Reduced pulmonary oxygen diffusion at 36 weeks of postmenstrual age in small-for-gestational-age preterm infants of less than 32 weeks without bronchopulmonary dysplasia.

BACKGROUND: Small-for-gestational-age (SGA) preterm infants are at increased risk of developing bronchopulmonary dysplasia (BPD). There is limited information on pulmonary oxygen diffusion of SGA preterm infants, particularly in those without BPD. OBJECTIVE: To compare the pulmonary oxygen diffusion of SGA to that of appropriate-for-gestational-age (AGA) preterm infants without BPD. STUDY DESIGN: Preterm infants with a gestational age (GA) between 24.0 and 31.6 weeks were studied. The oxygen saturation (SpO2 ), fraction to inspired oxygen (FiO2 ), and the SpO2 to FiO2 ratio (SFR) were compared between SGA and AGA infants. The association between SGA and SFR at 36 weeks was assessed using a multiple regression analysis. In the subgroup without BPD, SGA were match-paired for GA and gender with AGA infants. RESULTS: We analyzed 1189 infants surviving at 36 weeks: 194 (16%) were SGA and 995 (84%) AGA. The incidence of BPD was significantly higher in SGA than AGA infants (32% vs. 13%; p = .000). Out of the 995 infants without BPD, 132 (13%) were SGA and 863 (87%) AGA. SGA was negatively associated with the SFR value at 36 weeks, independently from BPD. SGA infants without BPD had significantly higher (better) SFR at birth, but lower (worse) SpO2 and SFR and from 33 to 36 weeks than their matched AGA counterpart. At 36 weeks, median SpO2 and SFR values were 97.7 versus 98.4 (p = .006) and 465 versus 468 (p = .010) in match-paired SGA and AGA, respectively. CONCLUSION: Among preterm infants of less than 32 weeks and without BPD, SGA infants had a reduced pulmonary oxygen diffusion at 36 weeks in comparison with AGA infants.

Minipuberty assessment in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia: a single-center case-control study.

Introduction: The aim of our single-center case-control study is to evaluate whether minipuberty occurs in patients with hypoxic ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). We intend to conduct this evaluation by confronting the values of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and the values of testosterone in males and estradiol in females between newborns with HIE and in subsequent TH and healthy controls. Methods: We enrolled 40 patients (age: 56-179 days; 23 males), of whom 20 met the inclusion criteria for the case group and who underwent TH. A blood sample was taken from each patient at approximately 10 weeks of age to evaluate FSH and LH from the serum samples of all patients and to evaluate 17-beta estradiol (E2) and testosterone levels, respectively, from the serum samples of female and male patients. Results: It was found that minipuberty occurred in the case group patients, with no significant differences reported from the control group and with hormonal serum levels comparable to healthy infants of the control group (FSH 4.14 mUI/ml ± 5.81 SD vs. 3.45 mUI/ml ± 3.48 SD; LH 1.41 mUI/ml ±1.29 SD vs. 2.04 mUI/ml ±1.76 SD; testosterone in males 0.79 ng/ml ± 0.43 SD vs. 0.56 ng/ml ± 0.43 SD; 17-beta estradiol in females 28.90 pg/ml ± 16.71 SD vs. 23.66 pg/ml ± 21.29 SD). Discussion: The results of the present study may pave the way for further research and the evaluation of more possible advantages of TH.

Who Needs a Second Dose of Exogenous Surfactant?

OBJECTIVE: To identify prenatal and postnatal risk factors associated with surfactant redosing. STUDY DESIGN: Retrospective, single-regional center study including all infants born from 24 + 0 to 31 + 6 weeks of gestation in the Marche Region, Italy, and admitted to a single level III regional NICU from January 1, 2004, to February 28, 2021. Clinical factors associated with surfactant redosing were identified through logistic regression analysis. RESULTS: Of 1615 consecutive admissions, 662 infants were treated with exogenous surfactant: 462 (70%) received a single dose and 200 (30%) received more than 1 dose (25.5% two doses and 4.5% three doses). Risk of redosing was higher for infants born to mothers with hypertension in pregnancy (OR 3.95, P < .001), for small for gestational age (SGA) infants (OR 3.93, P < .001) and when the first surfactant dose was 100 mg/kg instead of 200 mg/kg (OR 4.56/4.61, P < .001). Infants with greater GA, delayed first surfactant administration, and milder respiratory distress syndrome had reduced risk of redosing. Infants who required multiple surfactant doses had a higher rate of bronchopulmonary dysplasia and mortality, as well as longer duration of respiratory support than patients that received 1 dose. CONCLUSIONS: Hypertension in pregnancy and SGA status were found to be statistically and clinically significant predictors of surfactant redosing. Understanding the pathophysiology of these conditions requires further investigation.

