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The thyroid gland and disorders of thyroid function 

The thyroid gland and disorders of thyroid function

The thyroid gland and disorders of thyroid function

Anthony P. Weetman


July 30, 2015: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.


Chapter reviewed July 2012—no significant alteration required.

Updated on 28 Nov 2012. The previous version of this content can be found here.
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date: 30 March 2017

The iodine-containing thyroid hormones triodothyronine (T3) and thyroxine (T4) have diverse effects on metabolism and are essential for normal development, particularly of the fetal brain. The active principle, T3, binds to nuclear receptor isoforms and serves as a transcriptional regulatory factor, thus explaining the protean actions.

Thyroid hormone release is regulated by thyrotropin (TSH) from the anterior pituitary, which is itself modulated by the hypothalamic tripeptide, thyrotropin-releasing hormone (TRH). Thyroid hormones exert negative feedback control on the pituitary gland and on the synthesis of TRH.

A normal TSH level rules out primary thyroid dysfunction, but when TSH levels are abnormal, or when pituitary or hypothalamic abnormalities are possible, it is essential to confirm thyroid status by measuring circulating thyroid hormone levels, which is best achieved by immunoassay of free T3 and free T4. Thyroid-antibody measurement and imaging by scintiscanning are useful in determining the aetiology of thyroid disease when this is not obvious clinically.


Endemic goitre—which is particularly common in the Himalayas, the Andes, and parts of Africa—is mainly due to iodine deficiency, can cause massive thyroid enlargement, but rarely leads to compressive symptoms. Its main impact on health is the association with endemic cretinism, which can be prevented by iodine supplementation, achievable by iodization of salt or bread, intramuscular or oral iodized oil as a single annual dose, or iodination of drinking water.

Sporadic goitre—cause unknown; presentation is with neck swelling or sensation of pressure or discomfort; most patients are euthyroid and do not require treatment.


Aetiology—iodine deficiency and neonatal hypothyroidism remain major challenges for public health in many countries, but the most frequent cause of thyroid dysfunction in iodine-sufficient areas is autoimmunity, where the follicular gland structure is destroyed by autoreactive T cells.

Clinical features—manifests in the adult with the gradual onset of a constellation of symptoms and signs including tiredness, feeling cold, weight gain, hoarseness of the voice, and slow-relaxing tendon reflexes. A goitre may (Hashimoto’s thyroiditis) or may not (atrophic thyroiditis/primary myxoedema) be present. Biochemical diagnosis of primary hypothyroidism is confirmed by a high serum TSH and a low free T4, with autoimmune hypothyroidism associated with the presence of thyroid peroxidase autoantibodies (against the ‘microsomal’ antigen). Treatment is with thyroxine (100–150 µg/day, but beginning with a low dose in older people or those with heart disease).

Myxoedema coma—this is the most dramatic presentation of hypothyroidism and a medical emergency with high mortality: management requires (1) supportive treatment; (2) identification and treatment of any precipitating condition, often infective; (3) parenteral thyroid hormone replacement.


Aetiology—Graves’ disease, which is caused by TSH receptor stimulating autoantibodies, is responsible for 60 to 80% of cases, and nodular thyroid disease (toxic multinodular goitre and toxic adenoma) accounts for most of the rest.

Clinical features—presents with a wide range of symptoms and signs including hyperactivity, palpitations, fatigue, weight loss (despite increased appetite), sinus tachycardia (or atrial fibrillation), tremor, and eye signs (including lid retraction and lid lag). Biochemical diagnosis of primary hyperthyroidism is confirmed by a low serum TSH and a high free T4 and/or T3, with autoimmune hyperthyroidism associated with the presence of thyroid peroxidase autoantibodies in most patients with Graves’ disease. β‎-blockers can rapidly relieve symptoms, but definitive treatment requires antithyroid drugs (usually carbimazole or propythiouracil), radio-iodine (131I), or surgery.

Thyroid-associated ophthalmopathy—this often causes anxiety and social embarrassment, but severe cases are a threat to vision and may require treatment with corticosteroids, radiotherapy, other immunosuppressive agents, or orbital decompression.

Thyrotoxic crisis or storm—this is the most dramatic presentation of hyperthyroidism and a medical emergency with high mortality. Manifestations include fever (>38.5 º C), delirium or coma, seizures, vomiting, diarrhoea and jaundice. Management requires (1) supportive treatment; (2) identification and treatment of any precipitating condition, including infection; (3) antithyroid treatment, e.g. loading dose of propylthiouracil, followed 1 h later by stable iodine (e.g. Lugol’s iodine or ipodate).

Other conditions

Acute thyroiditis—usually caused by bacterial infection; presents with severe thyroid pain, fever and malaise; thyroid function is rarely disturbed.

Subacute (or de Quervain’s) thyroiditis—due to viral infection and commonly presents with thyroid pain; there may be transient thyrotoxicosis, followed by hypothyroidism, before restoration of normal thyroid function; diagnosis depends on demonstration of raised inflammatory markers and low/absent radio-iodine uptake by the thyroid.

Amiodarone—inhibits T4 deiodination and hence leads to free T4 levels that are in the upper half of the reference range or mildly elevated; may cause hypothyroidism or hyperthyroidism, the latter being difficult to treat.

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