HNF1A gene mutations and premature ovarian failure (POF): evidence from a clinical paradigm combining MODY 3 and POF.

Premature ovarian failure (POF) defines the occurrence of ovarian failure prior to the age of 40. It occurs in one out of 100 women but is very rare before age 20 (1:10,000). Maturity-onset diabetes of the young (MODY), caused by mutations in the HNF1A gene, is also a rare disorder; all types of MODY account for 1-2% of adult diabetic cases. These two rare nosologic entities coexisted in an adolescent girl evaluated for delayed puberty. Although this combination could represent a chance association, an interrelation might exist. We examined HNF1A expression in human fetal and adult ovaries by immunohistochemistry using a polyclonal HNF1A antibody. HNF1A protein was expressed in both the fetal and adult human ovaries. Based on these findings, we hypothesize that HNF1A participates in ovarian organogenesis and/or function and that mutations in the HNF1A gene might represent another molecular defect causing POF, possibly in combination with other genetic factors. The study underlines the importance of rare clinical paradigms in leading the way to elucidation of the pathogenetic mechanisms of rare diseases.

Development of a pediatric differentiated thyroid carcinoma registry within the EuRRECa project: rationale and protocol.

Background: Although differentiated thyroid carcinoma (DTC) is the most frequent endocrine pediatric cancer, it is rare in childhood and adolescence. While tumor persistence and recurrence are not uncommon, mortality remains extremely low. Complications of treatment are however reported in up to 48% of the survivors. Due to the rarity of the disease, current treatment guidelines are predominantly based on the results of small observational retrospective studies and extrapolations from results in adult patients. In order to develop more personalized treatment and follow-up strategies (aiming to reduce complication rates), there is an unmet need for uniform international prospective data collection and clinical trials. Methods and analysis: The European pediatric thyroid carcinoma registry aims to collect clinical data for all patients ≤18 years of age with a confirmed diagnosis of DTC who have been diagnosed, assessed, or treated at a participating site. This registry will be a component of the wider European Registries for Rare Endocrine Conditions project which has close links to Endo-ERN, the European Reference Network for Rare Endocrine Conditions. A multidisciplinary expert working group was formed to develop a minimal dataset comprising information regarding demographic data, diagnosis, treatment, and outcome. We constructed an umbrella-type registry, with a detailed basic dataset. In the future, this may provide the opportunity for research teams to integrate clinical research questions. Ethics and dissemination: Written informed consent will be obtained from all participants and/or their parents/guardians. Summaries and descriptive analyses of the registry will be disseminated via conference presentations and peer-reviewed publications.

Aquagenic wrinkling of the palms in a cohort of Greek children diagnosed with cystic fibrosis: Associated clinical parameters.

BACKGROUND: Aquagenic wrinkling of the palms (AWP) is an excessive and early palmar wrinkling occurring after brief immersion to water (BIW), and has been reported as a frequent finding among Cystic Fibrosis (CF) patients. OBJECTIVES: To investigate any associations of CF patients presenting AWP with other disease characteristics and explore the pathomechanism of AWP phenomenon. METHODS: We evaluated AWP in CF patients and assessed the AWP parameters of palmar wrinkling, oedema, papules, pruritus and pain at 3, 7 and 11 min after a BIW test with other disease characteristics. Statistical analyses explored the associations of AWP with genotype, lung function, pancreatic insufficiency, hyperhidrosis, personal and family history of atopy and sweat chloride levels. RESULTS: One hundred CF patients (mean age 10.4 years) were included in the analysis. The genotypic distribution was ΔF508/ΔF508: 47%, ΔF508/other: 41% and other/other: 12%. Statistically significant associations of Kaplan-Meier curves of the AWP parameters with various disease characteristics and personal/family history were detected. Wrinkling was associated with history of atopy, hyperhidrosis and levels of sweat chloride test. The time to presentation of oedema and the appearance of papules were associated with history of hyperhidrosis and age at diagnosis. Finally, time to appearance of pruritus was related to history of atopy and of hyperhidrosis. Regarding TEWL regression analysis showed significant associations with age at diagnosis (p = 0.024), sweat chloride test levels (p = 0.005), history of hyperhidrosis (p = 0.033), history of atopy (p = 0.002) and hepatic-pancreatic involvement (p = 0.027). CONCLUSIONS: The existence of a statistically significant association between AWP and the history of hyperhidrosis, atopy, sweat chloride levels and hepatic-pancreatic function in CF patients was detected. A strong association between AWP and CF was detected. AWP after BIW could be elicited easily and possibly can be used as an initial screening tool to diagnose an individual with symptoms and signs that raise the likelihood of CF.

