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BACKGROUND: Delayed diagnosis of hypothyroidism may result in atypical presentations. Here, we report a case with decreased serum level and activity of von Willebrand factor due to untreated profound hypothyroidism. OBSERVATION: A 9-year-old girl, presented with prolonged gingival bleeding after dental extraction. Clinical findings of the case were consistent with hypothyroidism, and the laboratory workup results revealed decreased serum level and activity of von Willebrand factor associated with profound hypothyroidism. Restoration of euthyroidism normalized the coagulation parameters. CONCLUSION: Delayed diagnosis of hypothyroidism may lead to atypical presentations such as bleeding diathesis. Profound hypothyroidism should be considered in the differential diagnosis of acquired von Willebrand disease to avoid undue treatment.
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Transtornos Hemorrágicos , Hipotireoidismo , Doenças de von Willebrand , Feminino , Humanos , Criança , Fator de von Willebrand , Hipotireoidismo/complicações , Doenças de von Willebrand/complicações , Extração Dentária/efeitos adversosRESUMO
PURPOSE: Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by absent puberty and subsequent infertility due to gonadotropin-releasing hormone (GnRH) deficiency. IHH can be accompanied by normal or compromised olfaction (Kallmann syndrome). Several semaphorins are known potent modulators of GnRH, olfactory, and vomeronasal system development. In this study, we investigated the role of Semaphorin-3F signaling in the etiology of IHH. METHODS: We screened 216 IHH patients by exome sequencing. We transiently transfected HEK293T cells with plasmids encoding wild type (WT) or corresponding variants to investigate the functional consequences. We performed fluorescent IHC to assess SEMA3F and PLXNA3 expression both in the nasal region and at the nasal/forebrain junction during the early human fetal development. RESULTS: We identified ten rare missense variants in SEMA3F and PLXNA3 in 15 patients from 11 independent families. Most of these variants were predicted to be deleterious by functional assays. SEMA3F and PLXNA3 are both expressed along the olfactory nerve and intracranial projection of the vomeronasal nerve/terminal nerve. PLXNA1-A3 are expressed in the early migratory GnRH neurons. CONCLUSION: SEMA3F signaling through PLXNA1-A3 is involved in the guidance of GnRH neurons and of olfactory and vomeronasal nerve fibers in humans. Overall, our findings suggest that Semaphorin-3F signaling insufficiency contributes to the pathogenesis of IHH.
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Hipogonadismo , Semaforinas , Moléculas de Adesão Celular , Células HEK293 , Humanos , Hipogonadismo/genética , Proteínas de Membrana , Proteínas do Tecido Nervoso/genética , Receptores de Superfície CelularRESUMO
BACKGROUND: The aim of the study is to identify the effect of salt intake and diabetes itself on blood pressure (BP) profile and microalbuminuria in children with type one diabetes mellitus (T1DM). Our hypothesis is that higher amount of salt consumption and/or hyperglycemia may impair blood pressure pattern in children with T1DM. METHODS: This cross-sectional study included 84 children and adolescents with T1DM (62% females, age 13.9 ± 3.2 years, disease duration 7.3 ± 3.1 years, 43% poorly controlled diabetes) and 54 aged- and sex-matched healthy children with an adequately collected 24-h urine samples. Urine sodium, creatinine, and microalbumin were measured and salt intake was assessed on the basis of sodium excretion in 24-h urine. Blood pressure profile of the children with T1DM was evaluated with 24-h ambulatory blood pressure monitoring. RESULTS: Compared to the children with well-controlled diabetes, children with poorly controlled diabetes had significantly higher standard deviation scores (SDS) of nighttime systolic BP (0.22 ± 1.28 vs - 0.87 ± 0.76, p = 0.003) and lower dipping in diastole (13.4 ± 5.9 vs 18.4 ± 8.1, p = 0.046). Among T1DM group, children with the highest quartile of salt intake had higher nighttime systolic and diastolic BP-SDS (0.53 ± 1.25 vs - 0.55 ± 0.73, p = 0.002 and 0.89 ± 1.19 vs 0.25 ± 0.63, p = 0.038, respectively) and lower dipping in systole compared to their counterparts (7.7 ± 5.0 vs 11.5 ± 6.1, p = 0.040). High averaged HbA1c was independently associated with higher both daytime and nighttime systolic BP-SDS (p = 0.010, p < 0.001) and nighttime diastolic BP-SDS (p = 0.001), and lower diastolic dipping (p = 0.001). High salt intake was independently associated with higher nighttime systolic BP-SDS (p = 0.002) and lower systolic dipping (p = 0.019). A 24-h MAP-SDS was the only independent risk factor for microalbuminuria (p = 0.035). CONCLUSION: Beside poor diabetic control, high salt consumption appears to be an important modifiable risk factor for impaired BP pattern, which contributes to the development of diabetic kidney disease in children with T1DM.
