Case report of GNAS epigenetic defect revealed by a congenital hypothyroidism.

Pseudohypoparathyroidism (PHP) is a group of disorders characterized by end-organ resistance to the parathyroid hormone (PTH). PHP type 1A includes multihormone resistance syndrome, Albright's hereditary osteodystrophy, and obesity and is caused by mutations in GNAS exon 1 through 13. PHP type 1B (PHP1B), caused by epigenetic changes in the GNAS locus, was initially described as an isolated resistance to PTH. Epigenetic changes in GNAS have also been reported in patients who display mild Albright's hereditary osteodystrophy or mild thyroid-stimulating hormone (TSH) resistance without mutation of GNAS. Here we report a case of PHP caused by epigenetic changes in GNAS in a patient with congenital hypothyroidism. The patient was referred for a positive newborn screening for hypothyroidism (TSH 50 mIU/L). She exhibited severe clinical features of congenital hypothyroidism. The thyroid was in place, and etiologic explorations were negative. TSH was normalized under L-thyroxin, and the symptoms disappeared, except for a macroglossia. In childhood, PHP was suspected in addition to elevated PTH, obesity, brachydactyly, and a rounded face. Sequencing, methylation analysis, and large deletion research were performed in GNAS. No genetic mutations were found. Methylation analysis revealed a broad epigenetic defect without deletion in GNAS consistent with sporadic PHP1B. The multilocus methylation analysis were negative. This finding expands the known onsets of PHP1B and emphasizes the need for a new PHP classification system. This case report has important consequences for the etiologic diagnosis of congenital hypothyroidism because it adds a new cause of the disease.

Hipotiroidismo congénito: aspectos clínicos y ultrasonográficos / Clinical and ultrasound features of congenital hypothyroidism

Congenital hypothyroidism is a condition where a newborn has decreased or absent thyroid function and thyroid hormone production. It is the most common cause of preventable mental retardation and its early diagnosis can only be achieved through systematic neonatal screening because its clinical manifestations are usually late. The etiologic study of this condition relies heavily on nuclear medicine and ultrasound, describing various findings. This research analyzed the characteristics of the ultrasound patterns observed in these children and their correlation with the most common etiologies. The use of ultrasound allows selecting children that require scintigraphic studies, decreasing the use of radiation in neonates.

El hipotiroidismo congénito se define como la condición de déficit de la producción de hormonas tiroideas, que se encuentra presente desde el nacimiento. Corresponde a la causa más común de retardo mental prevenible y su diagnóstico precoz sólo se logra a través de la pesquisa sistemática neonatal, debido a que las manifestaciones clínicas son habitualmente tardías. El estudio etiológico específico se apoya fundamentalmente en la medicina nuclear y el ultrasonido, describiéndose hallazgos variados. Revisamos las características de los patrones ultrasonográficos observados en estos niños y su correlación con las etiologías más frecuentes. El uso de ultrasonografía permite seleccionar los niños que requieren estudio cintigráfico, disminuyendo el uso de radiación en neonatos.

[Care continuity for patients with congenital hypothyroidism during transition from childhood to adulthood].

Since the nation-wide neonatal screening programs for congenital hypothyroidism(CH) had been implemented in 1979, the diagnosis and treatment of CH are now provided in the first 2-3 weeks of birth in Japan. The goals of treatment are to raise the serum T4 as rapidly as possible into the normal range, and maintain normal growth and development while avoiding overtreatment. Because transient hypothyroidism may occur frequently, a reevaluation after 3 years is needed in such patients. Patients with CH had normal growth in general, suggesting that the neonatal screening system is being performed efficiently from detection to treatment of the disease in Japan. Pediatric and adult thyroidologists are engaging in processes to promote the continuity of care for patients with CH.

Iodine deficiency disorders in school children of Sikkim.

Sikkim is a small state in the eastern Himalayas. A survey was conducted to determine the prevalence of iodine deficiency disorders in the state. A two stage sampling procedure was adopted. In stage one, all villages in the state were listed and 249 were randomly selected for the survey. In stage two, households, were randomly selected from the selected villages using the electoral lists. The basic sampling unit was a household and all members of the households were studied. A total of 17,837 subjects were studied from 3,197 households of 249 villages. Overall prevalence of goitre and cretinism in the community as a whole, were 54.03% and 3.46% respectively. Of the population studied, 5939 were children in the age group of 5 to 16 years. There were 3,005 boys and 2,934 girls. Goitre was detected in 3,381 (56.9%). Goitre prevalence in the boys was 55.4% and in girls it was 58.5% (p = < 0.05). Grade I goitre was seen in 2,472 (73.1%), grade II in 888 (26.3%) and grade III in 21 (0.6%). Endemic cretinism was diagnosed in 175 subjects (2.9%). Cretinism prevalence in the boys was 3.1%, and in girls in was 2.8% and this difference was not significant. Neurological; cretinism was the predominant form (98.3%). Estimation of urinary iodine concentration in 167 subjects revealed the mean concentration to be 3.64 u/dl (SD 2.47). The median value was ug/dl indicating the skewed distribution of the urinary iodine concentration. The study shows the existence of severe iodine deficiency in the school-aged children of Sikkim.(ABSTRACT TRUNCATED AT 250 WORDS)

[A comparative study of EEG in patients with neurological and myxedematous cretinism].

A comparative study of EEG between neurological and myxedematous cretins was carried out in a total of 61 cases. The results were as follows: (1) The changes of EEG in myxedematous cretins appeared to be more obvious than those in neurological cretins; (2) The degree of mental retardation in cretins was not parallel to the degree of the abnormality of EEG; (3) with thyroid therapy, EEG in cretins was improved. The improvement rate in myxedematous cretins was higher than that in neurological cretins; (4) Brain CT scan was carried out in 50 cases of those cretins. It was found that the abnormality of certain intracerebral structure in myxedematous cretins appeared to be more obvious than that in neurological cretins. The change of EEG appeared in the same way as well. This is in contradiction to the traditional knowledge that the defect of neurological system in neurological cretinism was more severe than that in myxedematous cretinism. The current classification of cretins into neurological and myxedematous cretins does not reflect the changes of pathophysiology properly.