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