About this course:
The purpose of this module is to provide an overview of the most common laboratory tests, their normal ranges, and clinical indications.
By the completion of this module, the nurse should be able to:
- Identify the most common types of laboratory tests, their indications, and identify key patient teaching points
- Identify normal reference ranges for each test and the clinical implications and reporting of abnormal results.
Understanding laboratory values is a core aspect of patient care and nursing practice. It is important for nurses to be knowledgeable about laboratory tests in order to make informed clinical decisions regarding the results to safeguard patient care. To assist nurses with developing and enhancing this skillset, this module will provide a basic overview of the most common laboratory tests, including the complete blood count, comprehensive metabolic panel, lipid panel, thyroid function tests, fasting blood glucose, glycated hemoglobin, and coagulation profile. As with all aspects of patient care, in order to fully comprehend laboratory data, the results must always be correlated with the patient's clinical signs and symptoms. All laboratory data and values listed within this module are compiled from the American Board of Internal Medicine (ABIM) guide to laboratory reference ranges and refer to healthy, non-pregnant adults. However, it is important to recognize that normal reference ranges will vary between laboratories (ABIM, 2019).
Abnormal Laboratory Results
Laboratory reports routinely flag abnormal values to alert the healthcare professional that there is a resulting value outside of the normal reference range. The flag can have variable presentations, but the most common flagging methods include an "L" for a result that is below the lower limit of normal, an "H" denoting a value above the upper limit of normal, or an arrow pointing up or down. For critically abnormal values, the result may be accompanied by a "c" for critical or an exclamation point (!) to direct attention to the value. Table 1 provides an example of a lab report highlighting several low blood counts accompanied by small red arrows pointing down (MedlinePlus, 2020a).
Critical Laboratory Values Communication
Critical results of laboratory tests are those that fall significantly outside the normal range and can potentially indicate a life-threatening situation. The reporting and treatment of critical laboratory values are fundamental to the delivery of safe and quality patient care. The efficient and timely communication of laboratory test results needing urgent clinical decision making is an essential responsibility of the recipient to optimize the clinical management. The Joint Commission (TJC) includes this concept as part of the National Patient Safety Goals for Laboratory Programs. It is not uncommon for nurses to be the first recipient of the verbal communication that a patient has a critically abnormal laboratory result. While each healthcare institution has their own policy governing the reporting and communicating of critical laboratory results, the standard practice involves a verbal “readback” communication in which the nurse must repeat the critical results back to the laboratory personnel reporting it to ensure accurate understanding, followed by acknowledgement of the party on the other end of the line. However, by accepting the critical result, the nurse has a legal and ethical obligation to contact the patient’s licensed provider to communicate the results in a timely fashion. Nurses should become familiar with their institution policy on the reporting and communicating of critical results, as well as the acceptable length of time between the availability, reporting, and successful communication with the licensed provider of critical test results (TJC, 2020).
Complete Blood Count (CBC)
Blood contains of both liquid and solid components, and is comprised of four main constituents: plasma, red blood cells (RBCs), white blood cells (WBCs), and platelets. Plasma is the liquid part and is comprised primarily of water. It functions to carry nutrients, proteins, and hormones throughout the body, as well as transport waste products to the kidneys and digestive tract for removal. The solid components of the blood include the fundamental elements of the CBC test: the WBCs, RBCs, and platelets (Longo, 2019). The CBC is one of the most common laboratory tests performed across healthcare settings, and it consists of several tests in one. It is used as an indicator of the patient's overall health and to detect and monitor a wide range of conditions, including infection, anemia, bleeding, and other blood-related abnormalities. Patients generally do not need to fast or take any special precautions prior to the test (Mayo Clinic, 2018a). The CBC test can be performed in one of two ways: with differential (CBC w/diff) or without. While the basic CBC test measures the number of the number of RBCs, WBCs, platelets, hemoglobin, hematocrit, and types of WBCs, the CBC w/diff includes a more detailed account of the quantities of each type of WBC present in the blood. It is useful for delineating blood abnormalities to diagnose and monitor various conditions. Table 2 demonstrates the parts of the CBC w/diff, including normal reference ranges (Longo, 2019).
Erythrocytes are mature RBCs, which have an average lifespan of 120 days. Their primary function is to carry hemoglobin, the protein that transports oxygen from the lungs to all the tissues within the body. It is also the pigment component of the RBC that is responsible for its characteristic red color. The body relies on oxygen as a critical component for all cellular functioning and processes. Hemoglobin also carries waste products (mainly carbon dioxide) from the tissues back to the lungs, where waste is expelled through breathing. The RBC result is reported as the number of cells per volume (microliter [μL)]) and the hemoglobin is the amount of protein (in grams [g]) per volume (deciliter [dL]). Hematocrit reflects the percentage, by volume, of RBCs in a given amount of blood. Under normal conditions, the hemoglobin and hematocrit usually exist in a 1:3 ratio, so that 1 g of hemoglobin is equivalent to 3% of hematocrit (Longo, 2019).
