Thyroxine neonatal

Use of measurement of blood thyroxine or thyroid-stimulating hormone (TSH) in the neonatal diagnosis of congenital hypothyroidism. 

Li Z, Li FX, Byrd D, Deyhle GM, Sesser DE, Skeels MR, Lamm SH (2000) Neonatal thyroxine level and perchlorate in drinking water. J Occup Environ Med 42 200-205... 

Amitai Y, Winston G, Sack J, Wasser J, Lewis M, Blount BC, Valentin-Blasini L, Fisher N, Israeli A, Leventhal A (2007) Gestational exposure to high perchlorate concentrations in drinking water and neonatal thyroxine levels. Thyroid 17 843-850... 

Iodine concentrations in breast milk and in random urine in neonates and the serum concentrations of neonatal TSH and free thyroxine on day 5 after delivery were measured after the use of povidone-iodine for disinfection after delivery (36). Iodine concentrations in the breast milk and neonatal TSH were significantly raised. Perinatal iodine exposure causes transient hypothyroidism in a significant number of neonates, in whom careful monitoring and follow-up of thyroid gland function are needed. It is better to avoid the use of iodine-containing antiseptics in pregnancy and neonates, especially if follow-up cannot be guaranteed. 

Serum TSH and thyroxine concentrations have been measured 57 days after birth in 365 healthy newborns whose umbilical stump had been treated with 10% povidone-iodine (41). The prevalence of high TSH concentrations was significantly higher in this group than in the general population (3.1% versus 0.4%), as was the rate of transient hypothyroidism (2.7% versus 0.25%). All the children were normal when retested 1 week later. Transient hypothyroidism due to skin contamination with povidone-iodine occurred in a neonate with an omphalocele (42). 

Graves disease may occur in the newborn infant, either due to passage of TSH-R Ab [stim] through the placenta, stimulating the thyroid gland of the neonate, or to genetic transmission of the trait to the fetus. Laboratory studies reveal an elevated free thyroxine, a markedly elevated T3, and a low TSH—in contrast to the normal infant, in whom TSH is elevated at birth. TSH-R Ab [stim] is usually found in the serum of both the child and the mother. 

And why is it that, while we could evoke these enzymes by cortisol (e.g. alanine aminotransferase) or thyroxine (malic enzyme) in neonatal life, we could not do so prenatally The explanation can clearly cannot lie in receptor availability since the same hormones do induce alternative enzymes at the same fetal stage. 

Because the irreversible mental retardation caused by neonatal hypothyroidism can be prevented by early treatment with thyroid hormone, the importance of early diagnosis of this disease has been emphasized. The difficulty of its early diagnosis by clinical features alone and its relatively high incidence have prompted the organization of various mass screening programs that include measuring thyroxine (T4) (D5) or TSH (13, Mil) by radioimmunoassay. 

Free Thyroxine. Measurement of free T4 radioimmunoassay in dried blood samples has been found to be useful to avoid false-positive results for low TBG in neonatal hypothyroid screening. Enzyme immunoassay of free T4 in serum was developed by Weetall et al. (W7) and subsequently by us (16). 

Neonates born to mothers taking lithium included a boy with a goiter and chemical hypothyroidism who required temporary treatment with oral thyroxine for 11 weeks... 

Iodine concentrations in breast milk and in random urine in neonates and the serum concentrations of neonatal TSH and free thyroxine on day 5 after dehvery were measured after the use of povidone-iodine for disinfection... 

Effects on the testis were evaluated in adult male rats that were neonatally exposed to either Aroclor 1242 ( iO, 40, or 80 mg/kg/day) or Aroclor 1254 ( 40 or 40 mg/kg/day) by daily subcutaneous injection from birth to PND 25 (Cooke et al. 1996). Examinations at 135 days of age showed significantly increased testis weight at 40 mg/kg/day Aroclor 1242 and 40 mg/kg/day Aroclor 1254, and increased daily sperm production at 10 mg/kg/day Aroclor 1242 and 40 mg/kg/day Aroclor 1254. Sertoli cell proliferation was also increased in exposed rats (only examined in 15-day-old pups treated with 40 mg/kg/day Aroclor 1242). Both Aroclor 1242 and 1254 also suppressed serum thyroxine (T4) concentrations and T4 replacement decreased or eliminated the testicular effects. As discussed in Section 3.2.2.8 (Endocrine Effects), other studies also indicate that hypothyroidism is involved in PCB-induced testicular effects in neonatal rats. Fertility tests showed that all Aroclor 1242-treated rats successfully impregnated unexposed females (Aroclor 1254 was not tested). 

