Thyroid disease in pregnancy and thyroid eye disease

• Thyroid physiology changes in pregnancy: thyroxine (T4) demand rises, thyroid-stimulating hormone (TSH) is suppressed early by human chorionic gonadotropin (hCG), and thyroxine-binding globulin (TBG) rises. These shifts push reference ranges downward in the first trimester.
• Newer 2026 guidance from the American Thyroid Association (ATA) and the 2025 Royal College of Obstetricians and Gynaecologists (RCOG) guideline move away from fixed trimester TSH cutoffs such as 2.5, 3.0 and 3.5 mU/L; when no laboratory-specific range exists they use a diagnostic threshold around 4.0 mU/L, and they emphasise confirming an abnormal result before starting treatment.
• Propylthiouracil (PTU) is preferred to methimazole (MMI) in the first trimester and through preconception because methimazole carries a 2 to 4% embryopathy risk; switch to methimazole after 16 weeks in women who still need treatment. ^[1][2]
• Postpartum thyroiditis (PPT) occurs in roughly 30 to 50% of women who were thyroid peroxidase antibody (TPOAb) positive in pregnancy; it usually starts as transient thyrotoxicosis, may pass through a hypothyroid phase, and often needs beta blockers, then levothyroxine. ^[3][6]
• Graves orbitopathy (GO) is managed by activity and severity: vitamin and selenium support and local measures for mild disease; intravenous glucocorticoids as first-line for moderate-to-severe active disease in the European Group on Graves Orbitopathy (EUGOGO) 2021 guideline; IGF-1 receptor (IGF-1R) blockade with teprotumumab as preferred in the 2022 ATA/European Thyroid Association (ETA) consensus. Sight-threatening disease is an endocrine emergency. ^[5]

By the end of this page you should be able to:

1. Explain how pregnancy changes thyroid hormone binding, clearance and requirements, and why trimester reference ranges differ.
2. Choose and dose antithyroid and thyroid replacement therapy in pregnancy, and say when to switch drug and when to stop.
3. Manage postpartum thyroiditis, including who needs follow-up and who becomes permanently hypothyroid.
4. Classify Graves orbitopathy by activity and severity, and select investigation and treatment for each stage, including dysthyroid optic neuropathy.
5. Plan TSH-receptor antibody (TRAb) monitoring in pregnancy and neonatal follow-up for women with autoimmune thyroid disease.
6. Recognise where older guideline cutoffs and newer guidelines disagree, and state both values honestly.

Graves orbitopathy (also called thyroid eye disease or thyroid-associated ophthalmopathy) is an autoimmune inflammation of the orbital contents and periocular tissues, usually arising in people with current or past Graves hyperthyroidism, and occasionally in euthyroid or hypothyroid autoimmune thyroiditis.

A useful working classification of the thyroid side of the problem is: hypothyroidism vs hyperthyroidism; pre-existing disease vs disease diagnosed in pregnancy; gestational (transient) vs persistent; postpartum thyroiditis as a distinct autoimmune syndrome; and TRAb-positive vs antibody-negative disease, which drives fetal risk. Graves orbitopathy is classified by activity (active or inactive) and by severity (mild, moderate-to-severe, or sight-threatening), as set out in the EUGOGO 2021 guidelines^[5] and the 2022 ATA/ETA consensus statement^[5].

Thyroid autoantibodies are found in about 5 to 15% of women of childbearing age, and in one recent review the rate of thyroid autoimmunity in pregnancy was reported as high as 15 to 25%, varying with population, iodine status and the assay used^[6]. Thyroid antibody positivity is the strongest risk factor for gestational thyroid dysfunction and is the primary risk factor for postpartum thyroiditis, which occurs in about 30 to 50% of antibody-positive women^[6].

Overt hypothyroidism is uncommon in pregnancy and subclinical hypothyroidism is more common, especially in antibody-positive women. Graves disease is the commonest cause of hyperthyroidism in pregnancy. Thyroid eye disease affects about 30% of people with Graves disease in a clinically meaningful way, and in 6 to 7% of cases it appears in people who are euthyroid or hypothyroid with chronic autoimmune thyroiditis^[5].

