Testicular microlithiasis in paediatric patients with Klinefelter syndrome from infancy till adolescence: early start of degenerative process in the testes-preliminary results.

To present the results of testicular ultrasonography supported by clinical and hormonal aspects in paediatric patients with Klinefelter syndrome (KS). Prospective analysis of medical files of 20 patients diagnosed with KS between 2016 and 2022. Assessed data included analysis of causes of referral, ultrasound, and clinical characterisation with hormonal evaluation of serum FSH, LH, testosterone, inhibin B, and anti-Müllerian hormone. Non-mosaic Klinefelter syndrome (47, XXY) was diagnosed in 65% of cases (13/20) by the geneticist (including 7 cases prenatally), in 25% (5/20) by the endocrinologist and in 10% (2/20) by the hematologist. Ultrasound assessment revealed bilateral testicular microlithiasis (TM) in all patients. The youngest KS patient with TM was 3 months old. TM patterns have not changed during follow-ups of up to 6 years in any of the patients. In all KS patients markedly reduced echogenicity and in pubertal KS patients, also irregular echostructure of the testes was observed. The hormonal patterns observed in the study group were typical for those already described in KS. Sertoli and Leydig cell function was intact in prepubertal patients and deteriorated after the start of puberty. CONCLUSION: Although the degenerative process in the testicular tissue starts very early in the testes in KS and is reflected in morphological changes seen in ultrasonography, Sertoli and Leydig cell hormonal function is normal in prepubertal KS patients. WHAT IS KNOWN: • So far, normal Leydig and Sertoli cell function was observed in infants and prepubertal KS patients. WHAT IS NEW: • The morphological changes in the testes in KS may already be seen in early infancy.

Raman Spectroscopy as a Potential Adjunct of Thyroid Nodule Evaluation: A Systematic Review.

The incidence of thyroid nodules (TNs) is estimated at 36.5% and 23% in females and males, respectively. A single thyroid nodule is usually detected during ultrasound assessment in patients with symptoms of thyroid dysfunction or neck mass. TNs are classified as benign tumours (non-malignant hyperplasia), benign neoplasms (e.g., adenoma, a non-invasive follicular tumour with papillary nuclear features) or malignant carcinomas (follicular cell-derived or C-cell derived). The differential diagnosis is based on fine-needle aspiration biopsies and cytological assessment (which is burdened with the bias of subjectivity). Raman spectroscopy (RS) is a laser-based, semiquantitative technique which shows for oscillations of many chemical groups in one label-free measurement. RS, through the assessment of chemical content, gives insight into tissue state which, in turn, allows for the differentiation of disease on the basis of spectral characteristics. The purpose of this study was to report if RS could be useful in the differential diagnosis of TN. The Web of Science, PubMed, and Scopus were searched from the beginning of the databases up to the end of June 2023. Two investigators independently screened key data using the terms "Raman spectroscopy" and "thyroid". From the 4046 records found initially, we identified 19 studies addressing the differential diagnosis of TNs applying the RS technique. The lasers used included 532, 633, 785, 830, and 1064 nm lines. The thyroid RS investigations were performed at the cellular and/or tissue level, as well as in serum samples. The accuracy of papillary thyroid carcinoma detection is approx. 90%. Furthermore, medullary, and follicular thyroid carcinoma can be detected with up to 100% accuracy. These results might be biased with low numbers of cases in some research and overfitting of models as well as the reference method. The main biochemical changes one can observe in malignancies are as follows: increase of protein, amino acids (like phenylalanine, tyrosine, and tryptophan), and nucleic acid content in comparison with non-malignant TNs. Herein, we present a review of the literature on the application of RS in the differential diagnosis of TNs. This technique seems to have powerful application potential in thyroid tumour diagnosis.

Nocturnal non-dipping on 24-h Ambulatory Blood Pressure Monitoring in children and adolescents with obesity is associated with higher total cholesterol levels.

