Thyroid gland is a butterfly-shaped endocrine organ located in the front of throat below the prominence of thyroid cartilage. The two lobes, about 5 × 3 × 2 cm each, are connected by isthmus, also consisting of thyroid tissue; in some people, isthmus is missing. The shape and size of thyroid is variable, but typically thyroid gland weighs about 25 g in adults. Thyroid is surrounded by a double-layer fibrous capsule. Parathyroid glands (usually 2 on each side) are located between the layers, behind the thyroid.
Thyroid uses tyrosine and iodine to make and release two thyroid hormones (TH), tri-iodothyronine (T3) and thyroxine (T4). T3 and T4 affect all tissues, via intracellular nuclear thyroid hormone receptors TR-α1, TR-α2, TR-β1, and TR-β2, modulating DNA transcription to increase metabolic rate. T3 and T4 production is controlled by thyroid stimulating hormone (TSH), released from the anterior pituitary gland. TSH release from pituitary is regulated by thyrotropin releasing hormone (TRH) produced in the hypothalamus.
Thyroid gland contains follicles, less than 1 mm in diameter, which produce the T3 and T4 hormones. The core of thyroid follicles consists of colloidal matter, thyroglobulin, which is an iodinated glycoprotein. Surrounding the core is a single layer of follicle cells, which produce thyroglobulin. Follicle cells collect I- from blood via sodium/iodide symporter (NIS), and release it into the follicular space via iodide-chloride antiporter (pendrin). In the follicular space iodide is oxidized to iodine, and thyroid peroxidase attaches iodine to the tyrosine residues of thyroglobulin. In response to TSH, follicle cells transport and process thyroglobulin into T3 and T4, and release the hormones into the blood. In blood, T3 and T4 are bound to thyroxine-binding globulin, transthyretin, and albumin. T4 is converted to T3 by iodothyronine deiodinases in other organs. Catecholamines released by sympathetic nerves can stimulate the conversion rate in tissue-specific manner. During cold exposure brown adipose tissue may be a major source of systemic T3. On the other hand, thyroid hormones increase the capacity of tissues to respond to catecholamines.
Parafollicular cells (C cells) are dispersed between follicles and among follicular cells. Parafollicular cells secrete (thyro)calcitonin, which is a 32-amino acid polypeptide hormone. Calcitonin inhibits osteoclast activity in the bones and reabsorption of Ca2+ and phosphate in renal tubules, thus lowering blood [Ca2+].
Perfusion in thyroid gland can be measured using PET and [15O]H2O.
Kinetics of iodide can be studied with 124I (Gühne et al., 2017; Santhanam et al., 2017), but iodine analogue [18F]TFB provides more favourable dosimetry, and can be used to measure the import of iodide in tissues (NIS expression) and as biomarker for thyroid cancer (Marti-Climenti et al., 2015; Jiang et al., 2017; O'Doherty et al., 2017).
[18F]FDG can be used to detect thyroid cancers (Amdur & Mazzaferri, 2005; Lauridsen et al., 2015). [18F]FDG and [18F]FDOPA can be used to detect medullary thyroid cancer (Kauhanen et al., 2011). Somatostatin tracers may be used to select medullary and non-medullary thyroid cancer patients for radionuclide therapy (Salavati et al., 2016; Serfling et al., 2022). Pretargeted immuno-PET has given promising results in thyroid carcinomas (Bodet-Millet et al., 2016). As a marker of neovascular formation, PSMA expression is upregulated in differentiated thyroid cancer and may predict tumour aggressiveness and patient outcome (Sollini et al., 2019).
The parathyroid glands secrete parathyroid hormone (PTH), which binds to receptors in bones and kidney leading to increase in plasma Ca2+ concentration. High extracellular [Ca2+] activates Ca2+-sensing receptor (CaSR) causing suppression of PTH secretion. [18F]Cinacalcet is studied as a CaSR radioligand (Pees et al., 2021).
In hyperparathyroidism the PTH levels are persistently elevated, causing osteoporosis and kidney stones. Kidney, liver, and bowel diseases may cause low Ca2+ levels, leading to secondary hyperparathyroidism. [18F]fluorocholine PET can be used to localize hyperactive parathyroid glands. SUVmax and SUV liver ratio are higher for adenomas than for hyperplasias (Jacquet-Francillon et al., 2022).
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Updated at: 2022-12-01
Created at: 2017-12-30
Written by: Vesa Oikonen