Central Precocious Puberty in Italian Boys: Data From a Large Nationwide Cohort.

CONTEXT: There are only a few nationwide studies on boys with central precocious puberty (CPP) and the last Italian study is a case series of 45 boys that dates back to 2000. OBJECTIVE: We aimed to evaluate the causes of CPP in boys diagnosed during the last 2 decades in Italy and the relative frequency of forms with associated central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) compared to idiopathic ones. METHODS: We performed a national multicenter retrospective study collecting data from 193 otherwise normal healthy boys with a diagnosis of CPP. Based on MRI findings, the patients were divided into: Group 1, no CNS abnormalities; Group 2, mild abnormalities (incidental findings) unrelated to CPP; and Group 3, causal pathological CNS abnormalities. RESULTS: The MRI findings show normal findings in 86%, mild abnormalities (incidental findings) in 8.3%, and causal pathological CNS abnormalities in 5.7% of the cases. In Group 3, we found a higher proportion of patients with chronological age at diagnosis < 7 years (P = .00001) and body mass index greater than +2 SDS (P < .01). Gonadotropin-releasing hormone analogue therapy was started in 183/193 subjects. The final height appeared in the range of the target height in all groups and in 9 patients in whom the therapy was not started. CONCLUSION: In our study on a large nationwide cohort of boys referred for precocious puberty signs, the percentage of forms associated with CNS abnormalities was one of the lowest reported in the literature.

The diagnostic role of arginine-stimulated copeptin in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in pediatric age.

PURPOSE: In recent years, copeptin stimulation through arginine administration has been evaluated as a new potential tool in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in adults; to date very few data, all retrospective, exist in pediatric age. The aim of this prospective study is to evaluate the diagnostic performance of the arginine-stimulation test for copeptin in a cohort of pediatric patients affected by PPS. METHODS: All children (<18 years) referred to the Department of Pediatric Endocrinology of the Regina Margherita Children Hospital for polyuria-polydipsia in the period January 2021-June 2023 were enrolled. The Arginine-stimulation test for copeptin was performed in all patients presenting PPS after water deprivation test (WDT). Patients with polyuria-polydipsia were then classified as having primary polyuria (PP), complete and partial central diabetes insipidus (CDI), according to the standardized interpretation. Arginine-stimulation test for copeptin was also performed in a control cohort. RESULTS: A significant difference in arginine-stimulated copeptin values was observed at baseline (p = 0.005), at 60 min (p = 0.01), and at 90 min (p = 0.005) in 7 subjects presenting PP, 6 patients affected by CDI and 50 subjects of the control cohort. Plasma osmolality values remained stable at all measurements. The arginine-stimulated copeptin test demonstrated sensitivity and specificity of 100%, whereas the sensitivity of the WDT test was 83.3% and the specificity was 85.7%. CONCLUSION: Given the reliability and the minor adverse effects and costs, the copeptin level after arginine administration could replace the WDT in the diagnostic workup of these in pediatric age.

Perinatal asphyxia and hypothermic treatment from the endocrine perspective.

Introduction: Perinatal asphyxia is one of the three most important causes of neonatal mortality and morbidity. Therapeutic hypothermia represents the standard treatment for infants with moderate-severe perinatal asphyxia, resulting in reduction in the mortality and major neurodevelopmental disability. So far, data in the literature focusing on the endocrine aspects of both asphyxia and hypothermia treatment at birth are scanty, and many aspects are still debated. Aim of this narrative review is to summarize the current knowledge regarding the short- and long-term effects of perinatal asphyxia and of hypothermia treatment on the endocrine system, thus providing suggestions for improving the management of asphyxiated children. Results: Involvement of the endocrine system (especially glucose and electrolyte disturbances, adrenal hemorrhage, non-thyroidal illness syndrome) can occur in a variable percentage of subjects with perinatal asphyxia, potentially affecting mortality as well as neurological outcome. Hypothermia may also affect endocrine homeostasis, leading to a decreased incidence of hypocalcemia and an increased risk of dilutional hyponatremia and hypercalcemia. Conclusions: Metabolic abnormalities in the context of perinatal asphyxia are important modifiable factors that may be associated with a worse outcome. Therefore, clinicians should be aware of the possible occurrence of endocrine complication, in order to establish appropriate screening protocols and allow timely treatment.

