RESUMEN
A 5-month-old intact male domestic shorthair cat presenting for routine vaccinations was diagnosed with congenital hypothyroidism. His primary presenting symptom was incomplete dentition with delayed dental eruption. Congenital hypothyroidism was confirmed by baseline thyroxine (T4), free T4, and thyroid-stimulating hormone testing. The cat was treated with oral thyroid hormone supplementation and 16 weeks after initiation of therapy the cat was clinically normal with age-appropriate dentition. No surgical intervention was necessary to achieve normal dental eruption.
Asunto(s)
Enfermedades de los Gatos , Hipotiroidismo Congénito , Masculino , Gatos , Animales , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Hipotiroidismo Congénito/etiología , Hipotiroidismo Congénito/veterinaria , Tiroxina/uso terapéutico , Tirotropina , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/etiologíaRESUMEN
BACKGROUND: Permanent congenital hypothyroidism (CH) is usually a more severe type of CH. However, the molecular etiology and clinical features of permanent CH remain unclear. METHODS: We recruited 42 patients who were diagnosed with CH and followed-up after diagnosis. Demographic information and data at diagnosis and treatment were recorded. Genetic analyses were performed using whole exome sequencing. Based on the presence or absence of variants and differences in clinical features, we grouped the study participants and analyzed their characteristics. RESULTS: A total of 29 patients (69.0 %) were identified as having variants potentially related to their disease. Among the 24 patients with normal-sized thyroid gland-in-situ (GIS) or goiter, 23 (95.8 %, P < 0.001) had variants. This is compared to 18 patients with thyroid dysgenesis (TD), of which six (33.3 %) had genetic variants. We detected 55 variants in six genes, the most frequently mutated gene being DUOX2 (70.9 %). Biallelic DUOX2 variants were detected in 14 of 24 (58.3 %) GIS or goiter patients. Compared to the cases with variants, the L-T4 dose at 2 and 3 years of age and current dose were higher in the unmutated cases. At 2 years of age, patients with TD required higher doses of L-T4 supplementation. Patients with DUOX2 variants showed lower doses of L-T4 being required at 2 and 3 years of age and current. Furthermore, patients with GIS or goiter with DUOX2 variants showed lower doses of L-T4. CONCLUSIONS: Patients with CH, whether TD or GIS or goiter, are at risk of developing a permanent condition. Compared with patients with TD, the detection of variants was higher in patients with GIS or goiter. The most frequently mutated gene was DUOX2, with a biallelic type. Patients with TD required higher doses of L-T4 supplementation with age, whereas those patients with the DUOX2 variant required relatively lower doses.
Asunto(s)
Hipotiroidismo Congénito , Bocio , Disgenesias Tiroideas , Humanos , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Hipotiroidismo Congénito/genética , Oxidasas Duales/genética , NADPH Oxidasas/genética , MutaciónRESUMEN
We report a patient with congenital hypothyroidism due to athyreosis complicated by a heterozygous thyroid hormone receptor beta (THRß) gene mutation (R320L), resulting in a severe resistance to thyroid hormone beta phenotype. The proband inherited the mutant allele from his father, presenting a very mild phenotype. While the precise reason for this discrepancy remains unknown, we postulate the possibility of de novo mutation and mosaicism in the father. Correlating thyrotropin (TSH) with free thyroxine (fT4) allowed us to predict the amount of fT4 required to normalize the proband's TSH, which supported the treatment with high dose of levothyroxine.
