High frequency of D727E polymorphisms in exon 10 of the TSHR gene in Brazilian patients with congenital hypothyroidism.

Congenital Hypothyroidism affects between 1:3000 and 1:4000 newborn infants in iodine-sufficient regions. Some studies have shown that mutations and polymorphisms in the TSH receptor gene are responsible for this disease. In the present study, mutations of exon 10 of the TSH receptor gene were investigated in Congenital Hypothyroidism patients. In the present study a sample of 90 Brazilian patients with primary congenital hypothyroidism was analyzed. Genomic DNA was isolated from peripheric blood samples. Exon 10 of the TSH receptor gene was amplified by PCR, and amplicons were automatically sequenced. Three nucleotide alterations were identified: c.1377G>A (A459A), c.1935G>A (L645L), and c.2181C>G (D727E). A459A polymorphism was also described previously in patients with thyroid cancer. The nucleotide alteration L645L was found in a single patient. This is the first time the L645L mutation has been described. D727E polymorphism showed high frequency (allele frequency 10%) in present study when compared to others reports.

One-year clinical evaluation of single morning dose prednisolone therapy for 21-hydroxylase deficiency

Esquemas de reposição com hidrocortisona (HC) para a D21OH são, em geral, insatisfatórios e parcialmente eficientes quanto ao crescimento. Não aderência é comum já que a meia-vida da HC requer administração de 3 doses diárias. Mesmo várias doses não reproduzem a cronobiologia do cortisol e podem prejudicar os ritmos mediados pelo hipotálamo. Como glicocorticóides sintéticos podem melhorar o controle clínico, avaliamos os possíveis benefícios da terapia por um ano com fosfato de prednisolona (PD) em dose única matinal em 44 pacientes com D21OHD randomizados em 2 grupos: um (n=23) recebeu PD (2,4-3,5mg/m2SC) e o outro (n=21), HC 3 vezes ao dia (10-15mg/m2SC). Após um ano, a taxa de maturação óssea manteve-se estável no grupo PD (de 1,20 para 1,14), tendo aumentado discretamente (de 1,21 para 1,29) no grupo HC. A velocidade de crescimento (em SDS) foi preservada no grupo PD (de 1,2 para 1,2 no total de pacientes; 0,79 para 1,13 nos pré-púberes), enquanto discreto aumento ocorreu nos pré-púberes sob HC (1,1 to 1,9); a estatura para a IO (em SDS) elevou-se após um ano do uso de PD. Assim, pacientes com D21OH tratados por um ano com dose única matinal de PD parecem alcançar melhor controle clínico e hormonal do que aqueles usando 3 doses diárias de HC, permitindo inclusive a redução da dose. Nosso esquema atual de reposição com PD (1,5-3mg/m2SC/dia), sugere uma relação de bioequivalência HC:PD de 6-8:1.

One-year clinical evaluation of single morning dose prednisolone therapy for 21-hydroxylase deficiency.

Replacement schedules with hydrocortisone (HC) to treat 21OHD are generally unsatisfactory and partially successful regarding growth. Noncompliance is common since its short half-life requires TID administration. Even multiple daily HC doses do not reproduce cortisol chronobiology and may disturb hypothalamic-mediated rhythms. Because synthetic glucocorticoids could improve clinical control, we evaluated the possible benefits of a one-year treatment period with a single morning oral dose of prednisolone (PD) phosphate in 44 patients with 21OHD randomized to two sex and age-matched groups: one (n=23) receiving PD (2.4-3.5 mg/m2 BSA) and the other (n=21) TID HC (10-15 mg/m2 BSA). After one year, bone maturation ratio was kept stable in the PD group (from 1.20 to 1.14), whereas a slight increase was seen in the HC group (from 1.21 to 1.29). Growth velocity (SDS) was preserved in the PD group (from 1.2 to 1.2 in all; 0.79 to 1.13 in pre-pubertals), whereas a slight increase occurred in the pre-pubertal HC-treated patients (from 1.1 to 1.9); height SDS for BA increased significantly in the PD group. Thus, patients with 21OHD treated for one year with a single morning dose of PD appear to achieve a better clinical and hormonal control than those on TID HC, permitting a reduction of the replacement dose. The current PD schedule used by our group (1.5-3 mg/m2 BSA/day) suggests a higher HC:PD bioequivalence ratio of 6-8:1.