Adrenal insufficiency management in the pediatric emergency setting and risk factors for adrenal crisis development.

BACKGROUND: In patients with adrenal insufficiency (AI), adrenal crisis (AC) represents a clinical emergency. Early recognition and prompt management of AC or AC-risk conditions in the Emergency Department (ED) can reduce critical episodes and AC-related outcomes. The aim of the study is to report the clinical and biochemical characteristics of AC presentation to improve their timely recognition and proper management in a ED setting. METHODS: Single-centre, retrospective, observational study on pediatric patients followed at the Department of Pediatric Endocrinology of Regina Margherita Children's Hospital of Turin for primary AI (PAI) and central AI (CAI). RESULTS: Among the 89 children followed for AI (44 PAI, 45 CAI), 35 patients (21 PAI, 14 CAI) referred to the PED, for a total of 77 accesses (44 in patients with PAI and 33 with CAI). The main causes of admission to the PED were gastroenteritis (59.7%), fever, hyporexia or asthenia (45.5%), neurological signs and respiratory disorders (33.8%). The mean sodium value at PED admission was 137.2 ± 1.23 mmol/l and 133.3 ± 1.46 mmol/l in PAI and CAI, respectively (p = 0.05). Steroids administration in PED was faster in patients with CAI than in those with PAI (2.75 ± 0.61 and 3.09 ± 1.47 h from PED access, p = 0.83). Significant factors related to the development of AC were signs of dehydration at admission (p = 0.027) and lack of intake or increase of usual steroid therapy at home (p = 0.059). Endocrinological consulting was requested in 69.2% of patients with AC and 48.4% of subjects without AC (p = 0.032). CONCLUSION: children with AI may refer to the PED with an acute life-threatening condition that needs prompt recognition and management. These preliminary data indicate how critical the education of children and families with AI is to improve the management at home, and how fundamental the collaboration of the pediatric endocrinologist with all PED personnel is in raising awareness of early symptoms and signs of AC to anticipate the proper treatment and prevent or reduce the correlated serious events.

Pediatric Myxedema Due to Autoimmune Hypothyroidism: A Rare Complication of a Common Disorder.

In children, hypothyroidism usually presents non-specific symptoms; symptoms can emerge gradually, compromising a timely diagnosis. We report the case of a 13-year-old male, who was admitted to the hospital due to swelling of the torso and neck. Besides these symptoms, the child was healthy, except for a significant growth delay. Ultrasound evaluation and blood tests led to the diagnosis of myxedema secondary to severe hypothyroidism, which was due to autoimmune thyroiditis. Further investigations revealed pericardial effusion and pituitary hyperplasia, with hyper-prolactinemia. Treatment with levothyroxine led to edema regression and clinical, hemato-chemical and radiological improvement. After 6 months, growth velocity increased, although the recovery of growth already lost was not guaranteed. Brain MRI showed regression of pituitary hyperplasia. The diagnostic delay in this case was probably due to the patient's apparent good health, and the underestimation of growth restriction. This report underlines the importance of growth monitoring in adolescence, a critical period for identifying endocrine conditions; if undiagnosed, these conditions can lead to serious complications, such as myxedema in hypothyroidism, with potential effects beyond growth on multiple organs.

Clinical features of thyroid cancer in paediatric age. Experience of a tertiary centre in the 2000-2020 period.