Asunto(s)
Hipotiroidismo Congénito , Disgenesias Tiroideas , Síndrome de Resistencia a Hormonas Tiroideas , Hipotiroidismo Congénito/tratamiento farmacológico , Hipotiroidismo Congénito/genética , Humanos , Mutación , Receptores beta de Hormona Tiroidea/genética , Síndrome de Resistencia a Hormonas Tiroideas/tratamiento farmacológico , Síndrome de Resistencia a Hormonas Tiroideas/genética , Hormonas Tiroideas/uso terapéutico , Tirotropina/uso terapéutico , Tiroxina/uso terapéuticoRESUMEN
Objective: Initial high-dose sodium levothyroxine (Na-LT4) (10-15 µg/kg/day) replacement for primary congenital hypothyroidism (CH) is recommended in guidelines. However, high-dose Na-LT4 risks iatrogenic hyperthyroidism. The aim of this study was to investigate the normalizing effect of varying initial doses of Na-LT4 on serum thyroid hormone levels. Methods: Fifty-two patients were analyzed retrospectively. The patients were classified into mild (27/51.9%), moderate (11/21.1%) and severe (14/26.9%) CH, based on initial free thyroxine (fT4) levels. Time taken to achieve target hormone levels was compared within groups. Results: Initial mean Na-LT4 doses for mild, moderate and severe disease were 6.9±3.3, 9.4±2.2 and 10.2±2 µg/kg/day. Serum fT4 levels reached the upper half of normal range (>1.32 ng/dL) in a median of 16, 13 and 16 days in patients with mild, moderate and severe CH with the mean time from initial treatment to first control visit of 14.8±6 days (range 1-36). There was no significant difference in terms of time to achieve target fT4 hormone levels according to disease severity (p=0.478). Seven (25.9%), eight (72.7%) and eight (57.1%) patients experienced hyperthyroxinemia (serum fT4 >1.94 ng/dL) in the mild, moderate, and severe CH groups at the first visit, respectively (p=0.016). Conclusion: Not all patients diagnosed with CH require high-dose Na-LT4. Initial dose of Na-LT4 may be selected on the basis of pre-treatment thyroid hormone levels. Some patients with moderate and severe CH, experienced iatrogenic hyperthyroxinemia even though the dose was close to the lower limit of the recommended range in guidelines. We suggest that lower initial doses may be appropriate with closer follow-up within the first week.
Asunto(s)
Hipotiroidismo Congénito/tratamiento farmacológico , Terapia de Reemplazo de Hormonas , Tiroxina/administración & dosificación , Tiroxina/sangre , Biomarcadores/sangre , Toma de Decisiones Clínicas , Hipotiroidismo Congénito/sangre , Hipotiroidismo Congénito/diagnóstico , Femenino , Terapia de Reemplazo de Hormonas/efectos adversos , Humanos , Hipertiroxinemia/sangre , Hipertiroxinemia/inducido químicamente , Enfermedad Iatrogénica , Recién Nacido , Masculino , Tamizaje Neonatal , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Tiroxina/efectos adversos , Resultado del TratamientoRESUMEN
Congenital hypothyroidism (CH) in humans is most commonly caused by disruption of thyroid gland development (dysgenesis) or an inherited defect in thyroid hormone biosynthesis (dyshormonogenesis). CH has not been previously documented in great apes. This report describes the clinical presentation, diagnosis, and treatment of CH in a 9-mo-old male Bornean orangutan (Pongo pygmaeus) and a 6-wk-old female Sumatran orangutan (Pongo abelii). Primary CH due to thyroid dysgenesis was confirmed in the Bornean orangutan using sonography and radioisotope scintigraphy. Although commercial thyroid immunoassays are not validated for use in orangutans, in comparison to age-matched controls, thyroid-stimulating hormone level was markedly elevated, and serum thyroxine (T4) and free T4 levels were markedly decreased in both cases. Oral supplementation with levothyroxine sodium resulted in noticeable clinical improvement in both orangutans within 30 days of initiating treatment.
Asunto(s)
Enfermedades del Simio Antropoideo/congénito , Hipotiroidismo Congénito/veterinaria , Pongo/clasificación , Tiroxina/uso terapéutico , Envejecimiento , Animales , Enfermedades del Simio Antropoideo/tratamiento farmacológico , Enfermedades del Simio Antropoideo/patología , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Femenino , Masculino , Especificidad de la Especie , Tirotropina/sangre , Tiroxina/sangreRESUMEN
Congenital feline hypothyroidism was diagnosed in a 10-month-old kitten. The kitten appeared to have disproportionate dwarfism, with the clinical signs of incompletely erupted permanent dentition covered by thickened gingival tissue, short stature, a broad, flattened face, short neck, pendulous abdomen, kitten-like hair coat, and goiter. Hypothyroidism was confirmed with baseline T4, freeT4, and thyroid-stimulating hormone testing. The kitten was treated with thyroid hormone supplementation and monitored. The kitten appeared clinically like a normal healthy cat at 22 months of age on thyroid supplementation.
