Autoimmune Thyroid Disease — Hashimoto's & Graves' Disease Guide — Symptoms, Causes & Treatment | MyMedicPlus

Autoimmune thyroid disease (AITD) encompasses two main immune-mediated disorders of the thyroid gland that together represent the most common organ-specific autoimmune diseases in humans. Hashimoto's thyroiditis (chronic lymphocytic thyroiditis) is characterised by progressive lymphocytic infiltration of the thyroid parenchyma, follicular destruction, and loss of thyroid function — it is the most common cause of hypothyroidism worldwide, affecting approximately 5% of the general population. Graves' disease is caused by stimulating TSH receptor autoantibodies (TRAb/TSHR-Ab) that mimic TSH and drive continuous thyroid hormone overproduction, resulting in hyperthyroidism — it is the most common cause of sustained hyperthyroidism, accounting for 60-80% of cases. Both conditions share HLA-DRB1, CTLA-4, PTPN22, and CD40 genetic risk loci. AITD collectively affects 5-10% of the population and is 7-10 times more common in women than men, reflecting the predominance of women in most autoimmune conditions — likely related to oestrogen's immunomodulatory effects, X-linked gene dosage, and hormonal fluctuations during puberty, pregnancy, and the postpartum period. The postpartum period is a particularly high-risk time for onset or exacerbation of AITD — postpartum thyroiditis affects approximately 5-7% of women in the first year after delivery. Early diagnosis and treatment dramatically reduce morbidity and long-term complications.

AITD results from a breakdown of immune self-tolerance to thyroid antigens driven by both genetic and environmental factors. In Hashimoto's thyroiditis, autoreactive CD4+ and CD8+ T-cells infiltrate the thyroid gland, causing follicular damage and apoptosis; the B-cell response generates anti-thyroid peroxidase (anti-TPO) antibodies — present in 95% of Hashimoto's patients — and anti-thyroglobulin (anti-Tg) antibodies; these antibodies are markers of the autoimmune process rather than the primary cause of destruction. In Graves' disease, B-cells produce IgG TRAb (TSHR-stimulating antibodies) that bind to and persistently activate the TSH receptor on thyroid follicular cells, driving thyroid hormone overproduction independent of TSH regulation; TRAb also stimulates orbital fibroblast differentiation in Graves' ophthalmopathy. Genetic risk: AITD is highly familial — first-degree relatives of Hashimoto's patients have 5x higher risk; concordance in monozygotic twins for Graves' is approximately 35% (highlighting the essential role of environmental triggers). Key genetic risk loci: HLA-DR3 (Graves'), PTPN22, CTLA-4, CD40, FOXP3. Environmental triggers: iodine excess (particularly after abrupt increased iodine intake — e.g., amiodarone use, iodine-containing contrast agents) triggers destructive thyroiditis in susceptible individuals; selenium deficiency impairs glutathione peroxidase antioxidant protection of follicular cells; postpartum immune rebound (Th1 reactivation after Th2 pregnancy-associated suppression); viral infections (EBV, HTLV-1, hepatitis C); interferon-alpha therapy (used in hepatitis C and oncology — triggers hypothyroidism or Graves' in up to 30% of patients); checkpoint inhibitor immunotherapy (PD-1/CTLA-4 inhibitors — thyroiditis in 5-10%).

Symptoms of Hashimoto's hypothyroidism develop insidiously over months to years as thyroid function gradually declines: profound fatigue and lethargy, unexplained weight gain despite no change in diet, cold intolerance, dry and coarse skin, hair loss and thinning of the outer third of eyebrows (madarosis — a characteristic sign), constipation, slowed speech and movements, depression and cognitive slowing ('brain fog'), bradycardia, hoarse voice (vocal cord myxoedema), menstrual irregularity (oligomenorrhoea or menorrhagia), infertility, and a firm enlarged goitre (in some cases). Subclinical hypothyroidism (raised TSH with normal FT4) may cause subtle symptoms. Graves' disease hyperthyroidism symptoms: weight loss despite increased or normal appetite, heat intolerance and excessive sweating, palpitations (sinus tachycardia or atrial fibrillation — the most common cause of new AF in persons under 50), fine tremor of the outstretched hands, anxiety, irritability, emotional lability, hyperreflexia, frequent loose bowel movements, oligomenorrhoea, infertility, and a smooth, diffuse goitre with bruit (from increased vascularity). Extrathyroidal manifestations unique to Graves' disease: Graves' ophthalmopathy (thyroid eye disease — affects 25-50% of Graves' patients: periorbital oedema, proptosis/exophthalmos, lid retraction, lid lag, restricted eye movements, diplopia, chemosis, and — in severe cases — corneal exposure ulceration and optic neuropathy causing vision loss); pretibial myxoedema (raised, orange-peel textured skin lesions on the shins and dorsal feet); thyroid acropachy (rare — digital clubbing with periosteal new bone formation). Thyroid storm is an acute life-threatening thyrotoxic crisis with hyperthermia (above 40°C), severe tachycardia, hypertension, agitation or psychosis, vomiting, and multi-organ failure requiring intensive care.