Cyclic neutropenia and concomitant IgA nephropathy: a case report.

BACKGROUND: IgA nephropathy (IgAN) is universally recognized as one of the most common primary glomerular diseases in all ages. Cyclic neutropenia (CN) is a rare haematologic disorder that is associated with mutations of the ELANE gene. The co-occurrence of IgAN and CN is extremely rare. This is the first case report of a patient with IgAN and genetically confirmed CN. CASE PRESENTATION: We report a case of a 10-year-old boy who presented with recurrent viral upper respiratory tract infections accompanied by several episodes of febrile neutropenia, haematuria, proteinuria and acute kidney injury. Upon first admission, his physical examination was unremarkable. His kidney function was impaired, whereas his urine microscopy showed evidence of macroscopic haematuria and proteinuria. Further workup showed elevated IgA. The renal histology was consistent with mesangial and endocapillary hypercellularity with mild crescentic lesions, while immunofluorescence microscopy showed IgA-positive staining, which was characteristic of IgAN. Moreover, genetic testing confirmed the clinical diagnosis of CN, therefore Granulocyte colony-stimulating factor (G-CSF) was initiated to stabilize the neutrophil count. Regarding proteinuria control, the patient was initially treated with an Angiotensin-converting-enzyme inhibitor for approximately 28 months. However, due to progressive proteinuria (> 1 g/24 h), Corticosteroids (CS) were added for a period of 6 months according to the revised 2021 KDIGO guidelines with favorable outcome. CONCLUSIONS: Patients with CN are more susceptible to recurrent viral infections, which can trigger IgAN attacks. In our case CS induced remarkable proteinuria remission. The use of G-CSF contributed to the resolution of severe neutropenic episodes, viral infections and concomitant AKI episodes, contributing to better prognosis of IgAN. Further studies are mandatory to determine whether there is a genetical predisposition for IgAN in children with CN.

Aquagenic wrinkling of the palms after brief immersion to water test as a screening tool for cystic fibrosis diagnosis.

BACKGROUND: Aquagenic wrinkling of the palms (AWP) is an excessive and early palmar wrinkling occurring after Brief Immersion to Water (BIW), and has been reported as a frequent finding among cystic fibrosis (CF) patients. OBJECTIVES: To evaluate and assess the diagnostic performance of BIW test as an initial screening tool for CF diagnosis. METHODS: We measured AWP in CF patients, CF-heterozygotes (CF-het) and normal controls. The AWP parameters of palmar wrinkling, oedema, papules, pruritus and pain were assessed at 3, 7 and 11 min after a BIW test was performed for all the participants. Statistical analyses explored the progression of AWP in time for the three groups and assessed the diagnostic performance of BIW test as a diagnostic screening tool for CF. RESULTS: A total of 250 individuals (100 CF patients, their 50 CF-het parents, 100 healthy controls) were included in the analysis. The average age in years (mean ± SD) was 10.4 ± 4.0 for CF, 35.9 ± 6.1 for CF-het and 10.5 ± 4.0 for controls. The rate of positives for AWP at 3 min among CF patients, CF-het and controls was 68%, 8% and 0%, respectively (P < 0.01). Kaplan-Meier analysis showed a clear trend towards earlier appearance of all five parameters in the direction controls < hetCF < CF (P values <0.01). The best diagnostic performance in detecting between CF patients and non-CF was achieved by the presence of papules and wrinkling at 7 min (sensitivity/specificity: 94.0%/98.3% and 100.0%/92.0%, respectively). CONCLUSIONS: A strong association between AWP and CF was detected. AWP after BIW could be elicited easily and possibly can be used as an initial screening tool to assess if an individual with symptoms and signs that raise the likelihood of CF is a CF patient.