Asunto(s)
Enfermedades de los Gatos/diagnóstico , Hipotiroidismo Congénito/veterinaria , Tiroxina/uso terapéutico , Animales , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/patología , Gatos , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Hipotiroidismo Congénito/patología , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: Iodine is necessary for fetal thyroid development. Excess maternal intake of iodine can cause fetal hypothyroidism due to the inability to escape from the Wolff-Chaikoff effect in utero. CASE REPORT: We report a case of fetal hypothyroid goiter secondary to inadvertent excess maternal iodine ingestion from infertility supplements. The fetus was successfully treated with intra-amniotic levothyroxine injections. Serial fetal blood sampling confirmed fetal escape from the Wolff-Chaikoff effect in the mid third trimester. Early hearing test and neurodevelopmental milestones were normal. CONCLUSION: Intra-amniotic treatment of fetal hypothyroidism may decrease the rate of impaired neurodevelopment and sensorineural hearing loss.
Asunto(s)
Hipotiroidismo Congénito , Enfermedades Fetales , Bocio , Yodo/efectos adversos , Tiroxina/administración & dosificación , Adulto , Hipotiroidismo Congénito/sangre , Hipotiroidismo Congénito/inducido químicamente , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Femenino , Enfermedades Fetales/sangre , Enfermedades Fetales/inducido químicamente , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/tratamiento farmacológico , Bocio/sangre , Bocio/inducido químicamente , Bocio/diagnóstico , Bocio/tratamiento farmacológico , Humanos , Yodo/administración & dosificación , Masculino , Embarazo , Diagnóstico PrenatalRESUMEN
Context: The optimal levothyroxine (LT4) dose to treat congenital hypothyroidism (CH) remains unclear, with debate over whether higher starting doses (>10 µg/kg) are necessary and safe for a normal intelligence quotient (IQ). Objective: To examine psychomotor, metabolic, and quality of life (QoL) outcomes in patients with CH treated with a mean high initial LT4 dose. Design, settings, participants: A cross-sectional cohort study of patients with CH identified in the Berlin newborn screening program from 1979 to 2003; 76 patients with CH (mean age, 18 years; mean initial LT4 dose, 13.5 µg/kg) and 40 siblings completed the study. Main outcome measures: Psychomotor (Wechsler Intelligence Test, CNS Vital Signs), QoL (short form-36 Health Survey), anthropometric (body mass index, height), and metabolic (intima media thickness, laboratory parameters) outcomes were compared with those of healthy siblings. Mean values and percentage of episodes of elevated thyroxine (T4) and tri-jod-thyronin (T3) and suppressed thyrotropin (TSH) before age 2 years were analyzed. A meta-analysis of CH treatment studies was performed. Results: There were no significant differences in IQ, QoL, or other outcome measures in patients with CH compared with controls. Most T4 levels were high before age 2 years and during subsequent testing, but mean T3 and TSH levels remained normal. The meta-analysis showed a significant IQ difference in severe vs mild CH cases only when treatment started with an LT4 dose <10 µg/kg. Conclusions: High initial LT4 dosing was effective and safely achieved optimal cognitive development in patients with CH, including those severely affected. Supranormal T4 values during infancy were not associated with impaired IQ in adolescence.
