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This module explores the epidemiology, pathophysiology, risk factors, clinical manifestations, diagnosis, management, and complications related to thyroid dysfunction based on the most recent practice guidelines and up-to-date research.
Thyroid Dysfunction (for APRNs)
This module explores the epidemiology, pathophysiology, risk factors, clinical manifestations, diagnosis, management, and complications related to thyroid dysfunction based on the most recent practice guidelines and up-to-date research.
By the completion of this exercise, learners will be able to:
- review the normal anatomy and physiology of the thyroid gland and related endocrine organs
- differentiate hyperthyroidism, hypothyroidism, and central hypothyroidism
- discuss the epidemiology, pathophysiology, and risk factors of thyroid dysfunction
- describe the clinical manifestations of thyroid dysfunction
- describe the process for diagnosing thyroid dysfunction
- discuss the medical treatment of thyroid dysfunction
- identify the potential complications related to thyroid dysfunction
The endocrine system is complex and vital in orchestrating cellular interactions, metabolism, growth, aging, reproduction, and response to adverse conditions. This interconnected network of glands works with the nervous system to maintain the delicate balance of homeostasis. APRNs need to understand both the function of the endocrine system and how alterations in its function can lead to the pathologies discussed within this module. Disorders of the endocrine system are manifested as hypofunction or hyperfunction. Diabetes mellitus (DM) is the most common endocrine disorder in the US and is associated with significant health complications, including heart disease, vision loss, kidney failure, and lower extremity amputation. Disorders of the endocrine system contribute significantly to healthcare expenses each year. They are included in the top six medical condition-based spending categories, along with conditions of the respiratory and circulatory systems, among others. It is estimated that DM and other endocrine disorders account for 7% of US healthcare expenditures, equating to $159 billion. DM alone contributes to 3.4%, or $77 billion, of healthcare dollars spent annually in the US. Aside from the monetary costs, the loss of work, impaired quality of life, and ongoing personal disparities caused by endocrine disorders pose a significant burden to patients and their families. The estimated prevalence of endocrine disorders is over 5% of the US adult population for each major disease, including DM, obesity, metabolic syndrome, osteoporosis, erectile dysfunction, dyslipidemia, and thyroiditis. Thyroid disorders and osteoporosis/osteopenia have the highest incidence in females, while erectile dysfunction has the highest incidence in males. Black and Hispanic individuals have higher rates of DM (Hinkle et al., 2021; Kamal et al., 2019; Physiopedia, n.d.).
Anatomy and Physiology of the Endocrine System
The endocrine system consists of glands that produce and secrete hormones to regulate cell and organ activity, as well as the body's growth, metabolism, sexual function, and development. These hormones serve as the body's chemical messengers, which transfer information from one organ to another, coordinating functions between various body parts. The integral pieces of the endocrine system include the hypothalamus, pituitary, thyroid, adrenals, pancreas, parathyroids, pineal body, and ovaries/testes. Each gland secretes a set of hormones that help regulate the body's functions, much like a thermostat regulates the temperature in a building. Hormones may also be produced by specialized tissues, including those found in the gastrointestinal (GI) system, the kidneys, and white blood cells (WBCs). The GI mucosa produces hormones (e.g., secretin, gastrin, enterogastrone, cholecystokinin) essential to the digestive process, while the kidneys produce erythropoietin, which stimulates the bone marrow to produce red blood cells. WBCs also produce cytokines, which actively participate in immune and inflammatory responses. Chemicals, such as neurotransmitters released by the nervous system, can also function as hormones (Hinkle et al., 2021).
Slow hormonal action of the endocrine system helps regulate organ function in conjunction with the rapid-acting nervous system, creating a dual regulatory system. These two systems balance each other, allowing for precise control of organ function based on changes within and outside the body. The amount of circulating hormones depends on the body's unique needs; in a healthy individual, hormone concentration in the bloodstream is relatively constant. The endocrine system regulates itself based on a feedback system that involves stimulating and releasing hormones; it is responsible for maintaining a balance of hormone levels within the bloodstream. Releasing hormones are sent to the pituitary from the hypothalamus, prompting the pituitary to secrete various stimulating hormones. The stimulating hormones signal the target glands to release hormones into the circulation. As the circulating level of the desired hormone from the target gland increases, the hypothalamus secretes less of the releasing hormone, and/or the pituitary gland decreases the secretion of the stimulating hormone. This process signals the target gland to decelerate its hormone secretion (Hinkle et al., 2021). Figure 1 illustrates the glands of the endocrine system.
The Endocrine System
(Assessment Technologies Institute [ATI], 2019a)
The butterfly-shaped thyroid gland in the lower neck, anterior to the trachea, is the largest endocrine gland (see Figure 2). The thyroid gland consists of two lateral lobes connected by the isthmus and is about 5 cm long and 3 cm wide. The thyroid cannot be seen and is barely felt unless it becomes enlarged, known as a goiter. In children, the thyroid supports bone growth, brain development, and nervous system development. The thyroid helps maintain normal blood pressure (BP), heart rate (HR), muscle tone, and reproductive functions in adults. Additionally, the thyroid gland regulates body temperature and metabolism and produces and releases calcitonin. Specifically, metabolic rate, oxygen consumption, caloric needs, carbohydrate and fat metabolism, and brain and nervous system function are affected by thyroid hormones (American Thyroid Association [ATA], n.d.-c; Braunstein, 2022c; Harding et al., 2021; Institute for Quality and Efficiency in Health Care, 2018).
The thyroid gland produces three different hormones, including triiodothyronine (T3), tetraiodothyronine or thyroxine (T4), and calcitonin (see Figure 3). The follicular epithelial cells of the thyroid produce T3 and T4. Iodine is essential for this hormone's production. The human body does not produce endogenous iodine, so dietary iodine is essential. After being absorbed through the bowel, iodine is directed to the thyroid gland to be utilized in hormone production. T4 makes up 90% of the thyroid hormone produced by the thyroid gland; however, T3 has a much higher potency and more significant metabolic effect. A large portion of the T4 released into the bloodstream is converted into T3, occurring in the liver and other tissues. Approximately 80% of circulating T3 results from this conversion, while the thyroid gland directly secretes the remaining 20% of T3. The conversion of T4 to T3 can be influenced by the body's needs and the presence or absence of illnesses. Most of the T4 and T3 in the bloodstream are not circulating freely but instead are bound to a protein called thyroxine-bi
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As demonstrated in Figure 3, the release rate of T3 and T4 is controlled by the anterior pituitary gland and hypothalamus, which act as sensory controllers. The process is initiated by the hypothalamus, which emits thyrotropin-releasing hormone (TRH). TRH prompts the release of thyroid-stimulating hormone (TSH) from the anterior pituitary gland. TSH is critical for modulating the release of T4 by the thyroid, which is then converted to T3. The pituitary constantly measures the amount of T3/T4 and responds to changes to maintain an appropriate balance. The amount of TSH that the pituitary releases into the bloodstream depends on the amount of T4 that the pituitary perceives, as it functions on a negative feedback system. If the pituitary senses insufficient T4, it will boost TSH production, signaling the thyroid gland to produce more T4. Once T4 reaches an acceptable level in the blood, TSH production decreases (ATA, n.d.-c; Braunstein, 2022c; Harding et al., 2020).
The two most common disorders of the thyroid gland are hyperthyroidism and hypothyroidism. Hyperthyroidism is an overactive state of the thyroid gland with hypersecretion of thyroid hormones. Hypothyroidism consists of a scarcity of thyroid hormones, which causes a general slowing of the metabolic rate. Hypothyroidism may be classified as primary (due to thyroid disease) or secondary/central (due to pituitary and/or hypothalamic dysfunction). Primary hypothyroidism is much more common than secondary/central hypothyroidism, accounting for over 95% of cases (Harding et al., 2020; Ross, 2022a).
The Thyroid Feedback Loop
Epidemiology and Etiology of Thyroid Disease
According to the ATA (n.d.-a), over 12% of the US population will develop a thyroid condition during their lifetime. In addition, an estimated 20 million Americans have thyroid dysfunction, with up to 60% unaware of their condition. One in eight women will develop thyroid dysfunction during their lifetime and are 5 to 8 times more likely than men to develop thyroid problems. Thyroid dysfunction is a somewhat common condition, and the cause of these disorders is often unknown. If left undiagnosed, it can have detrimental side effects (i.e., cardiovascular disease, osteoporosis, and infertility) and may lead to death. Pregnant women with undiagnosed hypothyroidism are at increased risk of preterm delivery, miscarriage, and developmental problems in children (i.e., lower IQ and impaired psychomotor development). Thyroid diseases are life-long conditions; however, they can be effectively managed with treatment (ATA, n.d.-a).
Hyperthyroidism is a disorder involving excess thyroid hormone secretion by the thyroid gland, leading to elevated levels of free T4, free T3, or both. These elevated levels lead to a hypermetabolic state of thyrotoxicosis. The prevalence of hyperthyroidism is just over 1%. All thyroid diseases are more common in females than males. Males who develop thyroid disease are more likely to develop hyperthyroidism than hypothyroidism. Hyperthyroidism is more common in individuals over the age of 60. Most hyperthyroidism cases (60% to 80%) are related to Graves' disease, an autoimmune condition of unknown etiology. The annual incidence of Graves' disease is approximately 0.5 per 1,000 people in the US, and women are five times more likely to develop Graves' disease than men. Other forms of hyperthyroidism include toxic multinodular goiter (Plummer disease) and toxic adenoma. Toxic multinodular goiter accounts for 15% to 20% of thyrotoxicosis and most frequently occurs in regions with iodine deficiency. Toxic adenoma accounts for 3% to 5% of thyrotoxicosis cases. The incidence of Graves disease and toxic multinodular goiter changes with iodine intake; compared to regions with lower iodine intake, the US has more Graves disease and fewer toxic multinodular goiters. Hyperthyroidism increases an individual's risk for thyroid malignancy; it is also a risk factor for myocardial infarction and ischemic stroke in females, especially those who are non-obese and over the age of 50 (Braunstein, 2022a; Lee, 2022b; National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK], 2021a; Ross, 2023d).