Evolution of Ultrasound-Assessed Lung Aeration and Gas Exchange in Respiratory Distress Syndrome and Transient Tachypnea of the Neonate.

OBJECTIVE: To use clinical, lung ultrasound, and gas exchange data to clarify the evolution of lung aeration and function in neonates with respiratory distress syndrome (RDS) and transient tachypnea of the neonate (TTN), the most common types of neonatal respiratory failure. STUDY DESIGN: In this prospective observational cohort study, lung aeration and function were measured with a semiquantitative lung ultrasound score (LUS) and transcutaneous blood gas measurement performed at 1 hour (time point 0), 6 hours (time point 1), 12 hours (time point 2), 24 hours (time point 3) and 72 hours (time point 4) of life. Endogenous surfactant was estimated using lamellar body count (LBC). LUS, oxygenation index (OI), oxygen saturation index (OSI), and transcutaneous pressure of carbon dioxide (PtcCO2) were the primary outcomes. All results were adjusted for gestational age. RESULTS: Sixty-nine neonates were enrolled in the RDS cohort, and 58 neonates were enrolled in the TTN cohort. LUS improved over time (within-subjects, P < .001) but was worse for the RDS cohort than for the TTN cohort at all time points (between-subjects, P < .001). Oxygenation improved over time (within-subjects, P = .011 for OI, P < .001 for OSI) but was worse for the RDS cohort than for the TTN cohort at all time points (between-subjects, P < .001 for OI and OSI). PtcCO2 improved over time (within-subjects, P < .001) and was similar in the RDS and TTN cohorts at all time points. Results were unchanged after adjustment for gestational age. LBC was associated with RDS (ß = -0.2 [95% CI, -0.004 to -0.0001]; P = .037) and LUS (ß = -3 [95% CI, -5.5 to -0.5]; P = .019). CONCLUSIONS: For the first 72 hours of life, the RDS cohort had worse lung aeration and oxygenation compared with the TTN cohort at all time points. CO2 clearance did not differ between the cohorts, whereas both lung aeration and function improved in the first 72 hours of life.

Respiratory distress syndrome in preterm infants of less than 32 weeks: What difference does giving 100 or 200 mg/kg of exogenous surfactant make?

BACKGROUND: Surfactant dosing and effective delivery could affect continuous positive airways pressure (CPAP)-failure. Nevertheless, information on exogenous surfactant dosing with current administration methods is limited. OBJECTIVE: To describe the effect of 100 or 200 mg/kg of surfactant as first-line treatment of respiratory distress syndrome in preterm infants of less than 32 weeks gestation. STUDY DESIGN: A retrospective single-center cohort study comparing two epochs, before and after switching from 100 to 200 mg/kg surfactant therapy. RESULTS: Six hundred and fifty-eight of the 1615 infants of less than 32 weeks were treated with surfactant: 282 received 100 mg/kg (S-100) and 376 received 200 mg/kg (S-200). There were no differences between S-100 and S-200 in perinatal data including prenatal corticosteroids, medication use, age at first surfactant administration and respiratory severity before surfactant. The S-200 vs. S-100 had fewer retreatments (17.0% vs. 47.2%, p < 0.001) and a shorter duration of oxygen therapy and mechanical ventilation (315 vs. 339 h, p = 0.018; 37 vs. 118 h, p = 0.000, respectively). There was no difference in postnatal corticosteroid use (S-200 10.0% vs. S-100 11.0%, p = 0.361). Bronchopulmonary dysplasia (BPD) was significantly lower in S-200 vs. S-100 when comparing either the 4 and 6-year periods before and after the dose switch (29.4% vs. 15.7%, p = 0.003, and 18.7% vs. 27.3%, p = 0.024, respectively) CONCLUSIONS: The switch from 100 to 200 mg/kg was associated with a marked reduction in the need for surfactant redosing, respiratory support, and BPD. This information could be important when designing a study in the modern era of less invasive administration as surfactant dosing and its effective delivery may affect the outcome.