Iodine deficiency remains the commonest cause of hypothyroidism worldwide, particularly in pregnancy, and in many low-resource settings it is still the dominant driver of preventable fetal and maternal thyroid disease.

Risk factors that warrant checking thyroid function when pregnancy is confirmed include a history of thyroid disease, thyroid surgery, radioiodine ablation or head and neck irradiation; other autoimmune disease such as type 1 diabetes, Addison disease, pernicious anaemia or vitiligo; Down or Turner syndrome; two or more miscarriages; infertility; use of drugs that disturb thyroid function such as amiodarone, lithium, phenytoin, carbamazepine or cancer immunotherapy; residence in an iodine-deficient area; and a family history of autoimmune thyroid disease^[3]. Maternal age, body mass index and parity are no longer risk factors for testing in the 2026 ATA guidance^[3].

For Graves hyperthyroidism, newly diagnosed disease in reproductive age is usually managed medically, and remission rates of 50 to 55% are expected after 12 to 18 months of treatment in non-pregnant adults^[1]. Smoking, a large goitre, high free thyroxine at diagnosis and high TRAb predict relapse; smoking also worsens Graves orbitopathy.

In pregnancy, oestrogen increases hepatic synthesis of TBG, so total T4 rises; the physiologically important free T4 often stays within the normal non-pregnant range, but the reference intervals for free T4 shift downward. The thyroid is stimulated early by hCG, which shares an alpha subunit with TSH; free T4 rises and TSH is suppressed in the first trimester. From the mid-second trimester onward, placental deiodinases and increased renal iodine losses combine with rising fetal demand to increase daily thyroid hormone requirements by 20 to 30% initially, and by as much as 50% by 20 weeks, in someone already on levothyroxine^[3].

Understanding these mechanisms matters for treatment decisions. A low TSH in the first trimester is expected, not necessarily evidence of over-replacement. A fall in free T4 in the second and third trimesters is expected if the levothyroxine dose is not increased. A woman who is euthyroid with replacement before conception will therefore usually need a higher dose, not the same dose, throughout pregnancy.

The fetus depends on maternal thyroxine until 10 to 12 weeks gestation, when fetal thyroid synthesis begins, between 17 and 19 weeks when secretion begins, and by 20 weeks when fetal pituitary TSH control is established^[3]. This is why replacing maternal hypothyroidism early matters more than it does later in gestation.

Symptoms of hypothyroidism in pregnancy are easy to blame on pregnancy itself: fatigue, constipation, cold intolerance, weight gain and dry skin. Biochemistry, not symptoms, confirms the diagnosis. Hyperthyroidism announces itself with palpitations, tremor, heat intolerance, weight loss, anxiety and insomnia; in women over 35 an "apathetic" presentation with weight loss and atrial fibrillation should be considered.

Graves orbitopathy presents with grittiness, watery eyes, photophobia, retrobulbar ache (worse on upward gaze), diplopia, and visible changes: lid retraction, lid swelling and erythema, conjunctival injection and chemosis, exophthalmos and, in severe cases, exposure keratopathy or loss of colour vision.

Examination for orbitopathy uses the Clinical Activity Score (CAS) and severity criteria from the EUGOGO 2021 guideline. A CAS above 3 of 7 at baseline, or above 4 of 7 on follow-up, indicates active disease; which features are scored is summarised in the table below. ^[4]

Severity is then divided into mild, moderate-to-severe and sight-threatening as in the EUGOGO 2021 guideline:

Hypothyroidism in pregnancy must be distinguished from normal pregnancy symptoms and from anaemia, depression, and non-thyroid illness. Hyperthyroidism in pregnancy may be physiological (gestational hyperthyroidism from hCG, usually mild, self-limiting, without TRAb) rather than Graves disease, and treating hCG-mediated gestational thyrotoxicosis with antithyroid drugs is not appropriate.

In Graves disease with orbitopathy, the differential for the red eye and proptosis includes orbital cellulitis, idiopathic orbital inflammatory disease, carotid-cavernous fistula and orbital tumour; TRAb, thyroid dysfunction and a thyrotoxic pattern separate Graves orbitopathy from these.

