Thyroxine cretinism

A deficiency of iodine results iu insufficient synthesis of thyroxine and a low plasma level, so that secretion of TSH is increased in an attempt to stimulate synthesis but this results in enlargement of the thyroid gland (goitre). Iodine deficiency in pregnancy impairs brain development in the foetus, causing mental retardation (known as cretinism). Indeed iodine deficiency is one of the major public health issues worldwide an estimated 200 million people are affected. 

Too little thyroxine may lead to cretinism in children, with poor growth and mental deficiency, or myxoedema in adults, resulting in a slowing down of all body processes. 

Thyroxine. The thyroid gland of the neck secretes a hormone whose primary function seems to lie in a regulation of the body s energy metabolism. Those whose thyroid gland is deficient suffer from hypothyroidism. They are slow, soporific, and apparently lazy they put on weight but never seem to have the energy to act. If the disease occurs in early childhood, the infant becomes a cretin ... 

In Papua New Guinea, Pharoah and Connolly (1987) have described varying scenarios ranging from stillbirths to cretinism, and less severe neurological defects of motor and cognitive performance. These effects could be correlated with the level of maternal thyroxine (T4), but not with maternal triiodothyronine (T3), indicating the importance of maternal T4 to the fetus. 

Iodine deficiency is the most preventable cause of mental retardation. The food produced in iodine-deficient areas fails to provide sufficient iodine intake, resulting in reduced production of the thyroid hormone thyroxin, which is critical for brain development (Bernal et ai, 2003). Depending on its severity, iodine deficiency affects mental and physical development up to the most severe form of hypothyroidism and cretinism. 

Figure 108.1 Human fetal and neonatal hypothyroid syndromes iodine defioienoy and endemic cretinism. If environmental iodine deoreases, maternal iodine deficiency in early pregnancy will not provide the fetal thyroxine required for neural development. Insuffioient supply of iodine leads to fetal and neonatal hypothyroidism.

Excessive levels of thyroxine cause which one of the following (a) Hyperactivity (h) Cretinism... 

This is further indicated by evidence of the relation of maternal thyroxine levels to the risk of cretinism and the psychomotor defect from studies in Papua New Guinea (26). The subsequent lack of fetal thyroid hormones due to the inadequate supply of iodine in iodine deficiency would exacerbate the effects of maternal thyroid insufficiency and the combination of effects, which were represented experimentally in the sheep by maternal thyroidectomy before conception (21) combined with fetal thyroidectomy at 98 days (12), might be expected to produce the multiple defects of neurological cretinism. 

The first 3 cases (serial nos 604, 638, 515) in the table had hormonal profiles entirely consistent with severe hypothyroidism although these women did not exhibit the clinical features of hypothyroidism In all three cases the pregnancy outcome was a stillblrth/early neonatal death In the succeeding 3 cases (serial nos 568, 245, 430) the maternal total and free thyroxine values were low but triiodothyronine values were within the normal range In one of these the outcome was a stillbirth/early neonatal death and one child has a hearing/speech defect but no other abnormality and, by our definition, cannot be labelled as an endemic cretin ... 

Another case (serial no 398) is of particular interest in that the child exhibits the clinical features of cretinism The maternal thyroxine and TSH values were abnormal and consistent with hypothyroidism but the triiodothyronine values were within the normal... 

SERUM THYROXINE LEVELS IN CRETINS NORMAL ADULTS IODISED OIL SALINE... 

There is a spectrum of Impairment ranging from death through clinical endemic cretinism and subclinical deficits of motor and cognitive performance, to normality. This spectrum of effects appears to be associated with maternal thyroxine during pregnancy. No association with maternal triiodothyronine was found. 

The myxoedematous form of endemic cretinism, which is still prevalent in many parts of the world (CoNTEMPRE et al. 1991), is not only due to the lack of iodine, but also of selenium. The selenoprotein type 1 5 -deiodinase catalyses the deiodination of the prohormone L-thyroxine (3,3 ,5,5 -tetraiodo-L-thyronine, T4) to the biologically active form 3,3 ,5-triiodo-L-thyronine (L-T3). During fetal development the maternal organism contributes at least minimal amounts of thyroid hormone for the fetus. After birth, the baby then slowly reaches the condition of thyroid hormone deficiency, because contin-... 

In patients with the coupling defect, iodine uptake by the thyroid is high, but the release of the radioactive halogen from the gland follows an almost normal pattern. Chemical analysis of thyroid biopsies of such cretins yields high levels of MIT and DIT. In contrast, thyroxine is virtually absent from the gland. 

The mechanism by which the absence of the dehalogenase leads to low thyroxine levels and cretinism is not clear. Two different theories have been proposed. The first postulates the existence of an additional defect namely, an inability to couple iodotyrosine to form T3 and T4. The second proposes that the absence of dehalogenase leads to a glandular hyperfunction in which hormone precursors are released before they can be used for thyroglobulin biosynthesis. It has now been established that the dehalogenase defect results from the absence of a single autosomal recessive gene. 

Thyroxine (also known as Levothyroxine or T4) is the ultimate metabolism regulator. Its reactions and products influence carbohydrate metabolism, protein synthesis and breakdown, and cardiovascular, renal, and brain function. Thyroxine is essential to an animal s functions and it is essential for development in the young. Tadpoles won t develop into frogs, for example. Untreated human babies will develop cretinism, a condition marked by severe mental and physical retardation. Adult humans with low thyroxine levels (hypothyroidism) suffer mental slowness, weight gain, depression, and fatigue. ... 

Supplying a missing protein or metabolite if its production is blocked, e.g. injections of antihaemophilic globulin to haemophiliacs, thyroxine administration to goitrous cretins, blood transfusion for thalassaemic patients. 

Further data from Papua New Guinea indicates a relationship between the level of maternal thyroxine with the outcome of current and recent past pregnancies including mortality and the occurrence of cretinism. There were proportionally more perinatal (i.e., stillbirths and neonatal) deaths, and cretins, among the offspring of women who showed the lowest levels of serum thyroxine ... 

At least 1 billion people live in iodine-deficient areas, and 200 million suffer from goiter (Onuma Okezie 1998). A severe iodine deficiency during pregnancy can cause extreme and irreversible mental and physical retardation, known as cretinism. Iodine is essential for the synthesis of thyroxin, and tri-iodothyronine or thyroid hormones necessary for normal cell metabolism. Its deficiency affects approximately 6 million people worldwide, and can be averted by early diagnosis and treatment. A worldwide effort to provide iodized salt has been very successful in preventing cretinism. 

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