Pediatric growth hormone therapy in Greece: analysis of the Hellenic cohort of the GeNeSIS study.

PURPOSE: To describe the data from the Greek cohort of the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS). METHODS: GeNeSIS was a prospective, open-label, multinational, observational study collecting information on clinical outcomes and treatment safety of children with growth disorders treated with growth hormone (GH), according to national indications. After informed consent, 305 patients (143 females), including 255 patients with growth hormone deficiency (GHD) and 30 with Turner syndrome (TS), from eight investigational sites, were enrolled in Greece. Demographic data, treatment efficacy, and adverse events were reported at the discretion of attending physicians. RESULTS: Treatment with GH was undertaken for 247/255 patients with GHD and 29/30 with TS. The majority of patients treated with GHD (73.7%) and TS (84%) with recorded Tanner stage were prepubertal at enrolment. Among patients treated with GHD and TS, 70.45% and 55% were GH-naïve at study entry, respectively. Height standard deviation score (SDS), height velocity SDS, and height SDS-target height SDS numerically improved during the 4-year observation period. The effect of GH treatment was more prominent in the first year of treatment, especially in the GHD group. CONCLUSIONS: In the Greek cohort of GeNeSIS, GHD is the most frequent indication for GH treatment, followed by TS. While the latter is diagnosed somewhat earlier, GH treatment is not as efficacious as for patients with GHD. No major safety issues were reported during follow-up. The results, which are in accordance with the international literature, should be interpreted in the context of observational studies.

Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium.

This update, written by authors designated by multiple pediatric endocrinology societies (see List of Participating Societies) from around the globe, concisely addresses topics related to changes in GnRHa usage in children and adolescents over the last decade. Topics related to the use of GnRHa in precocious puberty include diagnostic criteria, globally available formulations, considerations of benefit of treatment, monitoring of therapy, adverse events, and long-term outcome data. Additional sections review use in transgender individuals and other pediatric endocrine related conditions. Although there have been many significant changes in GnRHa usage, there is a definite paucity of evidence-based publications to support them. Therefore, this paper is explicitly not intended to evaluate what is recommended in terms of the best use of GnRHa, based on evidence and expert opinion, but rather to describe how these drugs are used, irrespective of any qualitative evaluation. Thus, this paper should be considered a narrative review on GnRHa utilization in precocious puberty and other clinical situations. These changes are reviewed not only to point out deficiencies in the literature but also to stimulate future studies and publications in this area.

The spectrum of clinical, hormonal and molecular findings in 280 individuals with nonclassical congenital adrenal hyperplasia caused by mutations of the CYP21A2 gene.

BACKGROUND: Nonclassical congenital adrenal hyperplasia (NC-CAH) is caused by mutations of the CYP21A2 gene. The clinical manifestations and hormonal derangements of NC-CAH are quite variable. OBJECTIVES: (i) To define the phenotype and its relation to genotype according to gender and age and (ii) to evaluate the validity of currently applied hormonal criteria for establishing the diagnosis of NC-CAH. PATIENTS AND METHODS: The clinical, hormonal and molecular data of 280 subjects (235 female) with NC-CAH and a median age of 17·6 years were analysed. CYP21A2 genotyping was performed in all subjects. RESULTS: The majority of females aged less than 8 years presented with premature pubarche (88·3%), while those older than 8 presented with a polycystic ovary-like phenotype (63·2%). A total of 7·7% of the females and 51·1% of the males were asymptomatic at the time of diagnosis. In the total group, 50·4% of the subjects were compound heterozygotes for one classical (C) and one nonclassical (NC) mutation, while 46% of the alleles studied carried the p.V281L mutation. Basal 17OHP values were below 6 nm (2 ng/ml) in 2·1% of the subjects with NC-CAH, but none had peak 17OHP values post-ACTH lower than 30 nm (10 ng/ml). CONCLUSIONS: NC-CAH has a variable phenotype depending on the age, gender and the presence of a classical mutation. A peak cut-off value of 17OHP post-ACTH lower than 30 nm excludes the diagnosis of NC-CAH, whereas basal 17OHP <6 nm may represent a false-negative result. A significant number of patients harboured a classical mutation, a finding which requires genotyping of the partner for genetic counselling.