Hypothyroidism, often referred to as thyroid hormone deficiency, is the most common type of thyroid dysfunction. Primary thyroid deficiency occurs when the thyroid gland cannot produce sufficient amounts of thyroid hormone. Whereas, with secondary hypothyroidism, the thyroid gland is normal but receives insufficient stimulation because of inadequate secretion of TSH from the pituitary gland. It is estimated that 3.7% of Americans ages 12 and older have hypothyroidism, although as many as 4% to 10% have subclinical hypothyroidism with mild or minimal symptoms. The prevalence of hypothyroidism increases significantly between the ages of 40 and 50 and is 5 to 8 times more common in women than men. The most common form of hypothyroidism in the US is primary hypothyroidism, caused by atrophy of the thyroid gland—often secondary to autoimmune disease—that is termed Hashimoto's thyroiditis. Worldwide, the most common cause of hypothyroidism is iodine deficiency. Americans typically ingest sufficient iodine through iodized table salt, shellfish, eggs, soymilk, cow's milk, and cheese. Primary deficiency can also be due to defective hormone synthesis. Thyroiditis is typically characterized by a self-limiting and transient increase followed by a decrease in hormone levels. Secondary or central hypothyroidism is caused by a failure of the anterior pituitary gland to secrete adequate amounts of TSH. This may be due to decreased levels of TRH (hypothalamic dysfunction) or pituitary dysfunction. The condition occurs in approximately 1 in 20,000 to 80,000 people. Decreased thyroid hormones during pregnancy or early infancy lead to neonatal or congenital hypothyroidism (CH), sometimes called cretinism. CH is the most common form of hypothyroidism in children, affecting 1 in 1,500 infants (Daniel, 2023b; NIDDK, 2021b; Orlander, 2022b; Ross, 2023a; Willis, 2019; Yani, 2019).
Pathophysiology and Risk Factors
Hyperthyroidism is a hyperactive clinical syndrome of the thyroid gland characterized by thyrotoxicosis. Thyrotoxicosis is defined as an excess of T3 and T4 in the circulation. Due to increased T3 and T4 levels, the TSH should be low if the pituitary gland can appropriately sense excessive amounts of thyroid hormone in the body. Hyperthyroidism can develop due to thyroiditis (typically transient and self-limiting), excessive iodine intake, pituitary tumors, thyroid cancer, toxic adenoma, and toxic multinodular goiters (an enlarged gland with varying nodule sizes that show hyperplasia). Additional risk factors for hyperthyroidism include a family history of thyroid disease, nicotine consumption, pernicious anemia, or type I or II diabetes. However, the most common cause is Graves' autoimmune disease. In this disease, the immune system reacts inappropriately by producing antibodies (most often thyroid-stimulating antibodies [TSab] or thyroid-stimulating immunoglobin [TSI]) that act as TSH receptor agonists and overstimulate the thyroid gland, causing a marked increase in T3 and T4. In addition to female patients, those with a personal or family history of other autoimmune disorders have an increased risk of Graves' disease. Autoimmune thyroid disease occurs with lower frequency in Black patients (Braunstein, 2022a; Lee, 2022b, 2022c; NIDDK, 2021a; Ross, 2023b).
Thyroid nodules may be singular or multiple. Toxic adenoma is caused by a somatic mutation in the TSH receptor of the GS alpha gene, typically resulting in a single thyroid nodule. Toxic multinodular goiter involves the expansion of clonogenic cells with an activating TSH receptor mutation, leading to multiple palpable nodules. Toxic multinodular goiter occurs more commonly in areas of the world that are prone to iodine deficiency and is typically present in people over 50. Drug-induced thyroiditis, hyperemesis gravidarum, postpartum thyroiditis, and subacute granulomatous thyroiditis are less common etiologies of hyperthyroidism. Lithium (Lithobid, an antipsychotic medication), interferon-alpha (Intron A), and interleukin 2 (Proleukin) may cause a release of preformed thyroid hormones. Amiodarone (Cordarone, a class III antiarrhythmic medication) may cause an overproduction of thyroid hormones (thyrotoxicosis type 1) or a release of preformed thyroid hormones (thyrotoxicosis type 2). Hyperthyroidism can also be related to the administration of tyrosine kinase inhibitors or antiretrovirals. Rare etiologies include factitious thyrotoxicosis, metastatic follicular thyroid cancer, struma ovarii (ovarian tumor defined by the presence of thyroid tissue), trophoblastic tumors, germ cell tumors, and TSH-secreting pituitary adenomas (Braunstein, 2022a; Lee, 2022b, 2022e; NIDDK, 2021a; Ross, 2023b).
Iodine ingestion can also contribute to the development of hyperthyroidism. Patients who regularly ingest an iodine-deficient diet often develop a nodular goiter. If these individuals move to a different area or adjust their diet to allow for sufficient iodine intake, the sudden increase in iodine ingestion can trigger thyrotoxicosis. In these instances, iodine may act as an immune stimulator, precipitating autoimmune thyroid disease. Although they do not prompt true hyperthyroidism, subacute thyroiditis and exogenous intake of excessive amounts of thyroid hormone can cause thyrotoxicosis, mimicking the signs and symptoms of hyperthyroidism. Subacute thyroiditis typically occurs in three phases, causing 4 to 10 weeks of thyrotoxicosis, then up to 2 months of mild hypothyroidism, and finally returning to a previously healthy state. Subacute granulomatous (painful) thyroiditis causes approximately 15% of cases of thyrotoxicosis in the US and 10% of cases of hypothyroidism. Subacute granulomatous thyroiditis may be associated with a viral illness related to a post-infectious complication of influenza, adenovirus, mumps, or coxsackievirus. Silent (painless or subacute lymphocytic) thyroiditis is characterized by thyroid tissue damage causing an excessive release of previously formed thyroid hormones. It is most likely autoimmune, but this is not definitively known. As mentioned previously, certain medications can also trigger thyroiditis. Patients with subacute lymphocytic thyroiditis are more likely to develop goiters, and some develop permanent hypothyroidism. A third form of subacute thyroiditis occurs within a year of pregnancy and is termed subacute postpartum thyroiditis (Braunstein, 2022a; Lee, 2022b, 2022c; NIDDK, 2021a; Ross, 2023b).
Signs and Symptoms
Hyperactive thyroid hormone synthesis and secretion commonly cause tremors, anxiety, palpitations, fatigue (often due to insomnia), weight loss despite an increased appetite, polydipsia (increased urination), excessive perspiration, and heat intolerance. Upon inspection, a goiter (enlarged thyroid gland) may be palpable. Approximately 25% of patients diagnosed with Graves' disease develop exophthalmos (bilateral protrusion of the eyeballs). Graves' ophthalmopathy or orbitopathy can occur because the body's T-cells attack the tissues in the orbital space. This leads to the thickening of the muscles and an increase in adipose and connective tissue volume around the eye, as the tissue in the retro-orbital space may share antigenic epitopes with thyroid follicular cells. Ophthalmopathy can present as periorbital edema, exophthalmos, or diplopia (Lee, 2022a; Matthew et al., 2023; Pokhrel & Bhusal, 2023; Ross, 2022c). Figure 4 demonstrates exophthalmos and goiter.
Exophthalmos (top) and Goiter (bottom)
(ATI 2016, 2019b)
A patient can develop a goiter with either hypothyroidism or hyperthyroidism, so additional testing should be performed to determine the type and cause. Goiters related to Graves' disease are typically smooth, with a positive thrill to palpation and a positive bruit on auscultation. Goitrogens are foods or medications that may cause a goiter to develop (Pokhrel & Bhusal, 2023; Ross, 2022c, 2023b). See the list below for types of goitrogens:
- propylthiouracil (PTU)
- methimazole (Tapazole)
- large doses of iodine
- p-aminosalicylic acid (Paser)
- lithium (Lithobid)
- amiodarone (Cordarone)
- brussels sprouts
- mustard seeds
- turnips (Pokhrel & Bhusal, 2023; Ross, 2022c, 2023b)
Acropachy is a less common extrathyroidal manifestation. It is characterized by digital clubbing and edema of the fingers. Patients with autoimmune thyroid disease may develop myxedema, an altered physical appearance of the skin and subcutaneous tissues due to the accumulation of hydrophilic mucopolysaccharides (hyaluronic acid) in the dermis and surrounding tissues. Myxedema may manifest with periorbital (around the eyes) edema, facial puffiness, and a masklike face, or it may be pretibial (affecting the anterior lower legs). Many individuals with myxedema struggle with an altered self-image. Pretibial myxedema may not be confined to the pretibial area but may also affect the skin of the ankle, dorsum of the foot, knees, shoulder, elbows, or upper back. Pretibial myxedema can cause nonpitting edema, erythema, and skin thickening. Patients rarely report associated pain or pruritus. Orbitopathy, pretibial myxedema, and thyroid acropachy are pathognomonic for Graves' disease (Gill, 2020; Lee, 2022a; Matthew et al., 2023; Pokhrel & Bhusal, 2023; Ross, 2022c). See Table 1 for other body systems that may be affected by hyperthyroidism.
Other Clinical Manifestations of Hyperthyroidism
(Lee, 2022a; Matthew et al., 2023; Pokhrel & Bhusal, 2023; Ross, 2022c)
Older adults may have different signs and symptoms of hyperthyroidism, particularly with toxic nodular goiter. This atypical presentation (apathetic or masked hyperthyroidism) can include a loss of appetite, depression, or withdrawal from social situations. Atrial fibrillation, heart failure, weakness, syncope, and altered sensorium can occur. Older adults with hyperthyroidism often do not exhibit tremors or exophthalmos. These variations can make diagnosis challenging, and hyperthyroidism can be mistaken for depression or dementia (Braunstein, 2022a; NIDDK, 2021a).
