Overt hypothyroidism

Anti-TPOAb Less than 1 00 units/mL Present in autoimmune hypothyroidism predicts more rapid progression from subclinical to overt hypothyroidism... 

A TSH level of 4.5 to 10 milliunits/L constitutes mild or sub-clinical hypothyroidism, and some patients with a TSH level of 2.5 to 4.5 milliunits/L also may be mildly hypothyroid. A TSH level greater than 10 milliunits/L signifies overt hypothyroidism." The free T4 level will be normal (0.7-1.9 ng/dL or 9.0-24.5 pmol/L) in mild or subclinical hypothyroidism and low (less than 0.7 ng/dL or 9.0 pmol/L) in patients with obvious signs and/or symptoms. 

LT4 is indicated for patients with overt hypothyroidism.22 However, the need for treatment is controversial in patients with mild or subclinical disease (TSH less than 10 milli-units/L). There are no large clinical trials that show an outcome benefit with treating these patients, and the therapeutic decision must be individualized.1,23 Many patients with subclinical hypothyroidism do, in fact, have subtle symptoms that improve with LT4 replacement. If the patient s serum cholesterol is elevated,24 or if serum anti-TPOAbs are present, many clinicians recommend LT4 therapy. 

In patients younger than age 65 with overt hypothyroidism, the average LT4 replacement dose is 1.6 mcg/kg per day (use ideal body weight in obese patients25). If there is no history of cardiac disease, these patients may be started on the full replacement dose. The full replacement dose in patients over age 75 is lower, about 1 mcg/kg per day.26 In the elderly, the starting dose is 25 to 50 meg/day, and the dose is titrated to the... 

Provide LT4 replacement to patients with overt hypothyroidism. 

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. 

Clinical manifestations of overt hypothyroidism are usually obvious though minor deficiencies may be more easily missed they may have pronounced adverse effects on patients well-being. The diagnosis nowadays should always be confirmed biochemically (with detection of low serum T4 and high TSH levels), and highly sensitive and specific immunoassays are now readily available in most countries. 

Since thyroid illness is commonly associated with depression, especially in women, it has long been observed that treating the thyroid abnormalities also can reverse the depression. This is especially true for treating hypothyroidism with thyroid hormone replacement (either T3 or T4). It has even been observed that giving supplemental thyroid hormone to depressed patients unresponsive to first-line antidepressants but without overt hypothyroidism can boost the antidepressant response of the first-line antidepressant (thyroid combo in Fig. 7—30). Thyroid hormone is also commonly administered to bipolar patients resistant to mood stabilizers, particularly those with rapid cycling (see discussion of combinations for bipolar disorders below). 

The complexity of the interaction between iodine intake and autoimmune thyroid disease has been highlighted by reports of evidence that iodide (compared with thyroxine) induces thyroid autoimmunity in patients with endemic (iodine deficient) goiter (43), while in those with pre-existing thyroid autoimmunity, evidenced by the presence of antithyroid (thyroid peroxidase) antibodies, administration of iodine in an area of mild iodine deficiency led to subclinical or overt hypothyroidism (44). 

Patients with beta-thalassemia major have an increased risk of primary hypothyroidism. In 23 patients with beta-thalassemia amiodarone was associated with a high risk of overt hypothyroidism (33 versus 3% in controls) (43). This occurred at up to 3 months after starting amiodarone. The risk of subclinical hypothyroidism was similar in the two groups. In one case overt hypothyroidism resolved spontaneously after withdrawal, but the other patients were given thyroxine. After 21-47 months of treatment three patients developed thyrotoxicosis, with remission after withdrawal. There were no cases of hyperthyroidism in the controls. The authors proposed that patients with beta-thalassemia may be more susceptible to iodine-induced hypothyroidism, related to an underlying defect in iodine in the thyroid, perhaps associated with an effect of iron overload. 