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Pressão Sanguínea , Diabetes Mellitus Tipo 1/complicações , Hipertensão/etiologia , Cloreto de Sódio na Dieta/efeitos adversos , Adolescente , Albuminúria/urina , Monitorização Ambulatorial da Pressão Arterial , Estudos de Casos e Controles , Criança , Creatinina/urina , Estudos Transversais , Diabetes Mellitus Tipo 1/urina , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Fatores de Risco , Cloreto de Sódio na Dieta/urina , AçúcaresAssuntos
Antitireóideos/uso terapêutico , Doença de Graves/diagnóstico , Proteinúria/diagnóstico , Adolescente , Biópsia , Feminino , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Doença de Graves/urina , Humanos , Rim/patologia , Metimazol/uso terapêutico , Proteinúria/etiologia , Proteinúria/patologia , Proteinúria/urinaAssuntos
Antitireóideos/uso terapêutico , Glomerulonefrite Membranosa/diagnóstico , Doença de Graves/diagnóstico , Proteinúria/diagnóstico , Adolescente , Biópsia , Diagnóstico Diferencial , Feminino , Membrana Basal Glomerular/patologia , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/etiologia , Glomerulonefrite Membranoproliferativa/diagnóstico , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/patologia , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Doença de Graves/urina , Humanos , Metimazol/uso terapêutico , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/etiologia , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Proteinúria/patologia , Rituximab/uso terapêutico , Resultado do TratamentoRESUMO
Introduction: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease resulting from isolated glucocorticoid deficiency or unresponsiveness to adrenocorticotropic hormone. Patients with FGD usually present in infancy or early childhood with hyperpigmentation, recurrent infections, and hypoglycemia. The salt-wasting crisis is rare. Case Presentation: A term female neonate was admitted to the neonatal intensive care unit due to respiratory distress. On physical examination, she had generalized hyperpigmentation. Initial laboratory work-up yielded normal serum electrolytes and glucose. Hyponatremia and hyperkalemia emerged on follow-up. The patient was diagnosed as having primary adrenal insufficiency (PAI) with elevated plasma adrenocorticotropin hormone and reduced cortisol levels and hydrocortisone. We started on oral sodium (5 mEq/kg/day) and fludrocortisone (FC) (0.2 mg/day) treatment to the patient. Ultrasonography revealed hypoplastic adrenal glands. Molecular genetic analysis revealed a previously reported homozygous pathogenic variant NM_000529.2: c.560delT (p.V187fs*29) in the MC2R gene. FC dose was tapered to 0.05 mg/day on the third month of life and was stopped at tenth months of age with maintenance of normal serum electrolytes and clinical findings. Conclusion: FGD due to MC2R gene mutation may rarely present with a salt-wasting crisis in the neonatal period. Identifying the causative gene with the pathogenic variant in PAI may serve to individualize a treatment plan.
