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Article ; Online: Only as strong as the weakest link: Adrenal insufficiency in the COVID-19 storm.

Hasenmajer, Valeria

2023 Volume 295, Issue 3, Page(s) 278–280

MeSH term(s)	Humans ; COVID-19/complications ; Adrenal Insufficiency/complications ; SARS-CoV-2
Language	English
Publishing date	2023-12-31
Publishing country	England
Document type	Editorial
ZDB-ID	96274-0
ISSN	1365-2796 ; 0954-6820
ISSN (online)	1365-2796
ISSN	0954-6820
DOI	10.1111/joim.13763
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Article ; Online: COVID-19 pandemic and adrenals: deep insights and implications in patients with glucocorticoid disorders.

Cozzolino, Alessia / Hasenmajer, Valeria / Newell-Price, John / Isidori, Andrea M

Endocrine

2023 Volume 82, Issue 1, Page(s) 1–14

Abstract: Purpose: Coronavirus disease-19 (COVID-19) has spread throughout the world. It was initially defined as a potentially severe syndrome affecting the respiratory tract, but it has since been shown to be a systemic disease with relevant extrapulmonary ... ...

Abstract	Purpose: Coronavirus disease-19 (COVID-19) has spread throughout the world. It was initially defined as a potentially severe syndrome affecting the respiratory tract, but it has since been shown to be a systemic disease with relevant extrapulmonary manifestations that increase mortality. The endocrine system has been found to be vulnerable to COVID-19 infection. The current review aims to evaluate the available data on the impact of COVID-19 infection and treatment, as well as COVID-19 vaccines, on adrenal gland function, particularly in patients with GC disorders. Methods: A thorough search of published peer-reviewed studies in PubMed was performed using proper keywords. Results: Adrenal viral tropism and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the adrenal glands have been demonstrated, and adrenal insufficiency (AI) is a rare, but potentially severe complication in COVID-19 disease, whose recognition can be difficult if only for the empirical treatments administered in the early stages. Glucocorticoid (GC) treatment have had a pivotal role in preventing clinical deterioration in patients with COVID-19, but long-term GC use may increase COVID-19-related mortality and the development of iatrogenic AI. Patients with GC disorders, especially AI and Cushing's syndrome, have been identified as being at high risk of COVID-19 infection and complications. Published evidence suggests that AI patient awareness and proper education may help adjust GC replacement therapy appropriately when necessary, thereby reducing COVID-19 severity. The COVID-19 pandemic has had an impact on AI management, particularly in terms of adherence to patients' care plans and self-perceived challenges. On the other hand, published evidence suggests that the clinical course of COVID-19 may be affected by the severity of hypercortisolism in patients with CS. Therefore, to ameliorate the risk profile in these patients, cortisol levels should be adequately controlled, along with careful monitoring of metabolic and cardiovascular comorbidities. To date, the COVID-19 vaccine remains the only available tool to face SARS-CoV-2, and it should not be treated differently in patients with AI and CS. Conclusion: SARS-CoV-2 infection has been linked to adrenal damage and AI is a rare complication in COVID-19 disease, requiring prompt recognition. Educational efforts and patient awareness may reduce COVID-19 severity in patients with AI. Control of cortisol levels and monitoring of complications may improve the clinical course of COVID-19 in patients with CS.
MeSH term(s)	Humans ; Glucocorticoids/adverse effects ; COVID-19/complications ; Hydrocortisone/therapeutic use ; COVID-19 Vaccines ; Pandemics ; SARS-CoV-2 ; Adrenal Insufficiency/epidemiology ; Adrenal Insufficiency/etiology ; Cushing Syndrome/drug therapy ; Adrenal Glands ; Disease Progression
Chemical Substances	Glucocorticoids ; Hydrocortisone (WI4X0X7BPJ) ; COVID-19 Vaccines
Language	English
Publishing date	2023-06-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1194484-5
ISSN	1559-0100 ; 1355-008X ; 0969-711X
ISSN (online)	1559-0100
ISSN	1355-008X ; 0969-711X
DOI	10.1007/s12020-023-03411-w
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Article: Non-Canonical Effects of ACTH: Insights Into Adrenal Insufficiency.

Hasenmajer, Valeria / Bonaventura, Ilaria / Minnetti, Marianna / Sada, Valentina / Sbardella, Emilia / Isidori, Andrea M

Frontiers in endocrinology

2021 Volume 12, Page(s) 701263

Abstract: Introduction: Adrenocorticotropic hormone (ACTH) is produced from proopiomelanocortin, which is predominantly synthetized in the corticotroph and melanotroph cells of the anterior and intermediate lobes of the pituitary gland and the arcuate nucleus of ... ...

