Hypothyroidism

Signs and symptoms

• Common symptoms
  • • Fatigue
    • Cold intolerance
    • Depression and poor concentration
    • Dry skin, brittle hair or hair loss
    • Bradycardia
    • Puffy eyes
    • Weight gain
    • Anaemia
• Less common symptoms
  • • Constipation
    • Carpal tunnel syndrome
    • Oedema
    • Hoarseness
    • Menorrhagia
    • Cerebellar signs and deafness
    • Psychiatric symptoms
    • Angina and hypertension
    • Myalgia
    • Serositis / effusions
    • Slow relaxing reflexes
    • Erythema ab igne
    • Increased risk of miscarriage/congenital abnormalities (increase thyroxine dose in pregnancy)

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Causes

• 90% of cases are caused by
  • • Hashimoto’s autoimmune thyroiditis – this is the most common, usually irreversible and needs lifelong treatment
    • Post radio-iodine / thyroidectomy
    • Therefore detailed investigation of cause not usually required
• Other causes
  • • Atrophic thyroiditis – possibly end stage Hashimoto’s
    • Post-partum thyroiditis – hypothyroidism comes after the hyperthyroid phase, often reversible
    • Drugs – Amiodarone, lithium, antithyroid drugs
    • Iodine deficiency
    • Congenital – short, learning disability
    • Thyroid infiltration
    • Secondary hypothyroidism
      • • Pituitary disease (do not use TSH as guide to treatment)
        • Usually due to a tumour or craniopharyngioma, surgery or radiotherapy
    • Tertiary hypothyroidism
      • • Deficient TSH from hypothalamus
        • Less common than secondary
    • Reidel’s thyroiditis
    • Thyroid hormone resistance

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Investigations

• TFTs – TSH increased, and this antedates a decline in T4
• Can check FBC, U&Es, CRP, LFTs, CK, lipids, cortisol, haematinics
• Anti-TPO antibodies
  • • More common in population than hypothyroidism – they only increase the risk
    • But present in 90% of Hashimoto’s (so negative does not exclude it), 75% of Graves and 15% of normal people
• Anti-thyroglobulin antibodies
  • • Have low sensitivity and specificity, so only used if suspected thyroid cancer
    • Present in 5% of the general population
• Consider other associated autoimmune disease
  • • Cortisol – consider co-existing hypoadrenalism
      • • Replacing thyroxine without steroids is dangerous
        • Thyroid function can normalise with steroids – hypoadrenal patients tend to have an elevated TSH and normal/slightly low T4 mimicking subclinical hypothyroidism
    • B12 – pernicious anaemia
• Mild anaemia is common
• CK can be elevated
• Abnormal lipids – typically high TC and high LDL. Usually don’t treat the lipids initially – just recheck, thyroxine will often correct them
• ECG
• Pregnancy test – untreated hypothyroidism in pregnancy is associated with learning disabilities in children

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Treatment

• Thyroxine
  • • Dosing
      • • Start at 1.6mcg/kg (or 50-100mcg) if aged <65 with no history of CV disease
        • If elderly, known IHD, or longstanding and severe hypothyroidism – start at 25-50 mcg OD
        • Might have to increase dose if patient takes oestrogens or anti-seizure medications
        • Once appropriate dose established it remains constant in most patients
        • If symptoms persist, can adjust dose to achieve wellbeing as long as TFTs stay in range. Could also measure T4
    • Advise to take without food / other meds – especially iron which reduces the absorption of levothyroxine
    • Safe in breastfeeding – only very small amounts pass into milk
    • Check TFTs every 3/12 until stabilised, then every 6 or 12 months
    • If a patient gets sicker when levothyroxine commenced – consider hypoadrenalism
• If TSH remains high at 6 weeks
  • • Increase dose by 25mcg (or 50mcg) daily and repeat TSH in 6-8 weeks.
    • Consider coeliac screen
    • Consider thyroxine absorption test
    • Check not taking iron or calcium or other drugs at the same time that interfere with absorption (people can lose 60% of their thyroxine if not taking it correctly)
    • TSH can take months to normalise if it was very high – as long as it’s continuing to fall, and T4 normal, you could leave the dose alone
    • If there’s a history of thyroid cancer – aim for TSH <0.05
• If T4 is high but TSH normalises – not a problem, continue on the same dose
• In pregnancy – Increase dose by 50mcg. Measure TSH in each trimester
• In secondary hypothyroidism – T4 used to guide treatment instead. Aim for T4 in upper half of normal range and disregard TSH
• Levothyroxine can be administered once weekly in select patients unlikely to adhere to tx
• If a patient remains symptomatic – consider other causes (such as vitamin deficiencies, OSA)

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Subclinical hypothyroidism

• Common, especially women > 60 yrs
• Can lead to weight gain
• High TSH but normal T3/4
• Recheck TFTs in 3-6 months – 50% will normalise
• If persistent changes consider thyroxine, and have a lower threshold to treat if
  • • Very symptomatic
    • TSH>10
    • Young or planning pregnancy
    • Previous radio-iodine treatment
    • High risk of progressing to actual hypothyroidism (check anti-tpo antibodies – if present, risk of actual hypothyroidism is 60% in 9 years)
• Always then monitor TFTs
• Always treat in pregnancy

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Myxoedema coma

• Usually occurs in longstanding autoimmune or iatrogenic hypothyroidism, and usually in elderly obese females
• Mortality >50% if not quickly diagnosed, and even then still 25% (worse if old, hypothermic, very bradycardic, septic, recent MI)
• Often insidious at onset
• Can be precipitated by
  • • Intercurrent illness – MI, CVA, infection, HF, trauma
    • Poor adherence to treatment
    • Cold weather
    • Drugs – sedatives, lithium, amiodarone
• Ask about adherence to thyroxine, previous radioiodine or surgery
• Clinical features
  • • May be decreased heart rate, temperature, GCS, blood pressure, glucose, sodium and oxygen saturations
    • Can be heart failure, non-specific ECG changes, VT, a pericardial effusion, pleural effusions, OSA/hypercapnia
    • Lethargy / delirium / coma (but patients don’t have to be comatose)
    • May be an AKI and hyponatraemia
    • Megacolon/ileus
    • Hypoventilation with elevated pCO2
    • Can be high CK and MCV
    • TSH has to be >45 (usually >80) and T4 < 5
• Management
  • • Cardiac monitor / HDU
    • Send cortisol
    • Warming – passive, aim for slow rise ie 0.5 °C/hour
    • Septic screen
    • Four hourly CBGs and treat hypoglycaemia with IV dextrose
    • Steroids – hydrocortisone 100mg IM and every 6 hours until cortisol result
    • Liothyronine (T3) 5-10mcg PO/NG, but non-urgent. Do NOT give IV. Short half-life
    • Then at 6 hours, can give 10 mcg liothyronine, then continue giving 10 mcg every 12 hours, then give 20 mcg BD
    • Then introduce levothyroxine 25 mcg at day 4, give with liothyronine for 5 days, then stop liothyronine
    • Alternatively: treat with 300-500 mcg IV T4, followed by 50-100 mcg daily. Can add 10 mcg of T3 TDS IV if no improvement
    • You do not need to reverse thyroid biochemistry fast, and doing so could be harmful. Treat the precipitant
    • Monitor TFTs. TSH should fall by 50% if you’re giving full replacement of thyroid hormones
    • IV pressors and thyroxine can cause VF/VT
    • Sometimes NIV used
    • Cautious IV fluids if low BP. Vasopressors usually ineffective for hypotension
    • Water restrict if hyponatraemic
    • Treat precipitants
    • Consider antibiotics