RESUMO
BACKGROUND: Mycophenolate mofetil (MMF) plays an increasingly important role in the treatment of children with nephrotic syndrome, especially in steroid sparing protocols. Recent publications show the relationship of exposure to its active moiety mycophenolic acid (MPA) and clinical efficacy. Performance of full-time pharmacokinetic (PK) profiles, however, is inconvenient and laborious. Established limited sampling strategies (LSS) to estimate the area under the concentration (AUC) versus time curve of MPA (MPA-AUC) in pediatric renal transplant recipients cannot be easily transferred to children suffering from nephrotic syndrome, mainly because of the lack of concomitant immunosuppressive therapy. We therefore aimed for the generation and validation of a LSS to estimate MPA exposure to facilitate therapeutic drug monitoring in children with nephrotic syndrome. METHODS: We performed 27 complete PK profiles in 23 children in remission [mean age (±SD):12.3 ± 4.26 years] to generate and validate an LSS. Sampling time points were before administration (C0) and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours after the administration of MMF. MPA was measured by enzyme multiplied immunoassay technique. There was no concomitant treatment with calcineurin inhibitors. RESULTS: Mean daily dose of MMF was 927 ± 209 mg/m of body surface area resulting in a mean MPA-AUC0-12 value of 59.2 ± 29.3 mg × h/L and a predose level of 3.03 ± 2.24 mg/L. Between-patient variability of dose-normalized MPA-AUC0-12 was high (coefficient of variation: 45.5%). Correlation of predose levels with the corresponding MPA-AUC0-12 was moderate (r = 0.59) in a subgroup of 18 patients (20 PK profiles, generation group). An algorithm based on 3 PK sampling time points during the first 2 hours after MMF dosing (estimated AUC0-12 = 8.7 + 4.63 × C0 + 1.90 × C1 + 1.52 × C2) was able to predict MPA-AUC with a low percentage prediction error (3.88%) and a good correlation of determination (r = 0.90). Validation of this algorithm in a randomized separate group of 6 patients (7 PK profiles, validation group) resulted in comparably good correlation (r = 0.95) and low percentage prediction error (5.57%). CONCLUSIONS: An abbreviated profile within the first 2 hours after MMF dosing gives a good estimate of MPA exposure in children with nephrotic syndrome and hence has the potential to optimize MMF therapy.
Assuntos
Monitoramento de Medicamentos/métodos , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/uso terapêutico , Síndrome Nefrótica/sangue , Adolescente , Criança , Feminino , Humanos , Masculino , Ácido Micofenólico/sangueRESUMO
BACKGROUND: Myb-like, SWIRM, and MPN domains 1 (MYSM1) is a transcriptional regulator mediating histone deubiquitination. Its role in human immunity and hematopoiesis is poorly understood. OBJECTIVES: We sought to investigate the clinical, cellular, and molecular features in 2 siblings presenting with progressive bone marrow failure (BMF), immunodeficiency, and developmental aberrations. METHODS: We performed genome-wide homozygosity mapping, whole-exome and Sanger sequencing, immunophenotyping studies, and analysis of genotoxic stress responses. p38 activation, reactive oxygen species levels, rate of apoptosis and clonogenic survival, and growth in immune and nonimmune cells were assessed. The outcome of allogeneic hematopoietic stem cell transplantation (HSCT) was monitored. RESULTS: We report 2 patients with progressive BMF associated with myelodysplastic features, immunodeficiency affecting B cells and neutrophil granulocytes, and complex developmental aberrations, including mild skeletal anomalies, neurocognitive developmental delay, and cataracts. Whole-exome sequencing revealed a homozygous premature stop codon mutation in the gene encoding MYSM1. MYSM1-deficient cells are characterized by increased sensitivity to genotoxic stress associated with sustained induction of phosphorylated p38 protein, increased reactive oxygen species production, and decreased survival following UV light-induced DNA damage. Both patients were successfully treated with allogeneic HSCT with sustained reconstitution of hematopoietic defects. CONCLUSIONS: Here we show that MYSM1 deficiency is associated with developmental aberrations, progressive BMF with myelodysplastic features, and increased susceptibility to genotoxic stress. HSCT represents a curative therapy for patients with MYSM1 deficiency.