Asunto(s)
Hipotiroidismo Congénito/tratamiento farmacológico , Inteligencia/efectos de los fármacos , Tiroxina/uso terapéutico , Adolescente , Índice de Masa Corporal , Grosor Intima-Media Carotídeo , Hipotiroidismo Congénito/sangre , Hipotiroidismo Congénito/psicología , Estudios Transversales , Femenino , Humanos , Recién Nacido , Masculino , Tamizaje Neonatal , Calidad de Vida , Tiroxina/administración & dosificación , Tiroxina/sangre , Triyodotironina/sangre , Escalas de Wechsler , Adulto JovenRESUMEN
BACKGROUND: Hemizygous mutations in the immunoglobulin superfamily member 1 (IGSF1) gene have been demonstrated to cause congenital central hypothyroidism in males. This study reports a family with a novel mutation in the IGSF1 gene located on the long arm of the X chromosome. PATIENT FINDINGS: A two-month-old boy was diagnosed with central hypothyroidism because of prolonged jaundice. A thyrotropin-releasing hormone (TRH) stimulation test indicated dysfunction in both the hypothalamus and the pituitary gland, and prompted the IGSF1 gene to be analyzed. The patient had a novel nonsense variant, c.2713C>T (p.Q905X), in exon 14 of the IGSF1 gene. Studies of the family revealed that the patient's sister and mother were heterozygous carriers of the IGSF1 mutation. The patient's maternal uncle carried the same mutation as the proband but had no overt symptoms. The mother and uncle started levothyroxine supplementation because of subclinical hypothyroidism. SUMMARY: A novel mutation (c.2713C>T, p.Q905X) of the IGSF1 gene was identified that causes congenital central hypothyroidism in a Japanese family. The findings further expand the clinical heterogeneity of this entity.
Asunto(s)
Hipotiroidismo Congénito/genética , Hipotiroidismo/genética , Inmunoglobulinas/genética , Proteínas de la Membrana/genética , Mutación , Adulto , Hipotiroidismo Congénito/tratamiento farmacológico , Análisis Mutacional de ADN , Terapia de Reemplazo de Hormonas , Humanos , Hipotiroidismo/tratamiento farmacológico , Lactante , Masculino , Linaje , Tiroxina/uso terapéuticoRESUMEN
UNLABELLED: A recent study in children suggested that levothyroxine requirements are higher in congenital than in acquired hypothyroidism but did not match for severity of disease. Here, we studied only children with congenital or acquired hypothyroidism who had an undetectable fT4 at diagnosis. There were eight girls with congenital hypothyroidism due to athyreosis and eight girls with acquired hypothyroidism due to autoimmune thyroid disease. The median levothyroxine dose received at the most recent visit when serum TSH was <5.0 mU/L (at a median age of 7.86 and 14.29 years, respectively) was 3.2 mcg/kg/day in the former and 2.4 mcg/kg/day in the latter (N.S.). Combining both groups, the levothyroxine requirement decreased by 0.5 mcg/kg/day for every 4-year period. CONCLUSION: When strictly matched for severity of disease, levothyroxine requirements are similar in school-age children with congenital or acquired hypothyroidism and decrease with age. Thus, in congenital hypothyroidism treated early with high-dose levothyroxine, pituitary resistance to thyroxine feedback does not appear to be present at school age. WHAT IS KNOWN: ⢠Pediatric studies unmatched for severity have suggested that levothyroxine requirements are higher in congenital than in acquired hypothyroidism. What is new: ⢠When strictly matched for severity, levothyroxine requirements are similar in children with congenital or acquired hypothyroidism and decrease with age.
Asunto(s)
Hipotiroidismo/tratamiento farmacológico , Tiroxina/administración & dosificación , Adolescente , Factores de Edad , Niño , Preescolar , Hipotiroidismo Congénito/tratamiento farmacológico , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Hipotiroidismo/etiología , Recién Nacido , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Tiroiditis Autoinmune/complicacionesRESUMEN
The active thyroid hormone tri-iodothyronine (T3) is essential for a normal development of children. Especially within the first years of life, thyroid hormone is pivotal in enabling maturation of complex brain function and somatic growth. The most compelling example for a life without thyroid hormone are those historical cases of children who came to birth without a thyroid gland - as shown in autopsy-studies- and who suffered from untreated hypothyroidism, at that time initially called "sporadic congenital hypothyroidism" (CH). In the last decades huge achievements resulted in a normal development of these children based on newborn screening programs that enable an early onset of a high dose LT4-treatment. Further progress will be necessary to further tailor an individualized thyroid hormone substitution approach and to identify those more complex patients with congenital hypothyroidism and associated defects, who will not benefit from an even optimized LT4 therapy. Besides the primary production of thyroid hormone a variety of further mechanisms are necessary to mediate the function of T3 on normal development that are located downstream of thyroid hormone production. Abnormalities of these mechanisms include the MCT8-transport defect, deiodinase-insufficiency and thyroid hormone receptor alpha-and beta defects. These thyroid hormone resistant diseases can not be treated with classical LT4 substitution alone. The development of new treatment options for those rare cases of thyroid hormone resistance is one of the most challenging tasks in the field of congenital thyroid diseases today.