How to improve CPAP failure prediction in preterm infants with RDS: a pilot study.

We aimed to test the diagnostic accuracy in predicting continuous positive airway pressure (CPAP) failure in premature infants with respiratory distress syndrome (RDS) by integrating oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) (SF ratio) with the measurement of peak velocity of the right diaphragmatic excursions (RD-PV), during the inspiration (I-Peak) and expiratory (E-Peak) phases, performed by pulsed-wave Tissue Doppler imaging. This is a prospective, observational pilot study conducted over a 2-year period. Neonates at ≤ 32 weeks gestation supported by early CPAP were eligible. Natural surfactant was delivered via a minimally invasive technique. We performed serial measurements of SF ratio and RD-PV during the early post-natal hours to test the accuracy in predicting surfactant administration as well as invasive ventilation support within 72 h from birth because of the RDS worsening. Of 56 preterm infants enrolled, 34 (61%) failed CPAP support. SF ratio showed a significant inverse relationship with both Silverman-Andersen score at birth (rho = - 0.417; P = .001) and RD-PV [E-Peak] (rho = - 0.361; P = .007). We achieved a high accuracy in predicting CPAP failure (AUC = 95%; 95% CI, 89-100%) by integrating gender, SF ratio, and RD-PV [E-Peak] at the restricted, multivariate analysis.Conclusions: SF ratio and RD-PV, as measured by pulsed-wave Tissue Doppler, may help physicians to improve their confidence in optimizing therapeutic options in preterm infants with RDS. What is Known: • Continuous positive airway pressure is the recommended first-line treatment for respiratory distress syndrome in preterm infants, but failure rates remain unacceptably high. • Choosing the optimal treatment in terms of non-invasive ventilation effectiveness and timeliness of surfactant administration for these patients is often challenging, also due to our inability to identify a worsening respiratory failure. What is New: • The integration of oxygen saturation, as measured by SpO2/FiO2, with right diaphragm peak motion velocities, as measured by pulsed-wave tissue Doppler, allows for high prediction accuracy of non-invasive ventilation support failure in premature infants at risk of respiratory distress syndrome. • These measurements may help physicians in providing optimal supportive therapy for these patients.

Role of Small Intestinal Bacterial Overgrowth (SIBO) and Inflammation in Obese Children.

Knowledge of the real incidence of small intestinal bacterial overgrowth (SIBO) in obese children and its role in obesity development seems essential for a more effective approach to the treatment of this condition. In this prospective, single-blind study, presence of SIBO was evaluated in a group of children with overweight/obesity. A blood sample for evaluation of cytokine profile was collected to establish the potential relationship with inflammatory condition and lactulose breath test (LBT) to diagnose SIBO was performed. A total of 36 patients with excess of adipose tissue were recruited. Among them, 16 (44.4%) were overweight and 20 (45.6%) were obese. Overall, 26 (72.2%) children had a positive LBT and were considered suffering from SIBO, 12 (75.0%) among those overweight and 14 (70.0%) among those obese. Measurement of cytokines (IL-1α, IL-1ß, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-17, IFN-α2, IFN-γ, TNF-α), cytokine antagonists (IL-1ra), chemokines (IP10, MCP-1, MIP1α, MIP1ß), and growth factors (EGF, G-CSF, GM-CSF, and VEGF) secreted in culture supernatants by PHA activated-PBMCs revealed that in the study population proinflammatory cytokines IL-1, IL-6, IL-8, IL-12, IFN-γ, IL-18, and TNF-α were high, whereas anti-inflammatory mediators IL-4 and IL-10 were low. However, no significance difference between children with SIBO and those without were evidenced. Evaluation of relationship of severity of SIBO showed a significant positive relationship between EGF or IFN-α2 and H2 but not CH4 levels and an inverse significant relationship with CH4 but not H2. Despite its limitations and further studies are needed, this study seems to indicate that SIBO is extremely common in overweight and obese children and can be demonstrated not only in severely obese subjects but also in moderately overweight patients. The inflammatory state seems to precede obesity development and SIBO does not seem to have relevance in obesity development, with no relationship found between severity of SIBO and inflammatory state.

Different Clinical Presentations and Management in Complete Androgen Insensitivity Syndrome (CAIS).

Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive genetic disorder resulting from maternally inherited or de novo mutations involving the androgen receptor gene, situated in the Xq11-q12 region. The diagnosis is based on the presence of female external genitalia in a 46, XY human individual, with normally developed but undescended testes and complete unresponsiveness of target tissues to androgens. Subsequently, pelvic ultrasound or magnetic resonance imaging (MRI) could be helpful in confirming the absence of Mullerian structures, revealing the presence of a blind-ending vagina and identifying testes. CAIS management still represents a unique challenge throughout childhood and adolescence, particularly regarding timing of gonadectomy, type of hormonal therapy, and psychological concerns. Indeed this condition is associated with an increased risk of testicular germ cell tumour (TGCT), although TGCT results less frequently than in other disorders of sex development (DSD). Furthermore, the majority of detected tumoral lesions are non-invasive and with a low probability of progression into aggressive forms. Therefore, histological, epidemiological, and prognostic features of testicular cancer in CAIS allow postponing of the gonadectomy until after pubertal age in order to guarantee the initial spontaneous pubertal development and avoid the necessity of hormonal replacement therapy (HRT) induction. However, HRT is necessary after gonadectomy in order to prevent symptoms of hypoestrogenism and to maintain secondary sexual features. This article presents differential clinical presentations and management in patients with CAIS to emphasize the continued importance of standardizing the clinical and surgical approach to this disorder.

Vitamin D and growth hormone in children: a review of the current scientific knowledge.

BACKGROUND: Human growth is a complex mechanism that depends on genetic, environmental, nutritional and hormonal factors. The main hormone involved in growth at each stage of development is growth hormone (GH) and its mediator, insulin-like growth factor 1 (IGF-1). In contrast, vitamin D is involved in the processes of bone growth and mineralization through the regulation of calcium and phosphorus metabolism. Nevertheless, no scientific study has yet elucidated how they interact with one another, especially as a dysfunction in which one influences the other, even if numerous biochemical and clinical studies confirm the presence of a close relationship. MAIN BODY: We reviewed and analyzed the clinical studies that have considered the relationship between vitamin D and the GH/IGF-1 axis in pediatric populations. We found two main areas of interest: the vitamin D deficiency status in patients affected by GH deficit (GHD) and the relationship between serum vitamin D metabolites and IGF-1. Although limited by some bias, from the analysis of the studies presented in the scientific literature, it is possible to hypothesize a greater frequency of hypovitaminosis D in the subjects affected by GHD, a reduced possibility of its correction with only substitution treatment with recombinant growth hormone (rGH) and an improvement of IGF-1 levels after supplementation treatment with vitamin D. CONCLUSIONS: These results could be followed by preventive interventions aimed at reducing the vitamin D deficit in pediatric age. In addition, further research is needed to fully understand how vitamin D and growth are intertwined.

Corticosteroids in Moderate-To-Severe Graves' Ophthalmopathy: Oral or Intravenous Therapy?

BACKGROUND: Ophthalmopathy is a rare extra-thyroid manifestation of Graves' disease, in paediatrics. Intravenous corticosteroids are the main treatment of moderate-to-severe Graves' orbitopathy. In this paper, we describe a moderate-to-severe active Graves' ophthalmopathy in a child and the response to oral therapy with prednisone. CASE PRESENTATION: A nine-year-old male child suffering for a few months, from palpitations, tremors, and paresthesia was hospitalized in our Pediatric Clinic. At admission, the thyroid function laboratory tests showed hyperthyroidism with elevated free thyroxine (FT4) and free triiodothyronine (FT3) levels and suppressed thyroid-stimulating hormone (TSH) levels. These findings, combined with the clinical conditions-an ophthalmologic evaluation (that showed the presence of exophthalmos without lagophthalmos and visual acuity deficiency), thyroid ultrasound, and TSH receptor antibody positivity-led to a diagnosis of Graves' disease. Therefore, methimazole was administered at a dose of 0.4 mg/kg/day. After 4 months, thyroid function was clearly improved, with normal FT3 and FT4 values and increasing TSH values, without adverse effects. Nevertheless, an eye examination showed ophthalmopathy with signs of activity, an increase in the exophthalmos of the right eye with palpebral retraction, soft tissue involvement (succulent and oedematous eyelids, caruncle and conjunctival hyperaemia and oedema) and keratopathy, resulting from exposure. We began steroid therapy with oral administration of prednisone (1 mg/kg/day) for four weeks, followed by gradual tapering. After one week of therapy with prednisone, an eye assessment showed reduced retraction of the upper eyelid of the right eye, improvement of right eye exophthalmometry and reduction of conjunctival hyperaemia. After four weeks of therapy with prednisone, an eye assessment showed reduction of the right palpebral retraction without conjunctival hyperaemia and no other signs of inflammation of the anterior segment; after twelve weeks, an eye assessment showed a notable decrease in the right palpebral retraction and the absence of keratitis, despite persisting moderate conjunctival hyperaemia. No adverse event associated with steroid use was observed during the treatment period and no problem in compliance was reported. CONCLUSION: Prednisone seems a better choice than intravenous corticosteroids, for treating moderate-to-severe and active Graves' ophthalmopathy, keeping in mind the importance of quality of life in pediatric patients.