Assuntos
Doenças da Medula Óssea/imunologia , Dano ao DNA/imunologia , Proteínas de Ligação a DNA/metabolismo , Deficiências do Desenvolvimento/imunologia , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência/imunologia , Fatores de Transcrição/metabolismo , Células Cultivadas , Consanguinidade , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Estudo de Associação Genômica Ampla , Genótipo , Histonas/metabolismo , Humanos , Linhagem , Deleção de Sequência/genética , Transativadores , Fatores de Transcrição/genética , Proteases Específicas de Ubiquitina , Ubiquitinação , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoAssuntos
Atresia das Cóanas/genética , Fenda Labial/genética , Fissura Palatina/genética , Displasia Ectodérmica/genética , Anormalidades do Olho/genética , Pálpebras/anormalidades , Mutação , Dermatopatias/genética , Pele/patologia , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Atresia das Cóanas/diagnóstico , Fenda Labial/diagnóstico , Fissura Palatina/diagnóstico , Análise Mutacional de DNA , Displasia Ectodérmica/diagnóstico , Anormalidades do Olho/diagnóstico , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Fenótipo , Dermatopatias/diagnósticoRESUMO
UNLABELLED: Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), also termed Hashimoto's encephalopathy (HE), is a rare immune-mediated disorder and is also affecting children and adolescents. It is characterized by altered mental status, seizures, and cognitive dysfunction. Therapeutic options include steroid treatment and prognosis range from complete recovery, a relapsing course to long-term cognitive sequelae. We describe a previously healthy 13-year-old girl presenting to the emergency room with coma and refractory status epilepticus. Generalized tonic-clonic seizures persisted after pre-hospital infusion of antiepileptic medication. She was found to have highly elevated levels of thyroid-stimulating hormone and anti-thyroid peroxidase antibodies not only in blood but also in cerebrospinal fluid while showing negative results for traumatic, infectious, metabolic, toxic, neoplastic, or other known specific autoimmune diseases. Cranial neuroimaging revealed no abnormality. A diagnosis of SREAT was established, and the patient improved rapidly on corticosteroids and levothyroxine therapy. However, 3 months after the discontinuation of steroid treatment, the girl relapsed. The current literature regarding SREAT is reviewed and summarized. CONCLUSION: In children with SREAT, early diagnosis and treatment with corticosteroids is crucial and can lead to rapid clinical improvement. Clinicians should be aware of this uncommon but treatable condition, especially in female adolescents with unexplained seizures or an encephalopathic state.
Assuntos
Encefalopatias/diagnóstico , Coma/etiologia , Doença de Hashimoto/diagnóstico , Estado Epiléptico/etiologia , Adolescente , Encefalopatias/complicações , Encefalite , Feminino , Doença de Hashimoto/complicações , HumanosRESUMO
Turner's syndrome (TS) is a sex chromosome disorder caused by a partial loss, complete absence or structural abnormality of one X chromosome in females. Special ocular features are often found. Some of the abnormalities are only cosmetic, such as the abnormalities of the eyelashes. The present prospective study with 12 TS and 12 control patients demonstrates the higher number of eyelashes as well as the greater vertical distance between the roots of the eyelashes in patients with TS compared with the control group. Increased awareness of this ophthalmological abnormality could be an additional diagnostic tool for early clinical suspicion of TS diagnosis.
