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Article ; Online: An evaluation of pharmacological options for Cushing's disease: what are the state-of-the-art options?

Martino, Marianna / Aboud, Nairus / Lucchetti, Beatrice / Salvio, Gianmaria / Arnaldi, Giorgio

2023 Volume 24, Issue 5, Page(s) 557–576

Abstract: Introduction: Untreated Cushing's syndrome (CS) is associated with significant morbidity and mortality. Cortisol normalization is a key goal to treatment. Pituitary surgery remains the first-line approach for Cushing's disease, but sometimes it is ... ...

Abstract	Introduction: Untreated Cushing's syndrome (CS) is associated with significant morbidity and mortality. Cortisol normalization is a key goal to treatment. Pituitary surgery remains the first-line approach for Cushing's disease, but sometimes it is impracticable, unsuccessful, or complicated by recurrence. Medical therapy has been historically considered a palliative. However, in the latest years, interest on this topic has grown due to both the availability of new drugs and the reevaluation of the old, commonly used drugs in clinical practice. Areas covered: In this article, we will discuss the current options and future directions of medical therapy for CS, aiming at fitting best patients' features. An extensive literature search regarding already approved and investigational principles was conducted (PubMed, ClinicalTrials.gov. Available drugs include inhibitors of ACTH secretion, steroidogenesis inhibitors, and glucocorticoid receptor antagonists; drugs acting at different levels can be also combined in uncontrolled patients. Expert opinion: Since there is still no standardized pharmacological approach and the superiority of one drug over another has not been established yet in the absence of comparative studies, each time clinicians' choices should be patient-tailored. Age, gender, tumor features, severity of hypercortisolism, comorbidities/complications, rapidity of action, side effects, drug-drug interactions, contraindications, availability, patients' preferences, and costs should be all considered.
MeSH term(s)	Humans ; Pituitary ACTH Hypersecretion/drug therapy ; Pituitary ACTH Hypersecretion/complications ; Cushing Syndrome/drug therapy
Language	English
Publishing date	2023-03-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1080/14656566.2023.2192349
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Article ; Online: Acromegaly and male sexual health.

Salvio, Gianmaria / Martino, Marianna / Balercia, Giancarlo / Arnaldi, Giorgio

Reviews in endocrine & metabolic disorders

2022 Volume 23, Issue 3, Page(s) 671–678

Abstract: Acromegaly is a rare pathology characterized by chronic hypersecretion of Growth Hormone (GH) and Insulin-like Growth Factor-1 (IGF-1) that causes somatic, metabolic, and systemic changes. The somatotropic axis acts physiologically favoring gonadal ... ...

Abstract	Acromegaly is a rare pathology characterized by chronic hypersecretion of Growth Hormone (GH) and Insulin-like Growth Factor-1 (IGF-1) that causes somatic, metabolic, and systemic changes. The somatotropic axis acts physiologically favoring gonadal function, but when GH is produced in excess it has deleterious effects on many aspects of male sexuality. It is widely demonstrated, in fact, that acromegaly induces hypogonadism through different mechanisms, both through direct mass effect on gonadotropic cells and through increased plasma levels of prolactin. Moreover, hypogonadism is also one of the factors linking acromegaly to erectile dysfunction (ED), but also metabolic complications of acromegaly and, probably, GH itself contribute to the genesis of this disorder. There are few data in the literature on the impact of the disease on fertility and testicular volume. Finally, knowledge of the role of GH hypersecretion on the occurrence of prostatic diseases such as benign prostatic hypertrophy and prostatic cancer appears to be of fundamental clinical importance in the long-term management of these patients.
MeSH term(s)	Acromegaly/complications ; Acromegaly/metabolism ; Growth Hormone ; Human Growth Hormone/metabolism ; Humans ; Hypogonadism/complications ; Insulin-Like Growth Factor I/metabolism ; Male ; Sexual Health
Chemical Substances	Human Growth Hormone (12629-01-5) ; Insulin-Like Growth Factor I (67763-96-6) ; Growth Hormone (9002-72-6)
Language	English
Publishing date	2022-04-01
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2185718-0
ISSN	1573-2606 ; 1389-9155
ISSN (online)	1573-2606
ISSN	1389-9155
DOI	10.1007/s11154-022-09721-0
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Zs.A 6069: Show issues

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Article ; Online: Androgens in Cushing's Syndrome.

Arnaldi, Giorgio / Martino, Marianna

Frontiers of hormone research

2019 Volume 53, Page(s) 77–91

Abstract: ... by other disturbances that increase their pretest probability (e.g., osteoporosis/bone fractures). Approximately 70-80 ...