Asunto(s)
Hipotiroidismo Congénito/tratamiento farmacológico , Terapia de Reemplazo de Hormonas/métodos , Hidrolasas/deficiencia , Yoduro Peroxidasa/deficiencia , Discapacidad Intelectual Ligada al Cromosoma X/tratamiento farmacológico , Hipotonía Muscular/tratamiento farmacológico , Atrofia Muscular/tratamiento farmacológico , Receptores de Hormona Tiroidea/agonistas , Síndrome de Resistencia a Hormonas Tiroideas/tratamiento farmacológico , Tiroxina/uso terapéutico , Triyodotironina/análogos & derivados , Humanos , Recién Nacido , Tamizaje Neonatal , Triyodotironina/uso terapéuticoRESUMEN
BACKGROUND: With early initiation of thyroxine supplementation, children with congenital hypothyroidism (CH) retain some subtle deficits, such as attention and inhibitory control problems. This study assessed the effects of atomoxetine on cognitive functions in treatment of attention deficit hyperactivity disorder (ADHD) symptoms in children with CH. METHODS: In a 6-month, open-labeled pilot study, 12 children were recruited and received atomoxetine. The measures of efficacy were scores on the Swanson, Nolan and Pelham Teacher and Parent Rating Scale, version IV (SNAP-IV) and Clinical Global Impression-Severity scale (CGI-S). The cognitive functions were evaluated with the Wechsler Intelligence Scale for Chinese Children, Digit Span, Wisconsin Card Sorting Test, and Stroop test. RESULTS: A statistically significant difference was found between the mean CGI-S and SNAP-IV scores before and after treatment (p < 0.01). All the indicators of cognitive functions at the endpoint were improved compared with those at baseline. No serious adverse events were reported. CONCLUSION: Atomoxetine appears to be useful in improving ADHD symptoms, as well as cognitive functions, in children with CH. Larger, randomized, double-blinded, clinical trials are required to replicate these results.
Asunto(s)
Inhibidores de Captación Adrenérgica/uso terapéutico , Clorhidrato de Atomoxetina/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Cognición/efectos de los fármacos , Hipotiroidismo Congénito/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/psicología , Niño , Hipotiroidismo Congénito/tratamiento farmacológico , Hipotiroidismo Congénito/psicología , Femenino , Humanos , Masculino , Pacientes Ambulatorios , Proyectos Piloto , Pruebas Psicológicas , Resultado del TratamientoRESUMEN
OBJECTIVE: Our objective was to evaluate effects of levothyroxine (l-T4) supplementation against neurodevelopmental outcomes at 18 months of corrected age in very-low-birth-weight (VLBW) infants with hypothyroxinemia but without elevated thyroid-stimulating hormone (TSH) concentration. METHODS: VLBW infants who had plasma TSH concentrations <10 µU/mL and free thyroxine (FT4) concentrations <0.8 ng/dL between 2 and 4 weeks of age were enrolled. They were randomly assigned to either the Treated (n=25) or Untreated group (n=45). The Treated group received l-T4 at a dose of 5 µg/kg/day. We compared growth and neurodevelopmental outcomes at 18 months of corrected age in the two groups. RESULTS: There were no significant differences in growth, the incidences of developmental delay, cerebral palsy, visual impairment, and hearing impairment in the two groups. CONCLUSIONS: In such infants, l-T4 supplementation at a dose of 5 µg/kg/day did not affect FT4 levels and showed no beneficial effect at 18 months of corrected age.
