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Here we describe three patients with neurodevelopmental disorders characterized by mild-to-moderate intellectual disability, mildly dysmorphic features, and hirsutism, all of which carry de novo sequence variants in the WW domain-containing adaptor of the coiled-coil (WAC) gene; two of these-c.167delA, p.(Asn56I1efs*136) and c.1746G>C, p.(Gln582His)-are novel pathogenic variants, and the third-c.1837C>T, p(Arg613*)-has been previously described. Diseases associated with WAC include DeSanto-Shinawi syndrome; to date, de novo heterozygous constitutional pathogenic WAC variants have caused a syndromic form of intellectual disability and mild dysmorphic features in 33 patients, yet potential associations with other clinical manifestations, such as oligomenorrhea and hyperandrogenism, remain unknown, because the phenotypic spectrum of the condition has not yet been delineated. The patient bearing the novel c.167delA WAC gene variant presented a normal psychomotor development, oligomenorrhea, hyperandrogenism, and hirsutism, and hirsutism was also observed in the patient with the c.1746G>C WAC gene variant. Hypertrichosis and hirsutism have been described in nine DeSanto-Shinawi patients, only in 17 of the 33 aforementioned patients thus far reported this aspect, and no hormonal-pattern data are available. In conclusion, we note that the pathogenic c.167delA WAC variant may be associated with a mild phenotype; and in addition to the neurodevelopmental problems nearly all DeSanto-Shinawi patients experience (i.e., intellectual disability and/or developmental delay), we recommend the addition of mild dysmorphic features, hirsutism, and hypertrichosis to this clinical presentation.
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Hiperandrogenismo , Hipertricose , Deficiência Intelectual , Humanos , Feminino , Deficiência Intelectual/genética , Hirsutismo/genética , Hipertricose/genética , Oligomenorreia , FenótipoRESUMO
OBJECTIVE: To evaluate (i) the prevalence and association of euthyroid sick syndrome (ESS) [decreased FT3 and/or FT4 and normal/decreased TSH] with severity indexes of type 1 diabetes mellitus (T1DM) onset such as diabetic ketoacidosis (DKA) and kidney damage [acute kidney injury (AKI) based on KDIGO criteria, acute tubular necrosis (ATN), renal tubular damage (RTD)], (ii) relationship between clinical/metabolic parameters at T1DM onset and thyroid hormones, and (iii) ESS as a prognostic indicator of delayed recovery from kidney damage. METHODS: A total of 161 children with T1DM onset were included. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin (NGAL) and/or tubular reabsorption of phosphate <85% and/or fractional excretion of Na>2%. ATN was defined by RTD+AKI. RESULTS: Of 161 participants, 60 (37.3%) presented ESS. It was more prevalent in case of more severe T1DM presentation both in terms of metabolic derangement (DKA) and kidney function impairment (AKI, RTD and ATN). Only ATN, however, was associated with ESS at adjusted analysis. FT3 inversely correlated with serum triglycerides and creatinine, and urinary calcium/creatinine ratio and NGAL. Participants with euthyroidism showed earlier recovery from AKI than those with ESS. ESS spontaneously disappeared. CONCLUSIONS: ESS is associated with T1DM onset severity and spontaneously disappears. ESS delayed the recovery from AKI. IMPACT: This is the first longitudinal study describing in detail the relationship between clinical/metabolic factors at type 1 diabetes mellitus (T1DM) onset and thyroid hormones, with particular attention to the relationship between diabetic ketoacidosis (DKA)-related kidney function impairment and euthyroid sick syndrome (ESS). Participants with more severe T1DM onset presentation both in terms of metabolic derangement and kidney function impairment had an increased prevalence of ESS. Children with ESS had a slower recovery from acute kidney injury compared with those without ESS. ESS spontaneously disappeared in all participants.
