Hipertiroidismo en niños y adolescentes: experiencia en un hospital universitario en Colombia / Hyperthyroidism in children and adolescents: Experience in a university hospital in Colombia

Introducción. El hipertiroidismo es una condición heterogénea caracterizada por la producción excesiva de hormonas tiroideas. Su aparición en la edad pediátrica representa un reto diagnóstico y terapéutico. Objetivo. Describir las características clínicas y paraclínicas, así como la evolución y las diferencias entre las principales causas etiológicas de los pacientes con hipertiroidismo atendidos por el Servicio de Endocrinología Pediátrica del Hospital Universitario San Vicente Fundación en Medellín, Colombia, entre el 1° de julio de 2015 y el 30 de junio de 2020. Materiales y métodos. Se hizo un estudio observacional transversal con recolección retrospectiva de la información. Resultados. Se incluyeron 54 pacientes con una edad media de 11,9 años, 72,2 % de ellos mujeres. El 11,1 % tenía antecedentes familiares de enfermedad de Graves y 29,6 % de otras enfermedades tiroideas. El bocio fue la manifestación clínica más frecuente (83,3 %). El 92,6 % había recibido terapia con metimazol, el 79,6 % requirió betabloqueador y el 11,2 % necesitó una terapia farmacológica adicional. Se presentaron reacciones adversas a la medicación en el 16,7 %. En el 20,4 % de los pacientes hubo resolución del hipertiroidismo (espontánea: 9,3 %; posterior a la ablación con yodo radiactivo: 9,3 %, y después de la cirugía: 1,9 %). Conclusión. El hipertiroidismo es una enfermedad con manifestaciones clínicas diversas. La causa más frecuente es la enfermedad de Graves, seguida por la hashitoxicosis. En este estudio, la hashitoxicosis fue más frecuente que en estudios previos. La duración y los efectos secundarios del tratamiento farmacológico fueron similares a los reportados previamente, pero es de resaltar la mayor frecuencia de agranulocitosis en nuestra población.

Introduction: Hyperthyroidism is a heterogeneous condition characterized by the excessive production of thyroid hormones. It represents a diagnostic and therapeutic challenge. Objective: To describe the clinical and paraclinical characteristics and the evolution and differences between the main etiologies in patients with hyperthyroidism treated by the Pediatric Endocrinology Service at the Hospital Universitario San Vicente Fundación in Medellín, Colombia, between July 1st., 2015, and June 30th., 2020. Materials and methods: We conducted a cross-sectional observational study with retrospective data collection. Results: We included 54 patients with a mean age of 11.9 years, 72.2% of whom were female; 85.2% had no history of comorbidities related to autoimmunity; 11.1% had a family history of Graves' disease, and 29.6% of other thyroid diseases. Goiter was the most frequent clinical manifestation (83.3%) and 92.6% of the patients received treatment with methimazole, 79.6% required beta-blockers, and 11.2% additional drug therapy. Adverse drug reactions occurred in 16.7% of the patients and in 20.4% there was a resolution of hyperthyroidism (spontaneous: 9.3%; after radio-iodine ablation: 9.3%, and after surgery: 1.9%). Conclusion: Hyperthyroidism is a disease with diverse clinical manifestations. Its most frequent cause is Graves' disease followed by hashitoxicosis, which in this study had a higher frequency than that reported in the literature. The duration and side effects of pharmacological treatment were similar to those previously reported, but the higher frequency of agranulocytosis is noteworthy.

New STAG3 gene variant as a cause of premature ovarian insufficiency / Nueva variante del gen STAG3 causante de insuficiencia ovárica prematura

Objectives: To describe a case of ovarian failure secondary to a homozygous pathogenic variant in the STAG3 gene not previously reported. Materials and Methods: A 16-year-old patient with primary amenorrhea and absence of secondary sexual characteristics, with documented autoimmune hypothyroidism, poor genital and gonadal streak development which prompted the performance of clinical exome sequencing. A homozygous pathogenic variant not previously reported in the STAG3 gene, which has been associated with premature ovarian insufficiency (POI), was identified. Conclusions: In this case, clinical exome sequencing was key for identifying a STAG gene abnormality, probably associated with POI and long term prognosis for the patient. A new pathogenic variant c.2773delT; p.Ser925Profs*6 of the STAG3 gene associated with POI was established.

