Secondary Logo

Journal Logo

Special Communication

Thyroid Function and Nutrient Status in the Athlete

Larson-Meyer, D. Enette PhD, RD, FACSM; Gostas, Demetre E. MS

Author Information
Current Sports Medicine Reports: February 2020 - Volume 19 - Issue 2 - p 84-94
doi: 10.1249/JSR.0000000000000689
  • Free

Abstract

Introduction

Thyroid disorders are common in the United States and worldwide and affect an estimated 5% to 6% of the U.S. population (1). While thyroid disorders may be caused by a number of underlying pathologies, autoimmune disorders are a common cause in the United States and can result in both hypothyroidism and hyperthyroidism. Thyroid health and the pathogenesis of thyroid disorders also are influenced by dietary factors (2). These include the intake/status of key nutrients (iodine, selenium, iron, vitamin D, and total energy) and exposure to dietary goitrogens (2,3) and food- and water-born contaminants, which can impair thyroid hormone synthesis (3,4). Intense exercise training also can have an impact but its influence and importance are not well understood. The development of thyroid related disorders has the potential to impact health and peak performance in athletes and active individuals (5). This article reviews thyroid function and general pathologies in active populations and discusses how to look for thyroid-related issues and how to perform dietary, anthropometric, biochemical, and clinical assessment of thyroid function in the clinical, wellness, and sports settings.

Thyroid Hormone Synthesis

Thyroid hormone is synthesized by the follicular cells of the thyroid gland, which sits just below the Adams apple (laryngeal prominence). The thyroid consists of two lobes joined by a band of tissue called the ishmus. In its normal state, the thyroid is approximately 2 to 2.5 cm in width and depth and 4 cm in length (6) and weighs 15 to 20 g. Thyroid hormone is unique in that the structure of thyroxine (T4) and triiodothyronine (T3) contain significant amounts of the trace mineral iodine (Fig.). Synthesis also requires the nonessential amino acid tyrosine (2).

Figure
Figure:
Summary of the steps involved in thyroid hormone synthesis including: (a) iodide transport into the thyroid follicular cell and colloid space; (b) iodination (or organification) of tyrosine residues of thyroglobulin; (c) coupling of thyroid hormone precursors MIT and DIT; and (d) mobilization and release of thyroid hormone. Multiple steps in this process are mediated by the enzyme TPO including organification of thyroid and coupling of thyroid hormone precursors MIT and DIT to form T3 and T4.

Biosynthesis of thyroid hormone is dependent on the hypothalamic-pituitary-thyroid axis, as well as peripheral tissues, and is controlled by specific feedback mechanisms. Synthesis is stimulated by release of hypothalamic thyrotrophic-releasing hormone (TRH) which acts on the thyrotrope cells of the anterior pituitary to stimulate secretion of thyroid-stimulating hormone (TSH). In the thyroid gland, TSH binds to the G protein-coupled TSH receptor and stimulates the synthesis and secretion of thyroid hormone (6,7).

The initial step in the synthesis of thyroid hormone involves transport of plasma iodide (I) into the thyroid follicular cells by the sodium iodide (Na+/I) symporter (NIS) (6,7)(Fig.). This ATP-dependent process is linked to cotransport of sodium and occurs against an electrochemical gradient (8). Uptake of iodine into the thyroid (9) and its organification, however, are somewhat “autoregulated” and occurs in proportion to the stores of inorganic iodide within the thyroid cell (e.g., the (Wolff Chaikoff effect) (6). This assures maximal uptake when iodine stores are low, and decreased uptake when stores are replete. TSH further mediates the organification process and incorporation of iodide into the tyrosine residues via the heme-containing enzyme thyroid peroxidase (TPO) in a reaction that requires hydrogen peroxidase. This occurs in the follicular colloid on the structure of tyrosine-rich thyroglobulin, which serves as a “scaffold” for thyroid hormone synthesis and is dependent on the degree of TSH stimulation.

The majority of thyroid hormone produced by the thyroid is T4 rather than more biologically active T3. Newly synthesized thyroid hormone is stored in the thyroid colloid space which has a considerable reserve of thyroid hormone. This reserve provides prolonged protection of circulating hormone to maintain the euthyroid state for approximately 50 d (6). Release of thyroid hormone into the bloodstream involves formation of phagolysosomes and proteolysis of the thyroglobulin molecule to release T4 and T3. In the blood, both forms are bound to proteins including thyroid-binding globulin as well as albumin and transthyretin (6,10,11). It is estimated that only 0.03% of circulatory T4 and 0.3% of T3 are in biologically active free form (10). The binding proteins serves to both maintain serum free T4 and T3 concentrations within a narrow range and ensure both are immediately and continuously available to tissues (6).

The final step in the biosynthetic process involves deiodination of T4 to T3 in peripheral tissues by various selenium-containing deiodinases. Type 1 deiodinase (DIO1) is located in the liver, kidney and thyroid and is primarily responsible for generating systematic T3, whereas type 2 deiodinase (DIO2) is found in the central nervous system, pituitary, thyroid, heart (6), and skeletal muscle (12) and serves as a source for local tissues (6). DIO2 has a higher affinity for T4 than DIO1, and a shorter half-life (20 to 30 min vs 12 h) (6). DIO2 also is located intracellularly and thereby provides newly formed T3 immediate nuclear access. DIO2 is thought to be especially important for regulating the hypothalamic-pituitary-thyroid axis as its activity increases in response to decreasing serum T3 concentrations, such as with iodine deficiency. A third deiodinase (type 3, DIO3) present in liver, CNS (6), and skeletal muscle (12) removes iodine from T4 at the inner rather than outer ring and produces the biologically inactive isomer known as reverse T3 (rT3). DIO3 enzymatic activity is enhanced in conditions of thyroid hormone excess and decreased in states of thyroid hormone deficiency and also may be altered with iodine deficiency and malnutrition (6). The balance between T3 and rT3 production helps dictate overall thyroid activity. To complete the feedback loop, T3 feeds back directly to the pituitary to inhibit TSH secretion, whereas T4 provides indirect feedback following conversion to T3.

