Adult hypothyroidism

Evidence does exist that small differences in the LT4 dose can result in large changes in TSH. The impact on TSH of small changes in LT4 dose was assessed in 21 adult hypothyroid patients.21 When the daily dose was reduced by 25 meg, 78% had an elevated TSH level. When the daily dose was increased by 25 meg, 55% had a low TSH level. Clearly, differences in the LT4 dose or bioavailability within the FDA-allowed variance for bioequivalent products can cause significant changes in TSH. 

This disease is characterized by a decrease or lack of endogenic thyroid hormone secretion. When originating in childhood, it can be clinically described as cretinism (infantile hypothyroidism), and in adults as myxedema (adult hypothyroidism), which is expressed in a loss of mental or physical ability to work, suppression of metabolic processes in the body, and edema. Since thyroid function cannot be restored, the clinical effect is only visible when using thyroid hormones. Using thyroid hormones in hypothyroidism is a replacement therapy that does not correct the disease itself. 

There are many forms of hypothyroidism, differing in their cause and age of onset (see Table 31-1). Severe adult hypothyroidism (myxedema) may occur idio-pathically or may be caused by specific factors such as autoimmune lymphocytic destruction (Hashimoto disease). In the child, thyroid function may be congenitally impaired, and cretinism will result if this condition is untreated. Hypothyroidism may result at any age if the dietary intake of iodine is extremely low. Several other forms of hypothyroidism that have a genetic or familial basis also exist.54... 

Although Brian is tired and weak, with a puffy face and significantly increased body weight, all of which may be observed in myxoedema (a severe form of adult hypothyroidism), his thyroid hormones and TSH concentration are normal. In hypothyroidism T3 and T4 concentrations are usually low, which leads to an increase in TSH because of reduced negative feedback between the thyroid hormones and the anterior pituitary gland. 

Hypothyrodism and hyperthyroidism can both be due to a number of causes, one of which is metabolic dysfunction. Hypothyroidism is caused by undersecretion, of thyroid hormones. In one form of childhood hypothyroidism, children born with abnormally small thyroids produce insufficient levels of the thyroid hormones T3 and T4, which are important for metabolically directed bone development. If detected in the first 6 months of life, this disorder can be treated with synthetic thyroid hormones such that its effects can be avoided. The most severe early onset hypothyroidisms are characterized by Cretinism, a type of dwarfism, and mental retardation. Adult hypothyroidism is called myxedema. Myxedema symptoms include slowed speech, yellowed skin, and generally slowed body functions. Myxedema can also be treated with synthetic T4, but if left untreated, can lead to coma. 

Liel Y, Harman-Boehm I, Shany S. Evidence for a clinically important adverse effect of fiber-enriched diet on the bioavailability of levothyroxine in adult hypothyroid patients. J CUn Endocrinol Metab 1996 81 857-859. 

Thyroid hormone is used in adult hypothyroidism, in adult myxedema, and in cretiifism and juvenile hypothyroidism. 

RELATION OF IODINE TO THYROID FUNCTION Normal thyroid function requires an adequate intake of iodine without this, thyroid hormone cannot be made, TSH is secreted in excess, and the thyroid becomes hyperplastic and hypertrophic. The enlarged and stimulated thyroid becomes remarkably efficient at extracting the residual traces of iodide from the blood, developing an iodide gradient that may be 10 times normal. In mild-to-moderate iodine deficiency, the thyroid usually succeeds in producing sufficient hormone, in part by preferentially secreting T. In more severe deficiency, as is common in some parts of the world, adult hypothyroidism or cretinism may occur. 

Endemic cretinism (neurologic cretinism) Congenital hypothyroidism Myxedema (adult hypothyroidism)... 

In contrast, these problems do not arise in adult patients. Instead, adult hypothyroid patients suffer from a different... 

Morreale de Escobar, Reversible morphological alterations of cortical neurons in juvenile and adult hypothyroidism in the rat. Brain Res. 185 91-102 (1980). 

Z. Gottesfeld, C.J. Garcia and R.B. Chronister, Perinatal, not adult, hypothyroidism suppresses dopaminergic axon sprouting in the deafferented olfactory tubercle of adult rat, J. Neurosci. Res. 18 568 (1987). 

Iodine. Of the 10—20 mg of iodine in the adult body, 70—80 wt % is in the thyroid gland (see Thyroid and antithyroid preparations). The essentiahty of iodine, present in all tissues, depends solely on utilisation by the thyroid gland to produce thyroxine [51-48-9] and related compounds. Well-known consequences of faulty thyroid function are hypothyroidism, hyperthyroidism, and goiter. Dietary iodine is obtained from eating seafoods and kelp and from using iodized salt. 

