Neonates with hypothyroidism

Brain MRS Findings in Neonates with Hypothyroidism due to Intrauterine Iodine Deficiency ... 

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)... 

The median urinary iodine (MUI) concentration provided a measure of the current nutritional status of iodine. MUI was performed in spot urine samples obtained from all mothers and their neonates 5 days after delivery, by using the Sandell—Kolthoff reactions. Decreased MUI excretion of both neonates with hypothyroidism and their mothers was classified as mild-to-moderate iodine deficiency according to the WHO criteria. The mean total thyroid volume (TTvol) of the neonates and their mothers was increased on ultrasonography, whereas no palpable thyroid tissue was detected on physical examination (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... 

Table 65.2 Thyroid hormone ieveis of neonates with hypothyroidism and heaithy neonates (mean SD) ...

Hormone Neonates with hypothyroidism pefore therapy, 5-7 days of age) (n = 8) Healthy neonates (newborn 5-7 days of age) (n = 8) p value Neonates with hypothyroidism (after 8 weeks of therapy) (n = 8) Healthy neonates (after 8 weeks of therapy) (n = 8) p value... 

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). 

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 ... 

The principal change seen in the spectra of neonates with hypothyroidism is the presence of lower NAA/Cr ratios. As stated above NAA, almost exclusively present in the CNS, is the most sensitive CNS metabofite. Also called neuroaxonal marker, its decline is generally thought to reflect neuronal loss, damage, or dysfunction (Martin et al., 2005 Baslow, 2000). 

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). 

Many studies have shown NAA to be a good neuronal marker and, as such, its concentration (5—15mM) decreases with many injuries to the brain. Only functional neurons contain this metabolite. Metabolic disorders in childhood show low NAA/Cr ratios (Firat et aL, 2006). The lowest ratios are found in children with severe atrophy and white matter changes (Brockmann et al., 1996). Similar findings are also present in children with neuronal degenerative disorders. Recently, Akinci et al. (2006) have demonstrated the presence of decreased NAA/Cr ratios in neonates with congenial hypothyroidism. Patients with childhood adre-noleukodystrophy have decreased NAA/Cr ratios and increased Cho/Cr ratios (Tzika et al., 1993). 

In neonates with congenital hypothyroidism, brain metabolite changes may be detected by MRS. 

Cho level does not significantly differ among healthy neonates and in neonates with congenital hypothyroidism due to iodine deficiency. 

Interesting changes have been found in thyroid hormone levels in the neonatal period. It has been known for many years that serum T4 levels are normally higher in infancy than at any other time. Such elevations could well obscure a diminution in thyroid hormone levels associated with hypothyroidism, particularly partial hypothyroidism associated, for example, with dyshormonogenesis. Early detection of hypothyroidism is essential as treatment is simple and the consequences of delay in treatment are severe and to some extent, irreversible. 

In developing countries with more severe iodine deficiency, observations have now been made using blood taken from the umbilical vein just after birth. Neonatal chemical hypothyroidism was defined by a thyroxine level less than 3 ug/dl and TSH > 50 uU/ml). ... 

Developmentally, thyroid hormones interact with sex hormones such that hypothyroidism prolongs the critical period for testosterone-induced defeminization (see below) [3] in contrast, the hyperthyroid state prematurely terminates the sensitivity to testosterone [3]. Undoubtedly, an important link in these and other effects is synapse formation. Hypothyroidism increases synaptic density, at least transiently [3]. Interesting parallels with synapse formation are reported for learning behavior in rats neonatal hypothyroidism impairs learning ability, whereas hyperthyroidism accelerates learning initially, followed by a decline later in life [3]. 

Kallen and Robert (2000) found no adverse effects on congenital malformations, childhood cancer, infant mortality, low Apgar score, neonatal jaundice, or neonatal hypothyroidism among infants and children who lived in areas where drinking water was disinfected with chlorine dioxide, compared to controls living in... 

Neonatal goiter caused by the use of potassium iodine as an expectorant during pregnancy has been reported (67). The neonate, a girl, had acute hypothyroidism, with myxedema and respiratory distress. She was given levothyroxine for 6 months, with complete normalization of thyroid function. 

Neonatal hypothyroidism has been reported after maternal use of antithyroid drugs (106,107). Transient neonatal hyperthyroidism in a female child born to a mother who had been treated with potassium iodide and carbimazole during pregnancy was followed by sexual precocity (108). 

Refetoff S, Ochi Y, Selenkow HA, Rosenfield RL. Neonatal hypothyroidism and goiter in one infant of each of two sets of twins due to maternal therapy with antithyroid drugs. J Pediatr 1974 85(2) 240-4. 

The major adverse effect on the fetus is altered thyroid function (SEDA-13, 141 SEDA-14, 149 SEDA-19, 194 SEDA-20, 176). There have been individual reports of neonatal hyperthyroxinemia (79), goiter (80), and hypothyroidism (81). In the patient with goiter there was associated hypotonia, bradycardia, large fontanelles, and macroglossia (80). 

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. 

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... 

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