Low levels of RBC, hemoglobin, and/or hematocrit generally infer anemia. The components of the CBC provide essential characteristics and critical insight into the type of anemia, through the reporting of RBC indices (mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], and the red blood cell distribution width [RDW]). The MCV is a measure of the average size of the erythrocytes in femtoliters (fL). The MCH refers to the cell's color. Since hemoglobin provides the RBCs with its characteristic red color, the suffix –"chromic" is used. An RBC with a normal MCH has a typical red color and is called normochromic, whereas an RBC with a low MCH is pale in color and termed hypochromic. The MCHC is the average weight (concentration) of hemoglobin based on the volume of RBCs. The RDW is a measure of how many RBCs vary in size and volume. It reflects the degree of variation in RBC size and is often reported as anisocytosis on the results of the RBC morphology. The RDW is elevated when there is a wide variation in RBC size, which infers that the cells were produced under varying conditions. Minor variations in cell sizes are normal, so the RDW is only considered increased when it is greater than 15% (Longo, 2019).
The body's hydration status largely influences the hemoglobin level. In severe dehydration, the hematocrit can b
...purchase below to continue the course
WBCs are also called leukocytes and are the essential cells of the immune system. While WBCs only make up about 1% of all blood cells in healthy adults, they serve critical functions in the fight against infection and mediate the inflammatory process. WBCs have variable lifespans, as some live for only 24 hours; the average WBC lifespan is 13 to 20 days. There are five specific subtypes of WBCs: neutrophils, lymphocytes, monocytes, basophils, and eosinophils. Each subtype serves a distinct function and collectively they comprise the "differential" component of the CBC. When the total WBC count is abnormally elevated (leukocytosis), this is most commonly an indicator of an acute bacterial infection or an inflammatory process. However, a high WBC does not always indicate a pathologic process, as there can be physiological causes of leukocytosis such as stress, pregnancy, steroid therapy, or vigorous exercise. When leukocytosis occurs, the CBC's differential provides information about the relative percentage and the absolute number of each WBC subtype. A lower than normal WBC count is called leukopenia and increases the risk for acquiring an infection (Longo, 2019).
Neutrophils may also be referred to as segmented neutrophils (segs) or polymorphonuclear cells (polys or PMNs). They are the main WBC used for fighting and preventing infections, as they are primed to destroy and ingest any potential bacterial intruder. Neutrophils arrive first at the site of inflammation or injury. Therefore, elevations in neutrophils are usually seen early on in the course of an injury or illness. The absolute neutrophil count (ANC) measures the total number of neutrophils circulating in the blood, which correlates directly with the patient's risk level for acquiring an infection. This value is particularly important to monitor in patients undergoing myelosuppressive treatment for cancer. When the ANC drops below the normal range, the patient's risk for infection rises dramatically. Most laboratories designate an ANC level of less than 1500 as abnormal, or neutropenia. When a patient is neutropenic, they are at high risk for developing a serious illness, including life-threatening sepsis. Bands are immature neutrophils that are typically released following acute injury or inflammation. The presence of bands indicates that an inflammatory process is occurring, as the bone marrow has increased production of WBCs and is releasing them into circulation before they are fully mature. An increase in the number of bands is commonly referred to as a "left shift" or "shift to the left" (Pagana & Pagana, 2018).
Lymphocytes primarily fight viral infections, and there are two major types: B cells and T cells. B cells make antibodies in response to antigens (foreign substances) to provide future immunity to that specific antigen. T cells help to destroy cancer cells and also help to control the immune response against foreign substances. Monocytes are phagocytic cells that fight off viruses, fungi, and bacteria. Their job is to remove foreign materials such as dead or injured cells, microorganisms, and other particles from the site of injury to facilitate healing and prevent further injury or infection. Basophils help prevent blood from clotting within the microcirculation and are also involved in the inflammatory response, particularly with regards to modulating hypersensitivity reactions to allergens. In addition to their presence in the blood, basophils are also found within the gastrointestinal tract and skin, where they are referred to as mast cells. Mast cells contain heparin and histamine and are involved in allergic and stress responses. Eosinophils are also involved in mediating allergic and inflammatory reactions and serve an important role in fighting parasitic infections. Eosinophils are present in the respiratory tract and airway, serving similar functions in response to allergic reactions (Pagana & Pagana, 2018).