RESUMO
OBJECTIVES: The most suitable biochemical markers for therapy adjustment in patients with congenital adrenal hyperplasia are controversial. 11-Oxygenated androgens are a promising new approach. The objective of this study was to investigate the diurnal rhythm of 11-ketotestosterone in children and adolescents in saliva and to correlate it with salivary 17-hydroxyprogesterone. METHODS: Fifty-one samples of steroid day-profiles from 17 patients were additionally analysed for 11-ketotestosterone, retrospectively. All patients were treated in our university outpatient clinic for paediatric endocrinology between 2020 and 2022. Steroid day-profiles of 17 patients could be examined. The cohort showed a balanced sex ratio. The median age was 13 years. The measurements for 17-hydroxyprogesterone were carried out during routine care by immunoassay. The measurements of 11-ketotestosterone were performed from frozen saliva samples using an implemented in-house protocol for liquid chromatography-tandem mass spectrometry (LC-MS/MS). The most important outcome were the absolute values for 11-ketotestosterone, their diurnal rhythmicity and the correlation with 17-hydroxyprogesterone. RESULTS: Both steroids show a circadian diurnal rhythm. 17-hydroxyprogesterone and 11-ketotestosterone correlate significantly. 11-Ketotestosterone showed a positive correlation with BMI at all times of the day. CONCLUSIONS: 11-Ketotestosterone shows circadian rhythmicity in our cohort and correlates with 17-hydroxyprogesterone. These findings serve as an important basis for prospective research into 11-oxygenated androgens as therapeutic markers in paediatrics. However, 11-ketotestosterone appears to be very dependent on BMI.
Assuntos
17-alfa-Hidroxiprogesterona , Hiperplasia Suprarrenal Congênita , Ritmo Circadiano , Saliva , Testosterona , Testosterona/análogos & derivados , Humanos , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/metabolismo , Feminino , Saliva/química , Saliva/metabolismo , 17-alfa-Hidroxiprogesterona/análise , 17-alfa-Hidroxiprogesterona/metabolismo , Masculino , Adolescente , Criança , Testosterona/análise , Testosterona/metabolismo , Estudos Retrospectivos , Biomarcadores/análise , Biomarcadores/metabolismo , Prognóstico , Seguimentos , Pré-Escolar , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: Patients with congenital adrenal hyperplasia (CAH) require life-long glucocorticoid replacement, including stress dosing (SD). This study prospectively assessed adrenal crisis (AC) incidence, frequency, and details of SD and disease knowledge in adult and paediatric patients and their parents. DESIGN: Prospective, observational study. METHODS: Data on AC and SD were collected via a patient diary. In case of AC, medical records were reviewed and patient interviews conducted. Adherence to sick day rules of the German Society of Endocrinology (DGE) and disease knowledge using the German version of the CAH knowledge assessment questionnaire (CAHKAQ) were assessed. RESULTS: In 187 adult patients, the AC incidence was 8.4 per 100 patient years (py) and 5.1 in 100â py in 38 children. In adults, 195.4 SD episodes per 100â py were recorded, in children 169.7 per 100â py. In children 72.3% and in adults 34.8%, SD was performed according to the recommendations. Children scored higher on the CAHKAQ than adults (18.0 [1.0] vs 16.0 [4.0]; P = .001). In adults, there was a positive correlation of the frequency of SD and the incidence of AC (r = .235, P = .011) and CAHKAQ score (r = .233, P = .014), and between the incidence of AC and CAHKAQ (r = .193, P = .026). CONCLUSION: The AC incidence and frequency of SD in children and adults with CAH are high. In contrast to the paediatric cohort, the majority of SD in adults was not in accordance with the DGE recommendations, underlining the need for structured and repeated education of patients with particular focus on transition.
Assuntos
Hiperplasia Suprarrenal Congênita , Insuficiência Adrenal , Adulto , Criança , Humanos , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/complicações , Estudos Prospectivos , Insuficiência Adrenal/epidemiologia , Insuficiência Adrenal/etiologia , Glucocorticoides/uso terapêutico , Doença AgudaRESUMO
INTRODUCTION: Children with classical congenital adrenal hyperplasia (CAH) have an impaired steroid synthesis due to 21-hydroxylase dysfunction and require glucocorticoid replacement. Therapy management in children and adolescent is based on auxological, clinical, and laboratory monitoring. The measurement of steroid precursors in saliva is particularly suitable for patients in pediatric endocrinology. METHODS: In this retrospective and longitudinal study of 22 patients with CAH, we analyzed 546 saliva samples for 17-hydroxyprogesterone (s17-OHP) in prepubertal/pubertal patients. Additionally, we correlated them with auxological parameters such as delta-height standard deviation score. RESULTS: We analyzed a median observation period of 5.5 years per patient. No precocious pubertal development, abnormal vital signs, or Addison crises occurred. 57.1% of the samples were collected in prepubertal children. 72.5% of s17-OHP values were attributed to normal auxological development. In the total cohort, the median values for s17-OHP were 67.8 pg/mL (morning), 42.5 pg/mL (noon), and 25.0 pg/mL (evening). The difference in values between the group of normal/abnormal growing patients and between prepubertal/pubertal patients was not significant. DISCUSSION/CONCLUSION: The measurement of s17-OHP is an important sub-aspect in the overall assessment of treatment response in CAH. It can provide an indication of over-/undertreatment and allows the assessment of day profiles, especially in phases of changing (e.g., puberty) steroid requirements. We present here observational data from a larger cohort with longitudinal multiple measurements of s17-OHP. The values do not allow a significant differentiation between normal and abnormal growth or pubertal status. Thus, relying solely on s17-OHP is not advisable.
