Phd in ENDOCRINOLOGICAL SCIENCES

Research: Characterizing the cardiometabolic phenotype of pituitary tumors: the potential role of sglt2-inhibitors

Education and Training - PhD in Endocrinological Sciences, Sapienza University of Rome, Italy (ongoing, expected completion November 2026). Project: “Characterizing the cardiometabolic phenotype of pituitary tumors: the potential role of SGLT2 inhibitors.” - Visiting Researcher, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC/FIBICO), Córdoba, Spain, in the group of Prof. Raúl Luque: scientific collaboration within the PhD project and training in translational laboratory methodologies applied to the study of pituitary tumors. - Visiting Researcher, “Tumour Environment & Pituitary Oncology” team led by Prof. Gerald Raverot, Cancer Research Center of Lyon, INSERM 1052 (2022–2023): participation in multidisciplinary tumor boards within the French HYPO reference network and involvement in translational research activities on aggressive pituitary tumors and craniopharyngiomas. - Residency in Endocrinology and Metabolic Diseases, Sapienza University of Rome (2023) – 70/70 cum laude. Thesis: B-RAF and MEK Inhibitor Targeted Therapy in Papillary Craniopharyngiomas: Results from a Multicenter Study. - Medical Board Certification and registration with the Order of Physicians and Surgeons of Naples (2019). - Medical Degree (MD) in Medicine and Surgery, University of Naples Federico II (2018) – 110/110. Thesis: Combined treatment with inositol isomers and cabergoline in women with PCOS and hyperprolactinemia. - Clinical and Research Internship in Endocrinology, AOU Policlinico Federico II, Naples (2018). - Scientific High School Diploma, “Niccolò Copernico” High School, Naples – 100/100. Work Experience - Research Fellow, IRCCS Neuromed (2024–present): clinical and research activities focused on pituitary tumors, with particular interest in the genetic background and cardiometabolic implications of hormone hypersecretion. - Sub-Investigator in international sponsored clinical trials, Sapienza University of Rome (2020–present): CAHtalyst Trial (crinecerfont in congenital adrenal hyperplasia), ForesiGHt Trial (lonapegsomatropin in adult growth hormone deficiency), LINC6 Study (osilodrostat in Cushing’s syndrome) - Research Fellow, University of Naples Federico II (2019): participation in the ANDROKIT project aimed at developing diagnostic and predictive tests for male infertility. Skills Clinical skills - Thyroid ultrasound - Bone mineral density assessment by DXA - BLSD – Basic Life Support and Defibrillation certification Research and laboratory skills - Cell line culture and maintenance - Culture of primary human pituitary tumors - Plasmid-based transfection - Immunofluorescence and immunohistochemistry - Microscopy and image analysis - RNA extraction and reverse transcription - Gene expression analysis by qPCR - Protein expression analysis by Western blot Computational skills - Statistical analysis (SPSS, GraphPad) - Image analysis software (Zeiss ZEN Blue, NIS-Elements, Merge-Efilm) - Database management and reference management tools General Skills - Excellent communication skills with teachers, colleagues, and patients. - Ability to maintain long-term research collaborations; currently involved in research activities in collaboration between Sapienza University of Rome, the Cancer Research Center of Lyon, IRCCS Neuromed, the University of Naples Federico II, and the Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC/FIBICO). - High sense of responsibility and reliability. - Strong ability to work effectively in team settings. - Leadership skills, with responsibility for supervising junior resident physicians within the department. - Language skills: Italian and English (C2); French and Spanish (C1). Research