Platelets, or thrombocytes, are small blood cell fragments that serve a primary role in blood clotting. In response to an injury, laceration, or blunt trauma, platelets gather at the site of an injury to seal cuts or breaks in blood vessels in conjunction with proteins called clotting factors to control bleeding. Platelets have an average lifespan of 7 to 10 days. Thrombocytopenia occurs when the platelet count declines beneath the normal range, thereby heightening the patient's risk for bruising and acute bleeding events. Spontaneous hemorrhage and death can ensue in the most severe cases, particularly when the platelet count drops below 20,000 (Longo, 2019).
Blood Chemistry Testing
Comprehensive Metabolic Panel (CMP)
The CMP, otherwise referred to as the blood chemistry panel, provides information about several body systems and organ health. It measures the glucose levels, liver and kidney function, as well as the fluid and electrolyte balance. There is generally no special preparation prior to the test and patients generally do not need to fast for a routine CMP. However, the exception to this is if the liver function tests are being scrutinized with regards to response to a medication or other underlying condition, which may require the patient to fast. Table 3 provides a sample of a CMP results report highlighting the relevant components of the test and the accompanying normal reference ranges (Pagana & Pagana, 2018).
Embedded within the CMP are five serum electrolytes, including sodium, potassium, calcium, chloride, and bicarbonate (Bakerman et al., 2014).
Sodium helps regulate and maintain fluid balance within the body and serves a vital role in muscle contraction and nerve impulse. Hyponatremia occurs when sodium levels drop lower than the normal range and is a result of either water retention or sodium loss. Hyponatremia can occur due to fluid volume losses secondary to vomiting, diarrhea, or enforced diuresis from medication therapy. Symptoms of hyponatremia may include confusion, headache, muscle weakness, spasms/cramps, seizures, restlessness, and irritability. Hypernatremia occurs when the sodium level rises above the normal range and is typically due to water depletion secondary to insufficient water intake, excessive sweating, water loss, or excessive sodium intake. Symptoms of hypernatremia may include excessive thirst, lethargy, fatigue, and confusion. Hyponatremia and hypernatremia can also be due to the presence of more severe underlying conditions involving the liver, kidneys, or adrenal glands (Bakerman et al., 2014).
Potassium helps regulate the communication channels between nerve fibers and muscles, serving an important role in heart contraction and muscle functioning. Hypokalemia results when the potassium level drops below the normal range, and can occur from diuretic medications, diarrhea, vomiting, or in severe illness such as diabetic ketoacidosis. Symptoms of hypokalemia may include constipation, muscle weakness or spasms, numbness or tingling sensations, palpitations, and fatigue. Hyperkalemia occurs when the potassium level is higher than the upper limit of normal and can be due to excess dietary potassium intake, impaired renal clearance, or drug-induced from potassium-sparing diuretics. Symptoms of hyperkalemia may include muscle fatigue, weakness, paralysis, cardiac arrhythmias, and nausea. The collection process of the serum sample is important because if the sample becomes hemolyzed (cells are ruptured), hyperkalemia can be inaccurately reported on the lab results, thereby reinforcing the need to associate all laboratory data with the patient's clinical presentation. Since more than 90% of potassium is excreted in the urine, which is then filtered and reabsorbed proximally before being excreted by the distal tubules, it is not uncommon for patients with severe renal disease to exhibit abnormal potassium levels (Bakerman et al., 2014).
Calcium is one of the body's essential minerals required for muscle contraction, nerve function, healthy bones, and teeth. Calcium also serves important roles in blood clotting and cellular division. The CMP reports only the total calcium level in the bloodstream. Low levels of calcium, or hypocalcemia, may be a manifestation of hypoparathyroidism, renal failure, vitamin D deficiency or insufficiency, magnesium deficiency, acute pancreatitis, or several other conditions. Symptoms of hypocalcemia most commonly include paresthesia, muscle spasms or cramps, tetany, numbness, and in severe cases, seizures. Higher than normal calcium levels, or hypercalcemia, may be due to hyperparathyroidism, tuberculosis, or drug-induced secondary to diuretics, calcium-containing antacids, or excess vitamin D intake. Hypercalcemia also raises suspicion for malignancy, especially metastatic breast or lung cancer or multiple myeloma. Symptoms of hypercalcemia can include excessive thirst, frequent urination, bone pain, muscle weakness, confusion, fatigue, or rarely, palpitations or cardiac arrhythmias. It is important for nurses to understand that calcium in the blood is bound to albumin. Therefore, the total calcium level reported may be an inaccurate representation of the free (ionized) calcium in patients who have a high or low albumin level. The accurate calcium level can be determined in conjunction with the patient’s albumin level by using the corrected calcium formula listed in Figure 1 (Goltzman, 2020).