Assuntos
Hiperplasia Suprarrenal Congênita , Adolescente , Criança , Humanos , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , 17-alfa-Hidroxiprogesterona , Estudos Retrospectivos , Estudos Longitudinais , EsteroidesRESUMO
OBJECTIVES: Children with classical congenital adrenal hyperplasia (CAH) require glucocorticoid (GC) substitution due to impaired cortisol synthesis. To avoid over- or undertreatment, one has to consider auxology as well as biochemical parameters for adrenal derived steroids like androstenedione (A4) and 17-hydroxyprogesterone (17-OHP). There are no established reference values for A4 and 17-OHP in CAH. METHODS: We performed a retrospective study in 53 prepubertal patients with CAH. Datasets of patients were included if the plasma A4 values of the respective clinical visit were under the limit of quantification. Related 17-OHP values were extracted as well as height/length, weight, dose of hydrocortisone, HC regimen, bone age and stages of pubertal development. RESULTS: Median hydrocortisone doses were in most observations within the recommended reference ranges. Hydrocortisone has a significant negative influence on 17-OHP values and HSDS. Age has a positive significant influence on 17-OHP, BMI-SDS, and HSDS. Median height standard-deviation-score (HSDS) was beneath 0 at all times, but showed an increasing trend in both sexes. Median body mass index standard-deviation-score (BMI-SDS) was above 0 at all times and showed an increasing trend as well. CONCLUSIONS: With guideline-compliant doses of hydrocortisone, suppression of A4 at the respective time of day is possible in prepubertal children. Although HC has a significant negative influence on HSDS, increasing values for HSDS and HC are observed with increasing age. Thus, A4 suppression at the respective time point does not hinder regular growth. An increase in body mass index can already be observed as early as in prepuberty.
RESUMO
BACKGROUND: Glucocorticoids are crucial components of the treatment of leukemia and lymphoma. High doses can lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis and be causative for an impaired stress response during infection. This study aims to evaluate the cortisol response in pediatric oncologic patients during febrile episodes. METHODS: Totally, 75 children and adolescents (5 months-18 years) with fever during chemotherapy were consecutively enrolled in this study. In total, 47 patients received glucocorticoids as part of their treatment. Random serum cortisol and adrenocorticotropic hormone (ACTH) were analyzed in every patient. A low cortisol response (LCR) was defined as a cortisol level < 14.6 µg/dL. RESULTS: In total, 52 (69%) patients had a cortisol level < 14.6 µg/dL during fever. There was no significant difference between patients who received glucocorticoids and those who did not. Significantly lower cortisol levels were measured ≤7 days after last glucocorticoid intake compared to later time points. Nearly all patients treated with dexamethasone or prophylactic posaconazole demonstrated a LCR under stress (fever). CONCLUSION: The incidence of an impaired HPA axis in pediatric cancer patients might be underestimated since 69% of the children in our study had a LCR during fever. Intake of dexamethasone, posaconazole and a time period of ≤7 days from the last glucocorticoid intake were additional risk factors for an LCR. However, we could not confirm that patients with a LCR fared worse than patients with a high cortisol response (HCR). Therefore, a different cortisol threshold may be necessary for defining an impaired HPA axis in febrile oncologic patients without concomitant symptoms of AI.
