Thyroid hormone deficiency

The adult brain is endowed with nuclear as well as cytosolic and membrane T3 receptors that have been visualized by autoradiography and studied biochemically [30-33]. Both neurons and neuropil are labeled by [ 1251]T3, and the labeling is selective across brain regions. Functionally, one of the most prominent features of neural action of thyroid hormone in adulthood is subsensitivity to norepinephrine as a result of a hypothyroid state [27], These changes may be reflections of loss of dendritic spines in at least some neurons of the adultbrain. Clinically, thyroid hormone deficiency increases the probability of depressive illness, whereas thyroid excess increases the probability of mania (Ch. 52) in susceptible individuals [27],... 

Xiao Q, Nikodem VM (1998) Apoptosis in the developing cerebellum of the thyroid hormone deficient rat. Front Biosci 3 A52-A57... 

TSH, or thyrotropin, is a glycosylated protein of two subunits, a and p. TSH stimulates the thyroid gland to produce thyroid hormones. Deficiencies are treated by giving thyroxine itself rather than TSH, but TSH is available for diagnostic purposes to differentiate between pituitary and thyroid gland failure as causes of hypothyroidism (see Chapter 65). 

There is no such clear cut difTcrcnlialiun as metamorphosis in the mammal, but development is an extremely complex process and has been shown to depend upon the presence of adequate amounts of thyroid hormones. Deficient development, especially of the central nervous system, is marked in ehildren suffering from thyroid deficiency early in life, ansi this inadequacy cannot be overcome completely by medication commenced after the first few weeks. In the adult, thyroxine is important in the maintenance of energy turnover in most of the tissues of the body, such as the heart, skeletal muscle, liver, and kidney, Other physiological functions, most notably brain aclivity and reproduction, are also dependent upon thyroxine, although the metabolic rales of the tissues concerned in these functions do not seem to be altered. 

It has long been known that thyroid hormone deficiency, when established prior to the critical period of brain development, produces severe and permanent mental retardation both in humans ( cretinism ) and in experimental animals (see Refs. 6 and 101). Most of the early studies aimed at describing the behavioural, physiolog-... 

Thyroid disorders may be divided into over- and underproduction of the thyroid hormones. These may be caused by thyroid gland disorders or disorders of the pituitary gland (TSH production) or hypothalamus (thyrotropin-releasing hormone release). Thyroid hormone deficiency in infancy may cause mental retardation if it is not corrected immediately after birth. For this reason, many states require thyroid function tests in all newborns. In adults, thyroid deficiency may be caused by Hashimoto s thyroiditis, an immune disorder, or dietary iodine deficiency, in which case it is called simple goiter. The term "myxedema" has been used to refer to hypothyroidism of whatever cause. Myxedemas may... 

Hypothyroidism is characterized by decreased plasma concentration of thyroid hormones, T3 and T4, with increased concentration of TSH. Severe thyroid hormone deficiency is known as myxoedema. 

Many structural or functional abnormalities of the thyroid gland can lead to thyroid hormone deficiency (Box 52-2). Primary hypothyroidism is frequently caused by diseases or treatments that directly destroy thyroid tissue or interfere with thyroid hormone biosynthesis. Secondary hypothyroidism occurs as a result of pituitary or hypothalamic disease and/or disorders. 

Thyroid hormone is essential for normal growth and development during embryonic life. Thyroid hormone deficiency during fetal and neonatal development results in mental retardation. There is slowing of physical and mental activity, as well as of cardiovascular, gastrointestinal, and neuromuscular function. Depression may result from untreated hypothyroidism. ... 

Hypothyroidism can lead to a variety of end-organ effects and a wide range of disease severity, from entirely asymptomatic individuals to patients in coma with multisystem failure. In the adult, manifestations of hypothyroidism are varied and nonspecific. In the child, thyroid hormone deficiency may manifest as growth retardation. 

Hypothyroidism (thyroid hormone deficiency) may result from autoimmune disease (Hashimoto s disease) or from deficient synthesis of TSH or TRH (thyroid-stimulating hormone-releasing factor). Because adequate ingestion of iodine is a prerequisite for thyroid hormone synthesis, iodine deficiency also causes hypothyroidism. In children, thyroid hormone deficiency (called cretinism) causes depressed growth and mental retardation. Severe hypothyroidism in adults (myxedema) results in symptoms such as edema (abnormal fluid accumulation) and goiter. Hypothyroidism is usually treated with hormone replacement therapy. 

