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OBJECTIVES: Congenital hyperinsulinism (HI) is a heterogeneous clinical disorder with great variability in its clinical phenotype, and to date, pathogenic variants in 23 genes have been recognized.  Hyperinsulinism-hyperammonemia syndrome (HI/HA) is the second most frequent cause of this disease that shows an autosomal dominant pattern and is caused by an activating mutation of the GLUD1 gene, which responds favorably to the use of diazoxide. HI/HA syndrome presents with fasting hypoglycemia; postprandial hypoglycemia, especially in those with a high protein content (leucine); and persistent mild hyperammonemia. Neurological abnormalities, in the form of epilepsy or neurodevelopmental delay, are observed in a high percentage of patients; therefore, timely diagnosis is crucial for proper management. CASE PRESENTATION: We report the clinical presentation of two Peruvian children that presented with epilepsy whose genetic analysis revealed a missense mutation in the GLUD1 gene, one within exon 11, at 22% mosaicism; and another within exon 7, as well as their response to diazoxide therapy. To the best of our knowledge, these are the first two cases of HI/HA syndrome reported in Peru. CONCLUSIONS: HI/HA syndrome went unnoticed, because hypoglycemia was missed and were considered partially controlled epilepsies. A failure to recognize hypoglycemic seizures will delay diagnosis and adequate treatment, so a proper investigation could avoid irreversible neurological damage.

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Schimmelpenning-Feuerstein-Mims syndrome (SFM), an epidermal nevus syndrome characterized by skin lesions, has an estimated incidence of 1 per 10 000 live births. Nevus sebaceous, the most common cutaneous lesion, and verrucous nevus, the less frequent lesion, are coupled with a wide range of extracutaneous manifestations. As part of these manifestations, rarely, central precocious puberty can arise. We report the case of a 1-year-5-month-old girl who presented to the Endocrinology and Metabolism Department with breast enlargement that began at one year of age, growth of pubic and axillary hair three months later, and vaginal bleeding that occurred five months later. During clinical examination, melanocytic nevi, with a diameter ranging from 3 to 5 mm, were noted on the face. Verrucous nevi of variable size with a tendency for coalescence following the lines of Blaschko and melanocytic nevi with a diameter ranging from 3 to 6 mm were observed on the right hemibody and on the left hemibody, respectively. Right asymmetry of the lower extremities was observed. Laboratory findings showed a significant increase in the levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) after the gonadotropin-releasing hormone (GnRH) stimulation test; additionally, imaging demonstrated advanced bone age and pubertal changes in the internal genitals. Analyses of the H-RAS, K-RAS, and N-RAS genes in the blood and in the skin were performed, and a missense mutation in exon 2 of the gene, H-RAS c37G > C (p.G13R), was detected in the latter. Treatment with triptorelin, a GnRH analog, was initiated, and it gave good clinical response. Epidermal nevus syndrome has a wide and variable systemic involvement. Thus, it is important to consider the development of precocious puberty for a prompt diagnosis and to strategize a multidisciplinary approach from the beginning.

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La tiroiditis autoinmune es la causa más frecuente de hipotiroidismo adquirido en la edad pediátrica. El cuadro clínico al diagnóstico depende de la condición bioquímica en la que se encuentre y el seguimiento es fundamental para adoptar las medidas terapéuticas que garanticen un adecuado crecimiento y desarrollo. Objetivo. Describir la progresión clínica de la tiroiditis autoinmune en niños y adolescentes. Diseño. Estudio de serie de casos, longitudinal y retrospectivo. Lugar. Servicio de Endocrinología, Instituto Nacional de Salud del Niño, Lima, Perú (institución docente). Participantes. Niños y adolescentes con tiroiditis autoinmune. Intervenciones. Sesenta y cinco pacientes con tiroiditis autoinmune (58 mujeres y 7 varones), menores de 18 años, atendidos entre los años 2000 y 2012, tuvieron seguimiento por más de un año, con evaluaciones clínicas y bioquímicas periódicas. Se excluyó del estudio a los portadores de síndromes genéticos o diabetes mellitus tipo 1. Principales medidas de resultados. Progresión clínica de la tiroiditis autoinmune. Resultados. El bocio (78,5 por ciento) fue el signo predominante y a la vez factor de riesgo para evolucionar a hipotiroidismo establecido (adquirido) en quienes debutaron con hipotiroidismo subclínico. Al ingreso, el 48 por ciento de prepúberes presentó disfunción tiroidea frente al 26,6 por ciento de los púberes. De la población total, 46 por ciento tuvo hipotiroidismo establecido, 26 por ciento hipotiroidismo subclínico y 23 por ciento estado eutiroideo. El 27 por ciento de eutiroideos y 47 por ciento de hipotiroideos subclínicos evolucionaron a hipotiroidismo establecido. No hubo diferencia estadísticamente significativa de los puntajes Z promedio de talla o IMC al diagnóstico o durante el seguimiento. Conclusiones. Los niños y adolescentes con tiroiditis autoinmune que debutan en estado eutiroideo o hipotiroideo subclínico tienen riesgo alto de evolucionar a hipotiroidismo establecido, siendo...