Assuntos
Hidrocortisona , Neoplasias , Adolescente , Humanos , Criança , Glucocorticoides/efeitos adversos , Dexametasona/efeitos adversos , Sistema Hipotálamo-Hipofisário/fisiologia , Estudos Prospectivos , Sistema Hipófise-Suprarrenal , Neoplasias/complicações , Neoplasias/tratamento farmacológicoRESUMO
It has been postulated that in patients with congenital adrenal hyperplasia (CAH) with salt wasting (SW), fludrocortisone needs might be higher in those on synthetic glucocorticoid replacement therapy in comparison to conventional hydrocortisone due to the lower mineralocorticoid activity. Here we report the results of a cross-sectional single center study comparing mineralocorticoid needs between patients taking synthetic glucocorticoids (S-GC) (N = 24) and those on conventional hydrocortisone (HC) (N = 16). We could show that while both groups took comparable HC-equivalent dosages, there was no significant difference in FC dosage (GC: 0.075 mg; IQR 0.05-0.1; HC: 0.1 mg; IQR 0.05-0.1; p = 0.713). Although there was a trend for higher renin levels in the S-GC group (67.1 µU/ml; IQR 40.5-113.9 vs. 40.4 IQR 14.2-73.1; p = 0.066), this failed to reach significance. With regard to blood pressure, those taking S-GC had even significantly elevated mean systolic (125.0 mmHg, IQR 117.5-130.0 vs 116.5 mmHg IQR 111.8-124.8; p = 0.036) and diastolic (78.0 mmHg, IQR 74.3-83.8 vs 74.5mmHG, IQR 69.3-76.0; p = 0.044) during the day. Systolic dipping was however more pronounced in those on GC in comparison to those taking HC (11.3%; IQR 8.7-14.6 vs. 6.4 IQR 3.4-12.7; p = 0.031). In conclusion, we could show in this small, albeit well-balanced cohort that mineralocorticoid dosage does not significantly differ between patients receiving synthetic glucocorticoids or conventional hydrocortisone. Higher blood pressure values despite the tendency for higher renin levels in those on S-GC support the notion that the assessment of MR adequacy should be guided by the clinical picture and blood pressure on a regular basis.
Assuntos
Hiperplasia Suprarrenal Congênita , Glucocorticoides , Humanos , Adulto , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Hidrocortisona/uso terapêutico , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Mineralocorticoides/uso terapêutico , Renina , Estudos TransversaisRESUMO
Objective: Patients with congenital adrenal hyperplasia (CAH) require lifelong therapy with glucocorticoids to suppress androgen excess and substitute for deficient cortisol. An important aspect of care is the prevention of metabolic sequelae. In infants, potentially lethal nocturnal hypoglycaemia has been described. In adolescence, visceral obesity, hypertension, hyperinsulinism and insulin resistance are reported. To date, systematic studies of glucose profiles in this age group with CAH are lacking. Methods: This was a monocentric, prospective, observational study to determine the glucose profiles under different treatment regimens in a cohort of young patients with CAH. The continuous glucose monitoring device used was the latest generation FreeStyle Libre 3® sensor in blinded mode. Therapeutic and auxological data were obtained. Results: The cohort consisted of 10 children/adolescents with a mean age of 11 years. Three patients exhibited morning fasting hyperglycaemia. Overall, 6 out of 10 patients had unacceptably few total values in the desired range of 70-120 mg/dL. Tissue glucose values above 140-180 mg/dL were found in 5 of 10 patients. The mean value for glycosylated haemoglobin for the cohort was of 5.8%. All pubertal adolescents with reverse circadian regimens had significantly higher glucose levels at night. Two adolescents showed asymptomatic nocturnal hypoglycaemia. Conclusion: Most of the patients exhibited abnormalities in glucose metabolism. Two-thirds had elevated total 24h glucose values outside the age-appropriate reference values. Thus, this aspect may need to be addressed early in life by adjusting the doses, treatment regimen or dietary measures. Consequently, reverse circadian therapy regimens should be critically indicated and closely monitored due to the potential metabolic risk.
