Marco Bonomi

• MD
• Professor (Associate) at University of Milan

Primary ovarian insufficiency (POI) is a disorder of insufficient ovarian follicle function before the age of 40 years with an estimated prevalence of 3.7% worldwide. Its relevance is emerging due to the increasing number of women desiring conception late or beyond the third decade of their lives. POI clinical presentation is extremely heterogeneou...

Purpose Andrological pathologies in the adulthood are often the results of conditions that originate during childhood and adolescence and sometimes even during gestation and neonatal period. Unfortunately, the reports in the literature concerning pediatric andrological diseases are scares and mainly concerning single issues. Furthermore, no shared...

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 pr...

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...

Adult-onset isolated hypogonadotropic hypogonadism (HH) is an heterogeneous condition associated with signs and symptoms that can significantly impact on patients' quality of life through gynecomastia, osteoporosis, anaemia, sexual dysfunction and impaired fertility, and may also be linked with other chronic conditions such as osteoporosis, depress...

Objective Functional hypothalamic amenorrhea (FHA) is one of the foremost manifestations in anorexia nervosa (AN), but a subset of patients have menses despite marked weight loss and underweight. The aim of our study was to investigate parameters potentially influencing FHA in AN. Design and methods In this observational retrospective study, we se...

Purpose: The aim of our study was to compare the incidence of idiopathic central precocious puberty (CPP) in our highly specialized Endocrinological Center before and after the onset of COVID-19 lockdown; we also aimed to identify any potential difference between girls with CPP from the two different time periods. Methods: We retrospectively ana...

The history of diagnosing hypogonadism and hypotestosteronemia shows us the many steps that were necessary to achieve our current knowledge and the ability to improve these patients’ well-being. Moreover, so far, criteria for diagnosing hypotestosteronemia varies according to the underlying condition, and according to the consensus or guideline ado...

Objective: An evidence-based pubertal induction scheme in hypogonadal girls is still to be established. Interestingly, literature data reports suboptimal uterine longitudinal diameter (ULD) in >50% of treated hypogonadal women, negatively influencing their pregnancy outcomes. This study aims to investigate auxological and uterine outcomes of puber...

Benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon, is considered a common endocrine disrupting chemical (EDC) with mutagenic and carcinogenic effects. In this work, we evaluated the effects of BaP on the hypothalamo-pituitary-gonadal axis (HPG) of zebrafish embryos. The embryos were treated with 5 and 50 nM BaP from 2.5 to 72 hours post-ferti...

Sommario L’insufficienza ovarica prematura è caratterizzata da un esaurimento dell’attività ovarica prima dei 40 anni, con conseguente ipoestrogenismo, amenorrea e infertilità e interessa l’1% delle donne. L’importanza clinica di questa condizione è notevolmente aumentata nel corso degli ultimi decenni per diversi motivi. Una diagnosi tempestiva, u...

In vertebrate species, fertility is controlled by gonadotropin-releasing hormone (GnRH) neurons. GnRH cells arise outside the central nervous system, in the developing olfactory pit, and migrate along olfactory/vomeronasal/terminal nerve axons into the forebrain during embryonic development. Congenital hypogonadotropic hypogonadism (CHH) and Kallma...

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 hi...

Background Congenital hypogonadotropic hypogonadism (CHH) is a condition with a strong genetic background, caused by a deficient production, secretion, or action of gonadotropin-releasing hormone (GnRH). Published data on CHH cohorts indicate a male predominance, although this is not supported by our current understandings. Aims In order to unrave...

Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age due to either a lack/delay of the hypothalamo-pituitary-gonadal (HPG) axis activation or a gonadal failure. DP usually gives rise to concern and uncertainty in patients and their families, potentially affecting their immediate psychosocial w...

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 hypogonad...

Background Klinefelter syndrome (KS) is frustratingly under-diagnosed. KS have a broad spectrum of clinical features, making it difficult to identify. Objective We describe KS clinical presentation in a large Italian cohort. Design This is the first observational cohort study within a national network, the Klinefelter ItaliaN Group (KING). Prima...