PURPOSE: To describe the clinical features of a paediatric cohort affected by differentiated thyroid cancer (DTC) followed in a tertiary Department of Paediatric Endocrinology. METHODS: Clinical data of 41 patients affected by DTC in the 2000-2020 period were reviewed. RESULTS: The main risk factor was autoimmune thyroiditis (39%). Cytological categories were TIR3b in 39%, TIR4 in 9.8%, TIR5 in 51.2%. After total thyroidectomy, radioiodine treatment was performed in 38 subjects (92.7%). ATA low-risk category was assigned in 11 (30.5%), intermediate-risk category in 15 (41.7%), and high-risk category in 10 patients (27.8%). Age at diagnosis was 15.1 ± 0.92 years in low-risk category, 14.7 ± 0.59 in intermediate-risk category, 11.7 ± 0.89 years in high-risk category (p = 0.01). TIR3b was manly observed in low-risk class (63.6%), while TIR5 was mainly reported in intermediate and high-risk class (60 and 80% respectively) (p = 0.04). Post-surgery stimulated thyroglobulin was increased in high-risk class (407.8 ± 307.1 ng/ml) [p = 0.04]. Tumour size was larger in high-risk category (42.6 ± 2.6 mm), than in low and intermediate-risk categories (19.4 ± 3.5 mm and 28.5 ± 3.9 mm, respectively) (p = 0.008). Patients in intermediate and high-risk categories displayed more tumour multifocality (60 and 90% respectively) (p < 0.005). Disease relapse was mainly observed in high risk category (40%, p = 0.04). CONCLUSION: DTC in childhood is more aggressive than in adults, but the overall survival rate is excellent. The therapeutic approach is still heterogeneous, especially in low-risk category. Further studies are needed to standardise management and reduce disease persistence in childhood.

Pediatric thyroid surgery: Retrospective analysis on the first 25 pediatric thyroidectomies performed in a reference center for adult thyroid diseases.

Introduction: Pediatric thyroid carcinoma represents about 4-5% of all pediatric carcinoma with an incidence of 0.5 cases/100,000, compared to 2-10/100000 cases in the adult population. The aim of this study is to present the experience of a reference adult endocrine surgery unit in charge of the treatment of pediatric thyroid diseases. Materials and methods: From January 2019 to September 2022, 25 patients, aged 5-17, underwent thyroid surgery. We analysed indications for surgery, use of intraoperative nerve monitoring (IONM), definitive histological examination, postoperative outcomes and risk factors related. Results: Surgical indication was performed for Graves' disease (27%) and for nodular pathology (73%): of these, four were malignant lesions (TIR4/TIR5), eight with indeterminate characteristics (TIR3A/TIR3B) and four characterized as benign (TIR1/TIR2). Total thyroidectomy (TT) was performed in 76% of cases, three of which were prophylactic for the activation of the RET gene mutation in MEN 2A. IONM was used in eight cases (32%), all patients aged 11 years or less. FNA's accuracy was 100% for lesions typified as benign and malignant (TIR1/TIR2 and TIR4/TIR5). The overall malignancy rate achieved was 40% and in the final histological examination 75% of the TIR 3B lesions were malignant. Six patients (24%) developed hypoparathyroidism in the first postoperative day, with normalization of calcium values within thirty days in 5 patients. Conclusions: Pediatric thyroid nodules are rare and distinguished from adult thyroid disease by a worse prognosis and higher malignancy rates. Our work reports a much higher malignancy rate among indeterminate TIR 3B lesions than observed in the adult population and the three patients who underwent prophylactic total thyroidectomy for activating RET gene mutation had all a definitive histological diagnosis of medullary carcinoma. Post-surgical hypoparathyroidism is a common finding in these patients: in most cases the condition is transient and it benefits from supportive therapy. Intraoperative finding of a thinner recurrent laryngeal nerve in younger patients makes nerve isolation more difficult than in adult surgery: IONM is recommended in patients under 12. Pediatric thyroid surgery is challenging, we sustain it requires referral thyroid Centers for thyroid disease with highly skilled general endocrine surgeons.

Neonatal Screening for Congenital Hypothyroidism in Preterm Infants: Is a Targeted Strategy Required?

