Hypothyroidism — Causes, TSH Testing, Levothyroxine & Thyroid Replacement Guide — Symptoms, Causes & Treatment | MyMedicPlus

Hypothyroidism is a clinical syndrome resulting from inadequate production of thyroid hormones (thyroxine T4 and triiodothyronine T3) by the thyroid gland, causing widespread metabolic slowing and affecting virtually every organ system. It is one of the most common endocrine disorders, affecting approximately 2% of adults with a marked female predominance (7–10-fold higher in women). Subclinical hypothyroidism (elevated TSH with normal free T4 and no or minimal symptoms) is even more prevalent, affecting 4–8% of the general population. Overt hypothyroidism develops insidiously over months to years, often going unrecognised until symptoms are significant. Diagnosis and treatment with levothyroxine typically leads to complete resolution of symptoms. Untreated severe hypothyroidism can progress to myxoedema coma — a life-threatening emergency. The primary cause in iodine-sufficient regions is Hashimoto's thyroiditis — an autoimmune lymphocytic destruction of thyroid tissue, characterised by thyroid peroxidase (TPO) antibodies present in over 90% of patients, with a strong genetic predisposition (HLA-DR3 and HLA-DR5 associations).

Primary hypothyroidism (the vast majority — failure of the thyroid gland itself): Hashimoto's thyroiditis (autoimmune thyroiditis) — most common cause in iodine-sufficient countries, characterised by thyroid peroxidase (TPO) antibodies and lymphocytic infiltration causing progressive thyroid destruction; previous thyroid surgery (total or partial thyroidectomy); radioiodine (I-131) treatment for hyperthyroidism or thyroid cancer; external beam radiotherapy to the neck; iodine deficiency — most common cause of hypothyroidism globally, affecting developing regions; medications — amiodarone (contains iodine, causes both hypo- and hyperthyroidism; 10–35% of patients), lithium, interferon-alpha, immunotherapy checkpoint inhibitors (pembrolizumab, nivolumab), tyrosine kinase inhibitors. Secondary hypothyroidism (pituitary failure — rare): pituitary tumours, surgery, radiation, Sheehan syndrome (postpartum pituitary infarction) — low TSH with low free T4. Congenital hypothyroidism: thyroid dysgenesis; detected by neonatal screening.

Symptoms reflect the widespread metabolic slowing caused by thyroid hormone deficiency: fatigue and lethargy (most common complaint), weight gain (despite normal or reduced appetite), cold intolerance, constipation, dry skin and hair, hair loss (including lateral third of eyebrows — sign of Hertoghe), hoarse voice, menstrual irregularities (menorrhagia or oligomenorrhea), depression, memory impairment and cognitive slowing ('brain fog'), carpal tunnel syndrome (fluid accumulation), and bradycardia. Signs on examination: cool, dry, rough, pale skin; puffiness of the face and hands (myxoedema — from glycosaminoglycan deposition); slow-relaxing deep tendon reflexes (delayed relaxation phase — Woltman sign); diffuse non-pitting oedema; bradycardia; goitre (in Hashimoto's thyroiditis — initially firm and rubbery, later may shrink). Myxoedema coma: severe hypothermia, altered consciousness, hypoventilation, hypotension — medical emergency.

Thyroid-stimulating hormone (TSH): the most sensitive first-line test for primary hypothyroidism. Elevated TSH (above 4.2 mU/L) with normal free T4 = subclinical hypothyroidism. Elevated TSH with low free T4 = overt hypothyroidism. Low TSH with low free T4 suggests secondary hypothyroidism (pituitary disease — requires further pituitary evaluation). Free T4 (fT4): reflects the active hormone level; below the reference range confirms overt hypothyroidism. Free T3 (fT3): not routinely required for diagnosis but may be measured in amiodarone-induced or central hypothyroidism. Thyroid peroxidase antibodies (anti-TPO): positive in 90–95% of Hashimoto's thyroiditis; confirms autoimmune aetiology and predicts future progression from subclinical to overt hypothyroidism. Thyroid ultrasound: heterogeneous, hypoechoic gland in Hashimoto's; nodules or goitre; not routinely required for diagnosis. Lipid profile: hypothyroidism causes hypercholesterolaemia — TSH normalisation often reduces total cholesterol by 20–30%.

