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Article: Editorial: Functional acquired hypogonadotropic hypogonadism in males.

Cangiano, Biagio / Bonomi, Marco / Quinton, Richard

2024 Volume 15, Page(s) 1364634

MeSH term(s)	Male ; Humans ; Hypogonadism ; Testosterone
Chemical Substances	Testosterone (3XMK78S47O)
Language	English
Publishing date	2024-01-31
Publishing country	Switzerland
Document type	Editorial ; Comment
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2024.1364634
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Article: Use of testosterone replacement therapy to treat long-COVID-related hypogonadism.

Amodeo, Alessandro / Persani, Luca / Bonomi, Marco / Cangiano, Biagio

Endocrinology, diabetes & metabolism case reports

2024 Volume 2024, Issue 1

Abstract: Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can impair pituitary-gonadal axis and a higher prevalence of hypogonadism in post-coronavirus disease 2019 (COVID-19) patients compared with the general population has been ... ...

Abstract	Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can impair pituitary-gonadal axis and a higher prevalence of hypogonadism in post-coronavirus disease 2019 (COVID-19) patients compared with the general population has been highlighted. Here we report the first case of a patient affected with a long-COVID syndrome leading to hypogonadism and treated with testosterone replacement therapy (TRT) and its effects on clinical and quality of life (QoL) outcomes. We encountered a 62-year-old man who had been diagnosed with hypogonadotropic hypogonadism about 2 months after recovery from COVID-19 underwent a complete physical examination, general and hormonal blood tests, and self-reported questionnaires administration before and after starting TRT. Following the TRT, both serum testosterone level and hypogonadism-related symptoms were improved, but poor effects occurred on general and neuropsychiatric symptoms and QoL. Therefore, hypogonadism does not appear to be the cause of neurocognitive symptoms, but rather a part of the long-COVID syndrome; as a consequence, starting TRT can improve the hypogonadism-related symptoms without clear benefits on general clinical condition and QoL, which are probably related to the long-COVID itself. Longer follow-up might clarify whether post-COVID hypogonadism is a transient condition that can revert as the patient recovers from long-COVID syndrome. Learning points: Hypogonadism is more prevalent in post-COVID-19 patients compared with the general population. In these patients, hypogonadism may be part of long-COVID syndrome, and it is still unclear whether it is a transient condition or a permanent impairment of gonadal function. Testosterone replacement therapy has positive effects on hypogonadism-related clinic without clear benefits on general symptomatology and quality of life, which are more likely related to the long-COVID itself.
Language	English
Publishing date	2024-03-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2785530-2
ISSN	2052-0573
ISSN	2052-0573
DOI	10.1530/EDM-23-0097
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Article ; Online: Iron overload disorders: Growth and gonadal dysfunction in childhood and adolescence.

Tenuta, Marta / Cangiano, Biagio / Rastrelli, Giulia / Carlomagno, Francesco / Sciarra, Francesca / Sansone, Andrea / Isidori, Andrea M / Gianfrilli, Daniele / Krausz, Csilla

Pediatric blood & cancer

2024 , Page(s) e30995

Abstract: Hemochromatosis (HC) is characterized by the progressive accumulation of iron in the body, resulting in organ damage. Endocrine complications are particularly common, especially when the condition manifests in childhood or adolescence, when HC can ... ...

Abstract	Hemochromatosis (HC) is characterized by the progressive accumulation of iron in the body, resulting in organ damage. Endocrine complications are particularly common, especially when the condition manifests in childhood or adolescence, when HC can adversely affect linear growth or pubertal development, with significant repercussions on quality of life even into adulthood. Therefore, a timely and accurate diagnosis of these disorders is mandatory, but sometimes complex for hematologists without endocrinological support. This is a narrative review focused on puberty and growth disorders during infancy and adolescence aiming to offer guidance for diagnosis, treatment, and proper follow-up. Additionally, it aims to highlight gaps in the existing literature and emphasizes the importance of collaboration among specialists, which is essential in the era of precision medicine.
Language	English
Publishing date	2024-04-14
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.30995
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Article: Long Non-Coding RNAs: Role in Testicular Cancers.