BACKGROUND: Few studies indicate the occurrence of abnormal nocturnal dipping of blood pressure (BP) in 35-50% of children and adolescents with obesity. The relation between that phenomenon and metabolic complications of obesity remains unclear. To evaluate the association between disorders of glucose and lipid metabolism, and nocturnal non-dipping in pediatric patients with obesity. METHODS: In 207 children (53.14% girls, mean age 14 (range 2-17), mean BMI Z-SCORE 4.38, range 2.07-10.74) standard 24-h Ambulatory Blood Pressure Monitoring was performed. Normal dipping was defined as a ≥ 10% decline in BP during the night. RESULTS: There were 106 (51.21%) cases of non-dippers. The mean 24-h nocturnal systolic BP (SBP) reduction (%) was 9.9 ± 5.5. The mean 24-h nocturnal diastolic BP (DBP) reduction (%) was 15.8 ± 8.5. There was a significant correlation between BMI Z-SCORE and mean day-time SBP (r = 0.14 P = .042). There are positive correlations between 24-h heart rate (beats/min) and BMI Z-SCORE (r = 0.15, P = .027), between fasting glucose and systolic BP Z-SCORE (r = 0.17, P = .03) and between mean diastolic BP and LDL cholesterol (r = 0.23, P = .004). Total cholesterol level was significantly higher in non-dippers (4.34 vs. 3.99 mmol/L, P = .034). There were no significant differences between non-dippers and dippers regarding fasting glucose (4.6 vs. 4.8 mmol/L), 120'post load glucose (5.7 vs. 5.9 mmol/L), insulin (19 vs. 20.2 µIU/mL), HOMA-IR (2.36 vs. 2.44), LDL cholesterol (2.64 vs. 2.51 mmol/L), HDL cholesterol (1.06 vs. 1.03 mmol/L) or triglycerides (1.36 vs. 1.34 mmol/L) levels. CONCLUSION: Nocturnal non-dipping is frequent in pediatric patients with obesity. It is associated with higher total cholesterol levels.

Shall we diagnose metabolic syndrome in adolescents?

BACKGROUND: The clinical value of the diagnosis of metabolic syndrome (MS) in children and adolescents remains unclear. The aim of the present study was to assess the occurrence of metabolic complications, other than included in 2007 IDF MS definition, in obese children and adolescents METHODS: The study included 75 (33 boys) obese adolescents (mean age 13.9 years, mean BMI SDS 4.49). Classical (fasting glucose, TGL, HDL, blood pressure) and non classical (insulin resistance [HOMA-IR], creatinine, AST, ALT, uric acid, fibrinogen, liver US and 24h BP profile) risk factors were compared between groups with and without MS. 15(8 boys) met the 2007 IDF criteria for MS. RESULTS: Patients with MS presented with significantly lower: BMI SDS (4.2 vs. 5.8, p=0.02), mean 24h SBP (0.8 vs. 1.0, p=0.03), and uric acid level (352.1 vs. 414.0, p=0.01). In both groups a significant percentage of abnormal results of 24hABPM (up to 42.9 and 57.6%), insulin resistance (85.7 % and 61.1%), non alcoholic fatty liver disease (57.4 % and 38.9 %) and hyperuricemia (69.2 % and 55.3%) was observed. CONCLUSION: Recognizing the metabolic syndrome in adolescents does not provide any additional clinical benefits. It seems that in every obese child a wide, personalized diagnostic work-up should be performed.

Prepubertal ultra-low-dose estrogen therapy is associated with healthier lipid profile than conventional estrogen replacement for pubertal induction in adolescent girls with Turner syndrome: preliminary results.

PURPOSE: The metabolic effects of prepubertal low-dose estrogen replacement (LE) therapy in Turner syndrome (TS) have not been fully investigated to date. The present study aimed to compare glucose and lipids metabolism in adolescents with TS on LE and conventional estrogen replacement (CE). METHODS: In 14 TS (mean age 13.8), LE (17ß-estradiol, 62.5 µg daily) was introduced before age 12 (mean age 10.5), and followed by a pubertal induction regimen after age 12, and in 14 CE was started after age 12 (mean 14, SD 1.96). Before, and 3 years after starting 17ß-estradiol growth velocity, bone age, BMI, and selected parameters of glucose and lipids metabolism were assessed. RESULTS: There were no significant differences between LE and CE in the mean levels of any parameter before introduction of 17ß-estradiol [total cholesterol (TC): 4.1 vs 4.3 mmol/L, LDL cholesterol (LDLc): 2.2 vs 2.4 mmol/L, HDL cholesterol (HDLc): 1.6 vs 1.4 mmol/L, triglycerides: 0.9 vs 1.0 mmol/L, fasting glucose: 4.2 vs 4.4 mmol/L, post-load glucose: 4.8 vs 5.5 mmol/L; fasting insulin: 6.8 vs 8.0 post-load insulin: 21.3 vs 67.0 µIU/mL, HOMA-IR 1.3 vs 1.6]. After three years of treatment, TC and LDLc levels were significantly lower in LE group (3.8 vs 4.4 mmol/L, p = 0.004; 1.9 vs 2.4 mmol/L, p = 0.03). The other parameters did not differ significantly. There was no negative impact on growth course and bone age advancement nor on BMI in LE group. CONCLUSION: Prepubertal LE is associated with healthier lipid profile than CE in girls with TS.

