Cerebral hypothyroidism

There is much anecdotal evidence coming from observations in Europe over the past 150 years (Hetzel, 1989) supported by reports from China (Ma et ai, 1989), India, and Indonesia (Hetzel, 2004), indicating that iodine-deficient village populations suffer from general lethargy, poor work performance and defective school performance in children. These effects are due to hypothyroidism, particularly cerebral hypothyroidism. Beneficial effects of iodization programs on this state have also been described (Li and Wang, 1987 Hetzel, 2004). 

This is quantitatively probably the most frequent component of the IDD spectrum. Cerebral hypothyroidism refers to the effect of hypothyroidism on the brain in childhood and adult life, in contrast to the effect on the fetus and in early infancy. There is a more striking effect of hypothyroidism on the brain than on other organs. This produces the characteristic mental torpor and apathy characteristic of the iodine-deficient subjects - it can be reversed at the population level by correction of iodine deficiency, just as it can be reversed in an individual patient by treatment with thyroid hormones (Hetzei, 2004). In a severe endemic, 30-70% of the population may be suffering from cerebral hypothyroidism, as indicated by a low serum thyroxine level (T4) (Buttfield and Hetzei, 1967 Kochupillai ft (S /., 1973). 

Carlanega, A. Ruiz-Marcos, L. Lamas, F. Escobar del Rey, and G. Morreale de Escobar, Cerebral hypothyroidism in rats with adult-onset iodine deficiency. Endocrinology 115 1 (1984). 

Not all postnatal effects of ID are necessarily due to damage during the fetal and postnatal periods. A decrease in the amount of T3 in the brain and in cerebral nuclei, accompanied by decreased neuronal connectivity, may also be observed in "acquired" ID. Thus, some of the consequences of severe ID might be due to continuing post-natal cerebral hypothyroidism and be potentially reversible. 

Concomitant conditions Because of the possibility of an accidental reaction, use with caution in patients with diabetes mellitus, hypothyroidism, epilepsy, cerebral... 

In contrast to the type I deiodinase which shows a high preference for rT4 over T4 as the substrate (Table II), the type II enzyme is somewhat more effective in the deiodination of T4 than of rT3 (Table III). Under the conditions tested, the Km value of T4 for the type II enzyme is three orders of magnitude lower than the Km of T4 for the type I deiodinase. The Km of rT3 for the type II deiodinase is somewhat greater than that of T4 and differs less from the Km of rT3 for the type I enzyme. The Umax of the conversion of T4 to T3 by the type II enzyme depends on the tissue and the thyroid status of the animal (see below). In cerebral cortex of hypothyroid rats [82] it is roughly one-thousandth of the maximum T3 production by the hepatic type I deiodinase of euthyroid animals determined under similar conditions [32]. The VmiJKm ratio of this reaction is, therefore, similar for the type II deiodinase of hypothyroid rat brain and the type I deiodinase of euthyroid rat liver and much greater than that for the hepatic enzyme of hypothyroid rats [86], In view of the reaction kinetics of the type II deiodinase (see below), it is questionable if the Vm,JKm ratios estimated in vitro also apply to physiological conditions with unknown cofactor availability. 

Cerebral tumors and cerebrovascular disease Metabolic diseases Porphyria Hypothyroidism Hypercalcemia Pheochromocytoma Uremia... 

DeLong (1987), as a result of careful clinical neurological studies in a number of endemic diseases, has concluded that the major defaults are intellectual deficiency, deafness and motor rigidity, which indicate that the most affected parts of the CNS are the cerebral neocortex, the cochlea and the basal ganglia. They all undergo rapid changes in the second trimester, and would be vulnerable to the effects of iodine deficiency through maternal hypothyroidism at that time. 

In areas of iodine deficiency Karmarkar et al. (1993) found D2 activity in human cerebral cortex at 11—14 weeks gestational age, which did not respond to a decrease in maternal T4 caused by iodine deficiency. To which extent this indicates that a delay in the capacity of D2 to respond to hypothyroidism or the T4 levels in the brain should be much lower to observe increases in D2 activity remains to be studied. 