Bresesti, Chiara / Vezzoli, Valeria / Cangiano, Biagio / Bonomi, Marco

Frontiers in oncology

2021 Volume 11, Page(s) 605606

Abstract: In the last few years lncRNAs have gained increasing attention among the scientific community, thanks to the discovery of their implication in many physio-pathological processes. In particular, their contribution to tumor initiation, progression, and ... ...

Abstract	In the last few years lncRNAs have gained increasing attention among the scientific community, thanks to the discovery of their implication in many physio-pathological processes. In particular, their contribution to tumor initiation, progression, and response to treatment has attracted the interest of experts in the oncologic field for their potential clinical application. Testicular cancer is one of the tumors in which lncRNAs role is emerging. Said malignancies already have very effective treatments, which although lead to the development of quite serious treatment-related conditions, such as secondary tumors, infertility, and cardiovascular diseases. It is therefore important to study the impact of lncRNAs in the tumorigenesis of testicular cancer in order to learn how to exploit them in a clinical setting and to substitute more toxic treatments. Eventually, the use of lncRNAs as biomarkers, drug targets, or therapeutics for testicular cancer may represent a valid alternative to that of conventional tools, leading to a better management of this malignancy and its related conditions, and possibly even to the treatment of poor prognosis cases.
Language	English
Publishing date	2021-03-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.605606
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Article: FSH and bone: Comparison between males with central versus primary hypogonadism.

Giovanelli, Luca / Quinton, Richard / Cangiano, Biagio / Colombo, Stefano / Persani, Luca / Bonomi, Marco / Chiodini, Iacopo

Frontiers in endocrinology

2022 Volume 13, Page(s) 939897

Abstract: Objective: Experimental studies proposed a direct effect of follicle-stimulating hormone (FSH) on the skeletal metabolism, but results of human studies mainly conducted in females are controversial. The present study aims to investigate the possible ... ...

Abstract	Objective: Experimental studies proposed a direct effect of follicle-stimulating hormone (FSH) on the skeletal metabolism, but results of human studies mainly conducted in females are controversial. The present study aims to investigate the possible role of FSH excess in male bone health, by comparing for the first time primary and central hypogonadism. Design and methods: 119 men were enrolled in this cross-sectional observational study at the time of the first diagnosis of hypogonadism. All participants had spontaneous pubertal development. Regarding patients with hypergonadotropic hypogonadism (Hyper-H), Klinefelter syndrome (KS) patients were distinguished from the other forms (non-KS-Hyper-H) based on the onset of FSH elevation. Bone mineral density (BMD) at both lumbar spine (LS) and femoral neck (FN), as well as the prevalence of morphometric vertebral fractures (VFx), were assessed. Results: Across the whole cohort, higher LS and FN BMD were associated with older age at diagnosis and higher body mass index (BMI), respectively. After adjusting for potential confounders (age at diagnosis, BMI, smoking habits, degree of hypogonadism defined by calculated free testosterone, and 25OH vitamin D levels), non-KS-Hyper-H patients showed significantly lower LS BMD and tended to show lower FN BMD values, as compared to those with hypogonadotropic hypogonadism (Hypo-H). In KS men, LS BMD was significantly lower than in those with non-KS-Hyper-H. No significant differences in the prevalence of VFx were found between the groups. Conclusions: These findings suggest a potential negative effect of FSH excess on the male bone mass, especially at spine. The duration of high FSH levels may also contribute to these findings.
MeSH term(s)	Cross-Sectional Studies ; Female ; Femur Neck ; Follicle Stimulating Hormone ; Humans ; Hypogonadism ; Klinefelter Syndrome ; Lumbar Vertebrae ; Male
Chemical Substances	Follicle Stimulating Hormone (9002-68-0)
Language	English
Publishing date	2022-08-05
Publishing country	Switzerland
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.939897
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Article: Genetic architecture of self-limited delayed puberty and congenital hypogonadotropic hypogonadism.

