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5. 11β-HSD1 inhibition in men mitigates prednisolone-induced adverse effects in a proof-of-concept randomised double-blind placebo-controlled trial

Author

Othonos, Nantia, Pofi, Riccardo, Arvaniti, Anastasia, White, Sarah, Bonaventura, Ilaria, Nikolaou, Nikolaos, Moolla, Ahmad, Marjot, Thomas, Stimson, Roland H., van Beek, André P., van Faassen, Martijn, Isidori, Andrea M., Bateman, Elizabeth, Sadler, Ross, Karpe, Fredrik, Stewart, Paul M., Webster, Craig, Duffy, Joanne, Eastell, Richard, Gossiel, Fatma, Cornfield, Thomas, Hodson, Leanne, Jane Escott, K., Whittaker, Andrew, Kirik, Ufuk, Coleman, Ruth L., Scott, Charles A. B., Milton, Joanne E., Agbaje, Olorunsola, Holman, Rury R., and Tomlinson, Jeremy W.

Published
2023
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6. EMAS position statement: Testosterone replacement therapy in older men

Author

Kanakis, George A., Pofi, Riccardo, Goulis, Dimitrios G., Isidori, Andrea M., Armeni, Eleni, Erel, C. Tamer, Fistonić, Ivan, Hillard, Timothy, Hirschberg, Angelica-Lindén, Meczekalski, Blazej, Mendoza, Nicolás, Mueck, Alfred O., Simoncini, Tommaso, Stute, Petra, van Dijken, Dorenda, Rees, Margaret, and Lambrinoudaki, Irene

Published
2023
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8. Long‐term health consequences of congenital adrenal hyperplasia.

Author

Pofi, Riccardo, Ji, Xiaochen, Krone, Nils P., and Tomlinson, Jeremy W.

Subjects
*ADRENOGENITAL syndrome, *BONE health, *ADRENOCORTICOTROPIC hormone, *PATIENTS, *AGE groups
Abstract

Congenital adrenal hyperplasia (CAH) caused by 21‐hydroxylase deficiency accounts for 95% of all CAH cases and is one of the most common inborn metabolic conditions. The introduction of life‐saving glucocorticoid replacement therapy 70 years ago has changed the perception of CAH from a paediatric disorder into a lifelong, chronic condition affecting patients of all age groups. Alongside health problems that can develop during the time of paediatric care, there is an emerging body of evidence suggesting an increased risk of developing co‐morbidities during adult life in patients with CAH. The mechanisms that drive the negative long‐term outcomes associated with CAH are complex and involve supraphysiological replacement therapies (glucocorticoids and mineralocorticoids), excess adrenal androgens both in the intrauterine and postnatal life, elevated steroid precursors and adrenocorticotropic hormone levels. Alongside a review of mortality outcome, we discuss issues that need to be addressed when caring for the CAH patient including female and male fertility, cardio‐metabolic morbidity, bone health and other important long‐term outcomes of CAH. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Circadian clock disruption impairs immune oscillation in chronic endogenous hypercortisolism: a multi-levels analysis from a multicenter clinical trial

Author

Hasenmajer, Valeria, primary, Sbardella, Emilia, additional, Sciarra, Francesca, additional, Rizzo, Flavio, additional, Simeoli, Chiara, additional, Pivonello, Claudia, additional, Pivonello, Rosario, additional, Ceccato, Filippo, additional, Scaroni, Carla, additional, Arnaldi, Giorgio, additional, Pofi, Riccardo, additional, Cozzolino, Alessia, additional, Minnetti, Marianna, additional, Alunni, Fegatelli Danilo, additional, Conia, Simone, additional, Navigli, Roberto, additional, Gianfrilli, Daniele, additional, Anna, Venneri Mary, additional, and Isidori, Andrea, additional

Published
2024
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10. Predicting postoperative hypocortisolism in patients with non-aldosterone-producing adrenocortical adenoma: a retrospective single centre study

Author

Bonaventura, Ilaria, primary, Tomaselli, Alessandra, additional, Angelini, Francesco, additional, Ferrari, Davide, additional, De, Alcubierre Dario, additional, Hasenmajer, Valeria, additional, Sbardella, Emilia, additional, Cozzolino, Alessia, additional, Paganini, Alessandro, additional, Isidori, Andrea, additional, Minnetti, Marianna, additional, and Pofi, Riccardo, additional

Published
2024
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14. Phosphodiesterase-5 inhibition preserves renal hemodynamics and function in mice with diabetic kidney disease by modulating miR-22 and BMP7.

