Targeted Next Generation Sequencing molecular profiling and its clinical application in adrenocortical cancer.

Objective: Adrenal cortical carcinoma (ACC) is a rare malignancy with a generally poor but heterogeneous prognosis, especially depending on the tumour stage at diagnosis. Identification of somatic gene alterations combined with clinical/histopathological evaluation of the tumour can help improve prognostication. We applied a simplified targeted-Next-Generation Sequencing (NGS) panel to characterise the mutational profiles of ACCs, providing potentially relevant information for better patient management.

Hypogonadism and sexual function in men affected by adrenocortical carcinoma under mitotane therapy.

Purpose: Adrenocortical carcinoma (ACC) is a rare and aggressive tumor. ACC male patients under adjuvant mitotane therapy (AMT) frequently develop hypogonadism, however sexual function has never been assessed in this setting. The aim of this retrospective study was to evaluate in AMT treated ACC patients the changes in Luteinizing hormone (LH), Sex Hormone Binding Globulin (SHBG), total testosterone (TT) and calculated free testosterone (cFT), the prevalence and type of hypogonadism and sexual function, the latter before and after androgen replacement therapy (ART).

Severe sperm DNA fragmentation may persist for up to 3 years after cytotoxic therapy in patients affected by Hodgkin lymphoma and non-Hodgkin lymphoma.

Study Question: Does sperm DNA recover from damage in all men after 2 years from the end of cytotoxic treatments?

Summary Answer: The current indication of 2 years waiting time for seeking natural pregnancy after cytotoxic treatment may not be adequate for all men, since severe sperm DNA damage is present in a proportion of subjects even after this timeframe.

What Is Known Already: Data in the literature on sperm DNA fragmentation (SDF) in lymphoma patients after cytotoxic treatments are scarce. The largest longitudinal study evaluated paired pre- and post-therapy (up to 24 months) semen samples from 34 patients while one study performed a longer follow-up (36 months) in 10 patients.

FSCN1 as a new druggable target in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a high risk of relapse and metastatic spread. The actin-bundling protein fascin (FSCN1) is overexpressed in aggressive ACC and represents a reliable prognostic indicator. FSCN1 has been shown to synergize with VAV2, a guanine nucleotide exchange factor for the Rho/Rac GTPase family, to enhance the invasion properties of ACC cancer cells.

Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor.

Introduction: Testicular germ cell tumor is the most frequent neoplasia in men of reproductive age, with a 5-year survival rate of 95%. Antineoplastic treatments induce sperm DNA fragmentation, especially within the first year post-therapy. Data in the literature are heterogeneous concerning longer follow-up periods, and the large majority is limited to 2 years.

Bone phenotypes in multiple endocrine neoplasia type 1: survey on the MEN1 Florentine database.

Multiple endocrine neoplasia type 1 (MEN1) is a rare, inherited cancer syndrome characterized by the development of multiple endocrine and non-endocrine tumors. MEN1 patients show a reduction of bone mass and a higher prevalence of early onset osteoporosis, compared to healthy population of the same age, gender, and ethnicity. During the monitoring and follow-up of MEN1 patients, the attention of clinicians is primarily focused on the diagnosis and therapy of tumors, while the assessment of bone health and mineral metabolism is, in many cases, marginally considered.

ALPL Genotypes in Patients With Atypical Femur Fractures or Other Biochemical and Clinical Signs of Hypophosphatasia.

Context: Hypophosphatasia (HPP) is a rare metabolic disorder caused by deficiency of alkaline phosphatase (ALP) enzyme activity, leading to defective mineralization, due to pathogenic variants of the ALPL gene, encoding the tissue nonspecific alkaline phosphatase (TNSALP) enzyme. Inheritance can be autosomal recessive or autosomal dominant. An abnormal ALPL genetic test enables accurate diagnosis, avoiding the administration of contraindicated antiresorptive drugs that, in patients with HPP, substantially increase the risk of atypical femur fractures (AFFs) and worsen the fracture healing process that is usually already compromised in these patients.

Secretin Stimulation Test and Early Diagnosis of Gastrinoma in MEN1 Syndrome: Survey on the MEN1 Florentine Database.

Context: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited endocrine cancer syndrome. Multiple gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) affect 30% to 80% of MEN1 patients, with the most common functioning GEP-NET being gastrinoma. Biochemical identification of hypergastrinemia may help to recognize the presence of gastrinomas before they are detectable by instrumental screening, enabling early diagnosis and start of therapy, preferably before tumor progression and metastases occurrence.

Genetic Factors of Non-Obstructive Azoospermia: Consequences on Patients' and Offspring Health.

Non-Obstructive Azoospermia (NOA) affects about 1% of men in the general population and is characterized by clinical heterogeneity implying the involvement of several different acquired and genetic factors. NOA men are at higher risk to be carriers of known genetic anomalies such as karyotype abnormalities and Y-chromosome microdeletions in respect to oligo-normozoospermic men. In recent years, a growing number of novel monogenic causes have been identified through Whole Exome Sequencing (WES).

Bone and Mineral Metabolism Phenotypes in MEN1-Related and Sporadic Primary Hyperparathyroidism, before and after Parathyroidectomy.

Primary hyperparathyroidism (PHPT) is the most common endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Persistent levels of increased parathyroid hormone (PTH) result in a higher incidence of osteopenia and osteoporosis compared to the general population. Surgical removal of hyper-functioning parathyroid tissue is the therapy of choice.

Polymorphic variants of alkaline phosphatase gene correlate with clinical signs of adult hypophosphatasia?

Unlabelled: We analyzed polymorphism of the ALPL gene in patients with low serum levels of tissue-nonspecific alkaline phosphatase (TNAP). The presence of three or more of the less frequent alleles of ALPL polymorphisms was associated with significantly lower TNAP serum level and higher frequencies of metatarsal fractures, which may help confirm a clinical suspicion of adult hypophosphatasia.