Abstract	Although polycystic ovary syndrome (PCOS) is the most common androgen excess disorder, screening for Cushing's Syndrome (CS) should be considered in women with PCOS phenotype, particularly if they are also affected by other disturbances that increase their pretest probability (e.g., osteoporosis/bone fractures). Approximately 70-80% of women with CS present menstrual abnormalities, and PCOS findings are found in 46% of these patients. Diagnostic efforts should strengthen if the clinical picture is severe or of rapid onset in order to ensure the earliest and most appropriate treatment. If the diagnosis of CS is challenging, its differentiation from PCOS is not outdone: isolated PCOS may be associated to hypothalamic-pituitary-adrenal axis disruption, leading to false-positive results in screening tests. Because of this overlap, the diagnosis of CS is initially missed or delayed. Diagnostic utility of serum androgen assessment is controversial, but the widespread use of high-performance liquid chromatography and gas chromatography-mass spectrometry for urinary steroid profiling is showing promising results. According to the role of adrenocorticotropic hormone (ACTH) in adrenal androgen secretion, it is not surprising that the levels of dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and androstenedione (A4) are generally elevated or in the upper normal range in patients with ACTH-dependent CS. Conversely, adrenal androgens are generally low in patients with cortisol-secreting adrenocortical adenoma. However, androgen-secreting adrenal tumors (adenoma and carcinoma) can be also associated with severe hyperandrogenism. Regression of hypercortisolism after treatment causes disappearance of hyperandrogenism. However, signs of androgen excess may be detectable in well-controlled CS as a result of ACTH compensatory response to certain adrenal steroidogenesis inhibitors.
MeSH term(s)	Adrenocorticotropic Hormone/metabolism ; Androgens/metabolism ; Comorbidity ; Cushing Syndrome/diagnosis ; Cushing Syndrome/epidemiology ; Cushing Syndrome/metabolism ; Female ; Humans ; Hyperandrogenism/diagnosis ; Hyperandrogenism/epidemiology ; Hyperandrogenism/metabolism ; Polycystic Ovary Syndrome/diagnosis ; Polycystic Ovary Syndrome/epidemiology ; Polycystic Ovary Syndrome/metabolism
Chemical Substances	Androgens ; Adrenocorticotropic Hormone (9002-60-2)
Language	English
Publishing date	2019-09-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	1662-3762 ; 0301-3073
ISSN (online)	1662-3762
ISSN	0301-3073
DOI	10.1159/000494904
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Article ; Online: Osilodrostat oral tablets for adults with Cushing's disease.

Martino, Marianna / Aboud, Nairus / Lucchetti, Beatrice / Salvio, Gianmaria / Arnaldi, Giorgio

Expert review of endocrinology & metabolism

2022 Volume 17, Issue 2, Page(s) 99–109

Abstract: Introduction: Endogenous Cushing's syndrome (CS) is a rare, multi-systemic condition resulting from chronic glucocorticoid excess sustained by a pituitary adenoma (Cushing's disease, CD), an adrenal adenoma or, less frequently, a neuroendocrine tumor. ... ...

Abstract	Introduction: Endogenous Cushing's syndrome (CS) is a rare, multi-systemic condition resulting from chronic glucocorticoid excess sustained by a pituitary adenoma (Cushing's disease, CD), an adrenal adenoma or, less frequently, a neuroendocrine tumor. The optimal first-line option is surgery, but when it is contraindicated/refused, or in case of severe, life-threatening disease, medical treatment is a first-line choice. Osilodrostat (LCI699, Isturisa®) is a new, orally active adrenal steroidogenesis inhibitor currently approved by the FDA and EMA for the treatment of endogenous CS. Areas covered: We illustrate the pharmacologic profile of osilodrostat and summarize the efficacy and safety of osilodrostat from the first phase I studies to the most recent evidence. Expert opinion: Osilodrostat acts as a potent, reversible inhibitor of 11β-hydroxylase (CYP11B1) and 18-hydroxylase (or aldosterone synthase, CYP11B2), counteracting both gluco- and mineralocorticoid production. According to the results of the LINC1, LINC2, and LINC3 studies and the preliminary findings of LINC4, osilodrostat offers an excellent efficacy in controlling hypercortisolism with a good tolerability. The non-negligible risk of adrenal insufficiency/steroid withdrawal symptoms, hypokalemia, and hyperandrogenism disorders, and the possibility, albeit rare, of pituitary tumor enlargement, require further confirmation and careful monitoring.
MeSH term(s)	Adult ; Cushing Syndrome/drug therapy ; Humans ; Imidazoles/therapeutic use ; Mixed Function Oxygenases/therapeutic use ; Pituitary ACTH Hypersecretion/drug therapy ; Pituitary Neoplasms/drug therapy ; Pyridines ; Tablets/therapeutic use
Chemical Substances	Imidazoles ; Pyridines ; Tablets ; Osilodrostat (5YL4IQ1078) ; Mixed Function Oxygenases (EC 1.-)
Language	English
Publishing date	2022-02-28
Publishing country	England
Document type	Journal Article
ISSN	1744-8417
ISSN (online)	1744-8417
DOI	10.1080/17446651.2022.2044789
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Article: Using temperament and character dimensions (TCI) to analyze the personality profiles of adults and older adults with cancer managed in outpatient settings.