Abstract	Introduction: Adrenocorticotropic hormone (ACTH) is produced from proopiomelanocortin, which is predominantly synthetized in the corticotroph and melanotroph cells of the anterior and intermediate lobes of the pituitary gland and the arcuate nucleus of the hypothalamus. Although ACTH clearly has an effect on adrenal homeostasis and maintenance of steroid hormone production, it also has extra-adrenal effects that require further elucidation. Methods: We comprehensively reviewed English language articles, regardless of whether they reported the presence or absence of adrenal and extra-adrenal ACTH effects. Results: In the present review, we provide an overview on the current knowledge on adrenal and extra-adrenal effects of ACTH. In the section on adrenal ACTH effects, we focused on corticosteroid rhythmicity and effects on steroidogenesis, mineralocorticoids and adrenal growth. In the section on extra-adrenal effects, we have analyzed the effects of ACTH on the osteoarticular and reproductive systems, adipocytes, immune system, brain and skin. Finally, we focused on adrenal insufficiency. Conclusions: The role of ACTH in maintaining the function of the hypothalamic-pituitary-adrenal axis is well known. Conversely, if we broaden our vision and analyze its role as a potential treatment strategy in other conditions, it will be evident in the literature that researchers seem to have abandoned this aspect in studies conducted several years ago. We believe it is worth re-evaluating the role of ACTH considering its noncanonical effects on the adrenal gland itself and on extra-adrenal organs and tissues; however, this would not have been possible without the recent advances in the pertinent technologies.
MeSH term(s)	Adrenal Insufficiency/metabolism ; Adrenal Insufficiency/pathology ; Adrenocorticotropic Hormone/metabolism ; Animals ; Humans ; Pituitary-Adrenal System/physiopathology
Chemical Substances	Adrenocorticotropic Hormone (9002-60-2)
Language	English
Publishing date	2021-08-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.701263
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Article ; Online: Once-daily, modified-release hydrocortisone in patients with adrenal insufficiency - Authors' reply.

Isidori, Andrea M / Hasenmajer, Valeria / Venneri, Mary Anna

The lancet. Diabetes & endocrinology

2018 Volume 6, Issue 4, Page(s) 270–271

MeSH term(s)	Adrenal Hyperplasia, Congenital ; Adrenal Insufficiency ; Humans ; Hydrocortisone
Chemical Substances	Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2018
Publishing country	England
Document type	Letter ; Comment
ISSN	2213-8595
ISSN (online)	2213-8595
DOI	10.1016/S2213-8587(18)30040-8
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Article ; Online: Effects of licorice on sex hormones and the reproductive system.

Minnetti, Marianna / De Alcubierre, Dario / Bonaventura, Ilaria / Pofi, Riccardo / Hasenmajer, Valeria / Tarsitano, Maria Grazia / Gianfrilli, Daniele / Poggiogalle, Eleonora / Isidori, Andrea M

Nutrition (Burbank, Los Angeles County, Calif.)

2022 Volume 103-104, Page(s) 111727

Abstract: Objectives: The potential clinical effects of licorice (Glycyrrhiza spp.) and its extracts have been investigated since ancient times. Whether pseudohyperaldosteronism, with consequent arterial hypertension, is the only endocrine effect produced by ... ...

Abstract	Objectives: The potential clinical effects of licorice (Glycyrrhiza spp.) and its extracts have been investigated since ancient times. Whether pseudohyperaldosteronism, with consequent arterial hypertension, is the only endocrine effect produced by licorice is uncertain, and a role in the reproductive system has been proposed. This review aimed to summarize the current knowledge on the pharmacologic effects of licorice on male and female reproductive systems. Methods: Overall, 1462 records were extracted from electronic databases and systematically examined. A total of 28 studies were included in the final analysis. Results: Preclinical and clinical studies revealed estrogen-like activity of licorice components, especially flavonoids, isoflavonoids, and chalcones, showing a potential role of licorice in ameliorating symptoms associated with estrogen insufficiency. Preclinical studies also showed weak antiandrogen properties and beneficial effects of licorice on gonadal function in both sexes, but clinical studies yield to poor and conflicting results depending on the type and dose of licorice. Conclusions: Licorice consumption can affect the reproductive system. However, its role needs to be further explored, especially due to the great variability of bioactive compounds used in existing studies.
MeSH term(s)	Glycyrrhiza ; Plant Extracts/pharmacology ; Triterpenes ; Estrogens ; Gonadal Steroid Hormones ; Genitalia
Chemical Substances	Plant Extracts ; Triterpenes ; Estrogens ; Gonadal Steroid Hormones
Language	English
Publishing date	2022-05-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	639259-3
ISSN	1873-1244 ; 0899-9007
ISSN (online)	1873-1244
ISSN	0899-9007
DOI	10.1016/j.nut.2022.111727
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Zs.A 2290: Show issues

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

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

Andrology

2024

Abstract: Background: Data on sexual function in patients with adrenal insufficiency are scarce and largely controversial.: Objectives: To investigate sexual dysfunction in patients with primary and secondary adrenal insufficiency and the effects of switching ... ...

