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

By their standards, about 10% of the population is hypothyroid—double the 5% that is cited by mainstream endocrinology. Jeffrey Garber, American College of Endocrinology president, said hypothyroidism increasingly is being diagnosed in people who don’t have it, by endocrinologists whom Garber labeled as “alternative.” “The alternative crowd is saying, ‘Gee, this is why you’re not feeling better, because these mainstream doctors are clueless,’ ” Garber said. So if this reporting is accurate, Brown is looking at the same test results and seeing what he believes to be thyroid disease, where his peers see normal thyroid function. We conclude that TH abuse among Australian athletes undergoing antidoping tests is minimal with the prevalence of biochemical thyrotoxicosis no higher than the population risks of thyroid disease or valid T4 prescribing rather than TH doping. Prevalence of TH misuse or abuse in the general community, outside WADA surveillance, may be higher in certain niches such as regular gym attendees and bodybuilders than among these athletes studied. Whereas policing under WADA regulations of drug use within elite sports is a strong deterrent, there is no regulatory hindrance to use of substances for image enhancement in bodybuilding and related drug-based hobbies outside WADA compliance, for which THs are readily available without prescription over the internet.

Direct androgen doping involves administration of testosterone, natural or synthetic androgens whereas indirect androgen doping includes a variety of non-androgenic drugs which increase endogenous T.
However, another study using the same methodology found markedly lower prevalence estimates of 0.7% to 11.9% for recent use of banned doping (27).
Across the world, sport is a ubiquitous human social activity that forms an unique intersection of health, recreation, entertainment, and industry (1).
Similarly, only 2 of 509 DCFs declared usage of T4 and none for T3, also giving a prevalence of 4 (upper 95% CL 16) per 1000 athletes.
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.

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). MS-based methods have been reported to detect exogenous (88-102) and endogenous (91, ) androgens in human hair following long-term, but not single dose (107), exposure. However, hair analysis tests have yet to undergo the rigorous standardization and validation required to become acceptable anti-doping tests in their medicolegal context. Problems that remain to be fully overcome include matrix effects, low recovery and limited sensitivity as well as the impact of age, hair color, alopecia, and shaving or passive chemical (cosmetic) contamination of hair. Additionally nails and skin could also provide analogous information on past androgen exposure with relatively long windows of detection but suitably rigorous tests are yet to be convincingly developed (108). Saliva sampling has also been considered (109,110) for anti-doping application analogous to the use of salivary cortisol measurement for diagnosis of hypercortisolism (111).

Autologous Transfusion

There was a total of 779 declarations from 450 athletes reporting 1 or more substances used, consisting of reported use by each individual of 6 (1), 5 (1), 4 (11), 3 (61), 2 (165), 1 (211), and 0 (59) substances. Serum thyroid hormone concentrations across years of blood sampling among 498 Australian athletes including 183 females and 315 males. Serum TSH (left panel), T4 (upper middle panel), T3 (lower middle panel) and T3 to T4 ratio (right panel).

Thyroid metabolism and supplementation: A review framed in sports environment

These estimates were consistent with DCF analyses from international competitions and lower than the estimated T4 prescription rates in the age-matched Australian population. Across the world, sport is a ubiquitous human social activity that forms an unique intersection of health, recreation, entertainment, and industry (1). It is both a major economic activity as well as a profound influence on social behavior of individuals at home, work, and play. One practical and concise definition of sport is the organized playing of competitive games according to rules. In that context, rule breaking is cheating to achieve an unfair competitive advantage whether it involves using illegal equipment, match fixing, banned drugs, or any other prohibited means.

These philosophical issues are not considered further here and, recognizing that sport requires concrete, practical decisions, the establishment and enforcement of agreed rules is the basis of fair competition. An excellent discussion of the logic and morality of a decisive antidoping approach from an ethicist with extensive experience in sports anti-doping is recommended (16). Transfusion may involve either another person’s (homologous) or the athlete’s own (autologous) blood administered prior to a contest to acutely increase circulating hemoglobin. Homologous blood can be transfused at any convenient time to enhance performance in competition but when performed by untrained personal in non-clinical environments risks transfusion reaction, blood-borne infectious disease, and iron overload. By contrast, autologous transfusion reduces health risks but requires complex coordination as venesection itself is detrimental to performance, and it requires balancing recovery from blood withdrawal and loss of erythrocyte viability during long-term cryostorage with training and competition schedules.