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Introduction: Craniopharyngiomas (CPG) have complex challenges in treatment due to their proximity to vital structures, surgical and radiotherapeutic complexities, and the tendency for recurrence. This study aims to identify the prevalence of endocrine and metabolic comorbidities observed during initial diagnosis and long-term follow-up in a nationwide cohort of pediatric CPG patients. The study also highlights the associated difficulties in their management. Methods: Sixteen centers entered 152 patients into the ÇEDD NET data system. We evaluated the clinical and laboratory characteristics at presentation, administered treatments, accompanying endocrine, metabolic, and other system involvements, and the patient's follow-up features. Results: Of the evaluated patients, 64 were female, and 88 were male. At presentation, the mean age was 9.1 ± 3.67 (min:1.46-max:16.92) years. The most common complaints at presentation were headache (68.4%), vision problems (42%), short stature (15%), nausea and vomiting (7%). The surgical procedure applied to the patients was gross total resection (GTR) in 97 cases (63.8%) and subtotal resection in 55 cases (36.2%). Radiotherapy was initiated in 11.8% of the patients. In the pathological examination, 92% of the cases were adamantinamatous type, 8% were papillary type. Postoperatively, hormone deficiencies consisted of thyroid-stimulating hormone (92.1%), adrenocorticotropic hormone (81%), antidiuretic hormone (79%), growth hormone (65.1%), and gonadotropin (43.4%) deficiencies. Recombinant growth hormone treatment (rhGH) was initiated on 27 patients. The study showed hesitancy among physicians regarding rhGH. The median survival without relapse was 2.2 years. Median time of relapse was 1.82 years (range: 0.13-10.35 years). Relapse was related to longer follow-ups and reduced GTR rates. The median follow-up time was 3.13 years. Among the last follow-up visits, the prevalence of obesity was 38%, but of these, 46.5% were already obese at diagnosis. However, 20% who were not obese at baseline became obese on follow-up. Permanent visual impairment was observed in 26 patients, neurological deficits in 13 patients, and diabetes mellitus in 5 patients. Conclusion: Recurrence was predominantly due to incomplete resection and the low rate of postoperative radiotherapy. It also emphasized challenges in multidisciplinary regular follow ups and suggested early interventions such as dietary restrictions and increased exercise to prevent obesity.
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OBJECTIVE: The risk of malignancy in pediatric thyroid nodules is higher compared to the risk in adults. Our aim was to investigate the clinical, radiological, and histopathological characteristics of pediatric thyroid nodules. MATERIALS AND METHODS: The data of 132 children and adolescents who had thyroid nodules were collected retrospectively from medical records. RESULTS: The mean age of the patients was 12.07 ± 4.08 years and 67% were female. Fine-needle aspiration biopsy was performed in 86 patients (65%) and the results were as follows: benign in 53.4% (n = 46), atypia or follicular lesion of undetermined significance in 3.5% (n = 3), suspicious for follicular neoplasia in 2.3% (n = 2), and malignancy in 32.5% (n = 28). The overall malignancy rate was 22.7% (n = 30). Malignancy was detected after surgery in 2 thyroid nodules belonging to the atypia or follicular lesion of undetermined significance category. Malignancy was detected in 7 patients who had autoimmune thyroiditis and in 1 patient who had congenital dyshormonogenesis. The malignancy rate of the nodules in the patients, who had autoimmune thyroiditis, was found to be 13.4%. Mixed echogenicity, microcalcifications, nodules larger than 10 mm, abnormal lymph nodes, and irregular borders were more common in the malignant group. The nodule size, abnormal lymph nodes, and irregular borders were found to be significant in terms of predicting malignancy. CONCLUSION: We found malignancy in 22.7% of the thyroid nodules, and the malignancy rate of nodules in the patients, who had autoimmune thyroiditis, was 13.4%. The nodule size, abnormal lymph nodes, and irregular nodule borders emerged as the most significant risk factors for malignancy.