Hypothyroid myopathy occurs in about 30% of patients with hypothyroidism irrespective of its cause. Muscle pain, cramps, and stiffness may be seen, and are often exacerbated by cold weather. Pseudomyotonic features of delayed muscle contraction and relaxation are common. Myoedema (the mounding phenomenon) is due to the painless, electrically silent contracture produced on direct percussion. Muscle biopsy often shows a predominance of type 1 (slow-twitch) fibers, again analogous to that seen in experimental hypothyroidism (Figure 22). Muscle hypertrophy with weakness and slowness of movement occurs in the Debre-Semelaigne syndrome seen in severely hypothyroid children, and Hoffman s syndrome is a similar condition seen in adults with hypothyroidism, but is also accompanied by painful spasms. 

Congenital hypothyroidism is still seen in the United States, and all newborns in the United States undergo screening with a TSH level. As soon as the hypothyroid state is identified, the newborn should receive the full LT4 replacement dose. The replacement dose of LT4 in children is age-dependent. In newborns, the usual dose is 10 to 17 mcg/kg per day. LT4 tablets may be crushed and mixed with breast milk or formula. Serum FT4 levels (target 1.6-2.2 ng/dL or 20.59-28.31 pmol/L) are used for dose titration in infants because the TSH level may not respond to treatment as it does in older children and adults. By 6 months of age, the required dose is reduced to 5 to 7 mcg/kg per day, and from ages 1 to 10 years, the dose is 3 to 6 mcg/kg per day. After age 12, adult doses can be given. 

Children treated with GH replacement therapy rarely experience significant adverse effects, whereas adults are more susceptible to dose-related adverse effects. Treatment with GH may mask underlying hypothyroidism. GH-induced symptoms, such as edema, arthralgia, myalgia, and carpal tunnel syndrome, are common and necessitate dose reductions in up to 40% of adults. Benign increases in intracranial pressure may occur with GH therapy and generally are reversible with discontinuation of treatment. Often, GH therapy can be restarted with smaller doses without symptom recurrence. 

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],... 

Hypothyroidism in adults and children in whom growth and puberty are complete-The average full replacement dose of levothyroxine is approximately 1.7 mcg/kg/day (eg, 100 to 125 mcg/day for a 70 kg adult). 

Congenital hypothyroidism - Siarimg dose is 5 mcg/day, with a 5 meg increment every 3 to 4 days until the desired response is achieved. Infants a few months old may require only 20 mcg/day for maintenance. At 1 year of age, 50 mcg/day may be required. Above 3 years, full adult dosage may be necessary. 

In the adult population, the prevalence of overt hypothyroidism is 19 per 1000 women and 1 per 1000 men with annual incidence of overt hypothyroidism is 4 per 1000 women and 0.6 per 1000 men. Subclinical hypothyroidism is also more common in women, the incidence increases with age, with up to 10% of women older than 60 years having an increased thyroid-stimulating hormone concentration. Subclinical hypothyroidism is more common in people who have been treated for hyperthyroidism with radioactive iodine or surgery, and in those with organ-specific autoimmune diseases, such as pernicious anaemia, type 1 diabetes mellitus, or Addison s disease. 

In adults, the signs and symptoms of hypothyroidism include somnolence, slow mentation, dryness and loss of hair, increased fluid in body cavities (e.g., the pericardial sac), low metabolic rate, tendency to gain weight, hyperlipidemia, subnormal temperature, cold intolerance, bradycardia, reduced systolic and increased diastolic pulse pressure, hoarseness, muscle weakness, slow return of muscle to the neutral position after a tendon jerk, constipation, menstrual abnormalities, infertility, and sometimes myxedema (hard edema of subcutaneous tissue with increased content of proteoglycans in the fluid). A goiter (i.e., enlargement of the thyroid gland) may be present. 

Juvenile or adult patients with primary hypothyroidism (as indicated by low serum free T4 and high serum TSH concentrations) are usually treated with thyroxine with the aim of relieving symptoms and reducing the serum TSH concentration into the normal reference range. If the primary hypothyroidism is the result of iodine deficiency, then gradually increasing dietary iodine supplementation may also be instituted in addition to the thyroxine replacement therapy. Iodine supplementation alone may lead to the development of acute hyperthyroidism. 

The etiology and pathogenesis of hypothyroidism are outlined in Table 38-5. Hypothyroidism can occur with or without thyroid enlargement (goiter). The laboratory diagnosis of hypothyroidism in the adult is easily made by the combination of a low free thyroxine and elevated serum TSH (Table 38-2). 

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