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Hypothyroidism

SNOMED: 40930008954 words•Updated 03/03/2026
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Exam Tips

  • Pattern recognition is high yield: primary overt hypothyroidism = high TSH + low FT4; subclinical = high TSH + normal FT4; central = low FT4 with non-elevated TSH.
  • Before treating possible central hypothyroidism, check adrenal status first; giving levothyroxine first can precipitate adrenal crisis.
  • In older patients, non-specific symptoms are common and TSH can rise physiologically; avoid diagnosing subclinical disease on symptoms alone.
  • In pregnancy, use trimester-specific TSH ranges and increase levothyroxine early once pregnancy is confirmed.
  • Myxoedema coma is a medical emergency: hypothermia, bradycardia, altered consciousness, and a precipitating illness should trigger urgent ICU-level management.

Definition

Hypothyroidism is a clinical syndrome caused by deficient thyroid hormone action (mainly T4 and T3), leading to reduced metabolic activity across multiple organ systems. In UK practice, most cases are primary thyroid failure (commonly autoimmune), while a smaller group have central hypothyroidism from pituitary or hypothalamic disease; biochemically this is identified by a low free T4 with either raised TSH (primary) or inappropriately normal/low TSH (central).

Pathophysiology

The hypothalamic-pituitary-thyroid axis regulates thyroid hormone production via TRH (hypothalamus) and TSH (pituitary), with negative feedback from circulating T4/T3. In primary hypothyroidism, thyroid gland failure (usually autoimmune thyroiditis in iodine-sufficient regions such as the UK) reduces T4/T3 output, causing compensatory TSH elevation; overt disease usually has raised TSH with low FT4, while subclinical disease has raised TSH with normal FT4. In central hypothyroidism, pituitary/hypothalamic dysfunction causes inadequate TSH drive, so FT4 is low but TSH is not appropriately raised. Reduced thyroid hormone signaling lowers basal metabolic rate, slows cardiovascular and gastrointestinal function, impairs neuromuscular and cognitive performance, and alters lipid/carbohydrate handling. Severe longstanding deficiency can culminate in myxoedema coma (decompensated multi-organ hypothyroidism). See standard HPT-axis diagrams in endocrine physiology texts for visual correlation.

Risk Factors

  • Female sex and increasing age
  • Autoimmune thyroid disease (Hashimoto thyroiditis/atrophic autoimmune thyroiditis)
  • Personal/family history of autoimmune disease (for example type 1 diabetes, coeliac disease, pernicious anaemia)
  • Previous thyroid surgery, radioiodine, or neck radiotherapy
  • Postpartum period (postpartum thyroiditis)
  • Iodine deficiency or iodine excess (including iodine-containing supplements)
  • Drugs: amiodarone, lithium, interferon-alpha, sodium valproate, rifampicin, thalidomide, prolonged antithyroid-drug exposure
  • Pituitary/hypothalamic disease (tumour, surgery, trauma, infarction/Sheehan syndrome) for central hypothyroidism
  • Obesity and White ethnicity are associated with higher treated prevalence in UK datasets

Clinical Features

Symptoms

  • Fatigue, lethargy, reduced exercise tolerance
  • Weight gain and cold intolerance
  • Constipation
  • Dry skin, hair thinning, hoarse voice
  • Low mood, slowed thinking, memory/concentration difficulty
  • Menstrual disturbance, subfertility/infertility, reduced libido
  • Myalgia and muscle cramps
  • In severe disease: confusion, drowsiness, or reduced consciousness (myxoedema coma)

Signs

  • Bradycardia
  • Delayed relaxation of deep tendon reflexes
  • Dry coarse skin, brittle hair, loss of lateral eyebrows
  • Periorbital puffiness/non-pitting oedema (myxoedematous facies)
  • Goitre (especially autoimmune thyroiditis) or small atrophic thyroid
  • Hypothermia in severe disease
  • Carpal tunnel features or proximal muscle weakness
  • In central causes: features of pituitary disease (visual field defect, headaches, other hormone deficiencies)