Vespa, Anna / Giulietti, Maria Velia / Fabbietti, Paolo / Di Rosa, Mirko / Gattafoni, Pisana / Berardi, Rossana / Arnaldi, Giorgio / Balercia, Giancarlo / Spatuzzi, Roberta

Frontiers in psychology

2024 Volume 14, Page(s) 1289093

Abstract: Introduction: This study aimed to investigate profiles of personality evaluated by temperament and character dimensions (TCI) in 638 adult and older adult patients (CP) who had recently been diagnosed with breast, colon, lung, and other kinds of cancer ( ...

Abstract	Introduction: This study aimed to investigate profiles of personality evaluated by temperament and character dimensions (TCI) in 638 adult and older adult patients (CP) who had recently been diagnosed with breast, colon, lung, and other kinds of cancer (female and male subjects were assessed). Tests: Temperament and Character Inventory (TCI). Statistical analysis: cluster K-means analysis for personality traits. Results: Two different personality profiles emerged: "Low self-determination and pessimism" (Profile 1) and "Self-determination and self-caring (medium)" (Profile 2). The following significant differences were observed in the TCI dimensions between the two profiles: Temperament-Novelty-Seeking (NS) ( Conclusion: Personality screening allows a better understanding of the difficulties of the individual patient and the planning of targeted psychotherapeutic interventions that promote quality of life and good adaptation to the disease course.
Language	English
Publishing date	2024-01-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2563826-9
ISSN	1664-1078
ISSN	1664-1078
DOI	10.3389/fpsyg.2023.1289093
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Article: Hypothalamic-Pituitary Diseases and Erectile Dysfunction.

Salvio, Gianmaria / Martino, Marianna / Giancola, Giulia / Arnaldi, Giorgio / Balercia, Giancarlo

Journal of clinical medicine

2021 Volume 10, Issue 12

Abstract: ... with some pituitary diseases (e.g., Cushing's disease and acromegaly, hypopituitarism) can determine the development of ED ...

Abstract	Several hormones contribute to ensure penile erection, a neurovascular phenomenon in which nitric oxide plays a major role. Erectile dysfunction (ED), which is defined as the persistent inability to obtain or maintain penile erection sufficient for a satisfactory sexual performance, may be due to arteriogenic, neurogenic, iatrogenic, but also endocrinological causes. The hypothalamus-pituitary axis plays a central role in the endocrine system and represents a fundamental link between the brain and peripheral glands, including gonads. Therefore, the hormonal production of the hypothalamic-pituitary axis can control various aspects of sexual function and its dysregulation can compromise erectile function. In addition, excess and deficiency of pituitary hormones or metabolic alterations that are associated with some pituitary diseases (e.g., Cushing's disease and acromegaly, hypopituitarism) can determine the development of ED with different mechanisms. Thus, the present review aimed to explore the relationship between hypothalamic and pituitary diseases based on the most recent clinical and experimental evidence.
Language	English
Publishing date	2021-06-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10122551
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Article ; Online: Endocrinologists at work: management of hyponatremia in clinical practice.

Arnaldi, G / Arvat, E / Berton, A M / Corona, G / Faustini Fustini, M / Ferrante, E / Razzore, P / Peri, A

Journal of endocrinological investigation

2023 Volume 46, Issue 12, Page(s) 2453–2457

MeSH term(s)	Humans ; Hyponatremia/diagnosis ; Hyponatremia/etiology ; Hyponatremia/therapy ; Endocrinologists ; Diagnosis, Differential ; Inappropriate ADH Syndrome/diagnosis
Language	English
Publishing date	2023-07-15
Publishing country	Italy
Document type	Journal Article
ZDB-ID	432272-1
ISSN	1720-8386 ; 0391-4097 ; 1121-1369
ISSN (online)	1720-8386
ISSN	0391-4097 ; 1121-1369
DOI	10.1007/s40618-023-02147-8
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Zs.A 1480: Show issues

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Article ; Online: COVID-19 and endocrine and metabolic disorders: critical points and suggestions for a correct therapeutic management from a tertiary endocrine center in Italy.

Martino, Marianna / Salvio, Gianmaria / Cutini, Melissa / Arnaldi, Giorgio / Balercia, Giancarlo

Minerva endocrinology

2021 Volume 47, Issue 1, Page(s) 117–126

Abstract: ... osteoporosis and less common endocrine disorders (e.g., adrenal insufficiency) in this setting. ...

