Duhig, Thomas J.1; McKeag, Douglas2
The thyroid is a gland that secretes metabolically active hormones responsible for growth, maturation, energy expenditure, and body substrate turnover. Childhood obesity has placed some emphasis and a more aggressive approach to screen, although to date there is no agreement as to a routine screening for thyroid function at any age. In athletes with thyroid disorders, a decrease in performance usually is the presenting complaint to the clinician. This may elucidate suspicion of a hormonal cause. The signs may not be as pronounced in this population of patients, and the physician must use his or her clinical judgment in the laboratory workup. A retrospective report of 50 athletes with complaints of fatigue concluded that the yield from a selection of blood tests, including thyroid stimulating hormone (TSH), was low. In this case, audit, only three abnormal laboratory results (6%) were found that may have contributed to the diagnosis of medical disease as a cause for fatigue. Furthermore, abnormal thyroid stimulating hormone values were not implicated as a cause (7).
Thyroid disease occurs when the gland is enlarged (goiter) or there are alterations in the secretion of triiodothyronine (T3) or thyroxin (T4). The thyroid gland secretes both T3 and T4, but it only is responsible for approximately 20% of T3 secretion and is the only endogenous source of T4. The remainder of T3 in the body is the breakdown product of the peripheral conversion of T4 to T3.
These hormones are part of a negative feedback loop with the anterior pituitary gland. Negative feedback is seen when the output of a pathway inhibits inputs to the pathway controlling the release of thyroid stimulating hormone in response to circulating levels of thyroid hormone. Thyroid releasing hormone (TRH) is released by the hypothalamus stimulating release of TSH by the anterior pituitary. TSH binds to epithelial cells on the thyroid gland stimulating the release of thyroid hormones (T3 and T4). When the concentration of these hormones reaches a threshold, the TRH secretion is inhibited.
It has been shown that thyroid hormones regulate gene transcription in relation to skeletal muscle. Included are the genes responsible for coding Type I myosin heavy chain (MHC), the sarcoplasmic reticulum (SR), Ca21, ATPase pump, and actin. One can expect hyperthyroid states to increase Ca2+ uptake by the sarcoplasmic reticulum and hypothyroid states to decrease uptake. (3) The effects of thyroid hormone on MHC expression and Ca2+ uptake increases the shortening velocity of skeletal muscle with increased levels (4). Maintained within physiological normal limits, an increased thyroid activity may be associated with greater effectiveness of exercising muscles. Current studies have shown that an increase in TSH values correlate with an increase in exercise intensity (5). T3 increases initially, then decreases while fT4 and T4 levels increase with intensity as well. The increase in TSH with intensity shows that there is a proposed need for increased thyroid hormone at times of intense exercise, although the values reported remained within the range of normal values for TSH, T3, T4, and fT4.
Thyroid disorders include insufficient thyroid hormone secretion (hypothyroidism) and increased secretion (hyperthyroidism.) As reported in a systemic review, the estimated incidence of hypothyroidism in women is 350·100,000−1·yr−1 and in men, 80·100,000−1·yr−1; the incidence of hyperthyroidism is 80·100,000−1·yr−1 in women and 8·100,000−1·yr−1 in men (15). In people younger than 22 yr, prevalence of hypothyroidism is reported as 0.135%. In ages 11-18 yr, the prevalence is lower, at 0.113%. These values reflect a twofold increase from previous estimates, which may represent an increase in the overall incidence of autoimmunity (11). Hypothyroidism is associated with decreased caloric expenditure as its main feature, while hyperthyroidism is associated with increased metabolism, although both have additional systemic effects. Also, thyroid hormones are important regulators of cardiac function and myocardial arteriolar density. An enlarged thyroid gland can be associated with a hypo, hyper, or euthyroid picture metabolically.
Decreased amount of metabolically active thyroid hormone can affect heart contractility, reducing the amount of blood the heart ejects with each beat. The relaxation phase of the heart is also affected, which can lead to diastolic dysfunction. Hypothyroidism also has been shown to reduce the amount of nitric oxide in the vessel walls, leading to premature stiffening. Heart rate is modulated by thyroid hormone, so a decrease in metabolically active thyroid hormone can affect heart rate by 10 bpm in some cases.
In adolescents, the most common abnormality of thyroid function is caused most often by chronic autoimmune thyroiditis (6). Similar to adults, primary hypothyroidism and central hypothyroidism can be acquired hypothyroidism in children. A high serum thyrotropin with a normal serum thyroxine concentration, or a high serum TSH and a normal T4 may be subclinical or overt, complicating the diagnosis.
