Thyroid

Anatomy & Histology & Function

The thyroid gland is a butterfly-shaped gland located in the front of the neck, just below the larynx. It consists of two lobes, one on each side of the trachea, connected by a thin piece of tissue called the isthmus. As the thyroid gland is formed it moves from the base of the tongue to its final position in the neck via the thyroglossal duct. Because of this migration, the thyroid gland can sometimes be found in other locations, such as higher up in the neck or even in the chest, known as an ectopic thyroid gland. Most often you end up with a small strip of thyroid gland extending superiorily from the isthmus or one of the lobes called the pyramidal lobe.
Histologically the thyroid gland is made up of spherical structures called follicles, which are lined with a single layer of epithelial cells called follicular cells. The follicles are filled with a substance called colloid, which contains the precursor to thyroid hormones. (T3 and T4). Surrounding the follicles are parafollicular cells (also known as C-cells), which produce the hormone calcitonin. Between the follicles are connective tissue and blood vessels allowing for efficient transport of hormones.
Histology:
  1. Follicular cells (epithelial cells) take up iodine and release it into the colloid where it is used to make precursers of T3 and T4. Which is then taken up by the follicular cells, again, cleaved by proteases, and released into the blood stream as T3 and T4.
  2. Colloid contains thyroglobulin, a protein that is used to make thyroid hormones.
  3. Parafollicular cells (C-cells) produce the hormone calcitonin, which inhibits osteoclast activity (cells that break down bone and release calcium into the blood), and also promote the excretion of calcium and phosphate in the kidneys. This results in a decrease in blood calcium levels.
Thyroid anatomy

How to activate the thyroid gland: The journey start in the hypothalamus where the thyroid receptor hormone (TRH) is secreted. This hormone than stimulates the anterior pituitary gland to secrete thyroid stimulating hormone (TSH). TSH travels to the thyroid where it connects to a transporter on the outer side of the follicular cells, which then activates a channel called the sodium-iodide symporter (NIS). This channel then takes up iodine and along with natrium transports it from the blood into the follicular cell. The iodine is oxidized within the cell and transferred into the lumen of the follicle or the colloid. Here the iodine is combined to tyrosine inside a protein called thyroidglobulin, becoming MIP and DIP. MIP and DIP are then combined to form T3 and T4, which are still bound to the thyroglobulin. When the body needs thyroid hormones, the follicular cells endocytose some of the colloid containing the thyroglobulin with T3 and T4 attached. The vesicle containing the colloid fuses with a lysosome, where proteases cleave T3 and T4 from the thyroglobulin. The free T3 and T4 are then released into the bloodstream. In the blood, most of T3 and T4 are bound to carrier proteins, such as thyroxine-binding globulin (TBG), transthyretin, and albumin. Only a small fraction of T3 and T4 are free and biologically active. T4 is converted to the more active T3 in peripheral tissues by the enzyme deiodinase. T3 then enters cells and binds to thyroid hormone receptors in the nucleus, where it regulates gene expression and affects metabolism, growth, and development.
Thyroid anatomy

Diagnostic methods

Blood test

To test how the thyroids function, most often "TSH", "T3" and "T4" are checked.
  • Hypoactive thyroid Low levels of T3 & T4, with high levels of TSH. Here the thyroid is not responding to TSH, so in response the anterior pituitary increase its release of TSH in hopes of normalising the low levels.
  • Hyperactive thyroid High levels of T3 & T4, with low levels of TSH. Here the thyroid is secreting to much of T3 & T4 causing symptoms of a hyperactive thyroid gland. These high levels act as negative stimulus on the anterior pituitary which then decreases its TSH secreation. However, if TSH levels are also high, the problem does not lie within the thyroid gland, but in a hyperactive anterior pituitary, if TRH levels are normal or decreased, indicating a tumor within the anterior pituitary. And if TRH levels are high, the hypothalamus is the main problem, indicating that there might be a tumor there.
  • Subclinical thyrotoxicosis

