Thyroid Medication Will Remain Legal for Elite Athletes

In practice, the increased mortality due to administration of high dose GH in critical illness (202) has led to GH treatment not being widely adopted in clinical practice of treatment of burns. Similarly, the only well controlled study of GH effects on bone healing from fracture reported that, among over 400 patients with tibial fractures treated for up to 16 weeks with GH (1, 2 or 4 mg/day) or placebo, there was no benefit of GH for overall healing (203). Finally, while there are numerous experimental studies of GH or growth factors on wound healing in animal models a wide variety of findings are reported with detrimental, neutral, or beneficial effects but no well-controlled human studies are available. Other EPO mimetics such as hypoxia mimetic drugs including hypoxia-inducible factor (HIF) stabilizers and related small molecules represent growing threats as potential indirect hemoglobin doping agents (171). These non-peptide chemicals interfere with various steps of the molecular oxygen sensing mechanism to mimic renal hypoxia and thereby induce EPO secretion resulting in increased blood hemoglobin.

COMPONENTS OF SPORTS PERFORMANCE AND DOPING

Rules of sporting contest may change by agreement, but once set, represents the boundaries of fair competition. Nevertheless, fairness is an elastic, socially constructed concept which may change gradually over time. For example, a century ago deliberate training itself was considered an ungentlemanly breach of fairness as competition was then envisaged as a contest based solely on natural endowments. The philosophical foundations of the concept of fairness is a deep and complex issue (2,3) where the focus has been mainly on distributive justice with an implicit goal of equality of outcomes. Less attention has been given to the philosophical basis of fair competition in sport where the prior distribution of talent and training and the outcome valtrex synthroid of contest are intended to provide equality of opportunity, but not of outcome, between contestants. ConclusionThe Wall Street Journal‘s profile of Dr. Brown and his unorthodox management of elite athletes raises interesting questions about the basis of disease, the conditions for drug treatment, and the implications on the ethics of sports.

• This seems to be what Brown believes, seeing dysfunction where other physicians see normal thyroid activity.
• It is well understood that individual human genetic endowments are unequal and, among these, sporting prowess is at least partly genetically determined (17).
• The detection of the administration of TH, at least triiodothyronine (T3) and levothyroxine (T4) in urine could work when dealing with euthyroid individuals, either by applying cut-off values of ratios (for T3) or the presence of T1 (for T4).
• For privacy reasons, additional information was restricted to age, sex, and sport for each serum sample and DCF.

Is thyroid replacement a performance-enhancing drug?

Now is a good time to revisit a topic discussed in my previous BJSM blog(i), to coincide with guidelines on the management of thyroid disease released by National Institute of Clinical Excellence (NICE) in November 2019(ii), and summarised in the British Medical Journal (BMJ) last month(iii). In this healthy, young population, high serum TSH may be due to hypothyroidism when accompanied by low serum T4 (or FT4) and/or T3 (or FT3). There is minimal evidence for TH abuse among Australian athletes being tested for competing in WADA-compliant sports. Some well-known American distance runners, including former U.S. 5,000-meter record holder Bob Kennedy, two-time Olympian Kara Goucher, and U.S. 10,000-meter record holder Galen Rupp, are known to have been prescribed thyroid medication for hypothyroidism or other thyroid-related conditions.

Serum TSH (upper left panel), T4 (upper middle panel), T3 (upper right panel), rT3 (lower left panel), FT4 (lower middle panel), and FT3 (lower right panel). In each plot the horizontal dashed lines represent the upper and low empirical 95% confidence limits determined by nonparametric centiles from the data and the dashed lines represent the manufacturers expected reference range for serum TSH, FT4, and FT3. Among the substances declared by the athletes during the sample collection sessions and reported in the doping control forms (DCF), it is quite frequent to observe supplements or medication based on thyroid hormones. This supplements or medications contain not only levothyroxine (T4) or triiodotironine (T3) but some of their derivatives as Triacana (3,5,3’-triiodothyroacetic acid) or Tetrac (3,5,3’,5’-tetraidothyroacetic acid).

Until that time, the settled consensus was that exogenous androgens had no effect in eugonadal men whose androgen receptors were already saturated by endogenous testosterone (T) (20,34,35). The then alleged benefits of androgen doping were misattributed placebo responses together with training and nutritional effects. Using an exemplary placebo-controlled, randomized clinical trial design with a wide range of testosterone doses, Bhasin et al showed that T increased muscle mass and strength in eugonadal young men to a similar extent as exercise alone and with additive effects when combined with exercise (36) (figure 3).

