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Article: The association of hypogonadism with depression and its treatments.

Indirli, Rita / Lanzi, Valeria / Arosio, Maura / Mantovani, Giovanna / Ferrante, Emanuele

2023 Volume 14, Page(s) 1198437

Abstract: According to World Health Organization estimates, 5% of the adult population worldwide suffers from depression. In addition to the affective, psychomotor and cognitive symptoms which characterize this mood disorder, sexual dysfunction has been frequently ...

Abstract	According to World Health Organization estimates, 5% of the adult population worldwide suffers from depression. In addition to the affective, psychomotor and cognitive symptoms which characterize this mood disorder, sexual dysfunction has been frequently reported among men suffering from depression. The most common sexual manifestations are decreased libido, erectile dysfunction and orgasmic disorder. In addition, epidemiological studies have documented a reduction of testosterone concentrations in men with depression and, for these reasons, depressive disorders appear as one possible cause of male functional hypogonadism. Moreover, some largely used antidepressant medications can cause or worsen sexual complaints, thus depression and its treatments rise several andrological-relevant issues. The other way round, men with hypogonadism can manifest depressed mood, anxiety, insomnia, memory impairment which, if mild, may respond to testosterone replacement therapy (TRT). However, the prevalence of functional hypogonadism in depression, and of depressive symptoms in hypogonadal men, is not known. Severe depressive symptoms do not respond to TRT, while the effect of treating major depression on functional hypogonadism, has not been investigated. Overall, the clinical relevance of each condition to the other, as well as the physiopathological underpinnings of their relationship, are still to be clarified. The present review summarizes current evidence on the influence of testosterone on mood and of depression on the hypothalamic-pituitary-testis axis; the clinical association between male hypogonadism and depression; and the reciprocal effects of respective treatments.
MeSH term(s)	Adult ; Humans ; Male ; Depression/complications ; Depression/drug therapy ; Depression/epidemiology ; Testosterone/therapeutic use ; Behavior Therapy ; Depressive Disorder, Major ; Hypogonadism/complications ; Hypogonadism/drug therapy ; Hypogonadism/epidemiology
Chemical Substances	Testosterone (3XMK78S47O)
Language	English
Publishing date	2023-08-10
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.2023.1198437
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Article: Bone health in functional hypothalamic amenorrhea: What the endocrinologist needs to know.

Indirli, Rita / Lanzi, Valeria / Mantovani, Giovanna / Arosio, Maura / Ferrante, Emanuele

Frontiers in endocrinology

2022 Volume 13, Page(s) 946695

Abstract: In the original definition by Klinefelter, Albright and Griswold, the expression "hypothalamic hypoestrogenism" was used to describe functional hypothalamic amenorrhoea (FHA). Given the well-known effects of estrogens on bone, the physiopathology of ... ...

Abstract	In the original definition by Klinefelter, Albright and Griswold, the expression "hypothalamic hypoestrogenism" was used to describe functional hypothalamic amenorrhoea (FHA). Given the well-known effects of estrogens on bone, the physiopathology of skeletal fragility in this condition may appear self-explanatory. Actually, a growing body of evidence has clarified that estrogens are only part of the story. FHA occurs in eating disorders, overtraining, and during psychological or physical stress. Despite some specific characteristics which differentiate these conditions, relative energy deficiency is a common trigger that initiates the metabolic and endocrine derangements contributing to bone loss. Conversely, data on the impact of amenorrhoea on bone density or microarchitecture are controversial, and reduced bone mass is observed even in patients with preserved menstrual cycle. Consistently, oral estrogen-progestin combinations have not proven beneficial on bone density of amenorrheic women. Low bone density is a highly prevalent finding in these patients and entails an increased risk of stress or fragility fractures, and failure to achieve peak bone mass and target height in young girls. Pharmacological treatments have been studied, including androgens, insulin-like growth factor-1, bisphosphonates, denosumab, teriparatide, leptin, but none of them is currently approved for use in FHA. A timely screening for bone complications and a multidisciplinary, customized approach aiming to restore energy balance, ensure adequate protein, calcium and vitamin D intake, and reverse the detrimental metabolic-endocrine changes typical of this condition, should be the preferred approach until further studies are available.
MeSH term(s)	Humans ; Female ; Amenorrhea/etiology ; Bone Density ; Hypothalamic Diseases/complications ; Endocrinologists ; Bone Diseases, Metabolic ; Estrogens
Chemical Substances	Estrogens
Language	English
Publishing date	2022-10-11
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.2022.946695
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Article ; Online: Testosterone therapy does not affect coagulation in male hypogonadism: a longitudinal study based on thrombin generation.

