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Hyperthyroidism and thyrotoxicosis

Introduction and epidemiology

Thyrotoxicosis or hyperthyroxinaemia is the state where the level of circulating free T₃ and T₄ is elevated, causing hypermetabolism. It is most commonly caused by hyperthyroidism, which is the state where the thyroid is overactive, but it can also be caused by ectopic hormones or destruction of the thyroid. Because of this, the two terms are often used interchangeably.

Etiology

Thyrotoxicosis can be caused by many conditions:

• Primary hyperthyroidism
  • Graves disease
  • Toxic adenoma
  • Toxic multinodular goiter
• Destruction of the thyroid gland – causes release of stored thyroid hormone in the early phase of disease
  • Hashimoto thyroiditis
  • De Quervain thyroiditis
  • Postpartum thyroiditis
  • Drug and contrast-induced thyroiditis (amiodarone, contrast material)
• Secondary hyperthyroidism
  • Gestational thyrotoxicosis – hCG stimulates TSH receptors due to their structural similarity
  • Struma ovarii – an ovarian teratoma which produces thyroxine
  • TSH-producing pituitary adenoma

In regions without iodine deficiency, Graves disease is the most common cause of thyrotoxicosis. In iodine deficient regions, toxic adenoma and toxic multinodular goitre are more common.

Clinical features

Thyrotoxicosis can cause many symptoms, most of which are related to the hypermetabolic state and to the overactivity of the sympathetic nervous system:

• Weight loss despite increased appetite
• Warm, moist skin
• Tachycardia or arrhythmia
• Heat intolerance
• Palmar erythema
• Nervousness
• Diarrhoea
• Hypertension with widened pulse pressure
• Palpitations
• Fine tremor
• Anxiety, restlessness

Diagnosis and evaluation

The diagnosis of (primary) hyperthyroidism is based on the levels of TSH, the most sensitive biomarker. Free T4 and T3 are measured to look for subclinical hyperthyroidism.

	TSH	Free T4	Free T3
Euthyroidism	Normal	Normal	Normal
Subclinical hyperthyroidism	Decreased	Normal	Normal
Overt hyperthyroidism	Decreased	Increased	Increased

The clinical features, including the thyroid size, consistency, nodularity, as well as the presence of eye symptoms, can help narrow the differential diagnosis. The following investigations are important in determining the etiology:

• Autoantibodies against thyroid peroxidase (anti-TPO), thyroglobulin (anti-Tg), and TSH receptor (anti-TSHR)
• Ultrasound
• Thyroid scintigraphy (nuclear imaging)

Treatment

Specific treatment depends on the underlying etiology, but supportive treatment is also available. Beta blockers can be used, of which propranolol is the first choice as it inhibits conversion of T3 to T4. Benzodiazepines may also be used for anxiety.

Hypothyroidism

Introduction and epidemiology

(Overt) hypothyroidism refers to decreased production of T3 and T4 by the thyroid gland. It’s a common condition. Chronic hypothyroidism is almost always due to Hashimoto thyroiditis.

Subclinical hypothyroidism is very common, but despite being subclinical it may be associated with adverse outcomes on cardiovascular disease. Also, most patients with subclinical hypothyroidism progress into overt hypothyroidism.

Etiology

• Primary hypothyroidism
  • Thyroiditis
    • Hashimoto thyroiditis
    • De Quervain thyroiditis
    • Postpartum thyroiditis
  • Following surgical removal or radioiodine treatment
  • Iodine deficiency
  • Drugs
• Secondary hypothyroidism
  • TSH insufficiency
• Tertiary hypothyroidism
  • TRH insufficiency

Thyroiditis, especially Hashimoto thyroiditis, is the most common cause of hypothyroidism. Secondary and tertiary hyperthyroidism are rare.

Clinical features

Hypothyroidism can also cause many symptoms, most of which are opposite of those of thyrotoxicosis:

• Weakness
• Memory problems
• Depression
• Dry skin
• Myxoedema
• Hair loss
• Constipation
• Weight gain
• Cold intolerance
• Bradycardia
• Anaemia
• Menstruation problems
• Hypercholesterolaemia -> accelerated atherosclerosis

Diagnosis and evaluation

TSH is the most important biomarker in the evaluation of hypothyroidism as it’s much more sensitive than T3 and T4. T3 and T4 are only measured to diagnose subclinical hypothyroidism, the stage before overt hypothyroidism develops.

	TSH	Free T4	Free T3
Euthyroidism	Normal	Normal	Normal
Subclinical hypothyroidism	Increased	Normal	Normal
Overt hypothyroidism	Increased	Decreased	Decreased

To find the etiology, measurement of anti-thyroid antibodies (anti-TPO and anti-Tg), ultrasound, and FNAB are used.

Treatment

The treatment of hypothyroidism is thyroid hormone replacement with L-thyroxine. The dose must be adjusted until the laboratory results no longer show hypothyroidism. The beginning daily dose is 50 – 100 µg, but in elderly, who often have ischaemic heart disease and are therefore predisposed to arrhythmias or MI, the beginning dose must be lower.

The thyroxine dose must be increased during pregnancy as the requirement is higher in this stage.

The decision of whether to treat subclinical hypothyroidism is less clear. In general, thyroxine replacement is indicated for subclinical hypothyroidism in case of:

• Very high TSH or autoantibodies
• Infertility
• Depression

Graves disease

Treatment

The treatment options for Graves disease are thyreostatic drugs, radioiodine ablation, and surgery. There are advantages and disadvantages for all types, and so the appropriate treatment is based on the severity, the presence of ophthalmopathy, the characteristics of the goitre, as well as the age of the patient. Radioiodine treatment worsens Graves ophthalmopathy, for which it’s a contraindication.

The major thyreostatic drugs are thiamazole and propylthiouracil, although lithium carbonate is also an option for short-term treatment. These drugs may have life-threatening side effects, especially agranulocytosis and liver failure, and so must be followed up regularly.

All three treatment modalities may be curative. However, thyreostatic drugs treatment is curative in only 50% of cases.

The following are treatment options for endocrine ophthalmopathy:

• Smoking cessation
• Glucocorticoid treatment
• Retrobulbar irradiation
• Orbital decompression surgery or other ophthalmological surgery

Thyrotoxic crisis

Thyrotoxic crisis is a life-threatening complication of Graves disease. Even with treatment the mortality is 30%. It can be triggered by:

• Surgery
• Trauma
• Radioiodine treatment
• Iodine-containing drugs and contrast materials
• Infections
• Delivery

The symptoms are those of severe thyrotoxicosis, with severe tachycardia or arrhythmia, hyperpyrexia, and organ failure.

The treatment involves removal of excess thyroid hormone by plasmapheresis as well as inhibition of hormone production. The latter is accomplished by high dose thyreostatic drugs or inorganic iodine or lithium, which decrease the release of thyroid hormones.