In children, hypothyroidism can affect growth, cognitive performance, and pubertal development. In young adults with congenital hypothyroidism, there is an association with impaired diastolic function and exercise capacity and increased intima-media thickness with replacement therapy initiated within the first month of life (20). Most commonly, a declining growth velocity may be present for several years and is insidious in onset and may precede other symptoms, prompting a clinician to evaluate for hypothyroidism (19).
Other common symptoms include lethargy, cold intolerance, muscle aches and pains, and poor athletic performance. Headaches, visual symptoms, polyuria, and polydipsia may indicate a hypothalamic or pituitary disease.
Physical examination may yield fluid retention rather than obesity, puffy facies, placid expression, bradycardia, and poor or delayed deep tendon reflexes. The thyroid gland itself may present normal in size, diffuse enlargement, or may be nonpalpable. In athletes, the presentation of a decrease in exercise capacity or performance may arise clinical suspicion for thyroid disease.
Subclinical hypothyroidism is defined as elevated values of thyroid TSH and free thyroid hormones within normal value limits. Elevated levels of thyroid stimulating hormone (TSH) are between 5 and 10 mU·L−1 in nearly 70% of those with this condition, and nearly half of affected patients may progress to thyroid failure. The clinical symptoms may be representative of a significant fall from a previous level of T4, although still within the laboratory normal values. There are associations with subclinical hypothyroidism and hypercoagulability, impaired vascular function, atherosclerotic cardiovascular disease, and reduced submaximal exercise capacity (20). Progression to overt hypothyroidism occurs at a rate of approximately 5% per year in patients with raised TSH levels and detectable antithyroid antibodies (21). Symptoms of subclinical hypothyroidism include one or more of the findings of overt hypothyroidism (fatigue, dry skin, constipation, muscle cramps) including complaints of decrease in athletic performance or exercise capacity in athletes. Treatment initiation for subclinical hypothyroidism may be dictated by the clinician in response to the presence of symptoms and the potential benefit to treat. Risk of treatment is minimized with follow-up TSH levels and assurance that these values of TSH do not fall below the normal range. Treatment recommendations are similar to treatment recommendations for overt hypothyroidism with daily levothyroxine as the agent of choice.
Manifestations of hyperthyroidism include heat intolerance, tremulousness, anxiety, insomnia, and diaphoresis. Increase in basal metabolic rate by thyroid hormones is driven by increased oxygen consumption and heat production in body tissues; therefore, a hyperthyroid athlete may be more vulnerable to heat illness. Athletes may present with complaints of undesired weight loss, despite adequate nutrition, often increased appetite, and similar to hypothyroidism, a noted decrease in the level of performance. Often a resting tachycardia can be elicited in patients but due to athletic bradycardia, this is often not reliable in this population. Case study reports suggest that rhabdomyolsis also may be related to hyperthyroidism by an increase in energy consumption associated with depletion of muscle energy stores and substrates (1,12,20).
Elevation of T4 and subnormal TSH confirms the diagnosis. Treatments include antithyroid agents and surgical and radiation ablation. B-blockers have been used to treat the symptoms of hyperthyroidism including diaphoresis and irritability in the past but would not be recommended in the competitively active individual or athlete. B-blockers have been shown to lead to a decrease in exercise endurance, likely due to the hemodynamic effects of decreased heart rate, cardiac output, mean arterial pressure, and central venous pressure (2).
Subclinical hyperthyroidism may be caused by exogenous or endogenous factors: the most frequent causes are TSH suppressive therapy for thyroid disease with L-thyroxine (L-T4) for benign thyroid disease, thyroid cancer, or exogenous hormone replacement in patients with hypothyroidism. Consequences of subclinical hyperthyroidism include both psychological and somatic reduction in perceived quality of life in addition to signs and symptoms of excessive thyroid hormone action or hyperthyroidism as adrenergic over activity. Subclinical hyperthyroidism has shown cardiovascular effects such as tachycardia, increased risk of arrhythmias, ventricular hypertrophy, and reduced systolic performance on effort and decreased exercise tolerance (14). These signs lead to an increase in cardiovascular morbidity and mortality observed in these patients. There is also evidence that subclinical hyperthyroidism may accelerate the development of osteoporosis, possibly leading to increased incidence of stress fractures in athletes and increased bone vulnerability to trauma. Subclinical hyperthyroidism is reversible with appropriate treatment, and undiagnosed cases may lead to cardiovascular disease. Specifically, patients with new onset of atrial fibrillation may have occult subclinical hyperthyroidism and the treatment with antithyroid drugs may reverse the atrial fibrillation in these cases (16,17).
An acute inflammation of the thyroid gland may present with signs and symptoms of hyperthyroidism. De Quervain's or granulomatous thyroiditis - presents with focal tenderness of the gland classically - laboratory findings may vary although an increase in serum T4, decreased serum TSH. Varied presentation from hyperthyroidism to hypothyroidism and return to euthyroid is not unusual in the course of the disorder.