First-line tests are TSH and free T4, with TPOAb and TRAb as needed. TRAb is the key antibody in Graves disease. A sensitive binding assay (TBII) reports presence and concentration; a cell-based bioassay distinguishes stimulating from blocking antibody. In pregnancy, total T4 or free T4 indices can be measured if assay interference is suspected, since TBG rises but free hormone reference intervals change modestly.

Thyroid ultrasound is used to assess nodule disease and goitre size. Radioiodine is absolutely contraindicated in pregnancy and breastfeeding. Monitoring intervals are condition-specific and set out in the management section below.

Baseline pregnancy diagnosis and target ranges differ between older and newer guidelines, and the table below sets out the values each source supports.

For each trimester, local validated pregnancy-specific ranges, produced on the same assay, are preferred to any of these published values.

Thyroid storm and dysthyroid optic neuropathy (DON) are emergencies. Thyroid storm carries an estimated mortality of about 10% and needs multimodal treatment including intravenous antithyroid drug, glucocorticoid, beta blockade and intensive care^[1]. DON threatens sight and needs urgent intravenous glucocorticoids, with orbital decompression if response is poor or absent^[5]. Any pregnant woman with thyrotoxicosis and a high temperature, atrial fibrillation or confusion needs same-day assessment.

Overt hypothyroidism is always treated. Subclinical hypothyroidism is treated when TSH is above the pregnancy-specific reference range, and when autoantibody-positive with TSH more than 4.0 mIU/L, according to the consensus summarised in the most recent review^[6]. Euthyroid women with positive thyroid antibodies should not be treated routinely with levothyroxine^[6].

Levothyroxine is the drug of choice. In a woman already on replacement before conception, the dose is titrated to TSH, and most women need 20 to 30% more from a positive pregnancy test and up to 50% more by 20 weeks, as given in the 2026 guidance summarised above.^[3].

Monitoring: TSH and free T4 every 4 to 6 weeks in pregnancy for autoimmune thyroiditis^[6], and more frequently when treatment is started or changed, following standard thyroid follow-up. The dose is unnecessary and potentially harmful if overdone: TSH below the lower end of the reference range in treated hypothyroidism risks miscarriage and preterm delivery, and over-replacement is common.

Postpartum, women started on levothyroxine during pregnancy fall into two groups. About one third are long-term hypothyroid; the suspicion is higher when levothyroxine was started at TSH 3.8 mU/L or more, or when the maximum pregnancy dose reached 68.75 micrograms a day or more^[2]. Where levothyroxine was started at doses of 50 micrograms a day or less and TSH was low, a cessation trial after delivery is reasonable; the decision rests on autoantibody status, TSH at diagnosis and symptoms^[2].

Control of maternal thyrotoxicosis and its cause, not the free thyroxine alone, drives management. PTU is preferred preconception and in the first trimester; the dose is 50 to 200 mg a day in divided doses, titrated to maintain maternal free T4 at the upper limit of the pregnancy-specific range^[1]. MMI (5 to 15 mg a day, or carbimazole 10 to 30 mg a day) is preferred after the first trimester because of the PTU hepatotoxicity risk, and women on MMI should be switched to PTU when planning pregnancy and in the first trimester^[1]. The block-and-replace regimen is not used in pregnancy.

Starting doses of antithyroid drug in pregnancy depend on the severity of hyperthyroidism, and MMI embryopathy (aplasia cutis, choanal or oesophageal atresia, abdominal wall defects, facial changes) affects 2 to 4% of exposed offspring, especially between 6 and 10 weeks^[1]. Birth defects occur at a similar rate with PTU, but the spectrum is different and less severe, mainly face, neck and renal tract defects in males^[1]. Hence the advice that PTU is only a first-trimester strategy.

Thyroid function is monitored every 2 to 4 weeks in the first half of pregnancy, and every 4 to 8 weeks after 20 weeks^[3]. Aim for the free T4 in the upper part of, or just above, the pregnancy-specific range; TSH often stays suppressed and is not a reliable early treatment target. Using the lowest effective antithyroid drug dose reduces both relapse and fetal hypothyroidism.^[1]

TRAb status determines fetal risk. All women with autoimmune thyroid disease should have TRAb measured at the first antenatal visit, and again at 18 to 22 weeks if elevated; a late-pregnancy TRAb above 3 times the upper limit of normal signals a risk of fetal and neonatal hyperthyroidism and needs fetal monitoring throughout pregnancy^[1]. Women with TRAb below the cutoff are unlikely to relapse if the antithyroid drug is withdrawn: only 5% relapse within 8 weeks of stopping in pregnancy^[1]. In that situation, the drug can be stopped, with thyroid function checked every 2 weeks in the first trimester and every 4 weeks thereafter; antithyroid treatment is reinstated if the free T4 rises. This avoidance-first strategy matters because every week of unnecessary exposure carries embryopathy risk.