Assuntos
Hiperplasia Suprarrenal Congênita , Hipoglicemia , Lactente , Humanos , Criança , Adolescente , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/complicações , Glicemia , Estudos Prospectivos , Automonitorização da Glicemia , Hidrocortisona , Hipoglicemia/complicações , Glucose/uso terapêuticoRESUMO
OBJECTIVE: Poor growth early in life is associated with numerous adverse conditions including decreased bone mass. The aim is to investigate bone and body composition in young adults born small for gestational age (SGA). DESIGN: Observational study. PARTICIPANTS: A total of 76 young adults born SGA (34f) at a mean age of 19·68 ± 0·5 years were enrolled. METHOD: Bone mineral density (BMD), bone geometry and body composition were analysed using peripheral quantitative computed tomography. RESULTS: Adults born SGA had significantly lower z-score for height (-0.86 ± 0·87), weight (-0·61 ± 0·78) and BMI (-0·38 ± 1·04) as well as fat cross-sectional area (CSA) (-0·62 ± 0·80) compared with a healthy reference population (P < 0·05). Z-scores for trabecular and cortical BMD were normal. After correction for reduced height, z-scores for total CSA (-0·14 ± 1·11) and muscle CSA (-0·21 ± 0·99) were normal and medullary cavity (-0·71 ± 0·80) was reduced. Those with a birthweight of ≤ 1500 g had even lower height-corrected z-scores for medullary cavity (-1·12 ± 0·69) and total bone CSA (-0·58 ± 0·93) (P < 0·05). After adjustment for sex and weight, significant partial correlations were detectable between BMI at the age of 48 months and height-corrected z-scores for medullary cavity (r = 0·33, P = 0·020) and total CSA (r = 0·29, P = 0·04). CONCLUSION: Environmental factors early in life seem to influence bone geometry in adulthood. Young adults born SGA have normal total bone CSA but smaller medullary cavity. Those with very low birthweight, however, show compromised bone size development that may alter bone stability later in life.
Assuntos
Peso ao Nascer/fisiologia , Densidade Óssea/fisiologia , Adulto , Antropometria , Composição Corporal/fisiologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Masculino , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND: Cohen syndrome is a rare autosomal recessive disorder with a complex phenotype including psychomotor retardation, microcephaly, obesity with slender extremities, joint laxity, progressive chorioretinal dystrophy/myopia, intermittent isolated neutropenia, a cheerful disposition, and characteristic facial features. The COH1 gene, which contains 62 exons, is so far the only gene known to be associated with Cohen syndrome. Point mutations, deletions and duplications have been described in this gene. Oligonucleotide arrays have reached a resolution which allows the detection of intragenic deletions and duplications, especially in large genes such as COH1. METHOD AND RESULTS: High density oligonucleotide array data from patients with unexplained mental retardation (n=1523) and normal controls (n=1612) were analysed for copy number variation (CNV) changes. Intragenic heterozygous deletions in the COH1 gene were detected in three patients but no such changes were detected in the controls. Subsequent sequencing of the COH1 gene revealed point mutations in the second allele in all three patients analysed. CONCLUSION: Genome-wide CNV screening with high density arrays provides a tool to detect intragenic deletions in the COH1 gene. This report presents an example of how microarrays can be used to identify autosomal recessive syndromes and to extend the phenotypic and mutational spectrum of recessive disorders.