Background: Premature infants are at higher risk of developing congenital hypothyroidism (CH) but the neonatal screening strategy for this population is still debatable. The purpose of this retrospective study is to describe the results of a screening program for CH in a preterm infant cohort. Materials and Methods: All preterm newborns who underwent neonatal screening in the Italian region of Piedmont in the period January 2019-December 2021, were included in this retrospective cohort study. The first thyrotropin (TSH) measurement was performed at 72 hours, whereas the second at 15 days of life. Infants with TSH >20 mUI/L at first detection and >6 mUI/L at second were recalled for a full evaluation of thyroid function. Results: During the study period, 5930 preterm newborns were screened. Based on birthweight (BW), the mean TSH was 2.08 ± 0.15 for BW <1000 g, 2.01 ± 0.02 for BW 1001-1500 g, 2.28 ± 0.03 for BW 1501-2499 g, and 2.41 ± 0.03 mUI/L in normal-weight newborns (p < 0.005) at the first detection, with a significant difference observed at the second measurement (p < 0.005). Based on gestational age, the mean TSH at first detection was 1.71 ± 0.09 mUI/L for extremely preterm babies and 1.87 ± 0.06, 1.94 ± 0.05, and 2.42 ± 0.02 mUI/L for very preterm, moderately, and late preterm infants (p < 0.005), respectively. Significant between-group differences of TSH measurements were also at the second and third detections (p < 0.005 and p = 0.01). The 99% reference range in this cohort overlapped with the recommended TSH cutoffs for screening recall (8 mUI/L for first detection and 6 mUI/L for second detection). CH incidence was 1:156. Of the 38 patients diagnosed with CH, a eutopic gland was present in 30 (87.9%), with CH transient in 29 (76.8%). Conclusions: We observed no significant difference in the recall rate between preterm and at term infants screened in this study. Our current screening strategy therefore appears effective in avoiding misdiagnosis. CH screening approaches vary among countries. Development and testing of a uniform multinational screening strategy is needed.

Differences in the clinical picture at the onset of diagnosis of severe autoimmune hypothyroidism in children depending on the time of diagnosis: before or during the SARS-CoV-2 pandemic.

INTRODUCTION: There are few data about effects of COVID-19 on thyroid disease presentation in children, due to difficulties in healthcare services access. AIM OF THE STUDY: To assess the differences in hypothyroidism presentation before and during the COVID-19 pandemic. MATERIAL AND METHODS: All paediatric patients with autoimmune hypothyroidism (AIT) diagnosed from January 2017 to December 2022 were analysed. RESULTS: A total of 150 subjects were enrolled (94 in before and 56 during the pandemic period). Severe AIT was detected in 7.4% before and 12.5% during the pandemic. Age at the onset in the pre-pandemic period was lower ( p = 0.04). Diagnosis delay (time elapsed from onset of symptoms and diagnosis) was significantly different between the before and during the pandemic groups ( p = 0.02). In the pre-pandemic period the TSH value was 447.7 ±59.1, and it was 713.7 ±104.4 mUI/l during the pandemic ( p = 0.04), whereas mean fT4 values were 2.66 ±0.34 and 0.58 ±0.08 ng/l, respectively ( p = 0.0002). Significantly greater thyroid volume and bone age delay SDS were observed during the pandemic ( p = 0.04). Neurological symptoms were mostly observed during the pandemic, especially slow speech and impaired school performance. CONCLUSIONS: A higher rate of severe AIT was observed during the pandemic period, mostly related to difficulties in access to healthcare services. The diagnosis delay led to a more severe biochemical thyroid hormone profile, goitre, and more frequent presence of bone age delay and neurological symptoms at the onset. Recognizing hypothyroidism and recalling symptoms in child-hood, even if often non-specific, is fundamental for avoiding diagnosis delay.

Evaluation of the efficacy of EU-TIRADS and ACR-TIRADS in risk stratification of pediatric patients with thyroid nodules.