Function of Thyroid Hormone

Thyroid hormone functions to help regulate many metabolic functions of the body (13,14), including basal metabolism, body temperature, heart rate, protein synthesis, carbohydrate and fat metabolism, and skeletal muscle bioenergetics, myogenesis and repair. Specifically, thyroid hormone acts by altering the expression of target genes through interaction with the thyroid hormone nuclear receptor (TR) to alter protein synthesis and substrate turnover (6,15). In most cells, circulating T4 and T3 enter by diffusion but this process occurs by active transport in the brain (16). As previously mentioned, T3 also is produced locally from T4 deiodination via DIO2 (6). The metabolic effects of thyroid hormones ultimately result when T3 binds to occupy specific sites on the nuclear TR. This binding allows the T3-TR complex to bind to regulatory regions contained in genes that are responsive to thyroid hormone. Empty TR (without T3) bind to the nuclear receptor co-repressor as well as to these same regulatory regions but result in repression of gene expression. While thyroid hormone is important for virtually all tissues, tissue-specific actions are determined by variations in local T3 production and content of the alpha and beta TR isoforms (15,17).

Thyroid Dysfunction

Hypothyroidism

Hypothyroidism is a state of thyroid hormone deficiency, which results in an overall slowing of metabolic processes (10). Well recognized general signs and symptoms include: fatigue, weight gain, cold intolerance, bradycardia, and muscle cramps and weakness. Hypothyroidism is commonly defined as either subclinical or overt and caused by a dysfunction at the thyroid (primary), pituitary (secondary) or hypothalamus (tertiary) (Table 1). Primary overt hypothyroidism accounts for the majority of cases and refers to thyroid gland failure and is characterized by low free T4 along with elevated TSH (typically >10 mU·L−1) (10) due to reduced negative feedback of T4 and T3. Subclinical hypothyroidism refers to an elevated serum TSH but normal free T4 concentration (10). Subclinical hypothyroidism is more prevalent and accounts for the majority of cases. For example, the National Health and Nutrition Examination Survey (20) report that 4.3% of individuals had subclinical hypothyroidism (TSH > 4.5 mU·L−1) and 0.3% had overt disease whereas the Colorado Thyroid Disease Prevention study (21) found that 8.5% had subclinical disease (TSH > 5.0 mU·L−1) and 0.4% had overt disease. The prevalence of subclinical hypothyroidism, however, varies according to the reference range of TSH as well as with geographic and demographic factors (22).

Table 1
Table 1:
Thyroid disorders and expected general laboratory.

Secondary and tertiary hypothyroidism is characterized by insufficient TSH or TRH secretion by the pituitary or hypothalamus, respectively (23). These forms are not discussed in much detail in this review both because they are much less common than primary hypothyroidism (24) and not induced by diet or intense physical effort (24,25). A risk factor for central hypothyroidism, however, is head and neck injury (25,26) which could potentially be due to sport-injury related.

The most common cause of primary hypothyroidism worldwide is iodine deficiency due to inadequate daily intake (27). This impairs thyroid hormone synthesis and stimulates TSH, which can lead to goiter formation and/or hypothyroidism (28). In the United States and other iodine-sufficient areas of the world, the most common cause of hypothyroidism is a chronic autoimmune thyroiditis more commonly called Hashimotos thyroiditis (HT) (10). In HT, the immune system attacks and destroys specific proteins in the thyroid rendering a large portion of the gland dysfunctional over the years. The most frequent immune target is TPO but autoantibodies to thyroglobulin are often present (18,29). Reversal of the disease may be possible if autoimmunity is caught early and the triggers are removed (2).

Salt fortification has nearly eliminated iodine deficiency as the key cause of hypothyroidism in many countries; however, certain subpopulations are at risk due to deficiency of iodine (30) or other nutrients of importance to thyroid function (Table 2). This includes vitamin D deficiency, which is linked to autoimmune thyroid disease (AITD) (31,32) and can manifest as hypothyroidism or hyperthyroidism. Since nutrient status is not routinely assessed as part of the evaluation of hypothyroidism in the United States, it is possible some cases of hypothyroidism are due to iodine, iron, or selenium deficiency or brought on by vitamin D deficiency (2) and are treated unnecessarily with lifelong synthetic thyroid hormone replacement (see Treatment of Thyroid Disorders).

Table 2
Table 2:
Specific nutrients required for thyroid function.

Euthyroid sick syndrome

Another important but less frequently mentioned disease of hypothyroid is commonly referred to as euthyroid sick syndrome, low T3 syndrome, or nonthyroid illness (6). This condition is associated with nutritional deprivation or illness that results in decreased peripheral conversion of T4 to T3 and increased conversion of T3 to rT3 (2,6) (Table 1), and are likely driven by changes in activity of different deiodinases (6). TSH concentration initially remains in the normal range but is inappropriately low in the context of reductions in circulating T3. Such alterations are thought to have little medical consequence (10) and may be viewed as beneficial for energy- and nitrogen-sparing adaptation (6). In the sports arenia, euthyroid sick syndrome may occur in association with low-energy intake (33), anorexia nervosa (34), and overtraining (35) as well as with thermal injury or postsurgical stress, although research in this area is needed. Euthyroid sick syndrome is thought to be reversible if the underlying problem is resolved (2,10).

Primary hyperthyroidism

Hyperthyroidism is a state of thyroid hormone excess, which results in a hypermetabolic state. Well-recognized general signs and symptoms include fatigue, unexplained weight loss, heat intolerance, tachycardia, muscle weakness, and tremor. Hyperthyroidism is overall less prevalent than hypothyroidism and occurs in an estimated 1.3% of the population (1,20). Primary hyperthyroidism, in which the thyroid produces too much thyroid hormone, manifests with characteristic elevated T4 and low TSH concentrations (19) (Table 1). Secondary hyperthyroidism may result from a rare TSH-producing pituitary adenoma (36), but there are no known causes of tertiary (hypothalamic) hyperthyroidism. Like hypothyroidism, hyperthyroidism may be overt (low or undetectable serum TSH and elevated T3 and/or free T4 concentrations) or subclinical (low or undetectable serum TSH and normal T3 and T4) but the disease likely represents a continuum (19).

