52 research outputs found
Metabolic and cardiovascular risk factors in Klinefelter syndrome
No full textKlinefelter syndrome (KS), which normally presents with a 47,XXY karyotype, is the most common sex chromosome disorder in males. It is also the most common genetic cause of male infertility. KS subjects are typically tall, with small and firm testes, gynecomastia, broad hips, and sparse body hair, although a less evident presentation is also possible. KS is also characterized by a high prevalence of hypogonadism, metabolic syndrome (MetS) and cardiovascular disease. The aim of this article is to systematically review metabolic and the cardiovascular risk factors in KS patients. Hypogonadism has an important role in the pathogenesis of the changes in body composition (particularly visceral obesity) and hence of insulin resistance and MetS, but the association between KS and MetS may go beyond hypogonadism alone. From childhood, KS patients may show an increase in visceral fat with a reduction in lean body mass and an increase in glucose and impaired fat metabolism. Their increased incidence of congenital anomalies, epicardial adipose tissue, and thromboembolic disease suggests they have a higher risk of cardiovascular disease. There is conflicting evidence on the effects of testosterone therapy on body composition and metabolism
The role of scrotal ultrasonography from infancy to puberty
No full textBackground: Scrotal ultrasonography is an essential diagnostic tool in daily clinical practice. The availability of new-generation ultrasound machines characterized by clearly improved image quality, low health cost, and higher patient safety, represents only some characteristics of ultrasound investigation. The usefulness of scrotal ultrasonography is particularly evident in the period of life from infancy to puberty, during which males undergo important morphofunctional changes, and several pathological conditions may occur. Objectives: This pictorial review primarily aimed to investigate the aspects of ultrasonography related to the normal physiological development of the gonads from mini-puberty to pubertal onset. This study also aimed to provide an update on the use of ultrasonography in main andrological pathologies that may occur during this period. The conditions that are discussed in depth are: cryptorchidism, inguinoscrotal hernias, and hydrocele in the neonatal phase; acute scrotum, epididymo-orchitis, and testicular cancers in childhood; and hypogonadism, varicoceles, testicular microlithiasis, and oncohematological pathology in puberty. Discussion: We provided an ultrasound slant for all the above-mentioned pathologies while purposely avoiding excessive deepening of the pathogenetic, clinical, and therapeutic aspects. Studying the ultrasound aspects of the gonads also facilitates differential diagnosis between various conditions and represents a good aid in evaluating therapeutic success (e.g., in hypogonadism or postsurgical evaluation of varicoceles and cryptorchidism). Conclusion: Scrotal ultrasonography is now globally recognized as the necessary completion of clinical–laboratory overview in gonads evaluation. This diagnostic procedure is even more indispensable in the infancy–childhood–puberty period for the evaluation of normal gonadal development as well as diagnosis of other possible diseases
A combined form of hypothyroidism in pubertal patients with non-mosaic Klinefelter syndrome
No full textKlinefelter syndrome has been associated with thyroid abnormalities, the genesis of which is not yet fully clear. The aim of this study was to evaluate thyroid function
in Klinefelter syndrome subjects during the pubertal period. Chemiluminescent microparticle immunoassay was used to analyze Thyroid-Stimulating Hormone, fT3 and fT4 concentration
in serum samples from 40 Klinefelter syndrome pubertal boys with classic 47,XXY karyotype and 157 healthy age-matched controls. 13 Klinefelter syndrome
patients also underwent Thyrotropin-Releasing Hormone testing to evaluate hypothalamic-pituitary function. fT3 levels were significantly lower in Klinefelter syndrome
patients than in age-matched controls (p < 0.001). No significant differences were found for Thyroid-Stimulating Hormone (p = 0.138) or fT4 (p = 0.274), but the serum
levels of Klinefelter syndrome patients tended to cluster around the lower part of the reference range for the assay. Three of the thirteen Klinefelter syndrome patients undergoing
the Thyrotropin-Releasing Hormone test had an adequate response, one had a prolonged response at 60 min and nine responded inadequately. This study demonstrated
