THD

• Thyroid gland disease


  These are common, affecting some 5% of the population, predominantly females

  
• Thyroid axis


  Involved in the regulation of cellular differentiation and metabolism in virtually all nucleated cells, so that disorders of thyroid function have diverse manifestations

  
• Structural diseases in the thyroid gland, such as goitre, commonly occur without abnormal thyroid function

  
• T3 and T4


  Circulate in plasma almost entirely (> 99%) bound to transport proteins, mainly thyroxine-binding globulin (TBG)
• Free hormones


  The unbound hormones which diffuse into tissues and exert diverse metabolic actions
• The advantage of the free hormone measurements is that they are not influenced by changes in the concentration of binding proteins
• Common presentations of thyroid disease


  • Thyrotoxicosis (i.e. hyperthyroidism)
  • Hypothyroidism
  • Goitre (i.e. enlargement of the thyroid)

  
• Ready access to accurate tests of thyroid function and an increasing tendency to screen certain populations (e.g. elderly, hospitalised) have led to the identification of patients with abnormal results who are either asymptomatic or have non-specific complaints such as tiredness and weight gain

  
• Definitive treatment of thyrotoxicosis


  Depends on the underlying cause, and may include antithyroid drugs, radioactive iodine or surgery

  
• Non-selective β-adrenoceptor antagonist (β-blocker)

  Will alleviate but not abolish symptoms within 24-48 hours
• Beta-blockers cannot be recommended for long-term treatment, but they are extremely useful in the short term, e.g. for patients awaiting hospital consultation or following I131 therapy
• Atrial fibrillation in thyrotoxicosis


  Thyrotoxicosis is an important cause of atrial fibrillation; the incidence increases with age so that almost half of all males with thyrotoxicosis over the age of 60 are affected

  
• Subclinical thyrotoxicosis is a risk factor for atrial fibrillation

  
• Thrombo-embolic vascular complications


  Are particularly common in thyrotoxic atrial fibrillation so that anticoagulation with warfarin is required, unless contraindicated
• Once thyroid hormone and TSH concentrations have been returned to normal, atrial fibrillation will spontaneously revert to sinus rhythm in ∼50% of patients

  
• Thyrotoxic crisis ('thyroid storm)

  A rare and life-threatening increase in the severity of the clinical features of thyrotoxicosis

  
• Thyrotoxic crisis is most commonly precipitated by infection in a patient with previously unrecognised or inadequately treated thyrotoxicosis
• Management of thyrotoxic crisis


  1. Rehydration and broad-spectrum antibiotic

  2. Propranolol rapidly effective orally or intravenously

  3. Sodium ipodate to restore serum T3 levels to normal in 48-72 hours

  4. Dexamethasone and amiodarone have similar effects

  5. Oral carbimazole 40-60 mg daily inhibits the synthesis of new thyroid hormone

  
• Hypothyroidism management


  Most patients do not require specialist review and will require life-long thyroxine therapy

  
• Thyroxine dosage


  1. Start with 50 μg per day for 3 weeks, increase to 100 μg per day for 3 weeks, then maintenance dose of 100-150 μg per day

  2. Repeat thyroid function tests and adjust dose in increments of 25 μg per day, usually every 6 weeks

  
• Correct thyroxine dose


  That which restores serum TSH to within the reference range, with serum T4 usually in the upper part of the normal range or even slightly raised

  
• Some patients remain symptomatic despite normalisation of TSH and may wish to take extra thyroxine which suppresses TSH values, but this approach cannot be recommended
• It is important to measure thyroid function every 1-2 years once the dose of thyroxine is stabilised

  
• Thyroxine replacement in ischaemic heart disease


  Exacerbation of myocardial ischaemia, infarction and sudden death are well-recognised complications, even using doses as low as 25 μg per day

  
• Thyroxine introduction in patients with ischaemic heart disease


  1. Introduce at low dose and increase very slowly under specialist supervision

  2. T3 has an advantage over T4 as it has a shorter half-life and any adverse effect will reverse more quickly

  
• Approximately 40% of patients with angina cannot tolerate full replacement therapy despite the use of β-blockers and vasodilators
• Hypothyroidism in pregnancy


  Most pregnant women with primary hypothyroidism require an increase in the dose of thyroxine of ∼50 μg daily to maintain normal TSH levels

  
• Recent research suggests that inadequate maternal T4 therapy is associated with impaired cognitive development in their offspring
• Myxoedema coma


  A rare presentation of hypothyroidism in which there is a depressed level of consciousness, usually in an elderly patient who appears myxoedematous
• Treatment of myxoedema coma


  1. Triiodothyronine is given as an intravenous bolus of 20 μg followed by 20 μg 8-hourly until there is sustained clinical improvement

  2. Hydrocortisone 100 mg i.m. 8-hourly, pending the results of T4, TSH and cortisol concentration

  3. Slow rewarming, cautious use of intravenous fluids, broad-spectrum antibiotics and high-flow oxygen

  
• Subclinical thyrotoxicosis


  The serum TSH is undetectable and the serum T3&T4 lie in the upper parts of their respective reference ranges

  
• Patients with subclinical thyrotoxicosis are at increased risk of atrial fibrillation and osteoporosis
• Subclinical hypothyroidism

  The serum TSH is raised and the serum T4&T3 concentrations are usually in the lower part of their respective reference ranges
• There is a risk of progression to overt thyroid failure, particularly if antibodies to thyroid peroxidase are present in the serum or if the TSH rises above 10 mU/l

  
• Non-thyroidal illness ('sick euthyroidism)


  In patients with systemic illness there is decreased peripheral conversion of T4 to T3 and alterations of binding proteins and their affinity for thyroid hormones

  
• Biochemical assessment of thyroid function should not be undertaken in patients with non-thyroidal illness, unless there is good evidence of concomitant thyroid disease

  
• Autoimmune thyroid disease


  Thyroid diseases are amongst the most prevalent antibody-mediated autoimmune diseases and are associated with other organ-specific autoimmunity

  
• Graves' disease


  The most common manifestation is thyrotoxicosis with or without a diffuse goitre. Graves' disease also causes ophthalmopathy and rarely pretibial myxoedema

  
• Thyroid diseases are amongst the most prevalent antibody-mediated autoimmune diseases and are associated with other organ-specific autoimmunity

  
• Autoantibodies


  May produce inflammation and destruction of thyroid tissue resulting in hypothyroidism, goitre (in Hashimoto's thyroiditis) or sometimes even transient thyrotoxicosis ('Hashitoxicosis'), or they may stimulate the TSH receptor to cause thyrotoxicosis (in Graves' disease)