Lanzi, Valeria / Indirli, Rita / Tripodi, Armando / Clerici, Marigrazia / Bonomi, Marco / Cangiano, Biagio / Petria, Iulia / Arosio, Maura / Mantovani, Giovanna / Ferrante, Emanuele

The Journal of clinical endocrinology and metabolism

2024

Abstract: Context: Testosterone therapy has been variably associated with increased thrombotic risk but investigations of global coagulation in this setting are lacking.: Objective: To compare global coagulation of hypogonadal men before (T0) and 6 months ... ...

Abstract	Context: Testosterone therapy has been variably associated with increased thrombotic risk but investigations of global coagulation in this setting are lacking. Objective: To compare global coagulation of hypogonadal men before (T0) and 6 months after (T1) starting testosterone replacement therapy (TRT), and healthy controls. Design: Observational prospective cohort study. Setting: Two tertiary endocrinological ambulatory care centers. Patients: Thirty-eight men with hypogonadism (mean age 55, SD 13) and 38 age-matched healthy controls. Interventions: Thrombin generation assay (TGA) was performed at T0 and T1 in hypogonadal men and in controls. TGA is an in vitro procedure based on the continuous registration of thrombin generation and decay under conditions mimicking the process that occurs in vivo. Main outcome measures: The following TGA parameters were recorded: lag-time; thrombin-peak concentration; time-to-reach the peak, velocity index and endogenous thrombin potential (ETP), the latter representing the total amount of thrombin generated under the driving forces of procoagulants opposed by the anticoagulants. PC, antithrombin, factor (F)VIII, and fibrinogen were assessed. Results: No changes of TGA parameters were observed between T0 and T1. Hypogonadal men displayed significantly higher ETP, fibrinogen, and significantly lower antithrombin levels both at T0 and T1 compared to controls. Thrombin-peak of hypogonadal men was significantly higher than controls at T0 but not at T1. ETP and antithrombin were correlated with testosterone levels. Conclusions: Hypogonadal men display a procoagulant imbalance detected by increased thrombin generation. Short-term TRT does not worsen global coagulation, suggesting that the treatment can be safely prescribed to men diagnosed with hypogonadism.
Language	English
Publishing date	2024-05-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgae317
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Article: Bone Features of Unaffected Skeletal Sites in Melorheostosis: A Case Report.

Indirli, Rita / Messina, Carmelo / Longhi, Matteo / Guabello, Gregorio / Corbetta, Sabrina

Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry

2020 Volume 23, Issue 4, Page(s) 690–694

Abstract: Background: Melorheostosis is a rare sporadic sclerosing bone dysplasia, which commonly affects appendicular skeleton with bone hyperostosis and soft tissues sclerosis; fragility fractures are rare in melorheostotic patients. We investigated bone ... ...

Abstract	Background: Melorheostosis is a rare sporadic sclerosing bone dysplasia, which commonly affects appendicular skeleton with bone hyperostosis and soft tissues sclerosis; fragility fractures are rare in melorheostotic patients. We investigated bone features at unaffected sites in a postmenopausal woman with melorheostosis of the right lower limb and with a fracture of the melorheostosis-free T11 vertebral. Methodology: Melorheostotic lesions were evaluated by plain radiography, magnetic resonance of the right lower limb, and whole-body bone scintigraphy. Dual X-ray absorptiometry, trabecular bone score, and quantitative computed tomography were performed to investigate unaffected bone sites. Biochemical assessment of bone metabolism was obtained. Results: Dual X-ray absorptiometry was indicative of normal mineralization at femoral sites and osteopenia at lumbar spine (T-score -1.1), which was confirmed by spinal quantitative computed tomography (volumetric bone mineral density 89 mg/cm Conclusions: Fragility fractures at apparently unaffected sites may occur in adults with melorheostosis, in absence of significant demineralization diagnosed by dual X-ray absorptiometry, trabecular bone score, and quantitative computed tomography, which may underestimate the fracture risk in this set of patients. Treatment with zoledronate could be considered also to prevent fragility fractures.
MeSH term(s)	Absorptiometry, Photon ; Aged ; Bone Density ; Bone and Bones/diagnostic imaging ; Bone and Bones/pathology ; Female ; Femur Neck/diagnostic imaging ; Femur Neck/pathology ; Humans ; Lumbar Vertebrae/diagnostic imaging ; Lumbar Vertebrae/pathology ; Melorheostosis/diagnostic imaging ; Melorheostosis/pathology
Language	English
Publishing date	2020-01-11
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2040951-5
ISSN	1094-6950
ISSN	1094-6950
DOI	10.1016/j.jocd.2020.01.002
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Article: Post-surgical Thyroid Bed Pyoderma Gangrenosum Mimicking Recurrent Papillary Thyroid Carcinoma.