Objetivos: describir un caso de falla ovárica secundaria a una variante patogénica homocigota en el gen STAG3 no reportada previamente. Materiales y métodos: paciente de 16 años con amenorrea primaria y ausencia de características sexuales secundarias, en quien se documentó hipotiroidismo autoinmune, pobre desarrollo genital y cintilla gonadal, por lo cual se realizó secuenciación de exoma clínico. Se identificó una variante homocigota patogénica previamente no reportada en el gen STAG3, el cual ha sido relacionado con insuficiencia ovárica prematura (IOP). Conclusiones: en este caso, la realización de exoma clínico fue determinante para identificar una alteración del gen STAG, probablemente asociada a la IOP y el pronóstico a largo plazo de la paciente. Se establece una nueva variante patogénica c.2773delT; p.Ser925Profs*6 del gen STAG3 asociada a la IOP.

Nueva variante del gen STAG3 causante de insuficiencia ovárica prematura / New STAG3 gene variant as a cause of premature ovarian insufficiency

RESUMEN Objetivos: describir un caso de falla ovárica secundaria a una variante patogénica homocigota en el gen STAG3 no reportada previamente. Materiales y métodos: paciente de 16 años con amenorrea primaria y ausencia de características sexuales secundarias, en quien se documentó hipotiroidismo autoinmune, pobre desarrollo genital y cintilla gonadal, por lo cual se realizó secuenciación de exorna clínico. Se identificó una variante homocigota patogénica previamente no reportada en el gen STAG3, el cual ha sido relacionado con insuficiencia ovárica prematura (IOP). Conclusiones: en este caso, la realización de exorna clínico fue determinante para identificar una alteración del gen STAG, probablemente asociada a la IOP y el pronóstico a largo plazo de la paciente. Se establece una nueva variante patogénica c.2773delT; p.Ser925Profs*6 del gen STAG3 asociada a la IOP.

ABSTRACT Objectives: To describe a case of ovarian failure secondary to a homozygous pathogenic variant in the STAG3 gene not previously reported. Material and methods: A 16-year-old patient with primary amenorrhea and absence of secondary sexual characteristics, with documented autoimmune hypothyroidism, poor genital and gonadal streak development which prompted the performance of clinical exorne sequencing. A homozygous pathogenic variant not previously reported in the STAG3 gene, which has been associated with premature ovarian insufficiency (POI), was identified. Conclusions: In this case, clinical exorne sequencing was key for identifying a STAG gene abnormality, probably associated with POI and long term prognosis for the patient. A new pathogenic variant c.2773delT; p.Ser925Profs*6 of the STAG3 gene associated with POI was established.

[A Novel Pathogenic variant in NR0B1 gene associated with Congenital Adrenal Hypoplasia]. / Nueva Variante Patogénica en el Gen NR0B1 Asociada a Hipoplasia Adrenal Congénita.

X-linked adrenal hypoplasia congenita is a rare cause of primary adrenal insufficiency. Mutations in the NR0B1 gene cause a loss of function in the DAX1 receptor, which activates genes involved in the development and function of the hypothalamic-pituitary-gonadal axis. Objective: To describe a case of adrenal hypoplasia congenita secondary to a mutation in the NR0B1 gene and identified the differential diagnoses of the pediatric patient with adrenal insufficiency and hypogonadotropic hypogonadism. Clinical Case: A 4-year-old male patient with no relevant history and from a rural area was admitted to the emergency room due to a 15-days of emesis, asthenia, adynamia, myalgia, and ataxic gait. On the physical examination, hypotension, hyponatremia, and hyperkalemia, as well as mucosal hyperpigmentation and bilateral cryptorchidism were observed, therefore, adrenal crisis was diagnosed, starting fluid resuscitation with saline solution, hydrocortisone, and fludrocortisone, which stabilized the patient. Adrenal hyperplasia congenita, innate metabolic error, and infectious or autoimmune etiology were ruled out as etiology. A clinical exome test was performed which iden tified the variant c.1275A > T; p.Arg425Ser (Transcript ENST00000378970.5) in the NR0B1 gene consistent with X-linked adrenal hypoplasia congenita. Management of the patient continued with glucocorticoids and mineralocorticoids with favorable clinical course at 7 years of follow-up. Con clusion: A novel pathogenic variant associated with X-linked adrenal hypoplasia is described. Variants in the NR0B1 gene should be a differential diagnosis in a male patient with the association of primary adrenal insufficiency and hypogonadism.