Vezzoli, Valeria / Hrvat, Faris / Goggi, Giovanni / Federici, Silvia / Cangiano, Biagio / Quinton, Richard / Persani, Luca / Bonomi, Marco

Frontiers in endocrinology

2023 Volume 13, Page(s) 1069741

Abstract: Distinguishing between self limited delayed puberty (SLDP) and congenital hypogonadotropic hypogonadism (CHH) may be tricky as they share clinical and biochemical characteristics. and appear to lie within the same clinical spectrum. However, one is ... ...

Abstract	Distinguishing between self limited delayed puberty (SLDP) and congenital hypogonadotropic hypogonadism (CHH) may be tricky as they share clinical and biochemical characteristics. and appear to lie within the same clinical spectrum. However, one is classically transient (SDLP) while the second is typically a lifetime condition (CHH). The natural history and long-term outcomes of these two conditions differ significantly and thus command distinctive approaches and management. Because the first presentation of SDLP and CHH is very similar (delayed puberty with low LH and FSH and low sex hormones), the scientific community is scrambling to identify diagnostic tests that can allow a correct differential diagnosis among these two conditions, without having to rely on the presence or absence of phenotypic red flags for CHH that clinicians anyway seem to find hard to process. Despite the heterogeneity of genetic defects so far reported in DP, genetic analysis through next-generation sequencing technology (NGS) had the potential to contribute to the differential diagnostic process between SLDP and CHH. In this review we will provide an up-to-date overview of the genetic architecture of these two conditions and debate the benefits and the bias of performing genetic analysis seeking to effectively differentiate between these two conditions.
MeSH term(s)	Humans ; Puberty, Delayed/diagnosis ; Puberty, Delayed/genetics ; Hypogonadism/diagnosis ; Hypogonadism/genetics ; Hypogonadism/congenital ; Diagnosis, Differential
Language	English
Publishing date	2023-01-16
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.1069741
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Article: The diagnosis and management of central hypothyroidism in 2018.

Persani, Luca / Cangiano, Biagio / Bonomi, Marco

Endocrine connections

2019 Volume 8, Issue 2, Page(s) R44–R54

Abstract: Central hypothyrodism (CeH) is a hypothyroid state caused by an insufficient stimulation by thyrotropin (TSH) of an otherwise normal thyroid gland. Several advancements, including the recent publication of expert guidelines for CeH diagnosis and ... ...

Abstract	Central hypothyrodism (CeH) is a hypothyroid state caused by an insufficient stimulation by thyrotropin (TSH) of an otherwise normal thyroid gland. Several advancements, including the recent publication of expert guidelines for CeH diagnosis and management, have been made in recent years thus increasing the clinical awareness on this condition. Here, we reviewed the recent advancements and give expert opinions on critical issues. Indeed, CeH can be the consequence of various disorders affecting either the pituitary gland or the hypothalamus. Recent data enlarged the list of candidate genes for heritable CeH and a genetic origin may be the underlying cause for CeH discovered in pediatric or even adult patients without apparent pituitary lesions. This raises the doubt that the frequency of CeH may be underestimated. CeH is most frequently diagnosed as a consequence of the biochemical assessments in patients with hypothalamic/pituitary lesions. In contrast with primary hypothyroidism, low FT4 with low/normal TSH levels are the biochemical hallmark of CeH, and adequate thyroid hormone replacement leads to the suppression of residual TSH secretion. Thus, CeH often represents a clinical challenge because physicians cannot rely on the use of the 'reflex TSH strategy' for screening or therapy monitoring. Nevertheless, in contrast with general assumption, the finding of normal TSH levels may indicate thyroxine under-replacement in CeH patients. The clinical management of CeH is further complicated by the combination with multiple pituitary deficiencies, as the introduction of sex steroids or GH replacements may uncover latent forms of CeH or increase the thyroxine requirements.
Language	English
Publishing date	2019-01-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2668428-7
ISSN	2049-3614
ISSN	2049-3614
DOI	10.1530/EC-18-0515
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Article ; Online: Triple-A Syndrome (TAS): An In-Depth Overview on Genetic and Phenotype Heterogeneity.

