1. Subclinical hypothyroidism in pregnancy
Subclinical hypothyroidism is one of the most common thyroid disorders in pregnancy, with a prevalence of 3%-5% reported in the literature.
Subclinical hypothyroidism can lead to a 2-3 fold increase in the incidence of miscarriage and preterm birth, and can reduce the IQ of the offspring born by 8-10 points. With the popularization of knowledge about thyroid disorders in pregnancy, the desire of pregnant women in China to be actively screened for thyroid disorders has increased dramatically, and the problem of reasonable diagnosis of subclinical hypothyroidism has become more prominent.
2. The upper limit of pregnancy-specific thyroid stimulating hormone has different standards
It has been found that the serum TSH levels in pregnant women and women of childbearing age in China are significantly higher than those reported in foreign literature. Because the criteria for the upper limit of pregnancy-specific thyroid stimulating hormone (TSH) vary between sources, the corresponding prevalence of subclinical hypothyroidism derived from the studies also varies.
For example, with a pregnancy-specific TSH upper reference range of >5.64 mIU/L, the prevalence of subclinical hypothyroidism in the Tl phase of the study was 4.0%; with the upper reference range of TSH >4.12 mIU/L provided by the adoption kit (Roche), the prevalence of subclinical hypothyroidism in the Tl phase of the study was 6.7%.
When using TSH >2.5 mIU/L as the standard proposed by the American Thyroid Association ATA, the prevalence of subclinical hypothyroidism in study Tl stage is even as high as 27.8%, which means that one third of pregnant women in China need to receive levothyroxine (L-T4) replacement therapy during pregnancy.
Such a huge difference in prevalence makes us think about the rationality of applying the ATA proposed standard of TSH>2.5mIU/L in pregnant women in China.
3. How to set the upper limit of pregnancy-specific thyroid stimulating hormone to be reasonable?
Studies have shown that TSH > the upper limit of the pregnancy-specific reference range affects the intellectual development of the offspring. The reasonableness of the diagnostic criteria for subclinical hypothyroidism in pregnant women also depends on its negative effect on the course of pregnancy and its negative impact on the neurointellectual development of the offspring.
The main reason for this discrepancy in serum TSH during pregnancy is the general elevation of serum TSH levels in our population. This cause was recently confirmed by the epidemiological survey of thyroid disease and iodine nutrition, completed in cooperation with ten cities across the country.
The causes of elevated serum TSH can be divided into 2 main categories.
(1) Damage to thyroid tissue, decreased thyroid hormone production, and negative feedback mechanisms cause elevated TSH. Common clinical causes are autoimmune thyroiditis, surgical removal of the thyroid gland and radioactive iodine therapy.
(2) There is no damage to thyroid tissue, but serum TSH levels are elevated. Factors in this category include increased iodine intake, obesity or overweight, and medications.
With reference to the reference range of serum TSH in early pregnancy recommended by various societies’ guidelines and our own guidelines, we have the following recommendations according to our national situation.
(1) TSH>2.5mIU/L is not recommended as a diagnostic criterion for subclinical hypothyroidism in pregnancy.
(2) The gestation-specific reference range established by the SS method is the most trustworthy because it controls for the differences between individuals in the population.
(3) The gestation-specific reference range by the CS method is the reference range commonly used internationally today.
If your unit is not in a position to establish its own gestation-specific reference range, it is recommended that the reference range provided by our guidelines be adopted. However, care should be taken to match the assay reagents.
(4) If reagent-matched gestation-specific TSH reference ranges are not available. The TSH reference range for the general population provided by the kit can also be used for women within 7 weeks of gestation.
In conclusion, the development and application of appropriate upper limits of serum TSH reference ranges in pregnancy, especially in T1 of pregnancy, can both correct subclinical hypothyroidism in pregnant women in a timely manner and overcome the tendency to overdiagnose and overtreat.