TSH (thyroid-stimulating hormone) is the primary thyroid function screening test and the single most sensitive indicator of thyroid dysfunction — elevated TSH (above 4-5 mIU/L) confirms hypothyroidism; suppressed TSH (below 0.4 mIU/L) confirms hyperthyroidism. Free T4 (FT4) and free T3 (FT3) confirm the degree of hormone disturbance and distinguish overt from subclinical disease (subclinical hypothyroidism: high TSH with normal FT4; subclinical hyperthyroidism: low TSH with normal FT4/FT3). Thyroid autoantibodies: anti-thyroid peroxidase antibodies (anti-TPO) are elevated in 95% of Hashimoto's patients and 75% of Graves' disease; anti-thyroglobulin antibodies (anti-Tg) are less specific. TRAb (TSH receptor antibodies, either stimulating or blocking) measured by TSHR antibody assay: positive in 95-99% of active Graves' disease — confirms Graves' diagnosis and predicts relapse risk after antithyroid drug withdrawal; TRAb clearance during treatment predicts remission. Thyroid ultrasound: Hashimoto's shows characteristic heterogeneous hypoechoic parenchyma with fibrous bands and lymphoid follicles, reduced vascularity; Graves' shows diffusely enlarged, homogeneous, markedly hypervascular gland ('thyroid inferno' on Doppler ultrasound). Thyroid radionuclide scintigraphy (technetium-99m or iodine-123): Graves' disease shows diffusely increased uptake (confirms diagnosis and quantifies gland size for radioiodine dosimetry); toxic multinodular goitre shows patchy uptake; destructive thyroiditis (subacute, postpartum) shows markedly reduced uptake — distinguishing it from Graves' hyperthyroidism. Thyroid stimulation test/TRAb levels guide choice of antithyroid drug therapy duration. Orbital MRI for Graves' ophthalmopathy staging.

Treatment differs completely between hypothyroidism and hyperthyroidism. Hashimoto's hypothyroidism: levothyroxine (synthetic T4) is the gold standard treatment — taken as a single daily oral dose on an empty stomach, 30-60 minutes before food or other medications (food and calcium reduce absorption by up to 40%). Starting dose: 1.6 mcg/kg/day in young healthy adults; start low (25-50 mcg/day) in elderly patients or those with coronary artery disease and titrate cautiously. Target TSH: 0.4-2.5 mIU/L for most patients; 0.1-2.5 mIU/L in the first trimester of pregnancy; potentially lower targets for symptomatic patients. TSH should be rechecked 6-8 weeks after each dose change; annual review once stable. Most patients require lifelong levothyroxine. Combination T4+T3 (levothyroxine plus liothyronine) may benefit a subset of patients with persistent symptoms on T4 alone, particularly those with DIO2 polymorphisms impairing T4-to-T3 conversion. Graves' disease hyperthyroidism — three definitive treatment options: (1) Antithyroid drugs (ATDs): carbimazole 20-40 mg/day (first-line in UK) or propylthiouracil (PTU — preferred in first trimester of pregnancy or thyroid storm) — used for 12-18 month courses; 40-60% achieve remission; Titration or Block-and-Replace regimens; monitor for agranulocytosis (sore throat — stop ATD and check FBC immediately), hepatotoxicity (PTU risk), and vasculitis. (2) Radioactive iodine (I-131): the definitive and most commonly chosen treatment in many countries — a single oral capsule or drink ablates thyroid tissue; 80-90% are cured in one dose; subsequent lifelong hypothyroidism requiring levothyroxine; avoid in pregnancy, and avoid in active moderate-severe Graves' ophthalmopathy (worsens eye disease). (3) Total thyroidectomy: preferred when goitre is large, compressive symptoms exist, malignancy is suspected, patient is pregnant and ATD-intolerant, or moderate-severe ophthalmopathy. Graves' ophthalmopathy management: selenium 200 mcg/day (ETA-recommended for mild active disease); smoking cessation (essential — worsens both Graves' disease and ophthalmopathy); IV methylprednisolone (1 g weekly x 6 weeks) for moderate-severe active ophthalmopathy; teprotumumab (anti-IGF-1R monoclonal antibody, FDA-approved) for active moderate-severe TED; orbital decompression surgery for compressive optic neuropathy.

