Subclinical Hypothyroidism: To Treat or Not to Treat
An examination of subclinical hypothyroidism, and when it should be treated.
By Bridget Bellingar, DO
As serum TSH (thyroid stimulating hormone) assays have became the standard for the evaluation of thyroid function, subclinical hypothyroidism is becoming more frequently detected. Subclinical hypothyroidism not only has a narrow base of literature and research, the TSH level also has a much narrower window.
Controversy exists as to what is the best approach to treat this disorder. Who should be treated, if and when? The prevalence of subclinical hypothyroidism varies by age, sex, and iodine intake, with estimates ranging from 1.3 percent to 17.5 percent.(15)
The individual variation in peripheral thyroid hormone levels is much narrower than the laboratory reference range, as serial measurements in the same person vary little over a 12-month period.(1) A free thyroxine (T4) level may be significantly decreased in a patient, but still may be in the normal, accepted laboratory range. A slight reduction in serum thyroxine levels can be associated with an increase of TSH, despite a peripheral hormone level that is in the normal laboratory reference range. This condition is called subclinical hypothyroidism, or more appropriately, mildthyroid failure.(2, 3)
The accepted range of normal serum TSH is (0.3) to 5 mIU/L, although there is substantial debate that suggests that the normal range should be (0.3) to 3 mIU/L. If this new range were implemented, the results would be that one in five patients without a history of thyroid disease would be classified as biochemically hypothyroid.(4) Some studies show that patients whose TSH level is 3 to 5 mIU/L are more likely to test positive for thyroid antibodies and are at a higher risk for overt hypothyroidism.(13)
Most physicians elect to perform routine screening with serum TSH, or to measure TSH in patients with persistent nonspecific symptomatic complaints while including those patients that have risk factors for thyroid failure. However, in the elderly, with mild thyroid failure and hypothyroid symptoms and a serum TSH level between 3 and 5 mIU/L, any treatment could risk the suppression of TSH production and result in the adverse effects of hypothyroidism. Subclinical hypothyroidism is more common in women than in men, and findings indicate that approximately one woman in four with this condition will benefit from thyroxine treatment.(11)
Ruling Out Other Causes
Before a diagnosis of hypothyroidism can be made, other causes must be ruled out. Other such causes include acute hospitalization illness, nocturnal surge in TSH secretion, assay variability, medications, TSH-secreting adenomas and thyroid hormone resistance. Rheumatoid factor, renal or adrenal failure, and recent medication adjustment also need to be considered. In thyroid hormone resistance and adenomas, the peripheral thyroid hormone levels are elevated, whereas in subclinical hypothyroidism the free thyroxine are in the normal- or low-normal range.
Diagnosis of subclinical hypothyroidism is not based on a single TSH measurement. Two values within several weeks is preferred. There is no mention in the literature whether the TSH level is best checked in the morning or afternoon. Once medication is initiated, a serum TSH should be rechecked a minimum of six to eight weeks later and adjusted appropriately.
The causes of subclinical hypothyroidism include: Autoimmune thyroid disease (Hashimoto thyroiditis) inadequately treated hypothyroidism, inflammatory bowel disease (any mal-absorption syndrome), inadequately treated hypothyroidism, radiation therapy, postpartum thyroiditis, pregnancy, hyperthyroidism treatment, and medications (including iodine administration, lithium, amiodarone and quetiapine(6)). Medications such as oral contraceptives, tyramine, ferrous sulfate, antacids containing aluminum hydroxide, calcium supplements, anticonvulsants, rifampin, sulcralfate, high-fiber diet, carbamazepine, and soy can interfere with the absorption of thyroid replacement.
