrenal incidentaloma (Fassnacht et al. European Journal of Endocrinology 2016; Fassnacht et al. European Journal of Endocrinology 2023).
We also studied the long-term consequences of chronic exposure to glucocorticoids excess, or Cushing syndrome, (Puglisi et al., The Journal of Clinical Endocrinology and Metabolism 2023, Terzolo et al., European Journal of Endocrinology 2014) and the functioning of the hypothalamic-pituitary-adrenal axis in different pathophysiological conditions (Puglisi & Pizzuto et al., European Journal of Internal Medicine 2019, Reimondo et al., European Journal of Endocrinology 2017).
We are constantly looking for innovative and tailor-made approaches for patients with adrenal diseases and we have exciting work in progress in our main fields of research.
Adrenocortical carcinoma
- Development of new therapeutic strategies
- Analysis of genotype-phenotype correlations
- Identification of omic biomarkers for the early detection of recurrence following surgery
- Identification of prognostic factors and factors predictive of response to therapy
- Assessment of quality of life
Adrenal incidentaloma
- Development of new therapeutic strategies
- Analysis of genotype-phenotype correlations
- Characterization of the consequences of autonomous cortisol secretion
- Assessment of quality of life
Cushing syndrome
- Characterization of the consequences of chronic overt cortisol excess
- Assessment of quality of life
HPA axis
- Assessment of the function of the HPA axis in ageing
- Assessment of the function of the HPA axis in stress conditions
Progetti
- Antisecretory and antineoplastic activity of abiraterone in adrenocortical carcinoma: a preclinical and clinical study
- Integrating cutting-edge tools for targeted approach to patients with adrenocortical tumors
- Multiparametric characterization of adreno-cortical tumors (radiomic, immune and proteomic profiles) and association with extra-adrenal neoplasms (IMPROVE STUDY)
- Study of the interactions between environmental risk factors and germline genetic profiles in adrenocortical carcinoma
Prodotti della ricerca
Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study
Terzolo M, Fassnacht M, Perotti P, Libé R, Kastelan D, Lacroix A, Arlt W, Haak HR, Loli P, Decoudier B, Lasolle H, Quinkler M, Haissaguerre M, Chabre O, Caron P, Stigliano S, Giordano R, Zatelli MC, Bancos I, Fragoso MCBV, Canu L, Luconi M, Puglisi S, Basile V, Reimondo G, Kroiss M, Megerle F, Hahner S, Kimpel O, Dusek T, Nölting S, Bourdeau I, Chortis V, Ettaieb MH, Cosentini D, Grisanti S, Baudin E, Berchialla P, Bovis F, Sormani MP, Bruzzi P, Beuschlein F, Bertherat J, Berruti A.
Lancet Diabetes Endocrinol 2023
doi: 10.1016/ S2213-8587(23)00193-6
Long-Term Consequences of Cushing's Syndrome: A Systematic Literature Review.
Puglisi S, Perini AME, Botto C, Oliva F, Terzolo M.
J Clin Endocrinol Metab 2023; dgad453
European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors.
Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, Pelsma I, Marina L, Lorenz K, Bancos I, Arlt W, Dekkers OM. Eur J Endocrinol. 2023; 189:G1-G42.
New findings on presentation and outcome of patients with adrenocortical cancer: results from a national cohort study.
Puglisi S, Calabrese A, Ferraù F, Violi MA, Laganà M, Grisanti S, Ceccato F, Scaroni C, Dalmazi GD, Stigliano A, Altieri B, Canu L, Loli P, Pivonello R, Arvat E, Morelli V, Perotti P, Basile V, Berchialla P, Urru S, Fiori C, Porpiglia F, Berruti A, Pia A, Reimondo G, Cannavò S, Terzolo M.
J Clin Endocrinol Metab 2023: dgad199.
The management of postoperative disease recurrence in patients with adrenocortical carcinoma: a retrospective study in 106 patients.
Calabrese A, Puglisi S, Borin C, Basile V, Perotti P, Pia A, Berchialla P, Volante M, Fiori C, Porpiglia F, Veltri A, Reimondo G, Terzolo M.