The most common cause of hyperthyroid disease in the United States and elsewhere is another autoimmune disorder referred to as Graves' disease (GD) (19,37,38). GD is more prevalent in women compared with men and is thought to be triggered by environmental and genetic factors. With GD, however, the implicated autoimmune reaction is directed against the TSH receptor (19). Although these antibodies may be classified as stimulating, blocking, or neutral (18), the offending immunoglobulin in GD stimulates the TSH receptor, increasing thyroid hormone production and release (19). A low serum TSH, presence of TSH autoantibodies (sensitivity/specificity for GD of 97% and 99%, respectively ([39])), and radioactive iodine uptake scan help determine the diagnosis of GD (19). Being that GD is fairly common in general population (1), it is not unheard of in the athlete (40). Although symptoms of hyperthyroid and GD vary widely, they can mimic overtraining syndrome or chronic fatigue, making it important to consider GD in the workup of athletes who report fatigue, depression, muscle weakness or menstrual irregularity (40). Other possible triggers of hyperthyroidism include stress, infection, low vitamin D status, excess iodine, gluten, environmental toxins, or trauma to the thyroid (2,41). Interestingly, the triggers of both hypothyroid and hyperthyroid AITD, including GD and HT, are similar despite different manifestations in the disease state (hypothyroidism vs hyperthyroidism).

Prevalence of Thyroid Disorders in Athletes

Little information is available on the specific prevalence of thyroid-related disorders in athletes and whether it differs from that of the general population. A handful of studies over the past 40 years, however, have brought to light the possibility that strenuous exercise or over-training may induced hypothyroidism, which may have both acute (42,43) and chronic implications and result in thyroid replacement therapy (44). Acutely, transient nonpathological hypothyroidism has been identified following both intense (43,45) and moderate, prolonged exercise (i.e., military training) (42) that resulted in suppressed free T3 and elevated rT3 (35). One recent study found that a 45-min bout of intensive interval training produced a suppression of peripheral conversion of T4 to T3 at 12 h postexercise and an elevated rT3 that was not evident following steady state running (35). More chronically, a study in highly trained female endurance athletes with and without amenorrhea found significantly reduced concentrations of free T3 and T4 (with normal TSH) in athletes experiencing amenorrhea for at least 6 months (33). A survey in 1222 female runners observed that 12.2% had been diagnosed with hypothyroidism (44). The risk of diagnosis was threefold higher in those who began running before the age of 10 (44). While the prevalence in this study was higher than that of the general population, it may reflect keener awareness of hypothyroid symptoms among runners and/or the lower threshold for health professionals to administer thyroid replacement to athletes (44). Additionally, there is some indication that T3 is sensitive to short-term weight changes and may be useful for monitoring progress throughout nutritional rehabilitation in individuals with eating disorders (34). Further studies, however, are needed to help clarify the prevalence of thyroid dysfunction in athletes and its influence on athlete training, recovery and performance.

Nutrient Status and Thyroid Function

Iodine

Iodine deficiency is a common nutrition deficiency worldwide (27,46,47) and is the most common cause of primary hypothyroidism in areas without fortified table salt. Although iodine deficiency is thought to be of little public health concern in the United States (48), a high prevalence of suboptimal iodine status and iodine deficiency may exist in the United States and across the globe. At risk individuals include those who do not use iodized salt (30), avoid seafood and/or dairy products (49), obtain a majority of their meat and produce from regions with iodine-poor soil (27), are vegetarian (50,51) or follow a Paleo diet (52). While studies in athletic populations are not available, individual athletes may be prone to low iodine intake for similar reasons (53). Recent emphasis by the American Heart Association to decrease sodium intake to a prudent 1500 mg·d−1 or less (54) may further limit table salt use and negatively impact iodine status (30), even in athletes. Although iodine is found in small concentrations in produce grown in iodine-replete soil, key sources (Table 2) include seafood, seaweed, and dairy products (due to feed supplementation and iodophor sanitizing agents (27). Intake of iodine also is negatively influenced by processed food consumption which typically does not utilize iodized salt (55). Iodine excess, including correction from previous iodine deficiency, also can impair thyroid function but typically only in those with underlying thyroid disorders.

Iron

Iron depletion also is a common nutrient deficiency worldwide and is known to be prevalent among some athlete populations (56–58) with female (56,59,60) and endurance athletes (61) of apparent higher risk. In athletes, iron depletion is most commonly attributed to insufficient energy and/or low intake of iron-rich foods (58) (Table 2) but it also can be impacted by acute inflammation (62), hepcidin response (63), and increased iron losses through gastrointestinal bleeding (64), heavy sweating (65), foot strike or intravascular hemolysis (66), high altitude training, hematuria (67), or heavy menstrual losses in female athletes (61). Although it is well recognized that compromised iron status can limit muscle function and work capacity (58,61), iron deficiency can impair activity of heme-containing TPO and result in increased TSH and decreased T4 and T3 concentrations (68).

Selenium

Most Americans consume adequate dietary selenium. According to data from the National Health and Nutrition Examination Survey (NHANES, 2009–2010), selenium intake is more than sufficient in the American diet and averages 197% of the RDA from food sources alone and 220% of the RDA when dietary supplements is considered (69). While selenium intake is typically higher in adult men and lower in women, it varies across the United States and Canada because of regional differences in selenium soil concentrations and foods consumed (70). Higher concentrations are reported in residents of the Midwestern and Western United States than in the Southern and Northeastern United States (70,71) but transport of food typically has allowed people living in low-selenium areas to obtain sufficient amounts of selenium. Nevertheless, low selenium status is possible in individual athletes.

Selenium is important to thyroid function, serving both as a cofactor in the deiodinase reactions, and as a part of the endogenous antioxidant glutathione peroxidase that protects body tissues from oxidative stress (72) (including exercising muscle and the thyroid). Thus, selenium deficiency may have a profound effect on thyroid hormone metabolism and on thyroid gland health. Data linking selenium deficiency to reduced T3 production in humans is limited (68) which could be due to the difficulty of assessing intake and status (due to poor sensitivity of biochemical markers of selenium status (73). In animals, selenium deficiency is associated with impaired deiodinase activity in the liver and kidney and with reduced T3 concentrations (2). In humans, there is evidence of a linear association between reduced selenium status and lower T3/T4 ratios even among individuals considered euthyroid (based on laboratory parameters) (2). Studies are recognizing that individuals with AITD have low selenium status and that selenium supplementation may be beneficial in the treatment of both HT and GD (72). Selenium supplementation specifically results in decreased TPO antibodies in HT (74) and decreased TSH receptor antibodies and orbitopathy in GD (74,75). Randomized, controlled trials of selenium supplementation in the general population, however, have produced mixed results. In one randomized, double-blind, placebo-controlled trial, 6-month supplementation with 100, 200, or 300 μg·d−1 selenium in 368 older healthy adults improved plasma selenium concentrations but had no effect on thyroid function (76). High levels of selenium also may exert a detrimental influence on thyroid hormone by depressing deiodinase activity (77).