Intima media thickness of common carotids and abdominal aorta in children and adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency in relation to their genotypes.

BACKGROUND: Patients with congenital adrenal hyperplasia (CAH) are at risk of vascular and metabolic complications due to steroid therapy and increased adrenal androgens exposure. OBJECTIVE: of the study was to evaluate the relation between patient's genotype and (1) intima media thickness of abdominal aorta (AIMT) and common carotid arteries (CIMT) and (2) metabolic profile. MATERIAL AND METHODS: In 71 patients (27 boys) aged from 1.5 to 17.9 years, with 21-hydroxylase deficiency (21OHD) CAH: 9 with nonclassic (NC) CAH, 62 with classic CAH: 10 with simple virilising (SV) and 52 with salt wasting (SW) CAH (13-Del/Del, 8-Del/I2G, 7-I2G/I2G and 24-other genotypes), and in 77 lean and 36 normotensive obese, age and gender matched controls, assessment of CIMT and AIMT as well as hormonal and biochemical evaluation were performed. RESULTS: The highest AIMT was observed in SW Del/Del and I2G/I2G groups and the highest CIMT in SV CAH subgroup. CIMT and AIMT correlated significantly with testosterone and free androgen index (FAI), and were significantly higher in patients with advanced bone age and obesity independent. Significantly higher HOMA, testosterone and FAI values were found in SV CAH. CONCLUSION: In CAH patients CIMT and AIMT are influenced by androgens and obesity independent. In the examined group vascular and metabolic abnormalities are pronounced more in certain subgroups of CAH (SV and SW: Del/Del) and in patients with advanced bone age.

Novel insights in ultrasound evaluation of thyroid gland in children with papillary thyroid carcinoma.

BACKGROUND: The coincidence of autoimmune thyroiditis (AIT) in patients with papillary thyroid carcinoma (PTC) is ranging between 10 and 58% in the general population. MATERIAL AND METHODS: In the present study retrospective ultrasound, clinical and autoimmune assessment of 24 patients diagnosed with papillary thyroid carcinoma between 2000-2016 was performed. RESULTS: The coexistence of PTC and AIT was found in 50% of patients with PTC. Patients were divided into two groups. PTC AIT (+) group involved 12 children at the mean age 14.9 years (range 11-20 years, 9 girls) and PTC AIT (-) 12 children at the mean age 12.9 years (range 7-18 years, 5 girls). Papillary thyroid microcarcinoma (PTMC) was diagnosed in 6 patients (in 5 with AIT). US characteristics of PTC was heterogenous: hypoechogenic with/without increased vascularisation, normoechogenic with halo, with/without microcalcifications. In 70% PTC AIT (+) and in all PTC AIT (-) patients ultrasound analysis revealed that the thyroid tissue of the whole gland was normoechogenic. Local metastases in lymph nodes were found in 40% of PTMC AIT (+). CONCLUSION: Lack of increased vascularization and microcalcifications and presence of``halo`in the nodule does not exclude malignancy. Due to the presence of lymph node involvement in PTMC in all children with PTC total thyroidectomy should be performed with lymph nodes verification.

Circadian blood pressure profiles and ambulatory arterial stiffness index in children and adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency in relation to their genotypes.