Treatment involves short duration prednisone in severe cases with replacement therapy of levothyroxine in some cases due to the fluctuation of the thyroid status.
With one of the effects of increased metabolism leading to weight loss, there has been some marketing toward athletes in the sports supplement industry regarding thyroid hormone and animal thyroid preparations. Currently the Food and Drug Administration prohibits active thyroid hormone in food or nutritional supplements. Human studies have shown a direct connection between thyroid status and response to adrenergic stimulation in subcutaneous fat; however, it is unclear whether there is a direct effect on lipolysis locally in the adipose tissue (9). No demonstrable effects of leptin levels have been demonstrated when subjects were administered exogenous thyroid hormone. However, subjects did show a decrease in abdominal adipose tissue by thyroxine affecting local norepinephrine (NE) levels and adrenergic postreceptor signaling in reported studies (10). Additionally, claims of willful abuse of L-thyroxine to accelerate the metabolizing of carbohydrates, proteins, and fat are found with even a cursory internet search. There also is evidence showing an increase in maximal shortening velocity of muscle reported in the literature (3). Dosage and frequency of L-thyroxine abuse are available on many sites targeting bodybuilders and athletes with weight dependence such as wrestling. There is evidence that acute thyroxine overdose can lead to myocardial infarction, signs of hyperthyroidism including lid lag and lid retraction, and in children there are cases of seizures in the literature (13). Exogenous hyperthyroidism should be considered when clinical suspicion arises, such as having signs and symptoms of hyperthyroidism without thyroid enlargement; confirmation can be reached with a low 24-h thyroid radioiodine update, and a low serum thyroglobulin concentration may confirm the diagnosis.
ANABOLICS AND THE THYROID
An increase in the use of anabolic steroids in athletics as well as for aesthetics is perceived through multiple sources, although the prevalence of anabolic steroid use is poorly documented. There is evidence that thyroid binding globulin (TBG) is decreased by the use of anabolic steroids resulting in the reduction of total serum T3 and T4, which depends upon the drug's susceptibility to aromatize into estrogen (4). Published studies have shown the effect of anabolic steroids upon thyroid function and report a proliferative effect on thyroid cells and involvement in the metabolism of peripheral thyroid hormones (8). The proliferative effect is likely related to the aromatization into estrogen and the hormonal relationship. A recent study shows an increase in 16alpha-hydroxyestrone activity compared with 2-hydroxyestrone activity and associated with proliferative thyroid disease. This may present as thyroid nodules, enlarged lymphatics, hoarseness or other symptoms of thyroid cancer to the clinician prompting further diagnostic testing such as an I-131 thyroid scan (4).
RETURN TO PLAY
To date there are no definable guidelines regarding return to full participation. However, there is evidence that subclinical hypothyroidism and subclinical hyperthyroidism places an increased risk of all-cause death compared with people with normal functioning thyroid, according to data presented at the 2008 Annual Meeting of the American Thyroid Association. Furthermore, there is an increased risk of cardiovascular death in patients with subclinical thyroid disease compared with people who have a normal thyroid profile. Because of these recent findings, there is some suggestion of a more aggressive approach to screening and treatment, such as obtaining a baseline TSH and fT4. A gradual increase in intensity and frequency of exercise seems to be the most prudent approach in those whose presenting factors were fatigue or cardiac manifestations. Clinical monitoring as well as laboratory monitoring of euthyroid state may be considered as competitive levels change or performance deviates from past performance in addition to pre-participation screening. Caution should be exercised in interpretation and timing of samples drawn due in part to the reported increase in T4, fT4, and TSH levels when an athlete achieves 90% of maximal heart rate and a fall in the rate of T3 and fT3 (5). In regards to pre-participation screening, there is no evidence to support routine thyroid screening. Most importantly, TSH levels in children and adolescents have a wider normal range than in adults and are affected by drugs and non-thyroidal illness. Additionally, heterophile and anti-T4 or anti-TSH antibodies can interfere with accurate T4 or TSH measurement (18).
The physical manifestations of thyroid disease are often varied, and clinical suspicion remains the trigger for further investigation. In athletes, the complaint of fatigue or decrease in performance may be the presenting sign of subclinical or overt thyroid disease. With the topic area lacking in completeness currently, it is important for the clinician to exercise judgment in obtaining and interpreting laboratory values. While thyroid function depends to a certain degree on the exercise intensity, serial testing may be warranted if no cause is elicited. Pre-participation screening for thyroid disease has not shown value to date and is not recommended at this time. Suspicion of thyroid disease may be followed by serial values obtained during different times of a competitive season as well as at season completion. Anabolic use has been shown to result in low values of T3 and T4 due to decrease in thyroid binding globulin and may be implicated in abnormal reported values. It is important for the clinician to recognize signs and symptoms of exogenous thyroxine use and to counsel athletes accordingly.