Autoimmune thyroiditis is the most common cause of hypothyroidism in children. Clinical diagnosis depends on biochemical condition and monitoring is essential to adopt therapeutic measures and ensure proper growth and development. Objective. To describe the clinical progression of autoimmune thyroiditis in children and adolescents. Design. Retrospective, longitudinal series of cases study. Setting. Department of Endocrinology, Instituto Nacional de Salud del Niño, Lima, Peru (a teaching institution). Participants.Children and adolescents suffering of autoimmune thyroiditis. Interventions. Sixty-five patients-58 women and 7 men- under the age of 18 suffering of autoimmune thyroiditis and admitted between 2000-2012 were followed with clinical and biochemical evaluations over one year; carriers of genetic syndromes or with type 1 diabetes mellitus were excluded. Main outcome measures. Clinical progression of autoimmune thyroiditis. Results. Goiter (78.5 per cent) was a predominant sign and risk factor for development of acquired hypothyroidism in those who debuted with subclinical hypothyroidism. At admission 48 per cent of prepubescent infants presented thyroid dysfunction compared with 26.6 per cent of pubescent subjects. Out of the total population 46 per cent suffered of acquired hypothyroidism, 26 per cent subclinical hypothyroidism, and 23 per cent were euthyroid; 27 per cent of euthyroid patients and 47 per cent of subjects with subclinical hypothyroidism evolved into acquired hypothyroidism. There was no statistically significant difference in the mean Z score for height or BMI at diagnosis nor during follow-up. Conclusions. Children and adolescents with autoimmune thyroiditis debuting as euthyroid or with subclinical hypothyroidism had a high risk of developing acquired hypothyroidism. It seems important to monitor thyroid function for timely initiation of hormone replacement therapy...

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A case is reported of a 7 year old patient with progressive dyspnea and genital development according to Marshall and Tanner criteria at the G2 VP3 stage. A mass of regular and well-defined borders was found in the chest, with calcifications and cystic areas of heterogeneous content. Basal measurements of FSH, LH and testosterone were <10 mIU/mL, 12.2 mIU/mL and 724 ng/dL, respectively. α-fetoprotein was 145.1 ng/mL. Excising the tumor improved respiratory symptoms, diminished hormone levels and stopped the process of precocious puberty. Pathology of the mediastinal tumor corresponded to a germ cell tumor with a predominant component of mature teratoma and choriocarcinoma. Neoplastic causes of precocious puberty are uncommon; its diagnosis is essential in order to provide timely treatment.

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Se reporta el caso de un paciente de 7 años de edad, que inicia su enfermedad con disnea progresiva, el desarrollo genital, de acuerdo con los criterios de Marshall y Tanner, muestra un estadio G2 VP3. En el tórax se halló una tumoración de bordes regulares y definidos, con presencia de calcificaciones y áreas quísticas de contenido heterogéneo. Las determinaciones basales de FSH, LH y testosterona fueron de < 10 mUI/mL, 12,2 mUI/mL y 724 ng/dL, respectivamente. La determinación de la α-feto proteína fue de 145,1 ng/mL. La exéresis del tumor mejoró el cuadro respiratorio, la remisión de los niveles hormonales y la detención del proceso de pubertad precoz. El estudio anatomopatológico de la tumoración mediastinal correspondió a un tumor de células germinales con componente predominante de teratoma maduro y coriocarcinoma. La pubertad precoz de etiología neoplásica es una causa rara, su diagnóstico es primordial para aplicar un tratamiento oportuno...