Author

Pofi, Riccardo, Fiore, Daniela, De Gaetano, Rita, Panio, Giuseppe, Gianfrilli, Daniele, Pozza, Carlotta, Barbagallo, Federica, Xiang, Yang Kevin, Giannakakis, Konstantinos, Morano, Susanna, Lenzi, Andrea, Naro, Fabio, Isidori, Andrea M, and Venneri, Mary Anna

Subjects
Kidney, Animals, Humans, Mice, Diabetic Nephropathies, Kidney Failure, Chronic, Hypertension, Creatinine, Albumins, MicroRNAs, Glomerular Filtration Rate, Gene Expression Regulation, Male, Hemodynamics, Cyclic Nucleotide Phosphodiesterases, Type 5, Receptors, Urokinase Plasminogen Activator, Bone Morphogenetic Protein 7, Phosphodiesterase 5 Inhibitors, Biomarkers, Kidney Failure, Chronic, Cyclic Nucleotide Phosphodiesterases, Type 5, Receptors, Urokinase Plasminogen Activator
Abstract

Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease. Preclinical and experimental studies show that PDE5 inhibitors (PDE5is) exert protective effects in DN improving perivascular inflammation. Using a mouse model of diabetic kidney injury we investigated the protective proprieties of PDE5is on renal hemodynamics and the molecular mechanisms involved. PDE5i treatment prevented the development of DN-related hypertension (P

Published
2017

18. Exploring sexual function in adrenal insufficiency: findings from the Dual RElease hydrocortisone versus conventionAl glucocorticoid replaceMent therapy in hypocortisolism (DREAM) trial

Author

Hasenmajer, Valeria, primary, De Alcubierre, Dario, additional, Ferrari, Davide, additional, Minnetti, Marianna, additional, Bonaventura, Ilaria, additional, Pofi, Riccardo, additional, Simeoli, Chiara, additional, Tomaselli, Alessandra, additional, Sciarra, Francesca, additional, Bottillo, Grazia, additional, Angelini, Francesco, additional, Cozzolino, Alessia, additional, Venneri, Mary Anna, additional, Jannini, Emmanuele A., additional, Gianfrilli, Daniele, additional, Pivonello, Rosario, additional, and Isidori, Andrea M., additional

Published
2024
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22. C-Cell Hyperplasia and Cystic Papillary Thyroid Carcinoma in a Patient with Type 1B Pseudohypoparathyroidism and Hypercalcitoninaemia: Case Report and Review of the Literature

Author

Ferrari, Davide, primary, Pandozzi, Carla, additional, Filice, Alessia, additional, Nardi, Christopher, additional, Cozzolino, Alessia, additional, Melcarne, Rossella, additional, Giacomelli, Laura, additional, Biffoni, Marco, additional, Di Gioia, Cira, additional, Merenda, Elisabetta, additional, Del Sindaco, Giulia, additional, Pagnano, Angela, additional, Pofi, Riccardo, additional, and Giannetta, Elisa, additional

Published
2023
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23. Effects of Dual-Release Hydrocortisone on Bone Metabolism in Primary and Secondary Adrenal Insufficiency: a 6-Year Study

Author

Hasenmajer, Valeria, primary, Ferrari, Davide, additional, De Alcubierre, Dario, additional, Sada, Valentina, additional, Puliani, Giulia, additional, Bonaventura, Ilaria, additional, Minnetti, Marianna, additional, Tomaselli, Alessandra, additional, Pofi, Riccardo, additional, Sbardella, Emilia, additional, Cozzolino, Alessia, additional, Gianfrilli, Daniele, additional, and Isidori, Andrea M, additional

Published
2023
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28. Preoperative 1 mg dexamethasone suppression test predicts hypothalamus-pituitary-adrenal axis recovery: A one-year retrospective study of adrenal incidentalomas undergoing unilateral adrenalectomy

Author

Bonaventura, Ilaria, primary, Tomaselli, Alessandra, additional, Angelini, Francesco, additional, Ferrari, Davide, additional, De, Alcubierre Dario, additional, Sada, Valentina, additional, Minnetti, Marianna, additional, Hasenmajer, Valeria, additional, Cozzolino, Alessia, additional, Sbardella, Emilia, additional, Isidori, Andrea, additional, and Pofi, Riccardo, additional

Published
2023
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30. Effects of Dual-Release Hydrocortisone on Bone Metabolism in Primary and Secondary Adrenal Insufficiency: A 6-Year Study.