Abstract	The Coronavirus-19 (COVID-19) pandemic, which began in December 2019 in Wuhan, China, has spread rapidly worldwide, affecting mostly frail individuals and resulting in high lethality among people with chronic conditions. The management of chronic endocrine disorders during the pandemic period proved particularly challenging, as they require close physician-patient contact for proper long-term management. In addition, acute endocrinologic conditions that presented during the COVID-19 period required timely management in an unusual clinical setting, providing an ongoing challenge for clinicians. This article summarizes the most recent guidance on the management and therapy of frequent conditions such as diabetes and osteoporosis and less common endocrine disorders (e.g., adrenal insufficiency) in this setting.
MeSH term(s)	Adrenal Insufficiency ; COVID-19 ; Diabetes Mellitus/epidemiology ; Humans ; Pandemics ; SARS-CoV-2
Language	English
Publishing date	2021-07-26
Publishing country	Italy
Document type	Journal Article
ZDB-ID	3062786-2
ISSN	2724-6116
ISSN (online)	2724-6116
DOI	10.23736/S2724-6507.21.03523-5
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Article: Investigating the aspect of asymmetry in brain-first versus body-first Parkinson's disease.

Lövdal, S S / Carli, G / Orso, B / Biehl, M / Arnaldi, D / Mattioli, P / Janzen, A / Sittig, E / Morbelli, S / Booij, J / Oertel, W H / Leenders, K L / Meles, S K

NPJ Parkinson's disease

2024 Volume 10, Issue 1, Page(s) 74

Abstract: Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Recent literature has proposed two subgroups of PD. The "body-first subtype" is associated with a prodrome of isolated REM-sleep Behavior ... ...

Abstract	Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Recent literature has proposed two subgroups of PD. The "body-first subtype" is associated with a prodrome of isolated REM-sleep Behavior Disorder (iRBD) and a relatively symmetric brain degeneration. The "brain-first subtype" is suggested to have a more asymmetric degeneration and a prodromal stage without RBD. This study aims to investigate the proposed difference in symmetry of the degeneration pattern in the presumed body and brain-first PD subtypes. We analyzed
Language	English
Publishing date	2024-03-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819218-7
ISSN	2373-8057
ISSN	2373-8057
DOI	10.1038/s41531-024-00685-3
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Article ; Online: Neuropsychological evaluation of phenoconversion risk in REM sleep behaviour disorder: A scoping review.

Fiamingo, Giuseppe / Capittini, Cristina / De Silvestri, Annalisa / Rebuffi, Chiara / Cerami, Chiara / Arnaldi, Dario / Terzaghi, Michele

Journal of sleep research

2023 Volume 32, Issue 5, Page(s) e13873

Abstract: The objective of this study was to assess the role of cognitive evaluation in the prediction of phenoconversion in polysomnography-confirmed idiopathic or isolated rapid eye movement sleep behaviour disorder, through a scoping review focussing on a ... ...

Abstract	The objective of this study was to assess the role of cognitive evaluation in the prediction of phenoconversion in polysomnography-confirmed idiopathic or isolated rapid eye movement sleep behaviour disorder, through a scoping review focussing on a longitudinal comprehensive neuropsychological assessment of patients with idiopathic REM sleep behaviour disorder. A literature search (2006-2022) yielded 1034 records, and 20 were selected for analysis. The sample included 899 patients from eight different cohorts and five countries. We extracted data on clinical evolution, mild cognitive impairment diagnosis, neuropsychological tests used, and classification of cognitive domains. Tests, cognitive domains, and mild cognitive impairment definitions were heterogeneous across the studies, precluding a meta-analysis. Ten studies (50%) evaluated the presence of mild cognitive impairment; 14 studies (70%) grouped neuropsychological tests into between three (6 studies, 21.4%) and seven (1 study, 7.1%) cognitive domains. The most frequently used tests were semantic fluency, Stroop colour word test, trail making test A and B, digit span, Rey auditory verbal learning test, and Rey-Osterrieth figure. All except digit span showed a role in predicting phenoconversion. The authors did not consistently assign tests to specific cognitive domains. In conclusion, we discuss methodological differences between the studies and highlight the need for a standardised framework for neuropsychological data acquisition and presentation, based on a multilevel approach covering test selection, domain assignment, and mild cognitive impairment diagnostic criteria.
MeSH term(s)	Humans ; Cognitive Dysfunction/diagnosis ; Neuropsychological Tests ; REM Sleep Behavior Disorder/diagnosis ; REM Sleep Behavior Disorder/psychology
Language	English
Publishing date	2023-03-23
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1122722-9
ISSN	1365-2869 ; 0962-1105
ISSN (online)	1365-2869
ISSN	0962-1105
DOI	10.1111/jsr.13873
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