Evaluate and manage thyroid and other endocrine disorders in pregnancy

In one line

Thyroid disease in pregnancy is won by anchoring every decision to trimester-specific TSH and physiology: drive overt hypothyroidism to a TSH below 2.5 mU/L from the moment a period is missed, treat hyperthyroidism with the least-teratogenic drug at the lowest effective dose while watching the fetus through the maternal TRAb, and resist treating biochemical-only subclinical disease for which the randomised evidence shows no neurodevelopmental benefit.

This chapter assumes the gland physiology, the booking-bloods groundwork and the first-line drug choices taught at Intermediate level — the hCG–TSH cross-talk, TBG-driven shifts in total hormone, the basic levothyroxine-vs-antithyroid-drug distinction. It spends its words on the consultant layer: telling the subtypes apart when the biochemistry is ambiguous, the exact thresholds and how the named treatment regimens differ, appraising the randomised trials that moved the guidelines, and the judgement calls in the refractory and atypical case.

Assessment

Thyroid biochemistry must be interpreted against the pregnancy-shifted reference range, not the non-pregnant one. hCG cross-stimulates the TSH receptor, so TSH falls (often below the non-pregnant lower limit) in the first trimester while free T4 rises; oestrogen raises thyroxine-binding globulin, inflating total T4/T3 and making free hormone and TSH the only reliable analytes. (That physiology is Intermediate groundwork; the harder question is what to do when the numbers are internally inconsistent.)

• Reference ranges. Use assay-/population-specific trimester ranges where available. When they are not — the SA public-sector reality — the ATA 2017 default is a TSH upper limit of 4.0 mU/L (the older 2.5/3.0 cut-offs over-diagnosed). A booking TSH should be read against this, not a lab printout flagged on adult norms.
• Hypothyroidism. Overt = raised TSH with low free T4 (or any TSH >10 mU/L). Subclinical = raised TSH (above the trimester limit, i.e. >4.0) with normal free T4. Isolated hypothyroxinaemia = normal TSH, low free T4. Check TPO antibodies: positivity raises miscarriage and progression risk and means closer monitoring, though on the 2026 ATA guidance it no longer decides who is treated for subclinical disease.
• Hyperthyroidism. Separate Graves disease (TRAb-positive, persists/worsens, may have orbitopathy) from gestational transient thyrotoxicosis (GTT) — an hCG-driven, self-limiting biochemical thyrotoxicosis of early pregnancy, classically with hyperemesis gravidarum. GTT is TRAb-negative, has no goitre or eye signs, and resolves by ~14–18 weeks; it needs no antithyroid drug.
• The single most important test in Graves disease is maternal TRAb, because IgG crosses the placenta and can cause fetal/neonatal thyrotoxicosis even in a euthyroid or post-ablation mother. Measure it in the first trimester and, if positive, again at 18–22 weeks.

Telling the subtypes apart — the consultant discriminators

The biochemistry only sorts patients if you read it against the mechanism generating it. Four discriminations carry most of the management consequences.

