Subclinical hypothyroidism is the early stage of thyroid failure, in which a compensatory rise in TSH (thyroid-stimulating hormone) keeps the thyroid hormone levels apparently normal. At this stage the loss of functioning follicular cells is not yet large enough to lower the hormone itself, but it is enough that the pituitary has to work harder: it raises TSH, and the higher TSH drives the remaining gland to keep the T4 (thyroxine) level normal. The condition is therefore defined by the combination of a raised TSH with a normal T4, and it is the opposite of overt hypothyroidism, where the loss is too large for the compensation to hold and the T4 itself falls.
Because the process is graded, hypothyroidism is often classified by the TSH:
| Category | T4 | TSH |
|---|---|---|
| Subclinical, grade 1 | normal | 5-9.9 mU/L |
| Subclinical, grade 2 | normal | 10-20 mU/L |
| Overt | low | above 20 mU/L |
A single raised TSH is not the diagnosis, because TSH fluctuates with illness, sleep and time of day. The measurement is repeated after about 3 months before subclinical hypothyroidism is confirmed and treatment decided.
A normal T4 does not make this stage harmless. The raised TSH is associated with three consequences, which are the reason the stage is recognized and sometimes treated.
Cardiovascular risk
The most important consequence of mild or subclinical hypothyroidism is a higher risk of cardiovascular events. The mechanisms are the changes the falling hormone produces across the system: a shift in the lipid profile towards higher cholesterol, endothelial dysfunction (impaired function of the vessel lining), coronary artery dysfunction, and others. Because these changes begin while the hormone level is still normal, early diagnosis and treatment are aimed at preventing the cardiovascular events that would follow.
Whether to treat is settled by age rather than by the TSH alone. Studies show that in quite old subjects it is better not to treat with levothyroxine to lower TSH to the normal range, whereas in younger subjects levothyroxine is suggested to lower the TSH and reduce the cardiovascular events.
Liver fibrosis
Beyond the cardiovascular events, subclinical hypothyroidism is associated with a higher risk of liver fibrosis, so levothyroxine can be considered as part of the regimen.
Pregnancy loss
Mild or subclinical hypothyroidism is also associated with a higher risk of pregnancy loss, so control of subclinical hypothyroidism reduces that risk.