Assuntos
Fenótipo , Proteínas de Transporte Vesicular/genética , Sequência de Bases , Pré-Escolar , Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Feminino , Dedos/anormalidades , Dedos/patologia , Genótipo , Humanos , Lactente , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Masculino , Microcefalia/genética , Microcefalia/patologia , Dados de Sequência Molecular , Hipotonia Muscular/genética , Hipotonia Muscular/patologia , Miopia/genética , Miopia/patologia , Obesidade/genética , Obesidade/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Degeneração Retiniana , Análise de Sequência de DNARESUMO
We present a 9-year-old boy with diabetes insipidus. The boy is treated with desmopressin (DDAVP) therapy. Under this therapy, the drinking quantity and the laboratory parameters were normal. No nocturia occurred any more. In the context of a clinically mild infection with SARS-CoV-2, the duration of action of DDAVP was significantly prolonged (approximately +50%). The original dosage was then reintroduced and was still sufficient until months later. A possible connection to the infection with SARS-CoV-2 can be suspected. Our case report should make physicians who care for patients with diabetes insipidus aware of such a possible prolongation of the effect of DDAVP. More frequent monitoring may be needed in such patients to assess the risk of symptomatic dilutional hyponatremia.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Diabetes Insípido Neurogênico , Diabetes Insípido , Diabetes Mellitus , Masculino , Humanos , Criança , Desamino Arginina Vasopressina/uso terapêutico , Diabetes Insípido Neurogênico/tratamento farmacológico , SARS-CoV-2 , Meia-Vida , COVID-19/complicações , Diabetes Insípido/tratamento farmacológico , Diabetes Mellitus/induzido quimicamenteRESUMO
Thyroid-stimulating hormone is generally regarded as a standard parameter for the evaluation of thyroid function. However, relying on this hormone alone can be misleading. Therefore, thyroxine/free-thyroxine levels are used in patients with levothyroxine substitution for the adjustment of therapy. Even with normal values for free thyroxine, decreased values for the free-triiodothyronine/free-thyroxine ratio have already been described in adults. In this study, the free-triiodothyronine/free-thyroxine ratio of 25 children with congenital hypothyroidism was compared with 470 healthy children seen for other reasons and then for thyroid dysfunction. Mean free thyroxine in congenital hypothyroidism was just below the upper limit of normal and significantly higher than in control group. Mean values for free triiodothyronine showed no significant difference between the two groups. The mean value for the free triiodothyronine/free-thyroxine ratio in control group was 3.23. Significantly lower ratios were found in the congenital hypothyroidism group with a mean value of 2.5, due to higher values for free thyroxine compared to free triiodothyronine. Furthermore, an increased free triiodothyronine/free-thyroxine ratio was found at higher thyroid-stimulating hormone values due to lower values for free thyroxine. In this study, we demonstrate that the free triiodothyronine/free-thyroxine ratio was significantly lower in children with congenital hypothyroidism compared to the control group. This is most likely due to the higher values for free thyroxine in this group compared to similar values for free triiodothyronine in both groups. Further studies with differentiated thyroid hormone therapy are needed in order to understand the role of peripheral euthyroidism.
RESUMO
OBJECTIVES: Consumptive hypothyroidism may occur in hepatic hemangioendothelioma. The altered expression of deiodinases inactivates peripheral thyroid hormones. As a result, serum levels of free triiodothyronine and free thyroxine are reduced to varying degrees. There are no established recommendations for the dosage of sirolimus for this particular indication. We describe for the first time the course of treatment with low-dose sirolimus. CASE PRESENTATION: We present a 5-week-old infant with hepatic hemangioendothelioma and severe consumptive hypothyroidism. Due to hepatic infiltration he showed signs of right heart strain. Therapy of hemangioendothelioma was initiated with propranolol and, in the absence of response, methylprednisolone was added. Treatment was continued with low-dose sirolimus (due to side effects) and propranolol. Hypothyroidism was managed with levothyroxine and liothyronine. CONCLUSIONS: Consumptive hypothyroidism due to cutaneous hemangioma and hepatic hemangioendothelioma can be managed with propranolol and low-dose sirolimus. Treatment of severe hypothyroidism may require a combinational therapy by substitution of both T3 and T4.