Dolci, Alessia / Indirli, Rita / Genovese, Giovanni / Derlino, Federica / Arosio, Maura / Marzano, Angelo Valerio

Frontiers in endocrinology

2019 Volume 10, Page(s) 253

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2019-04-18
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2019.00253
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Article ; Online: Cabergoline Withdrawal Before and After Menopause: Outcomes in Microprolactinomas.

Indirli, Rita / Ferrante, Emanuele / Sala, Elisa / Giavoli, Claudia / Mantovani, Giovanna / Arosio, Maura

Hormones & cancer

2019 Volume 10, Issue 2-3, Page(s) 120–127

Abstract: Natural course of prolactinomas after menopause is not fully elucidated. The aim of this study was to compare recurrence rate after cabergoline withdrawal in premenopausal vs. postmenopausal women with microprolactinoma. Sixty-two women with ... ...

Abstract	Natural course of prolactinomas after menopause is not fully elucidated. The aim of this study was to compare recurrence rate after cabergoline withdrawal in premenopausal vs. postmenopausal women with microprolactinoma. Sixty-two women with microprolactinoma treated with cabergoline for at least 1 year and followed for 2 years after drug withdrawal were retrospectively selected. Patients were divided into two groups: 48 patients stopped cabergoline before menopause ("PRE" group), while 14 after menopause ("POST" group). Recurrence was defined by prolactin levels above normal, confirmed on two occasions. Overall, 39/62 women relapsed. Patients who relapsed apparently had higher prolactin before withdrawal (median 216.2, range 21.2-464.3 mIU/L) compared with those in long-term remission (94.3, 29.7-402.8 mIU/L; p < 0.05), and the risk of recurrence seemed lower in POST women (4/14, 29%) than in PRE ones (35/48, 73%, p < 0.005, OR 0.149, 95% CI 0.040-0.558). However, none of the factors (prolactin before withdrawal, menopausal status, treatment duration, complete adenoma regression) showed a correlation with recurrence risk in multivariate analysis. The best strategy able to optimize CBG treatment and withdrawal's outcomes is still to be defined in microprolactinomas. Postmenopausal status cannot reliably predict long-term remission, and follow-up is needed also in women of this age.
MeSH term(s)	Adenoma/metabolism ; Adolescent ; Adult ; Cabergoline/administration & dosage ; Dopamine Agonists/administration & dosage ; Female ; Humans ; Hyperprolactinemia/drug therapy ; Middle Aged ; Pituitary Neoplasms/drug therapy ; Postmenopause ; Premenopause ; Prolactin/biosynthesis ; Prolactinoma/drug therapy ; Recurrence ; Remission Induction ; Retrospective Studies ; Risk ; Treatment Outcome ; Young Adult
Chemical Substances	Dopamine Agonists ; Prolactin (9002-62-4) ; Cabergoline (LL60K9J05T)
Language	English
Publishing date	2019-04-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2543318-0
ISSN	1868-8500 ; 1868-8500
ISSN (online)	1868-8500
ISSN	1868-8500
DOI	10.1007/s12672-019-00363-4
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Article: A Multicenter Cohort Study in Patients With Primary Empty Sella: Hormonal and Neuroradiological Features Over a Long Follow-Up.

