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
  • 

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