Growth Hormone (GH) Therapy During the Transition Period: Should We Think About Early Retesting in Patients with Idiopathic and Isolated GH Deficiency?

To investigate growth hormone (GH) secretion at the transition age, retesting of all subjects who have undergone GH replacement therapy is recommended when linear growth and pubertal development are complete to distinguish between transitional and persistent GH deficiency (GHD). Early retesting of children with idiopathic and isolated GHD (i.e., before the achievement of final height and/or the adult pubertal stage) can avoid possible over-treatment. Here, we report data from our population with idiopathic and isolated GHD to encourage changes in the management and timing of retesting. We recruited 31 patients (19 males) with idiopathic GHD who received recombinant GH (rGH) for at least 2 years. All of the patients were retested at the transition age at least 3 months after rGH discontinuation. Permanent GHD was defined as a GH peak of <19 ng/mL after administration of growth hormone⁻releasing hormone (GHRH) + arginine as a provocative test. Permanent GHD was confirmed in only five of 31 patients (16.13%). None of these patients presented low serum insulin-like growth factor (IGF)-1 levels (<-2 standard deviation score (SDS)). Only one male patient with an IGF-1 serum level lower than -2 SDS showed a normal GH stimulation response, with a GH peak of 44.99 ng/mL. Few patients with idiopathic and isolated GHD demonstrated persistence of the deficit when retested at the transition age, suggesting that the timing of retesting should be anticipated to avoid overtreatment.

Complex Investigation of a Pediatric Haematological Case: Haemophagocytic Syndrome Associated with Visceral Leishmaniasis and Epstein⁻Barr (EBV) Co-Infection.

BACKGROUND: Visceral leishmaniasis (VL) is an anthropozoonosis caused by an intracellular parasite belonging to the genus Leishmania. In the Mediterranean region, L. donovani and L. infantum are responsible for VL and dogs are the main reservoir. Haemophagocytic lymphohistiocytosis (HLH) represents a complication of VL and consists of unrestrained activation and proliferation of lymphocytes and macrophages, leading to uncontrolled immune activation. Haemophagocytic lymphohistiocytosis may also develop during viral infection, and Epstein⁻Barr virus (EBV) infection is one of the main HLH causes. Macrophage haemophagocytosis in the bone marrow aspirate is pathognomonic. CASE PRESENTATION: The case involves a 19-month-old male infant presenting with a high persistent fever with a fluctuating pattern, pancytopaenia, hepatosplenomegaly, and a high triglyceride level. Initial investigations showed an EBV infection. Considering the persistent signs and symptoms, bone marrow aspiration was performed and confirmed the suspicion of HLH. In addition, the presence of Leishmania infection was shown. The patient was treated with liposomal amphotericin B and had complete resolution of his symptoms. CONCLUSION: Diagnosis of VL represents a demanding challenge in endemic and non-endemic areas. Our case demonstrates that leishmaniasis should always be considered in the differential diagnosis in patients presenting with hepatosplenomegaly and cytopaenia with a persistent fever, even in cases of infectious mononucleosis. Moreover, the execution of bone marrow aspiration should not be delayed in order to diagnose and treat at an early stage the potential occurrence of VL, especially if complicated with HLH.

Hashimoto's Disease and Thyroid Cancer in Children: Are They Associated?