Carosi, Giulia / Brunetti, Alessandro / Mangone, Alessandra / Baldelli, Roberto / Tresoldi, Alberto / Del Sindaco, Giulia / Lavezzi, Elisabetta / Sala, Elisa / Mungari, Roberta / Fatti, Letizia Maria / Galazzi, Elena / Ferrante, Emanuele / Indirli, Rita / Biamonte, Emilia / Arosio, Maura / Cozzi, Renato / Lania, Andrea / Mazziotti, Gherardo / Mantovani, Giovanna

Frontiers in endocrinology

2022 Volume 13, Page(s) 925378

Abstract: Objective: primary empty sella (PES) represents a frequent finding, but data on hormonal alterations are heterogeneous, and its natural history is still unclear. Our aim was to evaluate the pituitary function of patients with PES over a long follow-up.!# ...

Abstract	Objective: primary empty sella (PES) represents a frequent finding, but data on hormonal alterations are heterogeneous, and its natural history is still unclear. Our aim was to evaluate the pituitary function of patients with PES over a long follow-up. Design: multicenter retrospective cohort study enrolling patients referred between 1984-2020 to five Pituitary Units, with neuroradiological confirmed PES and a complete hormonal assessment. Methods: we analyzed hormonal (including basal and dynamic evaluations), clinical and neuroradiological data collected at diagnosis and at the last visit (at least 6 months of follow-up). Results: we recruited 402 patients (females=63%, mean age=51.5 ± 16 years) with PES (partial, total, undefined in 66%, 13% and 21%, respectively). Hypopituitarism was present in 40.5% (hypogonadism=20.4%, hypoadrenalism=14.7%, growth hormone deficiency=14.7%, hypothyroidism=10.2%, diabetes insipidus=1.5%; multiple deficiencies=11.4%) and hypeprolactinemia in 6.5%. Interestingly, hormonal alterations were diagnosed in 29% of incidental PES. Hypopituitarism was associated with male sex ( Conclusions: this is the largest cohort of patients with PES reported. Hypopituitarism is frequent (40%) but hormonal deterioration seems uncommon (3%). Patients need to be carefully evaluated at diagnosis, even if PES is incidentally discovered.
MeSH term(s)	Adult ; Aged ; Cohort Studies ; Empty Sella Syndrome/complications ; Empty Sella Syndrome/diagnostic imaging ; Female ; Follow-Up Studies ; Humans ; Hypopituitarism/diagnostic imaging ; Male ; Middle Aged ; Retrospective Studies
Language	English
Publishing date	2022-06-23
Publishing country	Switzerland
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.925378
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Article ; Online: Impaired exocrine pancreatic function in different stages of type 1 diabetes.

Dozio, Nicoletta / Indirli, Rita / Giamporcaro, Gian Maria / Frosio, Laura / Mandelli, Alessandra / Laurenzi, Andrea / Bolla, Andrea Mario / Stabilini, Angela / Valle, Andrea / Locatelli, Massimo / Cavestro, Giulia Martina / Scavini, Marina / Battaglia, Manuela / Bosi, Emanuele

BMJ open diabetes research & care

2021 Volume 9, Issue 1

Abstract: Introduction: Aim of this study was to investigate the pancreatic exocrine function in patients with type 1 diabetes (T1D) by multiple non-invasive tests.: Research design and methods: The study is a single-center, cross-sectional study of pancreatic ...

Abstract	Introduction: Aim of this study was to investigate the pancreatic exocrine function in patients with type 1 diabetes (T1D) by multiple non-invasive tests. Research design and methods: The study is a single-center, cross-sectional study of pancreatic exocrine function in adult patients with new-onset or long-standing T1D and healthy controls. Results: Healthy controls, new-onset T1D, and long-standing T1D were similar for age at the time of the study, gender and body mass index (BMI) categories. Age of onset of T1D patients with long-standing disease was younger than that of patients with new-onset T1D (p<0.001). As expected, the three groups differed for C-peptide and hemoglobin A1c (HbA1c) levels. Lipase activity measured by Conclusions: Our results confirm that exocrine pancreatic impairment is a feature of T1D, with low fecal elastase-1, serum pancreatic amylase and lipase as specific markers, associated with reduced levels of nutritional indexes. Moreover, the evidence of more advanced insufficiency in long-standing disease reflects the chronic nature of this process, and its correlation with the residual β-cell function suggests parallel pathways for the impairment of the endocrine and exocrine pancreatic function.
MeSH term(s)	Adult ; Cross-Sectional Studies ; Diabetes Mellitus, Type 1 ; Glycated Hemoglobin A ; Humans ; Pancreatic Elastase ; Pancreatic Function Tests
Chemical Substances	Glycated Hemoglobin A ; Pancreatic Elastase (EC 3.4.21.36)
Language	English
Publishing date	2021-06-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2732918-5
ISSN	2052-4897 ; 2052-4897
ISSN (online)	2052-4897
ISSN	2052-4897
DOI	10.1136/bmjdrc-2019-001158
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Article: A Rare SPRY4 Gene Mutation Is Associated With Anosmia and Adult-Onset Isolated Hypogonadotropic Hypogonadism.

