Subclinical Hypothyroidism

Measurement of serum TSH is generally considered the best screening test for thyroid disease. Increased values indicate hypothyroidism. The test is both sensitive and specific.
Its sensitivity causes a dilemma however, as some patients are found to have elevated TSH levels, but have normal free thyroxine hormone levels, and may also be asymptomatic.

It is common in older people. One study found 7% of women and 3% of men aged 60-89 years had TSH level greater than 10 mU/l.¹ ( Normal range 0.5-4.5mU/l.)

Causes are the same as those of overt thyroid disease.

• The main cause is chronic autoimmune thyroiditis - Hashimotos disease.
• Treatment of hyperthyroidism - most commonly after radioactive iodine treatment.
  Hypothyroidism can occur in 5-25% of patients treated with surgery or anti-thyroid drugs.^2,3
• Less common causes are medications e.g. Lithium or amiodarone.
• Other causes include head and neck surgery or radiotherapy.

The term subclinical may be inaccurate, as some of the patients have symptoms.
In the elderly a diagnosis of hypothyroidism may be delayed by wrongly attributing the symptoms of e.g. fatigue and constipation to ageing.

Clinical manifestations can be explained by assuming that a T4 level of 6-7 mcg/dL, although inside the normal range, may represent a significant decrease from a previous normal of 10mcg/dL, and is low for this particular patient.

In one study symptoms in 33 patients with subclinical hypothyroidism were compared with euthyroid patients in the same clinic.⁴
Dry skin, cold intolerance and easy fatiguability were significantly more common in the patients with raised TSH levels. The symptoms improved after treatment with thyroxine.
Another study showed that in 69 female patients with subclinical hypothyroidism, the clinical index of signs and symptoms were more abnormal in those with higher TSH levels. Even when they had normal serum thyroxine levels.⁵

Recommendations about thyroid screening have been inconsistent. No organisation currently recommends routine screening. The U.S Preventative Services Task Force ⁶ has recommended that asymptomatic adults not be screened because of the insubstantial evidence of benefit.
Other authors disagree and the practical approach may be to measure TSH in those patients who have persistent, non-specific complaints, women in particular, and the elderly.
Borderline results may need to be repeated at a consistent time of day, with consistent fasting status.

Patients with full hypothyroidism have serum levels of triglycerides, total cholesterol and low density lipoprotein (LDL) cholesterol that are elevated. The same changes exist in subclinical hypothyroidism, but are less marked and less consistent.
It is important as a risk factor for cardiovascular disease.
Some studies have shown a decrease in LDL and total cholesterol levels after treatment with L-thyroxine, although others have refuted this.^7,8,4A sensitive measure of myocardial contractility, the ratio of pre-ejection period to left ventricular ejection time, has also been shown to improve in patients with subclinical hypothyroidism, treated with L-thyroxine, compared to those on placebo.

Drugs

The main point here is should we treat, and if so, when?
If the elevation of TSH level is large and it has been so for a long period of time, antithyroid antibodies will also have been present. This situation carries a greater likelihood of progression to overt hypothyroidism and therefore a greater potential benefit from treatment.

Hypercholesterolaemia. Coronary artery disease.

Risk of progression to overt hypothyroidism can be ranked according to serum TSH level.

• TSH 6-10 mU/L. No risk for future hypothyroidism
• TSH greater than 10mU/L has 1-20% risk of progression per year.⁹

• During the first trimester thyroxine is supplied exclusively by the mother. Fetal production begins at 10-12 weeks gestation. Thyroxine is important for fetal neural development throughout pregnancy, but particularly so in the first trimester. Maternal hypothyroidism has been associated with mental retardation in their euthyroid children, and with increased fetal loss.¹⁰
• Pregnant women with goitre, high anti-thyroid antibody titre, family history of thyroid disease or symptoms suggestive of hypothyroidism, should be screened early in pregnancy, or preferably prior to conception, and treated.