Introduction: Patients with congenital hypothyroidism (CH) may transiently show a certain degree of pituitary resistance to levothyroxine (LT4) which, however, normalizes subsequently. However, in some individuals TSH fails to normalize despite adequate LT4 treatment. Methods: Nine patients with CH followed in three Academic Centre who developed ov...

Primary ovarian insufficiency (POI) is one of the major causes of female infertility associated with the premature loss of ovarian function in about 3.7% of women before the age of 40. This disorder is highly heterogeneous and can manifest with a wide range of clinical phenotypes, ranging from ovarian dysgenesis and primary amenorrhea to post-puber...

Delayed puberty (DP) defines a lack of pubertal onset or progression beyond the expected age-range of occurrence. It can result from different disorders affecting the hypothalamus-pituitary-gonadal axis. It can impact adversely on psychosocial well-being and peer relationships in the short term and, when caused by permanent causes, is associated wi...

Abstract Background Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 (COVID-19). We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with interleukin 6 (IL-6) levels and with disease severity and mortality in COVID-19. Methods We prospectively studied 103 in-patients admitted to a North...

The cardiovascular (CV) benefit and safety of treating low testosterone conditions is a matter of debate. Although testosterone deficiency has been linked to a rise in major adverse CV events, most of the studies on testosterone replacement therapy were not designed to assess CV risk and thus excluded men with advanced heart failure or recent histo...

Female congenital hypogonadotropic hypogonadism (CHH) is a rare condition, with a strong genetic background, characterized by absent or incomplete pubertal development, for which inductive treatment with sex-hormone is required. Although the available data, mostly coming from studies in patients with Turner syndrome, indicate transdermal estradiol...

Purpose To investigate predictors of testicular response and non-reproductive outcomes (height, body proportions) after gonadotropin-induced puberty in congenital hypogonadotropic hypogonadism (CHH). Design A retrospective analysis of the puberty induction in CHH male patients, undergoing an off-label administration of combined gonadotropin (FSH a...

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 potent...

The differential diagnoses of pubertal delay include hypergonadotropic hypogonadism and congenital hypogonadotropic hypogonadism (CHH), as well as constitutional delay of growth and puberty (CDGP). Distinguishing between CDGP and CHH may be challenging, and the scientific community has been struggling to develop diagnostic tests that allow an accur...

Background: Loss of function mutations of thyrotropin receptor (TSHR) are one of the main causes of congenital hypothyroidism (CH). As for many disease-associated G-protein coupled receptors (GPCRs), these mutations often affect the correct trafficking and maturation of the receptor, thus impairing the expression on the cell surface. Several retai...

PurposeClassic Cushing’s syndrome (CS) is a severe disease characterized by central obesity, hypertension, easy bruising, striae rubrae, buffalo hump, proximal myopathy and hypertricosis. However, several CS cases have also been reported with unusual or camouflaged manifestations. In recent years, several authors investigated the prevalence of “hid...

A genetic basis of congenital isolated hypogonadotropic hypogonadism (CHH) can be deined 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 (...

Purpose Classic Cushing's syndrome (CS) is a severe disease characterized by central obesity, hypertension, easy bruising, striae rubrae, buffalo hump, proximal myopathy and hypertricosis. However, several CS cases have also been reported with unusual or camouflaged manifestations. In recent years, several authors investigated the prevalence of "hi...

Context Klinefelter syndrome (KS) is a condition at increased risk of thrombosis compared to 46,XY men. Objective To investigate the coagulation balance of KS patients by thrombin generation assay (TGA) and thromboelastometry. Design Observational, cross-sectional study. Setting Three tertiary endocrinological centers in Milan, Italy. Patients...

Introduction: The COVID-19 pandemic caused an increased mortality in nursing homes due to its quick spread and the age-related high lethality. Results: We observed a two-month mortality of 40%, compared to 6.4% in the previous year. This increase was seen in both COVID-19 positive (43%) and negative (24%) residents, but 8 patients among those te...