Fasting and protein energy malnutrition

Both energy intake and nutritional status influence thyroid function at the level of TSH secretion (i.e., down regulating the hypothalamic-pituitary-thyroid axis), but also can influence peripheral deiodination, that is, in the case of euthyroid sick syndrome. This is thought to be beneficial in energy sparing (2,6). Initially, DIO1 activity is inhibited (at the expense of maintaining CNS DIO2) which helps keep TSH within the normal range. With prolonged illness or fasting, hypothalamic function and synthesis of plasma protein carriers may be decreased. This leads to decreased free and total T4 and T3 concentrations that are observed along with suppressed resting metabolism (78).

Vitamin D

Vitamin D insufficiency and deficiency is common among certain athletic populations (79) which include those with higher body fat, dark-pigmented skin and who train predominantly indoors. Apart from its role in musculoskeletal health, vitamin D has been increasingly recognized as an important regulator of inflammation and immune modulation with deficiency recognized as a risk factor for a variety of autoimmune endocrine disorders, including AITD (80). An increasing number of studies have observed a higher prevalence of vitamin D deficiency and lower serum vitamin D concentration in patients with AITD, including HT, GD, and postpartum thyroiditis (31,32). A recent meta-analysis confirmed the association between serum vitamin D concentrations and AITD and found that patients with HD were 4.0 times more likely than control patients to have vitamin D deficiency, whereas patients with GD were 3.5 times more likely (32). Another study suggested that even a 5-nmol·L−1 increase in serum 25(OH)D concentration was associated with a 1.62-fold reduction in HT and a 1.55-fold reduction in GD (31). While studies evaluating the benefit of oral vitamin D supplementation or sun exposure to correct deficiencies are limited, a recent analysis of six randomized studies found a benefit of oral supplementation on autoimmunity in individuals with HT (32). For example, studies in patients with HT who were being treated with thyroid replacement (levothyroxine) found that daily supplementation with 2000 IU for 6 months increased serum 25-OH concentrations and reduced titers of antibodies to TPO and thyroglobulin (25). Another study in newly diagnosed patients not yet on thyroid replacement found that a weekly oral dose of 60,000 IU of vitamin D for 8 wk reduced TPO antibodies, and was more effective in patients with mildly elevated TSH concentrations (≤10 mIU·L−1) compared with those with more elevated concentrations (TSH > 10 mIU·L−1 (81). Studies evaluating the effect of vitamin D supplementation in patients with recently diagnosed GD are not yet available.

Dietary goitrogens

Goitrogens are naturally occurring agents found in food and in the environment that interfere with thyroid hormone productions and secretion. Interestingly, goitrogens were first described in 1928 when thyroid gland enlargement was observed in rabbits eating raw cabbage (27). In humans, goitrogens are not generally of concern unless intake is excessive and combined with iodine deficiency (2,27,46). Goitrogens include many cruciferous and other vegetables and soy products (Table 2) (2,27,46). Goitrogens act by inhibiting iodine thyroid transport (via the NIS), iodine oxidation and organification, thyroid hormone coupling and/or proteolysis and hormone release (3). Soybeans also interrupt the enterohepatic cycle of thyroid hormone metabolism (82) and the isoflavones genistein and diadzeine inhibit TPO activity (83). Other flavonoids may have similar antithyroid effects when consumed as isolated or concentrated botanicals (2,46,84) and have the potential to be converted into goitrogenic compounds by gut bacteria (46). The goitrogenic activity of food may vary based on cooking procedures (85).

Environmental contaminants

A number of environmental contaminants also have the potential to increase susceptibility to thyroid related disorders by inducing damage to the thyroid, provoking an autoimmune response or interfering with thyroid production. Several commonly encountered environmental chemicals augment iodine deficiency by competing with transport by the NIS (4). Although the NIS has a high affinity for iodide, anions, including thiocyanate, nitrate, and perchlorate, can compete with and be transported like iodide, thus decreasing intrathyroid iodide concentration. Thiocyanate is found in tobacco smoke (as well as cruciferous vegetables). Nitrate exposure comes from drinking water, processed meats, some root vegetables and even taking sports supplements (4,86,87). Perchlorate (CL04), however, may be the greatest concern (4). Perchlorate is a widespread environmental contaminant used industrially as an oxidizer for rocket fuels and in explosives including fireworks (4). As an inorganic anion, perchloride is 10 to 100 times more potent than iodide and other anions competing for the NIS and high-dose exposure is known to decrease thyroid function (88,89). Data collected from NHANES (2005–2006) found that 83% of 3,262 tap water samples contained perchlorate (87), whereas 74% of foods analyzed as part of the total diet study contained detectable perchlorate (90). The perchlorate content in most water samples, however, was small, and no samples had a perchlorate content above the U.S. EPA drinking water equivalent level (24.5 μg·L−1) (87). Additional data from NHANES found detectable perchlorate in spot urine samples (median urine perchlorate = 3.6 μg·g1 creatinine) that were observed to interfere with thyroid hormone economy even at background exposures (17). More specifically, female participants with lower iodine status and higher urinary perchlorate had higher serum TSH and lower serum T4 concentrations. Although the Environmental Protection Agency took initial steps in 2011 for a regulatory determination for perchlorate in accordance with the Safe Drinking Water Act (91), drinking water remains a potential source of perchlorates. Thus, it is possible that athletes with higher sweat rates and larger fluid volume intakes could be at increased risk for perchlorate exposure depending on their drinking water sources. As with goitrogens, dangers of perchlorate ingestion are evident only when iodine intake is insufficient.

Assessment of Nutrition and Thyroid Status

The assessment and diagnosis of thyroid disorders relies heavily upon laboratory tests. This is due to lack of specificity of typical clinical manifestations that can be highly variable and frequently confused with other health problems (18,24). For example, common symptoms of hypothyroidism including fatigue, cold intolerance, weight gain, constipation, dry skin, and menstrual irregularities, are nonspecific and could be explained by other factors including stress, iron deficiency, poor diet and excess training (73). In contrast, many signs and symptoms of hyperthyroidism can mimic overtraining (40). Although clinical practice guidelines recommend that serum TSH be ordered as the initial biochemical test in those with suspected thyroid disorders (10,18,24,37), diagnostic accuracy improves when free T4 and T3 are assessed at initial evaluation (19,37). Additionally, questions about dietary or environmental components may help identify (or exclude) underlying causes of thyroid malfunction due to nutrient deficiency(s) or environmental factors (2).