Hashimoto's thyroiditis (HT) is the most common cause of thyroid disease in children and adolescents. Along with significant modifications of thyroid function, HT in pediatric age can be accompanied by relevant thyroid structural alterations. Over time, benign thyroid nodules, carcinoma and, rarely, primary non-Hodgkin lymphoma can develop. However, the relationships between HT and neoplasms are poorly defined. The main aim of this paper is to discuss what is presently known regarding the coexistence of HT and thyroid tumors. Moreover, we attempt to define the pathogenesis of cancer development in children with HT. Literature analysis showed that despite its rarity and relatively promising prognosis, thyroid cancer is associated with HT. Although not all reasons for the coexistence of these diseases are clearly defined, children with HT should be considered at higher risk for thyroid cancer development. Strict correlations between high levels of serum TSH and anti-thyroid antibodies with cancer must be remembered. The same is true for the presence of nodules, especially if multiple nodules are present and ultrasonography and thyroid fine needle aspiration cytology should be promptly used in uncertain cases.

Up-To-Date Review About Minipuberty and Overview on Hypothalamic-Pituitary-Gonadal Axis Activation in Fetal and Neonatal Life.

Minipuberty consists of activation of the hypothalamic-pituitary-gonadal (HPG) axis during the neonatal period, resulting in high gonadotropin and sex steroid levels, and occurs mainly in the first 3-6 months of life in both sexes. The rise in the levels of these hormones allows for the maturation of the sexual organs. In boys, the peak testosterone level is associated with penile and testicular growth and the proliferation of gonadic cells. In girls, the oestradiol levels stimulate breast tissue, but exhibit considerable fluctuations that probably reflect the cycles of maturation and atrophy of the ovarian follicles. Minipuberty allows for the development of the genital organs and creates the basis for future fertility, but further studies are necessary to understand its exact role, especially in girls. Nevertheless, no scientific study has yet elucidated how the HPG axis turns itself off and remains dormant until puberty. Additional future studies may identify clinical implications of minipuberty in selected cohorts of patients, such as premature and small for gestational age infants. Finally, minipuberty provides a fundamental 6-month window of the possibility of making early diagnoses in patients with suspected sexual reproductive disorders to enable the prompt initiation of treatment rather than delaying treatment until pubertal failure.

Inhibin B in healthy and cryptorchid boys.

BACKGROUND: Cryptorchidism, the most common male genital abnormality observed in paediatrics, might often be associated with long-term functional consequences and can even reoccur after a successful orchidopexy. Serum markers that identify cryptorchid boys with gonadal dysfunction early should be useful in a decision-making process. Inhibin B, produced during all of childhood but altered in cryptorchid subjects, appears strictly related to Sertoli cells, and its levels directly reflect the status of the testis germinative epithelium. Unfortunately, its precise roles in bilateral and unilateral cryptorchidism are still debated and being unravelled. Herein, we report the most current knowledge about inhibin B in both healthy boys and those with cryptorchidism to discuss and clarify its potential clinical applications. DISCUSSION: Inhibin B represents a simple and repeatable serum marker and it seems to well asses the presence and function of the testicular tissue. Testicular tissue in prepubertal age is largely made up of Sertoli cells; inhibin B, coming from working Sertoli cells, allows to indirectly evaluate their function. Besides, inhibin B is produced throughout childhood, even before puberty, in contrast with central hormones, and it is not influenced by androgens during puberty, in contrast with other testicular hormones. Although further studies are needed, low levels of inhibin B have been related with low testicular score and/or with consistent alterations of testicular parameters at histological examination. This means that inhibin B could be an indirect marker of testicular functions that could even replace testicular biopsies, but current data are inconsistent to confirm this potential role of inhibin B in cryptorchidism. CONCLUSION: Inhibin B represents an effective candidate for early identification of testicular dysfunction after orchidopexy for cryptorchidism. Unfortunately, current data cannot exactly clarify the real role of inhibin B as a predictor of future testicular function in cryptorchidism and future long-term follow-up studies, with repeated inhibin B checks both in cryptorchid and in formerly cryptorchid children and adolescents, will permit to assess if previous normal levels of inhibin B would match with future normal pubertal development and fertility potential.

Rhabdomyolysis in a Young Girl with Van Wyk-Grumbach Syndrome due to Severe Hashimoto Thyroiditis.