OBJECTIVE: Lifelong steroid therapy and exposure to adrenal androgen excess in 21-hydroxylase deficient (21-OHD) congenital adrenal hyperplasia (CAH) children and adolescents may modify circadian blood pressure profile and result in vascular complications. The objective of the study was to evaluate vascular abnormalities in 21-OHD children and adolescents in relation to their genotypes. DESIGN: A cross-sectional study conducted at a tertiary referral center. PATIENTS: Seventy patients with 21-OHD CAH (27 boys), aged from 3 to 17.9 years: 9 with nonclassic CAH, 61 with classic CAH: 10 with simple virilising (SV) and 51 with salt wasting CAH (13-Del/Del, 8-Del/I2G, 7-I2G/I2G and 23-other genotypes). MAIN OUTCOMES MEASURES: The assessment of systolic and diastolic BP (SBP, DBP) loads, night dip% and arterial ambulatory stiffness index (AASI) in 21-OHD CAH patients.

The association between metabolic complications and arterial hypertension in obese adolescents.

OBJECTIVE: There is increasing evidence for the contribution of obesity and its metabolic sequels in the development of arterial hypertension (AH). METHODS: The casual blood pressure (CBP), 24hABPM, ambulatory arterial stiffness index (AASI) and symmetric (sAASI) ambulatory arterial stiffness index (both derived from a 24 h ABPM) and selected laboratory tests were performed in 130 obese (mean BMI SDS 4.2) adolescents at the mean age of 13.7 years. RESULTS: AH was diagnosed in 36.2%, and in 33.8% patients on the basis of CBP and 24hABPM respectively. There were significant correlations between: CBPSBP insulin level (fasting r=0.19, p=0.03 and post glucose load r=0.18, p=0.04), HOMA-IR (r=0.18, p=0.04), and uric acid (UA) level (r=0.35, p<0.001); CBPDBP and UA level (r=0.23, p=0.01). There were significant correlations between 24hABPM parameters and cortisol secretion: dSBP and urinary free cortisol (r=0.3, p=0.03), nDBP and nMAP and cortisol rhythm (r=0.21, p=0.03). There a correlation between sAASI and creatinine level (r=0.29, p=0.002) and negative correlation between AASI and eGFR (r=-0.23, p=0.009). CONCLUSIONS: The increase of the CBP parameters is associated with insulin resistance and hyperuricemia, while the increase of ABPM results is proportional to the cortisol secretion in obese adolescents.

Atypical cardiac myxoma in the course of Carney complex in the child. Case Report.

Cardiac tumors in infants and children are rare. Myxomas are the second (after rhabdomyomas) most common primary cardiac tumors in pediatric patients. Cardiac, cutaneous and mucous myxomas are likewise the second most frequent manifestation of the Carney complex, an autosomal dominant multi neoplasia syndrome, which consists of myxomas in different locations, spotty skin pigmentation and endocrine overactivity. We present a case of 13-years-old boy send to our department from a district hospital because of the large tumor in the right atrium discovered in the echo study. On admission he presented discrete signs of Cushing's syndrome and scarse pigmented nevi on the face and trunc. The detailed echo examination showed the large right atrial tumor with features of myxoma, protruding across the tricuspid valve into the right ventricle during diastolic period. Atypical location of cardiac myxoma as well as the signs of Cushing's syndrome suggested Carney's complex. Detailed endocrine studies confirmed the hypothesis. Thus two-step bilateral adrenalectomy was planned. The histopathologic study confirmed primary pigmented nodular adrenocortical disease.

Testicular adrenal rest tumors in congenital adrenal hyperplasia: a case report and literature overview.

OBJECTIVE: In this paper, the etiology, differential diagnosis, and therapy of testicular adrenal rest tumors (TARTs) is presented based on a patient presentation and an overview of the most recent literature concerning this subject. METHODS: Retrospective analysis of the clinical and biochemical data of an 18-year-old male patient diagnosed at the age of 2 weeks with the classic salt-wasting form of congenital adrenal hyperplasia that has been monitored in the pediatric and adolescent outpatient department since the age of 4 years. RESULTS: The results of adrenal hormone tests (17-hydroxyprogesterone, 17-ketosteroids, and pregnanes) had been unsatisfactory, particularly over the previous 5 years. Scrotal ultrasound detected TARTs bilaterally. After increasing the dose of hydrocortisone and introducing dexamethasone, considerable regression of the tumors was noted. CONCLUSION: Lack of complete regression of the lesions is caused by fibrosis and is probably due to decreased sensitivity of adrenocorticotropic hormone and angiotensin II receptors in this tissue.

Cerebral salt wasting in a postoperative period.