for the first time that pubertal Klinefelter syndrome patients have significantly lower fT3 serum levels than do healthy age-matched boys, whereas Thyroid-Stimulating Hormone
and fT4 are normal, albeit at the lower end of the reference range. Most patients showed an inadequate/prolonged response to pituitary stimulation with Thyrotropin-Releasing
Hormone. These findings suggest a combined form of both central and peripheral hypothyroidism in Klinefelter syndrome boys during pubertal development
Growth hormone deficiency during the transition phase
No full textThe growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis has several roles. While achievement of a satisfactory height is probably the most important and well-known, it is now clear that it also affects body composition, metabolism, muscle mass, and bone density during the transition period. Recombinant-growth hormone (Rec-GH) therapy is normally administered to GH-deficient children to achieve a reasonable final height. Retesting with a provocative test (insulin tolerance test or growth-hormone-releasing hormone + arginine test) is necessary during the transition period, after measuring IGF-1 levels. If the patient is still GH-deficient, rec-GH therapy should be restarted at 0.2-0.5 mg/day up to a final dosage of 0.8-1.0 mg/day (albeit there is no general consensus on the dosage). In fact, there is widespread literature evidence of the negative impact of GH-deficiency during the transition period, which provokes increased visceral fat and waist/hip ratio, decreased muscle mass and bone density and increased cardiovascular morbidity and mortality. © Touch Medical Media 2012
New perspectives in functional hypogonadotropic hypogonadism: beyond late onset hypogonadism
No full textFunctional hypogonadotropic hypogonadism (FHH) is an increasingly frequent condition, whose pathological mechanisms are not yet fully clarified. The concept of FHH has now completely replaced that of late onset hypogonadism, that only concerned the ageing man. FHH is the result of an impairment of the hypothalamic-pituitary gonadal axis (HPG-A) function, resulting in decreased testosterone concentrations associated with low or inappropriately normal gonadotropin levels and infertility; it can be diagnosed once organic causes of hypogonadism are excluded. The growing occurrence of FHH derives from its association with widespread conditions, such as obesity and diabetes mellitus, but also to the increasing ease and frequency of use of several drugs, such as opioids, glucocorticoids, and sex steroids. Moreover, given the tendency of many subjects to excessive physical activity and drastic reduction in caloric intake, FHH may also be secondary to low energy availability. Finally, the association with HIV infection should not be overlooked. Therefore, there is an important variability in the diseases that can lead to FHH. Despite the heterogeneity of the underlying pathologies, the mechanisms leading to FHH would seem quite similar, with the initial event represented by the impairment at the HPG-A level. Nevertheless, many different biological pathways are involved in the pathogenesis of FHH, therefore the aim of the current paper is to provide an overview of the main relevant mechanisms, through a detailed analysis of the literature, focusing specifically on pathogenesis and clinical, diagnostic and therapeutic aspects
HYPOTHALAMO-PITUITARY AXIS AND PUBERTY.
No full textPuberty is a complex process that culminates in the acquisition of psychophysical maturity and reproductive capacity. This elaborate and fascinating process marks the end of childhood. Behind it lies a complex, genetically mediated neuroendocrine mechanism through which the gonads are activated thanks to the fine balance between central inhibitory and stimulating neuromodulators and hormones with both central and peripheral action. The onset of puberty involves the reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, supported by the initial "kiss" between kisspeptin and the hypothalamic neurons that secrete GnRH (the GnRH "pulse generator"). This pulsatile production of GnRH is followed by a rise in LH and, consequently, in gonadal steroids. The onset of puberty varies naturally between individuals, and especially between males and females, in the latter of whom it is typically earlier. However, pathological variations, namely precocious and delayed puberty, are also possible. This article reviews the scientific literature on the physiological mechanisms of puberty and the main pathophysiological aspects of its onset
Endocrine and metabolic evaluation of classic Klinefelter syndrome and high-grade aneuploidies of sexual chromosomes with male phenotype: are they different clinical conditions?