Overt hypothyroidism is a risk factor for coronary artery disease. In subclinical hypothyroidism homocysteine levels are not elevated as in overt hypothyroidism. A study(5) suggests that levels of C-reactive protein are elevated in subclinical hypothyroidism, and are a strong indicator of risk for atherosclerosis and myocardial infarction.(9)
Defining Subclinical Hypothyroidism
The term “Subclinical Hypothyroidism” describes a condition that exhibits an elevated TSH levels and normal level of circulating thyroxine (T4).(7) The Third National Health and Nutrition Examination Survey (NHANES III) noted that subclinical hypothyroidism was present in 5.8 percent of white non-Hispanic women, 1.2 percent of black non-Hispanic women,
and 5.3 percent of Mexican-American women.(5)
The clinical features of hypothyroidism include fatigue, weight gain and fluid retention, dry skin, cold intolerance, coarse or thinning hair, hoarse voice, goiter, reflex delay, ataxia, constipation, lack of concentration, depression, pre-productive abnormalities, myalgias, bradycardia, myxedema and hypothermia. Some of these extreme symptoms are associated with overt hypothyroidism, and not with subclinical hypothyroidism. Data supporting the treatment for subclinical hypothyroidism with a TSH in the range of 3-5 with an associated relief of hypothyroid symptoms are few.
In one study(10) 33 patients having subclinical hypothyroid symptoms were compared with symptoms in 20 euthyroid patients in the same clinic. The dry skin, cold intolerance and easy fatigability were more common in the patients with elevated TSH, and these symptoms improved after thyroid hormone treatment. In another study(11) approximately one woman in four having subclinical hypothyroidism benefited from thyroxine treatment. In another study,(12) small changes in thyroxine (T4) dosage did not produce measurable changes in hypothyroid symptoms, well-being, or quality of life, despite the expected changes in serum TSH.
In healthy patients having a TSH level of 4-7, the frequency of hyperlipidemia and hypothyroid symptoms may be no different than euthyroid patients. Therefore, should the subclinical hypothyroidism be treated?(8) In this author’s private family practice, an attempt with a trial period of thyroid replacement to reach a TSH of 2mIU/L for relief of bothersome symptoms such as fatigue, cold intolerance, weight gain and depression is attempted. It is mandatory to fine-tune the serum TSH to avoid hyperthyroidism.
Treatment can fall into three categories:
Treatment of Subclinical Hypothyroidism
Treatment of subclinical hypothyroidism is based on the recognition that triiodothyroxine (T3) and thyroxine (T4) are the key hormones for a combination therapy. The finding that the active form of triiodothyroxine (T3) is from the deiodination of thyroxine (T4) indicated that monotherapy with thyroxine (T4) was adequate
to supply physiological levels of both hormones.(15)
Levothyroxine monotherapy is the conventional treatment for hypothyroidism. Nearly all physicians have seen patients with symptoms of hypothyroidism with a consistently normal TSH and adequate monotherapy. It remains unclear why these hypothyroid symptoms remain in these patients.(16) In a study,(17) patients taking triiodothyroxine (T3) and thyroxine (T4) demonstrated significantly improved cognitive performance, mood and physical well-being compared with those who received thyroxine (T4) alone while main-taining a normal TSH.
The author will also add triiodothyroxine (T3) and/or thyroxine (T4) combination in small doses at bedtime to alleviate these bothersome symptoms while again maintaining a normal TSH. Thyroid desiccated, liothyronine and liotrix are examples of these medications.
Recent studies have shown the important prognostic value of triiodothyroxine (T3) in patients with cardiovascular disease, and that the medication improves cardiovascular surgical outcomes and mortality without adverse effects.(18,19) In the absence of specific risk factors such as underlying cardiac disease or palpitations, or with persistent symptoms on levothyroxine despite normal serum TSH levels, patients may benefit from a low dose of triiodothyroxine (T3) supplementation.
Conclusion
The decision to treat subclinical hypothyroidism or mild thyroid failure is based on the fact that some symptoms may be reversed by hormone supplementation, and that therapy prevents progression to the overt stage of hypothyroidism.(13) The risk of harm to the patient is quite small, since the use of the sensitive TSH assay provides reassurance that we are not raising the blood thyroid levels too much as long as TSH does not fall below the normal range.
Although physicians depend upon trial evidence when making clinical decisions, ultimately the treatment and management of hypothyroidism and subclinical hypothyroidism must be tailored to the individual patient by obtaining an accurate history of their complaints. While treating a compliant patient, a trial of triiodothyroxine (T3), in an attempt to alleviate hypothyroid symptoms, may be an important step of reassurance.
Patient compliance is thus necessary for a lifelong management of thyroid disorders.
Bridget Bellingar, DO, is in practice in Largo, Florida.
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