Chloride and Bicarbonate
Chloride helps to regulate fluid balance within the body, and bicarbonate provides information regarding the acid-base status. These two values demonstrate an inverse relationship and are most useful when evaluated together, as well as in conjunction with the anion gap. The anion gap is a calculated result that measures how much acid is in the blood, which provides useful information for delineating the etiology of acid-base disturbances. These tests help to distinguish between respiratory alkalosis (acute versus chronic) and metabolic acidosis (Bakerman et al., 2014).
While the electrolyte panel provides important information regarding the renal function, three tests within the CMP are explicitly directed toward evaluating the health status and functioning of the renal system: blood urea nitrogen (BUN), creatinine, and estimated glomerular filtration rate (eGFR) (Bakerman et al., 2014).
Urea nitrogen is a normal waste product generated from the breakdown of dietary protein within the liver. It is released into the blood and circulates until it is filtered by the kidneys and excreted via the urine. The BUN is a measure of the amount of waste products in the blood. The BUN increases when the kidneys are not functioning properly but is most commonly elevated to dehydration. Patients who demonstrated elevated BUN levels should be counseled on the importance of staying consistently well hydrated and increasing oral fluid intake. Low BUN levels are uncommon and may be related to overhydration, though this is rare, or due to an underlying medical condition such as liver disease (Bakerman et al., 2014).
Creatinine is a chemical waste byproduct of creatinine phosphate that serves an essential role in creating muscle energy. Formed primarily in the liver, creatinine is transported to the muscles where it is phosphorylated into creatinine phosphate. Creatinine phosphate acts as a storage for muscle energy, until it is broken down and excreted by the kidneys. High creatinine levels are generally an indication of kidney dysfunction (Bakerman et al., 2014).
The eGFR is the most sensitive test to measure how well the kidneys are functioning and is used to stage existing kidney disease. The eGFR reflects the level of creatinine in the blood, utilizing a specific formula to calculate a result based on the patient's age, gender, and body size. The normal eGFR in adults is more than 90, but as demonstrated in Figure 2, a normal eGFR is commonly reported as greater than 60 ml/min/1.73 m2 (National Kidney Foundation [NKF], 2018).
Liver Function Tests (LFTs)
LFTs, often called the hepatic panel, is a group of tests that measures specific enzymes and proteins in the blood and provide information about the liver. As noted above, patients may be asked to fast for at least eight hours prior to having LFTs performed, as a higher than normal level can be related to liver disease, bile duct problems, or alcohol abuse. Patients may also be advised to avoid alcohol and certain prescription drugs the day prior to the test as they can affect the results (Murali & Carey, 2017).
Bilirubin is the normal byproduct of the breakdown of RBCs, and it is reported in three values: total, direct, and indirect. Total bilirubin is a combination of both direct and indirect bilirubin values. Indirect (unconjugated) bilirubin is the amount of bilirubin that is bound to albumin and circulating through the bloodstream. Indirect bilirubin is absorbed by the liver where it is conjugated with glucuronic acid. Direct (conjugated) bilirubin is then secreted into bile and transported through the gallbladder and digestive tract before being excreted. Hyperbilirubinemia occurs when indirect bilirubin builds up in the bloodstream. Since bilirubin is a yellowish substance, pathologic accumulation in the blood can lead to jaundice, or yellowing of the skin and eyes (scleral icterus). Hyperbilirubinemia can cause abdominal pain, fevers, chills, systemic pruritus, dark-colored urine, fatigue, weakness, nausea, or vomiting. When evaluating bilirubin values, it is essential to consider the patient's age and other health conditions. At least 90% of bilirubin should be indirect (unconjugated) in healthy adults. Direct (conjugated) bilirubin is considered the most sensitive test when evaluating for liver disease, so elevated levels of direct bilirubin are often accompanied by elevated liver enzymes. When direct bilirubin is elevated, it can spill over into the urine (Murali & Carey, 2017).
The alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) tests are used to further evaluate the function of the liver and to detect liver injury or disease. Elevations are most commonly drug-induced due to lipid-lowering statin therapy, chemotherapy, or numerous other medications processed through the liver.
ALT. ALT is an enzyme primarily produced by the liver that is found in high concentrations within the hepatocytes (liver cells). The ALT is considered the most specific test when evaluating for liver injury, as it is a direct indication of hepatocellular injury.
AST. AST is an enzyme found in RBCs and muscle tissue, as well as vital organs such as the heart, liver, kidneys, and pancreas. While elevations in AST can infer liver damage, they can also be seen in cases of acute cardiac muscle injury (i.e., myocardial infarction) or skeletal muscle injury.