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Injúria Renal Aguda , Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Síndromes do Eutireóideo Doente , Criança , Humanos , Lipocalina-2/urina , Diabetes Mellitus Tipo 1/complicações , Síndromes do Eutireóideo Doente/complicações , Cetoacidose Diabética/complicações , Estudos Longitudinais , Creatinina , Injúria Renal Aguda/epidemiologiaRESUMO
BACKGROUND: Basal levels of androgens, in particular 17-hydroxyprogesterone (17OHP), are widely debated as predictors of non-classical congenital adrenal hyperplasia (NCCAH) among patients with precocious pubarche (PP). Many authors have recommended the use of adrenocorticotropic hormone (ACTH) stimulation test in children with PP. The aim of our study was to identify clinical and biochemical predictors of NCCAH in children with PP. METHODS: We conducted a prospective study of 92 patients with PP undergoing an ACTH stimulation test. We tested the association of basal clinical and biochemical parameters with NCCAH diagnosis. Patients were suspected to have NCCAH if their stimulated 17OHP plasma levels were >10 ng/mL. In these patients, the diagnosis was confirmed by genetic test. RESULTS: Seven (7.6%) patients resulted having NCCAH. The best basal biochemical predictor for NCCAH was 17OHP level >2 ng/mL. In fact, a basal 17OHP level >2 ng/mL had 100% (95% confidence interval (CI), 59.04-100) sensitivity and 93% (95% CI, 85.3-97.37) specificity. The area under the receiver-operating characteristic curve for 17OHP was 0.99 (95% CI, 0.98-1.007). CONCLUSIONS: Basal 17OHP cut-off of 2 ng/mL was very effective in predicting NCCAH among our patients with PP. Assay-specific cut-off would probably be the best strategy to avoid unnecessary ACTH test.
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17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/diagnóstico , Puberdade Precoce/diagnóstico , Hiperplasia Suprarrenal Congênita/sangue , Hormônio Adrenocorticotrópico/sangue , Criança , Pré-Escolar , Feminino , Testes Genéticos , Cabelo/crescimento & desenvolvimento , Humanos , Hidrocortisona/sangue , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Puberdade Precoce/sangue , Curva ROC , Valores de Referência , Sensibilidade e Especificidade , Esteroide 21-Hidroxilase/genéticaRESUMO
BACKGROUND: Central precocious puberty (CPP) is often familial but its genetic cause is largely unknown. Very recently, the makorin RING finger protein 3 (MKRN3) gene, located on chromosome 15 in the Prader-Willi syndrome (PWS)-associated region (15q11-q13), has been found mutated in 5 families with familial precocious puberty. The MKRN3 is a maternal imprinted gene and the phenotype is expressed only when the MKRN3 mutations are localized on the allele inherited from the father. The function of this gene is not completely known and the phenotype caused by its defect is not yet fully elucidated. We report a new MKRN3 mutation (Pro160Cysfs*14) causing familial CPP. CASE PRESENTATION: The index case is a 7 years old girl showing Tanner stage 3 and pubic hair stage 1. Her bone age evaluated by TW2 method was 10.3 years. Her hormonal data confirmed the diagnosis of central precocious puberty. Familial medical history revealed precocious puberty in a cousin on paternal side. Paternal grandmother had menarche at the age of 9 years and 6 months and premature menopause when she was 36 years old. Genetic analysis revealed a new mutation (c477_485del; Pro160Cysfs*14) in the maternally imprinted MKRN3. Puberty onset was at 5 years in the other affected female family member. Precocious puberty was well controlled by pharmacological therapy. CONCLUSION: We expand the number of the MKRN3 mutations associated with CPP and highlight the importance of an accurate family medical history to disclose the peculiar pattern of inheritance of this gene.