The diagnosis of hyperthyroidism is evident when patients have clinical and biochemical manifestations. However, some patients will exhibit fewer and less obvious clinical signs but definitive biochemical hyperthyroidism. There is also a small subset of patients who will have little or no clinical signs and biochemically only have a low TSH, indicating subclinical hyperthyroidism (Ross, 2023c). There are no universal recommendations for screening for thyroid disease in adults. However, the ATA suggests screening every 5 years beginning at 35 years of age, particularly in high-risk groups such as:
- pregnant individuals
- women over 60 years of age
- patients with autoimmune diseases such as type 1 DM (T1DM)
- patients with a history of radiation to the neck or brain
- patients with other hypothalamus or pituitary hormone deficiencies
- patients with a prior history of traumatic brain injury (TBI) or pituitary/hypothalamus surgery (Orlander, 2022e; Ross, 2023a)
The US Preventive Services Task Force (USPSTF, 2015) found insufficient evidence regarding screening asymptomatic patients. The American Academy of Family Physicians recommends screening asymptomatic individuals over 60. At the same time, the American College of Physicians suggests screening women over 50 who have one or more clinical features of thyroid disease. It may be prudent to consider screening asymptomatic patients who fall under a high-risk category, such as those with a goiter on examination, a history of autoimmune disease, previous radioactive iodine ablation, previous radiation therapy to the head or neck, a family history of thyroid disease, or current use of medication(s) that may impair thyroid function. Finally, the American Association of Clinical Endocrinologists recommends TSH screening in all individuals of childbearing age before pregnancy or during the first trimester. However, the American College of Obstetricians and Gynecologists (ACOG) does not recommend universal screening of pregnant individuals for thyroid disease unless they are at increased risk (i.e., T1DM, symptoms of thyroid disease, or personal or family history of thyroid disease; Orlander, 2022e; Ross, 2022a).
A full history and physical examination should be performed to evaluate a patient for potential hyperthyroidism. Some symptoms of hyperthyroidism may manifest in patients with elevated estrogen levels, such as pregnant patients or those receiving hormone replacement therapy. The TSH and T4 levels in these individuals are typically within the expected reference range. This possible explanation for the patient's symptoms should be ruled out in female patients. In addition to the history and physical examination, a serum TSH level should be performed to establish a diagnosis. According to the USPSTF (2015), TSH is considered the first-line screening test for patients with suspected thyroid dysfunction. The level of circulating TSH in the blood helps determine if the thyroid is functioning normally, overactive, or underactive. If the TSH is low, the thyroid is likely producing too much T3/T4, raising the clinical suspicion for hyperthyroidism or secondary hypothyroidism. In thyrotoxicosis, TSH levels are usually unmeasurable (less than 0.05 μU/mL). T4 can be measured as total T4 or free (FT4). Total T4 measures both the free and the bound hormone available, whereas FT4 assesses the amount of T4 hormone freely circulating in the blood and available for use. FT4 is more commonly performed since it provides the best insight into the severity of an abnormal TSH level. FT4 is most accurate when performed with a TSH level, so these tests are usually ordered together (ATA, 2019; BCGuidelines, 2018; Lee, 2022e; Matthew et al., 2023).
A thyroid panel typically consists of three main tests: TSH, FT4, and free T3 (T3, Free) or total T3, as seen in Table 2 (American Board of Internal Medicine [ABIM], 2023). Free T3 is less reliable and not clinically indicated in suspected thyroid disease. The total T3 test is reserved for identifying hyperthyroidism or determining its severity, as patients with an overactive thyroid have elevated T3 levels. Reverse T3 is another thyroid test that is less commonly performed. It measures inactive thyroid hormone and is only indicated in the evaluation of patients with suspected hyperthyroidism (ATA, 2019; Lee, 2022e; Matthew et al., 2023).
0.5–4.0 μU/mL (0.5–4.0 mU/L)
If not performed concurrently as a panel of tests, the TSH should be drawn first; if TSH is low, FT4 and T3 should be added to determine the degree of hyperthyroidism. Many laboratories have algorithms that automatically measure FT4 and total T3 if the serum TSH is low. If a laboratory cannot add these additional tests, the patient must return for additional testing. Healthcare providers (HCPs) should consider ordering all three initially to avoid repeat testing. The reference range for total T3 is lower in adults over 50 (40-181 ng/dL; ATA, n.d.-c; Poduval, 2020; Ross, 2023c). When interpreting the thyroid function tests, the HCPs must consider several conditions that are commonly associated with transient elevations of the FT4, such as:
- amphetamine misuse
- high altitude exposure
- selenium deficiency
- hyperemesis gravidarum
- acute psychosis
- severe depression
- estrogen withdrawal (DeGroot, 2016; Ross, 2022e)
The most common thyroid conditions classified by TSH and FT4 values are demonstrated in Table 3 (ATA, n.d.-c). The USPSTF recommends that multiple tests over 3 to 6 months be performed to confirm abnormal results (USPSTF, 2015).
Thyroid Conditions and Lab Values
Mild or subclinical hypothyroidism
Lowered or normal
(ATA, n.d.-c; Orlander, 2022e)
Note: Biotin, a popular supplement for hair and nails, may interfere with immunoassays of many hormones, including thyroid hormones. The use of biotin can result in falsely elevated or suppressed values. The ATA recommends avoiding biotin at least 2 days before thyroid testing (Orlander, 2022e).
If both the TSH and FT4 are elevated, the rare presence of a TSH-secreting pituitary adenoma should be considered. A complete blood count (CBC) and hepatic panel should also be completed at baseline, especially in those diagnosed with Graves' disease. An electrocardiogram (ECG) may be indicated if the patient's heart rate is elevated and may demonstrate sinus tachycardia or dysrhythmias (Braunstein, 2022a; Lee, 2022d; Ross, 2023c).
Thyroid antibody tests are a separate subtype of thyroid function tests; they assess for the presence of thyroid antibodies. Thyroid peroxidase antibody, or antithyroid peroxidase antibody (TPO), is one of the most common antibody tests currently used in clinical practice. It is performed to determine if thyroid disease is autoimmune, such as Graves' disease. Repeat analysis is not indicated once a patient is known to be TPO antibody positive. TPO antibodies are usually low or absent in other causes of hyperthyroidism, including toxic multinodular goiter and toxic adenoma. Routine TPO screening should not be performed since a small percentage of healthy individuals will have mildly positive TPO titers. The presence of thyroid-stimulating immunoglobulin (TSI) or TSH-receptor-thyrotropin receptor antibody (TRAb) strongly supports a diagnosis of Graves' disease. These tests can determine the underlying etiology of hyperthyroidism in patients who cannot undergo a radioactive iodine uptake or a thyroid scan. If the TRAb levels are normal, the patient should undergo a radioactive iodine uptake (RAIU) test. A thyroid ultrasound should be performed if a patient presents with a thyroid nodule or goiter, but it is unnecessary if there is no palpable nodule or goiter. An ultrasound determines if a nodule is cystic (fluid-filled) or solid and measures the size of the nodule. If thyroid cancer is suspected, an ultrasound-guided fine needle biopsy may be performed (DeGroot, 2016; Lee, 2022e; Matthew et al., 2023; Ross, 2023c).
Thyroid Scintigraphy and Radioactive Iodine Uptake Test
If the patient's laboratory tests indicate hyperthyroidism, as evidenced by decreased TSH and elevated FT4, imaging with a nuclear medicine scan is indicated. Nuclear medicine imaging differs from conventional diagnostic imaging as it can visualize how the body functions at the cellular and molecular levels. Nuclear imaging uses small quantities of radioactive tracers (radiotracers) to diagnose and treat disease. The radiotracers are most commonly injected into a vein but may also be taken orally or inhaled. The radiotracer travels through the body, releasing energy in the form of gamma rays that are absorbed by specific tissues and organs. It is then detected by the external scanning device to provide information on organ function and cellular activity. The radiotracers are comprised of molecules bonded tightly to a radioactive atom, which vary greatly depending on the purpose of the scan. Radiotracers must meet US Food & Drug Administration (FDA) standards for safety due to radiation exposure. The Nuclear Regulatory Commission (NRC), the FDA, and individual states regulate radioactive materials for nuclear medicine to ensure the safety of patients, healthcare professionals, and the general public. Each nuclear medicine imaging test uses a specific radioactive agent (Lee, 2022e; National Institute of Biomedical Imaging and Bioengineering [NIBIB], 2019; Society of Nuclear Medicine & Molecular Imaging [SNMMI], n.d.).
There are two types of nuclear medicine imaging tests of the thyroid: thyroid scintigraphy (also called a thyroid scan) and RAIU test. Both scans use a small amount of radioactive iodine, usually in the form of sodium iodide-123 (I-123), as the thyroid gland is the only tissue within the body that absorbs and holds onto iodine. The radiation emitted by I-123 is harmless to thyroid cells and can be detected externally through thyroid scanning. In rare instances, sodium iodide-131 (I-131 or Iodotope) may be used with RAIU scans, but I-131 destroys thyroid cells. It is commonly reserved for treating thyroid disorders such as overactive thyroid, thyrotoxicosis, and thyroid cancers. The American College of Radiology (ACR, 2019) states that it is safe to use radioactive iodine in patients who report iodinated contrast allergies or seafood allergies, as the reaction is to the compound containing iodine and not the iodine itself. I-123 and I-131 readily cross the placenta, and their use should be avoided in pregnancy. If a thyroid scan is essential, the radioactive isotope technetium 99m is recommended (ACOG, 2017). Otherwise, an ultrasound is the recommended and safer imaging alternative for pregnant patients with suspected thyroid disease (Lee, 2022e; Matthew et al., 2023; Ross, 2023c).
A thyroid scan may be performed to obtain additional information about any structural abnormalities within the gland, such as nodules, masses, or inflammation. Thyroid scans are useful in, but not limited to, the evaluation of the following:
- the size and location of thyroid tissue
- the cause of overt and subclinical thyrotoxicosis
- suspected focal masses or diffuse thyroid disease
- clinical laboratory tests suggestive of abnormal thyroid function
- the function of thyroid nodules detected on clinical examination or other imaging examinations
- congenital thyroid abnormalities, including ectopia
- differentiating hyperthyroidism from other forms of thyrotoxicosis (ACR, 2019)
When undergoing a thyroid scan, the I-123 is administered intravenously within 30 to 60 minutes or orally as a pill or liquid. With oral administration, the I-123 must be taken approximately 4 to 6 hours before the scan to allow the radioactive iodine to reach and saturate the thyroid gland. The thyroid scan is painless, and patients are usually positioned lying flat (supine) on an examination table with their head tilted back to extend their neck. A scanner will take thyroid images from at least three different angles, and the patient is instructed to lie still for the duration of the test, which usually takes approximately 30 minutes (Iqbal & Rehman, 2022).
