High-dose intravenous methylprednisolone is effective in subacute thyroiditis unresponsive to oral steroids Simone Rodolfi, Guia Maria Vannucchi, Michela Perrino, Carla Colombo, Danila Covelli, Luca Persani, Laura Fugazzola, Irene Campi European Thyroid Journal, 2026 Objective Subacute thyroiditis (SAT) relapsing or refractory to standard of care oral prednisone (OP) therapy is rare, but affected patients experience significant discomfort due to prolonged and uncontrolled neck pain. Here, we report the efficacy of high-dose intravenous methylprednisolone (IVMP) therapy in the treatment of such cases. Methods In this pilot study, we included 14 patients diagnosed with SAT in the period 2014–2024, in a single center. Therapy consisted of 500 mg of IVMP, divided into two weekly infusions and titrated down based on clinical response. Thyroid function tests, thyroid ultrasound, and inflammatory markers were assessed at baseline and throughout the follow-up up to 3–6 months after IVMP discontinuation. Results At baseline, 4 and 10 patients had thyrotoxicosis or were euthyroid, respectively. The median (IQR) duration of treatment was 26 days (21–38). At the end of the treatment, we observed a complete clinical, ultrasonographic, and biochemical response in twelve patients (86%), whereas thirteen (93%) had immediate resolution of neck pain and thyrotoxicosis. Only one patient did not improve at the end of IVMP protocol, and she was the only one experiencing a delayed remission with persistent hypothyroidism. Mild grade 1 and 2 adverse events (hyperglycemia, arterial hypertension, and neutrophilia) occurred in 8 out of 14 patients. Conclusion IVMP therapy resulted in a rapid clinical and ultrasonographic improvement in most patients with relapsing SAT unresponsive to oral steroids. This response allowed for a shorter treatment duration, with good tolerability, minimal adverse events, and a low incidence of hypothyroidism during follow-up.
Vitamin D, adiposity, and cardiometabolic risk: Insights from a multivariable cross-sectional study Carla Colombo, Valentina Fabiano, Lucia Labati, Martina Loiodice, Daniele Ceruti, Irene Campi, Valentina Cuneo, Gianvincenzo Zuccotti, Valeria Calcaterra Obesity Research and Clinical Practice, 2026 INTRODUCTION: Vitamin D deficiency has been implicated in various metabolic disorders, but its relationship with adiposity and atherogenic risk remains not fully elucidated. We assessed associations between serum vitamin D levels and a wide range of metabolic, atherogenic, and adiposity-related markers in adults stratified by weight status. METHODS: A cross-sectional analysis was conducted on 130 adults categorized according to their body weight status into: normal weight, overweight, and obesity. Additionally, participants were grouped based on serum vitamin D levels (threshold 20 ng/mL) Clinical, metabolic, and anthropometric variables were compared across groups. A principal component analysis (PCA) was applied to explore underlying patterns of association. RESULTS: As expected, significant differences in cardiometabolic parameters emerged across weight categories (p < 0.05). However, vitamin D levels showed no significant correlation with most metabolic variables in either univariate or multivariate analysis. PCA revealed that vitamin D and body mass index (BMI) were consistently represented as opposing vectors, suggesting distinct but potentially interacting influences on metabolic risk. While BMI was associated with indices such as TG/HDL, atherogenic index of plasma, and cardiometabolic risk index, vitamin D correlated more closely with HDL, total cholesterol, and Triglyceride-Cholesterol Body Index. CONCLUSIONS: Findings indicate that vitamin D may influence cardiometabolic profiles through mechanisms that are at least partially independent of adiposity. Despite the lack of direct correlations, the divergent associations observed in PCA suggest possible interaction effects between BMI and vitamin D. Further longitudinal studies are needed to evaluate vitamin D's role as a context-dependent modulator of metabolic risk.
