Thyroid Hormone Abuse in Elite Sports: The Regulatory Challenge

Hence the yeast androgen bioassay was decisive in the first conviction for use of a designer androgen by proving that tetrahydrogestrinone (THG) was a potent androgen (84) and has also been used to screen synthetic synthroid kelp progestins to show that, unlike the original androgen-derived progestins, the modern generation of progestins are not androgenic (85). The illicit use of banned drugs (doping) to influence the outcome of a sporting contest, constitutes a fraud against competitors, spectators, sport, sponsors, and the public no different from other personal, professional, or commercial frauds. While performance enhancement is almost invariably the intent of cheating, impairing performance is also well known in horse racing and even, rarely, in human elite sports (e.g. drink-spiking of banned drugs, injurious physical assaults).

Serum TSH Immunoassay

There were 2 declarations of T4 use and none for T3 use, providing a prevalence estimate for T4 usage of 4 (upper 95% confidence limit 16) per 1000 athletes. In concert, these data provide a point estimate of prevalence of overt biochemical thyrotoxicosis (low serum TSH with high serum T4 or FT4) of 4 per 1000 athletes with the 95% upper confidence limit of 16 per 1000. Among the 55 with higher serum TSH concentrations than the expected reference range (data not shown), 4 had low and 2 had high T4 concentrations, 5 had high T3 and 1 low T3, with 1 having both T4 and T3 high and another with both low T4 and T3. Data were analyzed by descriptive methods, the unpaired t-test, and analysis of variance and covariance, as appropriate, using NCSS 2022 software (NCSS, Kaysville, UT, USA).

Thyroid Function in Athletes and Dancers

In 2017, of over 322,000 anti-doping tests ~1.5% were positive with 61% due to hormones, the vast majority (~99%) due to androgens. Further use of out-of-competition testing and blood samples together with more sensitive detection tests with longer windows of detection are required particularly for peptide hormones. To estimate the prevalence of TH abuse from TH measurements, we assume that high (supraphysiological) TH doses would increase net circulating TH action thereby suppressing serum TSH, forming a sensitive generic indicator of biochemical thyrotoxicosis. In euthyroid individuals, lower, subreplacement T4 doses titrated to not fully suppress serum TSH have no detectable effects on body composition or muscular function 36.

• They are best deployed to characterize products and substances for androgens or pro-androgen content rather than to detect androgens in complex biological samples.
• A low thyroid uptake could be due to exogenous T4 or T3 ingestion but could also be due to thyroiditis, for which additional tests (thyroglobulin, inflammatory and immune biomarkers) would be required.
• Sports that are highly dependent on explosive, short-term anaerobic power (sprinting, throwing, boxing, wrestling), typically ones which favor a stocky, muscular build, are most susceptible to androgen-induced increases in muscle mass and strength.
• The hematological module of the ABP currently employs an algorithm involving 8 parameters derived from routine hematological profile (hemoglobin, hematocrit, erythrocyte count, reticulocyte count and percentage, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) (158).
• This substitution of an individual’s own person-specific, in place of the population-based, thresholds allows for more sensitive and accurate detection of individual deviations in urine T/E ratio as evidence of T doping.

Materials and Methods

• From my personal perspective, I’m skeptical of medical mavericks who haven’t yet produced enough evidence to convince their peers and change the medical consensus.
• More examples of genetic (dis)advantages for sports performance are likely to be identified as genomics continues to expand our understanding of the biological basis of health, including natural human sporting prowess.
• In the short term, stress fractures in athletes are recognised as a consequence of low energy availabilityvi, which is the underlying aetiology of relative energy deficiency in sport (RED-S)(vii).

It is well understood that individual human genetic endowments are unequal and, among these, sporting prowess is at least partly genetically determined (17). However, little is still known of the genotype-phenotype correlations that underlie beneficial genetic endowments for sports performance. More examples of genetic (dis)advantages for sports performance are likely to be identified as genomics continues to expand our understanding of the biological basis of health, including natural human sporting prowess. In the context of sports doping, however, a person’s genetic endowment is a given creating a natural boundary whereby the use of exogenous drugs or chemicals (including DNA) may constitute drug cheating or doping. One of the differences that thyroid replacement has from other forms of sports supplementation is that there is a clear peak point – normal thyroid function. Thyroid replacement in the absence of real deficiency could create a hyperthyroid state which would possibly hurt athletic performance as much a hypothyroidism.