An RAIU scan is performed to evaluate the function of the gland or determine the etiology of hyperthyroidism, most commonly to differentiate Graves' disease from other forms of hyperthyroidism. It can also help guide treatment for patients who have thyroid cancer. The RAIU uses a specialized probe to measure how much tracer the thyroid gland absorbs. In most cases, the RAIU scan is performed alongside a thyroid scan to determine if the radiotracer is evenly distributed in the gland (Lee, 2022e; Matthew et al., 2023; Ross, 2023c). According to the ACR, while the RAIU scan does have overlapping indications with the thyroid scan, it is considered most useful in the following situations:
- differentiating hyperthyroidism from other forms of thyrotoxicosis (e.g., subacute or chronic thyroiditis and thyrotoxicosis factitial [exogenous thyrotoxicosis])
- assessing the necessity and calculating I-131 sodium iodide administered activity for patients to be treated for hyperthyroidism (ACR, 2019)
The RAIU scan requires administration of the radioactive iodine in liquid or capsule form, and scanning occurs at 4 to 6 hours after radiotracer administration and again at 24 hours. The administered dose for adults is typically 0.2 to 0.4 millicuries (mCi, or 7.4-14.8 megabecquerels [MBq]). The dose is typically weight-based for pediatric patients at 0.0075 mCi/kg (0.28 MBq/kg) within a range of 0.027-0.3 mCi (1-11 MBq). The patient is usually seated upright, and a small device called a radioactive detector (uptake probe) is placed against the patient's neck. The uptake probe takes measurements of radioactive iodine uptake, and a gamma camera records pictures of the thyroid gland. Both instruments detect and record the distribution of the radioactive material within the thyroid. The RAIU test usually takes several minutes. Oral administration is preferred for patients who undergo both thyroid and RAIU scanning, as this negates the need for a second dose of the radiotracer (ACR, 2019; Iqbal & Rehman, 2022; Lee, 2022e; Matthew et al., 2023; Ross, 2023c).
Agents containing iodine can decrease iodine uptake in the thyroid gland, leading to inaccurate test results. This includes many commonly used supplements, over-the-counter (OTC) agents, and certain prescription medications. Comprehensive medication reconciliation should be performed, and patients should discontinue thyroid hormones, antithyroid medications, and anything else that contains iodine. The period for which medication should be discontinued before the scan varies (e.g., levothyroxine [Synthroid] must be discontinued for 4 to 6 weeks, and iodine-containing cough syrups should be discontinued for 2 weeks; ACR, 2019). Please see Table 4 for medications that should be withheld prior to scanning and the timing recommended by the ACR.
Compounds That May Decrease Thyroid Iodine Uptake
Recommended Time to Withhold
Salicylates (large doses)
Iodine-containing cough medicines and vitamins
Iodine solution (Lugol's or SSKI**)
Iodine-containing topical agents
Thyroid extracts (desiccated thyroid extracts)
Intravenous (IV) iodinated contrast materials
Oil-based iodinated contrast materials
Patients should be advised to consume a low-iodine diet, avoiding the highest sources of dietary iodine (e.g., salt, grains, cereals, fish, poultry, and milk products) in the 1 to 2 weeks leading up to the scan (ATA, n.d.-b). Following the test, most radioactive material is cleared from the body within 1-2 days. No special precautions need to be taken since I-123 is harmless to thyroid cells (ACR, 2019). A patient with Graves' disease may have a highly elevated diffuse radioactive uptake of 35% to 95%, compared to a normal result of 3% to 16% (at 6 hours) and 8% to 25% (at 24 hours). While a moderately elevated uptake (25% to 60%) that appears homogenous indicates Graves' disease, an elevated uptake with a nodular appearance indicates either a toxic multinodular goiter (if found in multiple areas) or toxic adenoma (if found in a concentrated area). If the scan indicates reduced radiotracer uptake, this may indicate thyroiditis (<2%) or hyperthyroidism due to ectopic thyroid hormone production or exogenous hormone intake (Lee, 2022e; Matthew et al., 2023; Ross, 2023c).
Cases of subacute thyroiditis are typically self-limiting, resolving spontaneously within 6 months, and do not require specialized treatment. Supportive treatment may be recommended and should be directed toward relieving thyroid pain and tenderness and ameliorating symptoms of hyperthyroidism. Pain should be managed with nonsteroidal anti-inflammatory medications (NSAIDs) or prednisone (Deltasone). For mild to moderate neck pain, acetylsalicylic acid (Aspirin) 2,600 mg daily divided into four doses or an NSAID, such as naproxen (Aleve) 500mg to 1,000 mg daily divided into two doses or ibuprofen (Motrin) 1,200 mg to 3,200 mg daily divided into three or four doses is recommended. For severe pain or moderate pain that is not relieved by NSAIDs within two to three days, prednisone (Deltasone) 40 mg daily is recommended. Once pain relief is achieved, the dose of prednisone (Deltasone) should be decreased by 5 mg to 10 mg every 5 to 7 days. Symptomatic treatment with a beta-blocker such as propranolol (Inderal) 40 mg to 120 mg or atenolol (Tenormin) 25 mg to 50 mg daily for a few weeks may be prescribed to decrease adrenergic symptoms of tachycardia, nervousness, and irritability by inhibiting the sympathetic nervous system in any patient with hyperthyroidism. Thionamides should not be prescribed for subacute thyroiditis because the symptoms are not caused by excessive hormone synthesis. In addition, radioactive iodine therapy is not indicated since uptake is very low and the disease is self-limiting (Burman, 2021).
For a patient with hyperthyroidism related to amiodarone (Cardarone), the medication should not be discontinued unless it can be stopped safely due to the risk of related cardiovascular complications. Continuation of amiodarone (Cardarone) does not alter the basic treatment approach but does reduce the chances of successful treatment. Up to 20% of mild cases spontaneously resolve with the discontinuation of amiodarone (Cardarone), while other cases may take 3 to 5 months to resolve. Treatment varies by type of hyperthyroidism. Treatment for those with type 1, which involves the overproduction of thyroid hormones, should consist of a thionamide (an antithyroid medication). Methimazole (Tapazole) 40-60 mg/day or propylthiouracil (PTU) 600-800 mg/day should be prescribed to block thyroid hormone synthesis. If treatment with an antithyroid hormone is ineffective, adding potassium perchlorate (Peroidin) can be considered. However, potassium perchlorate (Peroidin) can cause aplastic anemia and is not FDA-approved for treating thyrotoxicosis. Type 2, characterized by thyroid tissue destruction, requires treatment with glucocorticoids, which reduce the conversion of T4 to T3. Prednisone (Deltasone) 30-40 mg/day should be prescribed with a taper over a few months until free T4 is within the reference range. A combination of glucocorticoids and thioamides can be used for patients whose mechanism is unknown. A rapid response to treatment indicated Type 2, and the thioamides can be tapered. A slower initial response suggests Type 1, and the glucocorticoids can be tapered. For a patient with hyperthyroidism related to other medications (e.g., lithium [Lithobid], interferon alfa (Intron A), tyrosine kinase inhibitors, or antiretrovirals), the offending medication should be safely tapered, discontinued, and replaced with an equivalent therapy (Gopalan, 2022).
Graves Disease, Toxic Multinodular Goiter, and Toxic Adenoma
Treatment options for other etiologies of hyperthyroidism are complex and depend on the underlying etiology. Treatment modalities can be divided into symptomatic (i.e., beta-blockers) and definitive therapy, including radioactive iodine (RAI) ablation, pharmacological therapy with a thionamide, and surgical intervention. Treatment choice should be based on the patient's underlying pathology, any contraindications to a particular treatment modality, the severity of the disease, and patient preference. Treatment is typically advocated in those with a TSH < 0.1 μU/mL (0.1 mU/L; Braunstein, 2022a; Lee, 2022d; Matthew et al., 2023).
Antithyroid medications usually take several weeks to become fully effective, leaving many patients with symptoms associated with adrenergic stimulation. The 2016 ATA guidelines for diagnosing and managing hyperthyroidism and other causes of thyrotoxicosis recommend beta-blocker treatment for all symptomatic thyrotoxicosis, especially in older adults with a resting heart rate above 90 bpm or coexistent cardiovascular disease (Ross et al., 2016). Symptomatic treatment with a beta-blocker such as propranolol (Inderal) 40 mg to 120 mg or atenolol (Tenormin) 25 mg to 50 mg daily titrated up to 200 mg/day divided into two doses is recommended to maintain a heart rate of 60 to 90 bpm. Beta-blocker treatment is usually helpful for tachycardia, tremors, anxiety, heat intolerance, and eyelid lag. However, it is less effective for manifestations related to a goiter, exophthalmos, weight loss, and increased oxygen consumption. Calcium channel blockers (CCBs), such as verapamil (Calan), can be used as a second-line treatment for hyperthyroid symptoms. CCBs are usually reserved for patients who are intolerant to or to which beta-blocker treatment is contraindicated (Braunstein, 2022a; Lee, 2022d; Matthew et al., 2023; Ross, 2021).
Radioactive Iodine Ablation. RAI ablation therapy has been the most common treatment utilized in the US for hyperthyroidism due to Graves' disease. RAI ablation is usually performed in an outpatient setting. A study by Wong and colleagues (2018) found that treatment with a single calculated RAI dose was effective in over 90% of 316 hyperthyroid patients with Graves' disease. RAI is administered as sodium iodide (I-131 or Iodotope) in a solution or capsule form. RAI can aggravate orbitopathy related to Graves' disease, which is considered a relative contraindication to RAI therapy in Graves' disease patients, especially those who smoke. RAI is typically considered the treatment of choice for patients with toxic adenoma or toxic multinodular goiter unless it is causing compressive symptoms. The advantages of RAI therapy include eliminating pharmacological side effects and perioperative risks. For three months leading up to the RAI administration, patients should avoid exposure to large amounts of nonradioactive iodine (e.g., iodinated contrast, amiodarone [Cordarone]). For a week before RAI administration, patients should also be counseled to avoid supplements containing iodine. Pregnancy should be ruled out within 48 hours of RAI administration. Breastfeeding patients should not be treated with RAI for 6 to 12 weeks after weaning (Braunstein, 2022a; Lee, 2022d; Ross, 2022b, 2022d; USPSTF, 2015).