Variable Diagnoses in Cases Referred for Discordant Thyroid Function Tests: Focus on Lymphoproliferative Disorders Antonio Musolino, Giacomo Fabio Antonio Grifoni, Simone Rodolfi, Massimiliano Andreasi, Ilaria Bulgarelli, et al. Thyroid, 2025 Background: Careful consideration of the differential diagnosis of discordant thyroid function tests (TFTs) is fundamental to prevent mismanagement, waste of resources, uncover rare thyroid disorders, or other underlying critical conditions in patients referred for the evaluation of this issue. Here, we describe the frequency of underlying diagnoses and focus on cases in which the identification of analytical interferences led to the discovery of lymphoproliferative disorders. Methods: This is a retrospective cross-sectional study including all consecutive patients referred to the Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano, for suspected central hyperthyroidism between January 2017 and February 2025. Inclusion criteria were based on laboratory findings of (1) elevated or inappropriately normal thyrotropin (TSH) with high FT4 and/or FT3, (2) elevated TSH with FT4 in the upper reference range, and (3) failure of TSH to normalize despite levothyroxine therapy, along with rising FT4 levels. The differential diagnosis was made by (1) reassessment of discrepant results in the hormone panel by different analytical methods or tandem mass spectrometry; (2) serum serial dilution or polyethylene glycol precipitation; (3) evaluation of rheumatoid factor, serum protein electrophoresis (SPEP), and cryoglobulins; and (4) deep clinical phenotyping and/or confirmatory genetic testing, as appropriate. Results: Among 144 patients referred for discordant TFTs mimicking central hyperthyroidism, 44% were genuine rare thyroid disorders—32% with resistance to thyroid hormone beta (RTHβ), 7% with TSH-secreting adenomas, and 5% other diagnosis—and 56% had assay interference. In this latter group, interfering clonal paraproteins were detected in 6/81 cases. One patient was ultimately diagnosed with multiple myeloma, another one with type 1 cryoglobulinemia due to indolent marginal zone B non-Hodgkin lymphoma, and the remaining four cases were found to have monoclonal gammopathy of uncertain significance. The clonal paraprotein was an IgM kappa/lambda in five cases and IgG kappa or IgA kappa in one case, respectively. Conclusions: In patients referred for discordant TFTs, RTHβ is the most prevalent thyroid disorder, but variable assay interferences represent the most frequent condition. In these cases, SPEP and hematological investigations are highly recommended.
Lifestyle Interventions to Tackle Cardiovascular Risk in Thyroid Hormone Signaling Disorders Simone Rodolfi, Giuditta Rurale, Federica Marelli, Luca Persani, Irene Campi Nutrients, 2025 Thyroid hormones (THs) play a central role in cardiovascular and metabolic regulation, influencing lipid metabolism, insulin sensitivity and resting energy expenditure. Inherited disorders of impaired sensitivity to THs—including resistance to thyroid hormone alpha (RTHα) and beta (RTHβ), monocarboxylate transporter 8 (MCT8) deficiency and selenoprotein deficiency—lead to complex, multisystemic clinical features. Although these conditions are rare, with RTHβ being the most common and affecting about 1 in 20,000 newborns, they share clinical features with more prevalent thyroid disorders, such as hypothyroidism and hyperthyroidism, as well as neurological manifestations including muscle wasting and spasticity. These conditions present abnormal patterns of thyroid function and are associated with tissue-specific comorbidities such as arrhythmias, heart failure, dyslipidemia, hepatic steatosis, insulin resistance, and metabolic syndrome. To date, no targeted or controlled studies have evaluated the impact of lifestyle modifications in these patient populations. Therefore, this narrative review proposes plausible management strategies based on pathophysiological insights into the effects of thyroid hormones on target organs, combined with clinical reasoning and evidence extrapolated from related disorders. Physical exercise and diet may complement pharmacological treatments (e.g., levothyroxine or TRIAC) to improve cardiovascular and metabolic outcomes. In RTHβ, aerobic exercise enhances cardiovascular health, while a Mediterranean diet supports lipid control and glycemic parameters. In RTHα, physical exercise may aid neuromotor development, and a fluid-rich, fiber-moderated diet can alleviate constipation. In MCT8 deficiency, physiotherapy may improve mobility and relieve contractures, while nutritional support (e.g., feeding tube, gastrostomy) can be necessary to tackle feeding difficulties and reduce pulmonary complications. In selenoprotein deficiency, low-to-moderate physical exercise and an antioxidant-rich diet may protect against oxidative stress at several tissue levels. Although quantitative evidence is limited, this narrative review synthesizes current insights, providing a meaningful basis for future validation and research.
