The use of prohibited substances for therapeutic reasons in athletes affected by endocrine diseases and disorders: the therapeutic use exemption (TUE) in clinical endocrinology.

To protect sporting ethics and athletes' health, the World Anti-Doping Agency (WADA) produced the World Anti-Doping Code and The Prohibited List of substances and methods forbidden in sports. In accordance with the International Standards for Therapeutic Use Exemption (ISTUE), to avoid rule violations and sanctions, athletes affected by different endocrine diseases and disorders (e.g., adrenal insufficiency, diabetes, male hypogonadisms, pituitary deficit, thyroid diseases, etc.) who need to use a prohibited substance for therapeutic reasons (e.g., medical treatments, surgical procedures, clinical diagnostic investigations) must apply to their respective Anti-Doping Organizations (ADOs) to obtain a Therapeutic Use Exemption (TUE), if specific criteria are respected. The physicians who treat these athletes (i.e., endocrinologists, andrologists and diabetologists) are highly involved in these procedures and should be aware of their specific role and responsibility in applying for a TUE, and in adequately monitoring unhealthy athletes treated with prohibited substances. In this paper, the prohibited substances commonly used for therapeutic reasons in endocrine diseases and disorders (e.g., corticotropins, beta-blockers, glucocorticoids, hCG, insulin, GnRH, rhGH, testosterone, etc.), the role of physicians in the TUE application process and the general criteria used by ADO-Therapeutic Use Exemption Committees (TUECs) for granting a TUE are described.

Why glucocorticosteroids should remain in the list of prohibited substances: a sports medicine viewpoint.

In addition to their therapeutic applications, glucocorticosteroids have been widely used and abused in the belief that these substances may enhance athletic performance. Analysis of athlete urine samples by antidoping laboratories around the world support this conclusion. It is commonly accepted in medical practice to use local glucocorticosteroid injections in the treatment of non-infectious local musculotendinous inflammatory conditions conveying symptom relief and often a speedier return to sporting activity. This practice is not to be considered illicit, but sports physicians must accept that such an intervention is not in itself an immediate cure and that an athlete will still require a period of recuperation before continuing sporting activity. How long such a period of recuperation should last is a matter of conjecture and there is little concrete data to support what is, or what is not, an acceptable period of inactivity. In the interest of athlete safety, we would propose to maintain systemic glucocorticosteroids on the World Anti-Doping Agency's (WADA) list of prohibited substances, both in and out-of-competition as well as a mandatory period of 48 hours of rest from play after receiving a local glucocorticosteroid injection.

Impact of different concentrations of human recombinant growth hormone on T lymphocytes.

The aim of the present study is to evaluate the effects induced by increasing concentrations of human recombinant growth hormone on T lymphocytes. Ten healthy volunteers and twelve subjects with symptomatic allergies were enrolled in the study. Peripheral blood mononuclear cells and purified T lymphocytes were cultured in the presence of graded concentrations of growth hormone. Following appropriate in vitro stimulations, the proportion of apoptotic T cells, the percentage of activated T lymphocyte subpopulations, the phytohemagglutinin responsiveness and the Th2 response were assessed by flow cytometry analysis. Moreover, in order to evaluate the phosphoinositol-3-kinase signaling pathway involvement, cells were also analyzed after treatment with LY294002. The treatment with different concentrations of growth hormone did not influence the activation pattern of un-stimulated T lymphocytes. On the contrary, growth hormone was able to modify the CD38/HLA-DR co-expression of T cells activated with phytohemoagglutinin. A different response was observed when samples obtained from healthy donors and from subjects with symptomatic allergies were analysed. Moreover, growth hormone treatment was able to increase the Th2 response in the samples obtained from healthy donors only. The results of the present study strongly support the hypothesis that growth hormone administration may play an important role in conditions of impaired/activated immune systems. The observation that growth hormone administration at high doses may reverse its effects and that it may promote a Th2-oriented response have significant clinical implications when considering the use of this hormone for artificially enhancing the physical performances of healthy athletes.

Urinary hepcidin identifies a serum ferritin cut-off for iron supplementation in young athletes: a pilot study.

The use of iron supplements should be a judicious choice, primarily when considering the possible risks deriving from an unjustified treatment. In trained athletes, levels of ferritin between 15 and 30 microg/L are frequently observed. Within this ferritin range, the usefulness of iron supplementation is still controversial. The aim of the present study is to evaluate the clinical usefulness of hepcidin assessment in the analysis of the iron status of young non-anemic athletes. Fifty young athletes were enrolled. The subjects were divided into 4 groups according to their ferritin levels. No statistically significant difference was found regarding hepcidin levels between athletes with ferritin lower than 15 microg/L and those in the 15-30 microg/L range. Similarly, no difference was found between athletes with ferritin higher than 50 microg/L and those in the 30-50 microg/L range. On the contrary, statistically significant differences were found between athletes with ferritin levels ranging from 15 to 30 microg/L and those in the 30-50 microg/L range. The present study suggests that serum ferritin levels below 30 microg/L indicate an asymptomatic iron deficiency status inhibiting hepcidin expression and that 30 microg/L should be considered the ferritin cut-off when considering an iron supplementation in young athletes.

Health risk screening in adolescents: a pilot study.

AIM: Even if youths are generally perceived to be healthy, adolescent years are associated with significant morbidity. Screening and counselling programmes seem to be cost-effective but adolescents prefer to rely on health care services for the treatment of diagnosed diseases or injuries rather than for preventive actions. Age oriented studies are needed for better understanding the health needs of adolescents in order to provide an adequate offer of preventive opportunities. METHODS: Eight hundred youths ranging from 13 to 18 years of age were recruited. Health status and risks were clustered into the following five categories: clinical assessment, substance use/abuse, nutritional habits, alcohol and tobacco consumption, physical status. Surprisingly, 33% of the youths were suggested to perform further clinical assessment and even more interestingly a significant number of them received a diagnosis of a symptomatic disorder for which he or she did not previously consider a medical visit to be necessary. RESULTS: As expected, alcohol consumption, tobacco smoking, drug use/abuse and sedentary habit represent the risky lifestyles commonly followed by adolescents. CONCLUSION: The present study confirms the importance of screening programs addressed to health issues and behavioural attitudes of adolescents even in light of the fact that they may underestimate even indicative symptoms.