Hyperthyroidism

Introduction

Abnormal levels of circulating thyroid hormone (thyroxine) and underlying diseases may lead to alterations in the appearance of skin, hair and nails. The thyroid gland can be overactive, resulting in hyperthyroidism, discussed here, or underactive, resulting in hypothyroidism.

What is hyperthyroidism?

Hyperthyroidism is due to excessive thyroxine. It is also known as thyrotoxicosis. It can lead to a variety of signs and symptoms.

Who gets hyperthyroidism?

Hyperthyroidism:

• Can occur at any age, but usually affects older adults aged 40–60 years.
• It is predominantly seen in females (5:1 female-to-male ratio).
• Hyperthyroidism is more common among individuals with a personal or family history of autoimmune disorders, such as type 1 diabetes, pernicious anaemia, vitiligo, lichen sclerosus and Addison disease.
• Other risk factors include smoking, high intake of dietary or supplemental iodine, and trauma to the thyroid gland (eg, surgery).

What causes hyperthyroidism?

There are several causes for hyperthyroidism.

Graves disease

Graves disease is the most common cause of hyperthyroidism (80%).

• It is an autoimmune disorder that involves antibodies activating the thyroid-stimulating hormone (TSH) receptor in thyroid cells.
• The thyroid follicular cells proliferate abnormally, resulting in goitre (a swelling in the neck) and excess thyroxine.
• There are a genetic predisposition and association with PTPN22, CTLA-4 and human leukocyte antigen (HLA) genotype.
• Neonatal hyperthyroidism can rarely occur in babies born to mothers with Graves disease.

Goitre 

Goitre 

Thyroid nodule or nodules

A thyroid nodule is a benign growth within the thyroid gland.

• A solitary nodule can manifest as toxic adenoma.
• Multiple nodules can manifest as toxic multi-nodular goitre.
• Active nodules interfere with the regulation of normal control of thyroxine production.

Medications

Hyperthyroidism arises from:

• Excessive intake of levothyroxine used to treat hypothyroidism. This is called factitious or iatrogenic hyperthyroidism
• Amiodarone, an iodinated drug used in heart disease, which can induce both hyperthyroidism and hypothyroidism
• Lithium, often used for mental illness and eating disorders. It can also induce hyperthyroidism and hypothyroidism

Subacute thyroiditis

Subacute thyroiditis is also known as De Quervain thyroiditis.

• Thyroiditis is inflammation of the thyroid gland.
• Subacute thyroiditis follows a viral infection or pregnancy.
• The gland is painful and tender for several months.
• Thyroiditis is usually self-limiting and resolves spontaneously without treatment.
• It initially causes temporary over-production of thyroid hormone (hyperthyroid phase), which is then followed by under-production (hypothyroid phase) before thyroid function returns to normal.

Rare causes of hyperthyroidism

Rare causes of hyperthyroidism include:

• Thyroid cancer, a malignant proliferation of thyroid tissue.
• Some forms of pituitary adenoma, a benign growth within the pituitary gland in the brain. Pituitary adenoma causes secondary hyperthyroidism.

What are the clinical features of hyperthyroidism?

Hyperthyroidism results in an increase in the body’s metabolic rate, which characterised by:

• Flushing of the face and hands
• Smooth, moist and warm skin
• Fine, soft and thinned scalp hair
• Distorted and overgrown nails (thyroid acropachy) that may lift off the nail bed (onycholysis)
• Generalised itching (pruritus)
• Urticaria

Thyroid acropachy 

Thyroid acropachy 

Thyroid acropachy 

Other common systemic features include palpitations, tremor, weight loss, heat intolerance, anxiety and menstrual disturbance (irregular or light period).

Graves disease may also cause thyroid dermopathy resulting in pretibial myxoedema and exophthalmos, which are associated with the presence of thyroid antibodies.

Thyroid ophthalmopathy 

Thyroid ophthalmopathy 

Thyroid ophthalmopathy 

• Pretibial myxoedema is due to mucinosis, a generalised excess of glycosaminoglycans in the dermis.
• It affects a small number of patients with Graves disease (0.5–4.3%) and commonly occurs 1–2 years after the diagnosis.
• Reddish, tender, swelling, nodules and plaques occur on the shins, calves and feet.
• There may be violaceous or yellow-brown discolouration of the overlying skin with prominent hair follicles giving an orange-peel appearance. It may also look warty.