Asunto(s)
Hipotiroidismo Congénito/tratamiento farmacológico , Terapia de Reemplazo de Hormonas , Enfermedades del Prematuro/tratamiento farmacológico , Tiroxina/uso terapéutico , Desarrollo Infantil/efectos de los fármacos , Hipotiroidismo Congénito/sangre , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/sangre , Recién Nacido de muy Bajo Peso , Masculino , Pruebas de Función de la Tiroides , Tiroxina/sangre , Resultado del TratamientoRESUMEN
Congenital hypothyroidism (CH) presenting as acute pseudo-obstruction is uncommon. We report two premature infants presenting with acute bowel obstruction subsequently diagnosed to have CH. Both responded well to medical management with thyroid supplementation.
Asunto(s)
Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Recien Nacido Prematuro , Seudoobstrucción Intestinal/diagnóstico , Enfermedades del Yeyuno/diagnóstico , Hipotiroidismo Congénito/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Seudoobstrucción Intestinal/diagnóstico por imagen , Seudoobstrucción Intestinal/terapia , Enfermedades del Yeyuno/diagnóstico por imagen , Enfermedades del Yeyuno/terapia , Laparotomía/métodos , Masculino , Tomografía de Emisión de Positrones/métodos , Enfermedades Raras , Medición de Riesgo , Muestreo , Tiroxina/uso terapéuticoRESUMEN
AIM: Iodine deficiency is one of the most important causes of congenital hypothyroidism. In addition to thyroid hormone replacement, iodine supplementation is also given to newborns with congenital hypothyroidism due to iodine deficiency. We aimed to determine whether it is beneficial to administer iodine supplementation in addition to the L-thyroxine (L-T4) treatment of newborns with congenital hypothyroidism due to iodine deficiency. MATERIALS AND METHODS: Of 51 newborns, 26 who were diagnosed with congenital hypothyroidism due to iodine deficiency were treated with L-T4. The remaining 25 cases were given L-T4 plus 100 µg/day of oral iodine. Free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), thyroglobulin (TG), thyroid volume, urine iodine and breast milk iodine levels were measured in the first and third months of treatment, and the data were compared between the two groups. RESULTS: First- and third-month values of fT3, fT4, TSH, TG and thyroid volume for both groups were statistically similar. There was no significant difference between the two groups in respect to falling levels of fT3 and TSH, the rate of increase of fT4 levels or the shrinkage rate of thyroid volume. CONCLUSION: In this study, the addition of oral iodine to L-T4 treatment provided no benefit compared to treatment with L-T4 alone.
Asunto(s)
Hipotiroidismo Congénito/tratamiento farmacológico , Yodo/administración & dosificación , Tiroxina/uso terapéutico , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Recién Nacido , Yodo/deficiencia , Yodo/orina , Leche Humana/química , Tiroglobulina/sangre , Glándula Tiroides/diagnóstico por imagen , Tirotropina/sangre , Triyodotironina/sangre , UltrasonografíaRESUMEN
OBJECTIVE: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). EVIDENCE: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. CONSENSUS PROCESS: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. RECOMMENDATIONS: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy.
Asunto(s)
Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Tamizaje Neonatal/normas , Educación del Paciente como Asunto , Tiroxina/uso terapéutico , Hipotiroidismo Congénito/sangre , Relación Dosis-Respuesta a Droga , Endocrinología , Europa (Continente) , Humanos , Recién Nacido , Pediatría , Índice de Severidad de la Enfermedad , Sociedades Médicas , Hormonas Tiroideas/sangreRESUMEN
A 3-month-old male domestic short-hair kitten was presented with chronic constipation and disproportionate dwarfism. Radiographs of the long bones and spine revealed delayed epiphyseal ossification and epiphyseal dysgenesis. Diagnosis of congenital primary hypothyroidism was confirmed by low serum total thyroxine and high thyroid stimulating hormone concentrations. Appropriate supplementation of levothyroxine was instituted. The kitten subsequently developed mild renal azotaemia and renal proteinuria, possibly as a consequence of treatment or an unmasked congenital renal developmental abnormality. Early recognition, diagnosis and treatment are vital as alleviation of clinical signs may depend on the cat's age at the time of diagnosis.