Untreated Hashimoto's hypothyroidism causes progressive cardiovascular risk from hypercholesterolaemia (LDL elevation due to reduced hepatic LDL receptors), diastolic hypertension, and cardiac dysfunction — significantly increasing atherosclerosis risk. Cognitive impairment ('brain fog'), depression, and psychosis ('myxoedema madness') occur in severe or prolonged hypothyroidism. Infertility results from anovulatory cycles; miscarriage risk increases with untreated hypothyroidism in pregnancy. Untreated severe hypothyroidism can progress to myxoedema coma — a life-threatening emergency precipitated by cold exposure, infection, or sedative drugs, with hypothermia, hypotension, bradycardia, CO2 retention, and hyponatraemia; mortality 20-50% despite treatment with IV levothyroxine (T4) and/or liothyronine (T3). In pregnancy, even subclinical hypothyroidism (TSH above 2.5 mU/L in first trimester) is associated with impaired foetal neurodevelopment, miscarriage, preterm birth, placental abruption, and pre-eclampsia — reflecting the foetus's complete dependence on maternal thyroid hormones in the first trimester. Untreated Graves' disease causes persistent tachycardia (promoting tachycardia-induced cardiomyopathy), atrial fibrillation (in 10-15% of cases — particularly in elderly patients who may present with isolated cardiac symptoms), bone loss (thyrotoxicosis stimulates osteoclast activity, reducing bone mineral density 10-20%), and muscle wasting (thyrotoxic myopathy — proximal muscle weakness). Graves' ophthalmopathy (thyroid eye disease — TED): active disease (class 2-6) causes corneal exposure, optic nerve compression, and permanent diplopia or vision loss if untreated; emergency orbital decompression surgery may be required. Thyroid storm (Burch-Wartofsky score above 45): a life-threatening emergency of extreme hyperthyroidism precipitated by infection, surgery, or iodine load — mortality 20-30% even with aggressive treatment (propylthiouracil, Lugol's iodine, IV corticosteroids, beta-blockade, cooling, ICU care).

AITD cannot be entirely prevented given the strong genetic component, but modifiable factors can be addressed. Selenium supplementation (200 mcg/day) reduces anti-TPO antibody levels in Hashimoto's and Graves' and may improve outcomes. Adequate iodine intake is important — both deficiency and excess worsen AITD. Quit smoking — smoking significantly worsens Graves' ophthalmopathy and is associated with higher AITD risk. Stress management, vitamin D optimisation, and a balanced diet support immune health. Regular TSH monitoring (annually or more frequently) is essential for patients with known AITD.

See your GP for: persistent unexplained fatigue with weight gain, cold intolerance, constipation, low mood, or hair loss — these suggest hypothyroidism (Hashimoto's). See a doctor for unexplained weight loss with palpitations, heat intolerance, tremor, anxiety, diarrhoea, or bulging eyes — these suggest hyperthyroidism (Graves' disease). Seek emergency care for myxoedema coma (severe hypothyroidism with confusion, hypothermia, and bradycardia) or thyroid storm (severe thyrotoxicosis with fever above 40°C, tachycardia, confusion, and cardiovascular collapse) — both are life-threatening emergencies. See an endocrinologist if TSH is very low or very high, if pregnant with thyroid disease, if thyroid eye disease (proptosis, diplopia) develops, or if thyroid nodule or goitre is found on examination.