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OBJECTIVES: The prevalences of pediatric obesity and its associated comorbidities such as metabolic syndrome (metS) are rising. The aim of this study was to evaluate the association of metS status with sensorineural hearing loss in pediatric obese patients. METHODS: A two-center observationalprospective study was designed. In this study, 252 consecutive treatment-naive pediatric obese patients aged 5.8-17.8 yr in a tertiary pediatric Endocrinology outpatient clinic were prospectively enrolled. Following standard clinical and biochemical evaluations, the obese patients were diagnosed as having metabolic syndrome (metS) or not according to Internetional Diabetes Federation Criteria. All the patients were evaluated with tympanometry and pure tone audiometry tests after otomicroscopic examination. Comparative analyses of audiometric evaluations were performed between metS+ and metS- subgroups of the obese patients. RESULTS: The median age of the patients was 12.5 yr (range: 6.0-17.8 yr) and 56.3% of the patients were male. Metabolic syndrome was diagnosed in 82 (32.5%) patients. Age, gender distribution, history of the ventilation tube, and pubertal stage of the metS + patients and metS- counterparts were not statistically different (p > 0.05 for all). Pure tone hearing thresholds at all frequencies (125, 250, 500, 1k, 2k, 4k, 8k) were significantly higher in the metS + group then the metS- group (pË0.05 for all). The tympanometry results were not statistically different between the two groups (pË0.05). Abdominal obesity, hypertension, fasting hyperglycemia and dyslipidemia were not associated with increased hearing thresholds in metS + patients (pË0.05 for all). CONCLUSION: Metabolic syndrome was associated with increased rates of subclinical hearing loss in our cohort. None of the investigated metS components emerged as a positive association with hearing loss in our cohort. Longitudinal follow-up of our cohort may help probe the causality of the association we found.
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Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Síndrome Metabólica , Obesidade Infantil , Humanos , Masculino , Criança , Feminino , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva/etiologia , Audição , Obesidade Infantil/complicações , Obesidade Infantil/diagnóstico , Obesidade Infantil/epidemiologia , Surdez/complicaçõesRESUMO
OBJECTIVES: Metabolically healthy obesity (MHO) has been reported with varying frequencies in children. The reasons of metabolically healthy phenotype in some obese subjects are unclear. Our aim was to identify the frequency of MHO in obese subjects, to assess the potential associations of demographic characteristics, serum uric acid, alanine transaminase (ALT), pediatric nonalcoholic fatty liver disease fibsosis score probability (PNFS p) with MHO status and to evaluate the differences between MHO and metabolically unhealthy obesity (MUO) with regard to metabolic syndrome surrogates. METHODS: 251 consecutive obese subjects (125 females) aged 7-18 years were included. Subjects were classified as having MHO according to Damanhoury's criteria. Several metabolic variables were measured, PNFS p was calculated by using the formula: z=1.1+(0.34*sqrt(ALT))+ (0.002*ALP)-(1.1*log(platelets)-(0.02*GGT). RESULTS: Median age of the subjects was 12.5 yr (range: 7.0-17.0 yr). The frequency of MHO was 41 %. Subjects with MHO were significantly younger, had lower waist circumference (WC) and waist height ratio (WHtR) and lower HOMA-IR than those without MHO(p<0.05 for all). Frequencies of hyperuricemia, hypertransaminasemia, hepatosteatosis and PNFS p values≥8 were similar betwen the groups. When putatively influential factors associated with MHO status were assessed with logistic regression analysis, only WC(ß=1.03) and HOMA-IR(ß=1.166) emerged as significant factors(Nagelkerke R2=0.142). None of the investigated demographic factors were associated with MHO status. CONCLUSIONS: We found a remarkably high frequency of MHO status. Nevertheless, the absence of decreased frequencies of hyperuricemia, hypertransaminasemia and PNFS in subjects with MHO may suggest the need to reconsider the validity of the criteria defining MHO.