Background: Pediatric thyroid nodules have a lower prevalence but a higher rate of malignancy (ROM) than those in adults. Ultrasound features suspected of malignancy lead to fine needle aspiration biopsy (FNAB) and subsequent cytological determination, upon which management is decided. Based on the characteristics of ultrasound, to standardize clinician decisions and avoid unnecessary FNAB, the European Thyroid Association and the American Radiology College have established guidelines for Thyroid Imaging, Reporting and Data System (EU-TIRADS and ACR-TIRADS) for ROM stratification of thyroid nodules. The aim of this study is to evaluate the diagnostic performance of ACR-TIRADS and EU-TIRADS in pediatric age. Materials and methods: Subjects younger than 18 years of age with thyroid nodules greater than 0.5 cm observed in the 2000-2020 period were included. Results: Data from 200 subjects were collected. The overall ROM was 13%, rising to 26% if nodules with a diameter >1 cm were considered. Patients with a malignant nodule were more likely to have a higher EU-TIRADS score (p=0.03). Missed cancer diagnoses were 26.9%. Using the EU-TIRADS system, 40% of FNABs could have been avoided, while this scoring system would have resulted in FNAB being performed in 12% of cases where the assessment of ultrasound features would not recommend FNAB. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 73.1%, 57.1%, 73.1%, and 50%, respectively. Even considering the ACR-TIRADS, a higher score correlated with a higher ROM (p<0.001). This system missed 6 diagnoses of cancer (23.1%). Using the ACR-TIRADS system, 45.3% of FNABs could have been avoided, while FNAB should have been performed in 12% of cases where it was not recommended by ultrasound characteristics. Sensitivity, specificity, PPV and NPV were 76.9%, 50%, 76.9%, and 42.9%, respectively. Conclusion: The present study confirms the correspondence of the EU-TIRADS and ACR-TIRADS categories with respect to malignancy but indicates not entirely satisfactory performance compared to FNAB alone. However, the use of the two TIRADS systems should be encouraged in multicentre studies to increase their performance and establish paediatric-specific points in the scoring criteria.

"Lymphocyte population in peripheral blood in children and adolescents with graves disease. Potential predictive tool for severity of the disease".

PURPOSE: To date, few data are available on the prognostic role of lymphocyte subsets in pediatric Graves' Disease (GD). The aim of this retrospective study is to analyze the role of lymphocyte subtypes in predicting the severity of GD. METHODS: Data of 10 pediatric subjects aged <18 years with GD onset in the period November 2017-April 2021 were collected. The lymphocyte population was assessed at the onset of GD as well as hormonal and clinical data. The follow-up period was 2.4 ± 0.8 years. RESULTS: Pearson correlation coefficient between CD4+ /CD8+ ratio and fT3 levels and thyroid volume at diagnosis was 0.72 (p = 0.04) and 0.81 (p = 0.004) respectively; that between CD4+ /CD8+ ratio and the TRAb titer at diagnosis and after 6, 12 and 24 months was 0.89, 0.89, 0.73 and 0.77 respectively (p = 0.02, p = 0.01, p = 0.03 and 0.04). The correlation coefficient of anti-thyroid drug (ATD) dose after 6 and 12 months with CD4+ /CD8 ratio was 0.88 and 0.78 (p = 0.001 and p = 0.02 respectively). Patients with a higher CD4+ /CD8+ ratio at diagnosis displayed higher fT3 levels (28.73 ± 2.18 vs 13.48 ± 2.19 pmol/L, p = 0.03) and higher TRAb titers (28.9 ± 11.2 vs 4.88 ± 0.97, p = 0.01). CONCLUSION: CD4+/CD8+ ratio appears as a promising predictive tool to be considered together with other prognostic factors to better manage pediatric GD. These preliminary data need to be confirmed over a longer follow-up period and in larger cohorts.

Comparison Among Two Liquid Formulations of L-thyroxine in the Treatment of Congenital Hypothyroidism in the First Month of Life: A Pilot Study.

