Sub-subclinical hypothyroidism?
  Normal serum TSH values are usually considered those between 0.40 and 4.00 mU/l, with small differences among the various laboratories, depending on the methods used. Normal ranges are commonly defined as the values between the 3rd and 97th percentile (or x ± 2SD) of a group of apparently normal persons. This presupposes that abnormally high (and also low) values are found in about 3% of the "normal" controls. But is this always true? The experience with serum cholesterol has shown that abnormally high (or undesirable) values are found in more than 3% of the population, and now a cholesterol value of 250 mg/dl (or 6.5 mmol/l) is not considered normal any more, even if it is found in a large percentage of the inhabitants of the industralised countries.

The same may be true for the serum TSH values, and there is now evidence, to which our group has contributed, that TSH values between 2.01 and 4.00 mU/l may not be normal, especially if associated with positive autoantibodies. The evidence is as follows:
  1. These persons frequently develop hypothyroidism if followed up35.


  2. Hypercholesterolemic patients have on average a higher serum TSH, in the high normal range18.


  3. This hypercholesterolemia improves with small doses (50 µg/d) of thyroxine, whereas this dose has no effect in hypercholesterolemic patients with a serum TSH between 0.41and 2.00 mU/l36.


  4. Endothelial dependent vasodilatation, a marker of atherosclerosis, is impaired in definite hypothyroidism with a TSH 10.00 mU/l, less impaired in subclinical hypothyroidism with a TSH between 4.01–10.00 mU/l, and even less impaired in the persons with a TSH of 2.01–4.00, but still with a significant difference from the persons with a TSH between 0.41–2.00 mU/l22. This is shown in graphic form in Fig. 1.

So, it seems appropriate to consider persons with a TSH between 2.01 and 4.00 as being not always entirely normal, but some being at a very early stage of hypothyroidism.


Table 1: Author’s Recommendations
    Screen with a sensitive TSH assay all males 50 yr. old and all females 35 yr., and also younger persons with lipid abnormalities and other symptoms or signs associated with hypothyroidism.

    If TSH <0.40 mU/l

    Check serum fT4 and fT3 for hyperthyroidism

    If TSH 0.40–2.00 mU/l

    Repeat screening after 5 years.

    If TSH 2.01–5.00 mU/l

    Check serum fT4 and AAB.

    1. If AAB (–) and fT4 normal, repeat screening after 1 yr. If TSH 4.00mU/l on two occasions, treat with thyroxine.


    2. If AAB (+) and/ or fT4 low or low normal, treat those with TSH 3.00 mU/l, follow-up the others.

    If TSH 5.00 mU/l

    Treat or hypothyroidism