Total osteocalcin levels are independently associated with worse testicular function and a higher degree of hypothalamic-pituitary-gonadal axis activation in Klinefelter syndrome.

PURPOSE: The role of osteocalcin (OCN) in pubertal development, male hypogonadism, and the effect of testosterone (Te) replacement therapy (TRT) remains unclear. We aimed to investigate the total OCN (tOCN) concentrations in male patients with Klinefelter syndrome (KS), a model of adult hypergonadotropic hypogonadism. METHODS: This retrospective longitudinal study investigated 254 male patients with KS (47,XXY) between 2007 and 2021 at an academic referral center, categorized as (1) prepubertal, (2) pubertal, and (3) adults. All prepubertal patients were Te-naïve. Adult patients were subcategorized as (1) eugonadal, (2) hypogonadal, and (3) receiving TRT. We also analyzed 18 adult patients with available tOCN levels before and 3 months after TRT commencement. RESULTS: The tOCN levels varied throughout the lifespan according to pubertal status, were highest in eugonadal and significantly lower in TRT subjects, correlated with both LH (p = 0.017) and FSH levels (p = 0.004) in adults, and significantly declined after 3 months of TRT (p = 0.006) in the adult KS cohort. HPG-axis hormones levels demonstrated no correlation in prepubertal boys. Adjustment for age and body mass index confirmed previous results and revealed significant inverse correlations with total Te (p = 0.004), calculated free Te (p = 0.016), the Te/LH (p = 0.010), and calculated free Te/LH ratios (p = 0.031). CONCLUSION: In KS, a model of male hypergonadotropic hypogonadism, tOCN levels were not associated with gonadal function during normal prepuberty and pubertal development but were associated with worse testicular function and a higher degree of HPG stimulation in adults. TRT acutely reduced tOCN levels in adults.

Update on bioethical, medical and fertility issues in gender incongruence during transition age.

PURPOSE: Many issues still remain unresolved in the management of pubertal patients with gender incongruence (GI). The aim of this review is to discuss the main aspects of the treatment of these patients to provide a practical approach for clinicians. METHODS: A comprehensive literature search within PubMed was performed to provide updates of available evidence regarding the impact on bioethical, medical and fertility issues in gender incongruence during transition age. RESULTS: Gender Affirming Hormone Treatment (GAHT) and Gender Affirming Surgery (GAS) can induce unsatisfaction with change, future regrets, and the risk of infertility. This raises ethical issues especially in the management of pubertal patients that remain unresolved. Therapy with GnRH analogues (GnRHa) is intended to delay puberty, so as to give the adolescent a longer period of time to decide whether to continue with the treatments. At the level of physical changes, this therapy may have an effect on bone mineralization and body composition; however, long-term longitudinal data are not yet available. An important feature related to the use of GnRHa is the risk of fertility. Gamete cryopreservation is the most established method of fertility preservation (FP) and should be counselled to transgender adolescents. However, these patients are not always interested in having biological children. CONCLUSION: Based on the current evidence, there is a need to conduct further research to clarify certain issues and to standardize clinical practice and improve counselling in transgender adolescent decision making and avoid regrets in the future.

Sexual Developmental Disorders in Pediatrics.

Abstract: Disorders of sex development (DSD) are a heterogeneous group of pathologies that result in an alteration in sex determination or differentiation. DSD are estimated to affect 1: 4,500 newborns and according to the 2006 Chicago Consensus classification, DSD can be divided into three categories: those with a 46 XX karyotype, those with a 46 XY karyotype and those relating to sex chromosomes. It is crucial to correctly identify the pathology already in the first days of life to direct the patient and his family to the best path of care. For this reason, the role of the pediatrician is fundamental in the correct identification of the clinical picture and in supporting the family during the long process that involves the management of these patients. To make a diagnosis, it is necessary to follow a path led by a multidisciplinary team that includes several steps such as the execution of the genetic analysis, the evaluation with diagnostic imaging methods and laboratory evaluations. The therapeutic management, on the other hand, is still very complex even if in recent years we have moved from an attitude of early gender reassignment to an approach of watchful waiting to let the patient choose when she/he is mature enough to do so, which gender she/he feels to belong. It should not be forgotten that throughout this process the pediatrician must be both supportive and clinically active in the management of the child and his family.

