Thyroid hormone synthesis and physiology
- Douglas S Ross, MD
Douglas S Ross, MD
- Section Editor — Thyroid Disease
- Professor of Medicine
- Harvard Medical School
Thyroid hormones are critical determinants of brain and somatic development in infants and of metabolic activity in adults; they also affect the function of virtually every organ system. Thyroid hormones must be constantly available to perform these functions. To maintain their availability there are large stores of thyroid hormone in the circulation and in the thyroid gland. Furthermore, thyroid hormone biosynthesis and secretion are maintained within narrow limits by a regulatory mechanism that is very sensitive to small changes in circulating hormone concentrations.
The processes of thyroid hormone synthesis, transport, and metabolism, and the regulation of thyroid secretion will be reviewed here. The actions of thyroid hormone are discussed elsewhere. (See "Thyroid hormone action".)
The thyroid gland weighs 10 to 20 grams in normal adults in the United States . Thyroid volume measured by ultrasonography is slightly greater in men than women, increases with age and body weight, and decreases with increasing iodine intake .
Microscopically, the thyroid is composed of spherical follicles, each composed of a single layer of follicular cells surrounding a lumen filled with colloid (mostly thyroglobulin). When stimulated, the follicular cells become columnar and the lumen is depleted of colloid; when suppressed, the follicular cells become flat and colloid accumulates in the lumen.
THYROID HORMONE BIOSYNTHESIS
There are two biologically active thyroid hormones: thyroxine (T4) and 3,5,3'-triiodothyronine (T3) (figure 1). They are composed of a phenyl ring attached via an ether linkage to a tyrosine molecule. Both have two iodine atoms on their tyrosine (inner) ring. They differ in that T4 has two iodine atoms on its phenyl (outer) ring, whereas T3 has only one. The compound formed if an iodine atom is removed from the inner ring of T4 is 3,3',5'-triiodothyronine (reverse T3 [rT3]), which has no biological activity.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Pankow BG, Michalak J, McGee MK. Adult human thyroid weight. Health Phys 1985; 49:1097.
- Hegedüs L. Thyroid size determined by ultrasound. Influence of physiological factors and non-thyroidal disease. Dan Med Bull 1990; 37:249.
- Kopp P. Thyroid hormone synthesis. In: The Thyroid: Fundamental and Clinical Text, 9th, Braverman LE, Utiger RD (Eds), Lippincott Williams and Wilkins, Philadelphia 2005. p.52.
- Spitzweg C, Heufelder AE, Morris JC. Thyroid iodine transport. Thyroid 2000; 10:321.
- Arvan P, Di Jeso B. Thyroglobulin structure, function, and biosynthesis. In: The Thyroid: Fundamental and Clinical Text, 9th, Braverman LE, Utiger RD (Eds), Lippincott Williams and Wilkins, Philadelphia 2005. p.77.
- Van Herle AJ, Vassart G, Dumont JE. Control of thyroglobulin synthesis and secretion. (First of two parts). N Engl J Med 1979; 301:239.
- Moreno JC. Identification of novel genes involved in congenital hypothyroidism using serial analysis of gene expression. Horm Res 2003; 60 Suppl 3:96.
- Moreno JC, Klootwijk W, van Toor H, et al. Mutations in the iodotyrosine deiodinase gene and hypothyroidism. N Engl J Med 2008; 358:1811.
- Bianco AC, Larsen PR. Intracellular pathways of iodothyronine metabolism. In: The Thyroid: Fundamental and Clinical Text, Braverman LE, Utiger RD (Eds), Lippincott Williams and Wilkins, Philadelphia 2005. p.109.
- Bianco AC, Kim BW. Deiodinases: implications of the local control of thyroid hormone action. J Clin Invest 2006; 116:2571.
- Maia AL, Kim BW, Huang SA, et al. Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. J Clin Invest 2005; 115:2524.
- Panicker V, Cluett C, Shields B, et al. A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine. J Clin Endocrinol Metab 2008; 93:3075.
- Panicker V, Saravanan P, Vaidya B, et al. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. J Clin Endocrinol Metab 2009; 94:1623.
- McAninch EA, Jo S, Preite NZ, et al. Prevalent polymorphism in thyroid hormone-activating enzyme leaves a genetic fingerprint that underlies associated clinical syndromes. J Clin Endocrinol Metab 2015; 100:920.
- Duntas LH. Selenium and the thyroid: a close-knit connection. J Clin Endocrinol Metab 2010; 95:5180.
- Engler D, Burger AG. The deiodination of the iodothyronines and of their derivatives in man. Endocr Rev 1984; 5:151.
- Accorroni A, Saponaro F, Zucchi R. Tissue thyroid hormones and thyronamines. Heart Fail Rev 2016; 21:373.
- Benvenga S. Thyroid hormone transport proteins and the physiology of hormone binding. In: The Thyroid: Fundamental and Clinical Text, 9th, Braverman LE, Utiger RD (Eds), Lippincott Williams and Wilkins, Philadelphia 2005. p.97.
- Bartalena L. Recent achievements in studies on thyroid hormone-binding proteins. Endocr Rev 1990; 11:47.
- Mendel CM, Weisiger RA, Jones AL, Cavalieri RR. Thyroid hormone-binding proteins in plasma facilitate uniform distribution of thyroxine within tissues: a perfused rat liver study. Endocrinology 1987; 120:1742.
