Subclinical 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. 

Patients with mild or subclinical hypothyroidism do not need to be started on the full replacement dose because they still have some endogenous hormone production. Start these patients on 25 to 50 meg/day, and titrate every 6 to 8 weeks based on TSH levels. Over time, it is likely that the LT4 dose will need to be increased slowly as the patient s thyroid gland loses residual function. 

Patients with subclinical hypothyroidism and marked elevations in TSH (greater than 10 miUi-intemational units per liter [mlU/L]) and high titers of TSAb or prior treatment with sodium iodide 131 may benefit from treatment with levothyroxine. 

Subclinical hypothyroidism - If this condition is treated, a lower levothyroxine... 

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. 

Kleiner, J., Altshuler, L., Hendrick, V, and Hershman, J.M. (1999) Lithium-induced subclinical hypothyroidism review of the literature and guidelines for treatment. / Clin Psychiatry 60 249-255. 

A common mistake is to treat bipolar depression in the same manner that one treats unipolar depression, overlooking the need for a mood stabilizer. In bipolar depression, the first pharmacological intervention should be to start or optimize treatment with a mood stabilizer rather than to start administering an antidepressant medication. In addition, thyroid function should be evaluated, particularly if the patient is taking lithium. Subclinical hypothyroidism, manifested as an increased thyroid-stimulating hormone level and normal triiodothyronine and thyroxine levels, may present as depression in affectively predisposed individuals. In such cases, the addition of thyroid hormones may be beneficial, even if there is no other evidence of hypothyroidism. 

Lithium Plus Thyroid Supplementation. Treatment-resistant and rapid-cycling bipolar patients may have an increased frequency of thyroid dysfunction. Further, some patients suffer from subclinical hypothyroidism and improve with the addition of thyroid supplementation. In this context, several case reports involving this population found that high doses of the thyroid hormone levothyroxine sodium (T ) were clinically beneficial (122,123 and 124). Kusalic (1.25) found that 6 of 10 rapid cyclers had hypothyroidism, based on their thyrotropin-releasing hormone stimulation tests. Further, the average number of mood episodes per year decreased by more than 75% (i.e., from 9.7 to 2.2) after thyroxine was added to the treatment regimen. 

Because lithium affects second-messenger systems involving both activation of adenylyl cyclase and phosphoinositol turnover, it is not surprising that G proteins are also found to be affected. Several studies suggest that lithium may uncouple receptors from their G proteins indeed, two of lithium s most common side effects, polyuria and subclinical hypothyroidism, may be due to uncoupling of the vasopressin and thyroid-stimulating hormone (TSH) receptors from their G proteins. 

Subclinical hypothyroidism, defined as an elevated TSH level and normal thyroid hormone levels, is found in 4-10% of the general population but increases to 20% in women older than age 50. The consensus of expert thyroid organizations concluded that thyroid hormone therapy should be considered for patients with TSH levels greater than 10 mlU/L while close TSH monitoring is appropriate for those with lower TSH elevations. 

Papi G et al Subclinical hypothyroidism. Curr Opin Endocrinol Diabetes Obes 2007 14 197. [PMID 17940439]... 

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. 

In 1989, in 150 patients at different stages of lithium therapy, thyroid function was assessed and subsequently 118 were reassessed at least once and 54 completed a 10-year follow-up (625). The annual rates of new cases of thyroid dysfunction were subclinical hypothyroidism 1.7%, goiter 2.1%, and autoimmunity 1.4%. While these figures were little different from those found in the general population, the authors acknowledged that lithium was a potential cause of thyroid dysfunction. 

Of 42 bipolar patients who had taken lithium for 4-156 months, three had subclinical hypothyroidism, three had subclinical hyperthyroidism, and one was overtly hyperthyroid (623). Ultrasonography showed that goiter was present in 38% and mild thyroid dysfunction was suggested in 48% because of an apparent increased conversion of free T4 to free T3. There was no correlation between the duration of lithium therapy and thyroid abnormalities. 

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). 

In a review of lithium-induced subclinical hypothyroidism (TSH over 5 mU/1, free thyroxine normal), a prevalence of up to 23% in lithium patients was contrasted with up to 10% in the general population. It was stressed that subclinical hypothyroidism from any cause can be associated with subtle neuropsychiatric symptoms, such as depression, impaired memory and concentration, and mental slowing and lethargy, as well as with other somatic symptoms. Management guidelines were discussed (628). 

A 63-year-old woman taking long-term lithium who developed subclinical hypothyroidism and primary hyperparathyroidism (641). 

Eiris-Punal J, Del Rio-Garma M, Del Rio-Garma MC, Lojo-Rocamonde S, Novo-Rodriguez I, Castro-Gago M. Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism. Epilepsia 1999 40(12) 1761-6. 

Aliasgharpour M, Abbassi M, Shafaroodi H, Razi F. Subclinical hypothyroidism in lithium-treated psychiatric patients in Tehran, Islamic Repubhc of Iran. East Mediterr Health J 2005 11 329-33. 

It has been suggested that thyroid hormone may minimize the cognitive effects of lithium (227) and a review of this suggested benefit in those patients taking lithium who had subclinical hypothyroidism (222). 

Of 42 bipolar patients who had taken lithium for 4—156 months, three had subclinical hypothyroidism, three had subclinical hyperthyroidism, and one was overtly hyperthyroid (256). Ultrasonography showed that goiter... 

In a review of lithium-induced subclinical hypothyroidism (TSH over 5 mU/1, free thyroxine normal), a... 

Cooper D S 2001 Subclinical hypothyroidism New England Journal of Medicine 345 260-265... 

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