Risk factors on testicular function in adolescents.

PURPOSE: Adolescence represents an important window for gonadal development. The aim of this review is to carry out a critical excursus of the most recent literature on endogenous and exogenous risk factors related to testicular function, focusing the research on adolescence period. METHODS: A comprehensive literature search within PubMed was performed to provide a summary of currently available evidence regarding the impact on adolescence of varicocele, cryptorchidism, cancer, diabetes, lifestyle factors, endocrine disruptors, obesity and sexually transmitted diseases. We focused on human studies that evaluated a possible impact of these factors on puberty timing and their effects on andrological health. RESULTS: Evidence collected seems to suggest that andrological health in adolescence may be impaired by several factors, as varicocele, cryptorchidism, and childhood cancer. Despite an early diagnosis and treatment, many adolescents might still have symptoms and sign of a testicular dysfunction in their adult life and at the current time it is not possible to predict which of them will experience andrological problems. Lifestyle factors might have a role in these discrepancies. Most studies point out towards a correlation between obesity, insulin resistance, alcohol, smoking, use of illegal drugs and testicular function in pubertal boys. Also, endocrine disruptors and sexually transmitted diseases might contribute to impair reproductive health, but more studies in adolescents are needed. CONCLUSION: According to currently available evidence, there is an emerging global adverse trend of high-risk and unhealthy behaviors in male adolescents. A significant proportion of young men with unsuspected and undiagnosed andrological disorders engage in behaviors that could impair testicular development and function, with an increased risk for later male infertility and/or hypogonadism during the adult life. Therefore, adolescence should be considered a key time for intervention and prevention of later andrological diseases.

INCIDENTAL PARATHYROIDECTOMY DURING TOTAL THYROIDECTOMY AS A POSSIBLE RISK FACTOR OF HYPOCALCEMIA. EXPERIENCE OF A SINGLE CENTER AND REVIEW OF LITERATURE.

CONTEXT: Post-operative clinical and biochemical hypocalcemia is a common complication of thyroid surgery and the correlation with incidental parathyroidectomy (IP) remains controversial. OBJECTIVE: To evaluate the incidence of IP during TT, its correlation to early post-surgery hypocalcemia, and its potential risk factors. PATIENTS AND METHODS: 77 consecutive patients submitted to thyroid surgery between January 2018 and December 2019. Demographic, clinical, biochemical, surgical and histopathological factors were assessed. Statistical multivariate analysis was performed to identify the risk of IP. RESULTS: IP was evident in 22 (28.5%) patients who underwent TT, TT with lymph node dissection of the central compartment (CLND) and reoperation for previous hemithyroidectomy with CLND. Early symptomatic hypocalcemia 24 hours after TT was demonstrated in 12/22 (54.5%) patients, with PTH value of <14pg/mL in 7/12 (58.3%) patients, and in 6 of these 7 patients (85.7%) the PTH value was <6.3pg/mL. In 5/22 (22.7%) patients the IP was associated with biochemical hypocalcemia <8.4mg/dL, and in 5/22 (22.7%) patients anatomical damage was not associated with a reduction in plasma calcium levels. The severity of early post-op hypocalcemia was not correlated with the number of parathyroid glands left in situ. The multivariate analysis did not show statistically significant values between the clinical-pathological variables and increased risk of IP. CONCLUSIONS: No IP clinical-pathological risk factors have been identified during thyroid surgery. In all cases of TT, with or without CLND, the meticulous identification of the parathyroid glands, whose incidental removal is frequently associated with clinical and biochemical hypocalcemia, is recommended.

PDE11A gene polymorphism in testicular cancer: sperm parameters and hormonal profile.

