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Dive into the research topics where Luigi Maione is active.

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Featured researches published by Luigi Maione.


Nature Reviews Endocrinology | 2012

Neonatal gonadotropin therapy in male congenital hypogonadotropic hypogonadism

Claire Bouvattier; Luigi Maione; Jérôme Bouligand; Catherine Dodé; Anne Guiochon-Mantel; Jacques Young

Congenital hypogonadotropic hypogonadism (CHH) causes pubertal failure and infertility in both women and men due to partial or total secretory failure of the two pituitary gonadotropins lutropin (LH) and follitropin (FSH) during periods of physiological activation of the gonadotropic axis. Men and women with CHH frequently seek treatment for infertility after hypogonadism therapy. Some etiologies, such as autosomal dominant or X-linked Kallmann syndrome, raise the question of hereditary transmission, leading to increasing demands for genetic counseling and monitoring of medically assisted pregnancies. Diagnosis and treatment of newborn boys is, therefore, becoming an increasingly important issue. In male individuals with complete forms of CHH, the antenatal and neonatal gonadotropin deficit leads to formation of a micropenis and cryptorchidism, which could undermine future sexual and reproductive functions. Standard treatments, usually started after the age of puberty, often only partially correct the genital abnormalities and spermatogenesis. The aim of this Review is to examine the possible additional benefits of neonatal gonadotropin therapy in male patients with CHH. Encouraging results of neonatal therapy, together with a few reports of prepubertal treatment, support the use of this novel therapeutic strategy aimed at improving sexual and reproductive functions in adulthood.


Human Reproduction | 2008

Homozygous mutation in the prokineticin-receptor2 gene (Val274Asp) presenting as reversible Kallmann syndrome and persistent oligozoospermia: Case Report

Antonio Agostino Sinisi; Roberta Asci; Giuseppe Bellastella; Luigi Maione; Dario Esposito; Andrea Elefante; Annamaria De Bellis; Antonio Bellastella; Achille Iolascon

Prokineticin 2 (Prok2) or prokineticin-receptor2 (Prok-R2) gene mutations are associated with Kallmann syndrome (KS). We describe a new homozygous mutation of Prok-R2 gene in a man displaying KS with an apparent reversal of hypogonadism. The proband, offspring of consanguineous parents, presented at age 19 years with absent puberty, no sense of smell, low testosterone and gonadotrophin levels. Magnetic resonance imaging showed olfactory bulb absence. The patient achieved virilization and spermatogenesis with gonadotrophin administration. Two years after discontinuing hormonal therapy, he maintained moderate oligozoospermia and normal testosterone levels. Prok2 and Prok-R2 gene sequence analyses were performed. The proband had a homozygous mutation in Prok-R2 exon 2 that harbours the c.T820>A base substitution, causing the introduction of an aspartic acid in place of valine at position 274 (Val274Asp). His mother had the same mutation in heterozygous state. This report describes a novel homozygous mutation of Prok-R2 gene in a man with variant KS, underlying the role of Prok-R2 gene in the olfactory and reproductive system development in humans. Present findings indicate that markedly delayed activation of gonadotrophin secretion may occur in some KS cases with definite gene defects, and that oligozoospermia might result from a variant form of reversible hypogonadotrophic hypogonadism.


Journal of Cellular Physiology | 2011

Raloxifene induces cell death and inhibits proliferation through multiple signaling pathways in prostate cancer cells expressing different levels of estrogen receptorα and β

Valeria Rossi; G. Bellastella; C. De Rosa; Ciro Abbondanza; Daniela Visconti; Luigi Maione; Paolo Chieffi; F Della Ragione; D. Prezioso; A. De Bellis; A. Bellastella; A. A. Sinisi

Raloxifene (RAL), a selective estrogen receptor (ER) modulator (SERM) seems to induce apoptosis in both androgen‐dependent and ‐independent prostate cell (PC) lines via activation of ERβ and an antagonistic effect on ERα. In this study, we evaluated the effects of RAL on epithelial PC growth using the two following in vitro models: the androgen‐dependent cell line EPN which expressed both ERs; and a stabilized epithelial cell line derived from a prostate cancer specimen (CPEC), which expressed low levels of ERβ and lacked ERα. In EPN cells, there was an increase in the pre‐G1 apoptotic peak and a reduction in the S phase of the cell cycle with G0/G1 arrest after E2 or RAL treatment; bcl‐2 mRNA and Bcl‐2 protein levels were significantly reduced, while activated caspase‐3 and Par‐4 levels increased significantly after either E2 or RAL treatment; in addition, c‐myc transcript was inhibited after 10−6 M RAL treatment. A dose‐dependent increase of metallothionein II gene RNA level was also induced by RAL in EPN. In CPEC, there was only a weak apoptotic peak associated with caspase‐3 activation and Par‐4 increase after either E2 or RAL treatment; while c‐myc transcript level increased. RAL induced a rapid but transient phosphorylation of ERK 1/2 in EPN cells but generated a sustained effect in CPEC. These findings suggest that RAL effects on PC growth control in vitro are cell‐specific, depending on ERβ or ERβ/ERα relative expression levels. Moreover, this study demonstrated that RAL affected both transcriptional regulation and non‐genomic signals, which resulted in the modulation of multiple signaling pathways of apoptosis and of cell cycle progression. J. Cell. Physiol. 226: 1334–1339, 2011.