Abstract	Background: Data on sexual function in patients with adrenal insufficiency are scarce and largely controversial. Objectives: To investigate sexual dysfunction in patients with primary and secondary adrenal insufficiency and the effects of switching to once-daily dual-release hydrocortisone on sexual function in outcome assessors blinded, randomized, multicenter, active comparator clinical trial. Materials and methods: Eighty-nine adrenal insufficiency patients on conventional, multiple daily doses of glucocorticoid replacement, enrolled in the Dual RElease hydrocortisone versus conventionAl glucocorticoid replaceMent in hypocortisolism (DREAM) trial, were randomly assigned to continue their therapy or to switch to an equivalent dose of dual-release hydrocortisone. Sixty-three patients (34 women) consented to sex steroid measurements and questionnaires completion for quality of life (Addison's disease-specific quality-of-life questionnaire) and sexual function evaluation (female sexual function index for women, International Index of Erectile Function-Erectile Function for men) at baseline and 24 weeks after randomization. Results: At baseline, sexual dysfunction was observed in 41% of women and 59% of men with adrenal insufficiency. In both sexes, no associations were found between sexual function and hormone levels, whereas Addison's disease-specific quality-of-life questionnaire total and fatigue domain scores positively correlated with total female sexual function index and International Index of Erectile Function-Erectile Function scores. At 24 weeks, there was no significant difference either in sexual function or sex steroid levels between study groups. In the dual-release hydrocortisone group, the variation in the female sexual function index desire domain score was positively associated with the change in Addison's disease-specific quality-of-life questionnaire's symptom domain score (ρ = 0.478, p = 0.045). Discussion: Sexual dysfunction is common in adrenal insufficiency patients and is likely explained by multiple factors. dual-release hydrocortisone treatment is not directly associated with sexual function improvement, but an indirect effect mediated by quality-of-life amelioration cannot be excluded.
Language	English
Publishing date	2024-03-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2696108-8
ISSN	2047-2927 ; 2047-2919
ISSN (online)	2047-2927
ISSN	2047-2919
DOI	10.1111/andr.13635
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Zs.A 6983: Show issues

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Article: Effects of licorice on sex hormones and the reproductive system

Minnetti, Marianna / De Alcubierre, Dario / Bonaventura, Ilaria / Pofi, Riccardo / Hasenmajer, Valeria / Tarsitano, Maria Grazia / Gianfrilli, Daniele / Poggiogalle, Eleonora / Isidori, Andrea M.

Nutrition. 2022 Apr. 28,

2022

Abstract: The potential clinical effects of licorice (Glycyrrhiza spp.) and its extracts have been investigated since ancient times. It is uncertain if pseudohyperaldosteronism, with consequent arterial hypertension, is the only endocrine effect produced by ... ...

Abstract	: The potential clinical effects of licorice (Glycyrrhiza spp.) and its extracts have been investigated since ancient times. It is uncertain if pseudohyperaldosteronism, with consequent arterial hypertension, is the only endocrine effect produced by licorice, and a role in the reproductive system has been proposed. This review aimed to summarize the current knowledge on the pharmacological effects of licorice on the male and female reproductive systems. : Overall, 1462 records were extracted from electronic databases and systematically examined. 28 studies were included in the final analysis. : Preclinical and clinical studies revealed an estrogen-like activity of licorice components, especially flavonoids, isoflavonoids and chalcones, showing a potential role of licorice in ameliorating symptoms associated with estrogen insufficiency. Preclinical studies also displayed weak antiandrogen properties and beneficial effects of licorice on gonadal function in both sexes, while clinical studies yield to poor and conflicting results, depending on the type and dose of licorice. : Licorice consumption can affect the reproductive system. However, its role needs to be further explored, especially due to the great variability of bioactive compounds used in existing studies.
Keywords	Glycyrrhiza ; chalcones ; estrogens ; females ; gonads ; hypertension ; isoflavonoids ; licorice ; males ; nutrition
Language	English
Dates of publication	2022-0428
Publishing place	Elsevier Inc.
Document type	Article
Note	Pre-press version
ZDB-ID	639259-3
ISSN	1873-1244 ; 0899-9007
ISSN (online)	1873-1244
ISSN	0899-9007
DOI	10.1016/j.nut.2022.111727
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Platelet-derived circRNAs signature in patients with gastroenteropancreatic neuroendocrine tumors.

