In one line
Pregnancy shifts every thyroid reference range, so the commonest error in this topic is reading a normal result as abnormal or an abnormal one as normal. The fetal brain runs entirely on maternal thyroxine until about 12 weeks, which is why an undertreated hypothyroid woman must have her dose raised the moment she has a positive pregnancy test, and why methimazole and carbimazole are avoided in exactly that window.
Where this sits. The hypothalamic-pituitary-thyroid axis and the normal control of thyroid hormone are taught in the Primary chapter on endocrine physiology. The consultant layer, including the harder judgement calls in Graves' disease and the management of thyroid storm, is the Finals chapter on thyroid disorders in pregnancy.
What pregnancy does to the thyroid axis
Three forces act, and every abnormal-looking result in this chapter comes from one of them.
Oestrogen raises thyroxine-binding globulin. Oestrogen increases both the synthesis of TBG and its sialylation, which prolongs its half-life. TBG concentrations rise substantially in the first half of pregnancy and stay high. Since most circulating thyroid hormone is protein-bound, total T4 and total T3 rise, by roughly 50%, without the woman being thyrotoxic.
The practical consequence is immediate: do not use total T4 or total T3 to assess thyroid status in pregnancy. Use TSH, and free T4 where needed, interpreted against pregnancy-specific ranges.
Human chorionic gonadotropin stimulates the TSH receptor. hCG and TSH share an identical alpha subunit and have similar beta subunits, so hCG is a weak agonist at the TSH receptor. As hCG peaks around 8 to 11 weeks, it drives a small rise in free T4 and a reciprocal fall in TSH. A suppressed or low TSH in the first trimester is therefore often a normal finding, and the effect is exaggerated where hCG is higher: multiple pregnancy, gestational trophoblastic disease, and hyperemesis gravidarum.
Iodine requirement rises. Renal iodine clearance increases with the rise in glomerular filtration rate, iodine is transferred to the fetus, and maternal thyroxine production rises. A woman with marginal iodine intake who was euthyroid before pregnancy may not stay euthyroid.
Why the first trimester is the one that matters
The fetal thyroid does not begin producing meaningful hormone until around 12 weeks. Before that, fetal brain development depends entirely on maternal thyroxine crossing the placenta.
That single fact organises the whole chapter:
- Maternal hypothyroidism matters most early, before she may even have booked.
- The levothyroxine dose must go up as soon as pregnancy is suspected, not at the first antenatal visit.
- The teratogenic window for antithyroid drugs coincides exactly with the period when the fetus cannot make its own hormone, so first-trimester decisions carry both risks at once.
Reading the tests
The 2017 American Thyroid Association guideline made an important correction that many clinicians have not absorbed. The older teaching set the first-trimester TSH upper limit at 2.5 mU/L and 3.0 mU/L thereafter. The ATA now recommends an upper reference limit of 4.0 mU/L, applied from the late first trimester, weeks 7 to 12, with a gradual return towards the non-pregnant range in the second and third trimesters.
Using the old 2.5 mU/L cut-off labels a large number of normal women as having subclinical hypothyroidism and starts them on lifelong-feeling treatment they do not need.
| Test | Behaviour in normal pregnancy | How to use it |
|---|---|---|
| TSH | Falls in the first trimester with the hCG peak, then rises towards the non-pregnant range | The primary test. Upper limit about 4.0 mU/L from weeks 7 to 12 onwards |
| Free T4 | Rises slightly in the first trimester, then falls; assay-dependent in pregnancy | Second-line, to characterise an abnormal TSH |
| Total T4 / total T3 | Rise about 50% because TBG rises | Do not use to assess thyroid status in pregnancy |
| TSH receptor antibody (TRAb) | Unaffected by pregnancy itself | Crosses the placenta; measured in Graves' disease to predict fetal and neonatal thyroid disease |
| Thyroid peroxidase antibody (TPOAb) | Unaffected | Marks autoimmune thyroid disease; changes the treatment threshold in subclinical hypothyroidism and predicts postpartum thyroiditis |
Where a laboratory can provide local trimester-specific reference ranges, use those in preference to any published figure.
Hypothyroidism
Why it matters
Untreated overt maternal hypothyroidism is associated with miscarriage, pre-eclampsia, placental abruption, low birth weight, preterm birth, stillbirth and impaired neurodevelopment in the child. Overt hypothyroidism is not a subtle condition and it is straightforward to treat, which is why detecting it is worth the effort.
Subclinical hypothyroidism, meaning a raised TSH with a normal free T4, is the more contested territory, and this is where TPO antibodies decide the answer.
Whom to treat
- Overt hypothyroidism (raised TSH with low free T4, or TSH above 10 mU/L whatever the free T4): treat, always.
- Subclinical hypothyroidism with positive TPO antibodies and a TSH above the pregnancy-specific reference range: treat.
- TPO-antibody-negative women with a TSH above 10 mU/L: treat.
- Intermediate positions (TPO-negative, TSH between the upper reference limit and 10) are a judgement call with weaker evidence, and levothyroxine may be considered.
Levothyroxine, and the dose that must go up immediately
Mechanism. Levothyroxine is synthetic T4, a prohormone converted peripherally by deiodinases to the active T3. Its long half-life, around seven days, is what makes once-daily dosing and weekly dose arithmetic possible.
Administration matters more than people allow for. Take it on an empty stomach, ideally 30 to 60 minutes before breakfast, and separate it by at least four hours from iron, calcium and antacids, all three of which bind levothyroxine in the gut and are the standard antenatal prescription. A pregnant woman handed levothyroxine and ferrous sulphate with no instruction to separate them will absorb neither properly. See Anaemia in pregnancy.