The components of a nutrition-focused assessment of thyroid function (that includes evaluation of status of key nutrients that may be responsible for or aggravate thyroid dysfunction) are outlined in Tables 2 and 3 using the A, B, C, D, E frameworks, anthropometrics, biochemical, clinical, diet, and environment (73). Anthropometrics along with weight history are an important part of the nutrition assessment for all athletes (73), but are particularly important in the assessment of thyroid related disorders. A recent unintentional weight gain could be a sign of hypothyroidism, whereas a history of unintentional weight loss could be a sign of hyperthyroidism. Thyroid disorders, however, should not be initially ruled out if weight change is not evident (2).

Table 3
Table 3:
Assessment of thyroid function, status of key nutrients and lifestyle factors important to thyroid health and function.

Biochemical testing for thyroid dysfunction typically begins with a serum TSH concentration because it reflects the body's regulation of thyroid hormone status and is considered the most sensitive marker of thyroid function (10,18). This is dictated by the negative log-linear relationship between serum TSH and free T4 concentrations (96) that permits earlier detection of very small changes in T4 through measurement of reciprocally large changes in serum TSH concentrations (10,18). Presently, however, there is considerable controversy over the appropriate upper limit of normal for serum TSH. While most laboratories have used ~4.5 to 5.0 mU·L−1 as the upper limit of the euthyroid reference range, the National Academy of Clinical Biochemistry has argued for a lower upper limit of 2.5 mU·L−1 (97) based on statistical data norms (95% confidence intervals) collected in rigorously screened euthyroid volunteers. Additional supportive data have observed that having a TSH concentrations greater than 2 mU·L−1 increases the probability of also having elevated thyroid antibodies and a greater 20-year risk of developing overt hypothyroidism (2,98). While further discussion is beyond the scope of this commentary, use of a lowered upper limit could help identify and treat underlying nutritional or environmental factors associated with subclinical hypothyroidism.

Assessment of other thyroid function markers can be ordered simultaneously with or after initial TSH screening (to save on unnecessary laboratory tests) often by reflex testing. In the United States, the “full” set of thyroid function tests typically include a TSH (third generation, immunometric chemiluminescent), a free T4 (automated “direct” competitive-binding chemiluminescent), and a total T3 or free T3 assay (18). Serum free T4 provides additional information to help distinguish overt compared with subclinical disease (Table 1), but T3 is typically important only in evaluation of hyperthyroidism because there are some forms of hyperthyroidism where serum T3 but not T4 is elevated (18) Measurement of rT3 is rarely recommended (and has limited utility for conventional practice) but may ultimately prove useful along with a full thyroid panel in monitoring training intensity, recovery, or disordered eating (34). Although routine measurement of antithyroid antibodies are not considered necessary for diagnosis of hypothyroidism (because almost all patients with overt primary hypothyroidism have chronic autoimmune thyroiditis ([18])), antithyroid antibody titers may help confirm autoimmune thyroiditis and/or exclude nutrient deficiency and predict the likelihood of progression to permanent overt hypothyroidism in patients with subclinical hypothyroidism. TSH autoantibody titers, on the other hand, are recommended in the diagnosis of GD (19,37). Measurement of iron, iodine, selenium, or vitamin D status may be useful when nutrient deficiency is suspected and/or to ensure effective treatment (Tables 2 and 3).

The history should address both personal and family history of thyroid disorders, autoimmune disorders (type 1 diabetes, celiac disease, etc.), training, illness, and injury history (including head or facial trauma). Physical examination findings should evaluate presence of thyroid nodule, goiter, altered heart rate, and impaired muscle function. Other signs and symptoms specific to hypothyroidism or hyperthyroidism and to specific nutrient deficiencies are summarized in Table 3. Signs and symptoms of vitamin D deficiency and selenium deficiency may be unremarkable even if biochemical detection of compromised status is evident. Documentation of current and recent medications should not be neglected even in the athlete.

The dietary assessment should focus on estimating adequacy of energy and carbohydrate intake relative to need (2), and on estimating intake of iodine, iron, selenium, and vitamin D (Table 2). Iodine (49) and vitamin D intake (99) can be assessed by evaluating consumption frequency of the limited natural and fortified sources of both nutrients that includes fish and seafood, dairy products, eggs, dietary supplements, iodized table salt, and vitamin D fortified juices. For iron, the evaluation of iron-containing food should be considered along with general caloric intake (as iron is tied to energy intake), and the inhibitors and enhancers of iron absorption (73). Evaluation of selenium intake, however, may prove difficult given that the selenium content of food is driven by soil conditions rather than food choice. Finally, assessment of intake of dietary goitrogenic foods and sources of environmental contaminants (including drinking water) — may be warranted.

Treatment

Recommendations for intervention or treatment of the athlete can be made following a detailed assessment. Athletes with overt hypothyroidism are typically treated with T4 replacement therapy (levothyroxine) (10,24). T4 replacement therapy is preferable to T3-replacement therapy because it has a longer half-life and produces steadier hormone concentrations and is typically effective as long as T4 can be converted to T3. Ensuring adequate selenium and vitamin D status may help ensure effective treatment with T4 and reduce autoantibodies in those with AITD. Food elimination diets including gluten free diets (41) also may prove useful with AITD (2). In athletes and other individuals with subclinical hypothyroidism, clinical practice guidelines recommend that decisions about T4 replacement be made on a case-by-case basis (10,24). In these individuals, however, it is important to consider nutrient deficiencies or excess as part of the equation (2). For example, athletes with low iodine status can be encouraged to use iodized salt (1/4 teaspoon provides ~45% of the U.S. RDA) or take iodine-containing multivitamin while those with low vitamin D status can be encouraged to take vitamin D supplementation or practices safe sun exposure (79). A multivitamin may additionally help ensure adequate intake of iron and selenium. Most multivitamins in the United States now contain 150 IU iodine along with iron, vitamin D but only a select few contain selenium (unpublished observations). As reviewed by Hess, there is evidence that providing iron (and maybe also selenium) along with iodine results in greater improvement in thyroid function (68). Caution should be taken when recommending iodine to patients with elevated autoantibodies as iodine supplementation can aggravate GD (2). Athletes with low energy intake or iron deficiency may benefit from medical nutrition therapy by a board-certified specialist in sports dietetics.