project The present PhD project aims to investigate the cardiometabolic phenotype of patients affected by pituitary neuroendocrine tumors (PitNETs). PitNETs are known to influence systemic metabolism and cardiovascular health through the aberrant secretion of pituitary hormones. Different tumor subtypes—particularly prolactinomas, somatotroph tumors, and corticotroph tumors—act on specific hormonal axes and intracellular pathways, profoundly affecting the regulation of glucose, lipid, protein, and hydro-electrolytic metabolism. As a consequence, patients frequently develop arterial hypertension, dysglycemia, and dyslipidemia, ultimately leading to cardiac structural and functional alterations and an overall deterioration of cardiovascular health. Recent evidence has also suggested that these hormonal alterations may induce a metabolic reprogramming of tumor cells, potentially contributing to tumor progression. To better characterize these aspects, the PhD project is structured into two main research areas. First, the project includes a series of clinical studies aimed at longitudinally investigating the cardiometabolic profile of patients with different PitNET subtypes. These studies evaluate echocardiographic, metabolic, immunological, and body composition parameters. Particular attention is given to the impact of several medical therapies commonly used in PitNET management, including somatostatin analogues and pegvisomant for GH-secreting tumors and cabergoline for lactotroph tumors. Second, the project includes a translational study aimed at investigating the direct effects of SGLT2 inhibitors (SGLT2i) on murine pituitary tumor cell lines (AtT-20, GH3, MMQ, LβT2) and on primary human PitNET cultures. These antidiabetic drugs have recently demonstrated the ability to reduce tumor growth in several preclinical models, including endocrine tumors, by promoting apoptosis and cell cycle arrest through activation of AMPK, a key cellular energy-sensing kinase. Experimental evidence indicates that AMPK activation may exert antitumor effects in endocrine neoplasms, including pituitary tumors, by modulating proliferation, apoptosis, and hormone secretion, mainly through inhibition of the mTOR pathway and the hypoxia-inducible factor HIF-1α. In this study, conducted in collaboration with the Department of Clinical Medicine and Surgery, Division of Endocrinology, University of Naples Federico II, the following parameters will be evaluated: Cell proliferation (MTT assay), Apoptosis (Caspase-Glo 3/7 assay), Hormone secretion (ELISA), Activation of AMPK/mTOR signaling pathways (RT-PCR and Western blot), Metabolic profiling using the Seahorse XF Analyzer to assess mitochondrial and glycolytic metabolism. These analyses will be performed before and after treatment with different concentrations of SGLT2 inhibitors, determined through dose–response curves. Primary cultures will be obtained from fresh tumor specimens collected from patients undergoing pituitary surgery and will be compared according to tumor invasiveness and functional subtype. In addition, SGLT2 protein expression will be assessed by immunohistochemistry on FFPE sections and through transcriptomic analyses. Finally, the effects of SGLT2 inhibitors will be compared with those of metformin and pituitary antisecretory drugs (pasireotide and cabergoline), administered alone or in combination. My contribution to the clinical studies focuses on data collection, statistical analysis, and manuscript preparation. Regarding the translational and basic science component of the project, my role includes project coordination, procurement of drugs and experimental materials, collection of human PitNET tumor samples (under an approved local Ethics Committee protocol), and active participation in laboratory experiments, within a