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Mutação/genética , Puberdade Precoce/genética , Ribonucleoproteínas/genética , Maturidade Sexual/genética , Criança , Feminino , Humanos , Masculino , Linhagem , Prognóstico , Puberdade Precoce/patologia , Ubiquitina-Proteína LigasesRESUMO
BACKGROUND: Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disorder (prevalence 1:125,000) characterised by broad thumbs and halluces, facial dysmorphism, psychomotor development delay, skeletal defects, abnormalities in the posterior fossa and short stature. The known genetic causes are point mutations or deletions of the cAMP-response element binding protein-BP (CREBBP) (50-60% of the cases) and of the homologous gene E1A-binding protein (EP300) (5%). CASE PRESENTATION: We describe, for the first time in literature, a RTS Caucasian girl, 14-year-old, with growth hormone (GH) deficiency, pituitary hypoplasia, Arnold Chiari malformation type 1, double syringomyelic cavity and a novel CREBBP mutation (c.3546insCC). CONCLUSION: We hypothesize that CREBBP mutation we have identified in this patient could be responsible also for RTS atypical features as GH deficiency and pituitary hypoplasia.
Assuntos
Malformação de Arnold-Chiari/genética , Proteína de Ligação a CREB/genética , Hipófise/anormalidades , Síndrome de Rubinstein-Taybi/genética , Anormalidades Múltiplas/genética , Adolescente , Feminino , Hormônio do Crescimento , Humanos , Mutação , Displasia Septo-Óptica/genéticaRESUMO
OBJECTIVES: Lower limb deformities in children need careful orthopedic evaluation to distinguish physiological forms from pathological ones. X-linked hypophosphatemia (XLH) is a rare hereditary condition caused by PHEX gene mutations where tibial varum can be the first sign. CASE PRESENTATION: We report a family presenting with severe tibial varum, harbouring a rare PHEX intron mutation, c.1586+6T>C. This is the first clinical description available in literature for this variant. Despite the previous prediction of a mild phenotype in functional study, our patients showed important bone deformities, rickets and impaired growth since infancy followed by severe bone pain, hearing loss and reduced life quality in adulthood. Burosumab therapy improved biochemical and radiological findings in children and ameliorated quality of life in adults. CONCLUSIONS: This case demonstrated c.1586+6T>C causes a severe XLH phenotype, responsive to Burosumab. Familial genetic screening, enlarged to intronic region analysis, when XLH is suspected, allows precocious diagnosis to start timely the appropriate treatment.
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Raquitismo Hipofosfatêmico Familiar , Raquitismo Hipofosfatêmico , Humanos , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Raquitismo Hipofosfatêmico Familiar/genética , Raquitismo Hipofosfatêmico Familiar/diagnóstico , Íntrons/genética , Qualidade de Vida , Raquitismo Hipofosfatêmico/genética , Mutação , Fenótipo , Endopeptidase Neutra Reguladora de Fosfato PHEX/genéticaRESUMO
DICER1 syndrome is a rare genetic disorder that predisposes patients to the development of malignant and non-malignant diseases. Presently, DICER1 syndrome diagnosis still occurs late, usually following surgical operations, affecting patients' outcomes, especially for further neoplasms, which are entailed in this syndrome. For this reason, herein we present a multicenter report of DICER1 syndrome, with the prospective aim of enhancing post-surgical surveillance. A cohort of seven patients was collected among the surgical registries of Pediatric Surgery at the University of Pisa with the General and Oncologic Surgery of Federico II, University of Naples, and the Pediatric Surgery, Regina Margherita Hospital, University of Turin. In each case, the following data were analyzed: sex, age at diagnosis, age at first surgery, clinical features, familial, genetic investigations, and follow-up. A comprehensive literature review of DICER1 cases, including case reports and multicenter studies published from 1996 to June 2022, was performed. Eventually, the retrieved data from the literature were compared with the data emerging from our cohort of patients.