Human Reproduction | 2008

Seminal anti-Müllerian hormone level is a marker of spermatogenic response during long-term gonadotropin therapy in male hypogonadotropic hypogonadism

A. A. Sinisi; D. Esposito; Luigi Maione; M.C. Quinto; Daniela Visconti; A.De Bellis; A. Bellastella; Giovanni Conzo; G. Bellastella

BACKGROUND In adult men, anti-Müllerian hormone (AMH) levels are higher in semen than in serum, but the significance and control of its seminal secretion are still unknown. This study evaluated seminal and serum AMH levels during long-term gonadotropin therapy in men with hypogonadotropic hypogonadism (HH). METHODS A total of 20 men with never treated prepubertal-onset HH received i.m. hCG to normalize testosterone (T) and induce puberty. Afterwards, 11 of them, requiring fertility, were treated with HCG plus recombinant FSH (rFSH) (75 IU) twice a week, whereas 9 continued to receive hCG alone for 12 months. Before and during therapy, serum AMH, inhibin B and T levels were assessed. Semen samples were also collected during therapy for sperm count and seminal AMH assay. RESULTS HCG alone decreased basal high serum AMH and stimulated T and inhibin B levels. rFSH plus hCG increased seminal AMH levels, which were consequently significantly higher than with hCG alone, and positively correlated to sperm densities and testicular volumes at 3 and 12 months (P < 0.001). CONCLUSIONS Our data demonstrate that rFSH, added to hCG, stimulates seminal AMH and spermatogenesis in HH. Thus, seminal AMH levels are under T and FSH control and are closely related to progression of spermatogenesis. Our results also suggest that an early seminal AMH increase may be a marker of good future response to gonadotropin therapy in HH.


The Journal of Clinical Endocrinology and Metabolism | 2013

Computed Tomography of the Anterior Skull Base in Kallmann Syndrome Reveals Specific Ethmoid Bone Abnormalities Associated With Olfactory Bulb Defects

Luigi Maione; Samir Benadjaoud; Corinne Eloit; Antonio Agostino Sinisi; Annamaria Colao; Philippe Chanson; Denis Ducreux; Farida Benoudiba; Jacques Young

CONTEXT Kallmann syndrome (KS) is characterized by congenital hypogonadotropic hypogonadism (CHH) and an impaired sense of smell related to defective development of the olfactory system. OBJECTIVE The aim of the study was to use high-resolution computed tomography (CT) to detect specific abnormalities in the ethmoid bone region surrounding the olfactory bulbs in patients with KS. PATIENTS Thirty-seven KS patients were compared to normosmic CHH (nCHH) patients (n = 15) and controls (n = 30) of similar age. DESIGN AND METHODS We conducted a prospective study in a single referral center. Subjects underwent CT in bone windows with axial, coronal, and sagittal reconstructions centered on the olfactory fossa (OF) and cribriform plate (CP). We characterized the OF structure by measuring OF height, width, and surface area and a series of angles. The CP foramina were counted bilaterally. Olfactory bulb magnetic resonance imaging, performed in parallel, was compared with CT findings. RESULTS OF height, width, and surface area were all significantly lower in KS patients than in nCHH patients and controls (P < .0001). KS patients also had wider angles than nCHH patients and controls (P < .0001). KS subjects with olfactory bulb agenesis on magnetic resonance imaging or who harbored KAL1 mutations had the most marked changes in OF measurements and angles. Coronal OF height distinguished KS patients from controls with the best sensitivity and specificity. The mean number of CP foramina was similar in KS, nCHH, and control subjects. CONCLUSIONS KS is associated with specific ethmoid bone abnormalities. The preserved number of CP foramina in KS patients suggests that the integrity of olfactory structures is not mandatory for their formation during fetal development or their maintenance in adult life.