ALP. ALP is an enzyme that is concentrated within the liver, bile duct, and bone cells. Elevations in ALP can indicate liver damage or bone problems such as rickets, Paget's disease, or the presence of cancer in the bones (primary bone tumors or metastatic bone lesions). When ALP is elevated with regards to liver pathology, it is primarily in response to cholestasis (a decrease in bile flow due to post-hepatic or obstructive jaundice) (Bakerman et al., 2014; Murali & Carey, 2017).
Lactate Dehydrogenase (LDH)
LDH, also known as lactic acid dehydrogenase, is an enzyme in the blood that plays an essential role in generating energy within the body. LDH is widespread throughout nearly all body tissues; when tissues become damaged, they release LDH into the blood, making it a nonspecific marker of tissue damage and inflammation (MedLinePlus, 2020b).
Protein is necessary for cellular growth, development, and overall health. The total protein is the sum of two circulating proteins in the blood: albumin and globulin.
Albumin. Albumin is produced within the liver and is the predominant protein within the bloodstream, accounting for approximately 60% of the total protein. The albumin provides important information about nutritional status as hypoalbuminemia (decreased albumin level) is commonly seen in malnutrition and malabsorptive disorders. The albumin also serves as a marker of liver and kidney damage, as albumin production within the liver is decreased in the presence of severe liver disease or inflammation. Typically, the only clinically significant cause of increased albumin levels is dehydration.
Globulins. Globulins comprise the remaining 40% of the protein in the bloodstream; they assist the immune system with fighting infection and transporting nutrients. Globulins may increase in the presence of infection, inflammation, or cancer.
A-G ratio. The A-G ratio refers to the ratio of albumin in relation to the amount of globulin present in the blood. It is calculated automatically by many labs and reported in CMP results. In healthy adults, the A-G- ratio should be slightly higher than 1. Higher than normal A-G ratios are often due to the underproduction of globulins and can be caused by hypothyroidism, glucocorticoid excess, blood cancer, or genetic disorders. Low A-G ratios may be a sign of an autoimmune disorder, cirrhosis, or kidney disease (Bakerman et al., 2014; Murali & Carey, 2017).
A lipid panel (or lipid profile) measures the amount of cholesterol and triglycerides within the blood. Lipids are fats and fatty substances within the blood that serve as sources of energy and are required by the body to maintain the health of cells and specific cellular functions. When cholesterol is present in excess, it can lead to atherosclerosis or the buildup of fatty plaque within the arteries. Plaque growth within the arteries leads to damage, narrowing, or blockage of the arteries and blood vessels, which can develop into coronary artery disease (CAD) and serious cardiovascular consequences including myocardial infarction (heart attack) and stroke (Mayo Clinic, 2018b).
Hyperlipidemia, or high cholesterol levels, is considered a significant risk factor for cardiovascular and blood vessel disease, but this usually do not cause any warning signs or symptoms. Therefore, the lipid panel provides valuable information regarding a patient's risk for atherosclerosis and is also performed when monitoring response to lipid-lowering therapy. As demonstrated in Table 4, a standard lipid panel includes total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. Since dietary intake can impact the lipid panel results, patients should be advised to fast for at least eight hours prior to the test. Patients should also be advised that they can take their usual medications with water only. The reference ranges listed in Table 4 are values based on fasting.
HDL-C is referred to as the good cholesterol, as high levels are considered cardioprotective and associated with a reduced risk of cardiovascular and blood vessel disease. Since HDL-C takes up excess cholesterol and carries it to the liver for removal, the higher the HDL-C, the better. Alternatively, decreased levels of HDL-C are associated with an increased risk of cardiovascular disease, especially in males. The LDL-C is considered the bad cholesterol, as high levels are linked to increased cardiovascular damage, atherosclerosis, and associated morbidity and mortality. LDL-C deposits excess cholesterol in the walls of blood vessels. In general, the higher the LDL-C, the greater the risk for fatty plaque buildup within the arteries. The basis for cholesterol management is centered on lipid-lowering agents and diets targeting a reduction in the LDL-C level. Similar to LDL-C, high triglyceride levels are associated with an increased risk of cardiovascular and blood vessel disease (Bakerman et al., 2014).