Cerebral salt wasting syndrome (CSW-cerebral salt wasting) was first described in 1950 by Peters. This syndrome can occur in patients who have sustained damage to the central nervous system (e.g. patients with subarachnoid bleeding, bacterial meningitis or after neurosurgery). Patients present with excessive natriuresis and hyponatremic dehydration. Differentiating this syndrome with the syndrome of inappropriate antidiuretic hormone secretion (SIADH-syndrome of inappropriate antidiuretic hormone secretion), which may occur in the same group of patients, is necessary in order to administer the correct treatment which consists of fluid restriction and sodium replacement in SIADH and fluid and sodium replacement as well as occasional mineralocorticoid therapy in CSW.

Ultrasound-Histopathological Presentation of Thyroid and Ovary Lesions in Adolescent Patients with DICER1 Syndrome: Case Reports and Literature Overview.

BACKGROUND: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic-solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli-Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. CONCLUSIONS: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening.

[Hypertension in obese children and adolescents]. / Nadcisnienie tetnicze u otylych dzieci i nastolatków.

BACKGROUND: The frequency of arterial hypertension (AHT) in children is around 3.2-4.5% nowadays, however 3-4 decades ago it was below 1.5%. In obese children AHT is 3-5 times more frequent than in lean children. AIM: Retrospective evaluation of frequency of AHT and metabolic complications in obese children and adolescents. MATERIAL AND METHODS: One hundred seventy children and adolescents (100 girls) at the mean age of 14.6 years (range: 10-18 years) diagnosed with simple obesity admitted to The Department of Pediatric and Adolescent Endocrinology in Krakow, Poland were assessed in the study. Patients were divided into three groups: 1- obese normotensive (n=43), 2- obese prehypertensive (n=31), 3- obese hypertensive (n=96). Blood pressure (BP) was assessed by Korotkow method. The result was expressed as a mean of 3 independent BP measurements. Biochemical analysis included oral glucose tolerance test with assessments of glucose, insulin and HOMA-IR (the homeostatic index for insulin resistance) as well as lipid profile and uric acid measurements. RESULTS: AHT was found in 96 patients (55.8%), in 53 girls (52%) and 43 boys (61.4%). Prehypertensive values of BP were found in 31 patients (18 girls). Systolic AHT was found in 90 patients (52.9%), diastolic AHT in 56 patients (32.9%), and both systolic and diastolic AHT in 50 patients (29.4%). In group 3. BMI was higher than in group 1. BMI correlated significantly with systolic and diastolic BP. Uric acid levels were higher in group 3. than in group 1., and higher in patients with diastolic AHT. Basal insulin levels were higher in diastolic AHT patients and poststimulatory insulin was higher in systolic AHT patients. HOMA-IR was higher in patients with diastolic AHT than in patients with normal diastolic BP. Lipid profile did not differ between the groups, however the highest percentage of patients with abnormal lipid profile was found in group 2. CONCLUSION: An early endocrine referral in pediatric obese patients is advisable to monitor complications of obesity.

The positive impact of lifestyle intervention on selected mio- and chemokines levels in prepubertal children with obesity.

INTRODUCTION: It is proven that life style modification (diet and physical exercises) have positive effect on the metabolic functions in pa-tients with obesity, even without significant weight reduction. AIM OF THE STUDY: The objective of the present study was to check whether the intensive controlled lifestyle intervention (personalized diet modification and monitored, regular physical activity) may have positive impact on the concentration of irisin and chemerin in children with obesity. MATERIAL AND METHODS: Twenty children (mean age 8.9) were included in the prospective, cross-over study. They were randomly assigned to group A (with three months intensive intervention), and B (standard intervention). After three months, the groups were switched. RESULTS: Mean irisin level increased significantly after the phase of intensive intervention (4.8 to 5.1 µg/ml; p = 0.03), regardless of whether the intervention was applied from the beginning (Group A) or after 3 months from the advice of healthy-lifestyle (Group B). A period without intensive monitoring was associated with a significant reduction of irisin level. For chemerin in the group A (starting from intensive intervention) mean level decreased after the phase of intensive intervention (65.8 to 57.0 ng/ml), and then increased to 67 ng/ml during the standard intervention. In the group B after the standard intervention period chemerin level increased 67.5 to 68.8 ng/ml (p = 0.03), and then after introduction the intensive intervention de-creased to 63.7 ng/ml. CONCLUSIONS: Personalized diet modification and regular, daily exercises may positively influence on the levels of irisin and chemerin.

