Overview

Hyperthyroidism describes the excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is a term used to describe the clinical manifestations of excess circulating thyroid hormones due to any cause, including hyperthyroidism. 

There are multiple causes of hyperthyroidism which are summarised in this chapter. Of these causes, Graves’ disease is the most common cause of thyrotoxicosis in the UK.

To help make sense of this chapter, it may be helpful to refer to Endocrine and Metabolic Physiology.

Thyroid Physiology

The thyroid gland controls the metabolic rate of tissues. The hypothalamus releases thyrotropin-releasing hormone (TRH) which acts on the anterior pituitary, causing it to release thyroid-stimulating hormone (TSH). The TSH acts on the thyroid gland to produce thyroxine (T4) and triiodothyronine (T3). T4 is inactive and is converted to T3 peripherally. T3 and T4 exert negative feedback on the hypothalamus and pituitary.

Causes

The following can cause hyperthyroidism, they are each discussed in more detail below:

  • Graves’ disease
  • Toxic multinodular goitre
  • Toxic thyroid adenoma
  • Hashimoto’s thyroiditis (acute phase)
  • Subacute (de Quervain’s) thyroiditis (acute phase)
  • Drugs (e.g. amiodarone)
  • Post-partum thyroiditis (acute phase)

General Presentation

Symptoms

Hyperthyroidism can be thought of as the body ‘working too fast’, giving the following symptoms:

  • Weight loss despite increased appetite
  • Restlessness
  • Heat intolerance:
    • Patients are often hot and sweaty in environments where it would not be expected
  • Tachycardia
  • Palpitations
  • Diarrhoea
  • Sweating
  • Tremor
  • Psychiatric problems:
    • This can range from anxiety to psychosis
  • Oligomenorrhoea or amenorrhoea

Signs

The following signs may be seen:

  • Sweaty and warm palms
  • Palmar erythema
  • Fine tremor
  • Tachycardia – can be atrial fibrillation:
    • High-output cardiac failure is common in the elderly
  • Hair thinning/loss
  • Brisk reflexes
  • Goitre (swelling of the neck due to enlargement of the thyroid gland)
  • Proximal myopathy
  • Lid lag
  • Thyroid acropachy (nail clubbing)

It is important to note that each underlying cause may have features unique to them. These are discussed below.

Investigations

  • Thyroid function tests (TFTs):
    • These measure TSH, T3, and T4
    • In hyperthyroidism:
      • TSH: low
      • T3: raised
      • T4: raised
    • More findings are discussed in each cause below
  • Thyroid autoantibodies:
    • TSH receptor antibodies (TRAb): positive in Graves’ disease
    • Thyroid peroxidase antibodies (TPOAb): positive in Hashimoto’s thyroiditis
  • Thyroid ultrasound:
    • Considered if a goitre is detected
  • Radioactive iodine uptake testing (thyroid scintigraphy):
    • Helps distinguish between different causes of goitre
    • More findings are discussed in each cause below

Graves’ Disease

Overview

Graves’ disease is an autoimmune condition characterised by the presence of TSH receptor antibodies (TRAb) binding to the TSH receptor, stimulating the thyroid gland to increase secretion of T3 and T4 leading to hyperthyroidism. Since more T3 and T4 are made, negative feedback reduces the release of TSH from the anterior pituitary gland.

Epidemiology

  • Graves’ disease is the most common cause of hyperthyroidism
  • More common in women
  • More common in those aged 30-50 years

Risk Factors

  • Smoking
  • Family history
  • Female sex

Presentation

Patients have features of hyperthyroidism (mentioned above), but there are features seen that are specific to Graves’ disease and not seen in other causes of hyperthyroidism:

  • Eye signs:
    • Exophthalmos – bulging/protruding eyeballs
    • Ophthalmoplegia – paralysis/weakness of one or more extraocular muscles
  • Pretibial myxoedema:
  • Non-pitting oedema
  • Eye signs usually precede pretibial myxoedema