    • Imaging

    Thyroid Scintigraphy

    Thyroid scintigraphy is a nuclear imaging technique that uses small amounts of radioactive material to evaluate the function and structure of the thyroid gland. The patient is injected with a small amount of radioactive iodine or technetium, which is taken up by the thyroid gland. A special camera, collimator, is used to detect and gather the radiation emitted by the radioactive material, and you are able to visualise the gland. As the radioactive material is also taken up by the salivary glands, most often they can be visualised as well.
    Pros:
    1. Great way to easily assess the thyroid tissue function
    Cons:
    1. Cannot detect lesions under 1 cm.
    2. Cannot detect cold/hypofunctioning lesions if there is normal thyroid tissue infront or behind (here a SPECT/CT would be preferred, as you can then inspect the uptake in 3D).
    3. Radioactive material is used.
    Thyroid anatomy
    Interpretation
    • Normal scan: Uniform uptake of the radioactive material throughout the thyroid gland, indicating normal function. You will also see uptake in the salivary glands.
    • Hyperactive thyroid or nodule (hot/toxic nodule): Increased uptake of the radioactive material throughout the thyroid or in a specific area, indicating hyperfunctioning tissue. Simulatiously, there will be decreased uptake in the salivary glands and also the rest of the thyroid gland (if it is a nodule) as the hyperfunctioning tissue is taking up most of the radioactive material.
    • Hypoactive thyroid nodule (cold nodule): Decreased uptake of the radioactive material in a specific area of the thyroid gland, indicating hypofunctioning tissue. As there is a small risk of a hypoactive nodule being malignant, further investigation with ultrasound is needed to evaluate the structure of the nodule, to further evaluate the risk of malignancy and the need for a biopsy. But this can also be due to benign causes such as cysts or colloid nodules.
    • Multinodular goiter: Multiple areas of increased and decreased uptake of the radioactive material throughout the thyroid gland, indicating the presence of multiple nodules with varying levels of function.
    • Diffuse decreased uptake of the radioactive material throughout the thyroid gland, and normal uptake in the salivary glands. Could indicate inflammation (thyroiditis) or be caused by iodine-induced hypothyroidism, or the presence of medications that interfere with iodine uptake (such as amiodarone or lithium, or levothyroxine (decreases TSH)) or iodine-containing contrast agents (used for CT-scans) that compete for thyroid uptake.
    • Artifacts:
      • Uptake in the esophagus or stomach if the patient has swallowed some of the radioactive material, that has been secreted into the saliva and then swallowed. Drinking water before the scan can help reduce this artifact.
      • High levels of circulating thyroid hormones, which can suppress the uptake of the radioactive material. This can be seen in patients with hyperthyroidism or thyroiditis.

    Thyroid anatomy



    Ultrasound

    Ultrasound is most often used to evaluate the size and shape of the thyroid, if there is a risk of malignant nodules in the thyroid or if there are cysts that can be drained.
    All nodules are classified according to the ACR TI-RADS system (American College of Radiology Thyroid Imaging, Reporting and Data System). This system uses a point system to classify the nodules from TR1-TR5, where TR1 is benign and TR5 is highly suspicious of malignancy. The points are given based on the following criteria:
    • Composition
        cystic (0)
        spongiform (0)
        mixed cystic and solid (1)
        solid or almost completely solid(2)
    • Echogenicity
        anechoic (0)
        hyperechoic or isoechoic (1)
        hypoechoic (2)
        very hypoechoic(3)
    • Shape
        wider-than-tall (0)
        taller-than-wide (3)
    • Margin
        smooth (0)
        ill-defined(0)
        lobulated or irregular (2)
        extra-thyroidal extension (3)
    • Echogenic foci
        none or large comet-tail artifacts (0)
        macrocalcifications (1)
        peripheral (rim) calcifications (2)
        punctate echogenic foci (3)
    Based on the total points, the nodule is classified as follows & recommendations for FNA:
    • TR1 (0 points): Benign => No FNA needed
    • TR2 (2 points): Not suspicious => No FNA needed
    • TR3 (3 points): Mildly suspicious => FNA if nodule is ≥2.5 cm
    • TR4 (4-6 points): Moderately suspicious => FNA if nodule is ≥1.5 cm
    • TR5 (7 or more points): Highly suspicious => FNA if nodule is ≥1.0 cm

    Pros:
    1. Great way to easily assess the thyroid tissue structure
    Cons:
    1. User dependent.
    2. Might lead to over-diagnosis of small benign nodules, leading to overuse of unnecessary biopsies.

    Thyroid anatomy