Investigation of pituitary dysfunction in retired professional soccer players / Investigação de disfunção hipofisária em jogadores de futebol profissionais aposentados / Investigación de disfunción hipofisaria en jugadores de fútbol profesionales retirados

ABSTRACT Introduction: It is well-known that pituitary dysfunction can develop as a result of traumatic brain injuries. One reason for such injuries is collision during contact sports. Objectives: The aim of this study was to investigate the effects of heading the ball and concussion on pituitary function in retired soccer players. Methods: Thirty-two retired soccer players, with an average age of 43.38 ± 5.49 (35-59) and 26 sedentary individuals with an average age of 43.31±6.38 (35-59) were included in this study. The subjects were questioned about their soccer-playing background, history of head trauma and concussion, and cardiometabolic diseases. One day one, blood samples were taken to investigate the baseline hematologic and biochemical parameters. On day two, the ACTH stimulation test was conducted, and on day three, glucagon stimulation tests were carried out. Resting EKG, transthoracic ECHO and exercise stress tests (for MET values) were also conducted. For the statistical analysis, The Student's t-test was used to compare the results of the two groups. The level of significance adopted was p<0.05. Results: It was identified that 5 out of 32 soccer players (16%) had experienced concussion during their soccer careers. The growth hormone (GH) levels of 3 retired soccer players (9.2%) and 3 sedentary individuals (10%) was below 1 ng/dl, which was accepted as the threshold value. There were no significant differences between hematological, biochemical and cardiometabolic parameters of the soccer players with low GH levels and those with normal GH levels. There was no significant relationship between the number of headers performed and GH deficiency. Conclusion: Although low GH levels were detected in almost 10% of the retired soccer players, the frequency of hypopituitarism was not higher than in the sedentary control group. Level of evidence I; Prognostic Studies.

RESUMO Introdução: É fato conhecido que a disfunção hipofisária sobrevém em decorrência de lesões cerebrais traumáticas. Uma das razões para essas lesões é a colisão durante esportes de contato. Objetivo: O objetivo deste estudo foi investigar os efeitos do cabeceamento de bola sobre a hipófise e suas funções em jogadores de futebol aposentados. Métodos: Participaram deste estudo 32 jogadores de futebol aposentados com média de idade de 43,38 ± 5,49 (35-59) e 26 indivíduos sedentários com média de idade de 43,31 ± 6,38 (35-59) que foram questionados quanto à experiência como jogador de futebol, história de traumatismo craniano, concussões e doenças cardiometabólicas. No primeiro dia, foram obtidas amostras de sangue para investigar os parâmetros hematológicos e bioquímicos basais. No segundo dia, foi realizado o teste de estimulação com ACTH; no terceiro dia, foram feitos os testes de estimulação com glucagon. Além disso, foram realizados ECG de repouso, ecocardiograma transtorácico e testes de esforço para obter o equivalente metabólico (MET). Na análise estatística, o teste t de Student foi usado na comparação dos resultados dos dois grupos. O nível de significância foi estabelecido em p < 0,05. Resultados: Identificou-se que cinco dos 32 jogadores de futebol (16%) sofreram uma concussão durante a carreira futebolística. Os níveis de hormônio de crescimento (GH) de três jogadores de futebol (9,2%) e de três indivíduos sedentários (10%) foram inferiores a 1 ng/dl, valor que foi aceito como limiar. Não houve diferença significativa entre os parâmetros hematológicos, bioquímicos e cardiometabólicos dos jogadores de futebol com deficiência de GH e os jogadores de futebol com nível normal de GH. Não houve relação significativa entre o número de cabeceamentos e a deficiência de GH. Conclusão: Embora a deficiência de GH tenha sido detectada em quase 10% dos jogadores aposentados, a frequência de hipopituarismo não foi maior do que a dos controles sedentários. Nível de evidência I; Estudos Prognósticos.

RESUMEN Introducción: Es un hecho conocido que la disfunción hipofisaria sobreviene a consecuencia de lesiones cerebrales traumáticas. Una de las razones para esas lesiones es la colisión durante deportes de contacto. Objetivo: El objetivo de este estudio fue investigar los efectos de la cabezada en la pelota sobre la hipófisis y sus funciones en jugadores de fútbol retirados. Métodos: Participaron en este estudio 32 jugadores de fútbol retirados con promedio de edad de 43,38 ± 5,49 (35-59) y 26 individuos sedentarios con promedio de edad de 43,31 ± 6,38 (35-59) que fueron cuestionados cuanto a la experiencia como jugador de fútbol, historia de traumatismo craneano, concusiones y enfermedades cardiometabólicas. En el primer día, fueron obtenidas muestras de sangre para investigar los parámetros hematológicos y bioquímicos basales. En el segundo día, fue realizado el test de estimulación con ACTH. En el tercer día, fueron hechos los tests de estimulación con glucagón. Además, fueron realizados ECG de reposo, ecocardiograma transtorácico y tests de esfuerzo para obtener el equivalente metabólico (MET). En el análisis estadístico se usó el test t de Student en la comparación de los resultados de los dos grupos. El nivel de significancia fue establecido en p<0,05. Resultados: Se identificó que cinco de los 32 jugadores (16%) sufrieron una concusión durante la carrera futbolística. Los niveles de hormona de crecimiento (HC) de tres jugadores de fútbol (9,2%) y de tres individuos sedentarios (10%) fueron inferiores a 1 ng/dl, valor que fue aceptado como umbral. No hubo diferencia significativa entre los parámetros hematológicos, bioquímicos y cardiometabólicos de los jugadores de fútbol con deficiencia de HC y los jugadores de fútbol con niveles normal de HC. No hubo relación significativa entre el número de cabezadas y la deficiencia de HC. Conclusión: Aunque la deficiencia de HC haya sido detectada en casi 10% de los jugadores retirados, la frecuencia de hipopituitarismo no fue superior a la de los controles sedentarios. Nivel de evidencia I; Estudios pronósticos.

Comparison of a combination test (1 µg ACTH test plus glucagon test) versus 1 µg ACTH test and glucagon test in the evaluation of the hypothalamic-pituitary-adrenal axis in patients with pituitary disorders

ABSTRACT Objective To investigate whether a combination of the low-dose (1 µg) adrenocorticotropin (ACTH) stimulation test and glucagon stimulation test (GST) could overcome the problem of equivocal results with the GST or ACTH test alone in patients with pituitary disorders. Subjects and methods The study included 41 adult patients with pituitary disorders and 20 healthy subjects who underwent evaluation of cortisol response to ACTH, GST, and a combination of both tests. Blood samples for cortisol measurement were obtained at baseline and 30, 60, 90, and 120 minutes after intravenous administration of ACTH 1 μg and 90, 120, 150, 180, 210, and 240 minutes after subcutaneous injection of glucagon 1 mg. The combination test was performed by injecting ACTH 1 µg at the 180-minute time point of the GST, with blood samples for cortisol measurement obtained at 210 and 240 minutes. Results Overall, 28 patients with normal cortisol response to both tests also had a normal cortisol response to the combination test. Ten patients with adrenal insufficiency in both tests also had adrenal insufficiency in the combination test, including a patient who had a peak cortisol value of 12.4 µg/dL (which is the cutoff value for the combination test). Two patients with adrenal insufficiency in the ACTH stimulation test and one patient with adrenal insufficiency in the GST had normal cortisol responses to the combination test. Conclusion By using an appropriate cutoff value, the combination test may offer additional information in patients with equivocal results in the GST and ACTH stimulation test.

Is biochemical hypoglycemia necessary during an insulin tolerance test?

ABSTRACT Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8