1. Alshanti M, Eledrisi MS, Jones E. Rhabdomyolysis associated with hyperthyroidism. Am. J. Emerg. Med
. 2001; 19:317.
2. Anderson RL, Wilmore JH, Joyner MJ, et al. Effects of cardioselective and nonselective beta-adrenergic blockade on the performance of highly trained runners. Am. J. Cardiol
. 1985; 55:149D-54D.
3. Caiozzo VJ, Herrick RE, Baldwin KM. The influence of hyperthyroidism on the maximal shortening velocity and myosin is form distribution in slow and fast skeletal muscles. Am. J. Physiol
. 1991; 261:285-C296.
4. Chan EK, Sepkovic DW, Yoo Browne HJ, et al. A hormonal association between estrogen metabolism and proliferative thyroid disease. Otolaryngol Head Neck Surg
. 2006; 134:893-900.
5. Ciloglu F, Peker I, Pehlivan A. Exercise intensity and its effects on thyroid hormones. Neuro. Endocrinol. Lett
. 2005; 26:830-4.
6. DeBoer M, Lafranchi H. Pediatric thyroid testing issues. Pediatr. Endocrinol. Rev
. 2007; 5 Suppl 1:570-7.
7. Du Toit C, Locke S. An audit of clinically relevant abnormal laboratory parameters investigating athletes with persistent symptoms of fatigue. J. Sci. Med. Sport
. 2007; 10:351-5.
8. Fortunato RS, Rosenthal D, de Carvalho DP. Abuse of anabolic steroids and its impact on thyroid function. Arq. Bras. Endocrinol. Metabol
. 2007; 51:1417-24.
9. Haluzik M, Nedvidkova J, Bartak V, et al. Effects of hypo- and hyperthyroidism on noradrenergic activity and glycerol concentrations in human subcutaneous abdominal adipose tissue assessed with microdialysis. Clin. Endocrinol. Metab
. 2003; 88:5605-8.
10. Haluzik M, Nedvidkova J, Bartak V, et al. Effects of hypo- and hyperthyroidism on nonadrenergic activity and glycerol concentrations in human subcutaneous abdominal adipose tissue assessed with microdialysis. J. Clin. Endocrinol. Metab
. 2003; 99:5605-8.
11. Hunter I, Greene SA, MacDonald TM, Morris AD. Prevalence and etiology of hypothyroidism in the young. Arch. Dis. Child
. 2000; 83:207-2010.
12. Lichstein DM, Arteaga RB. Rhabdomyolysis associated with hyperthyroidism. Am. J. Med. Sci
. 2006; 332:103-5.
13. Locker GH, Kotzmann H, Frey B, et al. Facticious hyperthyroidism causing acute myocardial infarction. Thyroid
. 1995; 5:465-7.
14. Mainenti MR, Teixeira PF, Oliveira FP, Vaisman M. Impact of subclinical hypothyroidism in cardiopulmonary response during effort and its recovery. Arq. Bras. Endocrinol. Metabol
. 1995; 51:1485-92.
15. McGrogan A, Seaman HE, Wright JW, de Vries CS. The incidence of autoimmune thyroid disease: a systematic review of the literature. Clin. Endocrin
. 2008; 69:687-96.
16. Mountantonakis SE, Cruz P. Sudden cardiac death complicating newly diagnosed atrial fibrillation in the setting of subclinical hyperthyroidism. J. Electrocardiol
. 2008; 41(6):659-61.
17. Patane S, Marte F. Paroxysmal ventricular tachycardia and paroxysmal atrial fibrillation associated with subclinical hyperthyroidism, chronic renal failure and elevation of prostate-specific antigen during acute myocardial infarction. Int. J. Cardiol
. Aug 20: 2008.
18. Rallison ML, Dobyns BM, Keating FR, et al. Occurrence and natural history of chronic lymphocytic thyroiditis in childhood. J. Pediatr
. 1977; 86:675-82.
19. Rallison ML, Dobyns BM, Meikle AW, et al. Natural history of thyroid abnormalities: prevalence, incidence, and regression of thyroid diseases in adolescents and young adults. Am. J. Med
. 1991; 91:363.
20. Salerno M, Oliviero U, Lettiero T, et al. Long-term cardiovascular effects of levothyroxine therapy in young adults with congenital hypothyroidism. J. Clin. Endocrin. Metab
. 2008; 93:2486-91.
21. Surks MI, Ocampo E. Subclinical thyroid disease. Am. J. Med
. 1996; 100:217-23.