Hypothyroidism
Description
- Deficient thyroid hormone action
| TSH | fT4 | |
|---|---|---|
| Primary (gland) | inc | dec |
| Subclinical | inc | Normal |
| Central (pit/hypothal) | Low or inappropriately normal | dec |
| Poor adherence | inc | Normal/inc |
- Central hypothyroidism is missed by TSH-only screening - if you suspect it, order fT4
- Hashimoto = commonest acquired cause in iodine-replete populations
- Autoantigens: TPO, thyroglobulin, pendrin
- Myxoedema coma - decompensated hypothyroidism: hypothermia, hyponatraemia, hypoventilation, hypotension, obtundation
Epidemiology
- Overt 1-2%; subclinical 5-10%, rising to ~15% women >60
- F>M ~8:1
- Congenital 1:2000-3000 births; thyroid dysgenesis commonest
- Asymptomatic at birth - maternal T4 crosses placenta. Hence newborn screening, not clinical detection
- Post-RAI/thyroidectomy is a large and growing share of adult cases
Aetiopathogenesis
Primary - with goitre
- Hashimoto (chronic lymphocytic thyroiditis)
- Iodine deficiency (commonest cause worldwide); iodine excess (Wolff-Chaikoff escape failure)
- Drugs - lithium, amiodarone, thionamide, checkpoint inhibitors, TKIs, interferon
- Dyshormonogenesis
Primary - without goitre
- Atrophic thyroiditis (blocking TRAb)
- Post-ablative: RAI, thyroidectomy, external beam/craniospinal irradiation
- Dysgenesis/agenesis, lingual thyroid
Central
- Pituitary macroadenoma, surgery, radiotherapy, Sheehan, hypophysitis (incl. checkpoint inhibitor)
- PROP-1/PIT-1 mutations
Transient
- Subacute, silent and postpartum thyroiditis (hypothyroid phase)
- Withdrawal of suppressive thyroxine
Drug mechanisms
- Amiodarone - iodine load + inhibits T4->T3 conversion
- Phenytoin, phenobarbitone, carbamazepine, rifampicin - inc hepatic T4 clearance (raises requirement in treated patients)
- Fe, Ca, PPI, cholestyramine, soy - dec absorption
Diagnosis
Clinical
- Cold intolerance, weight gain, constipation, fatigue, menorrhagia
- Myxoedema facies, dry skin, lateral eyebrow loss, husky voice
- Delayed relaxation phase of reflexes - the discriminating sign
- Bradycardia, pericardial/pleural effusion, non-pitting oedema
Biochemistry
- TSH first. Add fT4 if TSH abnormal or central disease suspected
- Anti-TPO -> confirms autoimmune aetiology, predicts progression
- Do not test TFTs in acute illness - sick euthyroid mimics central hypothyroidism
Subclinical
- inc TSH, normal fT4, confirmed at 2-3 months
- ~46% with TSH <7 normalise spontaneously within 2 years
- Persistent TSH >10 -> symptoms, inc CV events
Congenital
- Newborn screen: TSH on heel-prick day 2-3
- Earliest clinical sign = large anterior AND posterior fontanelles; jaundice, poor feeding, umbilical hernia later
- Treat within 2 weeks - irreversible neurodevelopmental damage otherwise
Non-specific findings
- inc CK, macrocytic anaemia, hyponatraemia, inc cholesterol, inc prolactin
Management
Overt primary
- Levothyroxine 1.6 microg/kg/day, single daily dose
- Start 25-50 microg if age >65, IHD, or long-standing disease - angina, AF, fracture
- Fasting, 30-60 min before food; separate 4h from Fe, Ca, PPI
- Recheck TSH at 6-8 weeks, then annually once stable
- Earlier is uninterpretable - TSH lags
- Target TSH in reference range; upper half of range if >70y
- T4/T3 combination not routine - RCTs show no consistent benefit
- Trial only in persistent symptoms with normal TSH, after excluding other causes; never desiccated thyroid extract
Central hypothyroidism
- Titrate to fT4 in the upper half of the range - TSH is uninterpretable
- *Exclude and treat adrenal insufficiency first* - thyroxine precipitates crisis
Subclinical
- Treat if:
- TSH >10 (especially age <70), OR
- Pregnant/planning pregnancy and TSH >4, OR
- Goitre, positive TPO with symptoms, or dyslipidaemia
- TSH 4-10 in the elderly: observe, repeat 6-12 monthly
- TRUST trial - no symptom or function benefit in >65s
Pregnancy
- Increase dose ~25-30% as soon as pregnancy confirmed (two extra tablets/week)
- Trimester-specific TSH targets; check every 4 weeks to mid-gestation
- Untreated maternal hypothyroidism -> miscarriage, pre-eclampsia, impaired neurodevelopment
Myxoedema coma
- ICU. IV levothyroxine loading (+/- liothyronine) and IV hydrocortisone before thyroid hormone
- Passive rewarming, treat precipitant, cautious fluid for hyponatraemia
Associations
- Other autoimmunity - T1DM, coeliac, Addison (APS-2), pernicious anaemia, vitiligo
- Neurological - carpal tunnel and other entrapments, proximal myopathy with inc CK, cerebellar ataxia, sensorineural deafness, unmasked myasthenia
- Pendred - AR pendrin (Cl/I transporter) mutation -> goitre + sensorineural deafness
- Down and Turner syndromes - screen annually
- Hashimoto -> primary thyroid lymphoma (rare, but a rapidly enlarging goitre)
- Dyslipidaemia, hyponatraemia, hyperprolactinaemia
Natural history & complications
- Anti-TPO positive subclinical -> overt at ~4%/year
- Adequately treated: normal life expectancy
- Untreated in childhood: height deceleration with preserved weight, delayed bone age and puberty
- Rarely precocious puberty (Van Wyk-Grumbach) from TSH cross-stimulating FSH receptors
- Catch-up growth incomplete if treatment late
- Craniospinal irradiation: ~30% primary hypothyroidism within 12 months, ~10% central
Complications
- Myxoedema coma - mortality 20-40%
- Accelerated atherosclerosis, pericardial effusion
- Over-replacement: AF and osteoporosis - check TSH is not suppressed
- Congenital, untreated: permanent intellectual disability, deafness, ataxia
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