Anatomy of the Thyroid Gland

Thyroid Anatomy and Physiology

• The thyroid gland consists of right and left lobes connected by a median isthmus, located in the neck between the sternal notch and thyroid cartilage.
• The parathyroids are located behind the thyroid lobes, with two superior and two inferior parathyroids.
• The recurrent laryngeal nerves course behind the thyroid gland.
• The thyroid gland contains parafollicular cells (C cells) and follicular cells.
• Parafollicular cells produce calcitonin, which inhibits bone resorption and plays a minor role in bone physiology.
• Follicular cells produce thyroid hormones thyroxine (T4) and triiodothyronine (T3).

Thyroid Hormone Regulation

• The hypothalamic-pituitary-thyroid axis regulates thyroid hormone synthesis and secretion.
• Hypothalamic thyrotropin-releasing hormone (TRH) triggers the pulsatile release of thyroid-stimulating hormone (TSH) from the anterior pituitary.
• TSH stimulates thyroid cell growth, iodide uptake, and thyroid hormone synthesis and secretion.
• T4 and T3 exert negative feedback on the hypothalamus and pituitary, which further moderates hormone synthesis.
• The thyroid gland is the exclusive source of T4, while approximately 80% of T3 is from peripheral T4 deiodination, primarily in the liver and kidney.
• Most T4 (99.96%) and T3 (99.6%) are bound to serum proteins, with only free T4 and T3 being biologically available.

Thyroid Function and Hormone Effects

• T3 binds with high affinity to cellular nuclear receptors, affecting gene transcription in target tissues.
• T3 has positive cardiac inotropic and chronotropic effects, enhances myocardial adrenergic sensitivity, increases myocardial diastolic relaxation, and augments intravascular volume.
• T3 also increases gastrointestinal motility, bone turnover, heat generation, and energy expenditure.

Thyroid Examination

• The thyroid gland is located in the neck between the sternal notch and thyroid cartilage.
• The thyroid gland attaches to the trachea posteriorly and elevates with swallowing and neck extension.
• Examination involves both inspection and palpation while the patient swallows liquid with the neck slightly extended.

Thyroid Nodules

• Palpable nodules are found in 5% of women and 1% of men.
• Approximately 40% of the U.S. population has nodules identified on ultrasound, with an increasing incidence with age.
• Causes of thyroid nodules range from benign cysts and inflammatory nodules to malignancies.
• The initial laboratory evaluation of a thyroid nodule begins with measuring TSH.
• Patients with a suppressed TSH level are evaluated with thyroid scintigraphy, while those with normal or elevated TSH are evaluated with ultrasonography.
• Thyroid nodule characteristics and size determine the need for fine-needle aspiration biopsy (FNAB).

Goiter

• Goiter is an enlarged thyroid gland, which can be associated with normal thyroid function, hypothyroidism, or hyperthyroidism.
• The most common cause of goiter worldwide is iodine deficiency.
• Patients with goiter should be questioned about iodine intake, rate of change in size, and thyroid cancer risk factors.
• Clinical history should focus on symptoms of thyroid hormone excess or deficiency and compression.
• Examination should note the thyroid size, symmetry, and consistency, as well as the presence of nodules or adenopathy and tracheal deviation.

Multinodular Goiter

• Multinodular goiter (MNG) is the most common cause of thyroid enlargement in older adults in the United States.
• Evaluation includes measurement of TSH and thyroid ultrasonography to evaluate discrete nodules.
• The frequency of malignancy in patients with MNG is similar to those with solitary thyroid nodules.
• Signs and symptoms of compression or suspected substernal extension require additional testing, such as CT or MRI of the neck and chest.

Thyroid Cancer

• Thyroid cancer is diagnosed in 13.9 per 100,000 people per year in the United States.
• Thyroid cancer incidence has increased during the past four decades, mainly due to the rise in the diagnosis of small noninvasive cancers.
• Risk factors for thyroid cancer include a history of ionizing radiation exposure and a personal or family history of thyroid cancer.
• The diagnosis is confirmed by FNAB, and surgery is the mainstay of thyroid cancer treatment.
• Postoperative 131I therapy should be considered for thyroid remnant ablation and adjuvant therapy for differentiated thyroid cancer with an intermediate to high risk of recurrence.

Thyroid Function Evaluation

• Serum TSH is the most sensitive thyroid function test in patients with normal pituitary function.

• If TSH is suppressed, free T4 and total T3 should be assessed to detect overt or subclinical hyperthyroidism.

• If TSH is elevated, free T4 should be assessed to detect overt or subclinical hypothyroidism.

• Measuring TSH alone as an initial test is sufficient except in suspected central hypothyroidism, for which free T4 measurement is preferred.### Thyroid Function Tests

• Accurate in most clinical settings, but may be inaccurate with significant perturbations (familial dysalbuminemic hyperthyroxinemia)

• Measuring free T4 by equilibrium dialysis is highly accurate, but expensive and rarely necessary

• Biotin supplements can interfere with thyroid function tests, causing falsely high free T4, free T3, total T4, and total T3, and falsely low TSH, mimicking thyrotoxicosis

Thyroid Function and Replacement

• Multiple drugs can affect thyroid function and replacement (Table 35)
• Patients taking > 5-10 mg/day of biotin should discontinue it 2-5 days before thyroid function testing

T3 Measurement

• Not necessary in hypothyroidism unless severe, as normal levels are maintained
• Recommended in three settings: evaluating thyrotoxicosis, assessing hyperthyroidism severity, and differentiating hyperthyroidism from destructive thyroiditis
• In T3 toxicosis, the T3-to-T4 ratio is often > 20 due to preferential secretion of T3

Key Points

• Serum TSH is the most sensitive test of thyroid function and is sufficient as an initial test unless central hypothyroidism is suspected
• Triiodothyronine measurement is not necessary in hypothyroidism; normal levels are maintained unless hypothyroidism is severe

Disorders of Thyroid Function

• Thyrotoxicosis describes high levels of circulating thyroid hormones (T4 and T3) from any cause
• Hyperthyroidism is thyrotoxicosis caused by excessive endogenous thyroid hormone production
• Prevalence of hyperthyroidism in the US is 1.3%

Clinical Features and Diagnosis

• Thyrotoxicosis may present with nonclassical symptoms and signs in older adults
• Lid lag (eyelid retraction) can be seen in thyrotoxicosis of any cause due to increased adrenergic tone
• Presence of a diffuse goiter and recently developed proptosis is sufficient for a diagnosis of Graves disease
• Thyrotoxicosis is diagnosed with a low TSH and elevated free T4 and/or total T3
• Thyroid scintigraphy with RAIU can verify the cause

This quiz covers the structure and location of the thyroid gland, including its relation to surrounding organs and nerves. It also touches on the potential symptoms of thyroid pathology.