Case Report: Challenges of an extremely delayed diagnosis of classic congenital adrenal hyperplasia in a completely virilized 46,XX patient Alice Casiraghi, Irene Campi, Silvia Federici, Franco Cernigliaro, Soara Menabò, Luca Persani Frontiers in Endocrinology, 2025 Classic Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency is typically diagnosed in early life. We report a 46,XX completely virilized 46,XX patient who was diagnosed with classic CAH at the age of 73 years. He was under follow-up for prostate hyperplasia and referred after the finding of giant bilateral adrenal myelolipomas. He presented with hormonal values initially interpreted as suggestive of hypogonadotropic hypogonadism, prompting further biochemical and genetic analysis. Next-generation sequencing identified heterozygous variants in X-linked genes, uncovering a 46,XX difference of sex development (DSD). Then, CYP21A2 molecular analysis revealed compound heterozygosity for two pathogenic variants (p.I173N, p.R357W), confirming simple virilizing CAH. The patient’s reticent attitude contributed to the diagnostic delay. However, this unique case reveals the challenges generated by the paraurethral glands hyperplasia - mimicking a prostate due to prolonged untreated hyperandrogenism - as well as the repeated failure to recognize Müllerian remnants on imaging and the critical issues related to diagnostic communication.
Increased cardiovascular morbidity and reduced life expectancy in a large Italian cohort of patients with resistance to thyroid hormone β (RTHβ) Irene Campi, Simona Censi, Flavia Prodam, Luisa Petrone, Giulia Brigante, Tommaso Porcelli, Rosaria Maddalena Ruggeri, Maria Cristina Vigone, Giuditta Rurale, Serafino Lio, Carla Pelusi, Luca Persani European Journal of Endocrinology, 2024 Objective Decreased survival and higher cardiovascular morbidity have been recently reported in a UK cohort of 61 RTHβ patients, but there is no evidence from other countries. Design Retrospective cohort study from an historical group of 284 Italian RTHβ patients, diagnosed between 1984 and 2023. Methods We collected data on diagnosis of 284 cases and longitudinal data of 249 RTHβ who carried heterozygous pathogenic variants in the THRB gene. We studied how thyroid function and recognized risk factors for cardiovascular disease, such as hypertension and diabetes, affected overall mortality and major cardiovascular events. Results The cumulative prevalence of sinus/supraventricular tachycardia and atrial fibrillation was 40% and 18%, respectively. FT4 values 57% higher than the upper limit of normal were associated with premature cardiovascular manifestations. Major cardiovascular events (MACEs) occurred in RTHβ patients at a median age (IQR) of 59.4 years (50.4-66.4) and early mortality resulted in a mean of 11 years of life lost. While at univariable analysis hypertension, dyslipidemia, high fasting glucose/diabetes were also associated with MACEs, at multivariable analysis only age at diagnosis, increased fT4 levels, and male gender remained significantly associated with MACEs and age at diagnosis and higher fT4 levels with mortality. Previous thyroidectomy or radioiodine therapy had no statistically significant effect in the prevention of major cardiovascular events or all-cause mortality. Conclusions These data should raise the general awareness on the cardiovascular risk and prompt a proactive cardiovascular monitoring in RTHβ, especially in men and those with fT4 levels above 30 pmol/L.
