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Thyroid Function

Thyroid Function
The thyroid gland has its embryological origin at the back of the tongue, migrating downwards to the midline, sitting anteriorly to the thyroid cartilage in the neck (Figure 9.1a). This embryological origin can lead to remnant tissue, which presents as a lingual thyroid or thyroglossal cyst.

Anatomical relations
The thyroid gland has a left and right lobe joined by a central isthmus (Figure 9.1a). Thyroid lesions can be distinguished from other neck lumps by their movement on swallowing. The anatomical relations of the thyroid are important in clinical practice. The recurrent laryngeal nerve lies laterally on each side and the parathyroid glands lie posteriorly (Figure 9.1a) – both may be damaged during thyroid surgery. The thyroid gland has a rich vascular supply from the inferior and superior thyroid arteries.
Thyroid tissue is made up of colloid (Figure 9.1b), which contains iodinated thyroglobulin. Thyroglobulin is synthesised by the surrounding follicular cells and is the large molecule from which thyroxine is made and stored in colloid. The thyroid is also made up of neuroendocrine cells (parafollicular or C cells), which are situated between the follicular cells, and secrete calcitonin, a physiologically active peptide. Calcitonin is relevant clinically as a biomarker for medullary thyroid cancer.

Thyroid hormones have a profound effect on metabolism. Iodination of the amino acid tyrosine forms thyroxine (T4) and triiodothyronine (T3). T4 is the main circulating hormone, which is converted peripherally to the more potent and shorter acting T3 (Figure 9.1c). Thyroid hormones are bound tightly to proteins in the circulation: thyroxine binding globulin (TBG), transthyretin and albumin. Only the free hormone acts on intracellular thyroid receptors (TR). There are two main types of thyroid receptor (TRα and TRβ), which are variably expressed in different tissues. Mutations in TRβ lead to the rare condition of thyroid hormone resistance. The local action of thyroid hormones on tissues is determined by a series of activating and de-activating enzymes (de-iodinase enzymes; DIO 1, 2 and 3).

Actions of thyroid hormones
Thyroid hormones increase basal metabolic rate and affect growth and development. They act on the cardiovascular system to increase heart rate and stroke volume, and receptors are widely expressed in the CNS and reproductive system (Figure 9.1d). Because of the widespread role of thyroid hormones in metabolism, patients with disorders of thyroid function can present to any specialty in clinical practice.

Interpreting thyroid function tests
Thyroid function tests (TFTs) are readily available and commonly requested in clinical practice. Understanding the feedback axis is the key to correct interpretation of thyroid results. The thyroid has a classic negative feedback system (Figure 9.1e). TRH stimulates pituitary TSH secretion, which acts on G-protein coupled receptors in the thyroid to stimulate T3 and T4 secretion. T3 and T4 exert their peripheral effects via TRα and TRβ. Thyroid hormones have minimal circadian rhythmicity and are not pulsatile, therefore basal levels are sufficient for interpretation, and dynamic tests are not needed.

Primary and secondary hypothyroidism
Primary hypothyroidism is caused by thyroid disease, commonly autoimmune in origin. It is characterised by reduced circulating T3 and T4 and compensatory elevation in TSH. Secondary hypothyroidism is caused by TSH deficiency, usually as a result of pituitary disease, and is characterised by low T3/T4 levels and non-elevated TSH – often TSH is normal rather than low.

Primaryhyperthyroidismischaracterisedbyincreasedcirculating T3 and T4, and suppressed TSH due to negative feedback. If TSH is not suppressed in the context of hyperthyroidism, rare conditions or assay interference should be considered. In this situation, the clinical picture is important to guide whether diagnosis is likely to be an assay problem or a genuinely rare pathology.

Factors affecting thyroid results
TFTs can be affected by non-thyroidal illness (‘sick euthyroid syndrome’), typically causing central TSH suppression, although any pattern of results can be seen. TFTs are therefore best measured in the outpatient setting when patients are relatively well, rather than during acute illness or hospitalisation. (e.g. lithium and amiodarone) and pregnancy can lso affect thyroid function results.