Identification of lifestyle patterns, including sleep deprivation, associated with insulin resistance in children: the Healthy Growth Study.

BACKGROUND/OBJECTIVES: Although diet, physical activity (PA), sedentary behavior and sleep deprivation are factors that have been individually associated with insulin resistance (IR) in childhood, the combined effect of these lifestyle behaviors has not been examined yet. The current study aimed to examine the association of lifestyle patterns with IR, combining all these indices, in children. SUBJECTS/METHODS: Socio-economic, demographic, anthropometric (body weight, height and waist circumference), biochemical (plasma glucose and serum insulin), clinical (pubertal stage) and lifestyle (dietary intake, PA level and sleeping habits) data were collected from a representative sample of 2026 children (50.1% girls) aged 9-13 years in Greece. Homeostasis model assessment (HOMA-IR) was calculated, and principal component analysis was used to identify lifestyle patterns, combining all these lifestyle indices. RESULTS: In multivariable regression analyses, the lifestyle pattern characterized by more screen time, shorter sleep duration and higher consumption of sugared beverages was positively associated with HOMA-IR (ß=0.043; P=0.040), whereas the pattern characterized by more time spent on moderate-to-vigorous PA (MVPA) and more frequent eating occasions was inversely associated with HOMA-IR (ß=-0.061; P=0.003). In logistic regression analyses, children with 72.2 min/day of MVPA and 5.05 eating occasions/day and children with 141.8 min/day of MVPA and 5.22 eating occasions/day were less likely of being insulin resistant based on HOMA-IR, compared with children with 20.0 min/day of MVPA and 4.09 eating occasions/day. CONCLUSIONS: A lifestyle pattern of >72 min of MVPA and 5 eating occasions/day was associated with reduced likelihood of IR in children.

Reproducibility of vibration perception threshold values in children and adolescents with type 1 diabetes mellitus and associated factors.

AIMS: To define the reproducibility of vibration perception thresholds (VPTs) and the possible associated factors, as an early index of peripheral diabetic neuropathy (PDN) in type 1 diabetes mellitus (T1DM) children and adolescents. METHODS: A single examiner studied 118 T1DM subjects (aged 13.5±3.4 years) and 79 controls (aged 12.0±3.07 years). Glycaemic control was assessed with HbA1c levels. VPT was measured twice on upper and lower limbs, using a Biothesiometer. Concordance between the two VPT measurements was evaluated using the Cohen's Weighted Kappa statistic (Kappa=0.41-0.60→moderate concordance, Kappa=0.61-0.80→substantial concordance). RESULTS: T1DM children had significantly higher VPTs than controls at all sites (p=0.001), but with lower Kappa values (0.64-0.70). VPT values increased in parallel with HbA1c (a.<8%, b. 8-9.5%, c.>9.5%) and T1DM duration (a.<5 years, b.5.1-10, c.>10 years). However, Kappa values were lower in the groups with the poorest control (HbA1c>9.5%) (Kappa=0.54-0.76) or the longest T1DM duration (>10 years) (Kappa=0.49-0.71). Although VPTs increased with stature and male gender, no effect on VPT reproducibility was observed. However, obesity was associated with lower VPT values and poorer concordance. CONCLUSIONS: These findings suggest that the reproducibility of VPTs is lower in the high-risk patients for early subclinical PDN development, who need a regular follow-up.

Peripheral neuropathy in children with type 1 diabetes.

Diabetic neuropathy (DN) is a major complication of type 1 diabetes mellitus (T1DM) with significant morbidity and mortality in adulthood. Clinical neuropathy is rarely seen in paediatric populations, whereas subclinical neuropathy is commonly seen, especially in adolescents. Peripheral DN involves impairment of the large and/or small nerve fibres, and can be diagnosed by various methods. Nerve conduction studies (NCS) are the gold-standard method for the detection of subclinical DN; however, it is invasive, difficult to perform and selectively detects large-fibre abnormalities. Vibration sensation thresholds (VSTs) and thermal discrimination thresholds (TDTs) are quicker and easier and, therefore, more suitable as screening tools. Poor glycaemic control is the most important risk factor for the development of DN. Maintaining near-normoglycaemia is the only way to prevent or reverse neural impairment, as the currently available treatments can only relieve the symptoms of DN. Early detection of children and adolescents with nervous system abnormalities is crucial to allow all appropriate measures to be taken to prevent the development of DN.