Background: Autoimmune hypothyroidism (Hashimoto thyroiditis; HT) is the most common postnatal thyroid disease. Clinical manifestations of HT vary according to disease severity. Due to the pleiotropic effects of thyroid hormone, less common signs and symptoms of HT can occur, leading to a delay in diagnosis. Case presentation: A 9-year-old girl of Indian origin was admitted for a one-week history of widespread myalgia, fatigue, muscle weakness, difficulty walking, and a significant increase in weight (approximately 2 kg) without any changes in daily habits. The only relevant medical history was several intermittent vaginal bleeding episodes since four years of age. Breast development was consistent with Tanner stage 2 without pubic or axillary hair; while height and weight were at the 10th percentile and the 38th percentile; respectively. Bone age from a left wrist X-ray was delayed 1 year. Pelvic ultrasonography revealed a uterine body/neck ratio of >1 (pubertal stage) and multifollicular ovaries. Her external genitalia had a childlike appearance. Laboratory examinations showed an increased thyroid-stimulating hormone, decreased free thyroxine, and positive anti-thyroglobulin antibody titres, as well as elevation of creatine phosphokinase, myoglobin, lactate dehydrogenase, serum aspartate aminotransferase, hypercholesterolemia, and a basal serum prolactin near the upper limit of normal. Follicle stimulating hormone and estradiol were slightly and significantly elevated, respectively. Thyroid ultrasound showed an increased gland size with irregular echostructures and high vascularization. Levothyroxine replacement therapy led to complete normalization of clinical and laboratory findings, including rhabdomyolysis indices. No further vaginal bleeding episodes were reported. Conclusion: This case report highlights how various can be the clinical picture of HT in children, and how rare clinical manifestations can be the only signs of disease at presentation leading to delayed diagnosis and treatment. In this girl, a never-described association of Van Wyk-Grumbach syndrome and acute rhabdomyolysis in a young girl with previously unrecognized HT is described. The importance of recognizing the signs and symptoms of rare complications of HT in order to begin appropriate therapy is stressed.

Pericardial Effusion as a Presenting Symptom of Hashimoto Thyroiditis: A Case Report.

Background: Hashimoto thyroiditis (HT) is the most frequent cause of acquired hypothyroidism in paediatrics. HT is usually diagnosed in older children and adolescents, mainly in females and is rare in infants and toddlers with cardiac involvement, including pericardial effusion, that can be found in 10% to 30% of adult HT cases. In this paper, a child with HT and pericardial effusion as the most important sign of HT is described. Case presentation: A four-year-old male child suffering for a few months from recurrent abdominal pain sometimes associated with vomiting underwent an abdominal ultrasound scan outside the hospital. This led to the identification of a significant pericardial effusion. At admission, his family history revealed that both his mother and maternal grandmother suffered from HT and that both were treated with l-thyroxine (LT4). The clinical examination did not reveal any pathological signs other than a palpable thyroid. His weight was 21 kg (78th percentile), his height was 101.8 cm (12th percentile) and his body max index (BMI) was 20.26 (96th percentile). On a chest radiograph, his heart had a globular appearance and the lung fields were normal. An echocardiography confirmed and determined the effusion amount (max, 23 mm; 600 mL) with light impairment of the heart kinetics. The ECG showed sinus bradycardia with a normal ST tract. Based on the blood test results, an infectious cause of the pericardial fluid excess was considered unlikely. Thyroid function testing revealed very high thyrotropin (TSH, 487 µIU/mL; normal range, 0.340-5.600 µIU/mL) and low serum-free thyroxine (fT4, 0.04 ng/dL; normal range, 0.54-1.24 ng/dL) levels. High thyroid peroxidase antibody titres in the blood were evidenced (>1500 UI/L; normal values, 0.0-9.0 UI/L). The thyroid ultrasound was consistent with thyroiditis. HT was diagnosed, and LT4 replacement therapy with levothyroxine sodium 1.78 µg/kg/die was initiated, with a gradual increase of the administered dose. The treatment was successful because a complete regression of the effusion after one month was evidenced, with a substantial modification towards normality of the thyroid function tests. One year later, the substitutive therapy led to complete normalization of the thyroid function indexes. A slight reduction of weight (BMI, 17.60 for age) and an increase of the velocity of height growth were evidenced. Conclusions: When fluid is identified in the pericardial space and pericarditis of unknown origin is diagnosed, the thyroid function should be immediately evaluated to prescribe substitutive hormonal therapy if necessary and thereby avoid overt hypothyroidism development and the risk of cardiac tamponade.