The Journal of Clinical Endocrinology and Metabolism | 2014

Impact of Successful Treatment of Acromegaly on Overnight Heart Rate Variability and Sleep Apnea

Denis Chemla; Pierre Attal; Luigi Maione; Anne-Sophie Veyer; Ghassan Mroue; Dany Baud; Sylvie Salenave; P. Kamenicky; Serge Bobin; Philippe Chanson

BACKGROUND Successful treatment of acromegaly improves disease-related cardiovascular mortality and morbidity, but its effects on autonomic modulation of the heart rate are unknown. OBJECTIVES We documented treatment-induced changes in time-domain heart rate variability, taking into account the confounding effects of obstructive sleep apnea. PATIENTS AND METHODS Sixteen consecutive patients (12 males, aged 43 ± 12 y) with newly diagnosed acromegaly underwent overnight (12:00-7:00 am) cardiac Holter recordings coupled with polysomnography. Data were obtained before and 10 ± 6 months after successful treatment of acromegaly. RESULTS IGF-1 levels fell from 807 ± 333 to 207 ± 69 μg/L and normalized in all patients. Seven patients (44%) had obstructive sleep apnea (apnea-hypopnea index 33 ± 21/h) at baseline. Treatment had no significant effect on polysomnographic indices. After treatment, increases were noted in the normal-to-normal heart period (NN), SD-NN, the percentage of NN differing from the previous NN by greater than 50 msec, and the root mean square of successive differences in NN (each P < .05). These heart rate variability results were not influenced by the type of treatment, and there was no relationship between changes in NN and changes in the apnea-hypopnea index (P = .58). CONCLUSION Early after successful treatment of acromegaly, we observed increased parasympathetic modulation/decreased sympathetic modulation of the nighttime heart rate, an effect that seems unrelated to changes in sleep apnea status. Treatments aimed at normalizing IGF-1 may improve cardiovascular homeostasis through improved cardiac autonomic nervous system modulation.


Endocrine-related Cancer | 2017

Acromegaly at diagnosis in 3173 patients from the Liege Acromegaly Survey (LAS) database.

Patrick Petrossians; Adrian Daly; Emil Natchev; Luigi Maione; Karin Blijdorp; Mouna Sahnoun Fathallah; Renata S. Auriemma; Alpha Mamadou Diallo; Anna-Lena Hulting; Diego Ferone; Vaclav Hana; Silvia Filipponi; Caroline Sievers; Claudia Nogueira; Carmen Fajardo Montañana; Davide Carvalho; Günter K. Stalla; Marie-Lise Jaffrain-Rea; B. Delemer; Annamaria Colao; Thierry Brue; Sebastian Neggers; Sabina Zacharieva; Philippe Chanson; Albert Beckers

Acromegaly is a rare disorder caused by chronic growth hormone (GH) hypersecretion. While diagnostic and therapeutic methods have advanced, little information exists on trends in acromegaly characteristics over time. The Liège Acromegaly Survey (LAS) Database, a relational database, is designed to assess the profile of acromegaly patients at diagnosis and during long-term follow-up at multiple treatment centers. The following results were obtained at diagnosis. The study population consisted of 3173 acromegaly patients from ten countries; 54.5% were female. Males were significantly younger at diagnosis than females (43.5 vs 46.4 years; P < 0.001). The median delay from first symptoms to diagnosis was 2 years longer in females (P = 0.015). Ages at diagnosis and first symptoms increased significantly over time (P < 0.001). Tumors were larger in males than females (P < 0.001); tumor size and invasion were inversely related to patient age (P < 0.001). Random GH at diagnosis correlated with nadir GH levels during OGTT (P < 0.001). GH was inversely related to age in both sexes (P < 0.001). Diabetes mellitus was present in 27.5%, hypertension in 28.8%, sleep apnea syndrome in 25.5% and cardiac hypertrophy in 15.5%. Serious cardiovascular outcomes like stroke, heart failure and myocardial infarction were present in <5% at diagnosis. Erythrocyte levels were increased and correlated with IGF-1 values. Thyroid nodules were frequent (34.0%); 820 patients had colonoscopy at diagnosis and 13% had polyps. Osteoporosis was present at diagnosis in 12.3% and 0.6–4.4% had experienced a fracture. In conclusion, this study of >3100 patients is the largest international acromegaly database and shows clinically relevant trends in the characteristics of acromegaly at diagnosis.


Clinical Endocrinology | 2012

Healthy birth after testicular extraction of sperm and ICSI from an azoospermic man with mild androgen insensitivity syndrome caused by an androgen receptor partial loss-of-function mutation.