Neck circumference: a useful screening tool of cardiovascular risk in children.

OBJECTIVE: Early identification of cardiovascular risk factors consists an essential target for public health. The current study aims to examine the association between neck circumference and several cardiovascular risk factors and to compare it with well-established anthropometric indices. METHODS: Demographic, anthropometric (body weight and height, waist, hip and neck circumference [WC, HC and NC, respectively]), biochemical (total cholesterol, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, triglycerides [TG], fasting plasma glucose and serum insulin), clinical (pubertal stage, systolic and diastolic blood pressure [SBP and DBP, respectively]) and lifestyle (dietary intake, physical activity level) data were collected from 324 children (51.5% boys; 48.5% girls) aged 9-13 in Greece. Body mass index z-score (BMI z-score), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and fasting glucose to insulin ratio (FGIR) were calculated. RESULTS: All indices (BMI z-score, NC, WC, HC, WHR and WHtR) were correlated with SBP, HDL and insulin-related indices (insulin, HOMA-IR, QUICKI and FGIR) and all indices except WHR with TG. LDL was correlated with BMI z-score, WC, WHR and WHtR, whereas DBP was correlated with BMI z-score, WC, HC and WHtR. In multivariate analysis, HDL, TG, SBP, insulin, HOMA-IR, QUICKI and FGIR were associated with all anthropometric indices; DBP with WC, HC, NC and WHtR; LDL with BMI z-score, WC, HC and WHtR. CONCLUSIONS: NC is associated with most cardiovascular disease risk factors. These associations are comparable with those observed for BMI z-score, WC, HC, WHR and WHtR. NC could be a simple, alternative screening tool of cardiovascular risk in children.

Retinol Binding Protein 4 in children with Inflammatory Bowel Disease: a negative correlation with the disease activity.

OBJECTIVES: Retinol Binding Protein-4 (RBP-4), the action of which was initially thought to be only the transport of vitamin A, is a major circulating adipocytokine involved in the inflammation. We evaluated the serum RBP-4 levels in children with inflammatory bowel disease (IBD) and correlated them with transthyretin (TTR), inflammation markers, disease activity, and body mass index (BMI). DESIGN: In 41 children of mean age 11.9 ± 3.6 years (range 5-17.7 y) with IBD (19 with Crohn's disease (CD) and 22 with Ulcerative colitis (UC) serum RBP-4, TTR, Amyloid A (SAA), C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), disease activity and BMI were prospectively determined and compared with those of 42 matched controls. RESULTS: No difference in the RBP-4 and TTR serum levels, between patients and controls as well as between active and remission state of the disease was noticed. A negative correlation of serum RBP-4 with the disease activity, SAA and ESR and a positive correlation with TTR was found, but no significant correlation with CRP or BMI was found. Inflammation markers were significantly increased in patients compared to controls and had a positive correlation with the disease activity. CONCLUSIONS: RBP-4 negatively correlated with disease activity of children with IBD probably indicating a protective anti-inflammatory mechanism of action in addition to transport of vitamin A.

Enhanced oxidative stress and platelet activation combined with reduced antioxidant capacity in obese prepubertal and adolescent girls with full or partial metabolic syndrome.

