Thyroid metabolism and supplementation: A review framed in sports environment

The empirical reference range for serum FT4 and FT3 was only minimally higher than the manufacturer’s recommended expected range, though the origins of those reference ranges are not disclosed. Australia’s national state of mild iodine deficiency 51 was rectified by the introduction of mandatory iodine salt fortification in 2009, so slow resolution of residual effects of iodine deficiency may explain the progressive temporal changes in TH concentrations and relativities. Whether regular training may explain such small effects on TH concentrations cannot be excluded based on the variable effects reported of long-term exercise on serum TSH and TH concentrations 52, 53. However, there are few studies of TH measurements over long-term frozen storage, and none using LCMS measurements of serum T4 or T3.

Experience suggests that such innovator products can enter the doping black market before marketing approval (150,171). Despite the profusion of pre-clinical leads, they represent families of related chemical structures disclosed in patents for which LC and/or GC-MS detection tests should, in principle, be effective. Understanding the metabolism of these drugs when they come to market may identify long-lasting metabolites that can extend the windows of detection.

MeSH terms

In practice, creating enforceable boundaries for drugs in sport is unavoidable whether it is prohibition or, even under the most idealistic libertarian scenarios, by age or dosage. Within the limitations of unverifiable self-report regarding an illicit activity (7,8), surveys indicate athletes support antidoping testing mainly to prevent cheating but also to promote safety (9-11). Motivating factors for, and routes by which athletes get involved in doping are complex but include the use of non-banned nutritional supplements as a gateway to doping (12) and the suspicion of athletes or their entourage that their rivals may be using illicit drugs, the so-called “false consensus belief” (7,13-15).

IGF and Insulin Doping

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. Consecutively raised TSH levels, with paired levels of T4 below the normal range indicate primary hypothyroidism. Among those with decreased serum FT4, 3 had a high serum TSH (47.1, 16.5, 10.3 mIU/L) with the remainder having normal serum TSH.

The use of LCMS measurements for TH for which valid reference standards exist, may offer better accuracy 72, 73, 77 when operating within WADA laboratories with extensive LCMS expertise, but they remain not widely available in general clinical pathology laboratories. For the unscrupulous in pursuit of the unlawful, the increasingly stringent synthroid confusion 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. These are within the size range of automated bulk custom peptide synthesis and are marketed cheaply by chemical manufacturers.

COMPONENTS OF SPORTS PERFORMANCE AND DOPING

Hypothyroidism has been demonstrated to reduce cardiopulmonary function and result in musculoskeletal symptoms, such as fatigue and muscle stiffness. Symptoms of hypothyroidism, including depression, fatigue, and impaired sleep, are similar to those reported in overtraining. These patients may have hypothalamic-pituitary dysfunction that may complicate interpretation of basal thyroid-stimulating hormone and free T4. Research to more clearly define hypothyroidism using provocative testing, evaluate the potential for thyroid medication to enhance performance, and examine whether training may induce hypothyroidism in athletes is desirable.

• 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.
• 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).
• 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.
• 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.
• Although not all assessed parameters showed significant differences, there was observed a tendency to decrease steroid concentrations in the group of athletes who declared the consumption of levothyroxine.

• HIF is a key generic biological mechanism for tissue sensing of hypoxia and triggering local (neovascularization, angiogenesis) and systemic (EPO) defensive reactions.
• 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).
• 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).
• Overall, detection of direct androgen doping is now so effective that in WADA-compliant elite competitions it is restricted to the ill-informed, often using counterfeit or unlabeled products (120).

Subsequent dose-response studies showed that administration of T increased muscle mass and strength by 10% without and 20-37% with exercise (where exercise alone increased them by 10-20%) together with additive effects from 3% increase in circulating hemoglobin. These benefits extended from below to well above physiological T doses or blood levels without evidence of plateau (37,38) and regardless of age (39). Additional underutilized options to detect androgen doping is the use of alternative biological matrices such as hair, skin or nails as well as saliva and exhaled breath (86).

Thyroid Function in Athletes and Dancers

The latter may resemble the loss of immunoassayable hCG in prolonged frozen storage at −20 °C, but not −80 °C, due to dissociation of glycoprotein hormone subunits which hinders dual-site immunoassays with epitopes on different subunits 61. Time-series analysis of elite sports performance (235) is consistent with the occurrence of IGF-1 doping but its prevalence is unknown (56). As the biological basis for ergogenic effects of IGFs is due to its GH-like effects, this remains largely speculative and accompanied by the same safety concerns.

Associated Data

Median serum TSH did not differ significantly between male and female athletes (Fig. 1) nor across the years of sampling (Fig. 2). WADA’s science director, Dr. Olivier Rabin, told the Wall Street Journal that WADA concluded thyroid medication doesn’t improve athletic performance in people who don’t have a medical need for it. 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 requested that WADA ban thyroid medication, because of concerns that athletes take it to improve performance. One alleged way thyroid medication could be performance-enhancing is by speeding recovery, which would theoretically allow harder training than would otherwise be possible. Anti-Doping Agency and its British counterpart, the World Anti-Doping Agency will continue to allow elite athletes to take thyroid medication.

Brown said he knows of no other endocrinologists treating athletes for hypothyroidism, a fatigue-causing condition that typically strikes women middle-aged or older. Using the expected reference ranges, there were 4 with low TSH, with all having normal serum T4 and rT3. Of the 8 athletes with serum TSH between the lower limits of expected (0.28 mIU/L) and empirical (0.68 mIU/L) reference ranges (Table 2), none had any out-of-range TH concentrations. Two athletes had biochemical thyrotoxicosis giving a prevalence of 4 per 1000 athletes (upper 95% confidence limit CL 16). 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.