Thyroid Anatomy and Physiology of Its Hormones

Thyroid Gland Anatomy

The thyroid is a butterfly-shaped gland located in the front of the neck just above the trachea, weighing approximately 15-20g in adult humans 1
The gland produces and releases two potent hormones into circulation: thyroxine (T4) and triiodothyronine (T3) 1

Thyroid hormone production is primarily regulated by thyroid stimulating hormone (TSH) from the pituitary gland, which controls multiple aspects of thyroid hormone synthesis including iodide uptake, activation of thyroid peroxidase enzyme, and regulation of iodide oxidation and organification 2
Adequate iodine intake (150 μg/day in adults) is essential for proper thyroid hormone synthesis 2
Thyroglobulin, an iodoglycoprotein, plays a crucial role in thyroid hormone synthesis, with multiple tyrosine residues becoming iodinated to form mono-iodotyrosine (MIT) and di-iodotyrosine (DIT) 3
T4 formation involves oxidative coupling between two DIT side chains, while de novo T3 formation involves coupling between an MIT donor and a DIT acceptor 3
The thyroid actively extracts circulating iodide and translocates it into the central intrafollicular compartment for thyroglobulin iodination 4

Thyroid hormones influence basal metabolic processes and enhance oxygen consumption in nearly all body tissues 1
They also influence linear growth, brain function (including intelligence and memory), neural development, dentition, and bone development 1
The physiological actions of thyroid hormones are produced predominantly by T3, with approximately 80% of circulating T3 derived from T4 by deiodination in peripheral tissues 5
Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis by diffusing into the cell nucleus and binding to thyroid receptor proteins attached to DNA 5

Absorption of orally administered T4 ranges from 40% to 80%, with the majority absorbed from the jejunum and upper ileum 5
Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA) 5
Only unbound hormone is metabolically active 5
T4 has a half-life of 6-7 days in euthyroid patients (3-4 days in hyperthyroidism, 9-10 days in hypothyroidism), while T3 has a half-life of ≤2 days 5
The major pathway of thyroid hormone metabolism is through sequential deiodination, with the liver being the major site of degradation for both T4 and T3 5
Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (rT3) 5

Primary hypothyroidism is characterized by elevated TSH and low free T4 levels 6
Treatment is with levothyroxine (T4) therapy, with dosing based on patient characteristics 7
For patients <70 years without cardiac disease or multiple comorbidities, the full replacement dose is approximately 1.6 mcg/kg/day 6
For patients >70 years or with cardiac disease/multiple comorbidities, treatment should start with a lower dose of 25-50 mcg/day and titrate gradually 6
TSH and free T4 levels should be monitored every 6-8 weeks while titrating hormone replacement, and once adequately treated, repeat testing every 6-12 months 6

Characterized by low TSH and elevated free T4 levels 6
Transient thyroiditis is the most common cause of immune-related hyperthyroidism, with approximately 40% presenting as symptomatic thyrotoxicosis and 60% as subclinical followed by hypothyroidism 6
Treatment options include beta-blockers for symptomatic relief, antithyroid medications, radioactive iodine, or surgery 6, 8

TSH is the most sensitive test for monitoring thyroid function with a sensitivity above 98% and specificity greater than 92% 7
Free T4 and T3 measurements provide additional information about thyroid status 2
Low TSH with a low free T4 is consistent with central hypothyroidism, while low TSH with elevated free T4 indicates hyperthyroidism 6
Drawing both TSH and free T4 is especially important when patients are symptomatic and hypothyroidism is suspected 6

Levothyroxine sodium is a synthetic T4 hormone that exerts the same physiologic effect as endogenous T4 5
Overtreatment with levothyroxine can lead to iatrogenic hyperthyroidism, increasing the risk for osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy 6, 7
About 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, highlighting the importance of regular monitoring 7
Development of low TSH on therapy suggests overtreatment or recovery of thyroid function; dose should be reduced or discontinued with close follow-up 6
Levothyroxine should not be used for the treatment of obesity or for weight loss 5

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 2
Many drugs and foods affect T4 absorption, including soybeans and dietary fiber 5
Levothyroxine should be administered once daily, preferably on an empty stomach, one-half to one hour before breakfast with a full glass of water 5
Administer at least 4 hours before or after drugs that are known to interfere with absorption 5