The liquid formulation of L-thyroxine is the most used in the substitutive treatment of congenital hypothyroidism (CH). This formulation has higher TSH suppression rates with respect of L-thyroxine tablets and thus lower doses are indicated. Two types of liquid L-thyroxine (Tirosint© and Tifactor©) are currently approved in Italy for use in pediatric age and to date there are no data available in the Literature comparing the two liquid formulations. The aim of this study is to compare the efficacy of both formulations in normalizing TSH and fT4 levels in the first month of life and to compare the L-thyroxine requirement for both formulations over the same period. All newborns diagnosed with primary CH at the neonatal screening program in the Piedmont region of Italy in the period May 2020 - May 2021 were enrolled and divided into two groups according to the liquid formulation used: TS Group with Tirosint© and TF Group with Tifactor©. No difference was observed between the two groups considering the TSH at dried blood spot (DBS) at neonatal screening, the serum levels of TSH, fT4 and fT3 and initial dose of L-thyroxine. At 15 days the serum TSH in the TF Group was 0.08 ± 0.02 mcUI/ml, while in the TS Group it was 36.7 ± 14.7 mcUI/ml p=0.04). No differences were observed between the two groups considering fT4 levels and L-thyroxine requirement. Among the subjects in the TF Group, 5/9 showed suppressed TSH at 15 days after starting treatment, while none of the subjects in the TS Group showed TSH levels below the normal lower limit (p=0.011). Among the subjects in the TF Group, 5/9 patients showed suppressed TSH at 30 days after starting treatment, while 1/12 subjects in the TS Group showed TSH levels below the normal lower limit (p=0.017). In conclusion, this study confirms the efficacy in normalizing the thyroid hormonal profile in newborns with CH among the liquid solutions although the response seem to be different in timing therefore an individual approach is necessary considering the type of formulation used, the diagnostic category of CH and clinical features.

Papillary thyroid microcarcinoma in a boy with Graves' disease: a case report and review of the literature.

A 16-years old boy with diagnosis of Grave's disease was treated with methimazole for one year before radical total thyroidectomy treatment due to persistence of clinical hormonal hyperthyroidism. Histological analysis revealed the presence of a papillary microcarcinoma. The management of Grave's disease in pediatric age is still under discussion. Therefore, close monitoring of the disease is required, as well as case-by-case tailored decision on how to manage treatment and when to perform the radical one, taking into account the association of Grave's disease with differentiated thyroid cancer in adults and the higher malignancy of thyroid cancer in childhood.

Diagnostic Re-Evaluation and Potential Predictor Factors of Transient and Permanent Congenital Hypothyroidism in Eutopic Thyroid Gland.

BACKGROUND: The incidence of congenital hypothyroidism (CH) has increased over the years, and many predictors for detecting newborns with transient forms (TCH) as early as possible have been considered. METHODS: All newborns diagnosed with primary CH and eutopic gland in the Piedmont region of Italy in the period of January 2014-June 2019 were enrolled and re-evaluated at the age of 2 years. RESULTS: 105 newborns were diagnosed with CH during the study period. Dyshormonogenesis was observed in 55/105. At re-evaluation, we found that 52.7% had permanent CH (PCH), while 47.3% had TCH. Male/female rate, TSH levels at diagnosis, levothyroxine requirement at withdrawal and extra-thyroid congenital malformations rate were higher in the PCH group (p = 0.02, p = 0.009, p = 0.02 and p = 0.01), while fT4 levels at diagnosis were lower (p = 0.03). Sensitivity of 72.4% and specificity of 80.7% for serum TSH above 60 mcUI/mL, sensitivity of 73% and specificity of 72.4% for serum fT4 level below 7.2 pg/mL and sensitivity of 66% and specificity of 68% for drug requirement above 2.25 mcg/kg/day were observed in PCH. CONCLUSIONS: Demographic, clinical and hormonal data at diagnosis and levothyroxine requirement during the first two years should be adequately monitored to identify infants who are most likely to discontinue therapy after the age of 24 months.

"Thyroid nodular disease and PTEN mutation in a multicentre series of children with PTEN hamartoma tumor syndrome (PHTS)".