Nurses should educate patients that elevated LDL-C and triglycerides levels are closely linked to unhealthy lifestyle choices such as a poor diet (excess intake of fatty foods and simple sugar), a sedentary lifestyle (lack of physical activity), obesity and excess weight, smoking or exposure to tobacco smoke, and excessive alcohol intake. Nurses should encourage patients to engage in lifestyle changes centered on healthy eating, routine physical activity, as well as smoking cessation to reduce cholesterol levels. In some cases, medication therapy may still be required to achieve cholesterol targets (American Heart Association [AHA], 2017). Hyperlipidemia and type 2 diabetes mellitus (T2DM) commonly occur together, with lipid abnormalities affecting up to 70% of patients with T2DM. Therefore, the American Diabetes Association (ADA) recommends patients with T2DM strive for lower target cholesterol levels than those listed in Table 4. Optimal cholesterol values for patients with T2DM include:
- LDL-C: less than 100 mg/dL,
- HDL-C: above 40 mg/dL (men) or above 50 mg/dL (women), and
- Triglycerides less than 150 mg/dL (ADA, 2020).
Triglycerides can also be elevated in certain disease processes or due to a strong family history. In some cases, elevations may be related to a genetic condition known as familial hypercholesterolemia (FH) which impairs the body's ability to remove excess LDL cholesterol from the bloodstream (The FH Foundation, n.d.).
Thyroid Function Tests (TFTs)
TFTs are performed to determine if the appropriate amount of thyroid hormone is present within the bloodstream. TFTs may be ordered individually or collectively as a group (thyroid panel). The thyroid gland has several important functions and is responsible for maintaining various aspects of homeostasis within the body, including regulating body temperature, metabolism, and calcitonin. It also impacts the way tissues outside the thyroid are functioning. There are two primary hormones generated by the thyroid gland: thyroxine (T4) and triiodothyronine (T3). T4 contains four iodine atoms and is converted to T3, which contains three iodine atoms and has a stronger and more rapid metabolic action than T4. The amounts of T4 and T3 secreted into the blood are regulated by the pituitary gland. As demonstrated in Figure 2, the release rate of T3 and T4 is controlled by the anterior pituitary gland and hypothalamus, which acts as a sensory controller. The process is initiated by the hypothalamus, which releases thyrotropin-releasing hormone (TRH). TRH is essentially the first thyroid messenger signal, as it is responsible for stimulating the release of thyroid-stimulating hormone (TSH) from the anterior pituitary gland. TSH is critical in modulating the release of T4, which is then converted to T3. 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. The pituitary is constantly measuring the amount of T3/4 and responding to changes to maintain an appropriate balance. If the pituitary senses that there is not enough T4, it will ramp up the TSH production, signaling the thyroid gland to produce more T4. Once the level of T4 reaches a specific level within the blood, TSH production decreases (American Thyroid Association [ATA], n.d.).
Thyroid disease is most commonly characterized as overactive (hyperthyroidism) or underactive (hypothyroidism). Hypothyroidism is classified as primary or secondary; primary is much more common. Hashimoto's thyroiditis, an autoimmune disease that causes the body to attack the thyroid gland, is the most common cause of primary hypothyroidism in the US. Secondary hypothyroidism is caused by the failure of the pituitary gland or hypothalamic disease, whereby the body does not make adequate amounts of TSH to stimulate the release of T3/4. Hyperthyroidism is characterized by the increased production and secretion of T3/4 from the thyroid gland and includes three basic subtypes: thyrotoxicosis, Grave's disease, and subacute thyroiditis. Thyrotoxicosis refers to a clinical disorder in which there is excess circulating T3/4, irrespective of the source (Yani, 2019). Graves' disease is an autoimmune disorder that leads to hyperthyroidism, as the body attacks the thyroid gland, inducing overactivity. While it carries many of the same symptoms of hyperthyroidism, Grave's disease has the characteristic physical signs including exophthalmos, prominence of the eyes, and extraocular muscle weakness (DeGroot, 2016). Table 5 outlines the most common clinical features of hypothyroidism and hyperthyroidism.
A thyroid panel is typically comprised of three main tests: free T4 (thyroxine [FT4]), free T3 or total T3 (triiodothyronine), and TSH, which are described in Table 6. Patients are not advised to fast prior to the test, as some clinical studies have demonstrated that early morning fasting leads to higher TSH levels compared to tests performed in the afternoon on patients who did not fast. Prior to TFTs, patients should be screened for any iodine contrast administration within the prior 10 days leading up to the test, as iodine is taken up by the thyroid and can skew results. TFT results can be altered in patients who are pregnant or those who take medications containing estrogen such has oral contraceptives (birth control pills) or hormone replacement therapy. Patients should also be counseled to stop biotin (an over-the-counter supplement rich in B vitamins) at least two days prior to having their TFTs performed, as this supplement is known to interfere with the accuracy of TFT results (ATA, n.d.).