framework of both national and international collaborations. Mobility International mobility period in progress (01/03/2026 – 01/09/2026) at the Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC/FIBICO), Córdoba, Spain, within the research group of Prof. Raúl Luque, aimed at scientific collaboration on the PhD project and advanced training in translational laboratory methodologies applied to pituitary tumor research. Patents/Clinical trials Sub-investigator in the following international clinical studies: - CAHtalyst Trial – crinecerfont in congenital adrenal hyperplasia - ForesiGHt Trial – lonapegsomatropin in adult growth hormone deficiency - LINC6 Study – observational study evaluating the long-term safety and efficacy of osilodrostat in Cushing’s syndrome No patents currently filed. Publications and Abstracts - Auriemma, R., Pirchio, R., De Alcubierre, D., Pivonello, R., & Colao, A. (2019). Dopamine Agonists-from the 1970s up to today. Neuroendocrinology. Epub 2019 Mar 11. doi: 10.1159/000499470. - Auriemma, R. S., De Alcubierre, D., Pirchio, R., Pivonello, R., & Colao, A. (2018). The effects of hyperprolactinemia and its control on metabolic diseases. Expert review of endocrinology & metabolism, 13(2), 99-106. doi: 10.1080/17446651.2018.1434412 - Auriemma, R. S., De Alcubierre, D., Pirchio, R., Pivonello, R., & Colao, A. (2019). Glucose abnormalities associated to prolactin secreting pituitary adenomas. Frontiers in endocrinology, 10, 327. doi: 10.3389/fendo.2019.00327 - De Alcubierre, D., Pofi, R. & Pozza, C. Testicular Adrenal Rest Tumours: fisiopatologia, diagnosi e trattamento. L'Endocrinologo 22, 22–27 (2021). doi: 10.1007/s40619-021-00816-5 - Cozzolino, A., Minnetti, M., Hasenmajer, Valeria, Sada, V., De Alcubierre, D., Pofi, R., Sbardella, E., Lenzi, A., Isidori, A. M. (2021). Terapia medica della sindrome di Cushing: aggiornamento su relacorilant e levoketoconazolo. L'Endocrinologo. 22. doi: 10.1007/s40619-021-00848-x - Minnetti, M., De Alcubierre, D., Bonaventura, I., Pofi, R., Hasenmajer, V., Tarsitano, M. G., ... & Isidori, A. M. (2022). Effects of licorice on sex hormones and the reproductive system. Nutrition, 103, 111727. doi: 10.1016/j.nut.2022.111727 - Feola, T., Carbonara, F., Verrico, M., Di Crescenzo, R. M., Gianno, F., Colonnese, C., De Alcubierre, D., …, & Jaffrain-Rea, M. L. (2022). Immunotherapy for aggressive and metastatic pituitary neuroendocrine tumors (PitNETs): state-of-the art. Cancers, 14(17), 4093. doi: 10.3390/cancers14174093 - Minnetti, M., Hasenmajer, V., Sbardella, E., Angelini, F., Simeoli, C., Di Paola, N., De Alcubierre D., ... & Isidori, A. M. (2022). Susceptibility and characteristics of infections in patients with glucocorticoid excess or insufficiency: the ICARO tool. European Journal of Endocrinology, 187(5), 719-731. doi: 10.1530/EJE-22-0454 - Ziverec, A., Chanal, M., Raymond, P., Ilie, M. D., De Alcubierre, D., Pasternack, A., ... & Bertolino, P. (2023). Inhibition of activin signalling reduces the growth of LbT2 gonadotroph pituitary tumours in mouse. Endocrine-Related Cancer, 30(3). doi: 10.1530/ERC-22-0245 - De Alcubierre, D., Ferrari, D., Mauro, G., Isidori, A. M., Tomlinson, J. W., & Pofi, R. (2023). Glucocorticoids and cognitive function: a walkthrough in endogenous and exogenous alterations. Journal of Endocrinological Investigation, 1-22. doi: 10.1007/s40618-023-02091-7 - De Alcubierre, D., Puliani, G., Cozzolino, A., Hasenmajer, V., Minnetti, M., Sada, V., ... & Venneri, M. A. (2023). Pituitary adenoma consistency affects postoperative hormone function: a retrospective study. BMC Endocrine Disorders, 23(1), 92. doi: 10.1186/s12902-023-01334-1 - Ilie, M. D., De Alcubierre, D., Carretti, A. L., Jouanneau, E., & Raverot, G. (2023). Therapeutic targeting of the pituitary tumor microenvironment. Pharmacology & Therapeutics, 108506. doi: 10.1016/j.pharmthera.2023.108506 - Sada, V., Puliani, G., Feola, T., Pirchio, R., Pofi, R., Sesti, F., De Alcubierre, D., ... & Sbardella, E. (2023). Tall stature and gigantism in transition age: clinical and genetic aspects—a literature review and recommendations. Journal of Endocrinological Investigation, 1-17. - De Alcubierre, D., Sbardella, E., Isidori, A.M. (2023). Hydrosaline Alterations in Cushing Disease. In: Caprio, M., Fernandes-Rosa, F.L. (eds) Hydro Saline Metabolism. