What metabolic functions does the thyroid gland regulate?

Thyroid Regulation of Metabolic Functions

Thyroid hormones regulate multiple critical metabolic functions through control of DNA transcription and protein synthesis, affecting energy expenditure, thermogenesis, glucose metabolism, and circadian rhythms throughout the body.

Mechanism of Action

• Thyroid hormones (T3 and T4) exert their physiologic actions by diffusing into cell nuclei and binding to thyroid receptor proteins attached to DNA, activating gene transcription and synthesis of messenger RNA and cytoplasmic proteins 1
• The physiological actions are produced predominantly by T3, with approximately 80% derived from T4 by deiodination in peripheral tissues 1
• Thyroid hormone receptors are ubiquitous, allowing thyroid hormones to interact with and influence most metabolic pathways in virtually all systems throughout life 2

Key Metabolic Functions Regulated by Thyroid Hormones

Energy Metabolism and Thermogenesis

• Thyroid hormones are major modulators of metabolic efficiency, energy expenditure, and thermogenesis 2, 3
• They control the coupling of mitochondrial oxidative phosphorylation and the cycling of extramitochondrial substrate/futile cycles 3
• Thyroid hormones regulate adenosine triphosphate (ATP) utilization, uncoupling synthesis of ATP, and mitochondrial biogenesis 4
• They play a critical role in controlling core body temperature, appetite, and sympathetic activity 4

Glucose Metabolism

• Thyroid hormones regulate daily rhythms in glucose metabolism, with faster glucose clearance occurring during the early active phase 5
• Both hyper- and hypothyroidism can affect glucose metabolism, potentially leading to insulin resistance and abnormal glucose handling 4
• Thyroid dysfunction may contribute to adverse glucose metabolism, affecting insulin sensitivity in peripheral tissues 4

Lipid Metabolism

• Thyroid hormones influence serum triglyceride levels and overall lipid metabolism 4
• They regulate lipolysis and fatty acid oxidation during fasting states 6
• Thyroid dysfunction can lead to abnormal serum triglyceride levels and contribute to dyslipidemia 4

Protein Synthesis and Growth

• Thyroid hormones are essential for normal growth and development through their effects on protein synthesis 1
• They interact with growth hormone to promote proper tissue development and maturation 5

Circadian and Metabolic Rhythms

• Thyroid hormones (TSH/T3) show distinct daily rhythmic patterns that differ between diurnal humans and nocturnal rodents 6, 5
• They regulate daily rhythms in hormones and metabolites, causing downstream intracellular signaling to peak at specific times of the day 6, 5
• Thyroid hormones interact with other hormonal systems that also show circadian patterns, including glucocorticoids, insulin, growth hormone, and melatonin 5

Regulation of Thyroid Hormone Production

• Thyroid hormone production is primarily regulated by thyroid stimulating hormone (TSH) from the pituitary gland 7
• TSH controls multiple aspects of thyroid hormone synthesis, including stimulation of iodide uptake, activation of thyroid peroxidase enzyme, regulation of oxidation and organification of iodide, and control of secretion of T4 and T3 into circulation 7
• Adequate iodine intake (150 μg/day in adults) is essential for proper thyroid hormone synthesis 7
• Iron and selenium are crucial for proper thyroid function, with iron deficiency impairing thyroid metabolism, and selenium required for the deiodination of T4 to T3 via the selenoenzyme Type 1 5'-deiodinase 7

Clinical Implications

• Thyroid dysfunction represents a continuum from asymptomatic biochemical changes to clinically symptomatic disease 6
• Subclinical hypothyroidism may be associated with increased risk of symptomatic hypoglycemia and reduced linear growth rate 6
• Hyperthyroidism alters glucose metabolism and usually causes deterioration of glycemic control 6
• Thyroid parameters follow specific circannual and circadian rhythms, which can affect diagnostic testing if sampling times are not standardized 5

Metabolism of Thyroid Hormones

• The major pathway of thyroid hormone metabolism is through sequential deiodination 1
• The liver is the major site of degradation for both T4 and T3, with T4 deiodination also occurring at additional sites including the kidney and other tissues 1
• Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (rT3) 1
• Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation 1
• Thyroid hormones are primarily eliminated by the kidneys, with approximately 20% of T4 eliminated in the stool 1