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Soy-based infant formulas (SFs) are often consumed by cow's milk allergic children. However, some concerns have risen since soy intake may adversely affect thyroid function in iodine-deficient or subclinical hypothyroid individuals. We report the first Italian case of SF induced goiter and hypothyroidism registered in our country since National Iodine program has been instituted. Finally, we review cases previously reported in literature. A 22-month-old toddler with a previous diagnosis of cow's milk protein allergy came to clinical attention for important goiter and overt hypothyroidism. Detailed dietary anamnesis revealed that he was on a restrictive dietary regimen based on soymilk since 12 months of age. A temporary levothyroxine substitution was instituted to avoid hypothyroidism complications. Adequate iodine supplementation and diet diversification completely reversed SF-induced hypothyroidism and goiter, confirming the diagnostic suspicion of soymilk-induced thyroid dysfunction in a iodine-deficient toddler. This case report demonstrates the importance of careful dietary habits investigation and adequate micronutrients supplementation in children on a restrictive diet due to multiple food allergies in order to prevent nutritional deficits.
Assuntos
Bócio , Hipotireoidismo , Iodo , Leite de Soja , Dieta , HumanosRESUMO
BACKGROUND: Increased incidence of central precocious puberty (CPP) after coronavirus infectious disease-19 lockdown has been reported. Our study aims in investigating changes in CPP rates and in sleep patterns in CPP and healthy controls. METHODS: CPP were retrospectively evaluated from April 2020 to April 2021. Parents of girls diagnosed with CPP during lockdown and of matched healthy controls filled out a questionnaire about sleep disturbances (SDSC questionnaire) and sleep schedules. RESULTS: Thirty-five CPP and 37 controls completed the survey. Incidence of new CPP cases significantly increased in 2020-2021 compared to 2017-2020 (5:100 vs 2:100, p = 0.02). Sleep disturbance rates did not differ between CPP and healthy controls before lockdown. During lockdown, CPP reported higher rates of sleep disturbs for total score (p = 0.005), excessive somnolence (p = 0.049), sleep breathing disorders (p = 0.049), and sleep-wake transition disorders (p = 0.005). Moreover, CPP group more frequently shifted toward later bedtime (p = 0.03) during lockdown compared to controls. Hours of sleep and smartphone exposure around bedtime did not differ between groups. CONCLUSIONS: Our study confirms the observation of increased incidence of CPP after lockdown measures. Additionally, CPP showed higher rates of sleep disturbances and later bedtime compared to controls. The causality link between sleep disturbances and CPP should be further investigated to gain knowledge in this association.
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COVID-19 , Puberdade Precoce , Transtornos do Sono-Vigília , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Feminino , Humanos , Pandemias , Puberdade Precoce/epidemiologia , Puberdade Precoce/etiologia , Estudos Retrospectivos , Sono , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologiaRESUMO
The Italian Cancer Registry Association has estimated that for the five-year period 2016-2020, in line with the previous five years, approximately 7000 neoplasms have been diagnosed among children and 4000 among adolescents. Leukemias, brain tumors and lymphomas together account for more than two-thirds of all pediatric cancers. Fortunately, the five-years survival rate has progressively improved reaching 80% thanks to the continuing improvement of therapeutic protocols but most of these cancer survivors will have at least one chronic health condition by 40 years of age. Long-term complications concern various organs and systems and have a multifactorial etiopathogenesis. Obesity, diabetes, and metabolic syndrome represent chronic diseases that affect life expectancy. Cardiovascular risk partly linked to therapies and genetic susceptibility and partly linked to the presence of obesity, diabetes and metabolic syndrome predispose childhood cancer survivors to heart failure, coronary artery disease, valvular disease, arrhythmia. Hence the cardio- metabolic risk of childhood cancer survivors can have a significant impact on their lives, families, and on society at-large. Therefore, it is very important to know the risk factors that predispose to the development of cardio-metabolic pathologies in childhood cancer survivors, the possible primary and secondary prevention strategies, the methods of surveillance and the therapeutic approaches.