PURPOSE: Testicular germ cell tumours (TGCTs) is the most common malignancy among young adult males. The etiology is multifactorial and both environmental and genetic factors play an important role in the origin and development of TGCT. Genetic susceptibility may result from the interaction of multiple common and low-penetrance genetic variants and one of the main candidate genes is PDE11A. Many PDE11A polymorphisms were found responsible for a reduced PDE activity in TGCT patients, who often also display impaired hormone and sperm profile. The aim of this study was to investigate testicular function and PDE11A sequence in testicular cancer cases. METHODS: Semen analysis was performed in 116 patients with unilateral and bilateral sporadic TGCTs and in 120 cancer-free controls. We also investigated hormone profile and PDE11A polymorphisms using peripheral blood samples. RESULTS: Our data revealed that TGCT patients showed lower testosterone levels, higher gonadotropins levels and worse semen quality than controls, although the mean and the medians of sperm parameters are within the reference limits. PDE11A sequencing detected ten polymorphisms not yet associated with TGCTs before. Among these, G223A in homozygosity and A288G in heterozygosity were significantly associated with a lower risk of testicular tumour and they displayed a positive correlation with total sperm number. CONCLUSIONS: Our findings highlight the key role of PDE11A in testis and suggest the presence of an underlying complex and fine molecular mechanism which controls testis-specific gene expression and susceptibility to testicular cancer.

Adverse pathophysiological influence of early testosterone therapy on the testes of boys with higher grade sex chromosome aneuploidies (HGAs): a retrospective, cross-sectional study.

PURPOSE: Higher grade aneuploidies (HGAs) of the male sex chromosomes are a rare genetic group of pathologies caused by nondisjunction meiotic events. The aim of this study was to evaluate the impact of early androgenic therapy on the testicular secretory hormone profile, and the pathophysiological implications. PATIENTS AND METHODS: In this cross-sectional study, 18 HGA subjects aged 6-8 years were recruited. They were divided into two groups, based on whether or not they had previously undergone testosterone therapy (group 1: 11 untreated subjects; group 2: 7 treated subjects). Serum FSH, LH, testosterone (T), inhibin B (INHB) and anti-Müllerian hormone (AMH) were determined, and auxological parameters were assessed. Five group 1 patients and four group 2 patients were treated with hCG (human chorionic gonadotropin) for inguinal cryptorchidism; their hormone profile and auxological parameters were assessed both pre- and post-hCG treatment. RESULTS: Group 1 subjects showed significantly higher testicular volume and higher levels of AMH and INHB (p < 0.0001). Subjects who had undergone hCG therapy showed a significantly higher testicular volume, penis length (respectively, p = 0.008 and p = 0.0005 for group 1 and p = 0.04 and p = 0.001 for group 2) and T (p = 0.005 for group 1 and p = 0.004 for group 2). CONCLUSIONS: HGA patients undergoing early testosterone therapy show an earlier and persistent suppression of testicular secretory function. At this age, the testes are still responsive to stimulation with hCG. The selection of patients to be treated must be accompanied by a thorough clinical and hormonal evaluation.

From mini-puberty to pre-puberty: early impairment of the hypothalamus-pituitary-gonadal axis with normal testicular function in children with non-mosaic Klinefelter syndrome.

PURPOSE: Klinefelter syndrome (KS) is a genetic disorder caused by the presence of an extra X chromosome in males. The aim of this study was to evaluate the hypothalamic-pituitary-gonadal (HPG) axis and the clinical profile of KS boys from mini-puberty to early childhood. PATIENTS AND METHODS: In this retrospective, cross-sectional, population study, 145 KS boys and 97 controls aged 0-11.9 years were recruited. Serum FSH, LH, testosterone (T), Inhibin B (INHB), sex hormone binding globulin (SHBG) and anti-Müllerian hormone (AMH) were determined. Auxological parameters were assessed. To better represent the hormonal and clinical changes that appear in childhood, the entire population was divided into 3 groups: ≤ 6 months (group 1; mini-puberty); > 6 months and ≤ 8 years (group 2; early childhood); > 8 and ≤ 12 years (group 3; mid childhood). RESULTS: During mini-puberty (group 1), FSH and LH were significantly higher in KS infants than controls (p < 0.05), as were INHB and T (respectively p < 0.0001 and p < 0.005). INHB was also significantly higher in KS than controls in group 2 (p < 0.05). AMH appeared higher in KS than in controls in all groups, but the difference was only statistically significant in group 2 (p < 0.05). No significant differences were found in height, weight, testicular volume, and penile length. CONCLUSIONS: No hormonal signs of tubular or interstitial damage were found in KS infants. The presence of higher levels of gonadotropins, INHB and testosterone during mini-puberty and pre-puberty may be interpreted as an alteration of the HPG axis in KS infants.

Hormonal and metabolic gender differences in a cohort of myotonic dystrophy type 1 subjects: a retrospective, case-control study.

