RESUMEN
OBJECTIVE: To study school achievement in grade 9 of compulsory school in children with congenital hypothyroidism (CH), both those detected by the national screening program and those with a normal screening result and thus diagnosed later. STUDY DESIGN: Nationwide study of children in the Swedish Medical Birth Register (n=1,547,927) from 1982 through 1997, linked to the neonatal screening CH cohort and the National School Register. Dried blood spot (DBS) samples are collected from all newborn infants, according to the neonatal screening program. Thyroid stimulating hormone (TSH) was used for CH screening. CH was defined as either having an abnormal screening result (DBS+) and treatment with levothyroxine, (LT4+), or having a normal screening result, but a CH diagnosis in the National Patient Register and treatment with LT4 (DBS-/ICD+/LT4+). Regression models were used to study school performance measured as grade point sum and national test results. Sibling analysis was also performed to account for unmeasured familial factors. RESULTS: There were 448 DBS+/LT4+ and 475 DBS-/ICD+/LT4+ children. Children with CH had lower grade point sum, adjusted ß=- 6.34 (95%CI: -11.7,-1.01) and adjusted ß= -10.3 (95% CI:-15.5,-5.20) for those with abnormal (DBS+/LT4+) and normal screening (DBS-/ICD+/LT4+) results, respectively. CH was also associated with lower result on the national tests, especially in mathematics. These associations remained in the sibling analyses. CONCLUSIONS: Youth with CH had slightly lower school achievements compared with those without CH and compared with their siblings. CH children with a normal screening result, and thus diagnosed later, presented the lowest results on grade point sum and national tests.
RESUMEN
There are 3 physiological waves of central hypothalamic-pituitary-gonadal (HPG) axis activity over the lifetime. The first occurs during fetal life, the second-termed "mini-puberty"-in the first months after birth, and the third at puberty. After adolescence, the axis remains active all through adulthood. Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by a deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) secretion or action. In cases of severe CHH, all 3 waves of GnRH pulsatility are absent. The absence of fetal HPG axis activation manifests in around 50% of male newborns with micropenis and/or undescended testes (cryptorchidism). In these boys, the lack of the mini-puberty phase accentuates testicular immaturity. This is characterized by a low number of Sertoli cells, which are important for future reproductive capacity. Thus, absent mini-puberty will have detrimental effects on later fertility in these males. The diagnosis of CHH is often missed in infants, and even if recognized, there is no consensus on optimal therapeutic management. Here we review physiological mini-puberty and consequences of central HPG axis disorders; provide a diagnostic approach to allow for early identification of these conditions; and review current treatment options for replacement of mini-puberty in male infants with CHH. There is evidence from small case series that replacement with gonadotropins to mimic "mini-puberty" in males could have beneficial outcomes not only regarding testis descent, but also normalization of testis and penile sizes. Moreover, such therapeutic replacement regimens in disordered mini-puberty could address both reproductive and nonreproductive implications.