The Endocrine Surgery Research Group is currently involved with a variety of projects, focused around different research areas, with particular attention on thyroid, parathyroid, and adrenal diseases. Ongoing research programs are focused on primary aldosteronism, hereditary primary hyperparathyroidism, pheochromocytoma, postoperative hypoparathyroidism and medullary thyroid carcinoma.

Translational research programs are conducted in close collaboration with the various national and international clinical and research Units, that through a multidisciplinary approach allow to integrate biomarkers, imaging, and insights from preclinical studies into the design of innovative clinical trials.

Ongoing projects

The skin-sodium compartment in human hypertension caused by aldosteronism

The skin-sodium compartment in human hypertension caused by aldosteronism. Salt intake is a major determinant of arterial hypertension, the most prevalent cardiovascular risk factor worldwide. The precise molecular mechanisms whereby Na⁺ retention raises blood pressure remained poorly defined. Experimental studies in animal models demonstrated that skin and muscle tissues can store Na⁺. A translational research program investigating the changes in skin-Na⁺ content before and after adrenalectomy in primary aldosteronism, the paradigm of salt-dependent HT and the most common cause of secondary HT, is currently ongoing.

Hereditary primary hyperparathyroidism

Hereditary primary hyperparathyroidism. Hereditary primary hyperparathyroidism represents 10% of all primary hyperparathryroidism. Putative genes have been scarcely studied and in some cases still unlnown. Among them, Hyperparathyroidism-jaw tumor syndrome is a variant of this phenotype, caused by mutations in the CDC73 oncosuppressor gene, encoding for a protein named parafibromin. Discovering novel CDC73 variants of unknown significance and their pathogenicity, the evaluation of parafibromin and parafibromin transcriptional targets level, subcellular localization, cell proliferation, apoptosis and activation of DNA repair mechanisms performing “in vitro” experiments, will improve the knowledge of parafibromin function, allowing a more tailored surgical approach and identification of new therapeutic targets. CDKN1b and GCM2 germline mutations have been also recently described as responsible for the development of novel variants of hereditary pHPT. Due to the peculiar features of hereditary primary hyperparathyroidism, the genetic, biochemical, clinical, pathological features and the surgical strategy  need to be studied in order to assess a tailored approach.

Medullary thyroid carcinoma

Medullary thyroid carcinoma. Medullary thyroid carcinoma is a rare and aggressive malignancy; it is mainly sporadic, but a hereditary pattern is present in 20–30% of cases. A general objective of the Endocrine Surgery Unit mission is to collect data from patients undergoing surgery for medullary thyroid carcinoma to gather relevant demographics, clinical and genetic features, extent of surgery, pathology finding, in order to create an extensive database including also follow-up data. Moreover, tumor tissue samples and adjacent normal tissue were also collected and analyzed for the molecular expression patterns of clinically relevant genes.

Postoperative hypoparathyroidism

Postoperative hypoparathyroidism. Postoperative hypoparathyroidism (HypoPTH) is the most common complication following total thyroidectomy; it is usually reported with variable prevalence, but it represents a relevant problem even in high-volume centers. Several predictive and risk factors have been reported, but data on postoperative follow-up are scarce. The identification of reliable markers of HypoPTH is essential to start preventive treatment, allowing a safe and possibly early hospital discharge before patients become symptomatic, since hypocalcemia may occur even very late (up to 64 h after surgery). Moreover, it is relevant to identify (and possibly eliminate) risk factors for definitive HypoPTH and differentiate patients with transient postoperative parathyroid insufficiency from those with protracted and permanent HypoPTH that need a different follow-up and have different clinical consequences. Our study aims to evaluate and compare the risk factors for post-surgical HypoPTH in a large series of patients at a tertiary academic, high-volume center, also focusing on the risk and protective factors for persistent HypoPTH.

Pheochromocytoma and paraganglioma

Pheochromocytomas and paragangliomas (PPGLs) are rare tumors that arise from chromaffin tissue of the adrenal medulla and the sympathetic and/or the parasympathetic chain, respectively. Most PPGLs are sporadic, but 25–40% occur in hereditary syndromes such as multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis type 1, von Hippel–Lindau syndrome, and hereditary PPGLs due to gene mutations in succinate dehydrogenase. Since 2017, and recently confirmed by the 2022 WHO classification, PPGLs are no longer categorized as “benign” and “malignant” but as “metastatic” and “not metastatic” since all PPGLs are considered malignant, although with a variable aggressiveness and tendency to metastasize. Most PPGLs are not metastatic; about 10% show metastatic behavior at onset, but this number rises (30%) when considering that metastases have been reported, even after several decades, after initial surgical resection. Metastases and recurrences have a significant impact on survival since the 5- and 10-year survival rates for metastatic PPGLs are approximately 65% and 35%, respectively.
Unfortunately, there are currently no clinical, biochemical, histopathological, or molecular markers available to accurately forecast the metastatic behavior of PPGLs at diagnosis. Over the last 20 years, significant progress has been achieved in the field of molecular biology and in the study of markers related to the aggressive behavior of PPGLs, but their clinical significance has yet to be fully clarified.  This research program focuses on the identification of pathogenetic molecular markers of metastatic behavior in PPGLs to identify cases with negative prognostic outcomes and, eventually, metabolic pathways that can be targeted for new drugs.

Pubblications

Torresan F, Rossi FB, Caputo I, Zanin S, Caroccia B, Mattarei A, Paccagnella M, Kohlscheen E, Seccia TM, Iacobone M, Rossi GP. Water and Electrolyte Content in Hypertension in the Skin (WHYSKI) in Primary Aldosteronism. Hypertension. 2024 Dec;81(12):2468-2478. doi: 10.1161/HYPERTENSIONAHA.124.23700.

Iacobone M, Watutantrige-Fernando S, Zovato S, Tognazzo S, Dughiero S, Augenti V, Camozzi V, Mian C, Torresan F, Nomine-Criqui C, Brunaud L. Germline mutations of GCM2 cause a novel variant of hereditary primary hyperparathyroidism. Updates Surg. 2025 May 6. doi: 10.1007/s13304-025-02179-0.

Torresan F, Censi S, Pennelli G, Galuppini F, Mian C, Iacobone M. Prophylactic and Early Thyroidectomy in RET Germline Mutation Carriers in Pediatric and Adult Population: Long-Term Outcomes of a Series of 63 Patients. Cancers (Basel). 2022 Dec 17;14(24):6226. doi: 10.3390/cancers14246226. PMID: 36551711; PMCID: PMC9776584. 

Dughiero S, Torresan F, Censi S, Mian C, Carrillo Lizarazo JL, Iacobone M. Risk and Protective Factors of Postoperative and Persistent Hypoparathyroidism after Total Thyroidectomy in a Series of 1965 Patients. Cancers (Basel). 2024 Aug 17;16(16):2867. doi: 10.3390/cancers16162867.

Torresan F, Beber A, Schiavone D, Zovato S, Galuppini F, Crimì F, Ceccato F, Iacobone M. Long-Term Outcomes after Surgery for Pheochromocytoma and Sympathetic Paraganglioma. Cancers (Basel). 2023 May 24;15(11):2890. doi: 10.3390/cancers15112890.

People involved: 

MAURIZIO IACOBONE, MD, FEBS (Endocrine Surgery)(Professor of Surgery)

Group members:

FRANCESCA TORRESAN, MD, PhD (Surgeon, Azienda Ospedaliera di Padova)
COSTANTINO PAGETTA, MD (Surgeon, Azienda Ospedaliera di Padova)
ERIC CASAL IDE, MD, PhD (Surgeon, Azienda Ospedaliera di Padova)