In adults, obesity is a main factor implicated in increased oxidative stress (OS), platelet activation (PA) and impaired antioxidant status (AS), all predisposing factors for cardiovascular disease leading to increased morbidity and mortality. Furthermore, the metabolic syndrome (MetS) is an important cardiovascular risk factor, which progressively develops and may already be present during late childhood or adolescence. However, scarce data exist on oxidative-antioxidant balance and PA in childhood and adolescence in the presence of partial (PMetS) or full MetS. The aim of the study was to evaluate OS, PA, and AS in prepubertal and adolescent obese girls with partial or full MetS. 96 girls with a clinical and metabolic evaluation for obesity and 44 healthy normal-weight sex- and age-matched girls were studied. IDF-adopted criteria were used to define full and partial MetS and the patient population was divided into 4 groups: the first comprised 31 pre-pubertal girls with PMetS (PR-PMetS), the second 37 adolescents with PMetS (AD-PMetS), the third 10 prepubertal girls with full MetS (PR-MetS), and the fourth 18 adolescents with full MetS (AD-MetS). The OS was evaluated by measuring plasma 15-F(2t)-Isoprostane levels (15-F(2t)-IsoP) and protein carbonyls, PA by thromboxane B(2) levels (TXB(2)), and AS by serum vitamin E and plasma total antioxidant capacity (TAC) levels. 15-F(2t)-IsoP, protein carbonyls, and TXB(2) levels were significantly gradually amplified, and vitamin E and TAC reduced, and significantly correlated with obesity from childhood to adolescence and from partial to full MetS. This study demonstrates the loss of the normal homeostatic balance between oxidant-antioxidant state in obese children and adolescents with manifestations of partial and full MetS.

Associations between circulating N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and adiponectin concentrations depend on obesity level in female adolescents: gender dimorphic findings.

N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) is an established biomarker for heart failure in adults, while its plasma concentrations are altered in adult obesity. Plasma adiponectin concentrations are decreased in obesity and low levels are associated with disorders with an increased cardiometabolic risk. A few studies support an association between these two markers in adults with coronary heart disease. Such relations have not been investigated in children with obesity, which is the most prevalent risk factor for cardiovascular disease. Ninety-six children, 24 obese/25 normal BMI boys, and 23 obese/24 normal BMI girls, aged 10-16, were studied. Plasma NT-proBNP was measured using electrochemiluminescence, and adiponectin and other metabolic risk factors, such as glucose, insulin, cholesterol, triglycerides (TG), HDL, and LDL using standard methodology. The findings were gender dimorphic. In overweight and obese females (mean BMI z-score: 2.65+/-1.69), plasma NT-proBNP concentrations correlated significantly with adiponectin levels (r=0.4, r(2)=0.05, p=0.013), while in those with obesity defined as BMI z-score >2.5 (mean BMI z-score: 3.67+/-1.08, n=20) this association was stronger (r=0.6, r(2)=0.22, p=0.005). Adiponectin also correlated significantly with BMI z-scores, TG, HDL, and insulin levels. In boys, there was no correlation between NT-proBNP and adiponectin. NT-proBNP correlated significantly with HDL, while adiponectin correlated with TG, fasting insulin, and the Homeostasis Assessment Model (HOMA) Index. The positive association between NT-proBNP and adiponectin depends on the severity of obesity and is gender dimorphic. This positive correlation in females might be a potential protective mechanism against atherosclerosis in later life.

Obesity and attenuated adiposity rebound in children with congenital hypothyroidism. Normalization of BMI values in adolescents.

An earlier adiposity rebound, suggestive of adult obesity, has been reported in children with congenital hypothyroidism. We undertook this study to evaluate the effect of congenital hypothyroidism on: 1) the timing of adiposity rebound, 2) the long-term prognosis of BMI status, and 3) the factors potentially affecting adiposity in subjects with congenital hypothyroidism. We found that in children with congenital hypothyroidism the BMI values were higher during the first years of life compared to normal population, but subsequently normalized. After the initial rise of BMI, the decline (nadir) and subsequent rise (adiposity rebound), usually occurring in normal children at an age greater than 30 months, was less evident in our group of children with congenital hypothyroidism. The severity of hypothyroidism affected BMI values at 6 and 12, but not at 36 months of age. In conclusion, in children with congenital hypothyroidism, 1) the high BMI values in early childhood normalize in adolescence, and 2) the normally expected BMI fluctuations during the first years of life are attenuated. These findings constitute indirect evidence that thyroid function during fetal and neonatal life affects BMI status during the first years of life.