Eur J Endocrinol. 2023; 188:lvad002.
Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study.
Deutschbein T, Reimondo G, Di Dalmazi G, Bancos I, Patrova J, Vassiliadi DA, Nekić AB, Debono M, Lardo P, Ceccato F, Petramala L, Prete A, Chiodini I, Ivović M, Pazaitou-Panayiotou K, Alexandraki KI, Hanzu FA, Loli P, Yener S, Langton K, Spyroglou A, Kocjan T, Zacharieva S, Valdés N, Ambroziak U, Suzuki M, Detomas M, Puglisi S, Tucci L, Delivanis DA, Margaritopoulos D, Dusek T, Maggio R, Scaroni C, Concistrè A, Ronchi CL, Altieri B, Mosconi C, Diamantopoulos A, Iñiguez-Ariza NM, Vicennati V, Pia A, Kroiss M, Kaltsas G, Chrisoulidou A, Marina LV, Morelli V, Arlt W, Letizia C, Boscaro M, Stigliano A, Kastelan D, Tsagarakis S, Athimulam S, Pagotto U, Maeder U, Falhammar H, Newell-Price J, Terzolo M, Fassnacht M.
Lancet Diabetes Endocrinol 2022; 10:499-508.
doi: 10.1016/S2213-8587(22)00100-0
Limited Role of Hair Cortisol and Cortisone Measurement for Detecting Cortisol Autonomy in Patients With Adrenal Incidentalomas.
Puglisi S, Leporati M, Amante E, Parisi A, Pia AR, Berchialla P, Terzolo M, Vincenti M, Reimondo G.
Front Endocrinol 2022; 13:833514.
doi: 10.3389/fendo.2022.833514
A Multicenter Epidemiological Study on Second Malignancy in Non-Syndromic Pheochromocytoma / Paraganglioma Patients in Italy.
Canu L, Puglisi S, Berchialla P, De Filpo G, Brignardello F, Schiavi F, Ferrara AM, Zovato S, Luconi M, Pia A, Appetecchia M, Arvat E, Letizia C, Maccario M, Parasiliti-Caprino M, Altieri B, Faggiano A, Modica R, Morelli V, Arosio M, Verga U, Pellegrino M, Petramala L, Concistrè A, Razzore P, Ercolino T, Rapizzi E, Maggi M, Stigliano A, Burrello J, Terzolo M, Opocher G, Mannelli M, Reimondo G.
Cancers 2021; 13:5831
What Is the Optimal Duration of Adjuvant Mitotane Therapy in Adrenocortical Carcinoma? An Unanswered Question.
Basile V, Puglisi S, Altieri B, Canu L, Libè R, Ceccato F, Beuschlein F, Quinkler M, Calabrese A, Perotti P, Berchialla P, Dischinger U, Megerle F, Baudin E, Bourdeau I, Lacroix A, Loli P, Berruti A, Kastelan D, Haak HR, Fassnacht M, Terzolo M.
J Pers Med 2021; 11:269
doi: 10.3390/jpm11040269
ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up.
Fassnacht M, Assie G, Baudin E, Eisenhofer G, de la Fouchardiere C, Haak HR, de Krijger R, Porpiglia F, Terzolo M, Berruti A;
Ann Oncol. 2020; 31:1476-1490.
doi: 10.1016/j.annonc.2020.08.2099
Mitotane Concentrations Influence Outcome in Patients with Advanced Adrenocortical Carcinoma
Puglisi S, Calabrese A, Basile V, Ceccato F, Scaroni C, Altieri B, Della Casa S, Loli P, Pivonello R, De Martino MC, Canu L, Russo M, Badalamenti G, Torlontano M, Stigliano A, Ferraù F, Arnaldi G, Saba L, Quirino A, Perotti P, Berchialla P, Terzolo M., Cancers 2020; 12:740
Unwanted Hormonal and Metabolic Effects of Postoperative Adjuvant Mitotane Treatment for Adrenocortical Cancer
Basile V, Puglisi S, Calabrese A, Pia A, Perotti P, Berruti A, Reimondo G, Terzolo M.