Beta blockers relieve adrenergic symptoms. Short-term propranolol 10 to 40 mg three or four times daily is used, but long-term treatment in pregnancy is avoided because of intrauterine growth restriction, fetal bradycardia and neonatal hypoglycaemia^[1]. Thiourea antithyroid drugs can worsen Graves orbitopathy early, so hyperthyroidism is controlled while orbitopathy is treated on its own merits.

Definitive treatment is reserved for the second trimester or after delivery: thyroidectomy, if needed for antithyroid drug allergy, large goitre or concern for malignancy, is safest in the second trimester^[3]; radioiodine (RAI) is absolutely contraindicated in pregnancy and for 6 months before conception.^[1]

Postpartum thyroiditis (PPT) is an autoimmune destructive thyroiditis arising in the first 6 to 12 months after delivery. It most often occurs in women with positive TPOAb, and roughly 30 to 50% of antibody-positive women develop it^[6]. The course can be transient thyrotoxicosis, transient hypothyroidism, or a biphasic hyper-then-hypothyroid phase, and a significant proportion of affected women develop permanent hypothyroidism over time^[6].

The thyrotoxic phase is driven by hormone release, not new synthesis, so antithyroid drugs have no role. Treatment is with a beta blocker for the initial thyrotoxic phase, and levothyroxine for the hypothyroid phase, reassessing TSH before deciding whether it can be stopped.^[3] Patient education to recognise palpitations, tremor and weight loss postpartum, and tiredness, cold intolerance and constipation later, is recommended so that testing happens early^[3].

Women who were antibody positive in pregnancy, or who needed levothyroxine during pregnancy, should have thyroid function rechecked at 6 to 12 months after delivery^[6]. Breastfeeding is not a contraindication; the drug quantities in milk are small, and the common advice to discard milk for 24 hours after anaesthesia is no longer recommended^[3].

Orbitopathy is graded by activity and severity as above, and treatment follows the comparison between EUGOGO 2021 and the 2022 ATA/ETA consensus statement published in 2025^[5].

General and preventive measures apply to every patient: stop smoking, achieve and maintain euthyroidism (both hyper- and hypothyroidism flare orbitopathy), treat the associated hyperthyroidism, and advise patients that RAI can flare orbitopathy. A 6-month course of selenium (sodium selenite) is used in mild active disease, particularly in selenium-deficient areas^[1]; selenium is not recommended for moderate-to-severe disease^[5]. Lubricating eye drops and protective taping at night deal with exposure symptoms.

Mild active orbitopathy is usually followed expectantly with topical measures, a selenium course, and low-dose oral glucocorticoids in selected cases with a significant impact on quality of life^[5]. Moderate-to-severe active disease is where the major guideline disagreement lies:

Intravenous methylprednisolone accumulates a total dose of 4.5 g given weekly over about 12 weeks; regimens using larger totals above 4.5 g are reported as high-dose but were abandoned early because of safety concerns in hepatic and cardiovascular disease^[4]. Glucocorticoid cover against osteoporosis, gastric irritation and infection is prescribed per local protocol.

For Graves hyperthyroidism, EUGOGO 2021 recommends that hyperthyroidism be controlled with antithyroid drugs in moderate-to-severe and active orbitopathy, and radioiodine is avoided; where radioiodine is chosen for other reasons, low-dose steroid prophylaxis is used in patients with mild or inactive disease, and, more strongly, in active mild disease^[5].

Teprotumumab, an IGF-1R antibody, is preferred first-line in the 2022 ATA/ETA consensus when exophthalmos is the main problem, approved by the European Medicines Agency in June 2025^[5], but durability may be limited and adverse effects including hyperglycaemia and hearing loss are reported^[5]. Tocilizumab and rituximab are alternatives in selected patients. A recent comparison of the two guidelines accepts that intravenous glucocorticoids (alone or with orbital radiotherapy) remain preferred when inflammatory soft-tissue change, rather than proptosis, is the main target^[5].