A case is reported of a 7 year old patient with progressive dyspnea and genital development according to Marshall and Tanner criteria at the G2 VP3 stage. A mass of regular and well-defined borders was found in the chest, with calcifications and cystic areas of heterogeneous content. Basal measurements of FSH, LH and testosterone were <10 mIU/mL, 12.2 mIU/mL and 724 ng/dL, respectively. α-fetoprotein was 145.1 ng/mL. Excising the tumor improved respiratory symptoms, diminished hormone levels and stopped the process of precocious puberty. Pathology of the mediastinal tumor corresponded to a germ cell tumor with a predominant component of mature teratoma and choriocarcinoma. Neoplastic causes of precocious puberty are uncommon; its diagnosis is essential in order to provide timely treatment...

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Objetivos: Describir la respuesta clínica y bioquímica al tratamiento del hipertiroidismo por enfermedad de Graves en pacientes pediátricos. Diseño: Estudio retrospectivo. Institución: Instituto Nacional de Salud del Niño, Lima, Perú. Participantes: Niños con enfermedad de Graves. Métodos: Se incluyó 32 pacientes con diagnóstico de hipertiroidismo por Enfermedad de Graves, entre 1996 a 2007. Se consideró remisión, cuando se encontraban asintomáticos y bioquímicamente eutiroideos, luego de 6 meses de suspendido el tratamiento; y recaída, si luego de este periodo de tiempo, se encontró valores hormonales alterados. Principales medidas de resultados: Remisión o recaída luego del tratamiento. Resultados: Al diagnóstico, la edad promedio fue 10,5 años (3,2 a 17,9 años); 26 pacientes (81,2 por ciento) fueron de sexo femenino, 13 (40,6 por ciento) púberes y 19 (59,3 por ciento) pre-púberes. Los síntomas y signos más frecuentes fueron bocio, sudoración, nerviosismo, pérdida de peso, taquicardia y exoftalmos. Se usó metimazol como primera opción terapéutica a una dosis inicial promedio de 0,78 mg/kg/ día (0,4 a 2 mg/kg/día). La TSH (57,1 por ciento) y el T4L (50 por ciento) alcanzaron valores normales entre los 6 y 8 meses. Se observó remisión en 11 pacientes (34,3 por ciento), 3 (9,3 por ciento) sufrieron recaída, 12 (37,5 por ciento) pasaron a tratamiento con radioyodo (I131) y 6 (18,7 por ciento) continuaron recibiendo metimazol. La remisión de la enfermedad se alcanzó a los 2,81±0,91 años de tratamiento (rango de 1.5 a 4,8); 4,1 por ciento remitió luego del primer año, y 35,3 por ciento, 37,5 por ciento y 25 por ciento luego del segundo, tercer y cuarto año de tratamiento, respectivamente. La edad promedio de los que recibieron I131 fue 14,6 años (7,1 a 19,6 años), a una dosis alrededor de 7mCi. El 75 por ciento de ellos remitió a los 0,64± 0,60 años (rango de 0,16 a 1,5 años). Conclusiones: El hipertiroidismo por enfermedad de Graves es de relativa frecuencia en...

Objectives: To describe the clinical and biochemical response to treatment of hyperthyroidism. Design: Retrospective study. Setting: Instituto Nacional de Salud del Niño, Lima, Peru. Participants: Children. Methods: From 1996 to 2007 32 patients with diagnosis of hyperthyroidism were studied. Remission was defined when patients were asymptomatic and biochemically euthyroid 6 months after the end of treatment; relapse when altered hormone levels were found after this period of time. Main outcome measures: Remission or relapse following treatment. Results: Mean age at diagnosis was 10.5 years (3.2-17.9 years), 26 patients (81.2 per cent) were female; 13 (40.6 per cent) were pubertal and 19 (59.3 per cent) prepubertal. The most frequent symptoms and signs were: goiter, sweating, nervousness, weight loss, tachycardia and exophthalmos. Methimazole was used as first therapeutic option. Initial dose was 0.78mg/kg/day (0.41-2mg/kg/day) average. TSH (57.1 per cent) and FT4 (50 per cent) reached normal values between 6 and 8 months. Remission was observed in 11 patients (34.3 per cent), 3 (9.3 per cent) relapsed, 12 (37.5 per cent) then received treatment with radioiodine (I-131) and 6 (18.7 per cent) continued receiving methimazole. Remission was achieved after 2.81 ± 0.91 years of treatment (range 1.5-4.8), 4.1 per cent after the first year, and 35.3 per cent, 37.5 per cent and 25 per cent respectively after the second, third and fourth year of treatment. Average age of those receiving I-131 was 14.6 years (7.1-19.6 years), at a dose about 7mCi; 75 per cent of them showed remission after 0.64 ± 0.60 year (range 0.16-1.5 years). Conclusions: Hyperthyroidism due to Graves disease is relatively common in children. Remission was obtained in 34.3 per cent of patients treated with methimazole in 2.81 ± 0.91 years average and remission was achieved in 75 per cent of patients treated with I131, in 0.64 +/- 0.60 years average...