Challenging diagnosis of resistance to thyroid hormone in a patient with COVID-19, pituitary microadenoma and unusual response to octreotide long-acting release test Cristian Petolicchio, Sara Brasili, Stefano Gay, Francesco Cocchiara, Irene Campi, Luca Persani, Lara Vera, Diego Ferone, Federico Gatto Endocrinology Diabetes and Metabolism Case Reports, 2024 Summary The resistance to thyroid hormone syndrome (RTHβ) occurs uncommonly and requires a high level of clinical suspicion and specific investigations to reach a precise diagnosis and to avoid unnecessary and potentially harmful therapies. We report a case of a young male patient referred to our unit for SARS-CoV-2 infection and atrial fibrillation with elevated thyroid hormones and non-suppressed thyroid-stimulating hormone (TSH), for which antithyroid therapy was prescribed. A mood disorder was reported in the medical history. The family history was unknown as the patient was adopted. Thyroid-specific antibodies were undetectable, and thyroid ultrasound revealed a normal thyroid gland without nodules. After the resolution of SARS-CoV-2 infection, the diagnostic workup continued, and the pituitary MRI revealed a small area ascribable to a microadenoma. Due to atrial fibrillation, the execution of the T3 test was contraindicated. The octreotide long-acting release (LAR) test showed an initial reduction of free thyroid hormones levels at first administration, which was consistent with the presence of a TSH-secreting pituitary tumour, although an escape from the response was observed after the following two injections of octreotide LAR. Indeed, the genetic investigation revealed a variant in heterozygosity of the THRβ gene (Pro453Ser), thus leading to an RTHβ diagnosis, and, therefore, medical treatment with triiodothyroacetic acid was initiated. After 2 years from the SARS-CoV-2 infection, the patient continues the follow-up at our outpatient clinic, and no other medical interventions are needed. Learning points RTHβ is a rare genetic syndrome characterised by discrepant thyroid function tests and by a dissociation between the observed hormone levels and the expected patient signs and symptoms. Features of thyroid hormone deficiency in TR-ß dependent tissues (pituitary gland, hypothalamus, liver and neurosensitive epithelia), as well as thyroid hormone excess in TR-α-dependent tissues (heart, bone, skeletal muscle and brain), may coexist in the same individual. Clinical pictures can be different even when the same variant occurs, suggesting that other genetic and/or epigenetic factors may play a role in determining the patient’s phenotype. Differentiating RTHβ from a TSH-secreting pituitary tumour is very difficult, especially when a concomitant pituitary adenoma is detected during diagnostic workup. The injection of long-acting somatostatin analogues can help differentiate the two conditions, but it is important to detect any interference in the dosage of thyroid hormones to avoid an incorrect diagnosis. Genetic testing is fundamental to prevent unnecessary and potentially harmful therapies. Medical treatment with triiodothyroacetic acid was demonstrated to be effective in reducing thyroid hormone excess and controlling symptoms.