PURPOSE: To report the incidence of 4-12% of differentiated thyroid cancer (DTC) and up to 50% of benign thyroid nodular disease and to describe nodular thyroid disease in a multicentre pediatric population with PTEN mutations. METHODS: Retrospective data of pediatric patients with PTEN mutations collected from tertiary Departments of Pediatric Endocrinology of Turin, Milan and Genua, Italy, in the period 2010-2020. RESULTS: Seventeen children with PTEN mutations were recruited in the study. Thyroid involvement was present in 12/17 (70.6%) subjects, showing a multinodular struma in 6/17 (35.3%), nodules with benign ultrasound features in 5/17 (29.4%) and a follicular adenoma in 1/17 (6%). No correlation was found between thyroid disease and gender, puberty, vascular manifestations, delayed development, or brain MRI abnormalities, while multiple lipomas were associated with thyroid disease (p = 0.03), as was macrocephaly. Standard Deviation (SD) score head circumference was 4.35 ± 1.35 cm in subjects with thyroid disease, 3 ± 0.43 cm (p = 0.02) in the group without thyroid disease. Thyroid involvement was present in all subjects with mutations in exon 6 (4/4) and exon 8 (3/3) of the PTEN gene (p = 0.02). CONCLUSION: In the presented cohort, benign thyroid disorders were prevalent, with no evidence of DTC. A correlation was found between thyroid lesions and head circumference and the occurrence of multiple lipomas. Future studies in larger cohorts should assess whether risk stratification is needed when recommending surveillance strategies in children or young adolescents with PTEN hamartoma syndrome.

Predictive factors of malignancy in pediatric patients with thyroid nodules and performance of the Italian classification (SIAPEC 2014) in the outcome of the cytological FNA categories.

PURPOSE: The rate of malignancy (ROM) among pediatric studies using the Bethesda System is 39.5% and 41.5% for atypia of undetermined significance/follicular lesion of undetermined significance and for suspected follicular neoplasm, respectively. Data reported on the basis of Bethesda System showed lower ROM in adults with indeterminate nodules (30.5 and 28.9% respectively). Studies on adults based on the Italian Society of Anatomic Pathology and Cytology (SIAPEC) classification, report ROM of 14.2% for TIR3a and 44.6% for TIR3b category, showing greater sensitivity in detecting malignancy. To date, no performance data are available about SIAPEC classification in pediatric age. METHODS: Retrospective data were collected from 200 pediatric subjects with thyroid nodules in the period 2000-2020. RESULTS: The distribution of cytological categories after fine needle aspiration biopsy (FNAB) was 7 TIR1, 4 TIR1c, 22 TIR2, 14 TIR3a, 9 TIR3b, 3 TIR4, and 16 TIR5. The surgical approach was performed in 40/200 subjects, with total ROM of 65% (0% for TIR1-TIR3a, 77.8% for TIR3b, and 100% for TIR4-TIR5). Total FNAB accuracy was 95%, while the sensibility and specificity were 92.3 and 92.6%, respectively. CONCLUSIONS: The reported data seem to confirm a greater sensitivity of SIAPEC classification to identify malignancy within the indeterminate category also in pediatric age and not only in adulthood. This finding may orient clinicians toward clinical follow-up for the indeterminate TIR3a group and toward surgical approach with total thyroidectomy in the indeterminate TIR3b group, although this indication should be confirmed in further national multicenter studies including larger cohorts.

"Primary Hyperparathyroidism (PHPT) in Children: Two Case Reports and Review of the Literature".

Primary hyperparathyroidism (PHPT) is a rare disorder in children and adolescents. Typical biochemical features are hypercalcemia and hypophosphatemia, but the clinical features can be heterogeneous, and in some cases, symptoms are vague and nonspecific, leading to misdiagnosis or late diagnosis. Herein, we report two cases of PHPT in pediatric age with different presenting symptoms, pain in the foot, and progressive alteration of the gait in the first case and recurrent abdominal pain with emotional lability in the second. Biochemical and radiological assessment confirmed PHPT. Both cases were treated surgically as definitive treatment, but in the second case, previous medical treatment with cinacalcet, a calcimimetic agent, was required to reduce serum PTH and calcium levels. After surgery, despite conventional treatment with calcium and calcitriol, case 1 developed a hungry bone syndrome. The analysis of the MEN-1 (Multiple Endocrine Neoplasia) gene was negative in both cases. A diagnosis of PHPT should be considered when children or adolescents present bone pain with radiological imaging of osteolytic lesion and biochemical feature of hypercalcemia associated with hypophosphatemia. In PHPT, the gold standard treatment is represented by surgery followed by strict postoperative endocrine monitoring to maintain adequate homeostasis of calcium and bone metabolism.