Indirli, Rita / Cangiano, Biagio / Profka, Eriselda / Mantovani, Giovanna / Persani, Luca / Arosio, Maura / Bonomi, Marco / Ferrante, Emanuele

Frontiers in endocrinology

2019 Volume 10, Page(s) 781

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2019-11-12
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2019.00781
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Article: Case Report: A Challenging Localization of a Pulmonary Ectopic ACTH-Secreting Tumor in a Patient With Severe Cushing's Syndrome.

Serban, Andreea Liliana / Rosso, Lorenzo / Mendogni, Paolo / Cremaschi, Arianna / Indirli, Rita / Mantovani, Beatrice / Rumi, Mariagrazia / Castellani, Massimo / Chiti, Arturo / Croci, Giorgio Alberto / Mantovani, Giovanna / Nosotti, Mario / Ferrante, Emanuele / Arosio, Maura

Frontiers in endocrinology

2021 Volume 12, Page(s) 687539

Abstract: Background: Ectopic adrenocorticotropic syndrome (EAS) is a rare cause of endogenous ACTH-dependent Cushing's syndrome, usually associated with severe hypercortisolism as well as comorbidities. Tumor detection is still a challenge and often requires ... ...

Abstract	Background: Ectopic adrenocorticotropic syndrome (EAS) is a rare cause of endogenous ACTH-dependent Cushing's syndrome, usually associated with severe hypercortisolism as well as comorbidities. Tumor detection is still a challenge and often requires several imaging procedures. In this report, we describe a case of an ectopic ACTH secretion with a misleading localization of the responsible tumor due to a concomitant rectal carcinoma. Case presentation: A 49-year-old man was referred to our Endocrinology Unit due to suspicion of Cushing's syndrome. His medical history included metastatic rectal adenocarcinoma, diagnosed 5 years ago and treated with adjuvant chemotherapy, radiotherapy and surgical resection. During follow-up, a thoracic computed tomography scan revealed two pulmonary nodules located in the superior and middle lobes of the right lung with a diameter of 5 and 10 mm, respectively. However, these nodules remained radiologically stable thereafter and were not considered relevant. All biochemical tests were suggestive of EAS (basal ACTH levels: 88.2 ng/L, nv 0-46; basal cortisol levels: 44.2 µg/dl, nv 4.8-19.5; negative response to CRH test and high dose dexamethasone suppression test) and radiological localization of the ectopic ACTH-secreting tumor was scheduled. The CT scan revealed a dimensional increase of the right superior lung nodule (from 5 to 12 mm). [ Conclusions: The present report describes a case of severe hypercortisolism due to EAS not detected by functional imaging methods, in which the localization of ACTH ectopic origin was puzzled by a concomitant metastatic rectal carcinoma. The multidisciplinary approach was crucial for the management of this rare disease.
MeSH term(s)	ACTH Syndrome, Ectopic/blood ; ACTH Syndrome, Ectopic/diagnostic imaging ; Adrenocorticotropic Hormone/blood ; Carcinoid Tumor/blood ; Carcinoid Tumor/diagnostic imaging ; Cushing Syndrome/blood ; Cushing Syndrome/diagnostic imaging ; Humans ; Lung Neoplasms/blood ; Lung Neoplasms/diagnostic imaging ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography
Chemical Substances	Adrenocorticotropic Hormone (9002-60-2)
Language	English
Publishing date	2021-07-09
Publishing country	Switzerland
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.687539
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