Association of COVID-19 mortality with serum selenium, zinc and copper: Six observational studies across Europe Kamil Demircan, Thilo Samson Chillon, Tommy Bracken, Ilaria Bulgarelli, Irene Campi, Gijs Du Laing, Samira Fafi-Kremer, Laura Fugazzola, Alejandro Abner Garcia, Raban Heller, David J. Hughes, Louis Ide, Georg Jochen Klingenberg, Pawel Komarnicki, Zbigniew Krasinski, Alain Lescure, Patrick Mallon, Arash Moghaddam, Luca Persani, Mirko Petrovic, Marek Ruchala, Morgane Solis, Linos Vandekerckhove, Lutz Schomburg Frontiers in Immunology, 2022
Tissue sensitivity to thyroid hormones may change over time Giorgio Radetti, Franco Rigon, Alessandro Salvatoni, Irene Campi, Tiziana De Filippis, Valentina Cirello, Silvia Longhi, Fabiana Guizzardi, Marco Bonomi, Luca Persani European Thyroid Journal, 2022
Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy Irene Campi, Luigi Gennari, Daniela Merlotti, Christian Mingiano, Alessandro Frosali, Luca Giovanelli, Camilla Torlasco, Martino F. Pengo, Francesca Heilbron, Davide Soranna, Antonella Zambon, Marta Di Stefano, Carmen Aresta, Marco Bonomi, Biagio Cangiano, Vittoria Favero, Letizia Fatti, Giovanni Battista Perego, Iacopo Chiodini, Gianfranco Parati, Luca Persani BMC Infectious Diseases, 2021
Hormones and Autoimmunity Roberta Gualtierotti, Carolina Artusi, Guia Maria Vannucchi, Irene Campi, Luca Persani, Pier Luigi Meroni Mosaic of Autoimmunity the Novel Factors of Autoimmune Diseases, 2019
Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves' orbitopathy (MINGO): a randomised, observer-masked, multicentre trial George J Kahaly, Michaela Riedl, Jochem König, Susanne Pitz, Katharina Ponto, Tanja Diana, Elena Kampmann, Elisa Kolbe, Anja Eckstein, Lars C Moeller, Dagmar Führer, Mario Salvi, Nicola Curro, Irene Campi, Danila Covelli, Marenza Leo, Michele Marinò, Francesca Menconi, Claudio Marcocci, Luigi Bartalena, Petros Perros, Wilmar M Wiersinga, Göksun Ayvaz, Lelio Baldeschi, Kostas Boborides, Antonella Boschi, Thomas H Brix, Lucy Clarke, Colin Dayan, Chantal Daumerie, A Jane Dickinson, Nicole Fichter, Laszlo Hegedüs, Onur Konuk, Gerassimos E Krassas, Carol Lane, John Lazarus, Dan S Morris, Maarten. Mourits, Marco Nardi, Chris Neoh, Jacques Orgiazzi, Simon H S Pearce, Georg von Arx, Milos Zarkovic Lancet Diabetes and Endocrinology, 2018
Graves’ disease Irene Campi, Mario Salvi Encyclopedia of Endocrine Diseases, 2018
Retinal photoreceptor functions are compromised in patients with resistance to thyroid hormone syndrome (RTHb) Irene Campi, Gabriella Cammarata, Stefania Bianchi Marzoli, Paolo Beck-Peccoz, Diletta Santarsiero, Davide Dazzi, Alessandra Bottari de Castello, Elena Giuliana Taroni, Francesco Viola, Caterina Mian, Sara Watutantrige-Fernando, Carla Pelusi, Marina Muzza, Maria Antonia Maffini, Luca Persani Journal of Clinical Endocrinology and Metabolism, 2017
Fetal cell microchimerism: A protective role in autoimmune thyroid diseases Valentina Cirello, Roberta Rizzo, Milena Crippa, Irene Campi, Daria Bortolotti, Silvia Bolzani, Carla Colombo, Guia Vannucchi, Maria Antonia Maffini, Federica de Liso, Stefano Ferrero, Palma Finelli, Laura Fugazzola European Journal of Endocrinology, 2015
Thyrotropin-secreting pituitary adenomas: Outcome of pituitary surgery and irradiation Elena Malchiodi, Eriselda Profka, Emanuele Ferrante, Elisa Sala, Elisa Verrua, Irene Campi, Andrea Gerardo Lania, Maura Arosio, Marco Locatelli, Pietro Mortini, Marco Losa, Enrico Motti, Paolo Beck-Peccoz, Anna Spada, Giovanna Mantovani Journal of Clinical Endocrinology and Metabolism, 2014
