Thyroid hormones in sport: Use or abuse? World Anti Doping Agency

Important caveats on interpreting these few well designed studies are that the effects of higher GH and T doses, as used in doping, have not been studied so that more potent higher dose and/or interactive effects cannot be excluded in the absence of well controlled, high dose, placebo-controlled studies. Anti-doping science history suggests that caution is required before rejecting evidence for claimed ergogenic effects without investigations replicating the pharmacological doses used. The WSJ suggests that there may be some relationship between the rigorous training and the thyroid function itself, in which case the thyroid supplementation is simply restoring “normal” function. This seems to be what Brown believes, seeing dysfunction where other physicians see normal thyroid activity. Setting aside whether or not these athletes actually do have “low” thyroid, we can ask if thyroid treatment is actually offering a performance benefit when administered to patients with a TSH between what appears to be Brown’s cutoff of 2 and the standard cutoff of 4 or 5.

One had a high serum T4 (153 nmol/L) and FT4 (24.8 pmol/L) with normal serum T3 and FT3, and the remainder had normal serum T4, T3, FT4, and FT3. The method was applied to the total urine fraction (free + glucuronide conjugates + sulfate conjugates) but can be applied to the fractions separately. It was based on extraction at neutral pH to have a global idea of the excretion in urine of acidic (thyronacetic acids) and basic (thyronamines) metabolites. From the latest research on sports injuries, to experiences and insights of those working at the coalface of the Sport and Exercise world, we aim to provide cutting-edge content to the Sport and Exercise Medicine community around the world.

Thyroid Hormone Abuse in Elite Sports: The Regulatory Challenge

• Nevertheless, the extensive quality control of the commercial TH immunoassays and in-house TH LCMS measurements using certified reference standards means that while the precise numbers may vary a little, the deduced patterns from this study are likely to remain the same with other comparable assays.
• Both these estimated TH usage rates were then compared with national age- and sex-specific prescription rates for TH in a young population comparable with the athletes undergoing antidoping tests.
• However, hair analysis tests have yet to undergo the rigorous standardization and validation required to become acceptable anti-doping tests in their medicolegal context.
• For the unscrupulous in pursuit of the unlawful, the increasingly stringent detection of androgen and hemoglobin doping, the two most potent classes of ergogenic drugs, has led to new, highly speculative form of doping involving peptide growth factors and GH releasing peptides.

Scott has also written about running for Slate, The Atlantic, the Washington Post, and other members of the sedentary media. The psychological and physical pressures experienced by athletes and dancers can sometimes have reversible impacts on the hypothalamic-pitutary-thyroid axis. On the other hand, athletes and dancers can also experience medical conditions, which impact this endocrine axis. The recognition of these different situations provides insights and a deeper understanding of overall endocrine function in this athletic population. MGF is a splice variant of IGF-I which, although not known to appear in the circulation, have any pharmacological effects, or be approved for human use (240), is advertised on the black-market and internet (241) for alleged anabolic or tissue repair/regeneration benefits. The empirical distribution of the serum TSH in this population of athletes was significantly higher than the manufacturer’s recommended reference range (Table 1, Fig. 1).

Associated Data

Sanctions involve suspension from any elite competitive sport and extend to support personnel and teams. This is generally believed to be longer than the ergogenic benefits of doping, although recent evidence suggests that androgen effects on muscle may create durable or even permanent effects (23) which might argue for much longer or permanent banning of androgen doping violators. Recent media have highlighted the controversy surrounding treatment of elite athletes for hypothyroidism. The World Anti-Doping Agency denied a request by the United States Anti-Doping Agency to ban the use of thyroid medication.

Serum thyroxine (T4), triiodothyronine (T3), and reverse T3 were measured by liquid chromatography–mass spectrometry and serum thyrotropin, free T4, and free T3 by immunoassays in 498 frozen serum samples from antidoping tests together with a separate set of 509 DCFs. Thyroid hormone (TH) abuse for performance enhancement in sport remains controversial and it is not prohibited in sports under the World Anti-Doping Code. Another approach to increase oxygen delivery to muscle has been to exploit the ability of 2,3 diphophoglycerate (2,3 DPG), whose binding to hemoglobin reduces its affinity for oxygen with the left-shift of its oxygen dissociation curve as an oxygen unloading mechanism in tissues. 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).