Abuse of androgens and erythropoietin has led to hormones being the most effective and frequent class of ergogenic substances prohibited in elite sports by the World Anti-Doping Agency (WADA). At present, thyroid hormone (TH) abuse is not prohibited, but its prevalence among elite athletes and nonprohibited status remains controversial. A corollary of prohibiting hormones for elite sports is that endocrinologists must be aware of a professional athlete’s risk of disqualification for using prohibited hormones and/or to certify Therapeutic Use Exemptions, which allow individual athletes to use prohibited substances for valid medical indications. This narrative review considers the status of TH within the framework of the WADA Code criteria for prohibiting substances, which requires meeting 2 of 3 equally important criteria of potential performance enhancement, harmfulness to health, and violation of the spirit of sport. Cheating is as old as sport itself, yet the present endemic of doping using pharmaceutical drugs to boost sports performance is largely a Cold War legacy. Eastern European national doping programs were established by governments aiming to achieve a short-cut propaganda victory over their Western rivals, a challenge quickly reciprocated and then taken up by individual coaches and athletes.

While potentially applicable to xenobiotic drugs, salivary testosterone immunoassay is not sufficiently accurate (112) and is not suitable to detect testosterone doping because even microscopic blood contamination (e.g. gingivitis, chewing hard food, tooth brushing) produces anomalous high readings. The existence of these renders salivary testosterone testing for antidoping purposes as unreliable by providing opportunity for claims of false positive for any adverse findings. High performance in any sport requires a characteristic blend of these dimensions although individual sports differ widely in that balance. Similarly, the major ergogenic drug classes have distinctive effects aligned predominantly along one of these dimensions so that the most effective ergogenic drug classes used in doping are dictated by these dimensions of sports performance (Figure 2).

Links to NCBI Databases

IGF-1, IGF-2 and their analogs (236) as well as insulin and its analogs (237) are all readily detectable by LC-tandem MS and preliminary evidence suggests that biomarkers for IGF-1 administration (IGF-2, IGFBP2) may widen the window of detection (238). In principle, detection of prohibited substances is ideally aimed at identifying a xenobiotic substance or its distinctive chemical signature(s) which do not occur naturally in the body, thereby distinguishing it categorically from normal body constituents. Such identification of a non-natural substance that can’t be of endogenous origin is congruent with the strict liability onus in proving an anti-doping rule violation (ADRV). Proving an ADRV is more difficult to achieve with administration of natural hormones or their analogs which must be distinguished from their endogenous counterparts. In this situation, the alternative requires developing valid biomarkers to prove the use of banned substances through their distinctive effects on the body and tissues. It is a formidable challenge to validate an indirect biomarker as proof of an ADRV capable of withstanding vigorous medico-legal challenge when a proven ADRV would prevent an athlete from pursuing their profession.

• Overt hyperthyroidism causes anxiety, insomnia, weakness, perspiration, and mood swings – nothing an athlete wants.
• 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.
• According to the National Institutes of Health, about 4.6 percent of the U.S. population has hypothyroidism, in which the body doesn’t naturally produce enough thyroid hormone.
• Anti-doping science history suggests that caution is required before rejecting evidence for claimed ergogenic effects without investigations replicating the pharmacological doses used.

The Prohibited List bans, at any time either in or out of competition, the use of performance enhancing hormones, including androgens, EPO and growth hormone and related substances or drugs which stimulate endogenous production of these hormones (Table 1). In addition, the S0 category bans non-approved substances, those without current regulatory approval for human therapeutic use. The prominence of hormones is reinforced by the WADA laboratory statistics for anti-doping tests where hormones remain the most frequently detected banned drugs (Table 2).

Overt hyperthyroidism causes anxiety, insomnia, weakness, perspiration, and mood swings – nothing an athlete wants. And long-term it has side effects including cardiovascular and bone risks – excess thyroid is a definite “bone eater”, with bone resorption stimulated and osteoporosis being the result. Other aberrations of TH measurements were mostly isolated deviations of a single TH from the reference range with uncertain significance. In this young healthy population the potential benefits or harms of mild or subclinical thyrotoxicosis are speculative and unlikely 42. Similarly, despite evidence from the unregulated bodybuilding internet sites encouraging T3 use as a more potent and faster-acting TH 1, there was no evidence of T3 toxicosis such as a disproportionate increase in serum T3 or FT3 with or without suppressed serum TSH in this athlete population. Dot and density plot of thyroid hormones among 498 elite Australian athletes comprising 183 females and 315 males.