Investigations

Serum TSH and free T4 (first-line thyroid function tests):Primary overt hypothyroidism: raised TSH (often >10 mU/L) with low FT4; subclinical hypothyroidism: raised TSH with normal FT4; central hypothyroidism: low FT4 with inappropriately normal/low (occasionally slightly raised but biologically weak) TSH
Thyroid peroxidase antibody (TPOAb):Often positive in autoimmune hypothyroidism; supports diagnosis and predicts progression risk in subclinical disease
Full blood count:May show normocytic or macrocytic anaemia
Lipid profile:Raised total cholesterol and LDL are common
Creatine kinase, U&Es, LFTs, glucose/HbA1c (as baseline/comorbidity screen):CK may be elevated; hyponatraemia can occur in severe disease; helps assess systemic impact
Pregnancy test and trimester-specific thyroid ranges when relevant:Pregnancy-specific TSH reference ranges should be used; maternal hypothyroidism is defined against trimester thresholds
Pituitary profile (9 am cortisol, prolactin, LH/FSH, IGF-1) and pituitary MRI if central hypothyroidism suspected:Evidence of multi-axis pituitary dysfunction and/or structural pituitary-hypothalamic pathology
ECG (if older or cardiac disease):Sinus bradycardia and low-voltage changes may be seen; useful before dose escalation

Management

Lifestyle Modifications

  • Explain chronic nature and expected recovery timeline (symptom improvement may lag behind TFT normalization)
  • Support medication adherence: take levothyroxine consistently on an empty stomach, typically 30-60 minutes before breakfast
  • Separate levothyroxine from iron, calcium, aluminium/magnesium antacids, and bile-acid sequestrants by at least 4 hours
  • Address cardiovascular risk factors (smoking, diet, weight, BP, lipids) because hypothyroidism is linked with adverse CV outcomes
  • In pregnancy or planning conception, arrange early thyroid testing and tighter monitoring

Pharmacological Treatment

Thyroid hormone replacement (first-line)

  • Levothyroxine sodium: typical adult initial dose 50-100 micrograms once daily; maintenance commonly 100-200 micrograms once daily
  • If age >65 years or coronary heart disease: start 25 micrograms once daily and increase by 25 micrograms every about 4 weeks according to TSH/FT4 and symptoms

BNF-style approach: titrate to biochemical euthyroidism and clinical response. Recheck TFTs about 6-8 weeks after dose changes. Use caution in ischaemic heart disease (risk of angina/arrhythmia with rapid up-titration). In suspected central hypothyroidism, assess/treat adrenal insufficiency before starting levothyroxine (to avoid precipitating adrenal crisis).

Special situations

  • Pregnancy: increase existing levothyroxine dose early (often by about 25-50 micrograms/day or ~20-30%) and monitor frequently with trimester-specific targets
  • Myxoedema coma (critical care): intravenous thyroid hormone (levothyroxine and/or liothyronine per specialist protocol) plus intravenous hydrocortisone 100 mg every 8 hours initially

Do not delay emergency treatment in myxoedema coma. Oral absorption may be unreliable in critical illness. Continuous cardiac monitoring is required during high-dose thyroid replacement.

Therapies generally not routine in primary care hypothyroidism

  • Liothyronine (T3) monotherapy
  • Combination levothyroxine-liothyronine therapy

Not routinely recommended; consider only under endocrinology supervision in selected persistent-symptom cases after exclusion of alternative causes. Watch for overtreatment (suppressed TSH), atrial fibrillation, and bone loss.

Complications

  • Coronary heart disease, myocardial infarction, and increased cardiac/all-cause mortality risk
  • Heart failure (including diastolic dysfunction; risk rises with higher TSH, especially >10 mU/L)
  • Dyslipidaemia and broader cardiometabolic risk
  • Subfertility/infertility and menstrual dysfunction
  • Pregnancy complications: miscarriage, pre-eclampsia, placental abruption, postpartum haemorrhage, stillbirth
  • Adverse neonatal outcomes: preterm birth, low birthweight, respiratory distress, neurocognitive effects
  • Neurocognitive impairment and increased depressive symptoms
  • Reduced quality of life and persistent functional symptoms
  • Myxoedema coma (rare, life-threatening emergency with high mortality)

Prognosis

With accurate diagnosis, appropriate levothyroxine dosing, and regular monitoring, prognosis is generally very good and most patients regain normal physical and psychological function. A minority (around 5-10%) report persistent symptoms despite normal TFTs, so clinicians should reassess adherence, interactions, comorbidity, and alternative diagnoses rather than escalating thyroid hormone indiscriminately.

Sources & References

💊BNF Drug References(32)

✅NICE Guidelines(1)

📖Textbook References(6)

  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1747)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1746, 1747)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1746, 1747)[context]
  • Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 939)[context]
  • Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 939)[context]
  • Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 939)[context]

Sources

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