Author

Hasenmajer, Valeria, Ferrari, Davide, Alcubierre, Dario De, Sada, Valentina, Puliani, Giulia, Bonaventura, Ilaria, Minnetti, Marianna, Tomaselli, Alessandra, Pofi, Riccardo, Sbardella, Emilia, Cozzolino, Alessia, Gianfrilli, Daniele, and Isidori, Andrea M

Subjects
LUMBAR vertebrae, SECONDARY metabolism, BONE metabolism, METABOLISM, ADRENAL insufficiency, BONE health
Abstract

Context Patients with primary (PAI) and secondary adrenal insufficiency (SAI) experience bone metabolism alterations, possibly due to excessive replacement. Dual-release hydrocortisone (DR-HC) has shown promising effects on several parameters, but bone metabolism has seldom been investigated. Objective We evaluated the long-term effects of once-daily DR-HC on bone in PAI and SAI. Methods Patients on immediate-release glucocorticoid therapy were evaluated before and up to 6 years (range, 4-6) after switching to equivalent doses of DR-HC, yielding data on bone turnover markers, femoral and lumbar spine bone mineral density (BMD), and trabecular bone score (TBS). Results Thirty-two patients (19 PAI, 18 female), median age 52 years (39.4-60.7), were included. At baseline, osteopenia was observed in 38% of patients and osteoporosis in 9%, while TBS was at least partially degraded in 41.4%. Higher body surface area–adjusted glucocorticoid doses predicted worse neck (P <.001) and total hip BMD (P <.001). Longitudinal analysis showed no significant change in BMD. TBS showed a trend toward decrease (P =.090). Bone markers were stable, albeit osteocalcin levels significantly varied. PAI and SAI subgroups behaved similarly, as did patients switching from hydrocortisone or cortisone acetate. Compared with men, women exhibited worse decline in TBS (P =.017) and a similar trend for neck BMD (P =.053). Conclusion After 6 years of chronic DR-HC replacement, BMD and bone markers remained stable. TBS decline is more likely due to an age-related derangement of bone microarchitecture rather than a glucocorticoid effect. Our data confirm the safety of DR-HC replacement on bone health in both PAI and SAI patients. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Altered Thyroid Feedback Loop in Klinefelter Syndrome: From Infancy Through the Transition to Adulthood

Author

Carlomagno, Francesco, primary, Minnetti, Marianna, additional, Angelini, Francesco, additional, Pofi, Riccardo, additional, Sbardella, Emilia, additional, Spaziani, Matteo, additional, Aureli, Alessia, additional, Anzuini, Antonella, additional, Paparella, Roberto, additional, Tarani, Luigi, additional, Porcelli, Tommaso, additional, De Stefano, Maria Angela, additional, Pozza, Carlotta, additional, Gianfrilli, Daniele, additional, and Isidori, Andrea M, additional

Published
2023
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36. Coagulation parameters in patients with adrenal incidentalomas and mild cortisol secretion: sex difference matters

Author

Bonaventura, Ilaria, primary, Minnetti, Marianna, additional, De, Alcubierre Dario, additional, Tomaselli, Alessandra, additional, Ferrari, Davide, additional, Sada, Valentina, additional, Angelini, Francesco, additional, Hasenmajer, Valeria, additional, Cozzolino, Alessia, additional, Sbardella, Emilia, additional, Pofi, Riccardo, additional, Lenzi, Andrea, additional, and Isidori, Andrea M., additional

Published
2023
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38. Hyperandrogenism in menopause: whose fault?

Author

Bonaventura, Ilaria, primary, Tomaselli, Alessandra, additional, Minnetti, Marianna, additional, De, Alcubierre Dario, additional, Tarantino, Chiara, additional, Cozzolino, Alessia, additional, Pofi, Riccardo, additional, Gianfrilli, Daniele, additional, Isidori, Andrea, additional, and Pozza, Carlotta, additional

Published
2023
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40. Bone metabolism and dual-release Hydrocortisone: results from a real-life study

Author

Ferrari, Davide, primary, Sada, Valentina, additional, Hasenmajer, Valeria, additional, De, Alcubierre Dario, additional, Puliani, Giulia, additional, Minnetti, Marianna, additional, Cozzolino, Alessia, additional, Bonaventura, Ilaria, additional, Tomaselli, Alessandra, additional, Pofi, Riccardo, additional, Lenzi, Andrea, additional, and M., Isidori Andrea, additional

Published
2023
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41. Testicular Dysfunction in 47,XXY Boys: When It All Begins. A Semilongitudinal Study