No full textKlinefelter syndrome (KS) is the most common sex chromosome aneuploidy in males. As well as classic KS, less frequent higher-grade aneuploidies (HGAs) are also possible. While KS and HGAs both involve testicular dysgenesis with hypergonadotropic hypogonadism, they differ in many clinical features. The aim of this study was to investigate the endocrinal and metabolic differences between KS and HGAs.Objective: Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy in males. As well as classic KS, less frequent higher-grade aneuploidies (HGAs) are also possible. While KS and HGAs both involve testicular dysgenesis with hypergonadotropic hypogonadism, they differ in many clinical features. The aim of this study was to investigate the endocrinal and metabolic differences between KS and HGAs. Design: Cross-sectional, case-control study. Methods: 88 patients with KS, 24 with an HGA and 60 healthy controls. Given the known age-related differences all subjects were divided by age into subgroups 1, 2 and 3. Pituitary, thyroid, gonadal and adrenal functions were investigated in all subjects. Metabolic aspects were only evaluated in subjects in subgroups 2 and 3. Results: FT4 and FT3 levels were significantly higher in HGA than in KS patients in subgroups 1 and 2; in subgroup 3, FT4 was significantly higher in controls than in patients. Thyroglobulin was significantly higher in HGA patients in subgroup 1 than in KS patients and controls. Hypergonadotropic hypogonadism was confirmed in both KS and HGA patients, but was more precocious in the latter, as demonstrated by the earlier increase in gonadotropins and the decrease in testosterone, DHEA-S and inhibin B. Prolactin was significantly higher in HGA patients, starting from subgroup 2. Total and LDL cholesterol were significantly higher in HGA patients than in KS patients and controls, while HDL cholesterol was higher in controls than in patients. Conclusions: KS and HGAs should be considered as two distinct conditions
Preliminary findings on the association between attachment patterns and levels of growth hormone in a sample of children with non-organic failure to thrive
No full textIntroduction. Deficiency of growth hormone (GH) in absence of pituitary injuries is one of the causes of short stature and of the non organic failure to thrive (NOFTT) condition. Advances in developmental psychology have highlighted the role of emotions and caregiving behaviors in the organization of child's personality and psychobiology, with the mother-son attachment bond being considered a fundamental developmental experience. The objective of the present preliminary study was to assess whether there are significant correlations between attachment patterns and GH levels in a sample of subjects with NOFTT. Methods. Overall, 27 children (mean age 9.49 +/- 2.63 years) with NOFTT were enrolled. Perceived attachment security was assessed through the Security Scale (SS) and its subscales focused on maternal and paternal security. Pearson partial correlation was used to test associations between GH levels and SS measures adjusting for confounding factors (i.e. age, gender and body mass index). Results. Across all subjects, GH was significantly positively correlated with general security (r=0.425; p=0.038) and maternal security (r=0.451; p=0.027) and not significantly correlated with paternal security (r=0.237; p=0.264). Discussion. These findings preliminarily suggest that the association between GH levels and perceived attachment security may play a role in the pathophysiology of NOFTT and add to the accumulating evidence that attachment patterns may be related with specific psychoendocrine underpinnings
The adult growth hormone multicentric retrospective observational study: a 24-month Italian experience of adherence monitoring via Easypod™ of recombinant growth hormone treatment in adult GH deficiency
No full textIntroductionNon-compliance to recombinant human growth hormone (rhGH) treatment is universally recognized as a key detrimental factor to achieve the expected clinical outcomes in adult GH deficiency (aGHD). The Easypod™ electronic device allows objective measurement of adherence. Adherence to treatment has been reported to be related with IGF-1 levels and consequently with clinical satisfactory results. The aim of this multicentric, observational, retrospective, 24- month study, is to objectively assess aGHD patients’ compliance to rhGH, using the Easypod™ device. Additionally, the study aims to compare the biochemical responses of adherent vs non-adherent patients.MethodsForty-three patients (28 females and 15 males) affected by aGHD and equipped with Easypod™ from 3 Italian centers were included in the study. Adherence to treatment was defined as the proportion of injections correctly administered during the observational period, out of the expected total number of injections. All patients were evaluated for IGF-1, glucose, insulin, HOMA and QUICKI index, total/LDL/HDL cholesterol and triglycerides.ResultsMean adherence rate was consistently under 85% across the 2-year observation period (73% at year 2). A trend toward significant difference in adherence was shown when comparing female and male patients (respectively 76% and 61%) after a 2-year period. Among the anamnestic features, the prescribed frequency of administration of rhGH and the number of administered therapies appeared to be the most relevant adherence-influencing factors. A strong direct correlation between IGF-1 z-score and adherence to rhGH therapy was detected in the whole population.DiscussionCompliance to rhGH therapy is still a major issue in aGHD treatment. Adherence relates to therapy efficacy in aGHD. The use of Easypod™ could be beneficial for physicians to better manage aGHD patients and to achieve improved better biochemical and clinical responses
NGF and BDNF in pediatrics syndromes
No full textNeurotrophins (NTs) as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) play multiple roles in different settings including neuronal development, function and survival in both the peripheral and the central nervous systems from early stages. This report aims to provide a summary and subsequent review of evidences on the role of NTs in rare and non-common pediatric human diseases associated with changes in neurodevelopment. A variety of diseases has been analyzed and many have been linked to NTs neurobiological effects, including chronic granulomatous disease, hereditary sensory and autonomic neuropathy, Duchenne muscular dystrophy, Bardet-Biedl syndrome, Angelman syndrome, fragile X syndrome, trisomy 16, Williams-Beuren syndrome, Prader-Willi syndrome, WAGR syndrome, fetal alcohol spectrum disorders, Down syndrome and Klinefelter Syndrome. NTs alterations have been associated with numerous pathologic manifestations including cognitive defects, behavioral abnormalities, epilepsy, obesity, tumorigenesis as well as muscle-skeletal, immunity, bowel, pain sensibility and cilia diseases. In this report, we discuss that further studies are needed to clear a possible therapeutic role of NTs in these still often uncurable diseases
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