Asunto(s)
Azotemia/veterinaria , Enfermedades de los Gatos/congénito , Hipotiroidismo Congénito/veterinaria , Enanismo/veterinaria , Animales , Azotemia/diagnóstico , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/tratamiento farmacológico , Gatos , Hipotiroidismo Congénito/complicaciones , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Enanismo/diagnóstico , Masculino , Tiroxina/administración & dosificación , Tiroxina/uso terapéuticoRESUMEN
"OBJECTIVE: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). EVIDENCE: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. CONSENSUS PROCESS: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. RECOMMENDATIONS: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy."
Asunto(s)
Humanos , Recién Nacido , Hipotiroidismo Congénito , Pediatría , Hormonas Tiroideas/uso terapéutico , Tiroxina/uso terapéutico , Índice de Severidad de la Enfermedad , Educación del Paciente como Asunto , Tamizaje Neonatal , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , EndocrinologíaRESUMEN
BACKGROUND: Despite newborn screening and early levothyroxine replacement, there are continued reports of mild neurocognitive impairment in children with congenital hypothyroidism (CHT). In Auckland, New Zealand, cases are identified by a neonatal screening program with rapid institution of high-dose levothyroxine replacement (10-15 µg/kg·d), producing prompt normalization of thyroid function. Subsequently, frequent monitoring and dose alterations are performed for 2 years. We aimed to assess whether the Auckland treatment strategy prevents impairment of intellectual and motor development. METHODS: This study encompassed all children with CHT born in 1993-2006 in Auckland and their siblings. Neurocognitive assessments included the following: 1) intelligence quotient via Weschler Preschool and Primary Scale of Intelligence III or Weschler Intelligence Scale for Children IV; 2) Movement Assessment Battery for Children; and 3) Beery Developmental Test of Visual-Motor Integration. Body composition was assessed by dual-energy x-ray absorptiometry. RESULTS: Forty-four CHT cases and 53 sibling controls aged 9.6 ± 3.9 years were studied. Overall intelligence quotient was similar among CHT cases and controls (95.2 vs 98.6; P = .20), and there were also no differences in motor function. Severity of CHT did not influence outcome, but greater time to normalize free T4 was associated with worse motor balance. There were no differences in anthropometry or body composition between groups. CONCLUSIONS: These findings suggest that a strategy of rapidly identifying and treating infants with CHT using high-dose levothyroxine replacement is associated with normal intellectual and motor development. The subtle negative impact on motor function associated with time to normalize free T4 levels is consistent with benefit from rapid initial correction.
Asunto(s)
Composición Corporal/efectos de los fármacos , Hipotiroidismo Congénito/tratamiento farmacológico , Inteligencia/efectos de los fármacos , Desempeño Psicomotor/efectos de los fármacos , Tiroxina/uso terapéutico , Composición Corporal/fisiología , Niño , Preescolar , Hipotiroidismo Congénito/fisiopatología , Femenino , Humanos , Lactante , Recién Nacido , Inteligencia/fisiología , Pruebas de Inteligencia , Estudios Longitudinales , Masculino , Tamizaje Neonatal , Pruebas Neuropsicológicas , Nueva Zelanda , Desempeño Psicomotor/fisiología , Índice de Severidad de la Enfermedad , Pruebas de Función de la Tiroides , Tiroxina/administración & dosificaciónRESUMEN
Congenital hypothyroidism (CH), one of the most common congenital endocrine disorders, causes irreversible intellectual disability in untreated patients. Today, the vast majority of patients receive early diagnosis and treatment in the context of newborn screening for CH, and achieve satisfactory cognitive development. However, a subset of patients with delayed onset are undetectable by newborn screening, and miss benefit from early intervention. Here, we report on a delayed-onset CH patient that had two contributing factors in the pathogenesis of CH simultaneously, i.e., a genetic defect and iodine excess. The patient was exposed to excessive iodine in utero because her mother consumed massive amounts of seaweed during pregnancy. Surprisingly, the patient had a negative result in newborn screening, but developed overt CH at age 3 months. She received thyroxine supplementation until when normalization of the thyroid function was confirmed at age 3 years (i.e., transient CH). Mutation screening for DUOX2, a causative gene for transient CH, showed biallelic mutations (p.[E327X] + [H678R]). This report provides a new example of environmental modification of phenotypes of CH due to a genetic defect, which can potentially distort screening results.