Author

Pozza, Carlotta, primary, Sesti, Franz, additional, Tenuta, Marta, additional, Spaziani, Matteo, additional, Tarantino, Chiara, additional, Carlomagno, Francesco, additional, Minnetti, Marianna, additional, Pofi, Riccardo, additional, Paparella, Roberto, additional, Lenzi, Andrea, additional, Radicioni, Antonio, additional, Isidori, Andrea M, additional, Tarani, Luigi, additional, and Gianfrilli, Daniele, additional

Published
2023
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42. Additional file 1 of Pituitary adenoma consistency affects postoperative hormone function: a retrospective study

Author

De Alcubierre, Dario, Puliani, Giulia, Cozzolino, Alessia, Hasenmajer, Valeria, Minnetti, Marianna, Sada, Valentina, Martines, Valentina, Zaccagnino, Antonella, Ruggeri, Andrea Gennaro, Pofi, Riccardo, Sbardella, Emilia, and Venneri, Mary Anna

Abstract

Additional file 1: Supplementary Table 1. Baseline and post-surgical characteristics of patients with fibrous pituitary adenomas.As per journal requirements, every additional file must have a corresponding caption. In this regard, please be informed that the caption was taken from the additional e-file itself. Please advise if the action taken is appropriate and amend if necessary.I confirm that the caption is appropriate.

Published
2023
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44. Susceptibility and characteristics of infections in patients with glucocorticoid excess or insufficiency: the ICARO tool

Author

Minnetti, Marianna, primary, Hasenmajer, Valeria, additional, Sbardella, Emilia, additional, Angelini, Francesco, additional, Simeoli, Chiara, additional, Di Paola, Nicola, additional, Cozzolino, Alessia, additional, Pivonello, Claudia, additional, De Alcubierre, Dario, additional, Chiloiro, Sabrina, additional, Baldelli, Roberto, additional, De Marinis, Laura, additional, Pivonello, Rosario, additional, Pofi, Riccardo, additional, and Isidori, Andrea M, additional

Published
2022
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46. "A morning cortisol is the most effective clinical predictor of short synacthen test outcome": A tertiary care centre experience.

Author

Mathara Diddhenipothage, Shani A. D., Beck, Katharina J., Loo, Helen, Amiyangoda, Gayana K., Pofi, Riccardo, Tomlinson, Jeremy W., and Pal, Aparna

Subjects
ADRENAL insufficiency, VERTIGO, TERTIARY care, HYDROCORTISONE, BLOOD pressure, SYMPTOMS, MORNING
Abstract

Objective: Increasing referrals to Endocrinology with nonspecific symptoms of suspected adrenal insufficiency (AI) has increased use of the short‐synacthen test (SST). Prevailing resource and safety concerns emphasise importance of patient selection criterion to optimise SST use. This study aimed to (1) document the adverse event profile of the SST (2) identify any pretest predictors of SST outcome. Design, Patients and Measurements: Retrospective data analysis of all patients referred for SST in Oxford from 2017 to 2021. Pretest clinical variables (age, sex, BMI, blood pressure and electrolytes), symptoms (fatigue, dizziness, weight loss) and pretest morning cortisol were included in the statistical model with the aim of identifying any variables that could predict SST outcome in Group 1 primary AI, Group 2 central AI and Group 3 glucocorticoid induced AI. Symptoms and signs during and post SST were also noted with the aim of describing adverse effects to synacthen across a large cohort. Results: A total 1480 SSTs (Males:38%, age 52 [39−66] years) were performed: 505 (34.1%) in Group 1, 838 (57%) in Group 2, and 137 (9.3%) in Group 3. Adverse‐effects were recorded in 1.8% of tests, including one episode of anaphylaxis. Pretest morning‐cortisol was the only predictor for an "SST pass" (whole cohort: B = 0.015, p < 0.001, Group 1: B = 0.018, p <.001; Group 2: B = 0.010, p < 0.012; Group 3: B = 0.018, p = <.001). A threshold of ≥343 nmol/l (receiver‐operating characteristic [ROC] area under the curve [AUC] = 0.725, 95% confidence interval [CI] 0.675−0.775, p < 0.001) for the whole cohort, ≥300 nmol/L (ROC AUC = 0.763, 95% CI 0.675 to 0.850, p < 0.001) for Group 1, ≥340 nmol/L (ROC AUC = 0.688, 95% CI 0.615 to 0.761, p < 0.001) for Group2, and ≥376 nmol/L [baseline cortisol] (ROC AUC = 0.783, 95% CI 0.708 to 0.859, p < 0.001) for Group 3, predicted an 'SST pass' with 100% specificity. Conclusions: Adverse effects to synacthen are rare. Pretest morning cortisol is a reliable predictor for SST outcome and is a helpful tool to rationalise use of the SST. Predictive morning‐cortisol thresholds vary according to the aetiology of AI. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the GoodFrom the Bad?