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Hiperuricemia , Síndrome Metabólica , Obesidade Metabolicamente Benigna , Obesidade Infantil , Feminino , Criança , Humanos , Síndrome Metabólica/metabolismo , Obesidade Infantil/complicações , Ácido Úrico , Hiperuricemia/complicações , Fenótipo , Fatores de Risco , Índice de Massa CorporalRESUMO
Introduction: Primary adrenal insufficiency associated with cardiomyopathy has been rarely reported in children. We report a case of left ventricular (LV) systolic dysfunction related to adrenal insufficiency with autoimmune polyendocrine syndrome type 1 (APS1). Case Presentation: A 7-year-old girl presented with a loss of consciousness. She had hyperpigmentation over joints and enamel hypoplasia. Laboratory tests showed hypoglycemia, hyponatremia, hypocalcemia, and hyperphosphatemia. Endocrine evaluations revealed low serum parathyroid hormone, low cortisol, and high ACTH. Echocardiography showed moderate to severe mitral regurgitation and LV systolic dysfunction. Serum pro-brain natriuretic peptide (pro-BNP) level was high (2,348 pg/mL). Adrenal insufficiency, hypoparathyroidism, and enamel dysplasia suggested APS1. A novel homozygous variant in the AIRE gene, NM_000383, p.Cys322Arg (c.964T>C) confirmed the diagnosis. Calcium, calcitriol, and hydrocortisone treatments were started. Serum pro-BNP level returned to normal, and LV systolic function improved. Conclusion: Here, we present a case of adrenal insufficiency and hypoparathyroidism associated with LV systolic dysfunction whose cardiac findings improved completely with hydrocortisone and calcitriol treatments. Our case is the second reported case of APS1 presenting with LV dysfunction.
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Objectives: This study aims to investigate the clinical and pathological features of patients with differentiated thyroid cancer (DTC) treated at our tertiary care institution. Methods: Thirty-two children and adolescents followed up with the diagnosis of DTC between 2001 and 2017 were enrolled. We classified patients with DTC into two groups as below and above 10 years of age, and compared their clinical and pathological features. Results: The mean age at presentation was 11.2±4 years. The female/male ratio was 7 (28:4). The diagnosis was papillary thyroid cancer (PTC) in 90.6% (n=29). The frequencies of lymph node and pulmonary metastases were 53.1% and 21.8%, respectively. The groups were comparable in terms of gender, initial clinical signs and tumor histopathology. The mean tumor size was greater in the younger age group (p=0.008). However, there was no difference between the two groups in terms of lymph node and pulmonary metastases. The pathological parameters associated with tumor aggressiveness were also similar between the groups, except lymphovascular invasion. Lymphovascular invasion was more frequent in the younger age group (p=0.01). Patients with lymph node and pulmonary metastases were more likely to have extrathyroidal extension and lymphovascular invasion. Conclusion: PTC was the most common type of DTC and presented with considerable rates of lymph node and pulmonary metastases. Tumor size was greater and lymphovascular invasion was more common in younger patients. Overall prognosis was favorable despite high rates of lymph node and pulmonary metastases.
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BACKGROUND: Transient hypothyroxinemia of prematurity (THOP) is defined as a low level of circulating thyroxine (T4), despite low or normal thyroid-stimulating hormone (TSH) levels. AIMS: We aimed to evaluate the incidence of THOP, the clinical and laboratory findings of preterm infants with this condition and the levothyroxine (L-T4) treatment. METHODS: Preterm infants (n = 181) delivered at 24-34 weeks of gestation were evaluated by their thyroid function tests that were performed between the 10th and 20th days of postnatal life and interpreted according to the gestational age (GA) references. Clinical and laboratory characteristics of the patients with THOP and normal thyroid function tests were compared. Patients with THOP and treated with L-T4 were compared with the ones who were not regarding laboratory, and clinical characteristics. RESULTS: Incidence of hypothyroxinemia of prematurity was 45.8% (n = 83). Euthyroidism, primary hypothyroidism, and subclinical hypothyroidism were diagnosed in 47.5% (n = 86), 5% (n = 9) and 1.7% (n = 3) of the patients, respectively. Mean birth weight (BW) and GA were significantly lower in the hypothyroxinemia group than in the euthyroid group (p < 0.001). L-T4 was started in 43% (n = 36) of the patients with THOP. Treatment initiation rate was 44.4% (n = 16) in 24-27 wk, 41.6% (n = 15) in 28-30 wk, and 13.8% (n = 5) in 31-34 wk. As the GA increased, the incidence of THOP and the rate of treatment initiation decreased (p < 0.001). The lowest free thyroxine (FT4) cut-off value was 0.72 ng/dl in the treated group. In addition, incidences of vancomycin + amikacin, caffeine, dopamine treatments, RDS, IVH, BPD, central catheter, FFP transfusion, and ventilator support were higher in the treated group (P < 0.05). CONCLUSION: This study revealed that prevalence of THOP increased as the GA and BW decreased. As the GA decreased, THOP patients requiring L-T4 treatment increased. Additionally, association with comorbid diseases increased the requirement of treatment.