RAI inhibits the release of T3 and T4 into the bloodstream by damaging thyroid tissue. It may be used in conjunction with a thionamide to achieve a euthyroid state or given short-term before surgery. RAI also decreases vascularity to the thyroid gland, improving surgical safety when given preoperatively. Patients can develop iodine toxicity if it is not properly dosed, which may involve buccal mucosa edema, excessive salivation, skin reactions, or nausea and vomiting. The patient should notify their medical team immediately if these symptoms occur. Underdosing can lead to inadequate results, and patients should be counseled on the possibility of future recurrence after successful treatment with RAI ablation. For this reason, higher doses are preferred, aiming for a hypothyroid state to limit the probability of treatment failure instead of a euthyroid state. The dose may be fixed or calculated using μCi or MBq per gram (g) of thyroid tissue based on 24-hour radioiodine uptake. Dosing for patients diagnosed with Graves' disease ranges from 150 to 200 μCi/g [5.9 to 7.4 MBq/g]. For fixed dosing, the ATA guidelines suggest 10-15 mCi (370-555 MBq) for adults with Graves' disease. Adults with toxic adenomas or multinodular goiters typically require a higher dose of 200 μCi/g (7.4 MBq/g) to treat effectively (Braunstein, 2022a; Lee, 2022d; Matthew et al., 2023; Ross et al., 2016; Ross, 2022b, 2022d).
It may take 6 to 18 weeks for the maximum desired effect of RAI to occur. Patients may experience a temporary exacerbation of hyperthyroidism symptoms immediately after RAI administration. An oral thionamide, such as methimazole (Tapazole), can alleviate this exacerbation, possibly returning thyroid function to a normal range faster. Pretreatment with methimazole (Tapazole) for 4 to 6 weeks may be especially beneficial for patients with severe symptoms of hyperthyroidism, severe thyrotoxicosis (two to three times the upper limit of normal), comorbidities that increase their vulnerability, and patients over the age of 60 or 65. Methimazole (Tapazole) should be withheld for 3 to 5 days before RAI administration and restarted 3 to 5 days after treatment. Then, this treatment can be continued for 4-18 weeks after RAI administration to manage hyperthyroidism symptoms while monitoring thyroid function tests and goiter size and awaiting the RAI to take effect fully. If levels remain elevated, the patient's TSH and FT4 should be reassessed approximately 4-8 weeks after RAI administration and every 4-6 weeks afterward. Patients with early symptoms or laboratory indications of hypothyroidism should begin thyroid hormone replacement. Pregnancy should be avoided for 6 months following RAI administration (Braunstein, 2022a; Lee, 2022d; Matthew et al., 2023; Ross, 2022b, 2022d; Ross et al., 2016).
Patients receiving RAI may develop thyroiditis or parotitis (inflammation of the parotid salivary glands). These complications may manifest with hoarseness, dry mouth, and throat irritation. The APRN should instruct the patient to gargle with salt water and take frequent sips of water for relief. Approximately 80% of patients develop post-treatment hypothyroidism within 2-6 months of treatment and require lifelong thyroid hormone replacement therapy. Patients should be counseled regarding this risk, including hypothyroidism symptoms and when to report them. Radiation exposure to patients and others is another risk that should be discussed with patients before treatment selection and administration (Braunstein, 2022a; Lee, 2022d; Matthew et al., 2023; Ross, 2022b, 2022d; Ross et al., 2016). The APRN should also review strategies with the patient to prevent exposing others to radiation. Home precautions include:
- using a private toilet
- flushing the toilet two or three times after each use
- washing laundry separately
- minimizing the time spent handling food while cooking for others
- avoiding contact with pregnant individuals and children for 7 days post-treatment (Ross, 2022b, 2022d)
Antithyroid Medications. Antithyroid medications (or thionamides) include propylthiouracil (PTU) and methimazole (Tapazole). These medications reach the thyroid gland via active transport, where they limit the synthesis of T3 and T4 by inhibiting thyroid peroxidase. Indications for antithyroid drugs are Graves' disease (especially in young patients), pregnant patients with a diagnosis of hyperthyroidism, and patients needing to establish a euthyroid state before RAI or surgical intervention. Propylthiouracil (PTU) inhibits the peripheral conversion of T4 to T3 and inhibits the production of thyroid hormones, thus achieving a euthyroid state more quickly than other drugs. However, it must be taken three times a day. The initial dosing is 100 to 150 mg/day taken orally every 8 hours, but rapid control can be achieved by increasing the starting dose to 150 to 200 mg/day every 8 hours. These higher doses are generally reserved for severely ill patients. The maintenance dose of propylthiouracil (PTU) is 50 mg twice or three times a day (Lee, 2022d; Matthew et al., 2023; Ross, 2022b; Ross et al., 2016). The ATA guidelines recommend a tiered approach to the initial dosing of methimazole (Tapazole):
- small goiters or mild hyperthyroidism (FT4 1 to 1.5 times the upper limit of normal): initial dose is 5 to 10 mg daily
- moderate hyperthyroidism (FT4 1.5 to 2 times the upper limit of normal): initial dose is 10 to 20 mg daily, tapered to a maintenance dose of 5 to 10 mg daily as the patient improves
- large goiters or severe hyperthyroidism (FT4 2 to 3 times the upper limit of normal): initial dose is 20 to 40 mg daily (divided into 10 mg two or three times a day or 15 mg twice a day), tapered to 5 to 10 mg daily as the patient improves (Lee, 2022d; Matthew et al., 2023; Ross, 2022b; Ross et al., 2016)
Since methimazole (Tapazole) can be given once daily, it is often used for the chronic treatment of hyperthyroidism in most patients, and propylthiouracil (PTU) is reserved for individuals in the first trimester of pregnancy, patients presenting in thyroid storm or crisis, and those with a methimazole (Tapazole) allergy or sensitivity. Clinical improvement typically happens within 1 to 2 weeks of initiating drug therapy, but optimal results do not occur for 4 to 6 weeks. Between 20% and 40% of patients with Graves' disease will experience spontaneous remediation after 6-15 months of treatment. However, patients should be cautioned that abruptly discontinuing the medication can cause regression of their hyperthyroidism. Propylthiouracil (PTU) is safe during the first trimester of pregnancy, but methimazole (Tapazole) may lead to congenital disabilities and should be avoided in the first trimester (Lee, 2022d; Matthew et al., 2023; Ross et al., 2016; Ross, 2022b).
Thionamides may control hyperthyroidism in patients with toxic adenoma or multinodular goiter but do not induce remission in these patients; therefore, they are not the ideal treatment choice. Potential benefits of pharmacological treatment include no exposure to radiation, no perioperative risks, and no risk of permanent hypothyroidism. If they use a pharmacological agent, patients should be counseled about the potential risks, such as agranulocytosis, hepatotoxicity (boxed warning associated with propylthiouracil [PTU]), and rash. FT4 and total T3 should be reassessed 4 weeks after starting a thionamide and then every 4-8 weeks until the patient is stable. Once stable, labs should be repeated every 3 months, and treatment should continue for at least 12-18 months. A taper should be considered if the patient's TSH has returned to the reference range. Thyroid function should continue to be monitored every 1 to 3 months for a year. Relapse occurs in 30% to 70% of patients with Graves' disease, generally within the first year (Lee, 2022d; Matthew et al., 2023; Ross et al., 2016; Ross, 2022b).
Surgical Thyroidectomy. Surgical thyroidectomy may be indicated for those with tracheal compression from a nodule/goiter, an inadequate response to thionamide therapy, or thyroid cancer. Patients are typically treated with RAI or a thionamide before surgery to achieve a euthyroid state. High doses of oral potassium iodide (SSKI, ThyroShield) can suppress the release of thyroid hormone as a short-term therapy, for example, 10-14 days before surgical thyroidectomy (Lee, 2022d; Matthew et al., 2023; Ross et al., 2016; Ross & Sugg, 2022). The preferred surgical intervention is a subtotal thyroidectomy (see Figure 5).
Generally, surgery aims to remove 90% of the thyroid. If a subtotal or partial thyroidectomy is performed, a patient can live in a euthyroid state without additional treatment. Endoscopic or robotic assistance is preferred for patients with small benign nodules and a healthy body mass index (BMI) due to smaller incisions leading to a faster recovery and less postoperative pain. Patients should be counseled regarding the potential benefits (e.g., lack of medication side effects, absence of radiation exposure, and decreased risk of recurrence) and risks (e.g., anesthesia reaction, as well as others discussed below) of surgery. For these reasons, surgery is typically reserved for those with compressive symptoms or contraindications to RAI or thioamides (Lee, 2022d; Matthew et al., 2023; Ross et al., 2016; Ross & Sugg, 2022).
Postoperative complications following thyroidectomy are uncommon, affecting 1% to 3% of patients. The patient should be monitored closely for airway obstruction. Laryngeal stridor may occur due to excess edema, hematoma, hemorrhage, or inflammation at the surgical site. A suction set and a tracheostomy kit should be readily available at the patient's bedside. Thyroidectomy procedures also carry an associated risk of damage to the recurrent laryngeal nerve, leading to voice changes (most likely hoarseness) or respiratory distress (Lee, 2022d; Matthew et al., 2023; Ross et al., 2016; Ross & Sugg, 2022).