Beyond the Metabolic Syndrome: Non-Obvious Complications of Obesity in Children.

Obesity is currently one of the most significant public health challenges worldwide due to the continuous increase in obesity rates among children, especially younger children. Complications related to obesity, including serious ones, are increasingly being diagnosed in younger children. A search was performed from January 2023 to September 2023 using the PubMed, Cochrane Library, Science Direct, MEDLINE, and EBSCO databases. The focus was on English-language meta-analyses, systematic reviews, randomized clinical trials, and observational studies worldwide. Four main topics were defined as follows: disorders of glucose metabolism; liver disease associated with childhood obesity; the relationship between respiratory disorders and obesity in children; and the effects of obesity on the hypothalamic-pituitary-gonadal axis and puberty. Understanding potential complications and their underlying mechanisms can expedite the diagnostic process and enhance the effectiveness of treatment. We aspire that this study will bring insight into the often-overlooked complications associated with obesity.

Ultrasound evolution of parenchymal changes in the thyroid gland with autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma - a follow-up study.

Background: Follicular cell-derived thyroid carcinoma represents the vast majority of paediatric thyroid cancers (TCs). Papillary thyroid carcinoma (PTC) accounts for over 90% of all childhood TC cases, and its incidence in paediatric patients is increasing. The objective of this follow-up study was to present the outcome of ultrasound (US) and laboratory monitoring of paediatric patients with autoimmune thyroiditis (AIT) prior to the development of PTC. Patients and methods: This prospective study included 180 children and adolescents (132 females; 73.3%) with a suspicion of thyroid disorder referred to the Outpatient Endocrine Department. The patients were divided into four groups: 1) 28 patients with a mean age of 10.7 [standard deviation (SD), 3.1] y, in whom PTC was detected during the active surveillance of AIT [AIT(+), PTC(+) follow up (F)]; 2) 18 patients with a mean age of 12.8 (SD, 3.4) y, in whom PTC and AIT were detected upon admission (A) [AIT(+), PTC(+) A]; 3) 45 patients with a mean age of 13.0 (SD, 3.4) y, in whom PTC was detected upon admission and AIT was excluded [AIT(-), PTC(+) A]; and 4) an age- and sex-matched control group of 89 patients with AIT and with a mean age of 9.4 (SD, 3.0) y. The analysis included clinical, US, and laboratory assessment results of children on admission (groups 1-4) and during follow-up (groups 1 and 4) in the Paediatric Endocrine Outpatient Department. Results: Upon admission of those in group 1, the US evaluation revealed a hypoechogenic thyroid gland in 12 and an irregular normoechogenic gland in 16 patients. US monitoring revealed an increase in thyroid echogenicity and an increased irregularity of the thyroid structure during the follow-up period of all of the patients from group 1. Such changes were not noticed in group 4. PTC was diagnosed at the mean time of 3.6 y (3 mo-9 y) since AIT confirmation in group 1. The mean maximum PTC diameter as per the US was significantly smaller in group 1 than in groups 2 and 3 [13.2 (10.8) mm vs. 22.2 (12.8) and 22.05 (15.4) mm]. Fewer patients in group 1 were referred to 131I than in groups 2 and 3 (71.4% vs. 94.4 and 93.3%). Interestingly, significant differences were observed in the thyroglobulin antibody (TgAb)/thyroid peroxidase antibody (TPOAb) ratio between groups 2 and 3, as opposed to group 4, at the beginning of observation [15.3 (27.6) and 3.5 (8.8] vs. 0.77 (1.9)]. In group 1, after the follow-up, an increase in the TgAb/TPOAb ratio was observed [1.2 (9.8) to 5.2 (13.5)]. There were no significant differences between groups 1-3 in labeling index Ki67, lymph nodes metastasis, extrathyroidal extension, and angioinvasion. There were no associations between thyroid-stimulating hormone, TgAb, and the extent of the disease. Conclusion: The use of thyroid US focused on the search for developing tumours in the routine follow-up of patients with AIT may not only help in the early detection of thyroid malignancies that are not clinically apparent but may also influence the invasiveness of oncological therapy and reduce the future side effects of 131I therapy. We propose that the repeat evaluation of TPOAb and TgAb warrants further exploration as a strategy to determine TC susceptibility in paediatric patients with AIT in larger multicentre studies.