• One study of two elite athletic competitions provided estimates of 43.6% and 57.1% for recent (last year) and 70.1% of ever use of banned doping methods (26).
• Although TH function tests are adequate for clinical care in conjunction with medical history, physical examination, and thyroid uptake scans, laboratory antidoping tests primarily operate in isolation and require a medico-legal standard sufficient to potentially bar professional athletes from conducting their profession.
• The main goal is to monitor thyroxine hormones (TSH, freeT3, freeT4 and freeT4/freeT3 ratio) in athlete’s serum and investigate the best biomarkers in urine focusing the attention in their potential inclusion in the ABP endocrinological module.
• Conversely, levels of TSH below the normal range with paired levels of T4 above the upper end of the normal range indicate an overactive thyroid.

TSH acts on the thyroid gland to release T4, which in turn is converted peripherally to the more active T3. As with all biological homeostatic mechanisms, there is some physiological variation within the normal range for an individual. Significant changes, beyond that expected from biological and analytical variation can be calculated using the system recently described in BMJ (v).

At present, there is no scientific evidence that thyroid medication has the potential to enhance performance. Clinical practice guidelines are not definitive in regard to what classifies a patient as having hypothyroidism. Thyroid-stimulating hormone and free T4 are recommended to screen for thyroid disease; however, the thyrotropin-releasing hormone stimulation test is still advocated by some for detecting the earliest stages of hypothyroidism.

• 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).
• This is generally believed to be longer than the ergogenic benefits of doping, although recent evidence suggests that androgen effects on muscle may create durable or even permanent effects (23) which might argue for much longer or permanent banning of androgen doping violators.
• By contrast, despite availability of a pure gravimetric T4 standard, the diversity and incongruence of commercial T4 immunoassays remains suboptimal even for clinical care 70, 71, with analogous or greater problems arising for T3 immunoassays 70, 72, 73.
• As unregistered drugs, this growing range of peptides appears to constitute a greater threat to athlete’s health than a risk of effective cheating.

Using the national sex- and age-specific population at the median age of the athletes in the 2 samples within this study, the estimated national prevalence of T4 prescriptions (per 1000) at the age of years was 10 for men, 65 for women, and 37 for all persons. Approval for use of stored serum samples and DCFs from consenting athletes was provided by Sports Integrity Australia. For privacy reasons, additional information was restricted to age, sex, and sport for each serum sample and DCF. The main goal is to monitor thyroxine hormones (TSH, freeT3, freeT4 and freeT4/freeT3 ratio) in athlete’s serum and investigate the best biomarkers in urine focusing the attention in their potential inclusion in the ABP endocrinological module. Once the method developed and biomarkers chosen, the proposed approach will be applied to different thyroid conditions and the profiles under some administrations evaluated.

P values are shown from nondirectional 1-way analysis of variance and for downward linear trend by linear contrast. We investigated TH use among Australian athletes undergoing synthroid diazepam antidoping tests for competition in World Anti-Doping Agency (WADA)–compliant sports by measuring TH in serum and surveying mandatory doping control form (DCF) declarations by athletes of all drugs used in the week prior to the antidoping test. A method to detect thyroid hormones (TH) and some related metabolites in serum was validated using the LCMS/MS technique. The correlation of the validated method with RIA showed adequate results and one of the advantages of the LCMS technique with respect to RIA is that it does not show cross-interferences as is the case of T3 with triiodo-thyronacetic acid, which could happen with other metabolites.

Other than its proper medical use in diabetics, the use of insulin and its analogs for doping is based solely on its easy availability coupled with anecdotal information from other drug users. There are no clinical studies showing any ergogenic effects of insulin or its analogs in non-diabetic individuals. The doping folklore appears to arise from the classification of insulin as being “anabolic”, in a loose generalization and mistaken analogy to androgens. In healthy non-diabetic individuals, insulin and its synthetic analogs stimulate weight gain via hypoglycemia and increasing appetite, but produce fat rather than muscle gain. The adverse effects include hypoglycemia, hypokalemia, injection-related infections and weight (fat) gain. Doping detection tests for insulin and its analogs continue to evolve and focus on highly sensitive and specific quantitative MS-based proteomics (244).