A novel albumin gene mutation (R222I) in familial dysalbuminemic hyperthyroxinemia Nadia Schoenmakers, Carla Moran, Irene Campi, Maura Agostini, Olivia Bacon, Odelia Rajanayagam, John Schwabe, Sonia Bradbury, Timothy Barrett, Frank Geoghegan, Maralyn Druce, Paolo Beck-Peccoz, Angela O'Toole, Penelope Clark, Michelle Bignell, Greta Lyons, David Halsall, Mark Gurnell, Krishna Chatterjee Journal of Clinical Endocrinology and Metabolism, 2014
The IGSF1 deficiency syndrome: Characteristics of male and female patients S. D. Joustra, N. Schoenmakers, L. Persani, I. Campi, M. Bonomi, G. Radetti, P. Beck-Peccoz, H. Zhu, T. M. E. Davis, Y. Sun, E. P. Corssmit, N. M. Appelman-Dijkstra, C. A. Heinen, A. M. Pereira, A. J. Varewijck, J. A. M. J. L. Janssen, E. Endert, R. C. Hennekam, M. P. Lombardi, M. M. A. M. Mannens, B. Bak, D. J. Bernard, M. H. Breuning, K. Chatterjee, M. T. Dattani, W. Oostdijk, N. R. Biermasz, J. M. Wit, A. S. P. van Trotsenburg Journal of Clinical Endocrinology and Metabolism, 2013
Thyroid hormone resistance: A novel mutation in thyroid hormone receptor beta (THRB) gene - case report Turkish Journal of Pediatrics, 2013
Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement Yu Sun, Beata Bak, Nadia Schoenmakers, A S Paul van Trotsenburg, Wilma Oostdijk, Peter Voshol, Emma Cambridge, Jacqueline K White, Paul le Tissier, S Neda Mousavy Gharavy, Juan P Martinez-Barbera, Wilhelmina H Stokvis-Brantsma, Thomas Vulsma, Marlies J Kempers, Luca Persani, Irene Campi, Marco Bonomi, Paolo Beck-Peccoz, Hongdong Zhu, Timothy M E Davis, Anita C S Hokken-Koelega, Daria Gorbenko Del Blanco, Jayanti J Rangasami, Claudia A L Ruivenkamp, Jeroen F J Laros, Marjolein Kriek, Sarina G Kant, Cathy A J Bosch, Nienke R Biermasz, Natasha M Appelman-Dijkstra, Eleonora P Corssmit, Guido C J Hovens, Alberto M Pereira, Johan T den Dunnen, Michael G Wade, Martijn H Breuning, Raoul C Hennekam, Krishna Chatterjee, Mehul T Dattani, Jan M Wit, Daniel J Bernard Nature Genetics, 2012
Mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy Alison Sleigh, Anna Stears, Kerrie Thackray, Laura Watson, Alessandra Gambineri, Sath Nag, V. Irene Campi, Nadia Schoenmakers, Soren Brage, T. Adrian Carpenter, Peter R. Murgatroyd, Stephen O'Rahilly, Graham J. Kemp, David B. Savage Journal of Clinical Endocrinology and Metabolism, 2012
Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans Erik Schoenmakers, Maura Agostini, Catherine Mitchell, Nadia Schoenmakers, Laura Papp, Odelia Rajanayagam, Raja Padidela, Lourdes Ceron-Gutierrez, Rainer Doffinger, Claudia Prevosto, Jian’an Luan, Sergio Montano, Jun Lu, Mireille Castanet, Nick Clemons, Matthijs Groeneveld, Perrine Castets, Mahsa Karbaschi, Sri Aitken, Adrian Dixon, Jane Williams, Irene Campi, Margaret Blount, Hannah Burton, Francesco Muntoni, Dominic O’Donovan, Andrew Dean, Anne Warren, Charlotte Brierley, David Baguley, Pascale Guicheney, Rebecca Fitzgerald, Alasdair Coles, Hill Gaston, Pamela Todd, Arne Holmgren, Kum Kum Khanna, Marcus Cooke, Robert Semple, David Halsall, Nicholas Wareham, John Schwabe, Lucia Grasso, Paolo Beck-Peccoz, Arthur Ogunko, Mehul Dattani, Mark Gurnell, Krishna Chatterjee Journal of Clinical Investigation, 2010
TSH-secreting adenomas Paolo Beck-Peccoz, Luca Persani, Deborah Mannavola, Irene Campi Best Practice and Research Clinical Endocrinology and Metabolism, 2009
Resistance to thyroid hormone and cardiovascular risk Irene Campi, Deborah Mannavola, Paolo Beck-Peccoz, Clinical Fellow, Research Assistant, Full Professor of Endocrinology, Director, School of Specialization in Endocrinology, Metabolic Diseases, Fondazione Policlinico-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Milan US Endocrinology, 2009