• GTT vs first-presentation Graves. Both give a suppressed TSH and a high free T4 in early pregnancy, and both can occur in a vomiting woman. The mechanism splits them: GTT is receptor cross-stimulation by hCG — a transient, dose-dependent agonism that tracks the hCG curve, peaks at 9–11 weeks and fades as hCG falls. Graves is autonomous TRAb-driven stimulation that does not care about gestation. The bedside discriminators that flow from this: GTT has no goitre, no orbitopathy, no pre-pregnancy thyroid history, a free T3 that is usually only mildly raised (hCG drives T4 more than T3), and it is TRAb-negative; the hyperthyroidism is proportionate to the vomiting and improves as the woman stops vomiting. A T3-predominant picture, a goitre with a bruit, eye signs, or a positive TRAb pulls you firmly toward Graves. The trap is starting carbimazole on a hyperemetic woman with a suppressed TSH — you are then treating a self-limiting hCG effect with a teratogen.
• Subclinical hypothyroidism vs assay artefact vs early overt disease. A "raised" TSH above 4.0 with a normal free T4 is only subclinical hypothyroidism if it is real and persistent. Reasons it may be neither: a non-pregnant reference range applied by the lab, an isolated transient rise, biotin interference (high-dose biotin supplements spuriously lower TSH and raise free T4/T3 on immunoassays — a recognised cause of a "thyrotoxic" panel in a clinically euthyroid woman), heterophile antibodies, or a free-T4 immunoassay that under-reads in the protein-shifted third trimester. The consultant move is to repeat with the gestation noted, ask about supplements, and — where the free T4 looks discordant late in pregnancy — recognise that total T4 (×1.5 the non-pregnant range) or the free T4 index can be more reliable than a third-trimester free-T4 immunoassay.
• Isolated hypothyroxinaemia. Normal TSH, low free T4. This is the subtype that looks like it should be treated and is not — the randomised evidence (below) shows no neurodevelopmental gain, and a low third-trimester free T4 is frequently an assay phenomenon rather than true maternal hypothyroxinaemia. Naming it correctly stops a reflex levothyroxine start.
• TPO-antibody status as a modifier, not a diagnosis. TPO positivity does not itself define disease; it shifts the trajectory and the threshold. A TPO-positive euthyroid woman has a higher rate of progression to overt hypothyroidism across pregnancy (so she needs repeat TSH even if the booking value is normal), a higher background miscarriage and preterm rate, and a higher risk of postpartum thyroiditis. It is the variable that tips a TSH-of-3.5 woman toward closer monitoring and repeat testing; note that on the 2026 ATA guidance TPO status no longer decides who is treated for subclinical hypothyroidism, which now turns on overt disease, a TSH above 10, and the timing of the diagnosis.

Severity and the atypical presentations

• Thyroid storm is the severity endpoint of hyperthyroidism and is a clinical, not biochemical, diagnosis — the degree of free-T4 elevation does not distinguish storm from uncomplicated thyrotoxicosis. The Burch–Wartofsky point scale (temperature, CNS dysfunction, GI–hepatic dysfunction, tachycardia, congestive failure, atrial fibrillation, and a precipitant) formalises it: a score ≥45 is highly suggestive, 25–44 impending. In pregnancy the precipitants are labour, caesarean, infection, pre-eclampsia and abruption — so storm characteristically declares itself intrapartum or immediately postpartum in a woman whose Graves was under-treated.
• Fetal thyrotoxicosis is the atypical presentation that has no maternal biochemical signature at all — the mother can be euthyroid, hypothyroid on replacement, or years post-ablation, yet her persisting TRAb crosses the placenta and drives a fetal tachycardia, goitre, growth restriction, advanced bone age or hydrops. The only way to anticipate it is to have measured TRAb; the only way to detect it is fetal surveillance.
• The decompensating myxoedematous picture is rare but is the hypothyroid severity endpoint — profound untreated hypothyroidism presenting with hypothermia, bradycardia and obtundation, usually in a woman lost to follow-up. It is mentioned because the management (cautious IV levothyroxine, steroid cover for possible co-existing adrenal insufficiency, treat the precipitant) diverges sharply from routine oral replacement.

Management

Frame immediate → ongoing → long-term, keeping the maternal and fetal threads explicit. The first-line drug choices are Intermediate groundwork; the consultant content here is the exact dosing, the regimen comparisons, the monitoring thresholds and the SA-specific substitution.

Hypothyroidism — immediate. A woman on levothyroxine who confirms pregnancy must increase her dose by ~25–30% at once — the pragmatic instruction is "take two extra tablets per week" (i.e. nine days' worth over seven), without waiting for a clinic TSH. Requirements rise because of TBG, transplacental transfer and increased volume of distribution. Newly diagnosed overt hypothyroidism is started on full replacement (~1.6 µg/kg/day) immediately.