Objectives: Sex steroids, administered as a priming before GH stimulation tests (GHST) to differentiate between growth hormone deficiency (GHD) and constitutional delay of growth and puberty (CDGP), or as growth-promoting therapy using Low Dose Sex Steroids (LDSS) in CDGP, is much debated. We aimed to compare auxological outcomes of CDGP or GHD ch...

Klinefelter syndrome (KS) is one of the most common chromosomal disorders in male, affecting around 1:600 live male births. It is an aneuploidy affecting the sex chromosomes, and it is characterized by the presence of two or more extra copies of the X chromosome in a male subject. The supernumerary X chromosome comes from the mother and the father...

PurposeKlinefelter syndrome (KS) is characterized by late adolescence/young adulthood onset of primary hypogonadism. Hypogonadotropic hypogonadism (HH), when congenital, is usually associated with absent/incomplete puberty and low/normal gonadotropins. We report the clinical and genetic features of two subjects with KS and an unexpected HH hormone...

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...

The initiation of puberty is driven by an upsurge in hypothalamic gonadotropin-releasing hormone (GnRH) secretion. This, in turn, depends on the development of a complex GnRH neuroendocrine network during embryonic life. Delayed puberty (DP) affects up to 2% of the population, is a strongly genetically determined trait and is associated with advers...

The initiation of puberty is driven by an upsurge in hypothalamic gonadotropin-releasing hormone (GnRH) secretion. In turn, GnRH secretion upsurge depends on the development of a complex GnRH neuroendocrine network during embryonic life. Although delayed puberty (DP) affects up to 2% of the population, is highly heritable, and is associated with ad...

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

Distinguishing between Constitutional Delay of Growth and Puberty (CDGP) and Congenital Hypogonadotropic Hypogonadism (CHH) may be challenging. CDGP and CHH appear to belong to the same clinical spectrum (with low sex hormones and low LH and FSH), although one is classically transient and known as a self-limited form of delayed puberty (CDGP) while...

CHH is a rare disease characterized by a failure to enter (complete forms) or to complete (partial forms) pubertal development. It has a strong genetic background and it needs a treatment to allow the puberty to complete. In male this goal could be achieved either by the classic testosterone replacement therapy or by the exogenous gonadotropins (Gn...

Prokineticin receptors (PROKR1 and PROKR2) are G protein-coupled receptors which control human central and peripheral reproductive processes. Importantly, allelic variants of PROKR2 in humans are associated with altered migration of GnRH neurons, resulting in congenital hypogonadotropic hypogonadism (CHH), a heterogeneous disease characterized by d...

The association between diabetes mellitus (and its micro- and macro-vascular complications) and erectile dysfunction is widely known and the presence of hypogonadism may further complicate sexual dysfunction and quality of life, given the association between hypogonadism and reduced libido, ejaculatory disorders, and depressive symptoms. However, t...

Purpose: The triple A syndrome (AAAS) is an inherited condition associated with mutations in the AAAS gene, which encodes a protein of 546 amino acids known as ALADIN (alacrima achalasia adrenal insufficiency neurologic disorder) whose function is not well understood. This protein belongs to the WD-repeat family of regulatory proteins and is locat...

Purpose Selenium is frequently in nutraceuticals for pregnancy, given its role on fertility and thyroid metabolism. However, most evidence rise from non-controlled studies. We aimed to evaluate the protective effect of selenium against thyroid autoimmunity during and after pregnancy. Methods A multicenter, randomized, double-blind, placebo-control...

Background: Isolated hypogonadotropic hypogonadism (IHH) is a rare, clinically heterogeneous condition, caused by the deficient secretion or action of gonadotropin releasing hormone (GnRH). It can manifest with absent or incomplete sexual maturation, or as infertility at adult-age; in a half of cases, IHH is associated with hypo/anosmia (Kallmann s...