Nevertheless, sports medicine doctors and administrators receive anecdotal reports of nonprescribed TH use by athletes, especially those competing in weight-classified sports (weightlifting, combat sports) aiming to “make-weight” at formal precompetition weigh-in, and remain concerned about the prevalence, safety, and doping uses of THs. Yet, the prevalence of TH abuse among athletes undergoing antidoping tests for competition in WADA-compliant sports has not been studied systematically. Hence the present study aimed to use a multimodality approach to estimate the prevalence of TH use among such athletes. This consisted of investigating circulating TH concentrations in randomly selected, frozen stored serum samples leftover from routine antidoping tests as well as the prevalence of TH use reported in a separate random sample of doping control forms (DCFs), which must be completed with every antidoping test. 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.

Notably, during hypoxia the expression of HIFα in renal cortical cells stimulates EPO gene expression so that HIF stabilization by prolyl hydroxylase inhibitors leads to increased EPO secretion and circulating hemoglobin. Hence inhibiting prolyl hydroxylase activity via blocking its required cofactors (ascorbate, ketoglutarate, iron) using cobalt, nickel, iron chelation, ketoglutarate analogs or mechanism-based chemical inhibitors can result in increased hemoglobin via stimulation of EPO secretion (171). Similarly, small molecule GATA inhibitors potently stimulate circulating EPO, hemoglobin and performance in mice (173) although none have yet been marketed so their human efficacy and safety remain to be determined. The most renowned running coach at Nike, Alberto Salazar, calls Brown the best sports endocrinologist in the world. And athletes in growing numbers are coming to share Brown’s belief that heavy training can suppress the body’s production of the thyroid hormone, leaving them too exhausted to perform at peak.

Serum TSH Immunoassay

Moreover, it is well documented that thyrotoxicosis is a risk factor for bone fracture in the long term. 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). Increased metabolic rate as a consequence of endogenous or exogenous excess thyroxine could theoretically lead to a situation of unintentional low energy availability and the adverse clinical sequalae of RED-S. The major category of oligopeptides used for doping is the class of GH releasing peptides analogs of the endogenous GH releasing peptides, GHRH and ghrelin, whereby their analogs aim to increase endogenous GH secretion and are therefore banned (table 5).

Like any laboratory measurement, what’s considered a “normal” TSH is based in synthroid adderall part on clinical studies, but also on the testing standard. Most labs identify an upper limit of TSH at 4 to 5 mU/L, but there are proponents of both higher and lower thresholds. Consequently there will be variations in practice between physicians in what they consider a “high” TSH and what’s considered “normal”. There is also some debate about a condition called “subclinical hypothyroidism”, where there are some laboratory signs of a thyroid dysfunction (a “normal” T4 and a slightly elevated TSH), but it’s not sufficient to warrant a diagnosis.

Nevertheless, WADA does not consider thyroxine to confer a performance advantage, which is why this hormone is not on the banned list.
Like any laboratory measurement, what’s considered a “normal” TSH is based in part on clinical studies, but also on the testing standard.
It could continue to be treated like inhaled anti-asthma medications, where asthmatic athletes who require treatment would otherwise be at a serious disadvantage in athletic competitions.
Indirect methods to increase hemoglobin include administration of recombinant human EPO or its analogs as well as hypoxia-mimetic drugs (hypoxia-inducible factor stabilizers, iron chelation, cobalt, 2,3 diphosphoglycerate analogs) or artificial oxygen carriers (perfluorocarbons, hemoglobin-based oxygen carriers).

Thyroid Therapy or Dysfunction in Athletes: Is it Time to Revisit the Clinical Practice Guidelines?

Furthermore, despite internet encouragement to use T3 as the more potent TH, there was no evidence of selective T3 usage. Another limitation is that athletes undergoing antidoping tests can refuse to allow their samples to be used for unspecified future research because such research is often aimed to develop more sensitive antidoping detection tests that could hypothetically lead to retrospective disqualification for using banned substances. Although DCFs survey only the last week prior to testing, even truthful completion may not include earlier use of substances; however, the unusually long half-life of T4 (1 week vs 1 day for T3) means that T4 doping is less likely to be missed by the 1-week time window of DCFs. Nevertheless, if the faster onset/offset of T3 was being exploited to “make-weight” in weight-classified sports, the maximum effect would be at the time of precompetition weigh-in, thereby within a 1 week recall of the DCFs and a suppressed serum TSH would be evident. As nonprescribed TH use by athletes aiming to improve performance is not based on sound science, the motivation for usage is likely to arise from social influencers such as coaches, team members, or friends, which could lead to isolated niches of TH abuse 35 that may be missed in surveys assuming a uniform patterns of usage.