Postoperative assessments for indications of hemorrhage and tracheal compression should be ordered at least every 2 hours for the first 24 hours. Symptoms may include frequent swallowing, choking, a saturated dressing, edema, dyspnea, or irregular breathing. Patients should remain in a semi-Fowler's position, supporting the head and neck with pillows to avoid tension on the suture lines. Vital signs should be monitored frequently, and calcium levels should be checked 6 hours and 1 day postoperatively. The parathyroid glands may be partially removed or unintentionally damaged during a thyroidectomy, causing hypocalcemia. In the first 24 hours after a total thyroidectomy, transient hypocalcemia occurs in 60% to 90% of patients. Severe hypocalcemia can lead to tetany, a series of involuntary muscle spasms, potentially worsening laryngeal stridor (Lee, 2022d; Matthew et al., 2023; Ross et al., 2016; Ross & Sugg, 2022). The patient should be monitored for signs of hypocalcemia, such as:
- a positive Trousseau's sign (carpopedal spasms that occur when a blood pressure cuff is inflated higher than the patient's systolic pressure)
- a positive Chvostek's sign (twitching of the facial muscles when the facial nerve is percussed over the cheek)
- tingling around the mouth
- tingling in the extremities
- muscle twitching (tetany; Lee, 2022d; Matthew et al., 2023; Ross et al., 2016; Ross & Sugg, 2022)
Calcium or calcitriol (Rocaltrol) supplementation can be given routinely or as needed for declining calcium levels. Routine supplementation is preferred when there is a high risk of post-thyroidectomy hypocalcemia (i.e., difficult surgery, parathyroid compromise, or parathyroid hormone [PTH] levels less than 10 to 15 pg/mL). A typical prophylactic dose of calcium carbonate is 2 to 3 g divided into two to four doses daily. Depending on serum calcium levels and hypocalcemic symptoms, this can be tapered over two to six weeks. Calcitriol (Rocaltrol) is dosed at 0.5 mcg daily for one to two weeks and increased or decreased after that based on calcium and intact PTH levels. If routine supplementation is not ordered, serum calcium levels should be measured on the evening of surgery and the next morning, and supplementation should be ordered based on the results (Ross & Sugg, 2022).
The patient typically can walk within a few hours of surgery if no complications occur. Oral fluids should be allowed as tolerated. A soft diet should begin the day after surgery. Postoperatively, the patient should be instructed to monitor for signs and symptoms of hypothyroidism and alert the medical team if these develop. Weight and caloric intake should be monitored to prevent weight gain. Education should be provided on appropriate iodine intake, often equating to one serving of seafood weekly or regular use of iodized salt. Regular exercise is essential to stimulate thyroid function (Lee, 2022d; Matthew et al., 2023; Ross et al., 2016; Ross & Sugg, 2022).
Children and Pregnant Women. Special considerations are needed to treat children and pregnant individuals who develop hyperthyroidism. The 2016 ATA guidelines for hyperthyroidism/thyrotoxicosis management recommend the following (Ross et al., 2016):
- Children with Graves' disease should be treated with methimazole (Tapazole), RAI therapy, or thyroidectomy. RAI therapy should be avoided in young children (under 5 years). RAI in children is acceptable if the activity is over 150 μCi/g (5.55 MBq/g) of thyroid tissue and for children between ages 5 and 10 years if the calculated RAI administered activity is under 10 mCi (370 MBq). Thyroidectomy should be chosen when definitive therapy is required, the child is too young for RAI (under 5), and a high-volume thyroid surgeon can perform surgery.
- In children with Graves disease who are prescribed methimazole (Tapazole), the medication should be tapered for those requiring low doses after 1 to 2 years to determine if spontaneous remission has occurred. It can be continued until the child reaches the age of definitive surgical therapy if needed.
- If surgery is chosen for children with Graves disease, a total or near-total thyroidectomy should be performed.
In 2017, the ATA released guidelines regarding the management of thyroid disease for individuals before pregnancy, during pregnancy, and in the postpartum period. These recommendations include the following (Alexander et al., 2017):
- Avoid scintigraphy or radioiodine uptake determination during pregnancy.
- If a decreased serum TSH is detected in the first trimester, a medical history, physical examination, and measurement of maternal FT4, TSab, and total T3 should be performed to help determine the etiology of thyrotoxicosis.
- Appropriate management of gestational transient thyrotoxicosis and/or hyperemesis gravidarum should include supportive therapy, dehydration management, and hospitalization if needed, but antithyroid drugs are not recommended. If necessary, beta-adrenergic blockers can be considered.
- Counseling on future pregnancy is recommended for individuals of childbearing age who are thyrotoxic or have Graves disease. This counseling should include the complexity of disease management in pregnancy and the association of congenital disabilities with antithyroid hormone use.
- Individuals with thyrotoxicity should be rendered stable euthyroid before attempting a pregnancy.
- Individuals taking methimazole (Tapazole) or propylthiouracil (PTU) should notify their HCP immediately following a positive pregnancy test.
Approximately 50% of patients with Graves' disease will develop mild signs and symptoms of thyroid eye disease, and another 5% will develop severe ophthalmopathy. Less severe cases should be treated with tight-fitted sunglasses worn whenever the patient is outside and saline drops as needed for comfort. If the eyelid does not fully close due to exophthalmos and the cornea is exposed at night, the patient will likely report irritation and tearing when awake. Treatment with saline gel or drops and covering the eyelids overnight with paper tape or goggles may keep the eyes moist and decrease discomfort. Elevation of the head during sleep can help reduce orbital congestion. Pharmacological treatment depends on the severity of the condition. Patients with mild symptoms who undergo RAI treatment should be given prednisone (Deltasone) 0.4-0.5 mg/kg/day one to three days after treatment and continued for one month, followed by a slow taper over two months. If severe orbital edema exists, optic nerve compression can occur, risking the loss of color vision and the development of orbital pain. These patients should be referred to an ophthalmologist with experience treating hormonal eye conditions for additional management. For moderate to severe cases, high-dose glucocorticoids may be given. Specifically, 100 mg of oral prednisone (Deltasone) for 1 to 2 weeks, then tapered over 6 to 12 weeks, or IV methylprednisolone (Solu-Medrol) 500 mg/week for 6 weeks, followed by 250 mg/week for 6 weeks. If high-dose glucocorticoids are ineffective, orbital decompression surgery and ocular radiation therapy may be necessary (Lee, 2022d; Pokhrel & Bhusal, 2023; Ross, 2022b).
Thyroid storm (also called acute thyrotoxicosis or thyrotoxic crisis) is an acute, rare complication of hyperthyroidism that occurs when excessive amounts of T3, T4, and calcitonin are released into circulation. This can result from trauma or increased stress in a patient with preexisting Graves' disease, toxic adenoma, or toxic multinodular goiter. Patients are also at risk during or immediately following a thyroidectomy due to the manipulation of the thyroid gland. Patients with hyperthyroidism can develop thyrotoxicosis following exposure to iodinated contrast, although this is a rare complication (Misra, 2022a; Ross, 2023e). The ACR (2023) does not recommend the restriction of contrast medium solely based on a history of hyperthyroidism but makes the following recommendations for two particular circumstances:
- "In patients with acute thyroid storm, iodinated contrast medium exposure can potentiate thyrotoxicosis; in such patients, iodinated contrast medium should be avoided. Corticosteroid premedication in this setting is unlikely to be helpful;
- In patients considering RAI ablation or in patients undergoing RAIU imaging of the thyroid gland, administration of iodinated contrast medium can interfere with the uptake of the treatment or diagnostic dose. If iodinated contrast medium was administered, a washout period is suggested to minimize this interaction. The washout period is ideally 3-4 weeks for patients with hyperthyroidism, and 6 weeks for patients with hypothyroidism" (ACR, 2023, p. 7).
Symptoms of thyroid storm mirror those of hyperthyroidism but to a greater degree, such as heart failure, extreme tachycardia, hypertension, vomiting, diarrhea, severe hyperthermia, excessive perspiration, shock, neurocognitive changes (agitation, restlessness, confusion), coma, and possibly death. The HCP should be familiar with the signs and symptoms of thyroid storm, as early initiation of treatment is crucial to avoid fatality. A thyroid storm can result in death within 2 hours if untreated. Thyroid storm is diagnosed clinically, and the Burch-Wartofsky point scale (BWPS) developed in 1993 can help the HCP assess a patient objectively. The BWPS assigns points for thermoregulatory dysfunction (based on hyperthermia), central nervous system disturbance (as evidenced by agitation, delirium, psychosis, seizure, or coma), gastrointestinal-hepatic dysfunction (as evidenced by nausea, vomiting, diarrhea, abdominal pain, or jaundice), cardiovascular dysfunction (as evidenced by tachycardia), congestive heart failure (as evidenced by pedal edema, rales, or pulmonary edema), atrial fibrillation, and precipitant history. A score under 25 is unlikely to represent a thyroid storm, a score of 25-44 indicates an impending storm, and a score over 45 indicates a thyroid storm (Ross, 2023e).
The treatment of thyroid storm consists of initial supportive therapies to manage the patient's airway, oxygenation (supplemental oxygen to maintain an oxygen saturation over 95%), dehydration (IV fluid resuscitation), and hyperthermia (a cooling blanket and antipyretics). Salicylates (e.g., aspirin [Bayer]) should be avoided as they may increase free T4/T3 levels. Acetaminophen (Tylenol) and ibuprofen (Motrin, Advil) may be administered to further reduce body temperature for patients with severe hyperthermia. Thionamides should be administered to inhibit thyroid hormone synthesis. Both methimazole (Tapazole) and propylthiouracil (PTU) can be administered orally, rectally, or via a nasogastric tube. Methimazole (Tapazole) can be started at 20 mg orally every 4-6 hours. Propylthiouracil (PTU) should be dosed at 200 mg orally every 4 hours. Propylthiouracil (PTU) also inhibits the peripheral conversion of T4 to T3 and may achieve a euthyroid state more quickly than other drugs. A saturated solution of potassium iodide (SSKI, ThyroShield) should be given orally (5 gtts every 6 hours) at least 1 hour after the thionamide to inhibit the release of any previously formed T3/T4. The beta-blockers esmolol (Brevibloc, 50-100 µg/kg/min IV), propranolol (Inderal, 60-80 mg PO every 4 hours), or metoprolol (Lopressor, 5-10 mg IV every 2-4 hours) should be administered to decrease the patient's heart rate. Diltiazem (Cardizem) can also be administered IV to patients with a contraindication to beta-blockers. Hydrocortisone (Solu-Cortef) 100 mg IV every 8 hours should be given to patients in order to decrease the conversion of circulating T4 to T3. Finally, the underlying cause of the thyroid storm should be evaluated and managed (Misra, 2022b; Ross, 2023e).
