Fatih Tanriverdi, MD; Kursad Unluhizarci, MD; Ismail Kocyigit, MD; Ibrahim S. Tuna, MD; Zuleyha Karaca, MD; Ahmet C. Durak, MD; Ahmet Selcuklu, MD; Felipe F. Casanueva, MD, PhD; Fahrettin Kelestimur, MD
Acknowledgment: The authors thank Caner Doğaneli (Head of Turkish Boxing Federation and General Secretary of World Boxing Federation), Faruk Hasetçi (Executive Member of Turkish Boxing Federation), and Dr. Mustafa Demirel (Member of Turkish Boxing Federation) for giving permission for the study. They also thank all the national boxers and trainers who participated in the study.
Grant Support: By the Scientific and Technical Research Council of Turkey (TÜBITAK, project no. SBAG-3017).
Potential Financial Conflicts of Interest:Consultancies: F.F. Casanueva (Pfizer). Honoraria: F.F. Casanueva (Pfizer). Grants received: F.F. Casanueva (Pfizer).
Reproducible Research Statement:Study protocol: Not available. Statistical code: Available by contacting Dr. Tanriverdi (e-mail, firstname.lastname@example.org). Data set: Not available.
Requests for Single Reprints: Fatih Tanriverdi, MD, Erciyes University Medical School, Department of Endocrinology, 38039, Talasyolu, Kayseri, Turkey; e-mail, email@example.com.
Current Author Addresses: Drs. Tanriverdi, Unluhizarci, Kocyigit, Tuna, Karaca, Durak, Selcuklu, and Kelestimur: Erciyes University Medical School, 38039 Talasyolu, Kayseri, Turkey.
Dr. Casanueva: Santiago de Compostela University, PO Box 563, San Francisco Street 1, E-15780 Santiago de Compostela, Spain.
Author Contributions: Conception and design: F. Tanriverdi, K. Unluhizarci, A. Selcukulu, F.F. Casanueva, F. Kelestimur.
Analysis and interpretation of the data: F. Tanriverdi, K. Unluhizarci, F.F. Casanueva, F. Kelestimur.
Final approval of the article: F. Tanriverdi, K. Unluhizarci, I. Kocyigit, I.S. Tuna, Z. Karaca, A.C. Durak, A. Selcuklu, F.F. Casanueva, F. Kelestimur.
Collection and assembly of data: F. Tanriverdi, I. Kocyigit, I.S. Tuna, Z. Karaca, A.C. Durak.
Tanriverdi F., Unluhizarci K., Kocyigit I., Tuna I., Karaca Z., Durak A., Selcuklu A., Casanueva F., Kelestimur F.; Brief Communication: Pituitary Volume and Function in Competing and Retired Male Boxers. Ann Intern Med. 2008;148:827-831. doi: 10.7326/0003-4819-148-11-200806030-00005
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Published: Ann Intern Med. 2008;148(11):827-831.
Recent data clearly demonstrated that traumatic brain injury (TBI) is an important public health problem and may result in hypopituitarism (1, 2). After TBI, 25% to 50% of patients have some degree of pituitary dysfunction—growth hormone (GH) deficiency in particular (1–3). Concussion is reported to be the main diagnosis after TBI. This injury is associated with such sports as boxing, kickboxing, and football (4). Recent data suggest that sports injury may cause TBI and pituitary dysfunction (5–7).
Universidad Nacional AutÃ³noma de MÃ©xico
June 10, 2008
Pituitary dysfunction in boxers
After reading the article by Tanriverdi et al(1),I would like to comment on pituitary dysfunction and hypotrophy of the pituitary gland in 38 of 61 boxers, especially in retired boxers(mean age,44 years) than in young boxers(mean age,17 years). The plasma concentration of Insulin-like growth factor I( IGF-I,also known as somatomedin C) vary between 500 to 1500 U per liter in healthy men of 20 to 40 years of age(2),and on almost all boxers,there were somatomedin C deficiency, particularly in retired boxers(1 ). The pathogenesis of pituitary dysfunction caused by traumatic brain injury has not yet been resolved.However, based on anatomical data (3,4) and neurosurgical findings(4,5),I believe that the reduction of the pituitary volume associated to a dysfunction observed in active or retired boxers is due to progressive ischemia,secondary to vascular deterioration of the collateral arteries derived from supraclinoid carotids,especially of the superior hypophysial arteries and its branches(4).Thus the hypothalamus,median eminence, infundibular stem and hypophysis is afffected during the chronic head trauma and/or subarachnoid hemorrhage in boxing.
Finally the movement of the brain during the boxing may also provoke vascular damage in the intraparenchymal territory of the anterior and posterior perforating arteries and thus,it may be cause of aging,type 2 diabetes,obesity,essential hypertension, AlzheimerÂ´s and ParkinsonÂ´s diseases,among others.
1-Tanriverdi F,Unluhizarci K,Kocygit I,et al. Brief communication:Pituitary volume and function in competing and retired male boxers.Ann Intern Med 2008;148:827-831.
2-Rduman D, Kutner MH,Roger CM,et al.Impaired growth hormone secretion in the adult population:Relation to age and adiposity.J Clin Invest 1981;67:1361-1369.
3-Daniel PM. The blood supply of the hypothalamic and pituitary gland. Br Med Bull 1966;22(3):202-208.