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La nefropatía constituye la complicación más grave de la diabetes mellitus tipo 1 (DMt1) siendo una de las manifestaciones iniciales la microalbuminuria. Objetivos: Determinar el comportamiento de los factores epidemiológicos, clínicos y bioquímicos en el desarrollo de microalbuminuria en pacientes con DMt1. Diseño: Estudio de casos y controles. Lugar: Servicio de Endocrinología del Instituto Nacional de Salud del Niño, Lima, Perú. Participantes: Pacientes diabéticos tipo 1 menores de 18 años. Intervenciones: Se estudió 64 pacientes portadores de DMt1, 22 con microalbuminuria y 42 sin esta manifestación, que constituyeron los casos y controles respectivamente. Se consignó como factores epidemiológicos la edad al diagnóstico, tiempo de evolución, género, antecedentes familiares de diabetes, nefropatía, dislipidemia, hipertensión arterial; como factores clínicos, el estado nutricional, desarrollo puberal (Tanner), presión arterial; y como factores bioquímicos, la hemoglobina glicosilada (HbA1c), microalbuminuria y perfil lipídico. Tanto los casos como los controles fueron seguidos durante un año. El análisis estadístico se hizo mediante pruebas de chi cuadrado, odds ratio y regresión logística, para establecer predominancia de factores. Principales medidas de resultados: Estadio puberal, perfil lipídico y HbA1c. Resultados: Los factores de riesgo hallados fueron la presión arterial diastólica elevada (p=0,037), la pubertad (p=0,008), HbA1c alta (p< 0,0001), hipertrigliceridemia (p= 0,007) y la hipercolesterolemia (p< 0,0001). Conclusiones: La HbA1c elevada, la hipercolesterolemia y la pubertad fueron los factores de riesgo de mayor preponderancia para el desarrollo de microalbuminuria. A fin de prevenir el desarrollo de microalbuminuria, se sugiere buen control metabólico y cuidadoso manejo de la dislipidemia, en especial en pacientes púberes.

Nephropathy constitutes the most serious type 1 diabetes mellitus (type 1 DM) complication and microalbuminuria is the initial manifestation. Objectives: To determine the role of epidemiological, clinical and biochemical factors in the development of microalbuminuria in type 1 DM patients. Design: Case and control study. Setting: Endocrinology Unit, National Institute of Child Health, Lima, Peru. Patients: Subjects less than 18 year-old with type 1 DM. Interventions: Sixty-four type 1 DM patients were studied, 22 patients with microalbuminuria (cases) and 42 patients without it (controls). Epidemiological factors studied were age at diagnosis, time from onset, gender, family history of diabetes, nephropathy, dyslipidemia, and/or hypertension; clinical factors studied were nutritional status, pubertal stage (Tanner method) and blood pressure; biochemical factors were glycated hemoglobin (HbA1c), microalbuminuria and lipid profile. Both cases and controls were followed for one year. Statistical analysis used chi square, odds ratio and multiple logistic regression calculations to determine main risk factors. Main outcome measures: Pubertal stage, lipid profile and HbA1c. Results: Risk factors determined were high diastolic blood pressure (p=0.037), puberty (p=0.008), high HbA1C (p<0.0001), hypertriglyceridemia (p=0.007), and hypercholesterolemia (p<0.0001). Conclusions: Elevated HbA1c, hypercholesterolemia and puberty were the more important risk factors for development of microalbuminuria. Main measures to prevent development of microalbuminuria were good metabolic control and good management of dyslipidemia, especially in pubertal patients.