PURPOSE: Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by CTG expansion in the DMPK gene. The aim was to investigate the endocrine and metabolic aspects of DM1. PATIENTS AND METHODS: Retrospective, case-control study. We compared pituitary, thyroid, adrenal, gonadal and liver function and glycolipid metabolism of 63 DM1 patients against 100 control subjects. Given age-related differences, 2 further subgroups were created to investigate the pituitary-gonadal axis: < 41 (1a) and ≥ 41 (1b) years old for male subjects and < 46 (2a) and ≥ 46 (2b) years old for female subjects. Testicular and thyroid ultrasounds were also performed in the DM1 group. RESULTS: FT3 and FT4 were significantly lower in DM1 men than controls, while for both males and females, thyroglobulin, ACTH and cortisol were significantly higher in the DM1 group. Gonadotropin levels were significantly higher and inhibin B and DHEA-S levels significantly lower in DM1 patients than controls for both male subgroups. Testosterone and SHBG were significantly higher in controls than in patients for subgroup 1a. Prolactin was significantly higher in patients in subgroups 1b, while testosterone was lower in subgroup 2a than in age-matched female controls. A correlation between the number of CTG repeats and the percentage of male hypogonadal subjects was found. Finally, there was a worse glucose and lipid pattern and significantly higher transaminase and gamma-GT levels in both male and female patients. CONCLUSIONS: The high frequency of endocrine and metabolic abnormalities in DM1 highlights the importance of endocrine monitoring to enable the prompt initiation of a suitable therapy.

Total thyroidectomy associated to chemotherapy in primary squamous cell carcinoma of the thyroid.

Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare malignant disease with rapid fatal prognosis. The onset is generally characterized by sudden bilateral latero-cervical lymphadenopathy. The Authors report patient of 58-year-old who referred for evaluation of rapidly aggravating bilateral latero-cervical lymphadenopathy. The US highlighted the presence of a hypoechoic nodular lesion characterized by peri and intra-nodular vascularization. Multilayer CT showed diffused involvement of mediastinal and bilateral latero-cervical lymph nodes, with no evidence of primary pulmonary neoplasia or elsewhere. The patient underwent total thyroidectomy. The peri-isthmic tissue was removed due to the presence of a small roundish formation, that was due to lymph node metastasis at histological examination. Histological diagnosis: PSCCT. The immunohistochemical panel of the thyroid lesion was indispensable for the differential diagnosis between PSCCT, medullary carcinoma, anaplastic carcinoma, and thyroid metastasis of neoplasia with unknown primitiveness. The patient underwent chemotherapeutic treatment with Carboplatin and Paclitaxel with modest improvement of dysphagia symptoms and reduction of 10-15% of the target lesions. The clinical course was characterized by loco-regional progression of the disease with exitus in 10 months after diagnosis. Survival and quality of life after surgical therapy and chemotherapy were like that of patients undergoing only chemotherapy. Due to the extreme rarity of the neoplasia, 60 cases described in Literature, no exclusive guidelines are reported for PSCCT. More extensive case studies are needed to evaluate the effects of total thyroidectomy with intent R0/R1 on improving survival and quality of life of patients with PSCCT.

Epicardial fat: the role of testosterone and lipid metabolism in a cohort of patients with Klinefelter syndrome.