Athletes with autoimmune hyperthyroidism are treated with long-term administration of thionamide drugs, such as methimazole and propythiouracil, that block thyroid hormone synthesis (19). Beta blockers are recommended initially to ameliorate symptoms caused by increased beta-adrenergic tone, including tachycardia, fatigability, shortness of breath, and heat intolerance (19) and are important in the athlete (40). If antithyroid drugs are not tolerated, other therapy options include radioiodine ablation and surgery (19). As with hypothyroidism, correction of low vitamin D status, selenium supplementation (32), and avoidance of environmental triggers may prove beneficial.

Conclusions

Sports medicine professionals should be aware of the signs and symptoms and potential causes of thyroid-related disorders. As thyroid disease is relatively common in the general population, especially in women, it also may be prevalent among athletes and could be brought on by nutritional factors. While over-exercise does not necessarily bring on thyroid problems, strenuous exercise may be associated with transient alterations in thyroid hormones that may prove important in monitoring health, training status and nutrition intake of the athlete. The assessment process should focus on anthropometric changes, biochemical tests (thyroid panel), personal and family history, examination for appropriate signs and symptoms, and diet and environmental assessment that includes adequacy of energy, iodine, iron, selenium, and vitamin D status along with excess stress and exposure to environmental contaminants and dietary goitrogens. General assessment is important for determining the cause of thyroid disorders and assisting in their treatment. Future studies are needed to evaluate the prevalence of nutritional- and nonnutritional-based thyroid disorders in athletes and their potential impact on athletic training, competition and recovery.

