Overview

Hypothyroidism describes the inadequate production of thyroid hormones by the thyroid gland. It may also be referred to as an underactive thyroid.

There are multiple causes of hypothyroidism which are summarised in this chapter. Of these causes, Hashimoto’s thyroiditis is the most common cause in the UK, and iodine deficiency is the most common cause in the developing world.

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

Primary hypothyroidism

  • Hashimoto’s thyroiditis
  • Iatrogenic (e.g. radiotherapy to the neck, radioactive iodine treatment)
  • Iodine deficiency
  • Some drugs (e.g. amiodarone and lithium)
  • Infiltrative causes (e.g. sarcoidosis or haemochromatosis)
  • Congenital (e.g. dysgenesis)
  • Postpartum thyroiditis

Secondary hypothyroidism

  • Any cause of hypopituitarism (e.g. neoplasm, trauma, infection, radiotherapy)
  • Any cause of hypothalamic dysfunction (e.g. neoplasm, trauma)

General Presentation

Symptoms

Features can be non-specific:

  • Fatigue
  • Lethargy
  • Cold intolerance:
    • Patients are often dressed with excessive layers of clothing compared to the environment they are in
  • Dry skin
  • Hair loss
  • Constipation
  • Decreased appetite with weight gain
  • Poor memory
  • Difficulty with concentration
  • Reduced libido
  • Menorrhagia

Signs

Some signs found on examination may be:

  • Dry and coarse skin
  • Cold peripheries
  • Myxoedema:
    • Non-pitting oedema of the face, hands, and feet
  • Bradycardia
  • Decreased tendon reflexes
  • Carpal tunnel syndrome

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: elevated
      • T3: reduced
      • T4: reduced
    • More findings are discussed in each cause below
  • Thyroid autoantibodies:
    • 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

Hashimoto’s thyroiditis

Overview

Hashimoto’s thyroiditis is an autoimmune condition characterised by the destruction of the thyroid gland cells. Although it causes hypothyroidism, there can be hyperthyroidism in the acute phase.

Epidemiology

  • Most common cause of hypothyroidism in the UK
  • Up to 20 times more common in women
  • Most often between adolescence and 50 years of age

Risk Factors

Presentation

  • Features of hypothyroidism above
  • Some patients may have a non-tender goitre

Investigations

  • TFTs:
    • TSH: increased (due to lack of negative feedback from insufficient T3 and T4)
    • T3 and T4: reduced (can be elevated in the acute hyperthyroid phase)
  • Autoantibodies:
    • Thyroid peroxidase antibodies (TPOAb): positive
    • Anti-thyroglobulin (anti-Tg) antibodies: positive

Management

  • 1st-line: lifelong thyroid hormone replacement (levothyroxine)
  • Surgery for goitres may be considered (e.g. if there are obstructive symptoms)

Levothyroxine

Adverse effects of thyroid hormone replacement therapy can be due to over-treatment, which can lead to features of hyperthyroidism such as:

Monitoring

  • TFTs are monitored regularly to avoid over- and undertreatment

Patient Advice

  • Patients should be educated on the signs and symptoms of hypothyroidism and hyperthyroidism and should seek help if they arise and have their dose readjusted.

Complications

Prognosis

  • Early diagnosis and treatment have a good prognosis, as many patients achieve a euthyroid status.

Subacute (de Quervain’s) thyroiditis

Overview

Also known as subacute granulomatous thyroiditis and de Quervain’s thyroiditis, subacute thyroiditis describes the inflammation of the thyroid gland leading to a triphasic presentation of hyperthyroidism, then hypothyroidism, then a return to euthyroidism. It is thought to be due to a viral infection.

A helpful way of remembering why subacute thyroiditis presents the way it does is by imagining the initial inflammation causing already-made thyroid hormone to ‘leak out’ from damaged cells into the circulation, leading to hyperthyroidism. Once all of this thyroid hormone has been ‘used up’, the hypothyroid stage follows, and then finally the thyroid gland returns to normal after the inflammation subsides.

Disease Course

Subacute thyroiditis has the following phases:

  • Hyperthyroid phase – 4-6 weeks in length
  • Hypothyroid phase – 2-6 months in length
  • Euthyroid phase

Risk Factors

  • Recent viral infection

Presentation

  • Features of hypothyroidism
  • Tender, firm, enlarged thyroid gland

Investigations

  • TFTs:
    • Hyperthyroid phase:
      • TSH: reduced
      • T3 and T4: elevated
    • Hypothyroid phase:
      • TSH: elevated
      • T3 and T4: reduced
    • Autoantibodies:
  • Thyroid peroxidase antibodies (TPOAb): negative
    • Anti-thyroglobulin (anti-Tag) antibodies: negative
  • ESR and CRP:
    • Usually elevated
  • U&Es:
  • Radioactive iodine uptake:
    • Very low uptake globally

Management

  • 1st-line: supportive management (e.g. NSAIDs for thyroid pain)
  • In some severe cases, corticosteroids may be used.

Monitoring

  • Patients have their TFTs rechecked regularly (usually around every 4-6 weeks) to assess if they return to a euthyroid state.

Complications

  • Permanent hypothyroidism and long-term levothyroxine requirement.

Prognosis

  • In most patients, subacute thyroiditis resolves spontaneously and they return to a euthyroid state.
  • Around 10% of patients may progress to having permanent hypothyroidism.

Other Causes

The following can cause hypothyroidism:

  • Riedel thyroiditis:
    • A rare cause of hypothyroidism where the thyroid tissue is replaced by fibrotic and scarred tissue.
  • Postpartum thyroiditis:
    • Phases are similar to subacute thyroiditis: hyperthyroidism, then hypothyroidism, then euthyroidism.
    • Management involves the use of propranolol for symptom control and levothyroxine in the hypothyroid phase.
  • Some drugs:
    • Lithium – reduces the activity of thyroid hormone.
    • Amiodarone – is structurally similar to thyroid hormones and contains iodine, meaning it can lead to both hyper- and hypothyroidism.
  • Iodine deficiency:
    • Iodine is necessary for the production of thyroid hormones
    • Most common in developing countries
  • Subclinical hypothyroidism:
    • TSH: high
    • T3 and T4: normal

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