Introduction: Alkaline phosphatases (ALPs) are membrane-bound enzymes that hydrolyze monophosphate esters at a high pH (pH 8-10).

Genetics of Azoospermia.

Azoospermia affects 1% of men, and it can be due to: (i) hypothalamic-pituitary dysfunction, (ii) primary quantitative spermatogenic disturbances, (iii) urogenital duct obstruction. Known genetic factors contribute to all these categories, and genetic testing is part of the routine diagnostic workup of azoospermic men. The diagnostic yield of genetic tests in azoospermia is different in the different etiological categories, with the highest in Congenital Bilateral Absence of Vas Deferens (90%) and the lowest in Non-Obstructive Azoospermia (NOA) due to primary testicular failure (~30%).

Quality of life in Italian patients with Multiple endocrine neoplasia type 1 (MEN 1): results of an extensive survey.

Background: MEN1 is a complex, rare, syndrome inherited in an autosomal dominant tract and characterized by the development of multiple neuroendocrine tumors, requiring lifelong surveillance and multiple medical and surgical therapies throughout the patient's life. For all these reasons, a diagnosis of MEN1 can be a psychological shock for the patient, as well as his/her relatives, more so than the diagnosis of a single tumor. In the last two decades, clinicians have started to consider the emotional, psychological, relational, and social aspects of their patients' lives.

Correction: gr/gr deletion predisposes to testicular germ cell tumour independently from altered spermatogenesis: results from the largest European study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetic dissection of spermatogenic arrest through exome analysis: clinical implications for the management of azoospermic men.

Purpose: Azoospermia affects 1% of men and it can be the consequence of spermatogenic maturation arrest (MA). Although the etiology of MA is likely to be of genetic origin, only 13 genes have been reported as recurrent potential causes of MA.

Methods: Exome sequencing in 147 selected MA patients (discovery cohort and two validation cohorts).

Age-Dependent De Novo Mutations During Spermatogenesis and Their Consequences.

Spermatogenesis is a highly complex biological process during which germ cells undergo recurrent rounds of DNA replication and cell division that may predispose to random mutational events. Hence, germ cells are vulnerable to the introduction of a range of de novo mutations, in particular chromosomal aberrations, point mutations and small indels. The main mechanisms through which mutations may occur during spermatogenesis are (i) errors in DNA replication, (ii) inefficient repair of non-replicative DNA damage between cell divisions and (iii) exposure to mutagens during lifetime.

gr/gr deletion predisposes to testicular germ cell tumour independently from altered spermatogenesis: results from the largest European study.

The association between impaired spermatogenesis and TGCT has stimulated research on shared genetic factors. Y chromosome-linked partial AZFc deletions predispose to oligozoospermia and were also studied in TGCT patients with controversial results. In the largest study reporting the association between gr/gr deletion and TGCT, sperm parameters were unknown.

Genetics of ncHH: from a peculiar inheritance of a novel GNRHR mutation to a comprehensive review of the literature.

Background: Normosmic congenital hypogonadotropic hypogonadism (ncHH) is caused by the deficient production, secretion, or action of gonadotropin-releasing hormone (GnRH). Its typical clinical manifestation is delayed puberty and azoospermia. Homozygous and compound heterozygous mutations in the GNRHR gene (4q13.

Correction to: Multiple endocrine neoplasia type 1: analysis of germline MEN1 mutations in the Italian multicenter MEN1 patient database.

The original version of this article unfortunately contained a mistake in Table 2. The table 2 was truncated in the original publication. The full table 2 is given below.

Multiple endocrine neoplasia type 1: analysis of germline MEN1 mutations in the Italian multicenter MEN1 patient database.

Purpose: Multiple endocrine neoplasia type 1 (MEN1) is caused by germline inactivating mutations of the MEN1 gene. Currently, no direct genotype-phenotype correlation is identified. We aim to analyze MEN1 mutation site and features, and possible correlations between the mutation type and/or the affected menin functional domain and clinical presentation in patients from the Italian multicenter MEN1 database, one of the largest worldwide MEN1 mutation series published to date.

The LARO-MEN1 study: a longitudinal clinical experience with octreotide Long-Acting Release in patients with Multiple Endocrine Neoplasia type 1 Syndrome.

Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary tumoral syndrome, featured by a combination of neoplasms of various endocrine and nonendocrine tissues. Approximately 33% of MEN1-related deaths are due to the malignant behaviour of well-differentiated neuroendocrine tumors (NETs), for which a preventive surgical treatment is not feasible. Somatostatin analogues (SSA) have been employed in the treatment of NETs in the stage of advanced or metastatic disease, in order to control the growth and secretion of tumor lesions.

Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database.

Objective: The aim of this study was to integrate European epidemiological data on patients with multiple endocrine neoplasia type 1 by creating an Italian registry of this syndrome, including clinical and genetic characteristics and therapeutic management.

Methods: Clinical, familial and genetic data of patients with multiple endocrine neoplasia type 1, diagnosed, treated, and followed-up for a mean time of 11.3 years, in 14 Italian referral endocrinological centers, were collected, over a 3-year course (2011-2013), to build a national electronic database.

Aortopulmonary window parathyroid gland causing primary hyperparathyroidism in men type 1 syndrome.

Primary hyperparathyroidism (HPT) is the most common endocrinopathy in Multiple Endocrine Neoplasia type 1 (MEN1) syndrome. Supernumerary and/or ectopic parathyroid glands, potentially causes of persistent or recurrent HPT after surgery, have been previously described. However, this is the first ever described case of ectopic parathyroid gland localized in the aortopulmunary window causing HPT in MEN1.