CONTEXT: Klinefelter syndrome (KS), in which subjects have additional copies of X chromosomes, is the most common male sex chromosome abnormality, with a prevalence of 1 in 660 and an incidence of about 1 in 500-700 newborns. Its sign and symptoms include infertility, generally low testosterone levels, and an increased prevalence of obesity and metabolic syndrome. Epicardial fat thickness (EFT) reflects visceral adiposity rather than general obesity. OBJECTIVE: The aim of this study was to analyze echocardiographic EFT in a cohort of patients with KS in comparison with non-obese and obese euploid controls, and to evaluate its correlation with biochemical parameters. DESIGN, SETTING AND PARTICIPANTS: Two hundred and twenty-one KS patients referred to our Rare Endocrine Diseases clinic and 77 age-matched controls underwent Doppler echocardiography and a full investigation of anthropometric and body composition, Serum levels of total testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG), fasting plasma glucose, insulin, cholesterol and triglycerides were obtained. All participants underwent dual energy X-ray absorptiometry (DEXA) scan to assess truncal body fat (TrBF). MAIN OUTCOME MEASURE: EFT, body composition and metabolic parameters in KS patients and how they are affected by genotype. RESULTS: EFT was greater in KS patients than in healthy non-obese (NOb) controls, but lower than in obese (OB) controls. When KS patients were divided into groups (hypogonadal; eugonadal; receiving testosterone replacement therapy [TRT]), EFT was greater in hypogonadal patients than in NOb controls and eugonadal patients, but showed no difference from the OB controls or TRT patients. Hypogonadal patients showed increased TrBF in comparison with NOb controls and eugonadal and TRT patients, and similar TrBF to OB controls. As expected, there was a strong correlation between BMI and EFT in both KS patients and controls (P < 0.0001). In contrast, there was a strong inverse correlation between testosterone and EFT in the control group, but not in KS patients. EFT was significantly correlated with TrBF in both populations (P < 0.0001). Multivariate analyses showed that the major determinants of both EFT and TrBF were BMI and the presence of KS itself. Testosterone and triglycerides were not included as variables in the models. CONCLUSION: EFT in hypogonadal KS subjects was similar to that of the obese eugonadal controls. Even though there was a direct correlation between BMI and EFT in both populations, the influence of TrBF on EFT was stronger. The presence of the supernumerary X chromosome appeared to be one of the strongest determinants of EFT and TrBF, independent of testosterone levels.

Long-term effect of testosterone replacement therapy on bone in hypogonadal men with Klinefelter Syndrome.

PURPOSE: To assess different aspects of bone damage in untreated adult patients with Klinefelter Syndrome (KS) before and during testosterone replacement therapy (TRT). METHODS: Fifteen untreated hypogonadal men with KS and 26 control subjects (C) matched for age and BMI were recruited. Sex hormone levels were measured in all subjects. Lumbar spine (LS) and femoral (neck: FN and total hip: TH) bone mineral density (BMD), trabecular bone score (TBS), hip structure analysis (HSA) and fat measures (percentage of fat mass, android/gynoid ratio and visceral adipose tissue) were evaluated by DEXA. In KS patients, blood analysis and DEXA measurements were assessed at baseline and repeated yearly for three years during TRT. RESULTS: Fat measures were significantly higher in KS than C (p < 0.01). In contrast, mean LS, FN and TH BMD were significantly reduced in KS compared to C (p < 0.01), while there was no difference in TBS. HSA revealed a significantly lower cortical thickness and significantly higher buckling ratio in KS compared to C at all femoral sites (p < 0.01). In KS patients, TRT significantly increased BMD at LS only, but did not improve TBS and HSA parameters. Fat measures were inversely associated with TBS values, and TRT did not influence this relationship. CONCLUSIONS: In untreated hypogonadal men with KS, lumbar and femoral BMD was reduced, and femoral bone quality was impaired. Adiposity seemed to have a detrimental effect on lumbar bone microarchitecture, as indirectly evaluated by TBS. However, TRT failed to remedy these negative effects on bone.

Bilateral hydrocele. Uncommon clinical presentation of primary testicular lymphoma in the elderly.

Primary testicular lymphoma (PLT) represents 5% of testis tumors, the incidence increases in patients older than 60 years of age. Bilateral hydrocele is an unusual clinical presentation. Relapse in the central nervous system and in the contralateral testis is often observed. The US shows hypoechoic nodular lesions with a complete structural involvement of didymus and hypervascularization at Color Doppler. Orchiectomy should be performed in all cases as it is indispensable for the histopathological diagnosis and to characterize the immunophenotypic features. The most common histotype is diffuse large-B cell lymphoma. Combined biological approach and chemotherapy with rituximab and doxorubicin has radically changed the prognosis of disease. The authors report two patients of 81 and 82 years-old who referred for evaluation of massive bilateral hydrocele causing severe limitation of deambulation. Negative cytological findings for neoplastic cells in the scrotal effusion made difficult the differential diagnosis between inflammatory and malignant disease. Histopathologic findings made a diagnosis of high grade diffuse large B-cell NHL, respectively stage IV-E and stage III-E. The 82 years old patient was treated with 6 chemotherapy cycles of rituximab, cyclophosphamide, vincristine, prednisone. The exitus was dued to the umbilical hernia complications. In the 81 years old patient, cognitive deficit and severe impairment of general conditions constituted an absolute contraindication to polychemotherapy treatment. Rapid tumor progression led the patient to exitus 2 months after diagnosis. In both patients the delayed diagnosis of PLT was probably due to the reduction of welfare protection in the elderly with adverse social conditions.