Cancers 2020; 12:2615
Adrenal incidentalomas are tied to increased risk of diabetes: findings from a prospective study
Reimondo G, Castellano E, Grosso M, Puglisi S, Pia A, Pellegrino M, Borretta G, Terzolo M.
J Clin Endocrinol Metab 2020; 105: dgz284
Adjuvant mitotane therapy is beneficial in non-metastatic adrenocortical carcinoma at high risk of recurrence
Calabrese A, Basile V, Puglisi S, Perotti P, Pia A, Saba L, Berchialla P, Porpiglia F, Veltri A, Volante M, Reimondo G, Berruti A, Terzolo M.
Eur J Endocrinol 2019; 180:387-396
doi: 10.1530/EJE-18-0923
Mitotane Concentrations Influence the Risk of Recurrence in Adrenocortical Carcinoma Patients on Adjuvant Treatment.
Puglisi S, Calabrese A, Basile V, Ceccato F, Scaroni C, Simeoli C, Torlontano M, Cannavò S, Arnaldi G, Stigliano A, Malandrino P, Saba L, Altieri B, Della Casa S, Perotti P, Berchialla P, De Filpo G, Canu L, Loli P, Reimondo G, Terzolo M.
J Clin Med 2019; 8:1850
doi: 10.3390/jcm8111850
European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors.
Fassnacht M, Dekkers OM, Else T, Baudin E, Berruti A, de Krijger R, Haak HR, Mihai R, Assie G, Terzolo M.
Eur J Endocrinol. 2018; 179:G1-G46.
doi: 10.1530/EJE-18-0608
Determination of salivary cortisol to assess time-related changes of the adrenal response to stress in critically ill patients.
Puglisi S, Pizzuto A, Laface B, Panero F, Aprà F, Palmas E, Perotti P, Reimondo G, Boccuzzi A, Terzolo M.
Eur J Intern Med 2019; 68:66-70.
doi: 10.1016/j.ejim.2019.08.001
Effects of mitotane on the hypothalamic-pituitary-adrenal axis in patients with adrenocortical carcinoma.
Reimondo G, Puglisi S, Zaggia B, Basile V, Saba L, Perotti P, De Francia S, Volante M, Zatelli MC, Cannavò S, Terzolo M.
Eur J Endocrinol. 2017; 177:361-367
doi: 10.1530/EJE-17-0452
Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors.
Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, Tabarin A, Terzolo M, Tsagarakis S, Dekkers OM.
Eur J Endocrinol. 2016; 175:G1-G34.
doi: 10.1530/EJE-16-0467
Surgical remission of Cushing's syndrome reduces cardiovascular risk.
Terzolo M, Allasino B, Pia A, Peraga G, Daffara F, Laino F, Ardito A, Termine A, Paccotti P, Berchialla P, Migliaretti G, Reimondo G.
Eur J Endocrinol. 2014 Jul;171(1):127-36.
doi: 10.1530/EJE-13-0555
Combination chemotherapy in advanced adrenocortical carcinoma.
Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, Welin S, Schade-Brittinger C, Lacroix A, Jarzab B, Sorbye H, Torpy DJ, Stepan V, Schteingart DE, Arlt W, Kroiss M, Leboulleux S, Sperone P, Sundin A, Hermsen I, Hahner S, Willenberg HS, Tabarin A, Quinkler M, de la Fouchardière C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Müller HH, Skogseid B; FIRM-ACT Study Group.
N Engl J Med. 2012; 366:2189-97
Adjuvant mitotane treatment for adrenocortical carcinoma
Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, Rossetto R, Buci L, Sperone P, Grossrubatscher E, Reimondo G, Bollito E, Papotti M, Saeger W, Hahner S, Koschker AC, Arvat E, Ambrosi B, Loli P, Lombardi G, Mannelli M, Bruzzi P, Mantero F, Allolio B, Dogliotti L, Berruti A.
N Engl J Med 2007; 356:2372-80
doi: 10.1056/NEJMoa063360
Tag: Adrenal diseases, adrenal tumors, Cushing's syndrome