Levothyroxine (LT4, synthetic T4) is the standard treatment for overt hypothyroidism: initial dose 1.6 mcg/kg ideal body weight daily (lower starting doses of 25–50 mcg in elderly or those with cardiovascular disease — to avoid precipitating cardiac ischaemia or arrhythmia). Taken on an empty stomach 30–60 minutes before food (or 4 hours after calcium supplements, iron, antacids — which impair absorption). TSH should be rechecked after 6–8 weeks and dose adjusted by 12.5–25 mcg increments until TSH is within target range. Target TSH: 0.4–2.5 mU/L for most adults; 0.1–2.5 mU/L in pregnancy; 1.0–4.0 mU/L in elderly (to avoid overtreatment and AF risk). Once stable, annual TFTs suffice. Subclinical hypothyroidism: treat if TSH above 10 mU/L (consistent evidence); consider treatment if TSH 4.5–10 mU/L with symptoms, positive anti-TPO, pregnancy, or age under 65. Combination LT4 + liothyronine (T3) is not recommended routinely but may be trialled in selected patients with persisting symptoms despite adequate LT4 therapy. Myxoedema coma: IV levothyroxine (200–400 mcg bolus), IV liothyronine, IV hydrocortisone, warming blankets, ICU monitoring.

Myxoedema coma is the most life-threatening complication of severe, untreated hypothyroidism — characterised by progressive obtundation, profound hypothermia (core temperature below 32°C), bradycardia, hypotension, hyponatraemia, and respiratory depression with CO2 retention; mortality is 20–50% even with optimal treatment. Precipitants include cold exposure, infection, sedatives, and surgical stress. Treatment requires IV liothyronine (T3) or levothyroxine, IV hydrocortisone (to prevent relative adrenal insufficiency from T3 administration), passive warming, IV fluids, and ventilatory support. Cardiovascular complications: hypothyroidism causes hyperlipidaemia (elevated LDL cholesterol from reduced LDL-receptor activity), hypertension, and cardiac dysfunction — pericardial effusion occurs in 30–80% of severe hypothyroidism (usually haemodynamically insignificant); atherosclerotic cardiovascular disease risk is elevated from dyslipidaemia, hypertension, and endothelial dysfunction. Neuromuscular complications: carpal tunnel syndrome (from myxoedematous infiltration of the transverse carpal ligament — in up to 70%), myalgia and myopathy with elevated CK, cerebellar ataxia, and peripheral neuropathy in severe cases. Hypothyroid myopathy: Hoffman syndrome (pseudohypertrophic myopathy with muscle cramps and weakness) is a rare but characteristic complication. Infertility and pregnancy complications: hypothyroidism (TSH above 4.0 mIU/L) impairs ovulation, increases miscarriage risk (2-fold), and, if untreated in pregnancy, causes irreversible fetal neurodevelopmental impairment — including reduced IQ and motor developmental delay. Psychiatric manifestations including psychosis ('myxoedema madness') in severe cases. Normochromic or macrocytic anaemia from reduced erythropoietin and impaired folate absorption.

Hashimoto's thyroiditis (autoimmune hypothyroidism) cannot be prevented. Adequate dietary iodine intake (recommended 150 mcg/day adults; 220 mcg in pregnancy) prevents iodine-deficiency hypothyroidism — achieved through iodised salt and dairy consumption in most developed countries. Screen and monitor thyroid function regularly in: women planning pregnancy or during pregnancy (thyroid screening at booking); patients treated with amiodarone, lithium, or immune checkpoint inhibitors; those who have had previous thyroid surgery or radioiodine therapy; patients with type 1 diabetes or other autoimmune conditions; and first-degree relatives of people with autoimmune thyroid disease. Levothyroxine-treated patients should be aware that certain medications (iron supplements, calcium, cholestyramine, PPIs, antiepileptics) and foods (soya, high-fibre diets) can impair absorption — report any new medications to your GP.

Consult your GP if you experience unexplained fatigue, weight gain, hair loss, cold intolerance, constipation, or low mood lasting several weeks — these may indicate hypothyroidism. Women planning pregnancy or who are pregnant should have thyroid function tested early in the first trimester — uncontrolled hypothyroidism in pregnancy increases the risk of miscarriage, preterm birth, and impaired child neurological development. Seek emergency assessment for: confusion, hypothermia, or loss of consciousness in a person known to have hypothyroidism — these signs may indicate myxoedema coma requiring urgent ICU treatment. If already on levothyroxine and symptoms recur or worsen, or you feel overmedicated (palpitations, anxiety, weight loss), contact your GP for repeat TSH testing — do not adjust doses without medical advice.