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Neoplasias Encefálicas , Sobreviventes de Câncer , Doenças Cardiovasculares , Adolescente , Criança , Humanos , Sistema de Registros , Taxa de SobrevidaRESUMO
Neck ultrasound (nUS) is the cornerstone of clinical management of thyroid nodules in pediatric patients, as well as adults. The current study was carried out to explore and compare the diagnostic performance of the main US-based risk stratification systems (RSSs) (i.e., the American College of Radiology (ACR), European (EU), Korean (K) TI-RADSs and ATA US RSS criteria) for detecting malignant thyroid lesions in pediatric patients. We conducted a retrospective analysis of consecutive children and adolescents who received a diagnosis of thyroid nodule. We included subjects with age <19 years having thyroid nodules with benign cytology/histology or final histological diagnosis. We excluded subjects with (a) a previous malignancy, (b) a history of radiation exposure, (c) cancer genetic susceptibility syndromes, (d) lymph nodes suspicious for metastases of thyroid cancer at nUS, (e) a family history of thyroid cancer, or (f) cytologically indeterminate nodules without histology and nodules with inadequate cytology. We included 41 nodules in 36 patients with median age 15 years (11-17 years). Of the 41 thyroid nodules, 29 (70.7%) were benign and 12 (29.3%) were malignant. For both ACR TI-RADS and EU-TIRADS, we found a sensitivity of 41.7%. Instead, for both K-TIRADS and ATA US RSS, we found a sensitivity of 50%. The missed malignancy rate for ACR-TIRADS and EU-TIRADS was 58.3%, while that for K-TIRADS and ATA US RSS was 50%. The unnecessary FNA prevalence for ACR TI-RADS and EU-TIRADS was 58.3%, while that for K-TIRADS and ATA US RSS was 76%. Our findings suggest that the four US-based RSSs (i.e., ACR-TIRADS, EU-TIRADS, K-TIRADS, and ATA US RSS) have suboptimal performance in managing pediatric patients with thyroid nodules, with one-half of cancers without indication for FNA according to their recommendations.
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BACKGROUND: Recently, mutations of makorin RING finger protein 3 (MKRN3) have been identified in familial central precocious puberty (CPP). Serum levels of this protein decline before the pubertal onset in healthy girls and boys and are lower in patients with CPP compared to prepubertal matched pairs. The aim of our study was to investigate longitudinal changes in circulating MKRN3 levels in patients with CPP before and during GnRH analogs (GnRHa) treatment. METHODS: We performed a longitudinal prospective study. We enrolled 15 patients with CPP aged 7.2 years (range: 2-8) with age at breast development onset < 8 years and 12 control girls matched for the time from puberty onset (mean age 11.8 ± 1.2 years). Serum values of MKRN3, gonadotropins, and 17ß-estradiol were evaluated before and during treatment with GnRHa (at 6 and 12 months). The MKRN3 gene was genotyped in CPP patients. In the girls from the control group, only basal levels were analyzed. RESULTS: No MKRN3 mutations were found among CPP patients. MKRN3 levels declined significantly from baseline to 6 months of GnRHa treatment (p = 0.0007) and from 6 to 12 months of treatment (p = 0.003); MKRN3 levels at 6 months were significantly lower than in the control girls (p < 0.0001). CONCLUSIONS: We showed that girls with CPP had a decline in peripheral levels of MKRN3 during GnRHa treatment. Our data suggest a suppression of MKRN3 by continuous pharmacological administration of GnRHa.