Rare XXY/XX mosaicism in a phenotypic male with Klinefelter syndrome: case report.

Klinefelter syndrome represents the most commonly found human sex chromosomal abnormality. It is characterized by small, firm testes with hyalinization of the seminiferous tubules, elevated gonadotropins and azoospermia. Males with Klinefelter syndrome may have a 47,XXY or a mosaic 47,XXY/46,XY constitutional karyotype and varying degrees of spermatogenic failure. Mosaicism 47,XXY/46,XX with clinical features suggestive of Klinefelter syndrome, is very rare and so far only 10 cases have been described in literature [1,2,5,8,10,15,22,23,25,44]. We report here a case of a mosaic 47,XXY/46,XX infertile male in whom detailed cytogenetic, histological and molecular studies were performed. Cytogenetic analysis revealed 80% and 50% mosaicism for the 46,XX cell line in blood lymphocytes and in skin fibroblasts, respectively, and the presence of 47,XXY cells only, in cultured testicular tissue. Testicular histopathology revealed atrophy of the testes with no spermatogenesis and absence of germ cells. Molecular analysis showed paternal inheritance of the extra X chromosome.

The impact of exercise on thyroid hormone metabolism in children and adolescents.

Thyroid hormones are important regulators of energy metabolism and may influence energy processes during physical exercise. There are controversial results concerning thyroid hormone metabolism during strenuous exercise in adult athletes and only scant data concerning the impact of strenuous exercise on thyroid hormone metabolism in children and adolescents. Although some studies demonstrate a transient change in thyroid hormones during intense physical performance, most studies agree that these changes are of minor impact, practically reflecting the relative negative energy balance during strenuous exercise. This state of hypometabolism during intense physical performance has also been confirmed in highly trained female young athletes, who may be also characterized by reproductive axis dysfunction, manifested either as luteal-phase deficiency or amenorrhea, alongside the typical constellation of low T3, insulin and leptin levels. More importantly, strenuous exercise during childhood or adolescence is mostly accompanied by a delay of skeletal maturation, and height and may have a long-lasting negative effect on growth and acquisition of maximum bone mass. In conclusion, although thyroid hormones are only transiently or insignificantly changed during strenuous exercise, adequate caloric intake should be guaranteed in highly performing young athletes in order to counteract the relative negative energy balance and prevent alterations in endocrine-metabolic profile. Moreover, when growth and pubertal progression in very young athletes are significantly impaired, a reduction in the intensity of the physical exercise should be advocated in order to guarantee better final height and adequate acquisition of bone mass.

Prevalence of thyroid dysfunction in Turner's syndrome: a long-term follow-up study and brief literature review.

Thyroid dysfunction, especially hypothyroidism caused by Hashimoto's thyroiditis is more frequently observed in girls with Turner's syndrome (TS). The aim of the present study was to evaluate prevalence, etiology, karyotype distribution and age at onset of thyroid pathology in girls with TS. Data recorded in 84 girls with TS attending our clinic were analyzed. The mean age +/- standard deviation [SD] at their initial evaluation was 10.3 +/- 3.7 years (range, 0.5 to 19 years) and the mean period of observation was 8.4 +/- 4.4 years. The thyroid function had been evaluated at least once per year in all patients and thyroid autoantibodies (ATA) were available in 51 (60.7%). Hypothyroidism was detected in 24% of the studied subjects and hyperthyroidism in 2.5%. Elevated values of thyroid autoantibodies were detected in 42% of girls with TS, whose ATA had been determined, and 65% had hypothyroidism. Thyroid dysfunction was first noted after the age of 8 years with no difference in the distribution of new cases at the different ages or pubertal stages. There was no difference in the incidence of thyroid dysfunction related to the type of karyotype abnormality. Thyroid dysfunction is more frequently encountered in girls with TS (hypothyroidism: 24% in the total group and 65% in those with positive ATA, hyperthyroidism: 2.5%). Thyroid dysfunction was observed after the age of 8 years with no difference in the occurrence of new cases in the various age groups thereafter. Hence, thyroid function should be evaluated yearly in girls with TS past the age of 8 years and more frequently in those with positive thyroid autoantibodies.