Pretibial myxoedema 

Pretibial myxoedema 

Pretibial myxoedema 

What are the complications of hyperthyroidism?

Untreated hyperthyroidism can cause serious systemic complications including:

• Atrial fibrillation (irregular heart rhythm)
• Cardiomyopathy (weak heart)
• Heart failure
• Stroke
• Osteoporosis and bone fracture

Medical emergencies associated with hyperthyroidism include thyroid storm and thyrotoxic periodic paralysis.

Thyroid storm

Thyroid storm is also called thyroid crisis.

• It is characterised by features of a hypermetabolic state, including confusion, agitation, psychosis, hyperthermia and tachycardia.
• It is rare (1%) but life-threatening and usually occurs in patients with undiagnosed or ineffectively treated hyperthyroidism.
• Thyroid storm is commonly precipitated by infection, trauma, surgery, radioiodine therapy or withdrawal of an anti-thyroid drug.

Thyrotoxic periodic paralysis

Thyrotoxic periodic paralysis is characterised by acute onset of hypokalaemia.

• Muscle paralysis is secondary to an intracellular shift of potassium, induced by thyroxine.
• It is rare but potentially fatal.
• Compared to other ethnicities, thyrotoxic periodic paralysis is more common in Asians, including Filipinos, Malaysians, Thais, Vietnamese and Koreans, in which it affects 2% of the hyperthyroid population.

How is hyperthyroidism diagnosed?

Hyperthyroidism is diagnosed with thyroid function tests (TFTs).

• Serum TSH is usually low.
• If there is a pituitary adenoma (rare), TSH can be high.
• Serum T4 (thyroxine) and T3 (triiodothyronine) levels are usually high.
• In subclinical hyperthyroidism, TSH is low in the presence of normal T4 and T3 level.

Serum autoantibodies are markers of autoimmune disease. They should include:

• Anti-thyroid peroxidase (TPO) antibodies. These are present in 75% of patients with Graves disease and are usually absent in multinodular goitre
• Anti-thyroglobulin antibodies
• TSH receptor antibodies

Full blood count and inflammatory markers, such as C-reactive protein, are routinely included to screen for anaemia (commonly associated with hyperthyroidism) and systemic infection causing thyroiditis.

Imaging should include:

• Ultrasound of the thyroid gland to detect a nodule.
• Thyroid uptake scan to detect cold areas (no activity), and overactive hot spots.

What is the treatment for hyperthyroidism?

Hyperthyroidism is either treated with medication, by radioactive iodine, surgery or a combination of these.

Anti-thyroid medication

• Carbimazole is the treatment of choice to reduce the production of thyroid hormone. It is a pro-drug of methimazole, which is available in some countries as an alternative to carbimazole.
• Dose varies from 10–40 mg daily, depending on the T4 level. It usually takes 4–8 weeks to be fully effective.
• Common side effects include nausea, rash and pruritus. It can also rarely cause bone marrow suppression (< 0.5%). Patients must be warned to seek urgent medical review and have blood tests, should they develop fever, mouth ulcers and sore throat.
• Carbimazole may be stopped when remission is achieved (usually after 18–24 months of starting treatment).
• Propylthiouracil is recommended in pregnant women and for those intolerant of the side effects of carbimazole.
• Beta blockers, such as propranolol, are also commonly used to control tremor and palpitations. Calcium channel blockers, such as verapamil, can be given as an alternative.

Radioactive iodine

Radioactive iodine is usually indicated for relapses of Graves disease and toxic nodular goitre. However, it has increasingly been used as first-line treatment for hyperthyroidism in teenagers.

• The radioactive substance is ingested and destroys some of the thyroid cells leading to a reduction in thyroxine production.
• It usually takes 3–4 months for treatment to show the full effect.
• Radio-iodine is contraindicated in pregnancy and breastfeeding. Women are strongly advised to not become pregnant for at least six months following radio-iodine treatment. Patients should limit prolonged contact with others, especially children and pregnant women, for at least 2–4 weeks post-treatment.

Surgery

Partial or total thyroidectomy is surgical removal of part or the whole of the thyroid gland respectively.

• It may be indicated for large goitre causing compressive symptoms such as shortness of breath and in those resistant to medical treatments.

What is the outcome for hyperthyroidism?

Treatment of hyperthyroidism is usually effective. Regular thyroid function tests are recommended following successful treatment, as some individuals develop further relapses, with annual blood tests long term.