Pathophysiology and Risk Factors
Hypothyroidism is a common endocrine disorder characterized by a deficiency of thyroid hormone. Most cases of hypothyroidism are considered primary when the thyroid gland cannot produce sufficient amounts of thyroid hormone. Hypothyroidism risk is increased in people with reduced size at birth or during childhood. Secondary hypothyroidism occurs when the thyroid gland is functioning normally but receives insufficient stimulation (i.e., low secretion of TSH from the pituitary gland). The inadequate secretion of TRH from the hypothalamus leads to inadequate release of TSH, known as tertiary hypothyroidism. Worldwide, iodine deficiency is the primary cause of hypothyroidism. However, in areas with adequate iodine intake, including the US, autoimmune thyroid disease (Hashimoto's disease) is the most common cause of hypothyroidism. In autoimmune thyroid disease, the body's immune cells attack the thyroid, causing inflammation and eventually decreasing hormone production. Eventually, the patient develops a significantly decreased T3/T4 and an elevated TSH. Patients with preexisting autoimmune diseases such as T1DM and celiac disease are more likely to develop Hashimoto's hypothyroidism. Gender, family history, previous radiation exposure, and age are risk factors for developing this condition. It most commonly affects middle-aged women. The two most common antibodies that cause thyroid dysfunction are thyroid peroxidase and thyroglobulin (Braunstein, 2022b; Orlander, 2022e; Patil et al., 2023).
As mentioned in the section on hyperthyroidism, certain medications often affect thyroid function. Hypothyroidism can develop due to the destruction of the thyroid gland from certain drugs. Amiodarone (Cordarone) has a high iodine content and can destroy the thyroid gland, blocking T3, T4, and calcitonin production. Approximately 14% of patients taking amiodarone (Cordarone) develop hypothyroidism. Lithium (Lithobid) may cause hypothyroidism by blocking thyroid hormone synthesis. Approximately 50% of patients taking it develop a goiter, usually within the first 2 years. Interferon-alpha (Intron A) and interleukin 2 (Proleukin) can also block the production of thyroid hormones. Iatrogenic hypothyroidism may develop due to damage to the thyroid gland in response to radiation therapy, surgery, or the overuse of RAI ablation for hyperthyroidism. As previously mentioned, iodine deficiency is a cause of hypothyroidism that is significantly more common outside of the US. Without iodine, the thyroid cannot produce thyroid hormones. Subacute thyroiditis typically leads to mild transient hypothyroidism that does not require treatment, although some patients with subacute lymphocytic thyroiditis develop permanent hypothyroidism (Braunstein, 2022b; Orlander, 2022c; Patil et al., 2023; Surks, 2023).
Congenital hypothyroidism (CH) develops during infancy due to a lack of thyroid hormone in fetal or neonatal development. In the US, all infants are screened for thyroid dysfunction at birth. CH is typically due to an anatomical defect in the thyroid gland, a metabolic dysfunction of the thyroid, or iodine deficiency. Central hypothyroidism may also be associated with deficiencies in other pituitary hormones, such as antidiuretic hormone (ADH), oxytocin, prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH), and adrenocorticotropic hormone (ACTH). It may result from a tumor, an infection, an infarction, or a TBI, causing damage to the hypothalamus or pituitary gland. Iatrogenic causes affecting pituitary/hypothalamus function include previous radiation therapy or surgical trauma. Regardless of the underlying pathology, a reduced circulating level of T3 and T4 leads to a slowed metabolic rate, reduced oxygen consumption, decreased oxidation of nutrients for energy, and decreased body heat (Braunstein, 2022b; Orlander, 2022c; Patil et al., 2023; Ross, 2023a; Shahid et al., 2023).
Signs and Symptoms
The initial signs and symptoms of hypothyroidism directly relate to slowing the metabolic processes discussed above. Symptoms may be vague and nonspecific, with extreme fatigue as the most common initial indication. Clinical manifestations diverge depending on the severity and extent of thyroid deficiency, as well as the patient's age at the time of diagnosis. Hashimoto's thyroiditis develops gradually; therefore, patients may be asymptomatic. Patients with Hashimoto's disease may present with a goiter. The gradual development of symptoms is common unless hypothyroidism occurs after a thyroidectomy, after RAI ablation, or as a result of thionamide medications. The most common symptoms of hypothyroidism include weight gain, cold intolerance, lethargy, fatigue, dry and flaky skin, hoarseness, and constipation. Patients with central hypothyroidism typically have milder symptoms than patients with primary disease (Braunstein, 2022b; NIDDK, 2021b; Patil et al., 2023; Surks, 2022).
Patients may develop cognitive and personality changes; these symptoms may be attributed to aging in older adult patients. The new onset of these symptoms in an older adult patient warrants an evaluation of thyroid function. Patients with preexisting cardiac disease have a higher risk of cardiac complications. Kidney function may also be affected, leading to a reduced glomerular filtration rate. Hypothyroidism is common among older adults; however, the clinical manifestations may be more subtle, making diagnosis challenging. Older adults often have fewer symptoms than younger adults, including confusion, anorexia, weight loss, decreased mobility, and incontinence. Hypothyroidism in older adults can mimic dementia or parkinsonism (Braunstein, 2022b; NIDDK, 2021b; Patil et al., 2023; Surks, 2022). In addition to the most common manifestations, patients diagnosed with hypothyroidism may also have specific organ-related manifestations (see Table 5).
Other Clinical Manifestations of Hypothyroidism
(Braunstein, 2022b; NIDDK, 2021b; Patil et al., 2023; Surks, 2022)
Babies with CH are typically born at term or post-term. If the condition is not recognized at birth and treated effectively, infants with CH typically present with:
- hoarse crying
- respiratory issues
- decreased physical activity
- a large anterior fontanelle
- failure to thrive (poor feeding, inadequate weight gain/growth)
- developmental delays
- constipation or decreased stools
- course facial features
- umbilical hernia
- skin that is mottled, pale, dry, and cool
- macroglossia (enlarged tongue)
- atrial or ventricular septal defects (Connelly & LaFranchi, 2023)
A lateral knee radiograph may indicate a distal femoral epiphysis, which suggests prenatal hypothyroidism. If left untreated, the child may develop dystrophy of the bones and muscles, spasticity, gait abnormalities, inadequate growth, mutism, and mental deficiencies. Patients with chronic, severe hypothyroidism may develop myxedema, which may appear as periorbital (around the eyes) edema, facial puffiness, or a masklike face (Connelly & LaFranchi, 2023; Daniel, 2023a; Willis, 2019).
In addition to the history and physical examination, a serum TSH level should be performed to establish a diagnosis of hypothyroidism as described previously for hyperthyroidism. A TSH level should be drawn first if not performed concurrently as a panel of tests. If TSH is high, the thyroid gland is likely not producing enough T3/T4, which would raise clinical suspicion for primary hypothyroidism. Conversely, if TSH is low, the thyroid may be producing too much T3/T4, raising clinical suspicion for hyperthyroidism or secondary hypothyroidism. In most cases, the TSH level should be repeated for confirmation if it is initially abnormal, along with an FT4 if it has not already been done. T3 testing is not clinically useful in patients with hypothyroidism, as TSH and FT4 are typically abnormal earlier than the T3 level. Even patients with severe hypothyroidism may present with a normal T3 level. Please refer to Table 2 for common reference ranges for thyroid function tests. In primary hypothyroidism, the patient's TSH is typically elevated, and their thyroid hormone levels are lower than expected. Patients with elevated TSH levels and normal FT4 levels are considered to have mild or subclinical hypothyroidism. With secondary hypothyroidism, the TSH level is typically normal or slightly decreased, and the FT4 level is decreased. For the most common thyroid conditions classified by TSH and FT4 values, please refer to Table 3. The differential diagnoses that should be considered or ruled out in a patient with an elevated TSH level include recent recovery from a nonthyroidal illness (if recently recovered, consider repeating labs in 4-6 weeks), a TSH-secreting pituitary adenoma (these patients typically present with elevated TSH and FT4 levels), primary adrenal insufficiency, or a rare resistance to TSH or T3/T4 (ATA, n.d.-c, 2019; BCGuidelines, 2018; Orlander, 2022e; Ross, 2022a). A CBC and metabolic profile should also be completed. Patients with hypothyroidism may exhibit:
- anemia, especially macrocytic anemia
- dilutional hyponatremia
- hyperlipidemia and elevated triglycerides
- elevations of transaminases, creatinine kinase, and alkaline phosphates (Orlander, 2022e; Ross, 2022a)
An ECG may indicate sinus bradycardia, flat or inverted T-waves, or low-voltage QRS complexes. In addition, adrenal function must be fully assessed with a fasting morning serum cortisol level, potentially requiring an ACTH stimulation test, before initiating corrective treatment for secondary hypothyroidism. Both conditions (central hypothyroidism and adrenal insufficiency) often occur simultaneously, and correcting hypothyroidism without first initiating treatment for adrenal insufficiency may trigger a life-threatening adrenal crisis. Thyroid scanning using technetium-99m, I-123, or an ultrasound can help provide information about the etiology of the disease, as previously described in the section regarding hyperthyroidism. RAIU is not useful for hypothyroidism. Thyroid antibody tests—TPO, as explained earlier—are performed to determine if thyroid disease is autoimmune, such as in Hashimoto's disease. In patients with suspected Hashimoto disease, anti-thyroglobulin antibody (Tg) testing may also be performed to confirm the diagnosis, as these patients typically have high levels of TPO and Tg (DeGroot, 2016; Orlander, 2022e; Ross, 2022a).