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Hipotireoidismo , Doenças do Recém-Nascido , Doenças Metabólicas , Recém-Nascido , Lactente , Humanos , Tiroxina/uso terapêutico , Recém-Nascido Prematuro , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/epidemiologia , Idade Gestacional , Peso ao NascerRESUMO
OBJECTIVE: Mercury poisoning is a condition with multiple-organ dysfunction that has effects on the central nervous system, gastrointestinal system, cardiovascular system, skin, lungs, and kidneys. It can be fatal or may result in sequelae such as neurological disturbances, if treated late or left untreated. The endocrinological effects of mercury exposure are not well-known. We aimed to evaluate patients with mercury poisoning. MATERIALS AND METHODS: A total of 6 cases of mercury poisoning from 3 families were included in the study. Clinical, laboratory, and follow-up data were recorded. RESULTS: Thyroid dysfunction was presented as high thyroid hormones and normal thyrotropin level (unsuppressed) in 5 cases (83.3%). On the other hand, pheochromocytoma-like syndrome was detected in 5 cases (83.3%) with hypertension. The 4 cases were the first to use methimazole for mercury poisoning due to tachycardia and hypertension despite antihypertensive treatment due to catecholamine excess and thyroid dysfunction. Hyponatremia was detected in 3 cases (50%). CONCLUSION: Mercury poisoning is difficult to diagnose because it is rare and presents with nonspecific physical and laboratory findings. Early diagnosis and providing appropriate treatment are essential in order to prevent sequelae. Mercury poisoning should be considered in patients with unexplained hypertension and tachycardia suggesting the involvement of thyroid hormones and catecholamines.
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OBJECTIVE: Spexin (SPX) is a novel peptide implicated in food intake and satiety. SPX levels are reduced in obese patients. AIM: This study aimed to compare serum SPX levels in obese adolescents versus healthy controls and to assess the associations of metabolic syndrome (metS) antecedents with serum SPX levels. METHODS: Eighty consecutive obese adolescents aged 10-18 years and 80 healthy peers were enrolled. Anthropometric measurements, pubertal examinations, and clinical blood pressure measurements were performed. Fasting blood samples were drawn for glucose, insulin, lipids, uric acid, alanine aminotransferase (ALT), and SPX. metS was diagnosed using International Diabetes Federation criteria. Associations of serum SPX with clinical and laboratory variables were assessed. RESULTS: Obese adolescents had lower serum SPX levels than healthy peers (50 pg/mL [25-75% IQR: 25-98 pg/mL] and 67.0 pg/mL [25-75% IQR: 32.5-126.0 pg/mL]; respectively, p = 0.035). Twenty (25%) obese adolescents were diagnosed as having metS. Obese adolescents with metS had lower SPX than those without metS (24.5 pg/mL [25-75% IQR: 15.3-49.5 pg/mL] and 69.0 pg/mL [25-75% IQR: 42.0-142.0 pg/mL]; respectively, p < 0.0001). The frequencies of hyperuricemia, IR, and elevated ALT were similar in obese adolescents with metS and those without metS (p > 0.05 for all). Serum uric acid levels were correlated significantly with serum SPX after correcting for BMI and HOMA-IR (r = -0.41, p < 0.05). A serum SPX level at a cutoff level of 49.5 pg/mL predicted the presence of metS in obese adolescents with 75% sensitivity and 71% specificity. CONCLUSIONS: Obese adolescents have reduced SPX levels, and this reduction is more pronounced in those with metS. Further research is needed to verify the utility of SPX as a biomarker in the diagnosis of metS in obese adolescents.