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-031-27119-9_15 - Carbonara, F., Feola, T., Gianno, F., Polidoro, M., Di Crescenzo, R.M., Arcella, A., De Angelis, M., Morace, R., De Alcubierre, D., Esposito, V., Giangaspero F., Jaffrain-Rea, M.L. (2023). Clinical and molecular characteristics of gonadotroph pituitary tumors according to the WHO classification. Endocrine Pathology. doi: 10.1007/s12022-023-09794-w. - Hasenmajer, V.*, Ferrari, D.*, De Alcubierre, D., Sada, V., Puliani, G., Bonaventura, I., Minnetti, M., Tomaselli, A., Pofi, R., Sbardella, E., Cozzolino, A., Gianfrilli, D., Isidori, A. M. (2023). Effects of Dual-Release Hydrocortisone on Bone Metabolism in Primary and Secondary Adrenal Insufficiency: a 6-Year Study. Journal of Endocrine Society - De Alcubierre, D., Carretti, A. L., Ducray, F., Jouanneau, E., Raverot, G., Ilie, M.D. (2023). Aggressive pituitary tumors & carcinomas: medical treatment beyond temozolomide. Minerva Endocrinology. doi: 10.23736/S2724-6507.23.04058-7 - Sada V, Puliani G, Feola T, Pirchio R, Pofi R, Sesti F, De Alcubierre D, Amodeo ME, D'Aniello F, Vincenzi L, Gianfrilli D, Isidori AM, Grossman AB, Sbardella E; TALENT group. Tall stature and gigantism in transition age: clinical and genetic aspects-a literature review and recommendations (2024). Journal of Endocrinological Investigations. doi: 10.1007/s40618-023-02223-z. - Hasenmajer V, De Alcubierre D, Ferrari D, Minnetti M, Bonaventura I, Pofi R, Simeoli C, Tomaselli A, Sciarra F, Bottillo G, Angelini F, Cozzolino A, Venneri MA, Jannini EA, Gianfrilli D, Pivonello R, Isidori AM. Exploring sexual function in adrenal insufficiency: findings from the Dual RElease hydrocortisone versus conventionAl glucocorticoid replaceMent therapy in hypocortisolism (DREAM) trial (20249. Andrology. doi: 10.1111/andr.13635. - Feola T, Cozzolino A, De Alcubierre D, Pofi R, Galea N, Catalano C, Simeoli C, Di Paola N, Campolo F, Pivonello R, Isidori AM, Giannetta E. Cardiac magnetic resonance reveals biventricular impairment in Cushing's syndrome: a multicentre case-control study (2024). Endocrine. doi: 10.1007/s12020-024-03856-7 - Auchus RJ, Hamidi O, Pivonello R, Bancos I, Russo G, Witchel SF, Isidori AM, Rodien P, Srirangalingam U, Kiefer FW, Falhammar H, Merke DP, Reisch N, Sarafoglou K, Cutler GB Jr, Sturgeon J, Roberts E, Lin VH, Chan JL, Farber RH; CAHtalyst Adult Trial Investigators (2024). Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia. New England Journal of Medicine. doi: 10.1056/NEJMoa2404656. - De Alcubierre D, Feola T, Cozzolino A, Pofi R, Galea N, Catalano C, Auriemma RS, Pirchio R, Pivonello R, Isidori AM, Giannetta E. The spectrum of cardiac abnormalities in patients with acromegaly: results from a case-control cardiac magnetic resonance study (2024). Pituitary. doi: 10.1007/s11102-024-01403-1. - Bonaventura I, Tomaselli A, Angelini F, Ferrari D, De Alcubierre D, Hasenmajer V, Sbardella E, Cozzolino A, Paganini AM, Isidori AM, Minnetti M, Pofi R. Predicting postoperative hypocortisolism in patients with non-aldosterone-producing adrenocortical adenoma: a retrospective single-centre study (2024). Journal of Endocrinological Investigation. doi: 10.1007/s40618-023-02283-1. - De Alcubierre D, Gkasdaris G, Mordrel M, Joncour A, Briet C, Almairac F, Boetto J, Mouly