Assuntos
Hormônio Liberador de Gonadotropina/agonistas , Puberdade Precoce/tratamento farmacológico , Ribonucleoproteínas/sangue , Ribonucleoproteínas/genética , Encefalopatias/sangue , Encefalopatias/tratamento farmacológico , Encefalopatias/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Hormônio Foliculoestimulante/sangue , Genótipo , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Estudos Longitudinais , Hormônio Luteinizante/sangue , Masculino , Puberdade Precoce/sangue , Puberdade Precoce/genética , Ubiquitina-Proteína LigasesRESUMO
PURPOSE: Recently, mutations of makorin RING-finger protein 3 (MKRN3) have been described in familial central precocious puberty. Serum levels of this protein decline before the pubertal onset in healthy girls and boys. The aim of the study is to investigate MKRN3 circulating levels in patients with central precocious puberty. METHODS: We performed an observational cross-sectional study. We enrolled 17 patients with central precocious puberty aged 7 years (range: 2-8 years) and breast development onset <8 years; 17 prepubertal control age-matched patients aged 6.3 years (2-8.2); and 10 pubertal stage-matched control patients aged 11.4 years (9-14). Serum values of MKRN3, gonadotropins, (17)estradiol and Anti-Müllerian Hormone were evaluated and the MKRN3 genotyped in central precocious puberty patients. RESULTS: No MKRN3 mutation was found among central precocious puberty patients. MKRN3 levels were lower in patients with central precocious puberty compared to prepubertal age-matched ones (p: 0.0004) and comparable to those matched for pubertal stage. MKRN3 levels were inversely correlated to Body Mass Index Standard Deviations (r:-0.35; p:0.02), Luteinizing Hormone (r:-0.35; p:0.03), FSH (r:-0.37; p:0.02), and (17)estradiol (r: -0.36; p:0.02). CONCLUSIONS: We showed that girls with central precocious puberty had lower peripheral levels of MKRN3 compared to age-matched pairs and that they negatively correlated to gonadotropins, estrogen, and BMI. Our findings support the MKRN3 involvement in central precocious puberty also in absence of deleterious mutations, although our sample size is small. In addition our data suggest the role of MKRN3 in the complex mechanism controlling puberty onset and its interaction with other factors affecting puberty such as nutrition.
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Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Puberdade Precoce/genética , Ribonucleoproteínas/genética , Adolescente , Fenômenos Fisiológicos da Nutrição do Adolescente , Hormônio Antimülleriano/sangue , Estudos de Casos e Controles , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Pré-Escolar , Estudos Transversais , Feminino , Hormônio Liberador de Gonadotropina/sangue , Humanos , Projetos Piloto , Puberdade Precoce/sangue , Maturidade Sexual/genética , Ubiquitina-Proteína LigasesRESUMO
OBJECTIVE: The insulin variable number of tandem repeats (VNTR) polymorphism located in the insulin gene promoter (INS VNTR) has been associated with insulin levels in obese children. Hyperinsulinemia is a pivotal factor in the development of metabolic syndrome, an emerging complication in childhood obesity. With the present study, we aimed to test the associations between INS VNTR and the metabolic syndrome in juvenile-onset obesity. SUBJECTS AND METHODS: We screened for the INS VNTR in 320 obese children (152 girls; mean age, 11.2 +/- 2.3 yr; mean z-score body mass index, 3.6 +/- 1.1). All of them underwent a standard oral glucose tolerance test; baseline measurements included blood pressure and plasma lipid and fasting insulin levels. By using the data derived from the oral glucose tolerance test, the whole-body insulin sensitivity and the insulinogenic index were calculated. RESULTS: The prevalence of metabolic syndrome reached 39%. No differences in INS VNTR genotype distribution were observed between obese subjects and 200 lean, age- and sex-matched children (P = 0.7). Among obese subjects, the prevalence of the metabolic syndrome was significantly higher in subjects with the I/I genotype (P = 0.006); the risk for developing the metabolic syndrome was significantly higher in subjects carrying the I/I genotype (odds ratio, 2.5; 95% confidence interval, 1.5-3.9). Obese subjects homozygous for the class I allele showed higher insulin levels and insulinogenic index but lower whole-body insulin sensitivity. CONCLUSIONS: We conclude that the I variant of the insulin promoter, when expressed in homozygotes, can predispose obese children to develop the metabolic syndrome.