Assuntos
Hemangioendotelioma , Hipotireoidismo , Neoplasias Hepáticas , Lactente , Masculino , Humanos , Propranolol/uso terapêutico , Neoplasias Hepáticas/complicações , Hipotireoidismo/complicações , Hipotireoidismo/tratamento farmacológico , Tiroxina , Hemangioendotelioma/complicações , Hemangioendotelioma/tratamento farmacológico , Tri-Iodotironina , Hormônios Tireóideos/uso terapêutico , Sirolimo/uso terapêuticoRESUMO
INTRODUCTION: The occurrence of ectopic prostate tissue in the female genital tract is rare and has only been described sporadically. The origin of these lesions is unclear, but their appearance seems to be associated with various forms of androgen excess, including androgen therapy for transgender treatment or disorders of sex development, such as classic congenital adrenal hyperplasia (CAH). This is the first described case of ectopic prostate tissue in the cervix uteri of a 46,XX patient with a confirmed diagnosis of non-classic CAH due to 21-OHD and a history of mild adrenal androgen excess. CASE PRESENTATION: We describe a 34-year-old patient with a genetic diagnosis of non-classic CAH due to 21-hydroxylase deficiency (21-OHD) with a female karyo- and phenotype and a history of mild adrenal androgen excess. Due to dysplasia in the cervical smear, conization had to be performed, revealing ectopic prostate tissue in the cervix uteri of the patient. CONCLUSIONS: An association between androgen excess and the occurrence of prostate tissue is likely and should therefore be considered as a differential diagnosis for atypical tissue in the female genital tract.
RESUMO
BACKGROUND: Type 1 diabetes mellitus is a generally accepted atherogenic risk factor. The aim of this prospective longitudinal study was to evaluate changes in carotid intima media thickness (cIMT) in children and adolescents with type 1 diabetes mellitus (T1DM) using standardized methods. METHODS: We re-evaluated cIMT in 70 (38 f) of initial 150 (80 f) patients with T1DM after 4 years. At re-evaluation, mean (±SD) age was 16.45±2.59 y, mean diabetes duration was 9.2±3.24 y and patients had a mean HbA1c of 8.14±1.06%. RESULTS: Mean cIMT z-scores increased significantly during 4 years (0.58±0.75, p<0.001) as well as BMI-z-score (0.41±0.81, p<0.01), systolic blood pressure (0.77±1.15, p<0.01) and HbA1c (0.90±1.07, <0.001). In a linear regression model systolic blood pressure z-score at first measurement (0.02, CI: 0.01, 0.04) was a significant predictor for the mean effect on cIMT z-score. In a logistic regression model significant risk factors for an increase in IMT of ≥1.5 z-scores were BMI z-scores (OR: 3.02, CI:1.11, 10.14), diabetes duration (OR:1.32, CI:1.04, 1.77) and systolic blood pressure (OR: 1.14, CI: 1.04, 1.27) at first measurement each. CONCLUSIONS: Longitudinal cIMT measurements revealed progression in subclinical atherosclerosis during a four year period in diabetic children and adolescents. Systolic blood pressure and BMI were related to cIMT increment. Control of these risk factors by lifestyle and medical intervention may prevent progression of cIMT in diabetic children.
Assuntos
Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Progressão da Doença , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Adolescente , Criança , Estudos Transversais , Feminino , Seguimentos , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Fatores de Risco , Fatores de Tempo , UltrassonografiaRESUMO
The LHX3 LIM-homeodomain transcription factor gene is required for normal pituitary and motoneuron development. LHX3 mutations are associated with growth hormone, prolactin, gonadotropin, and TSH deficiency; abnormal pituitary morphology; and may be accompanied with limited neck rotation and sensorineural hearing loss. We report on a boy, who presented with hypoglycemia in the newborn period. He is the second child of healthy unrelated parents. Short neck, growth hormone deficiency, and central hypothyroidism were diagnosed at a general pediatric hospital. Growth hormone and levothyroxine treatment were started, and blood sugar normalized with this treatment. On cerebral MRI, the anterior pituitary gland was hypoplastic. Sensorineural hearing loss was diagnosed by auditory testing. During follow-up, six repeatedly low morning cortisol levels (<1 µg/dl) and low ACTH levels (<10 pg/ml) were documented, so ACTH deficiency had developed over time and therefore hydrocortisone replacement was started at 1.5 years of age. Mutation analysis of the LHX3 gene revealed a homozygous stop mutation in exon 2: c.229C>T (CGA > TGA), Arg77stop (R77X). A complete loss of function is assumed with this homozygous stop mutation. We report a novel LHX3 mutation, which is associated with combined pituitary hormone deficiency including ACTH deficiency, short neck, and sensorineural hearing loss. All patients with LHX3 defects should undergo longitudinal screening for ACTH deficiency, since corticotrope function may decline over time. All patients should have auditory testing to allow for regular speech development.