Pogliaghi, Gabriele / Cangiano, Biagio / Duminuco, Paolo / Vezzoli, Valeria / Bonomi, Marco

Protein and peptide letters

2020 Volume 27, Issue 12, Page(s) 1192–1203

Abstract: Triple-A Syndrome (TAS) is a rare autosomal recessive disorder characterized by three cardinal symptoms: alacrimia, achalasia and adrenal insufficiency due to ACTH insensitivity. Various progressive neurological abnormalities and skin changes have been ... ...

Abstract	Triple-A Syndrome (TAS) is a rare autosomal recessive disorder characterized by three cardinal symptoms: alacrimia, achalasia and adrenal insufficiency due to ACTH insensitivity. Various progressive neurological abnormalities and skin changes have been described in association with the syndrome. The disease is caused by mutation in the AAAS gene on chromosome 12q13. Mutations in AAAS were identified in more than 90% of individuals and families with TAS. The protein encoded by AAAS was termed ALADIN and is part of the WD repeat family of proteins, that have been found to be involved in many different functions such as protein-protein interaction, RNA processing, cytoskeleton assembly, control of cell division, signal transduction and apoptosis. Immunohistochemical analysis showed that mutated or truncated ALADIN localizes to the cytoplasm rather than to the nuclear pore complex. The exact function of ALADIN and the mechanisms that lead to the ACTH-resistant adrenal phenotype remains largely unknown. Nonetheless, recent studies provided some insights on the role of ALADIN as a member of the Nuclear Pore Complex not only implicated in the import of proteins involved in DNA repair and oxidative stress homeostasis but also in the strengthening of the mitotic spindle assembly. Early identification of the syndrome is challenging, given the rarity of the condition and high phenotypic heterogeneity even among members of the same family. In this review, we aim to summarize the current knowledge of clinical and molecular profile of patients with TAS and recommendations for the diagnosis, management, and follow-up of patients.
MeSH term(s)	Adrenal Insufficiency/diagnosis ; Adrenal Insufficiency/genetics ; Adrenal Insufficiency/metabolism ; Chromosomes, Human, Pair 12/genetics ; Chromosomes, Human, Pair 12/metabolism ; DNA Repair/genetics ; Esophageal Achalasia/diagnosis ; Esophageal Achalasia/genetics ; Esophageal Achalasia/metabolism ; Genetic Association Studies ; Humans ; Mutation ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Nuclear Pore Complex Proteins/genetics ; Nuclear Pore Complex Proteins/metabolism ; Oxidative Stress/genetics
Chemical Substances	AAAS protein, human ; Nerve Tissue Proteins ; Nuclear Pore Complex Proteins
Language	English
Publishing date	2020-06-13
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1280776-x
ISSN	1875-5305 ; 0929-8665
ISSN (online)	1875-5305
ISSN	0929-8665
DOI	10.2174/0929866527666200613215449
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Article ; Online: Genetics of congenital hypogonadotropic hypogonadism: peculiarities and phenotype of an oligogenic disease.

Cangiano, Biagio / Swee, Du Soon / Quinton, Richard / Bonomi, Marco

Human genetics

2020 Volume 140, Issue 1, Page(s) 77–111

Abstract: A genetic basis of congenital isolated hypogonadotropic hypogonadism (CHH) can be defined in almost 50% of cases, albeit not necessarily the complete genetic basis. Next-generation sequencing (NGS) techniques have led to the discovery of a great number ... ...