A/-acetyl aspartate NAA 2.0 and 2.05 Largest peak in normal spectra Marker for functional neurons (reflects neuronal and axonal integrity) Increases with age Decreases in most cerebral insults, including degenerative diseases Decreases in hypothyroidism Increases only in Canavan disease... 

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 ... 

Hypothyroidism and Major Cerebral Metaboiites Effects of Thyroxine Therapy on /V-Acetyi Aspartate and Choiine Leveis... 

Bernal (2005) reviewed the morphological aspects in the brain of the hypothyroid rat and found (1) altered cell migration, particularly in the cerebellum and cerebral cortex (2) increments in cell density, caused by a reduction in the neuropil (3) markedly reduced dendritic arborization in the Purkinje cells of the cerebellum, and decreased and altered distribution of the pyramidal dendritic spines in the cortex layer V and finally (4) delayed myelination and poor myelin deposit in the white matter and fewer myelinated axons. This study further showed that hypothyroidism produces changes in the colossally projecting neurons, which may be due to the maintenance of juvenile patterns of projections. In addition, a recent report (Lavado-Autric et al., 2003) indicates that focusing on maternal hypothyroidism can produce migration defects in the fetal cortex, when... 

Abnormalities in specific regions of the cerebral cortex and its corticospinal projections, associative cortex and myelination are likely to contribute to neurological impairments in both rats and humans afflicted with hypothyroid disorders. However, although these findings provided us with information about the role ofTH in brain development, they do not provide insight into the developmental timing of TH action on specific brain areas that may underlie the aforementioned observations in children. 

Cerebral computed tomography (CT) scanning in patients with EC was reported to show basal ganglia calcification in 30% (15 of 50 cases) and mild cerebral atrophy in 8% (4 of 50 cases) (Halpern et al., 1991). AH three children in our study of infant-onset hypothyroidism who exhibited... 

Multiple neuroendocrine and metabolic finks exist between arterial hypertension and hypothyroidism. Metabolic and neuroendocrine alterations may be associated with arterial hypertension, inducing both adjunctive cardiovascular risk and vascular, cerebral, renal and cardiac pathologies (so-called hypertensive target organ damage ). A hypothyroid dysfunction may interact with all these factors and conditions. 

Similarly to arterial hypertension, hypothyroidism may induce left ventricular hypertrophy, diastofic and systolic dysfunction, glomerulosclerosis and renal insufficiency, cerebral edema, microvascular disease and dementia. 

Causes of constipation in infants and children include functional constipation, neurogenic constipation [aganglionosis, hypoganglionosis, neuronal intestinal dysplasia (NID)], chronic intestinal pseudo-obstruction, disorders of the spinal cord, cerebral palsy, constipation secondary to anal fissures and strictures, neonatal hypothyroidism and drug induced constipation (Potter 1998). 

Two of these incidents may have contributed to the death of a patient (a 10-fold morphine overdose in a premature, unstable patient and dysfunctional cerebral function monitoring that delayed treatment of seizures). Another five incidents were expected to result in permanent major harm 3-day delay in test results for congenital hypothyroid disorder, defective ventilator resulting in severe metabolic acidosis, arterial line occlusion resulting in foot necrosis, bums due to chlorhexidene, and skin necrosis after subcutaneous infusion of packed cell. 

Thus the Type I 5 deiodinase activity in cerebral cortex, like that in the liver, requires an active sulfhydryl group, the carboxymethylation of which causes enzyme inactivation. In hypothyroid animals, most of the rT3 is deiodinated by the Type II pathway, since the Type I activity is reduced, and Type II activity increased several fold. Further studies with brain and brown adipose tissue microsomes have shown that the sensitivity of Type II activity to PTU is inversely related to the DTT concentration used during the assay, so that it is important to keep this factor in mind when assessing the sensitivity of a particular enzymatic activity to inhibition by this agent (15,16). Interested readers are referred to these references for a more thorough discussion of this complex area. While the two 5 deiodinase activities are quite distinct enzymatically, until such time as the protein sequences are determined, a definitive answer as to their structural similarities cannot be given. 

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