Brouwer, A., P.J.H. Reijnders, and J.H. Koeman. 1989. Polychlorinated biphenyl (PCB)-contaminated fish induces vitamin A and thyroid hormone deficiency in the common seal (Phoca vitulina). Aquat. Toxicol. 15 99-106. 

Perhaps the most striking illustration of the pervasive developmental effects of thyroid hormones is provided by children with severe thyroid hormone deficiency from early childhood, a condition termed cretinism. This may either be endemic in regions of severe iodine deficiency or sporadic due to failure of the thyroid to develop normally or defects in the synthesis of thyroid hormone. Affected children are dwarfed with short extremities, have mental retardation, and are inactive and listless. Other manifestations include facial puffiness, enlarged tongue, dry and doughy skin, slow heart rate, and decreased body temperature. Eor full recovery, treatment of patients with cretinism must be initiated before these florid features are apparent. Thus, pregnant women in areas of endemic cretinism due to iodine deficiency are supplemented with iodine and aU newborns are screened for thyroid hormone deficiency in many developed nations. 

The thyroid gland is the only part of the body that absorbs iodine. Thyroid cells use iodine to produce thyroid hormones, which regulate metabolism. Low levels of iodine in the diet can lead to thyroid-hormone deficiencies and goiters, which are enlarged thyroid glands. In serious cases, low levels of thyroid hormones can cause birth defects and brain damage. In the United States, potassium iodide is added to most table salt to protect against dietary iodine deficiency. Even small amounts of added iodine can prevent iodine-deficiency disorders. However, there are parts of the world in which iodine deficiency is still prevalent. 

Table 64.1 Clinical features in neurological cretinism and in untreated congenital hypothyroidism Table 64.2 Conditions in which CNS damage has been associated with thyroid hormone deficiencies early in development and their prevention ...

Thyroid hormone deficiency during the development of CNS alters nerve cells, such as the pyramidal and Purkinje cells, and induces glial cell profiferation and differentiation. Under such conditions, neurons become hypoplastic, and have reduced axonal count, dendritic branching, synaptic spikes and interneuronal connections. 

Considering that T3 does not cross the placental membrane and, therefore, cannot be useful in treating fetal thyroid hormone deficiencies or in stimulating lung development immediately before premature birth, what would be your solution to overcome this problem ... 

In adult rats hypothyroidism does not appear to change the binding properties of the hepatic nuclear recetors [38-39] contrary to what is observed in the brain. The effect of thyroid hormone deficiency on brain nuclear receptors is not uniform in the anterior pituitary the Ka of the receptors increases [25,40] and their number decreases [25]. In the cerebral cortex however the affinity is significantly diminished [25,41] and the number of receptors increased [25,29,41,42]. The observations point to different regulatory mechanisms acting on thyroid hormone receptors in liver and brain, and within different areas of the brain. 

The specific brain and cerebral cortex molecular biological abnormalities that occur in the late gestation and neonatal period related to thyroid hormone deficiency that mi t have functional significance and... 

Since the hvt/hvt animals are deficient in thyroid hormcxie starting during late gestation, these animals afford a means of looking at the effects of thyroid hormone deficiency during a critical period of molecular biological and neuroanatomical development of brain with particular relevance for oer ral cortex. These animals may be used to... 

Microtubule ausserobly from hypothyroid preparations (Fig.2) was also tested (19,20) at day 15 postnatal the polymerization activity was similar to that measured at earlier stages O-S days) with the euthyroid preparations. Analysis of the MAPs present at day 15 postnatad also showed a hi ier proportion of immature Tau than in the control of the same age (20). Hiis suggested that the transition betsi een juvenile and mature Tau is delayed in hypothyroidism, a conclusion i ch mi it be sufficient to e3q)lain the lower polymerization activity produced by thyroid hormone deficiency. 

REVERSIBILITY OF THE CELL-TYPE SPECIFIC EFFECTS OF THYROID HORMONE DEFICIENCY DURING EARLY LIFE... 

---