The influence of residents in the outcome of elective laparoscopic surgery: a prospective study comparing a teaching hospital and a private community hospital in Italy.

OBJECTIVES: We compared the outcome of elective laparoscopic cholecystectomy (LC) in a teaching hospital and a private communityhospital to assess the impact of the involvement of residents. MATERIALS AND METHODS: The following parameters were studied prospectively in patients who underwent elective LC during the period from September 2014 to February 2016 in a teaching university hospital (group A) and in a private community hospital (group B): age, sex, body mass index (BMI), comorbidities, American Society of Anaesthesiologists (ASA) score, length of surgery from skin incision to skin closure, use of drain, 30-day perioperative morbidity and mortality, and length of postoperative hospital stay. RESULTS: The group A consisted of 93 elective LC and the group B of 167 elective LC. Operative time was significantly longer in group A. Intraoperative complications were similar and no conversion was necessary in both groups. An increased rate of postoperative complications was observed in group A. All postoperative complications were managed with conservative therapy. No mortality occurred. At logistic regression analysis, the only factor favouring the occurrence of complications was the hospital type. CONCLUSIONS: Our study shows that elective LC can be performed in a teaching hospital with comparable intraoperative morbidity and increased postoperative complications. The greater rate of morbidity found in the teaching hospital may be due to an increased vigilance linked to the presence of residents and not to the lack of expertise.

A multicenter evaluation of immunoassays for follicle-stimulating hormone, luteinizing hormone and testosterone: concordance, imprecision and reference values.

BACKGROUND: Numerous laboratories in Italy use radioimmunoassay to determine concentrations of sex hormones (FSH, LH, testosterone). A comparison of assay methods is thus an important starting point for the achievement of universally accepted reference values. AIM: To carry out an external quality assessment for FSH, LH, and testosterone. MATERIALS AND METHODS: Fifteen aliquots from 5 serum pools were assayed in multiple replicates by 16 Italian laboratories with 5 automated immunoassays (Abbott Architect, DiaSorin Liaison, Perkin-Elmer AutoDelfia, Roche Elecsys, Siemens Immulite 2000), and 1 radioimmunoassay (Adaltis). RESULTS: The variance was below 12% for FSH, between 11.61% and 14.76% for LH, and between 9.57% and 12.48% for testosterone. Assay precision was good, except for Elecsys at low concentrations of FSH and for Immulite at low concentrations of LH and testosterone. ARCHITECT showed a negative bias for FSH and LH and a positive bias for testosterone; Liaison a positive bias for LH; Elecsys a positive bias for FSH and a negative bias for testosterone; Immulite a positive bias for FSH; AutoDelfia a negative bias for FSH and a positive bias for testosterone. Reference ranges at the low end varied widely, even among laboratories using the same assay. CONCLUSIONS: The analytical performances of widely used immunoassays for FSH, LH, and testosterone show a fair to strong degree of consistency. A careful evaluation of reference ranges by clinical and laboratory experts needs to be carried out, in order to reach a consensus.

Reference ranges for thyroid hormones in normal Italian children and adolescents and overweight adolescents.

BACKGROUND: As thyroid hormones are essential for normal pubertal growth and sexual development, TSH, free T3 (FT3) and free T4 (FT4) levels undergo progressive modification during childhood and puberty. AIM: To establish thyroid hormone reference ranges in pre-pubertal children, pubertal adolescents, and adults and to evaluate any differences in thyroid function between overweight and normalweight pubertal subjects. SUBJECTS AND METHODS: Chemiluminescent microparticle immunoassay was used to analyze TSH, FT3 and FT4 concentrations in serum samples from 508 children and adolescents aged 6 to 18 yr and 100 healthy adults aged 30 to 60 yr, and from 68 overweight pubertal adolescents. As data were not normally distributed, we compared them through non-parametric tests for independent samples and the reference ranges were assumed to lie between the 2.5th and 97.5th percentile. RESULTS: We found a progressive and significant reduction in TSH, FT3, and FT4 levels in the three groups with increasing age. TSH levels were significantly higher in overweight patients than in the normal-weight group, but there were no significant differences for FT3 or FT4. CONCLUSIONS: This study revealed significant differences in levels of thyroid hormone between different age groups and allowed us to establish normal reference ranges for pre-pubertal children between 0.87-5.19 mIU/l for TSH, 4.75-8.59 pmol/l for FT3, and 13.09-20.61 pmol/l for FT4, and for pubertal adolescents between 0.76- 4.51 mIU/l for TSH, 4.26-8.46 pmol/l for FT3 and 10.94-19.09 pmol/l for FT4.