Ultrasound, laboratory and histopathological insights in diagnosing papillary thyroid carcinoma in a paediatric population: a single centre follow-up study between 2000-2022.

Background: Papillary thyroid carcinoma (PTC) often coincides with autoimmune thyroiditis (AIT); whether this association is incidental or causal remains debated. Objective: To evaluate the ultrasonographic, laboratory, and histopathological features of PTC in paediatric patients with and without AIT and its relationship to puberty. Design: A retrospective cohort study. Patients and methods: A retrospective analysis of medical records of 90 patients (69; 76.7% females). The mean age at PTC diagnosis was 13.8 years [range 6-18]. All patients were evaluated ultrasonographically before thyroid surgery. Thyroid nodules were categorised using the European Thyroid Imaging Reporting and Data System (EU-TIRADS PL), and cytopathology was assessed using Bethesda criteria. Neck ultrasound results and thyroid and autoimmune status were correlated with histopathological PTC assessment. Results: The coexistence of PTC and AIT was found in 48.9% (44/90) of patients. The percentage of AIT was increasing with age; AIT was present only in 1/3 of prepubertal, close to 50% in pubertal, and over 60% in adolescent patients. The youngest patients (aged <10 years old) presented more often with goitre and lymphadenopathy and less often with AIT than adolescents (15-18 years of age). There were no differences in TPOAb, TgAb, and TSH levels between the age subgroups. Presurgical TgAb levels were higher than those of TPOAb in the youngest patients. Histopathological analysis revealed that the solid subtype was observed more often in prepubertal children and diffuse sclerosing in children below 14 years of age, whereas the classic subtype dominated in late pubertal. Univariate and multivariate analyses revealed that lymph nodes metastases (LNM) were associated with PTC diameter and fT4 level, whereas extrathyroidal extension with age and angioinvasion with PTC diameter and age. The correlations between age and fibrosis, and the presence of psammoma bodies in malignant tissues were close to significant. We did not observe an association between TSH levels and the presence of autoimmunity and PTC variables. Conclusions: In paediatric patients the natural course of PTC may be less aggressive in adolescent patients than in younger children (especially < 10 years of age). We suggest that pre-operative evaluation of paediatric patients with thyroid nodules could include apart from assessment of thyroid hormones, evaluation of TPOAb, TgAb, and TRAb together with comprehensive neck ultrasonography.

Hormonal control during infancy and testicular adrenal rest tumor development in males with congenital adrenal hyperplasia: a retrospective multicenter cohort study.

IMPORTANCE: Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development. OBJECTIVE: This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development. DESIGN AND PARTICIPANTS: This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound. RESULTS: TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis. CONCLUSIONS AND RELEVANCE: A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life.

FGF23 contributes to insulin sensitivity in obese adolescents - preliminary results.

UNLABELLED: Fibroblast growth factor-23 (FGF23) is a hormonal regulator of circulating phosphate and vitamin D levels. Recent investigations revealed that besides a key role in the pathogenesis of calcium-phosphorus disorders, in some patients FGF23 may be an indicator of cardiovascular complications. As a 'hormone-like' factor, it may also be involved in some metabolic processes, especially in the metabolism of glucose and fat. Its potential contribution to metabolic syndrome (MS) development has not been confirmed yet. OBJECTIVE: The study was to examine the possible correlations between FGF23 serum levels and body composition, blood pressure and selected parameters of glucose, insulin and fat metabolism in adolescents with simple obesity. PATIENTS AND DESIGN: In 68 (35 female) adolescents (mean age 13·9 years) with simple obesity [mean BMI SDS 4·9 (95% CI 4·4-5·4)], the levels of FGF23, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides were measured. Standard oral glucose tolerance tests were performed with the assessment of fasting and after 120' postload glucose and insulin levels; the insulin resistance index HOMA-IR was calculated. RESULTS: Regardless of gender, there was a significant inverse correlation between FGF23 and fasting insulin level (r = -0·3), as well as HOMA-IR (r = -0·29). Multiple regression model showed the independent association between FGF23 and HOMA-IR. CONCLUSION: FGF23 seems to be a novel factor contributing to insulin sensitivity. Further investigations are needed to define its role in the development of MS.