Monotherapy for most cases of hypothyroidism should begin with a low dose of levothyroxine (Synthroid), which is a synthetic form of T4, in those with a TSH > 10 μU/mL (10 mU/L). The typical initial dose for adults with mild to moderate hypothyroidism is 50-75 µg/day. However, a younger adult may tolerate starting at the goal dose, and an older adult may be started at 25 µg. The goal of treatment is to replace the hormone that the thyroid is no longer making. Clinical benefits should occur within five days of initiating the medication and level off in about four weeks. Optimal results from levothyroxine (Synthroid) may take up to 8 weeks. Initial dosing and pediatric dosing may also be calculated using body weight. Most adult patients under 50 with minimal endogenous thyroid function require between 1.6 and 1.8 µg/kg of body weight or an average maintenance dose of 100-200 µg daily. There is some discrepancy about whether this should be calculated using actual or ideal body weight. The maximum dose is 200 µg daily. Levothyroxine (Synthroid) should be taken on an empty stomach first thing in the morning. If levothyroxine (Synthroid) dose requirements are much higher, the ATA guidelines recommend evaluating for GI disorders, such as H pylori, atrophic gastritis, or celiac disease (Braunstein, 2022b; Orlander, 2022d; Ross, 2023f; USPSTF, 2015).
A patient's TSH level should be rechecked 6 to 10 weeks after treatment initiation or dose changes if they have been diagnosed with primary hypothyroidism. Based on the patient's TSH level, levothyroxine (Synthroid) dosing should be adjusted every 4 to 6 weeks. Once stabilized, patients should have their TSH checked at least annually. The HCP should consider adding exogenous T3 in the form of liothyronine (Cytomel) if symptoms persist despite a stable TSH level within the desired range. This may be especially helpful for patients who have undergone total thyroidectomy. A combination product with levothyroxine/liothyronine (Armour Thyroid) may add convenience for patients requiring both hormones. However, patients should be cautioned about naturally occurring inconsistencies leading to fluctuations in hormone levels with the combination product, as it is derived from the thyroid of pigs. Desiccated thyroid medications (i.e., levothyroxine/liothyronine [Armour Thyroid]) have not been approved by the FDA, so they should be used with caution (Braunstein, 2022b; Jonklaas et al., 2014; Orlander, 2022d; Ross, 2023f).
Dosing for secondary hypothyroidism should be weight-based initially and then adjusted to keep the patient's FT4 in the upper normal reference range per the treatment guidelines from the ATA. The FT4 and the patient's report of symptoms should be the primary indicators for dose adjustments in central hypothyroidism, as the TSH level is not recommended for continuous monitoring of maintenance therapy. Treatment with glucocorticoids for adrenal insufficiency should begin before or concurrently with thyroid hormone replacement but not after (Braunstein, 2022b; Jonklaas et al., 2014; Orlander, 2022d; Ross, 2023f).
Special dosing considerations apply to certain patient populations. Children may require more frequent TSH level assessments and dosing changes as they grow to avoid mental and physical complications. Patients with thyroid cancer often require a levothyroxine (Synthroid) dose of 2.1- 2.7 µg/kg. Adults under 50 may only require 25-50 µg daily. Patients with ischemic heart disease should start at a quarter to half of the suggested adult starting dose. Pregnant patients should be universally screened for signs and symptoms of thyroid dysfunction and previous use of thyroid medications. Pregnant patients diagnosed with hypothyroidism should be treated with levothyroxine (Synthroid) based on their TSH level, as shown in Table 6. Serum TSH should be drawn every 4 weeks during the first 20 weeks of pregnancy in those newly diagnosed with hypothyroidism. Monitoring in the second half of pregnancy should be based on the patient's symptoms and prior laboratory testing consistency. Those who were previously diagnosed and on stable levothyroxine (Synthroid) dosing prior to pregnancy should be instructed to take two additional doses per week spread several days apart (e.g., Sunday and Thursday) once pregnancy is confirmed (Alexander et al., 2017; Braunstein, 2022b; Jonklaas et al., 2014; Orlander, 2022d; Ross, 2023f).
TSH Reference Ranges During Pregnancy
Stage of Pregnancy
≤4 μU/mL (mU/L)
Second and third trimesters
≤3 μU/mL (mU/L)
(Alexander et al., 2017)
The primary risk of levothyroxine is overdosing or underdosing. If too much thyroid hormone is taken, signs and symptoms of hyperthyroidism will result. If too little is taken, the clinical manifestations of hypothyroidism will persist. During annual clinical evaluations, a patient on levothyroxine (Synthroid) therapy should be evaluated for the classic symptoms of hypothyroidism or hyperthyroidism. The HCP should explain to patients that levothyroxine (Synthroid) is not a cure but a lifelong treatment requirement. It is absorbed in the small intestine as a daily dose. Oral antacids, iron, or calcium supplements should be separated by at least 4 hours from levothyroxine (Synthroid) administration. The HCP should counsel patients to promptly report neurologic excitability or cardiac symptoms (including palpitations; Braunstein, 2022b; Jonklaas et al., 2014; Orlander, 2022d; Ross, 2023f). Patients should be counseled regarding:
- the importance of maintaining lifelong thyroid hormone replacement and consistent follow-up care
- avoiding cold temperatures
- performing proper skincare/hygiene, avoiding perfumed soaps and body wash, and using fragrance-free lotion to moisturize their skin daily to prevent skin breakdown and lesions
- managing constipation by gradually increasing physical activity, dietary fiber, OTC stool softeners, adequate hydration, and developing regular bowel patterns
- monitoring for signs and symptoms of bleeding or blood loss in patients taking anticoagulants, as thyroid hormone replacement increases this risk
- monitoring heart rate daily and digoxin levels periodically in patients taking digoxin (Lanoxin), as thyroid hormone replacement may interact with this medication and decrease or increase circulating digoxin levels
- informing all HCPs of their condition and all current medications to avoid potential interactions
- discussing the use of any OTC medications, including herbal and other supplements, with their health care team for approval prior to starting to avoid products that may interact negatively with their thyroid medications
- avoiding commercial weight loss products
- maintaining a balanced diet (Braunstein, 2022b; Jonklaas et al., 2014; Orlander, 2022d; Ross, 2023f)
Infants are treated with oral levothyroxine (Synthroid) that is initially dosed at 10-15 µg/kg/day or 50 µg daily. Pills should be crushed in a small amount of liquid (breastmilk, formula, or water) and administered orally via a syringe. Dosing should be adjusted slowly to avoid thyrotoxicosis. In infants, this may present with perspiration, agitation, restlessness, loss of consciousness, and hypertension, in addition to the previously described symptoms of acute thyrotoxicosis. Toddlers can be allowed to chew pills (Braunstein, 2022b; Jonklaas et al., 2014; Orlander, 2022d; Ross, 2023f).
Hypothyroidism is common and relatively easy to manage. However, if not properly managed, it can have a high risk of morbidity and mortality. Severe or untreated hypothyroidism can lead to serious complications, including:
- bleeding tendencies
- benign intracranial hypertension
- atherosclerosis, decreased peripheral circulation, ischemic heart disease, heart failure, cardiomegaly, and other cardiac complications
- GI dysfunction, such as pernicious anemia, achlorhydria (lack of hydrochloric acid), megacolon, or obstruction
- iron-deficiency anemia
- psychiatric/mood disorders
- myxedema crisis/coma (Orlander, 2022a; Patil et al., 2023)
Myxedema coma was first described in the late 1900s as a result of long-standing, untreated hypothyroidism. It is now a rare complication, yet it remains a medical emergency with a mortality rate of 40%. Myxedema crisis and coma typically occur in patients with undiagnosed hypothyroidism. These effects may also be precipitated by infection, certain types of drugs (e.g., opioids, barbiturates, and sedatives), extreme cold exposure, or trauma. Patients who develop myxedema crises may have altered cognition, progressive lethargy, bradycardia, bradypnea, hypoglycemia, decreased cardiac output, and hypothermia (body temperature under 95°F). These manifestations can progress to multisystem organ failure, coma, and death if immediate treatment with IV thyroid hormone therapy is not initiated. The HCP should be familiar with the signs of a myxedema crisis, as the early initiation of treatment is crucial to avoid fatality (Braunstein, 2022b; Eledrisi, 2023b). Additional testing to diagnose myxedema can include:
- random serum cortisol to assess adrenal function (if this test is within the normal range, an ACTH stimulation test is needed to assess function)
- sodium level (typically indicates hyponatremia with low serum osmolality)
- serum creatinine level (usually elevated)
- serum glucose (expected hypoglycemia; Braunstein, 2022b; Eledrisi, 2023b)
Diagnostic tools like the one developed by Chiong and colleagues (2015) can screen for myxedema coma; however, these tools have only been tested in a few patients. This tool incorporates six criteria, which are:
- heart rate
- body temperature
- Glasgow coma scale score
- TSH level
- free thyroxine index (FTI)
- precipitating factors like infection, medication noncompliance, furosemide (Lasix) use, cold exposure, hypoglycemia, GI bleeding, heart failure, hypercapnia, or a cerebrovascular event (Chiong et al., 2015)
The ideal mode of therapy and doses of thyroid hormone for myxedema coma remain controversial due to the limited clinical trials available. The ATA guidelines recommend a combination of T4 and T3 therapy. A single dose of 300-600 µg (4 µg/kg) of IV levothyroxine (Synthroid), or divided doses depending on the patient's risk of cardiac disease and age, should be administered for myxedema crisis diagnosis to avoid coma. After 24 hours, given a dose of 100 µg IV levothyroxine (Synthroid) followed by 50-100 µg daily (1.2 µg/kg/d) until the patient can tolerate medications by mouth. Once the patient can tolerate medications by mouth, levothyroxine (Synthroid) dosing should continue at the standard daily oral replacement rate (1.6 µg/kg/day) or adjusted based on their TSH results. Levothyroxine (Synthroid) is incompatible with most other IV medications and should not be added to another infusion. The patient should be monitored closely for changes in vital signs, chest pain, tachycardia, neurological hyperexcitability, and ongoing thyroid laboratory values. Since the rate of conversion of T4 to the active form of T3 can be reduced in these patients, the addition of T3 is recommended. T3 therapy, liothyronine (Cytomel), is given as a 5-20 mcg IV bolus and continued at a 2.5-10 mcg dose every 8 hours, depending on the cardiac risk factors and age. Lower doses are recommended for smaller or older patients or those with a history of coronary artery disease or arrhythmias. If the patient takes an anticoagulant, their prothrombin time (PT) should also be monitored, as levothyroxine (Synthroid) can interact and cause excessive bleeding. IV glucocorticoid therapy should be added to the initial therapy for a myxedema crisis (Eledrisi, 2023a; Jonklaas et al., 2014).
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