• Hair has the advantages of minimally invasive sampling with simple, convenient storage and the potential for very long window of detection, according hair growth rates (87).
• It is both a major economic activity as well as a profound influence on social behavior of individuals at home, work, and play.
• The illicit nature of this market raises the risks of counterfeit and unsafe products with attendant risks of infection and residual toxic contaminants unlike the purity pharmaceutical product manufacturers are required to demonstrate by batch release testing.
• 2,3 DPG analogs, developed as radiation sensitizers for hypoxic radio-resistant tumors, enhance tissue oxygen delivery in vivo (174,175) but would feature only short-term, acute effects readily detectable by mass spectrometry (176,177).

Starting with power sports (20), the epidemic became entrenched as an endemic in sufficiently affluent circles. In 1967, following the introduction of anti-doping rules by some sports federations, the International Olympic Committee (IOC) established its Medical Commission, which published their first list of prohibited substances. During the 1970’s the IOC Medical Commission took an increasingly active role by banning androgens which required developing standardized, valid methods to detect and deter androgen doping. After discarding alternatives such as immunoassays and blood sampling, in the 1980s mass spectrometry (MS)-based tests became (21) and remain the standard for detecting synthetic androgens in urine. One unexpected finding from TH measurements is that serum TSH concentrations among this young athlete population are biased upwards from those of the general population, as reflected in the manufacturer’s expected reference range, which was based on a study of 516 healthy Europeans 50.

On the wall of the medical office of Jeffrey S. Brown is a photograph of Carl Lewis, the nine-time Olympic gold medalist. Lewis is one of several former or current patients of Brown’s who have climbed the Olympic podium, including Galen Rupp, who won a silver medal in the 10,000 meters at the London Olympics. Among endocrinologists, Brown stands almost alone in believing that endurance athletics can induce early onset of a hormonal imbalance called hypothyroidism, the condition with which he diagnosed Lewis and Rupp.

HEMOGLOBIN (BLOOD) DOPING

It is also claimed that GH may enhance injury healing, thereby facilitating more intensive training and/or recovery from muscle, connective tissue or bone injury, notably in contact sports. This claim is difficult to evaluate and no well controlled studies of recovery from sports injuries or tolerance of training intensity in elite athletes are reported. The most germane surrogate evidence available arises from investigations on the use of GH in recovery from injuries due to burns, fracture, or for wound healing.

These include measuring urinary excretion of phthalates, plasticizers that leach out from the polyvinylchloride blood packs used to store venesected blood (141). This test has brief window of detection (2 day) so will detect auto-transfusion during or immediately before events (characteristic in road cycling, according to convicted dopers) but may miss earlier auto-transfusion. Furthermore, the ubiquity of low-level environmental phthalate exposure requires establishing detection thresholds and non-plastic blood containers can be used. An alternative is the measurement of total hemoglobin mass (142), a measure with good stability and reproducibility even during exercise and circumvents influence of variations in plasma volume such as due to dehydration or dilutional masking (142,143). However, as this requires inhalation of carbon monoxide, which has transient detrimental effects on performance, it is not ideal for routine anti-doping use and its sensitivity may be insufficient to detect all EPO micro-dosing (144,145). Other hypothetical methods include the detection of microRNA (146) or immune reactions to transfusion (147) but the sensitivity and specificity of these proposed tests remains to be fully evaluated.

Like other short peptides, once chemical structures are known, detection is readily feasible using LC-MS (247,248). The illicit nature of this market raises the risks of counterfeit and unsafe products with attendant risks of infection and residual toxic contaminants unlike the purity pharmaceutical product manufacturers are required to demonstrate by batch release testing. According to American College of Endocrinology literature, the range of normal TSH level is broad, from 0.5 to an upper limit of near 5, depending on a patient’s gender, age and other factors. In practice, many endocrinologists consider TSH levels above 4—combined with symptoms such as fatigue—evidence of an underactive thyroid. Brown and a small camp of other endocrinologists argue that thyroid insufficiency can be signaled by a TSH level as low as 2, for which Brown cites some recently published research.

Scott is a veteran running, fitness, and health journalist who has held senior editorial positions at Runner’s World and Running Times. Much of his writing translates sport science research and elite best practices into practical guidance for everyday athletes. He is the author or coauthor of several running books, including Running Is My Therapy, Advanced Marathoning, and Meb for Mortals.