4-Rafael H. Rejuvenation after omental transplantation on the optic chiasma and carotid bifurcation. Case Rep Clin Pract Rev 2006;7:48-51. www.amjcaserep.com
5-Rafael H.Cerebral atherosclerosis and oxidative stress in some challenging diseases. J Neurol Sci (Turk) 2004;21(4):343-349.
October 12, 2008
effects of performance enhancing drugs on pituitary size
To the Editor:
I read with great interest the report on "pituitary consequences of chronic head trauma in boxing," presented by Unluhizarci, Kocyigit et al., in your most recent issue. The authors report that of 17 retired boxers, 8 had growth hormone deficiency. It was also noted that growth hormone deficiency correlated with small pituitary volume. The suggestion was made that the head trauma involved in boxing could be the explanation for this observation.
I would like to suggest an alternative explanation. Over the past year, much information has come to light regarding the use of performance enhancing drugs in professional sports in the United States, particularly in baseball. Growth hormone and steroids have been the most commonly mentioned performance enhancing drugs in the world of professional sports. Even in sports with careful regulation, it is difficult to detect the use of growth hormone, because of the difficulties involved in measuring exogenous growth hormone.
It is quite conceivable that athletes in other sports have used performance enhancing drugs. One might expect athletes who have taken exogenous growth hormone for years during their career and then stopped them on retirement, to have low growth hormone levels and a suppressed and shrunken pituitary gland. If chronic head trauma were responsible for the changes, one would expect to find other hormonal abnormalities associated with the pituitary gland. It is curious that the only abnormalities were found in growth hormone and adrenocorticotrophic hormone, those hormones associated with performance enhancement. The other hormone levels were normal.
The chronic use of growth hormone and steroids is a more plausible explanation of the clinical observation in the study. If this were the case, it would be extremely important to study this further in other athletes to understand the effects of long-term use of performance enhancing drugs.
Erciyes University Medical School, Department of Endocrinology, Kayseri, Turkey
October 23, 2008
Re: effects of performance enhancing drugs on pituitary size
To the editor,
In our study (1), using any kind of drug affecting the pituitary function was an exclusion criterion, and none of the retired amateur boxers had a history of using any performance enhancing drugs such as anabolic steroids or growth hormone (GH) during their sports life. Although the use of doping agents, GH in particular, is well known among professional athletes in Western countries (2), GH vials were not available in Turkey especially at the years of these retired boxers' active sports life. Moreover to avoid the use of doping agents, national and international amateur boxing federations have very strict regulations.
While there are not enough data regarding the effects of chronic use of GH on pituitary function and volume in athletes, one might expect the suppression of the GH axis and decreased pituitary volume as suggested. However after the cessation of GH or anabolic steroids, it is a well known phenomenon that the suppression of the relevant axis recovered over several months or rarely several years. The mean time since retirement was 16 years (range, 8-28 years) in our retired boxer group and this is a quite enough time for recovering of all the possible drug related changes. Additionally there were significant negative correlations between the length of boxing career and GH reserve. And if retired boxers had used GH as assumed, it would be expected that both GH deficient and GH normal boxers had decreased pituitary volume. However GH deficient retired boxers had significantly decreased pituitary volume when compared to GH normal retired boxers (1).
In a meta-analysis including the patients with head trauma induced hypopituitarism due to various causes other than sports, GH deficiency is the most common problem, and the rate of isolated hormone deficiencies are higher than the multiple hormone deficiencies (3). Therefore presence of the isolated hormone deficiencies, GH deficiency in particular, was not surprising in our boxer group. The anatomic localization of the GH secreting cells in the pituitary gland, which are located at the outer border and lateral wings, could be one possible explanation for the vulnerability of these cells to trauma. Moreover in a very recent study APO E3/E3 genotype was shown to decrease the risk of trauma induced hypopituitarism in boxers and kickboxers suggesting a genetic susceptibility (4).
In conclusion based on the above mentioned evidences hypopituitarism in retired boxers is due to sports related chronic head trauma, and it could not be simply explained by possible use of doping agents. In addition since this is not the case, assuming a misuse of GH by the boxers in this study leads to overlooking of the potential hazards of boxing on pituitary function. However it would be interesting to investigate the pituitary consequences of chronic use of doping agents in professional athletes who had a clear history.
1. Tanriverdi F, Unluhizarci K, Kocyigit I, Tuna IS, Karaca Z, et al. Brief communication: pituitary volume and function in competing and retired male boxers. Ann Intern Med. 2008;148: 827-31. [PMID: 18519929]
2. Duntas LH, Parisis C. Doping: a challenge to the endocrinologist. A reappraisal in view of the Olympic Games of 2004. Hormones (Athens). 2003;2:35-42. [PMID: 17003000]
3. Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A. Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA. 2007;298:1429-38. [PMID: 17895459]
4. Tanriverdi F, Taheri S, Ulutabanca H, Caglayan AO, Ozkul Y, Dundar M, et al. Apolipoprotein E3/E3 Genotype Decreases the Risk of Pituitary Dysfunction after Traumatic Brain Injury due to Various Causes: Preliminary Data. J Neurotrauma. 2008;25:1071-77. [PMID: 18707245]
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Endocrine and Metabolism, Neurology, Pituitary Disorders.
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