Lithium-induced hypothyroidism has been briefly reviewed (626). Some patients develop more persistent subclinical hypothyroidism (TSH over 5 mU/1, free thyroxine normal) and others overt hypothyroidism (higher risk in women, in those with pre-existing thyroid dysfunction, and those with a family history of hypothyroidism). Since subclinical hypothyroidism is not necessarily asymptomatic, treatment with thyroxine may be necessary in this group (627), as well as in those with more obvious hypothyroidism (628). 

In 1705 patients, aged 65 years or over, who had recently started to take lithium, identified from the 1.3 million adults in Ontario receiving universal health care coverage, the rate of treatment with thyroxine was 5.65 per 100 person-years, significantly higher that the rate of 2.70/100 person-years found in 2406 new users of valproate (629). Of 46 adults taking lithium in a psychiatric clinic, 17% developed overt hypothyroidism while 35% had subclinical hypothyroidism (raised concentrations of thyroid stimulating hormone, TSH) (630). 

No patients with depression had clinical hypothyroidism and the sole patient with overt hypothyroidism had no depressive symptoms. 

The occurrence of thyroid dysfunction in 72 patients treated with interferon alfa plus ribavirin (1.0-1.2 g/day) has been compared with that of 75 age- and sex-matched patients treated with interferon alfa alone for chronic hepatitis C (177). Of the former, 42 patients, and of the latter, 40 patients had received previous treatment with interferon alfa alone. There was no difference in the rate of thjroid autoimmunity (antithyroglobuUn, antithjroid peroxidase, and thyroid-stimulating hormone receptor antibodies) between the two groups, but the patients who received interferon alfa plus ribavirin developed subclinical or overt hypothyroidism more often (15 versus 4%). Similarly, the incidence of hypothjroidism increased to 19% in patients who underwent a second treatment with interferon alfa plus ribavirin compared with 4.8% after the first treatment with interferon alfa alone, while the incidence remained essentially the same in patients who had two consecutive treatments with interferon alfa alone... 

A small number of patients treated with Li develop diffuse thyroid enlargement patients usually remain euthyroid, and overt hypothyroidism is rare. In patients who do develop goiter, discontinuation of Li or treatment with thyroid hormone results in shrinkage of the gland. 

In Denmark, we studied the incidence of overt hypothyroidism before the Danish iodine program in two areas with a small difference in iodine intake caused by different iodine contents of groundwater. The population hv-ing in the area with only mild iodine deficiency had a considerably higher incidence of overt hypothyroidism than the population with moderate iodine deficiency, whereas the lower iodine intake was associated with more hyperthyroidism (Figure 47.5) (Billow Pedersen et aL, 2002). Subtyping of disease revealed that the difference in hypothyroidism was caused by 50% more cases of spontaneous autoimmune hypothyroidism in the area with the highest iodine intake (Carld et ai, 2006). 

The above-mentioned facts form the basis of a new concept of the adverse effects of not only maternal hypothyroidism, but also maternal hypothyroxinemia without overt hypothyroidism, on fetal brain development. This concept focuses on the necessity for therapeutic correction of maternal hypothyroxinemia detected in pregnancy. MRS, a quantitative laboratory and imaging technique, may be used to show the effects of hypothyroxinemia due to iodine deficiency and its correction in the human brain in an objective manner. 

For the vast majority of clinicians, hypothyroxinemia is regarded as a physiological condition, not requiring treatment and not to be included in the well-defined spectrum of thyroid underfunction disorders, such as subclinical or overt hypothyroidism. In 2000 however, the review by Gabriella Morreale de Escobar entitled... 

Over the normal Below the normal Overt hypothyroidism... 

Treatment with levothyroxine is favored in patients with elevated TSH, indicating subclinical or overt hypothyroidism, mostly due to Hashimoto s thyroiditis. In diffuse goiter and nodular thyroid disease, the former practice of sole levothyroxine administration, without additional measures to correct iodine deficiency, has become obsolete, unless the patient lives in an area of ample alimentary iodine supply. 

---