- Hennemann G, Docter R, Friesema EC, et al. Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability. Endocr Rev 2001; 22:451.
- Friesema EC, Ganguly S, Abdalla A, et al. Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem 2003; 278:40128.
- Armour CM, Kersseboom S, Yoon G, Visser TJ. Further Insights into the Allan-Herndon-Dudley Syndrome: Clinical and Functional Characterization of a Novel MCT8 Mutation. PLoS One 2015; 10:e0139343.
- Larsen PR, Silva JE, Kaplan MM. Relationships between circulating and intracellular thyroid hormones: physiological and clinical implications. Endocr Rev 1981; 2:87.
- Yen PM. Genomic and nongenomic actions of thyroid hormones. In: The Thyroid: Fundamental and Clinical Text, 9th, Braverman LE, Utiger RD (Eds), Lippincott Williams and Wilkins, Philadelphia 2005. p.135.
- Lim VS, Passo C, Murata Y, et al. Reduced triiodothyronine content in liver but not pituitary of the uremic rat model: demonstration of changes compatible with thyroid hormone deficiency in liver only. Endocrinology 1984; 114:280.
- Jolin T. Diabetes decreases liver and kidney nuclear 3,5,3'-triiodothyronine receptors in rats. Endocrinology 1987; 120:2144.
- Magner JA. Thyroid-stimulating hormone: biosynthesis, cell biology, and bioactivity. Endocr Rev 1990; 11:354.
- Shupnik MA, Ridgway EC, Chin WW. Molecular biology of thyrotropin. Endocr Rev 1989; 10:459.
- Dyess EM, Segerson TP, Liposits Z, et al. Triiodothyronine exerts direct cell-specific regulation of thyrotropin-releasing hormone gene expression in the hypothalamic paraventricular nucleus. Endocrinology 1988; 123:2291.
- Sawin CT, Hershman JM, Chopra IJ. The comparative effect of T4 and T3 on the TSH response to TRH in young adult men. J Clin Endocrinol Metab 1977; 44:273.
- Leboeuf R, Perron P, Carpentier AC, et al. L-T3 preparation for whole-body scintigraphy: a randomized-controlled trial. Clin Endocrinol (Oxf) 2007; 67:839.
- Jackson IM. Thyrotropin-releasing hormone. N Engl J Med 1982; 306:145.
- Wu P, Lechan RM, Jackson IM. Identification and characterization of thyrotropin-releasing hormone precursor peptides in rat brain. Endocrinology 1987; 121:108.
- Williams TC, Kelijman M, Crelin WC, et al. Differential effects of somatostatin (SRIH) and a SRIH analog, SMS 201-995, on the secretion of growth hormone and thyroid-stimulating hormone in man. J Clin Endocrinol Metab 1988; 66:39.
- Brabant G, Prank K, Hoang-Vu C, et al. Hypothalamic regulation of pulsatile thyrotopin secretion. J Clin Endocrinol Metab 1991; 72:145.
- Hollenberg AN. Regulation of thyrotropin secretion. In: The Thyroid: Fundamental and Clinical Text, 9th, Braverman LE, Utiger RD (Eds), Lippincott Williams and Wilkins, Philadelphia 2005. p.197.
- Vassart G, Dumont JE. The thyrotropin receptor and the regulation of thyrocyte function and growth. Endocr Rev 1992; 13:596.
- Kaplan MM, Utiger RD. Iodothyronine metabolism in rat liver homogenates. J Clin Invest 1978; 61:459.
- Danforth E Jr, Horton ES, O'Connell M, et al. Dietary-induced alterations in thyroid hormone metabolism during overnutrition. J Clin Invest 1979; 64:1336.
- van der Heyden JT, Docter R, van Toor H, et al. Effects of caloric deprivation on thyroid hormone tissue uptake and generation of low-T3 syndrome. Am J Physiol 1986; 251:E156.
- Silva JE, Leonard JL. Regulation of rat cerebrocortical and adenohypophyseal type II 5'-deiodinase by thyroxine, triiodothyronine, and reverse triiodothyronine. Endocrinology 1985; 116:1627.
- Heemstra KA, Soeters MR, Fliers E, et al. Type 2 iodothyronine deiodinase in skeletal muscle: effects of hypothyroidism and fasting. J Clin Endocrinol Metab 2009; 94:2144.
- THYROID HORMONE BIOSYNTHESIS
- Iodine economy
- Thyroid iodide transport
- Tyrosyl iodination
- Coupling of iodotyrosyl residues of thyroglobulin
- Thyroglobulin synthesis
- Endocytosis of colloid and hormone release
- Recycling of iodide
- Thyroglobulin secretion
- Extrathyroidal T3 production
- THYROID HORMONE METABOLISM
- Reverse triiodothyronine
- SERUM BINDING PROTEINS
- General functions
- Thyroxine-binding globulin
- CELLULAR HORMONE ENTRY AND BINDING
- T3-nuclear receptors
- REGULATION OF THYROID HORMONE PRODUCTION
- Thyroid hormone regulation of TSH secretion
- Thyrotropin-releasing hormone
- Other factors altering TSH secretion
- Mechanism of action of TSH
- Other thyroid-stimulating substances
- Regulation of extrathyroidal T3 production