Author

Pofi, Riccardo, Caratti, Giorgio, Ray, David W, and Tomlinson, Jeremy W

Abstract

It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, are associated with a significant health and economic burden. The precise cellular mechanisms underpinning the differential action of glucocorticoids to drive the desirable and undesirable effects are still not completely understood. Faced with the unmet clinical need to limit glucocorticoid-induced adverse effects alongside ensuring the preservation of anti-inflammatory actions, several strategies have been pursued. The coprescription of existing licensed drugs to treat incident adverse effects can be effective, but data examining the prevention of adverse effects are limited. Novel selective glucocorticoid receptor agonists and selective glucocorticoid receptor modulators have been designed that aim to specifically and selectively activate anti-inflammatory responses based upon their interaction with the glucocorticoid receptor. Several of these compounds are currently in clinical trials to evaluate their efficacy. More recently, strategies exploiting tissue-specific glucocorticoid metabolism through the isoforms of 11β-hydroxysteroid dehydrogenase has shown early potential, although data from clinical trials are limited. The aim of any treatment is to maximize benefit while minimizing risk, and within this review we define the adverse effect profile associated with glucocorticoid use and evaluate current and developing strategies that aim to limit side effects but preserve desirable therapeutic efficacy.Graphical Abstract

Published
2023
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49. Susceptibility and characteristics of infections in patients with glucocorticoid excess or insufficiency: the ICARO tool

Author

Minnetti, Marianna, Hasenmajer, Valeria, Sbardella, Emilia, Angelini, Francesco, Simeoli, Chiara, Di Paola, Nicola, Cozzolino, Alessia, Pivonello, Claudia, De Alcubierre, Dario, Chiloiro, Sabrina, Baldelli, Roberto, De Marinis Grasso, Laura, Pivonello, Rosario, Pofi, Riccardo, Isidori, Andrea M, Chiloiro, Sabrina (ORCID:0000-0001-9241-2392), De Marinis, Laura (ORCID:0000-0001-9916-0669), Minnetti, Marianna, Hasenmajer, Valeria, Sbardella, Emilia, Angelini, Francesco, Simeoli, Chiara, Di Paola, Nicola, Cozzolino, Alessia, Pivonello, Claudia, De Alcubierre, Dario, Chiloiro, Sabrina, Baldelli, Roberto, De Marinis Grasso, Laura, Pivonello, Rosario, Pofi, Riccardo, Isidori, Andrea M, Chiloiro, Sabrina (ORCID:0000-0001-9241-2392), and De Marinis, Laura (ORCID:0000-0001-9916-0669)

Abstract

Objective: Registry data show that Cushing's syndrome (CS) and adrenal insufficiency (AI) increase mortality rates associated with infectious diseases. Little information is available on susceptibility to milder forms of infections, especially those not requiring hospitalization. This study aimed to investigate infectious diseases in patients with glucocorticoid disorders through the development of a specific tool.Methods: We developed and administered the InfeCtions in pAtients with endocRinOpathies (ICARO) questionnaire, addressing infectious events over a 12-month observation period, to 1017 outpatients referred to 4 University Hospitals. The ICARO questionnaire showed good test-retest reliability. The odds of infection (OR (95% CI)) were estimated after adjustment for confounders and collated into the ICARO score, reflecting the frequency and duration of infections.Results: In total, 780 patients met the inclusion criteria: 43 with CS, 32 with adrenal incidentaloma and mild autonomous cortisol secretion (MACS), and 135 with AI, plus 570 controls. Compared to controls, CS was associated with higher odds of urinary tract infections (UTIs) (5.1 (2.3-9.9)), mycoses (4.4 (2.1-8.8)), and flu (2.9 (1.4-5.8)). Patients with adrenal incidentaloma and MACS also showed an increased risk of UTIs (3.7 (1.7-8.0)) and flu (3.2 (1.5-6.9)). Post-dexamethasone cortisol levels correlated with the ICARO score in patients with CS. AI was associated with higher odds of UTIs (2.5 (1.6-3.9)), mycoses (2.3 (1.4-3.8)), and gastrointestinal infections (2.2 (1.5-3.3)), independently of any glucocorticoid replacement dose.Conclusions: The ICARO tool revealed a high prevalence of self-reported infections in patients with glucocorticoid disorders. ICARO is the first of its kind questionnaire, which could be a valuable tool for monitoring infections in various clinical settings.

Published
2022

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