Nathalie Massin; H. Bry; Lavinia Vija; Luigi Maione; Elizabeth Constancis; Bassam Haddad; Yves Morel; Frank Claessens; Jacques Young

The androgen receptor (AR) is essential for the development and maintenance of the male phenotype, and for spermatogenesis. Mutations in the AR gene cause a wide variety of androgen insensitivity syndromes (AIS), ranging from complete feminization to phenotypic males with infertility.


European Journal of Endocrinology | 2017

Changes in the management and comorbidities of acromegaly over three decades. The French Acromegaly Registry.

Luigi Maione; Thierry Brue; Albert Beckers; B. Delemer; Patrick Petrossians; Françoise Borson-Chazot; Olivier Chabre; Patrick François; Jérôme Bertherat; Christine Cortet; Philippe Chanson

CONTEXT Acromegaly is a rare disease associated with chronic multisystem complications. National registries have been created in several countries. DESIGN The French Registry contains data on acromegaly epidemiology, management and comorbidities recorded over more than three decades, retrospectively until 1999 and prospectively from 1999 to 2012. RESULTS Data could be analyzed for 999 of the 1034 patients included in the registry (46% males). Disease control, defined as IGF-I normalization (adjusted for age and sex), was achieved in 75% of patients at the last follow-up visit. Half the patients with uncontrolled disease had IGF-I levels below 1.5 times the upper limit of normal (ULN). The proportion of patients with surgically cured disease did not change markedly over time, whereas the proportion of patients with uncontrolled disease fell and the proportion of patients with medically controlled disease rose. Cardiovascular, metabolic, respiratory and rheumatologic comorbidities and their outcomes were recorded for most patients, and no noteworthy overall deterioration was noted over time. Cancer occurred in 10% of patients, for a standardized incidence ratio of 1.34 (95% CI: 0.94-1.87) in men and 1.24 (0.77-1.73) in women. Forty-one patients died during follow-up, for a standardized mortality ratio of 1.05 (0.70-1.42). Most deaths were due to cancer. CONCLUSIONS The majority of patients with acromegaly now have successful disease control thanks to the multistep management. The incidence of comorbidities following diagnosis of acromegaly is very low. Life expectancy is now close to that of the general population, probably owing to better management of the GH/IGF-I excess and comorbidities.


The Journal of Clinical Endocrinology and Metabolism | 2015

Sex Steroids, Precursors, and Metabolite Deficiencies in Men With Isolated Hypogonadotropic Hypogonadism and Panhypopituitarism: A GCMS-Based Comparative Study

Frank Giton; Séverine Trabado; Luigi Maione; J. Sarfati; Yves Le Bouc; Sylvie Brailly-Tabard; Jean Fiet; Jacques Young

CONTEXT Both testicular and adrenal steroid secretions are impaired in men with panhypopituitarism (Hypo-Pit), whereas only testicular steroid secretion is impaired in men with isolated gonadotropin deficiency (IHH) caused by normosmic congenital hypogonadotropic hypogonadism or Kallmann syndrome. OBJECTIVE The objective of the study was to compare the serum levels of sex steroids, precursors, and metabolites between men with complete IHH and those with Hypo-Pit. PATIENTS We studied 42 healthy men, 16 untreated men with IHH (normosmic congenital hypogonadotropic hypogonadism/Kallmann syndrome) and 23 men with Hypo-Pit (14 with craniopharyngioma, 9 with congenital hypopituitarism) receiving hydrocortisone, thyroxine, and GH replacement therapy but not T. METHODS Gas chromatography/mass spectrometry (GCMS) was used to measure the serum levels of sex steroids [T, dihydrotestosterone (DHT), and estradiol (E2)], their precursors (pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenediol, progesterone, 17-hydroxyprogesterone, and androstenedione), and their metabolites (androsterone, estrone, and estrone sulfate) as well as pregnenolone and dehydroepiandrosterone sulfate esters. RESULTS All the above-mentioned steroids, and notably T, DHT, and E2, were significantly lower in IHH patients than in controls but remained well above the detection limit of the relevant assays. In Hypo-Pit men, all these steroids were dramatically and significantly lower than in IHH. Interestingly, T, DHT, and E2, as well as pregnenolone and dehydroepiandrosterone sulfate esters, were undetectable or barely detectable in the Hypo-Pit men. CONCLUSIONS Steroid deficiencies are marked but partial in men with complete IHH. In contrast, men with Hypo-Pit have a very severe overall steroid deficiency. These deficiencies could affect health and quality of life.

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Annamaria Colao

University of Naples Federico II

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A. Bellastella

University of Naples Federico II

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Antonio Agostino Sinisi

Seconda Università degli Studi di Napoli

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Giuseppe Bellastella

Seconda Università degli Studi di Napoli

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