Abstract	A genetic basis of congenital isolated hypogonadotropic hypogonadism (CHH) can be defined in almost 50% of cases, albeit not necessarily the complete genetic basis. Next-generation sequencing (NGS) techniques have led to the discovery of a great number of loci, each of which has illuminated our understanding of human gonadotropin-releasing hormone (GnRH) neurons, either in respect of their embryonic development or their neuroendocrine regulation as the "pilot light" of human reproduction. However, because each new gene linked to CHH only seems to underpin another small percentage of total patient cases, we are still far from achieving a comprehensive understanding of the genetic basis of CHH. Patients have generally not benefited from advances in genetics in respect of novel therapies. In most cases, even genetic counselling is limited by issues of apparent variability in expressivity and penetrance that are likely underpinned by oligogenicity in respect of known and unknown genes. Robust genotype-phenotype relationships can generally only be established for individuals who are homozygous, hemizygous or compound heterozygotes for the same gene of variant alleles that are predicted to be deleterious. While certain genes are purely associated with normosmic CHH (nCHH) some purely with the anosmic form (Kallmann syndrome-KS), other genes can be associated with both nCHH and KS-sometimes even within the same kindred. Even though the anticipated genetic overlap between CHH and constitutional delay in growth and puberty (CDGP) has not materialised, previously unanticipated genetic relationships have emerged, comprising conditions of combined (or multiple) pituitary hormone deficiency (CPHD), hypothalamic amenorrhea (HA) and CHARGE syndrome. In this review, we report the current evidence in relation to phenotype and genetic peculiarities regarding 60 genes whose loss-of-function variants can disrupt the central regulation of reproduction at many levels: impairing GnRH neurons migration, differentiation or activation; disrupting neuroendocrine control of GnRH secretion; preventing GnRH neuron migration or function and/or gonadotropin secretion and action.
MeSH term(s)	Alleles ; Animals ; Genetic Association Studies/methods ; Gonadotropin-Releasing Hormone/metabolism ; Humans ; Hypogonadism/congenital ; Hypogonadism/genetics ; Kallmann Syndrome/genetics ; Loss of Function Mutation/genetics ; Neuroendocrine Cells/metabolism ; Phenotype
Chemical Substances	Gonadotropin-Releasing Hormone (33515-09-2)
Language	English
Publishing date	2020-03-21
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	223009-4
ISSN	1432-1203 ; 0340-6717
ISSN (online)	1432-1203
ISSN	0340-6717
DOI	10.1007/s00439-020-02147-1
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Article ; Online: New and Consolidated Therapeutic Options for Pubertal Induction in Hypogonadism: In-depth Review of the Literature.

Federici, Silvia / Goggi, Giovanni / Quinton, Richard / Giovanelli, Luca / Persani, Luca / Cangiano, Biagio / Bonomi, Marco

Endocrine reviews

2021 Volume 43, Issue 5, Page(s) 824–851

Abstract: Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the hypothalamo-pituitary-gonadal axis activation or a gonadal failure. DP usually gives rise to concern and ... ...

Abstract	Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the hypothalamo-pituitary-gonadal axis activation or a gonadal failure. DP usually gives rise to concern and uncertainty in patients and their families, potentially affecting their immediate psychosocial well-being and also creating longer term psychosexual sequelae. The most frequent form of DP in younger teenagers is self-limiting and may not need any intervention. Conversely, DP from hypogonadism requires prompt and specific treatment that we summarize in this review. Hormone therapy primarily targets genital maturation, development of secondary sexual characteristics, and the achievement of target height in line with genetic potential, but other key standards of care include body composition and bone mass. Finally, pubertal induction should promote psychosexual development and mitigate both short- and long-term impairments comprising low self-esteem, social withdrawal, depression, and psychosexual difficulties. Different therapeutic options for pubertal induction have been described for both males and females, but we lack the necessary larger randomized trials to define the best approaches for both sexes. We provide an in-depth and updated literature review regarding therapeutic options for inducing puberty in males and females, particularly focusing on recent therapeutic refinements that better encompass the heterogeneity of this population, and underlining key differences in therapeutic timing and goals. We also highlight persistent shortcomings in clinical practice, wherein strategies directed at "the child with delayed puberty of uncertain etiology" risk being misapplied to older adolescents likely to have permanent hypogonadism.
MeSH term(s)	Adolescent ; Child ; Female ; Gonadotropins ; Humans ; Hypogonadism/drug therapy ; Male ; Puberty ; Puberty, Delayed/drug therapy ; Testosterone/therapeutic use
Chemical Substances	Gonadotropins ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2021-12-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603096-8
ISSN	1945-7189 ; 0163-769X
ISSN (online)	1945-7189
ISSN	0163-769X
DOI	10.1210/endrev/bnab043
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