The Y-chromosome genes are primarily involved in sex determination, stature control, spermatogenesis, and fertility. Among structural rearrangements of the Y chromosome, the isochromosome of Yp, i(Yp), appears to be the most uncommon. We describe a detailed evolution of puberty in a boy with 45,X/46,X,i(Yp). Array CGH found 2 cell lines, one with i...

Differences of sex development are conditions with discrepancies between chromosomal, gonadal and phenotypic sex. In congenital hypogonadotropic hypogonadism, a lack of gonadotropin activity results primarily in the absence of pubertal development with prenatal sex development being (almost) unaffected in most patients. To expedite progress in the...

Sommario L’ipotiroidismo centrale (ICe) è un difetto di produzione degli ormoni tiroidei dovuto a un’insufficiente stimolazione da parte della tireotropina (TSH) di una ghiandola tiroidea altrimenti normale. La frequenza dell’ICe nella popolazione generale è probabilmente sottostimata perché la misurazione del TSH perde la sua accuratezza diagnosti...

Multiple metabolic and inflammatory mechanisms are considered the determinants of acquired functional isolated hypogonadotropic hypogonadism in males, whereas classic IHH is a rare congenital condition with a strong genetic background.Since we recently uncovered a frequent familiarity for classic IHH among patients with mild adult-onset hypogonadis...

Background Low testosterone levels are associated with an increased incidence of cardiovascular (CV) events, but the underlying biochemical mechanisms are not fully understood. The clinical condition of hypogonadism offers a unique model to unravel the possible role of lipoprotein-associated abnormalities in CV risk. In particular, the assessment o...

Purpose The prevalence and the etiopathogenesis of thyroid dysfunctions in Klinefelter syndrome (KS) are still unclear. The primary aim of this study was to evaluate the pathogenetic role of hypogonadism in the thyroid disorders described in KS, with the scope to distinguish between patients with KS and hypogonadism due to other causes (Kallmann sy...

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. Her...

Multiple metabolic and inflammatory mechanisms are considered the determinants of acquired functional isolated hypogonadotropic hypogonadism (IHH) in males, whereas classic IHH is a rare congenital condition with a strong genetic background. Since we recently uncovered a frequent familiarity for classic IHH among patients with mild adult-onset hypo...

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 (4q13.2) are the most frequent genetic caus...

Objective: Ulnar–mammary syndrome (UMS) is characterized by ulnar defects, and nipple or apocrine gland hypoplasia, caused by TBX3 haploinsufficiency. Signs of hypogonadism were repeatedly reported, but the mechanisms remain elusive. We aim to assess the origin of hypogonadism in two families with UMS. Design: Clinical and genetic study in two male...

Aberrantly expressed G protein-coupled receptors in tumors are considered as potential therapeutic targets. We analyzed the expressions of receptors of gonadotropin-releasing hormone (GNRHR), luteinizing hormone/chorionic gonadotropin (LHCGR) and follicle-stimulating hormone (FSHR) in human adrenocortical carcinomas and assessed their response to G...

Objective Loss‐of‐function mutations in IGSF1 result in X‐linked central congenital hypothyroidism (CeCH), occurring in isolation or associated with additional pituitary hormone deficits. Intrafamilial penetrance is highly variable and a minority of heterozygous females are also affected. We identified and characterized a novel IGSF1 mutation and i...

Objectives: Central hypothyroidism (CeH) is a rare form of hypothyroidism characterized by insufficient thyroid stimulation due to disturbed pituitary and/or hypothalamic functioning. Due to its origin and the whole clinical context, CeH represents a challenging condition in clinical practice as it is characterized by suboptimal accuracy of clinic...

Conclusions: Based on our experience, we recommend that molecular analysis should be performed in the presence of alacrima and at least one more symptom of TAS. Our cases share many clinical features of TAS and underline the variability in this syndrome, as well as the need for thorough investigation following a multidisciplinary approach. What is...