References

1. Golden SH, Robinson KA, Saldanha I, et al. Clinical review: prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J. Clin. Endocrinol. Metab. 2009; 94:1853–78.
2. Dean S. Medical Nutrition Therapy for Thyroid, Adrenal, and Other Endocrine Disorders. In: Mahn LK, Raymond JL, editors. Krause's Food and the Nutrition Care Process. Saint Louis (MO): Elsevier; 2017, p. 619–30.
3. Gaitan E. Goitrogens in food and water. Annu. Rev. Nutr. 1990; 10:21–39.
4. Council on Environmental Health, Rogan WJ, Paulson JA, Baum C, et al. Iodine deficiency, pollutant chemicals, and the thyroid: new information on an old problem. Pediatrics. 2014; 133:1163–6.
5. Luksch JR, Collins PB. Thyroid disorders in athletes. Curr. Sports Med. Rep. 2018; 17:59–64.
6. Salvatore D, Davies TF, Schlumberger J, et al. Thyroid physiology and diagnostic evaluation of patients with thyroid disorders. In: Williams Textbook of Endocrinology. 13th ed. Philadelphia (PA): Elsevier; 2016, p. 334–68.
7. Rousset B, Dupuy C, Miot F, Dumont J. Chapter 2 thyroid hormone synthesis and secretion. In: Feingold KR, Anawalt B, Boyce A, et al, editors. Endotext. South Dartmouth (MA); 2000.
8. Spitzweg C, Heufelder AE, Morris JC. Thyroid iodine transport. Thyroid. 2000; 10:321–30.
9. Eng PH, Cardona GR, Fang SL, et al. Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. Endocrinology. 1999; 140:3404–10.
10. Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr. Pract. 2012; 18:988–1028.
11. Bartalena L. Recent achievements in studies on thyroid hormone-binding proteins. Endocr. Rev. 1990; 11:47–64.
12. Salvatore D, Simonides WS, Dentice M, et al. Thyroid hormones and skeletal muscle—new insights and potential implications. Nat. Rev. Endocrinol. 2014; 10:206–14.
13. Bloise FF, Cordeiro A, Ortiga-Carvalho TM. Role of thyroid hormone in skeletal muscle physiology. J. Endocrinol. 2018; 236:R57–68.
14. Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol. Rev. 2014; 94:355–82.
15. Brent GA. Mechanisms of thyroid hormone action. J. Clin. Invest. 2012; 122:3035–43.
16. Bernal J, Guadano-Ferraz A, Morte B. Thyroid hormone transporters—functions and clinical implications. Nat. Rev. Endocrinol. 2015; 11:406–17.
17. Mendoza A, Hollenberg AN. New insights into thyroid hormone action. Pharmacol. Ther. 2017; 173:135–45.
18. Ross DS. Laboratory assessment of thyroid function. In: UpToDate online. Wolters Kluwer; 2017.
19. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016; 26:1343–421.
20. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J. Clin. Endocrinol. Metab. 2002; 87:489–99.
21. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch. Intern. Med. 2000; 160:526–34.
22. Kim YA, Park YJ. Prevalence and risk factors of subclinical thyroid disease. Endocrinol Metab (Seoul). 2014; 29:20–9.
23. Samuels MH, Ridgway EC. Central hypothyroidism. Endocrinol. Metab. Clin. North Am. 1992; 21:903–19.
24. Ross DS. Diagnosis of and screening for hypothyroidism in nonpregnant adults. In: UpToDate online. Wolters Kluwer; 2017.
25. Persani L. Clinical review: central hypothyroidism: pathogenic, diagnostic, and therapeutic challenges. J. Clin. Endocrinol. Metab. 2012; 97:3068–78.
26. Benvenga S, Vigo T, Ruggeri RM, et al. Severe head trauma in patients with unexplained central hypothyroidism. Am. J. Med. 2004; 116:767–71.
27. Eastman CJ, Zimmermann MB. The iodine deficiency disorders. Endotext comprehensive free online endocrinology book. In: Feingold KR, Anawalt B, Boyce A, et al, editors. Endotext. South Dartmouth (MA); 2000. (updated Feb 2018).
28. Niwattisaiwong S, Burman KD, Li-Ng M. Iodine deficiency: clinical implications. Cleve. Clin. J. Med. 2017; 84:236–44.
29. Mariotti S, Caturegli P, Piccolo P, et al. Antithyroid peroxidase autoantibodies in thyroid diseases. J. Clin. Endocrinol. Metab. 1990; 71:661–9.
30. Tayie FA, Jourdan K. Hypertension, dietary salt restriction, and iodine deficiency among adults. Am. J. Hypertens. 2010; 23:1095–102.
31. Ma J, Wu D, Li C, et al. Lower serum 25-hydroxyvitamin D level is associated with 3 types of autoimmune thyroid diseases. Medicine. 2015; 94:e1639.
32. Wang J, Lv S, Chen G, et al. Meta-analysis of the association between vitamin D and autoimmune thyroid disease. Nutrients. 2015; 7:2485–98.
33. Loucks AB, Laughlin GA, Mortola JF, et al. Hypothalamic-pituitary-thyroidal function in eumenorrheic and amenorrheic athletes. J. Clin. Endocrinol. Metab. 1992; 75:514–8.
34. Swenne I, Stridsberg M, Thurfjell B, Rosling A. Triiodothyronine is an indicator of nutritional status in adolescent girls with eating disorders. Horm. Res. 2009; 71:268–75.
35. Hackney AC, Kallman A, Hosick KP, et al. Thyroid hormonal responses to intensive interval versus steady-state endurance exercise sessions. Hormones (Athens). 2012; 11:54–60.
36. Beck-Peccoz P, Brucker-Davis F, Persani L, et al. Thyrotropin-secreting pituitary tumors. Endocr. Rev. 1996; 17:610–38.
37. Kravets I. Hyperthyroidism: diagnosis and treatment. Am. Fam. Physician. 2016; 93:363–70.
38. Vanderpump MP. The epidemiology of thyroid disease. Br. Med. Bull. 2011; 99:39–51.
39. Barbesino G, Tomer Y. Clinical review: clinical utility of TSH receptor antibodies. J. Clin. Endocrinol. Metab. 2013; 98:2247–55.
40. Wang DH, Koehler SM, Mariash CN. Detecting Graves' disease: presentations in young athletes. Phys. Sportsmed. 1996; 24:35–40.
41. Liontiris MI, Mazokopakis EE. A concise review of Hashimoto thyroiditis (HT) and the importance of iodine, selenium, vitamin D and gluten on the autoimmunity and dietary management of HT patients. Points that need more investigation. Hell. J. Nucl. Med. 2017; 20:51–6.
42. Aakvaag A, Sand T, Opstad PK, Fonnum F. Hormonal changes in serum in young men during prolonged physical strain. Eur. J. Appl. Physiol. Occup. Physiol. 1978; 39:283–91.
43. Moore AW, Timmerman S, Brownles LL, et al. Strenuous, fatiguing exercise: relationship of cortisol to circulating thyroid hormones. Int. J. Endocrinol. Metab. 2005; 1:18–24.
44. Matsumura ME, Bucciarelli M, Perilli G. Relationship between training intensity and volume and hypothyroidism among female runners. Clin. J. Sport Med. 2015; 25:551–3.
45. Ciloglu F, Peker I, Pehlivan A, et al. Exercise intensity and its effects on thyroid hormones. Neuro Endocrinol. Lett. 2005; 26:830–4.
46. Vanderpas J. Nutritional epidemiology and thyroid hormone metabolism. Annu. Rev. Nutr. 2006; 26:293–322.
47. Pearce EN, Andersson M, Zimmermann MB. Global iodine nutrition: where do we stand in 2013? Thyroid. 2013; 23:523–8.
48. Caldwell KL, Makhmudov A, Ely E, et al. Iodine status of the U.S. population, National Health and Nutrition Examination Survey, 2005–2006 and 2007–2008. Thyroid. 2011; 21:419–27.
49. Gostas D, Larson-Meyer DE, Yoder HA, et al. Dietary relationship with urinary iodine concentrations of young adults in the Mountanous Region of Laramie, Wyoming. (in review).
50. Krajcovicova-Kudlackova M, Buckova K, Klimes I, Sebokova E. Iodine deficiency in vegetarians and vegans. Ann. Nutr. Metab. 2003; 47:183–5.
51. Remer T, Neubert A, Manz F. Increased risk of iodine deficiency with vegetarian nutrition. Br. J. Nutr. 1999; 81:45–9.
52. Manousou S, Stal M, Larsson C, et al. A paleolithic-type diet results in iodine deficiency: a 2-year randomized trial in postmenopausal obese women. Eur. J. Clin. Nutr. 2017.