Rehabilitative surgery for inactive disease is staged: orbital decompression first, then eye muscle surgery, then eyelid surgery. Definitive management of the thyroid in active moderate-to-severe orbitopathy is antithyroid drug therapy; surgery or RAI for the thyroid is considered when orbitopathy is inactive.

For the mother: miscarriage, pre-eclampsia, preterm delivery, gestational hypertension and gestational diabetes are all more common with thyroid dysfunction and with thyroid autoantibody positivity, even when she is clinically euthyroid^[6]. Thyroid storm in pregnancy carries an estimated maternal mortality of 10%. Antithyroid drug side effects include rash, arthralgia, agranulocytosis (about 0.1 to 1% overall; 0.6% with MMI, 1 to 1.5% with PTU) and hepatotoxicity (more frequent and more severe with PTU, especially in children)^[1].

For the fetus and neonate: undertreated maternal hypothyroidism risks impaired neurodevelopment; overtreatment risks fetal tachycardia and growth restriction. TT4 and free T4 should be kept in the pregnancy range. Fetal hyperthyroidism from maternal TRAb occurs in a minority of pregnancies in treated Graves disease and presents with fetal tachycardia, growth restriction, goitre and, after birth, neonatal thyrotoxicosis. Maternal TRAb above 3 times the upper limit of normal in late pregnancy is the trigger for fetal monitoring; neonates need assessment of thyroid status at delivery and for several weeks^[1]. PTU also crosses the placenta and can cause fetal hypothyroidism and goitre if overused.

For Graves orbitopathy: loss of vision from DON, severe exposure keratopathy and cosmetic and functional burden are the major complications. RAI for Graves disease is contraindicated in active moderate-to-severe orbitopathy because it can worsen orbital inflammation.

With adequate replacement, neonatal outcomes in maternal hypothyroidism are good. One third of women started on levothyroxine in pregnancy are long-term hypothyroid postpartum, so a cessation trial with follow-up is justified in most^[2]. Graves disease has remission rates of 50 to 55% after 12 to 18 months of treatment in adults^[1]; postpartum relapse is common in women who were antibody positive.

Graves orbitopathy is self-limiting over time, but severe disease is liable to permanent damage. Treatment reduces activity and recovers function, and rehabilitative surgery for established changes is elective and staged once disease is inactive.

Targeted screening, not universal, is recommended: test TSH at the confirmation of pregnancy in women with risk factors (history of thyroid or autoimmune disease, thyroid surgery, radioiodine ablation or irradiation, miscarriage, infertility, thyroid-disrupting drugs, iodine-deficient residence or family history)^[3]. Iodine supplementation for pregnant and lactating women where intake is low underpins prevention of deficiency-related hypothyroidism. Women with positive TPOAb who are euthyroid do not benefit from routine levothyroxine, but need biochemical follow-up because they may develop hypothyroidism.^[6]

For prevention of Graves orbitopathy, avoiding smoking and maintaining stable euthyroidism are the two measures with good evidence. Stress, excess iodine and smoking all increase the risk of Graves disease and its complications.

• If laboratory tests are limited, a small goitre, maternal symptoms of hypothyroidism and indicators of iodine deficiency (or endemic goitre) should prompt empirical iodine and levothyroxine where needed, and referral.
• A handheld or departmental TSH assay makes pregnancy-specific replacement possible; without one, clinical signs and a clinical score for risk factors guide selective treatment.
• PTU and methimazole are available on the WHO Model List of Essential Medicines and inexpensive; beta blockers are universally available. Radioiodine and thyroidectomy require referral centres.
• Graves orbitopathy with sight-threatening features and thyroid storm require emergency referral even where specialist centres are far away.
• Levothyroxine is needed for hypothyroid women; missed doses in late pregnancy are common when supply is interrupted, so dispensing generous quantities and counselling about the dose increase in pregnancy are worthwhile.

Thyroid function tests; hypothyroidism; hyperthyroidism; thyroiditis; Graves disease; thyroid neoplasms; neonatal hyperthyroidism.