Hypothyroidism in adults

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). 

The most common cause of hypothyroidism is failure of the thyroid gland this is known as primary hypothyroidism. In adults, the cause of primary hypothyroidism is often spontaneous autoimmune disease (e.g., Hashimoto s thyroiditis) or destructive therapy for hyperthyroid states... 

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. 

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

The frequency of secondary or central hypothyroidism in adult patients is clearly lower than that of primary thyroid failure (Table 106.1). This form of hypothyroidism arises from diseases that interfere with the synthesis and release of hypothalamic TRH or pituitary TSH (Rose, 2001 Asteria et ai, 2001). The most common causes are pituitary adenomas and their therapy by surgery or radiotherapy. Less frequent causes of central hypothyroidism are hypothalamic tumors (craniopharyngioma), infiltrative diseases, head trauma, lymphocytic hypophysitis, infections, infarction and metastases (Beck-Peccoz et ai, 1996 Rose, 2001). 

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. 

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. 

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. 

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). 

There has been a retrospective study of the frequency of amiodarone-associated thyroid dysfunction in adults with congenital heart disease (41). Of 92 patients who had taken amiodarone for at least 6 months (mean age 35, range 18-60 years), 36% developed thyroid dysfunction— 19 became hyperthyroid and 14 hypothyroid. The mean dosage was 194 (100-300) mg/day, and the median duration of therapy was 3 (0.5-15) years. Female sex (OR = 3) and unoperated or palliated cyanotic congenital heart disease (OR = 7) were significant susceptibility factors for thyroid dysfunction. The risk was also dose-related. Although the authors conceded that they may have over-estimated the... 

Hypothyroidism, known as myxedema in adults, when severe, is the most common disorder of the thyroid gland. Worldwide, hypothyroidism is most often the result of endemic iodine deficiency. In nonendemic areas, where iodine is sufficient in the diet, chronic autoimmune thyroiditis (Hashimoto s thyroiditis) accounts for the majority of cases. This disorder is primarily characterized by high levels of circulating antibodies against a key enzyme (thyroid peroxidase) in the processing of iodine in the thyroid gland. Blocking antibodies directed at the TSH receptor may also be present. Thyroid destruction may also occur via apoptotic cell death. 

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... 

Cimino JA, Jhangiani S, Schwartz E, and Cooperman JM (1987) Riboflavin metabolism in the hypothyroid human adult. Proceedings of the Society for Experimental Biology and Medicine 184,151-3. 

In adult horses, thyroid gland enlargement is usually caused by adenoma of the thyroid gland. These tumors are benign and do not, in the vast majority of instances, alter thyroid function. These masses should be removed surgically if they obstruct the trachea or esophagus or if hypothyroidism can be documented. 

Shapiro LE, Sachchidananda J. 1982. Regulation of proteins by thyroid hormone and glucocorticoid The responses of hepatic a2 i-globulin and pituitary growth hormone differ in adult male hypothyroid rats. Endocrinology 8 653-660. 

Thyroid hormone stimulates production of IGF-I directly (liver) and indirectly (via increased growth hormone, GH). In adults with hypothyroidism, basal serum GH levels are normal, but the GH responses to provocative stimuli, nocturnal GH secretion, and serum IGF-I are all subnormal. In cretinism (infantile hypothyroidism), linear growth is severely retarded and the resultant dwarfism is characterized by a retention of the high upper to lower body ratio of infancy. The growth retardation in persons with cretinism is primarily due to delayed appearance of ossification centers in long bone, and secondarily to a deficiency in growth factors. 

TRH deficiency also causes hypothyroidism. In both adults and children it may occur as a result of cranial irradiation, trauma, infiltrative diseases, or neoplastic diseases. Hypothalamic hypothyroidism... 

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. 

Effects on the testis were evaluated in adult male rats that were neonatally exposed to either Aroclor 1242 ( iO, 40, or 80 mg/kg/day) or Aroclor 1254 ( 40 or 40 mg/kg/day) by daily subcutaneous injection from birth to PND 25 (Cooke et al. 1996). Examinations at 135 days of age showed significantly increased testis weight at 40 mg/kg/day Aroclor 1242 and 40 mg/kg/day Aroclor 1254, and increased daily sperm production at 10 mg/kg/day Aroclor 1242 and 40 mg/kg/day Aroclor 1254. Sertoli cell proliferation was also increased in exposed rats (only examined in 15-day-old pups treated with 40 mg/kg/day Aroclor 1242). Both Aroclor 1242 and 1254 also suppressed serum thyroxine (T4) concentrations and T4 replacement decreased or eliminated the testicular effects. As discussed in Section 3.2.2.8 (Endocrine Effects), other studies also indicate that hypothyroidism is involved in PCB-induced testicular effects in neonatal rats. Fertility tests showed that all Aroclor 1242-treated rats successfully impregnated unexposed females (Aroclor 1254 was not tested). 

Figure 98.3 Relationship between thyroid radiation dose and hypothyroidism rate in individuals less than 18 years of age (left panel) as compared to outoomes observed in adults. Based on published data of Peters et al., (1995). The shaded area shows the 95% confidence interval r = 0.98, P < 0.01.

More recendy, an increased risk of stomach, kidney and breast cancer was observed in adults treated with Importandy, these increased risks were seen in those patients who did not become hypothyroid, and no increased risk for cancer was seen in those patients who became hypothyroid (Metso et al, 2007a). An increased risk of cardiovascular mortality has also been observed in adults with hyperthyroidism due to toxic multinodular goiters, but not in adults with Graves disease (Metso et al, 2007b). 

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