Investigations

  • TFTs:
    • Increased T3 and T4
    • Reduced TSH
  • Thyroid autoantibodies:
    • TSH receptor antibodies (TRAb): positive in 90% of patients
  • Radioactive iodine uptake testing:
    • Uptake is increased, diffuse, and homogenous (consistent throughout the thyroid gland)

Management

In primary care:

  • 1st-line: propranolol for symptomatic relief + referral to endocrinology
  • If symptoms are troublesome while awaiting referral: offer carbimazole

In secondary care:

  • 1st-line: carbimazole
  • 2nd-line: propylthiouracil
  • Consider radioiodine treatment

Complications

Thyroid eye disease:

  • Due to deposition retro-orbital inflammation
  • Patients should be offered topical lubricants to prevent exposure keratopathy

Prognosis

  • Mild cases of Graves’ disease often resolve spontaneously
  • Early diagnosis and management are associated with a better prognosis.

Toxic Multinodular Goitre

Overview

Toxic multinodular goitre (TMNG) is characterised by thyroid nodules that secrete excess T3 and T4 autonomously (without the need for TSH to stimulate them) leading to hyperthyroidism. 

Epidemiology

  • More common in women
  • Most common in 50-60 years of age

Risk Factors

  • Iodine deficiency – more common in developing countries
  • Head and neck irradiation
  • Female sex

Presentation

Patients have features of hyperthyroidism (mentioned above) and may have an irregularly-textured goitre. The absence of a goitre does not rule out the presence of TMNG.

Investigations

  • TFTs:
    • Increased T3 and T4
    • Reduced TSH
  • Thyroid autoantibodies:
    • None are present
  • Radioactive iodine uptake testing:
    • Uptake is patchy

Management

  • The treatment of choice is radioactive iodine

Prognosis

  • The prognosis is generally good; however, some patients can be left with hypothyroidism due to the radioactive iodine.

Toxic Thyroid Adenoma

Overview

A toxic adenoma is a singular thyroid nodule that releases thyroid hormones autonomously. They are almost always benign.

Risk Factors

  • Younger age – more common in those aged 20-40 years
  • Iodine deficiency – more common in developing countries

Presentation

Patients have features of hyperthyroidism (mentioned above) and may have a palpable thyroid nodule. The absence of a nodule does not rule out the presence of toxic adenoma.

Investigations

  • TFTs:
    • Increased T3 and T4
    • Reduced TSH
  • Thyroid autoantibodies:
    • None are present
  • Radioactive iodine uptake testing:
    • Uptake is in a focal area

Management

  • The options of choice are radioactive iodine or surgery

Prognosis

  • The prognosis is generally good; however, some patients can be left with hypothyroidism due to the radioactive iodine.

Other Causes

Overview

The following can cause hyperthyroidism:

  • Hashimoto’s thyroiditis:
    • This can cause hyperthyroidism initially (in the acute phase), followed by hypothyroidism.
    • This is covered more in detail in the Hypothyroidism chapter.
  • Subacute (de Quervain’s) thyroiditis:
    • Can cause hyperthyroidism initially (in acute phase), followed by hypothyroidism.
    • This is covered more in detail in the Hypothyroidism chapter.
  • Post–partum thyroiditis:
    • Can cause hyperthyroidism initially (in acute phase), followed by hypothyroidism.
  • Amiodarone:
    • Amiodarone is structurally similar to thyroid hormones and contains iodine, meaning it can lead to both hyper- and hypothyroidism.
  • Exogenous thyrotoxicosis:
    • Some people may take synthetic thyroid hormones when not needed (e.g. to lose weight), or take too much, leading to thyrotoxicosis.

Complications

  • Thyrotoxic crisis (thyroid storm):
  • Potentially life-threatening and can be triggered by infection, surgery, trauma, and pregnancy
  • Atrial fibrillation:
    • This can increase the risk of stroke
  • High-output cardiac failure:
    • More common in elderly people
  • Osteoporosis
  • Thyroid eye disease (in Graves’ disease)

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