TSH is the first-line screening test for patients with suspected thyroid dysfunction. The level of circulating TSH in the blood is used to determine if the thyroid is functioning normally, or if it is overactive or underactive (US Preventative Services Task Force [USPSTF], 2015). If the TSH is high, it indicates that the thyroid gland is not producing enough T3/4, which would raise the clinical suspicion for primary hypothyroidism. Conversely, if the TSH is low, it usually suggests that the thyroid is producing too much T3/4, raising clinical suspicion for hyperthyroidism. Less commonly, a low TSH level may be caused by an abnormality in the pituitary gland or hypothalamic disease, preventing the body from making adequate amounts of TSH to stimulate the release of T3/4 (ATA, 2019).
T4 can be measured as total T4 or FT4. Total T4 measures both the free and the bound hormone available, whereas FT4 is a measure of the T4 hormone that is freely circulating in the blood and available to be used. FT4 is more commonly performed as it provides the most useful insight into the severity of an abnormal TSH level. FT4 is most accurate when performed in conjunction with the TSH level, and therefore these tests are usually ordered together (ATA, 2019).
T3 can be evaluated as either total T3 or free T3; however, free T3 is less reliable. Patients with an overactive thyroid have elevated T3 levels. T3 testing is not clinically useful in hypothyroidism, as both the TSH and FT4 are typically abnormal earlier on in the course of the condition than the T3 level. Reverse T3 is another thyroid test that is less commonly performed. It is a measure of the inactive thyroid hormone, and it is also only indicated in the evaluation of patients with suspected hyperthyroidism (ATA, 2019).
Thyroid Antibody Tests
Thyroid antibody tests are a separate subtype of TFTs that measure the level of the blood's thyroid antibodies. Thyroid peroxidase antibody, otherwise called antithyroid peroxidase antibodies (TPO), is one of the most common antibody tests currently used in clinical practice. It is performed to determine if hyperthyroidism is autoimmune, such as in Grave's disease or Hashimoto disease (ATA, n.d.).
Fasting Blood Glucose (FBG) and Glycated Hemoglobin (HbA1C)
FBG and HbA1C are used to diagnose and monitor diabetes. The FBG is one of the most common routine tests. The test can be performed by drawing a blood sample or as a simple fingerstick with a glucometer machine. Patients should be advised to fast for at least eight hours prior to having the FBG test performed to ensure accuracy of the results. Patients may drink water and take any prescription medications but should not take anything else by mouth (American Association of Clinical Chemistry [AACC], 2020). The normal FBG should range between 70–99 mg/dL. According to the ADA (n.d.), diabetes occurs when the FBG is 126 mg/dL or higher, whereas an FBG of 100 mg/dL to 125 mg/dL is considered prediabetes. Prediabetes is the precursor to diabetes, in which the blood glucose levels are higher than normal but not high enough to meet the diagnostic classification of diabetes. The HbA1C is a measure of the average blood glucose levels over the past three months. The patient is not required to fast prior to the HbA1C test. The normal HbA1C for non-diabetic adults should be less than 5.7%. Diabetes is considered when the HbA1C is 6.5% or higher, whereas an HbA1C of 5.7% to 6.4% is considered prediabetes (ADA, n.d.).
A coagulation profile measures the blood's clotting capacity and typically includes the prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), platelets, and fibrinogen. These tests are commonly performed routinely prior to surgery to ensure patient safety. They may also be performed to evaluate why a patient is experiencing abnormal bruising or bleeding, or as a screening test for an underlying blood or blood clotting disorder. The normal values for a coagulation profile are listed in Table 7. PT is measured in seconds and refers to the amount of time it takes for the plasma portion of the blood to clot. The INR is a standardized number that is calculated from the PT result (AACC, 2019). Usually, the INR is reported and monitored in patients treated with blood-thinning medications, such as warfarin (Coumadin). Patients who are prescribed warfarin (Coumadin) are required to undergo routine blood tests at least monthly, but sometimes testing may occur more frequently, such as twice weekly. The testing ensures that the patient’s blood clotting time is within a safe and effective range, as the warfarin (Coumadin) dose is adjusted according to the INR. Higher than normal INR levels indicate a higher risk for bleeding events due to the body's impaired ability to clot blood. While on warfarin (Coumadin), it is essential that the INR does not exceed therapeutic thresholds, otherwise the risk for bleeding heightens. Similarly, it the patient’s INR is too low, blood clots may not be prevented. For most patients on warfarin (Coumadin) therapy, an INR range of 2.0 to 3.0 is generally considered an effective therapeutic range (National Blood Clot Alliance [NBCA], n.d.). The aPTT test is performed alongside the PT/INR in patients with suspected bleeding or blood clotting disorders. While the PT test assesses how well all of the coagulation factors in the extrinsic and common pathways of the coagulation cascade are functioning collectively, the aPTT evaluates the clotting factors within the intrinsic and common pathways (AACC, 2019).