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Resistência à Insulina , Síndrome Metabólica , Obesidade Infantil , Adolescente , Criança , Humanos , Insulina , Obesidade Infantil/complicações , Ácido ÚricoRESUMO
OBJECTIVES: Wolfram syndrome (WS) is a rarely seen autosomal recessive multisystem neurodegenerative disorder caused by mutations in the WFS1 gene. CASE PRESENTATION: Three sisters with WS had diabetes mellitus (DM) at 4 years of age and optic atrophy. In addition, the first case had hearing impairment, and the second case had diabetes insipidus and urinary incontinence. Linagliptin was administered to the first case as add-on therapy to intensive insulin treatment 15 years after the onset of DM, and her insulin need showed a dramatic decrease. The third case had a remission phase one month after the onset of DM. CONCLUSIONS: Even in cases with the same mutation, symptoms and findings may widely vary in WS. Remission of diabetes has rarely been reported in WS. Also, this report describes the first trial of a dipeptidyl peptidase-4 inhibitor in a patient with WS which provided a decrease in exogenous insulin need.
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Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Insulina/uso terapêutico , Proteínas de Membrana/genética , Mutação , Síndrome de Wolfram/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Linhagem , Prognóstico , Indução de Remissão , Síndrome de Wolfram/metabolismo , Síndrome de Wolfram/patologiaRESUMO
OBJECTIVE: We hypothesized that diabetic kidney disease (DKD) begins early, before albuminuria occurs. We therefore aimed to assess potential early urinary biomarkers of DKD in normoalbuminuric and normotensive children and adolescents with type 1 diabetes (T1D) to evaluate the relationship between these markers and clinical and laboratory risk factors for DKD. METHODS: This cross-sectional study included 75 children and adolescents with T1D (62% females, mean age 13.9 ± 3.2 years) with normoalbuminuria (an albumin/creatinine ratio [ACR] below 30 mg/g creatinine). Fifty-five age- and sex-matched healthy children and adolescents served as controls. For the assessment of early DKD, urinary levels of angiotensinogen (AGT), transferrin, nephrin, vascular endothelial growth factor-A (VEGF-A), and kidney injury molecule-1 (KIM-1) were measured in adequately collected 24-h urine samples using enzyme-linked immunoassays. RESULTS: The mean disease duration was 7.3 ± 3.2 (range 2.1-15.7) years, and the mean HbA1c level was 8.8 ± 1.4%. The median levels of urine VEGF-A/Cr, AGT/Cr, and transferrin/Cr were significantly higher in normoalbuminuric patients with T1D, compared with those of controls (p < 0.001, p = 0.02, and p = 0.001, respectively), but there was no difference in nephrin/Cr and KIM-1/Cr between the 2 groups. Although none of the patients had albuminuria, the median level of urine ACR was significantly higher in the patient group than the control group (p = 0.003). The ACR was positively correlated with glomerular filtration rate (GFR). Urinary transferrin/Cr, AGT/Cr, and VEGF-A/Cr were significantly correlated with ACR, but not with either GFR or diabetic risk factors including HbA1c or disease duration. CONCLUSION: Normoalbuminuric and normotensive children and adolescents with T1D have elevated urinary VEGF, AGT, and transferrin levels, which may indicate the development of DKD before albuminuria occurs.
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Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , Adolescente , Angiotensinogênio , Biomarcadores , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Transferrina , Fator A de Crescimento do Endotélio VascularRESUMO
Corticosterone methyloxidase deficiency type 2 is an autosomal recessive disorder presenting with salt loss and failure to thrive in early childhood and is caused by inactivating mutations of the CYP11B2 gene. Herein, we describe four Turkish patients from two families who had clinical and hormonal features compatible with corticosterone methyloxidase deficiency and all had inherited novel CYP11B2 variants. All of the patients presented with vomiting, failure to thrive and severe dehydration, except one patient with only failure to thrive. Biochemical studies showed hyponatremia, hyperkalemia and acidosis. All patients had normal cortisol response to adrenocorticotropic hormone stimulation test and had elevated plasma renin activity with low aldosterone levels. Three patients from the same family were found to harbor a novel homozygous variant c.1175T>C (p.Leu392Pro) and a known homozygous variant c.788T>A (p.Ile263Asn) in the CYP11B2 gene. The fourth patient had a novel homozygous variant c.666_667delCT (p.Phe223ProfsTer35) in the CYP11B2 gene which caused a frame shift, forming a stop codon. Corticosterone methyloxidase deficiency should be considered as a differential diagnosis in patients presenting with hyponatremia, hyperkalemia and growth retardation, and it should not be forgotten that this condition is life-threatening if untreated. Genetic analyses are helpful in diagnosis of the patients and their relatives. Family screening is important for an early diagnosis and treatment. In our cases, previously unreported novel variants were identified which are likely to be associated with the disease.