Campolo, Federica / Sesti, Franz / Feola, Tiziana / Puliani, Giulia / Faggiano, Antongiulio / Tarsitano, Maria Grazia / Tenuta, Marta / Hasenmajer, Valeria / Ferretti, Elisabetta / Verrico, Monica / Gianfrilli, Daniele / Venneri, Mary Anna / Isidori, Andrea M / Giannetta, Elisa

Journal of translational medicine

2023 Volume 21, Issue 1, Page(s) 548

Abstract: Background: Neuroendocrine tumors (NETs) early diagnosis is a clinical challenge that require a deep understanding of molecular and genetic features of this heterogeneous group of neoplasms. However, few biomarkers exist to aid diagnosis and to predict ... ...

Abstract	Background: Neuroendocrine tumors (NETs) early diagnosis is a clinical challenge that require a deep understanding of molecular and genetic features of this heterogeneous group of neoplasms. However, few biomarkers exist to aid diagnosis and to predict prognosis and treatment response. In the oncological field, tumor-educated platelets (TEPs) have been implicated as central players in the systemic and local responses to tumor growth, thereby altering tumor specific RNA profile. Although TEPs have been found to be enriched in RNAs, few studies have investigated the potential of a type of RNA, circular RNAs (circRNA), as platelet-derived biomarkers for cancer. In this proof-of-concept study, we aim to demonstrate whether the circRNAs signature of tumor educated platelets can be used as a liquid biopsy biomarker for the detection of gastroenteropancreatic (GEP)-NETs and the prediction of the early response to treatment. Methods: We performed a 24-months, prospective proof-of-concept study in men and women with histologically proven well-differentiated G1-G2 GEP-NET, aged 18-80 years, naïve to treatment. We performed a RNAseq analysis of circRNAs obtained from TEPs samples of 10 GEP-NETs patients at baseline and after 3 months from therapy (somatostatin analogs or surgery) and from 5 patients affected by non-malignant endocrinological diseases enrolled as a control group. Results: Statistical analysis based on p < 0.05 resulted in the identification of 252 circRNAs differentially expressed between GEP-NET and controls of which 109 were up-regulated and 143 were down-regulated in NET patients. Further analysis based on an FDR value ≤ 0.05 resulted in the selection of 5 circRNAs all highly significant downregulated. The same analysis on GEP-NETs at baseline and after therapy in 5 patients revealed an average of 4983 remarkably differentially expressed circRNAs between follow-up and baseline samples of which 2648 up-regulated and 2334 down-regulated, respectively. Applying p ≤ 0.05 and FDR ≤ 0.05 filters, only 3/5 comparisons gave statistically significant results. Conclusions: Our findings identified for the first time a circRNAs signature from TEPs as potential diagnostic and predictive biomarkers for GEP-NETs.
MeSH term(s)	Male ; Humans ; Female ; Neuroendocrine Tumors/genetics ; RNA, Circular/genetics ; Blood Platelets ; Prospective Studies ; RNA/genetics
Chemical Substances	RNA, Circular ; RNA (63231-63-0)
Language	English
Publishing date	2023-08-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-023-04417-8
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Article ; Online: Effects of Dual-Release Hydrocortisone on Bone Metabolism in Primary and Secondary Adrenal Insufficiency: A 6-Year Study.

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

Journal of the Endocrine Society

2023 Volume 8, Issue 1, Page(s) bvad151

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 ...

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 ( 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.
Language	English
Publishing date	2023-12-06
Publishing country	United States
Document type	Journal Article
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvad151
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Article ; Online: Use of glucocorticoids in patients with adrenal insufficiency and COVID-19 infection.

Isidori, Andrea M / Pofi, Riccardo / Hasenmajer, Valeria / Lenzi, Andrea / Pivonello, Rosario

The lancet. Diabetes & endocrinology

2020 Volume 8, Issue 6, Page(s) 472–473

MeSH term(s)	Adrenal Insufficiency/drug therapy ; Adrenal Insufficiency/immunology ; Adrenal Insufficiency/physiopathology ; Betacoronavirus/pathogenicity ; COVID-19 ; Comorbidity ; Contraindications, Drug ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Coronavirus Infections/physiopathology ; Critical Illness ; Cytokine Release Syndrome/physiopathology ; Glucocorticoids/administration & dosage ; Glucocorticoids/adverse effects ; Humans ; Hydrocortisone/administration & dosage ; Hydrocortisone/adverse effects ; Hypothalamo-Hypophyseal System/drug effects ; Pandemics ; Pituitary-Adrenal System/drug effects ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; Pneumonia, Viral/physiopathology ; Practice Guidelines as Topic ; SARS-CoV-2
Chemical Substances	Glucocorticoids ; Hydrocortisone (WI4X0X7BPJ)
Keywords	covid19
Language	English
Publishing date	2020-04-23
Publishing country	England
Document type	Letter
ISSN	2213-8595
ISSN (online)	2213-8595
DOI	10.1016/S2213-8587(20)30149-2
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