American Association of Clinical Chemistry. (2019). Prothrombin time and international normalized ratio (PT/INR). https://labtestsonline.org/tests/prothrombin-time-and-international-normalized-ratio-ptinr
American Association of Clinical Chemistry. (2020). Glucose tests. https://labtestsonline.org/tests/glucose-tests
American Board of Internal Medicine. (2019). ABIM laboratory test reference ranges - January 2019. https://www.abim.org/~/media/ABIM%20Public/Files/pdf/exam/laboratory-reference-ranges.pdf
American Diabetes Association. (n.d.). Diagnosis. Retrieved May 29, 2020, from https://www.diabetes.org/a1c/diagnosis
American Diabetes Association. (2020). Cardiovascular disease and risk management: Standards of medical care in diabetes-2020. Diabetes Care, 41(Suppl. 1), S111-S134. https://doi.org/10.2337/dc20-s010
American Heart Association. (2017). Causes of high cholesterol. https://www.heart.org/en/health-topics/cholesterol/causes-of-high-cholesterol
American Thyroid Association. (n.d.). Thyroid function tests. Retrieved May 29, 2020, from https://www.thyroid.org/thyroid-function-tests/
American Thyroid Association. (2019). Thyroid function tests FAQ. https://www.thyroid.org/wp-content/uploads/patients/brochures/thyroid_function_tests_faq.pdf
Bakerman, P., Strausbauch, P., & Bakerman, S. (2014). Bakerman’s ABC’s of interpretive laboratory data. (5th ed.). Interpretive Laboratory Data, Inc.
BCGuidelines. (2018). Thyroid function testing in the diagnosis and monitoring of thyroid function disorder. https://www2.gov.bc.ca/assets/gov/health/practitioner-pro/bc-guidelines/thyroid-function-testing.pdf
Cleveland Clinic. (2018). High hemoglobin count. https://my.clevelandclinic.org/health/diseases/17789-high-hemoglobin-count
DeGroot, L. J. (2016). Diagnosis and treatment of graves’ disease. Endotext [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK285548/
The FH Foundation. (n.d.). What is familial hypercholesterolemia? Retrieved May 30, 2020, from https://thefhfoundation.org/familial-hypercholesterolemia/what-is-familial-hypercholesterolemia
Goltzman, D. (2020). Diagnostic approach to hypocalcemia. UpToDate. https://www.uptodate.com/contents/diagnostic-approach-to-hypocalcemia#H2618010259
Haggstrom, M. (2009). Thyroid hormones [image]. https://commons.wikimedia.org/wiki/File:Thyroid_system.svg
The Joint Commission. (2020). National patient safety goals effective July 2020 for the laboratory program. https://www.jointcommission.org/-/media/tjc/documents/standards/national-patient-safety-goals/2020/npsg_chapter_lab_jul2020.pdf
Longo, D. L. (2019). Harrison’s hematology and oncology. (3rd ed.). McGraw-Hill Education.
Mayo Clinic. (2018a). Complete blood count (CBC). https://www.mayoclinic.org/tests-procedures/complete-blood-count/about/pac-20384919
Mayo Clinic. (2018b). Heart disease. https://www.mayoclinic.org/diseases-conditions/heart-disease/symptoms-causes/syc-20353118
MedlinePlus. (2020a). How to understand your lab results. https://medlineplus.gov/lab-tests/how-to-understand-your-lab-results/
MedlinePlus. (2020b). Lactate dehydrogenase (LDH) test. https://medlineplus.gov/lab-tests/lactate-dehydrogenase-ldh-test/
Murali, A. R., & Carey, W. B. (2017). Liver test interpretation – approach to the patient with liver disease: A guide to commonly used liver tests. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/guide-to-common-liver-tests/
National Blood Clot Alliance. (n.d.). INR self-testing. Retrieved June 21, 2020 from https://www.stoptheclot.org/about-clots/blood-clot-treatment/warfarin/inr-self-testing/
National Kidney Foundation. (2018). Estimated glomerular filtration rate (eGFR). https://www.kidney.org/atoz/content/gfr
Pagana, K. D., & Pagana, T. J. (2018). Mosby’s manual of diagnostic and laboratory tests. (6th ed.). Elsevier.
Selchick, F. (2020a). Laboratory report flagging abnormal results [image].
Selchick, F. (2020b). Comprehensive metabolic panel (CMP) [image].
US Preventative Services Task Force. (2015). Screening for thyroid dysfunction: Recommendation statement. American Family Physician, 91(11). 790A-790F. https://www.aafp.org/afp/2015/0601/od1.pdf
Yani, H. (2019). Differential diagnosis of thyrotoxicosis. Journal of Endocrinology & Metabolism, 9(5), 127-132. https://doi.org/10.14740/jem600