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Citocromo P-450 CYP11B2/genética , Hipoaldosteronismo/genética , Pré-Escolar , Feminino , Humanos , Hipoaldosteronismo/metabolismo , Hipoaldosteronismo/fisiopatologia , Lactente , Masculino , LinhagemRESUMO
Although it is well-known that autoimmune thyroid diseases are more common in most of the autoimmune connective tissue diseases, the relationship between autoinflammatory diseases and autoimmune thyroid diseases has not well-evaluated yet and still remains unclear. The aim of this study was to investigate the frequency of autoimmune diseases of the thyroid gland and to evaluate thyroid function tests in children with familial Mediterranean fever. Thyroxine, thyroid-stimulating hormone, and thyroid autoimmune markers such as thyroid peroxidase and thyroglobulin antibodies, and thyroid ultrasound findings of 133 patients with familial Mediterranean fever and 70 healthy controls were evaluated. Serum levels of thyroid-stimulating hormone, free thyroxine, and thyroid autoimmunity markers were similar in patients with familial Mediterranean fever compared with healthy controls. There was no relationship between the duration of the disease and thyroid-stimulating hormone, free thyroxine, anti-thyroid peroxidase, and anti-thyroglobulin levels. This study revealed that incidence of thyroid dysfunction and autoimmunity is not increased in patients with familial Mediterranean fever. In conclusion, routine screening of serum thyroid function tests and thyroid antibody levels is not required in patients with familial Mediterranean fever in the absence of clinical symptoms or family history. Key Points ⢠It is well-known that autoimmune thyroid diseases are common in autoimmune diseases. ⢠The relationship between autoimmune thyroid diseases and autoinflammatory diseases like familial Mediterranean fever is still unclear. ⢠In this study, we report the similar frequency of the autoinflammatory thyroid diseases in patients with familial Mediterranean fever and healthy controls. ⢠A routine screening of serum thyroid function tests and thyroid antibody levels may not be required in patients with familial Mediterranean fever in the absence of clinical symptoms or family history.
Assuntos
Febre Familiar do Mediterrâneo , Doenças da Glândula Tireoide , Criança , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/epidemiologia , Humanos , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologia , Tireotropina , TiroxinaRESUMO
Objective: To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey. Methods: The data of 52 PWS patients from ten centers was retrospectively analyzed. A nation-wide, web-based data system was used for data collection. Demographic, clinical, genetic, and laboratory data and follow-up information of the patients were evaluated. Results: The median age of patients at presentation was 1.5 years, and 50% were females. Genetic analysis showed microdeletion in 69.2%, uniparental disomy in 11.5%, imprinting defect in 1.9% and methylation abnormality in 17.3%. Hypotonia (55.7%), feeding difficulties (36.5%) and obesity (30.7%) were the most common complaints. Cryptorchidism and micropenis were present in 69.2% and 15.3% of males, respectively. At presentation, 25% had short stature, 44.2% were obese, 9.6% were overweight and 17.3% were underweight. Median age of obese patients was significantly higher than underweight patients. Central hypothyroidism and adrenal insufficiency were present in 30.7% and 4.7%, respectively. Hypogonadism was present in 75% at normal age of puberty. GH treatment was started in 40% at a mean age of 4.7±2.7 years. After two years of GH treatment, a significant increase in height SDS was observed. However, body mass index (BMI) standard deviation (SDS) remained unchanged. Conclusion: The most frequent complaints were hypotonia and feeding difficulty at first presentation. Obesity was the initial finding in 44.2%. GH treatment was started in less than half of the patients. While GH treatment significantly increased height SDS, BMI SDS remained unchanged, possibly due to the relatively older age at GH start.