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Lab test update - hypothryoidism

Clinical biochemist and GP Dr Berenice Lopez answers questions on how to use TSH and T4 tests in primary care

Clinical biochemist and GP Dr Berenice Lopez answers questions on how to use TSH and T4 tests in primary care

How close is the correlation between minor or borderline hypothyroidism and symptoms such as tiredness? How likely is it that treatment with thyroxine will resolve these symptoms?

41214901This state – an elevated TSH with a normal FT4 level – is referred to as subclinical hypothyroidism. The elevation of TSH reflects the sensitivity of the hypothalamic-pituitary axis to small decreases in circulating thyroid hormones. As the thyroid gland fails, the TSH level may increase above the normal reference range when FT4 levels may have only fallen slightly and remain within the reference range. Symptoms, if present, could be explained by assuming that the FT4 level, although ‘normal', is not normal for the particular individual and represents a significant fall from a previous set-point.

But there is no good evidence of a correlation between this diagnosis and symptoms. Neuropsychological function has not been shown to differ between patients with subclinical hypothyroidism and normal controls. Furthermore, there is no good evidence that treatment with thyroxine makes a difference, although decent trial data is scant.

How often does subclinical hypothyroidism progress to overt disease? Does the subclinical scenario require treatment?

On average about 2-4% of patients progress to overt disease every year but this figure may be closer to 20% in higher-risk groups. Risk appears to be largely related to initial serum TSH concentration and thyroid antibody titres. The underlying cause of the subclinical hypothyroidism may also be an important factor. For example, a past history of radioiodine treatment for hyperthyroidism may be an independent risk factor for progression.

41214903Make sure you have established the diagnosis before you consider treatment. Note that elevated TSH with normal FT4 may occur in conditions other than subclinical hypothyroidism (see box left). So when a high TSH is discovered, drug history should be reviewed and the test should be repeated on at least one further occasion three to six months later.

Think of adrenal insufficiency in patients with suggestive symptoms and risk factors. Treating these patients with thyroxine before the glucocorticoid deficiency is addressed could be catastrophic.

Uncertainty exists as to the benefits of treatment. Systematic reviews have shown that although treatment may reduce total cholesterol and LDL cholesterol levels, particularly when TSH levels are greater than 10mU/l, this is not associated with reductions in the rates of cardiovascular disease or mortality.

An important problem is the risk of overtreatment. A common error is failure to reduce thyroxine dose if TSH levels fall below the reference range with the attendant risks of cardiac dysrhythmias and osteoporosis.

Overall, treatment is indicated in the following situations:

• pregnancy – patients who are pregnant or seeking pregnancy with elevated TSH levels should be considered for treatment

• presence of a goitre

• TSH levels greater than 10mU/l.

If there are suggestive symptoms consider a six-month trial of thyroxine after discussing risks and benefits with the patient.

Does hypothyroidism affect other biochemical or haematological parameters?

Yes. Anaemia may be present. This may be normochromic and normocytic, reflecting red cell hypoproliferation, or macrocytic, most often secondary to an associated pernicious anaemia in patients with autoimmune thyroiditis. Premenopausal women may have a microcytic anaemia if menorrhagic.

Biochemical abnormalities may include hyponatraemia secondary to reduced free water clearance.

Note that hypothyroidism must be excluded in all patients with suspected Syndrome of Inappropriate ADH Secretion (SIADH). Decreased lipid clearance may result in increased total and LDL cholesterol and/or hypertriglyceridaemia.

There may be sex hormone abnormalities – for example men with hypothyroidism may have low serum testosterone and normal LH, possibly reflecting a direct effect of hypothyroidism on the pituitary gland. These patients may present with erectile dysfunction or loss of libido.

Hypothyroidism and subclinical hypothyroidism may also be associated with a subclinical myopathy and elevated CK levels. Be sure to check TSH in patients with unexplained raised CK, particularly if you are considering starting a statin.

Are other investigations warranted?

If serum TSH is elevated but less than 10mU/l, thyroid antibodies should be measured to help direct retesting strategy – see key points below.

When treating hypothyroidism, when should TFTs be measured to assess replacement? And how often should they be repeated in the future?

After initiation of thyroxine therapy, the patient should be re-evaluated and TFTs rechecked in four to eight weeks – depending on symptoms – and thyroxine dose adjusted accordingly.

The dose can be increased in patients who remain symptomatic and have a low FT4 after four weeks but be aware that TSH and FT4 concentrations at this time are not steady state values and serum TSH may still be falling. Achievement of a steady state after thyroxine is initiated or the dose is changed may take up to eight weeks.

The process of increasing thyroxine dose every four to eight weeks should continue until TSH returns to the reference range and TSH secretion has been normalised. Once the dose has been established, it remains constant in many patients.

Unfortunately, patients often think their thyroxine dose is inadequate when they feel tired or gain weight and a number prefer to run at low or suppressed TSH levels. It is also important to educate them about the risks of overtreatment with thyroxine, such as an increased risk of AF and cardiovascular mortality.

TSH should be checked annually or more often if there is an abnormal result or a change in the patient's status. Thyroxine requirement may change with ageing.
Dr Berenice Lopez is specialist registrar in clinical biochemistry and metabolic medicine at North Bristol NHS Trust and a part-time GP

Competing interests None declared

For more information on the use of lab tests in primary care go to which has 120 clinical scenarios for general practice

The case Blood test high TSH readings key points

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