53. Lis DM, Kings D, Larson-Meyer DE. Dietary practices adopted by track-and-field athletes: gluten-free, low FODMAP, vegetarian, and fasting. Int. J. Sport Nutr. Exe. 2019; 29:236–45.
54. Appel LJ, Frohlich ED, Hall JE, et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke: a call to action from the American Heart Association. Circulation. 2011; 123:1138–43.
55. Dasgupta PK, Liu Y, Dyke JV. Iodine nutrition: iodine content of iodized salt in the United States. Environ. Sci. Technol. 2008; 42:1315–23.
56. Malczewska J, Szczepanska B, Stupnicki R, Sendecki W. The assessment of frequency of iron deficiency in athletes from the transferrin receptor-ferritin index. Int. J. Sport Nutr. Exerc. Metab. 2001; 11:42–52.
57. Woolf K, St Thomas MM, Hahn N, et al. Iron status in highly active and sedentary young women. Int. J. Sport Nutr. Exerc. Metab. 2009; 19:519–35.
58. Thomas DT, Erdman KA, Burke LM. American College of Sports Medicine joint position statement. Nutrition and athletic performance. Med. Sci. Sports Exerc. 2016; 48:543–68.
59. Koehler K, Braun H, Achtzehn S, et al. Iron status in elite young athletes: gender-dependent influences of diet and exercise. Eur. J. Appl. Physiol. 2012; 112:513–23.
60. Petkus DL, Murray-Kolb LE, De Souza MJ. The unexplored crossroads of the female athlete triad and iron deficiency: a narrative review. Sports Med. 2017; 47:1721–37.
61. Hinton PS. Iron and the endurance athlete. Appl. Physiol. Nutr. Metab. 2014; 39:1012–8.
62. Peeling P, Dawson B, Goodman C, et al. Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones. Eur. J. Appl. Physiol. Occup. Physiol. 2008; 103:381–91.
63. Peeling P, Sim M, Badenhorst CE, et al. Iron status and the acute post-exercise hepcidin response in athletes. PLoS One. 2014; 9:e93002.
64. Robertson J, Maughan R, Davidson R. Faecal blood loss in response to exercise. Br. Med. J. 1987; 295:303–5.
65. Waller M, Haymes E. The effects of heat and exercise on sweat iron loss. Med. Sci. Sports Exerc. 1996; 28:197–203.
66. Eichner ER. Runner's macrocytosis: a clue to footstrike hemolysis. Runner's anemia as a benefit versus runner's hemolysis as a detriment. Am. J. Med. 1985; 78:321–5.
67. Jones GR, Newhouse I. Sport-related hematuria: a review. Clin. J. Sport Med. 1997; 7:119–25.
68. Hess SY. The impact of common micronutrient deficiencies on iodine and thyroid metabolism: the evidence from human studies. Best Pract. Res. Clin. Endocrinol. Metab. 2010; 24:117–32.
69. U.S. Department of Agriculture ARS. What we eat in America. 2009–10.
70. Kafai MR, Ganji V. Sex, age, geographical location, smoking, and alcohol consumption influence serum selenium concentrations in the USA: third National Health and nutrition examination survey, 1988–1994. J. Trace Elem. Med. Biol. 2003; 17:13–8.
71. Niskar AS, Paschal DC, Kieszak SM, et al. Serum selenium levels in the US population: Third National Health and Nutrition Examination Survey, 1988–1994. Biol. Trace Elem. Res. 2003; 91:1–10.
72. Kohrle J. Selenium and the thyroid. Curr. Opin. Endocrinol. Diabetes Obes. 2015; 22:392–401.
73. Larson-Meyer DE, Woolf K, Burke L. Assessment of nutrient status in athletes and the need for supplementation. Int. J. Sport Nutr. Exerc. Metab. 2018; 28:139–58.
74. Ventura M, Melo M, Carrilho F. Selenium and thyroid disease: from pathophysiology to treatment. Int. J. Endocrinol. 2017; 2017:1297658.
75. Zheng H, Wei J, Wang L, et al. Effects of selenium supplementation on Graves' disease: a systematic review and meta-analysis. Evid. Based Complement. Alternat. Med. 2018; 2018:3763565.
76. Rayman MP, Thompson AJ, Bekaert B, et al. Randomized controlled trial of the effect of selenium supplementation on thyroid function in the elderly in the United Kingdom. Am. J. Clin. Nutr. 2008; 87:370–8.
77. Kotwal A, Kotwal J, Prakash R, Kotwal N. Does iodine excess lead to hypothyroidism? Evidence from a case-control study in India. Arch. Med. Res. 2015; 46:490–4.
78. Liu G, Liang L, Bray GA, et al. Thyroid hormones and changes in body weight and metabolic parameters in response to weight loss diets: the POUNDS LOST trial. Int. J. Obes. (Lond). 2017; 41:878–86.
79. Larson-Meyer E. The importance of vitamin D for athletes. Sports Science Exchange. 2015; 28:1–6.
80. Altieri B, Muscogiuri G, Barrea L, et al. Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept. Rev. Endocr. Metab. Disord. 2017; 18:335–46.
81. Chaudhary S, Dutta D, Kumar M, et al. Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: an open-labeled randomized controlled trial. Indian J. Endocrinol. Metab. 2016; 20:391–8.
82. Gaitan E. Flavonoids and the thyroid. Nutrition. 1996; 12:127–9.
83. Divi RL, Chang HC, Doerge DR. Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action. Biochem Pharmacol. 1997; 54:1087–96.
84. Divi RL, Doerge DR. Inhibition of thyroid peroxidase by dietary flavonoids. Chem. Res. Toxicol. 1996; 9:16–23.
85. Chandra AK, Mukhopadhyay S, Lahari D, Tripathy S. Goitrogenic content of Indian cyanogenic plant foods & their in vitro anti-thyroidal activity. Indian J. Med. Res. 2004; 119:180–5.
86. Jones AM. Dietary nitrate supplementation and exercise performance. Sports Med. 2014; 44(Suppl. 1):S35–45.
87. Blount BC, Alwis KU, Jain RB, et al. Perchlorate, nitrate, and iodide intake through tap water. Environ. Sci. Technol. 2010; 44:9564–70.
88. Kirk AB. Environmental perchlorate: why it matters. Anal. Chim. Acta. 2006; 567:4–12.
89. Wolff J. Perchlorate and the thyroid gland. Pharmacol. Rev. 1998; 50:89–105.
90. Murray CW, Egan SK, Kim H, et al. US Food and Drug Administration's Total Diet study: dietary intake of perchlorate and iodine. J. Expo. Sci. Environ. Epidemiol. 2008; 18:571–80.
91. Environmental Protection Agency. Fact sheet: final regulatory determination for perchlorate. 2011. [cited 2019 March 20]. Available at https://www.epa.gov/dwstandardsregulations/perchlorate-regulatory-determination-fact-sheets.
92. Metso S, Hyytia-Ilmonen H, Kaukinen K, et al. Gluten-free diet and autoimmune thyroiditis in patients with celiac disease. A prospective controlled study. Scand. J. Gastroenterol. 2012; 47:43–8.
93. Lin TY, Shekar AO, Li N, et al. Incidence of abnormal liver biochemical tests in hyperthyroidism. Clin. Endocrinol. (Oxf). 2017; 86:755–9.
94. Ma ZF, Skeaff SA. Thyroglobulin as a biomarker of iodine deficiency: a review. Thyroid. 2014; 24:1195–209.
95. Ma ZF, Venn BJ, Manning PJ, et al. The sensitivity and specificity of thyroglobulin concentration using repeated measures of urinary iodine excretion. Eur. J. Nutr. 2018; 57:1313–20.
96. Spencer CA, LoPresti JS, Patel A, et al. Applications of a new chemiluminometric thyrotropin assay to subnormal measurement. J. Clin. Endocrinol. Metab. 1990; 70:453–60.
97. Baloch Z, Carayon P, Conte-Devolx B, et al; Guidelines Committee, National Academy of Clinical Biochemistry. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003; 13:3–126.
98. Hak AE, Pols HA, Visser TJ, et al. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann. Intern. Med. 2000; 132:270–8.
99. Larson-Meyer DE, Willis KS. Vitamin D and athletes. Curr. Sports Med. Rep. 2010; 9:220–6.
Copyright © 2020 by the American College of Sports Medicine.