It is usually performed either at birth, soon after the finding of elevated neonatal TSH levels, at 3 years of age after 1 month of L-thyroxine withdrawal, or on administration of RhTSH, which allows a precise diagnosis to be made and thus avoids the hypothyroid state. Finally the severe hypothyroidism resulting from TPO mutations should be promptly tteated with the thyroid hormone, in order to maintain TSH levels at the lower limit of the normal range. 

As stated above, MRS provides a noninvasive diagnostic tool for the biochemical characterization of pathophysiological processes in the brain. Therefore, in a recent study by Akinci et al. (2006), MRS was used to detect the changes in brain metabolites of neonates with hypothyroidism, born to mothers living in iodine-deficient areas before and after thyroxine replacement therapy. 

In that study, NAA, Cho and Cr were measured in frontal white matter (FWM), parietal white mater (PWM) and the thalamus of the eight full-term neonates with hypothyroidism. They were 5-7 days of age, and were born to mothers living in iodine-deficient areas. Their mothers had not received iodine supplementation in the pregestational or gestational period. A repeat MRS examination was performed after 8 weeks of thyroxine therapy. Metabolite levels of these patients were compared to levels obtained from eight full-term age-matched healthy neonates of mothers who had been using iodine-supplemented salt since the pregestational period. 

Serum total T4 (TT4), FT4 and TSH levels of the neonates and serum total T3 (TT3), TT4 and TSH levels of their mothers were measured. All the neonates with hypothyroidism had hormonal findings that were diagnostic of hypothyroidism. After 8 weeks of thyroxine therapy, euthyroidism was achieved in all the hypothyroid neonates (Table 65.2). The borderline elevation of TSH levels, accompanied by increased TT3 and near-normal TT4 levels, indicated the presence of subcfinical hypothyroidism in the mothers of neonates with hypothyroidism (Table 65.3)... 

All hypothyroid and healthy neonates underwent cranial MRS study between days 5 and 7 of life, just before thyroxine therapy, and this procedure was repeated after 8 weeks of thyroxine therapy in the neonates with hypothyroidism and 8 weeks after the first scanning in the healthy neonates. Cranial MRS was performed on a 1.5T scanner. Single-voxel spectroscopy was performed in all the hypothyroidand healthy neonates by using a point-resolved... 

Note Neonates with hypothyroidism had increased TSH ieveis and decreased TT4 and FT4 ieveis when compared with age-matched heaithy neonates. After 8 weeks of thyroxine therapy, thyroid hormones returned to normai ieveis (NS nonsignificant p> 0.05] TSH thyroid-stimuiating hormone TT4 serum totai T4 FT4 serum free T4). 

When compared with age-matched healthy neonates, hypothyroid neonates had lower NAA/Cr ratios in their PWM and thalamus before treatment p < 0.05) (Figure 65.2a, c). Interestingly, both groups did not differ significantly with regard to FWM NAA/Cr ratios (Table 65.4). After a thyroxine treatment for 8 weeks, NAA/Cr ratios in PWM and the thalamus were increased significantly... 

Figure 65.2 MR spectra in a neonate with hypothyroidism and an age-matched heaithy neonate. Neonate (patient) aged 5 days exhibits decreased NAA and increased Cho ieveis in pretreatment period (a) compared to its age-matched heaithy neonate (controi) (c). After 8 weeks of thyroxine therapy, NAA ievei increased (b) and reached the NAA ievei of the heaithy neonate (d).

The Cho/Cr ratios of the neonates with hypothyroidism in PWM, FWM and the thalamus were higher than the corresponding ratios of healthy neonates before initiation of the treatment. However, these differences were not statistically significant. At the end of 8 weeks of thyroxine... 

Notes Neonates with hypothyroidism had significantiy iower thalamic and parietal white matter NAA/Cr ratios than age-matched healthy neonates. After 8 weeks of thyroxine therapy, NAA/Cr ratios were normalized. Cerebral Cho/Cr ratios were not significantly affected in hypothyroidism (Cho ohoiine Cr creatine FWM frontai white matter NAA N-acetyl aspartate NS nonsignificant [p> 0.05] PWM ... 

Iodine is readily absorbed when PVP-I is applied to the skin of a newborn infant, because of high cutaneous permeability, and neonates are very sensitive to iodine overload, as described previously. Topical PVP-I therapy is associated with a significant risk of hypothyroidism in neonates, especially very-low-weight babies (Smerdely et ai, 1989). Many cases of hypothyroidism induced by topical use of PVP-I have been reported in newborn infants, mainly from iodine-deficient regions (Markou et ai, 2001). However, a case of severe hypothyroidism in a neonate was also reported from North America, an iodine-sufficient region (Khashu et al. 2005). A premature infant developed severe hypothyroidism that required L-thyroxine replacement therapy after application of PVP-I for 20 days. 

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