C, Larrieu-Ciron D, Vasiljevic A, Villa C, Sergeant C, Ducray F, Feuvret L, Chanson P, Baussart B, Raverot G, Jouanneau E. BRAF and MEK inhibitor targeted therapy in papillary craniopharyngiomas: a cohort study (2024). European Journal of Endocrinology. doi: 10.1093/ejendo/lvae091. - Pofi R, De Alcubierre D, Dong J, Tomlinson JW. New Approaches to the Treatment of Hypercortisolism (2025). Annu Rev Med. doi: 10.1146/annurev-med-071723-044849 - Cela E, De Alcubierre D, Sbardella E. Polycystic Ovary Syndrome in the Context of Pituitary Adenomas: Prevalence, Pathophysiology and Clinical Management (2024). Clin Endocrinol (Oxf). doi: 10.1111/cen.15182. - Bonaventura I, Minnetti M, Ferrari D, Hasenmajer V, Tomaselli A, De Alcubierre D, Lenzi A, Pofi R, Isidori AM. Impact of Female Sex and Mild Cortisol Secretion on Coagulation Profile in Adrenal Incidentalomas (2024).. J Endocr Soc. doi: 10.1210/jendso/bvae215. - Kaparounaki C, Ilie MD, De Alcubierre D, Anagnostis P, Haidich AB, Isidori AM, Dekkers OM, Goulis DG, Raverot G. Medical treatment in acromegaly: a network meta-analysis. (2025). Eur J Endocrinol. 2025 Oct 30;193(5):S83-S94. doi: 10.1093/ejendo/lvaf221. - De Alcubierre D, Feola T, Puliani G, Ferrigno R, Amodeo ME, d'Aniello F, Pirchio R, Sada V, Pandozzi C, Sesti F, Gianfrilli D, Isidori AM, Grossman AB, Sbardella E. Endocrine and metabolic consequences of childhood-onset craniopharyngioma during the transition age: A literature review by the TALENT study group. (2025) Rev Endocr Metab Disord. 2025 Dec;26(6):989-1008. doi: 10.1007/s11154-025-09972-7. - Feola T, De Alcubierre D, Puliani G, Cozzolino A, Sciarra F, Vincenzi L, Hasenmajer V, Sada V, Appetecchia M, Giannetta E, Sbardella E, Jaffrain-Rea ML, Venneri MA, Isidori AM. Circulating immune cell profile in patients with acromegaly: results from the PROMISE, a prospective clinical trial. (2025) Eur J Endocrinol. 2025 Apr 30;192(5):577-589. doi: 10.1093/ejendo/lvaf085. - Ferrari D, Bonaventura I, Simeoli C, Tomaselli A, Vincenzi L, De Alcubierre D, Sciarra F, Rizzo F, Cerroni L, Di Paola N, Minnetti M, Sbardella E, Venneri MA, Pofi R, Pivonello R, Gianfrilli D, Hasenmajer V, Isidori AM. Chronotherapy With Once-Daily Osilodrostat Improves Cortisol Rhythm, Quality of Life, and Sleep in Cushing's Syndrome. (2025) J Clin Endocrinol Metab. 2025 Nov 18;110(12):3525-3537. doi: 10.1210/clinem/dgaf206. - Carbonara F, Gianno F, Feola T, Mancinelli F, De Alcubierre D, Moroni M, Lucantonio E, Arcella A, Di Pardo A, Morace R, Isidori AM, Gambardella S, Esposito V, Jaffrain-Rea ML. New Insights from the Expression of the Mismatch Repair System in Pituitary Neuroendocrine Tumors. (2026) Endocr Pathol. 2026 Jan 2;37(1):2. doi: 10.1007/s12022-025-09896-7. - Gatto F, Arecco A, De Alcubierre D, De Simone M, Gentiluomo R, Lanzi V, Paglia F, Frara S, Ferraù F, Colao A, Auriemma RS. Gender differences in the glycometabolic and cardiovascular features of acromegaly. (2026) Pituitary. 2026 Jan 22;29(1):34. doi: 10.1007/s11102-025-01629-7. - De Alcubierre D, Ferrari D, Tomaselli A, Moscucci F, Bonaventura I, Francia A, Vozza E, Lospinuso I, Ettorre E, Hasenmajer V, Minnetti M, Sbardella E, Tenuta M, Morelli S, Paganini AM, Isidori AM, Pofi R. Long-Term Cardiac Effects of Adrenalectomy Versus Surveillance in Mild Cortisol Excess: 5-Year Results from the prospective ITACA Study. (2026) Eur J Endocrinol. 2026 Jan 23:lvag018. doi: 10.1093/ejendo/lvag018. - De Alcubierre D, Feola T, Gianno F, Verrico M, Carbonara F, Venditti E, Isidori AM, Esposito V, Minniti G, Jaffrain-Rea ML. Life-Threatening Radiation Necrosis After Complete Response to Pembrolizumab in a Patient With a Metastatic Silent PIT1 Pituitary Neuroendocrine Tumor (PitNET). J Immunother (2026) Feb 23. doi: 10.1097/CJI.0000000000000601. Online ahead of print. PMID: 41725077