Growth hormone deficiency in the transition period: body composition and gonad function.

Recombinant GH therapy is normally administered to GH-deficient children in order to achieve a satisfactory height - the main target during childhood and adolescence. However, the role of GH does not end once final height has been reached, but continues during the so-called transition period. In this phase of life, the body undergoes several changes, both physical and psychological, that culminate in adulthood. During this period, GH has a part in numerous metabolic functions. These include the lipid profile, where it increases HDL and reduces LDL, with the global effect of cardiovascular protection. It also has important effects on body composition (improved muscle strength and lean body mass and reduced body fat), the achievement of proper peak bone density, and gonad maturation. Retesting during the transition period, involving measurement of IGF-I plus a provocative test (insulin tolerance test or GHRH + arginine test), is thus necessary to establish any persistent GH deficiency requiring additional replacement therapy. The close cooperation of the medical professionals involved in the patient's transition from a pediatric to an adult endocrinologist is essential. The aim of this review is to point out the main aspects of GH treatment on body composition, metabolic and gonad functions in the transition period.

Effect of high-pressure homogenization on droplet size distribution and rheological properties of ice cream mixes.

The effect of different homogenization pressures (15/3 MPa and 97/3 MPa) on fat globule size and distribution as well as on structure-property relationships of ice cream mixes was investigated. Dynamic light scattering, steady shear, and dynamic rheological analyses were performed on mixes with different fat contents (5 and 8%) and different aging times (4 and 20 h). The homogenization of ice cream mixes determined a change from bimodal to monomodal particle size distributions and a reduction in the mean particle diameter. Mean fat globule diameters were reduced at higher pressure, but the homogenization effect on size reduction was less marked with the highest fat content. The rheological behavior of mixes was influenced by both the dispersed and the continuous phases. Higher fat contents caused greater viscosity and dynamic moduli. The lower homogenization pressure (15/3 MPa) mainly affected the dispersed phase and resulted in a more pronounced viscosity reduction in the higher fat content mixes. High-pressure homogenization (97/3 MPa) greatly enhanced the viscoelastic properties and the apparent viscosity. Rheological results indicated that unhomogenized and 15/3 MPa homogenized mixes behaved as weak gels. The 97/3 MPa treatment led to stronger gels, perhaps as the overall result of a network rearrangement or interpenetrating network formation, and the fat globules were found to behave as interactive fillers. High-pressure homogenization determined the apparent viscosity of 5% fat to be comparable to that of 8% fat unhomogenized mix.

Bacillus cereus cell and spore properties as influenced by the micro-structure of the medium.

AIM: To investigate the effect of different growth conditions on Bacillus cereus cell and spore properties. METHODS AND RESULTS: Bacillus cereus was grown on agar plates with different surface water conditions (wet and dry) or viscosity. Cell populations displayed different types of behaviour, and heterogeneity was manifested in cell motility and dimension. Spore populations were heterogeneous regarding their properties, namely size and thermal resistance. The smallest spores were produced from flagellated cells, which also displayed jet-motility, growing on the wettest agar. Cytometric analysis also revealed within the smallest spores a sub-population labelled by propidium iodide (PI), indicating that spore populations were partly damaged. Nonmotile cells grown on diffusion-limiting media were elongated and produced the least thermal-resistant spores. CONCLUSIONS: The micro-structural properties of the media were found to influence cell and spore properties. Abundant surface water enabled flagellar motility and resulted in a heterogeneous cell and spore population, the latter including small and damaged spores. High viscosity gave rise to filamentous cells and more heat-sensitive spores. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides useful information on conditions resulting in heterogeneous populations of damaged and heat-sensitive spores.