Hyperthyroidism

Primary hyperthyroidism: excess of thyroid hormone due to an abnormality of the thyroid gland.

Secondary hyperthyroidism: excess of thyroid hormone due to abnormal stimulation of a normal thyroid gland.

Thyrotoxicosis (vs hyperthyroidism): thyrotoxicosis can be excess circulating hormone of any source; hyperthyroidism is a result of excess production of new thyroid hormone.

Background and Epidemiology

  • Overt (clinical) hyperthyroidism is thought to affect ~1.9% of women (0.8/1000/year) and 0.16% of men (0.14/1000/year)
    • Subclinical hyperthyroidism is likely to be higher

Presentation

There are a wide range of symptoms and signs to possibly find in a patient with thyrotoxicosis:

  • Thyroid enlargement
    • Diffuse, unilateral, nodular
  • Dyspnoea, palpitations
    • sinus tachycardia, atrial fibrillation, heart failure, resting tachycardia, use-dependent oedema
  • Hyperactivity, emotional lability, insomnia, irritability, nervousness, anxiety, agitation
    • tremor
  • Exercise intolerance, fatigue, muscle (mainly proximal) weakness
    • Muscle wasting/weakness, proximal myopathy, hyperreflexia
  • Change in bowel habit (increased/diarrhoea)
  • Heat intolerance, increased sweating
    • Warm, moist skin (excess sweating- diaphoresis)
  • Increased appetite, weight change (loss or gain or stable despite intake change)
  • Infertility, oligomenorrhoea, amenorrhoea
  • Polyuria, thirst, generalised itch
    • Skin changes e.g. onycholysis, urticaria, diffuse pigmentation, diffuse non-scarring alopecia, palmar erythema,
  • Reduced libido; Gynaecomastia

NB There are also some symptoms/signs specific to different causes (see below)

Investigations

  • FBC, U&Es, LFTs
  • TFTs
    • TSH normal- no hyperthyroidism
    • TSH increased- Check free T4
      • Normal/low- consider hypothyroidism
      • Free T4 high- secondary hyperthyroidism (rare)
        • MRI/CT head/pituitary- look for tumour or lesion that might be the cause
      • TSH Low- check free T4
        • Normal- measure free T3
          • Normal- likely transient cause e.g. acute illness
          • High- T3 toxicosis (occurs in 10-15%)- further investigation
    • If TSH is low and free T3/T4 is high, consider a thyroid uptake scan 
      • Low uptake
        • Single cold nodule – consider thyroid cancer
        • Diffusely low uptake- measure thyroglobulin
          • If this is high- possible thyroiditis (ectopic thyroid hormone production or excess iodine also possible)
          • If low, it is likely that exogenous hormone is the cause.
      • High uptake
        • Diffusely hot- Grave’s disease
        • Single hot nodule- Toxic thyroid adenoma
        • Multiple hot nodules- Toxic multinodular goitre
  • Thyroid Antibodies
    • thy

Causes

  • Grave’s disease
  • Toxic Thyroid adenoma
    • <5% of all cases of thyrotoxicosis
    • More common in women and >40 years old
    • Solitary adenoma which secretes thyroid hormone (predominantly T3 thyrotoxicosis- and usually mild thyrotoxicosis.)
      • Inhibits TSH secretion and therefore the rest of the thyroid gland shuts down (shrinks/atrophy)
    • Symptoms are usually mild.  The patient may have a palpable nodule or it may only be detected by thyroid scintigraphy (uptake scan)
    • Treatment is usually radioiodine (because the inactive ‘normal’ thyroid fails to take up any radioactive iodine)
      • Risk of post-treatment hypothyroidism is relatively low
      • Surgery is an alternative
  • Toxic Multinodular goitre
    • Accounts for about 30-40% of hyperthyroid cases.
    • Also most common in women >40 years.  May develop from a diffuse (and often euthyroid) goitre.
    • In a similar fashion with toxic nodules- multinodular goitre releases thyroid hormone and suppresses TSH secretion
    • Patients can be asymptomatic (free T3/T4 may be within normal levels as well but TSH will always be low)
    • There will usually be a goitre present with palpable nodules
    • Treatment is usually with radioiodine (even if asymptomatic it may be appropriate if TSH is chronically and markedly suppressed as this can be a risk factor for AF and osteoporosis)
      • Risk of post-treatment hypothyroidism is relatively low
      • Surgery is an option for large, problematic (e.g. tracheal compression) goitres
  • Thyroiditis
  • TSH-secreting tumour
    • Extremely rare
    • Consider if there are features of hyperthyroidism with raised TSH and raised thyroid hormone
    • There may also be clinical signs of tumour (~80% are macroadenomas) e.g. visual disturbance, headaches
    • MRI/CT imaging is the investigation of choice
    • Treatment can be with octreotide and antithyroid drugs (+/- beta-blocker) but the mainstay is surgical resection
  • Amiodarone
    • Often causes a thyroiditis type picture
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