Thyrotoxicosis is a condition caused by an increase in the levels of thyroid hormone circulating in the blood. It is usually due to an overproduction of thyroid hormones by the thyroid gland itself (hyperthyroidism), but there are a variety of other conditions that may cause thyrotoxicosis other than thyroid hyperfunction. The two terms however, tend to be used interchangeably.

Hyperthyroidsim is less common than hypothyroidism, occurring in about 0.3% of the population in subclinical form, and 0.3% in overt symptomatic form. It is ten times more common in females than males, and in 40% of patients the disease is self-limiting.

Fig. 1: An example of thyrotoxic thyroid function tests, in this case induced by severe Graves' disease

Causes of thyrotoxicosis

There are four main causes of thyrotoxicosis, but in Australia the first two are the most common, especially Graves' disease (you can click on the subject in the list to go straight to the webpage):

  1. Graves' Disease (70%)
  2. Toxic multinodular goitre (15%)
  3. Toxic adenoma (5%)
  4. Thyroiditis (5%)

Other less common causes of thyrotoxicosis, accounting for the remaining 5%, are:

  • Factitious Thyrotoxicosis - patients taking too much thyroid hormone
  • Drug-induced Thyrotoxicosis (e.g. Iodine, Thyroid hormone or Amiodarone - see below)
  • Neonatal Thyrotoxicosis - the passage from mother to foetus of maternal immunoglobulins that stimulate the foetal thyroid
  • Post-partum Thyroiditis - transient thyrotoxicosis occurs in 20% of women who have had previous thyrotoxicosis and normal thyroid function during pregnancy
  • Ectopic Hyperthyroidism - from a TSH-secreting tumour
  • Struma ovarii


The symptoms of thyrotoxicosis depend on the severity and duration of the disease, the specific cause of the thyrotoxicosis and the age of the patient. Excessive thyroid hormone affects virtually all body systems, through the stimulation of metabolic processes and activation of the sympathetic nervous system.

In general, the clinical features are:

  • Weight loss (weight gain in 10% due to increased appetite)
  • Heat intolerance
  • Palpitations
  • Breathlessness
  • Heart failure in the elderly
  • Irritability and poor sleep
  • Nervousness, anxiety
  • Tiredness and lethargy
  • Diarrhoea
  • A fine tremor, with proximal muscle weakness (unable to climb stairs or rise from a sitting position)
  • Sweating
  • Tachycardia
  • Goitre
  • Vitiligo and alopecia
  • Pretibial myxoedema: skin thickening like orange peel, common over the shins
  • Eye changes - related to sympathetic stimulation and (in Graves) to antibody reactions:
    • lid retraction and lid lag (common to all causes of thyrotoxicosis)
    • thyroid eye disease (TED) of Graves' disease: proptosis, eye muscle involvement, corneal involvement and optic nerve compression

Subclinical hyperthyroidism

Subclinical hyperthyroidism is characterised by a biochemical rather than a clinical finding, although clinical consequences are possible. It is characterised by chronically suppressed TSH levels but normal serum free T4 and T3 levels. The condition must not be confused with the transient TSH suppression seen in acute illness or after drug therapy (eg: high-dose glucocorticoids). About 5-8% of patients with subclinical hyperthyroidism will develop clinical thyrotoxicosis per year.

It occurs commonly with multinodular goitre, a toxic single thyroid nodule and overreplacement with thyroxine. Despite being called subclinical it is associated with an increased risk of atrial arrhythmia in those aged over 60 years and loss of bone mineral density in postmenopausal women.

Antithyroid therapy should be considered in patients with subclinical hyperthyroidism at increased risk of complications, and reduction of thyroxine dose in those taking replacement therapy.

It is important to note that the TSH-suppressive doses of thyroxine used after treatment for thyroid cancer intentionally produce subclinical hyperthyroidism, but it is unnecessary to continue this therapy lifelong in low-risk patients or if it is likely that permanent eradication of carcinoma has been achieved.

It is also important to note that thyrotoxicosis also affects fertility, so that it is very difficult to get pregnant while toxic. This means that patients with infertility problems should have their thyroid function tested.

Changes after treatment

Having thyrotoxicosis makes you feel that you have lots of energy and drive, but it comes at the expense of the health of your heart and bones particularly. It is like over-revving the engine of a motor car; it may make you go faster for a while, but it wears out the engine faster too and you are more likely to crash!

When you are treated by any of the measures mentioned on these webpages, and your body's metabolism is brought back under control, you must expect some changes, some of which can be quite distressing for a time. These changes are more noticeable if you are having surgery for your thyrotoxicosis, as the effect is more abrupt, and thyroid function returns to normal much more quickly than with the other treatments. The changes are also more marked if you are still a little toxic at the time of your operation.

It is very common to feel tired and lethargic after the treatment, as you must get used to being "normal" again; a small amount of weight gain is also common, but usually no more than about 3 kg, and of course if you are prepared for it to happen, you can prevent the weight increase by raising your exercise levels and altering your diet to adjust to the new circumstances.

These symptoms can be very distressing at first, but gradually wear off with time as you adjust to the way your body should be functioning. Of course I will also check your thyroid function with a blood test, after surgery or other treatment, to make sure you have enough replacement tablets, or enough residual function in the remaining thyroid.

Amiodarone-induced Thyrotoxicosis

Fig.2: Histology of amiodarone-induced thyroiditis, showing foamy macrophages within the colloid (Picture: Justin Du Plessis)Amiodarone is a uniquely effective antiarrhythmic drug, but it is also highly rich in iodine, containing as much as 37% of each tablet's mass.  Because of this  it produces a unique form of thyrotoxicosis which develops in 3% of amiodarone-treated patients in iodine-rich areas and in 10% of those living in iodine deficient areas of the world.

Amiodarone however can also cause hypothyroidism, indicated by persistently elevated TSH. In fact, in the United States the prevalence of amiodarone-induced thyrotoxicosis is much lower (3%) than that of amiodarone-induced hypothyroidism (22%). However, in iodine-deficient areas such as Tuscany, Italy, amiodarone-induced thyrotoxicosis predominates (10%) over hypothyroidism (5%).

Amiodarone-induced thyrotoxicosis is split into two types: Type 1 and Type 2, based on whether the patient has a pre-existing thyroid disorder. Type 1 amiodarone-induced thyrotoxicosis is seen in patients with preexisting or latent thyroid disorders and is caused by unregulated hormonal synthesis. It is treated with antithyroid drugs and potassium perchlorate. Type 2 occurs in patients with a previously normal thyroid and is due to the release of preformed hormone by an inflammatory destruction of the gland (thyroiditis). This is the most common form of amiodarone-induced thyrotoxicosis in Australia. It is treated with corticosteroids.

The two types can be distinguished by clinical, laboratory, and imaging evidence. Color-flow Doppler ultrasound shows promise as a single reliable tool for early diagnosis. Patients with mixed or severe forms of amiodarone-induced thyrotoxicosis should be managed with combination therapy, to establish a quick clinical response. However, thyroidectomy is advised for patients with worsening thyrotoxicosis, despite all medical treatment efforts, and for those who must be kept on amiodarone but do not respond to aggressive medical treatment.

Histology of the thyroidectomy specimen in amiodarone induced thyrotoxicosis shows characteristic features of foamy macrophages in the colloid (Fig. 2).