Incidence of primary congenital hypothyroidism and relationship between diagnostic categories and associated malformations.

PURPOSE: The incidence of primary congenital hypothyroidism (CH) has grown progressively and literature data indicate an association between CH and congenital malformations. The purpose of this study is to establish the current incidence of CH in the Italian Region of Piedmont and verify the relationship between CH diagnostic categories and associated malformations. METHODS: The biochemical and clinical data of 105 newborns with CH diagnosed in the period January 2014 to December 2019 were analyzed. RESULTS: The incidence of CH in the Italian Piedmont region in the 2014-2019 period increased to 1:1090. Thyroid dysgenesis was responsible for 47.6% (50/105) of all cases, with agenesis in 14.3% (15/105), while ectopia and hypoplasia in 23.8% (25/105) and 9.5% (10/105) of the cases, respectively; dyshormonogenesis defects were found in 52.4% (55/105) of cases. Congenital extra-thyroid anomalies were identified in 33/105 (31.4%) of newborns with CH and mainly involve the cardiac system (17/85, 16.1%), urogenital tract (7/85, 6.7%), gastrointestinal tract (5/105, 4.8%), and the musculoskeletal system (5/105, 4.8%). The highest rate of malformations was observed in patients with thyroid agenesis and dyshormonogenesis, respectively, in 53.5% and 36.4% of cases, while in the presence of thyroid ectopia and hypoplasia, the rate was 12% and 20%, respectively, (p = 0.03). CONCLUSION: In the Italian region of Piedmont, the incidence of primary CH has been increased over time, with a variation in the percentage of the different forms of CH. Congenital malformations, especially affecting the cardiovascular, urogenital, gastrointestinal, and musculoskeletal systems, seem to be mainly associated with thyroid agenesis or defects in hormonogenesis.

Distribution of plasma copeptin levels and influence of obesity in children and adolescents.

In recent years, a more stable AVP surrogate, called copeptin, has been used as an adjuvant diagnostic tool for dysnatremia in adults and appears to be promising even in the pediatric age. The aim of this study is to present the distribution of plasma copeptin in a large pediatric cohort and to observe the influence of fluid consumption and obesity on its values. A cohort of 128 children and adolescents was divided into two groups on the basis of nocturnal deprivation (group A) or free access to oral fluids in the 6-8 h before blood collection (group B). At all distribution percentiles, copeptin levels were higher (p < 0.0001) in group A, as were plasma sodium levels and osmolality (p = 0.02 and p = 0.008, respectively). The influence of BMI on copeptin levels was investigated by dividing the cohort into nonobese (group C) and obese children and adolescents (group D). Copeptin levels were higher in group D (p = 0.04).Conclusion: The measurement of copeptin could represent a useful tool for the diagnostic pathway of dysnatremic conditions, but its interpretation should take into consideration the state of hydration. Furthermore, it could also be a promising marker for obesity and metabolic syndrome, although this hypothesis needs further studies to be confirmed. What is Known: • Copeptin use as a diagnostic tool in AVP-related disorders, such as diabetes insipidus or syndrome of inappropriate secretion of antidiuretic hormone, is well established in adults • In pediatric age, few studies are available, but the preliminary data, including our previous study, seems to be promising. What is New: • In this study, we represent the distribution of copeptin levels in a pediatric cohort and show the significant influence of fluid ingestion on its plasma levels. • Also BMI seems to be a significant variable on copeptin levels and may be used as an obesity marker in pediatric age.