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Variação Genética , Insulina/genética , Síndrome Metabólica/complicações , Síndrome Metabólica/genética , Obesidade/complicações , Obesidade/genética , Sequências de Repetição em Tandem , Adolescente , Glicemia/análise , Criança , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Humanos , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Síndrome Metabólica/epidemiologia , Fenótipo , PrevalênciaRESUMO
BACKGROUND: In infants under 3 years of age acquired primary hypothyroidism caused by autoimmune thyroiditis is very rare. Hypothyroidism can manifest with different signs and symptoms and has a wide range of presentations from subclinical hypothyroidism to overt form. We describe a child with acquired autoimmune thyroiditis during a very early period of life and with a severe hypothyroidism presentation. CASE PRESENTATION: A 22-month-old white male patient with normal neonatal screening presented with a six-month history of asthenia and cutaneous pallor. At general clinical and biochemical exams he showed weight gain, statural growth deceleration, poor movements, sleepy expression, instability while walking, myxoedema, bradycardia, open anterior fontanelle, changes in the face habitus, macrocytic anaemia, ascites, and high CPK, creatinine and cholesterol levels. Acquired autoimmune thyroiditis was the final diagnosis. The thyroxine replacement therapy normalized all the clinical and biochemical abnormalities but at the age of 30 months his mental age showed a delay of 6 months. CONCLUSIONS: Our case could give useful learning points: i) although the screening for congenital hypothyroidism is routinely performed, a severe hypothyroidism (for example due to autoimmune thyroiditis) can anyway occur early in life and the clinicians should consider this possibility; ii) hypothyroidism can have a misleading and multi-face clinical presentation; iii) anemia, rhabdomyolysis and high creatinine levels should always include the hypothyroidism in the differential diagnosis; iv) thyroxine replacement therapy is able to revert all the clinical manifestations related to the hypothyroidism; v) evaluating the patient's previous pictures could play an important role in resolving a diagnostic conundrum.
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Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/etiologia , Tireoidite Autoimune/complicações , Tireoidite Autoimune/diagnóstico , Tiroxina/uso terapêutico , Idade de Início , Seguimentos , Humanos , Hipotireoidismo/diagnóstico , Lactente , Masculino , Medição de Risco , Índice de Gravidade de Doença , Testes de Função Tireóidea , Tireoidite Autoimune/tratamento farmacológico , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: PATRO Children is an ongoing observational, longitudinal, non-interventional, global post-marketing surveillance study, which is investigating the long-term safety and effectiveness of Omnitrope®, a somatropin biosimilar to Genotropin®, in children with growth disturbances. The primary endpoint of PATRO Children is long-term safety and the secondary endpoint is effectiveness, which is assessed by analysing auxological data such as height (HSDS) and height velocity (HVSDS) standard deviation scores. Here, we report the data from the Italian interim analysis of PATRO Children data up to August 2015. METHODS: PATRO Children is enrolling children who are diagnosed with conditions of short stature requiring GH treatment and are receiving Omnitrope®. Adverse events (AEs) are assessed in all Omnitrope®-treated patients. Height is evaluated yearly to near-adult (final) height, and is herein reported as HSDS; height velocity is also assessed and reported as a standard deviation score (HVSDS). RESULTS: Up to August 2015, a total of 186 patients (mean age 10.2 years, 57.5 % males) were enrolled :156 [84 %] had growth hormone deficiency, 12 [6.5 %] were born small for gestational age, seven [3.8 %] had Prader-Willi syndrome, one [0.5 %] had Turner syndrome and one [0.5 %] had chronic renal insufficiency; seven [3.8 %] patients had other indication profiles. The mean treatment duration with Omnitrope® was 28.1 ± 19.1 months. AEs were reported in 35.6 % of patients and included headache, pyrexia, arthralgia, abdominal pain, leg and/or arm pain and increased blood creatine phosphokinase. Two serious AEs in two patients were thought to be drug-related; one patient experienced a minimal increase in a known residual craniopharyngioma, and another a gait disturbance with worsening of walking difficulties. Similar to investigational studies, Omnitrope® treatment was associated with improvements in both HSDS and HVSDS. CONCLUSIONS: Omnitrope® appears to be well tolerated and effective for the treatment of a wide range of paediatric indications, which is consistent with the outcomes from controlled clinical trials. These results need to be interpreted with caution until the data from the global PATRO Children study are available.