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Adrenal, thyroid and gonadal axes are affected at high altitude
We have studied the acute circulatory response to high altitude hypoxia and investigated the extent to which shifts in the circulating blood volumes, if any, could be related to the time lag and clinical features of these acute illnesses. Roy, S. Hamilton, W. Kety, S.
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Wood, J. Heart J. Severinghaus, J. Eckstein, J. Significantly lower concentrations were noted when exercise 6-h trek took place before the measurement. A significant increase in prolactin was also found in nine mountaineers in whom baseline prolactin levels were measured directly after climbing Mount Everest 5.
However, the increase was not significant. Thyroid function dysregulations are not clear according to previous studies. Nepal et al. Basu et al.
Hackney et al. In our study, the most striking differences were found for fT4, which increased with altitude. Results were not clear for fT3 and TSH, but overall, the thyroid axis was activated.
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As the thyroid gland releases mainly T4, which is metabolized to T3, and as T4 has a much longer half-life than T3, it can be speculated that the altitude adaptations of thyroid function are easier to be detected using T4 levels. TSH might also not be an ideal parameter for the detection of altitude-dependent functional changes as an increase in TSH may barely be detectable due to the negative feedback loop of T3 and T4 Although a comparison of the studies is only possible to a limited extent and the data are somewhat heterogeneous, there appears to be an overall activation of the thyroid with increasing altitude, which is not detected at a pituitary level but in the thyroid gland.
Gonadal axes have previously poorly been studied. In the study by Benso et al.
As LH stimulation regulates the production of testosterone 15 , it can be assumed that low testosterone concentrations are a result of suppressed LH. Acclimatization and its effects have not yet been investigated in other studies with a suitable study design. LH and total testosterone concentrations decreased significantly in 52 soldiers after 6 months at this altitude.
The hormone levels increased again within the next 6 months. Sperm concentration, motility and vitality were also significantly reduced after 6 months at this altitude. Sperm concentration improved over the following 6 months, but not motility. After returning to lower altitudes, semen analysis normalized again. The decrease of semen parameters at high altitude was potentially relevant for fertility. There was a moderate asthenozoospermia at altitude, corresponding with andrological subfertility. In our study, normalization of the stress axes in both sexes as well as the male gonadal axis after acclimatization was also demonstrated.
We were able to show that normalization begins after just a few days. All these study results raise the question of what causes these changes. Interestingly, the hormonal changes hardly correlated with parameters of oxygen transport such as O 2 saturation and pO 2 values, but only with altitude. Consequently, high-altitude hypoxia may not exclusively cause these changes, and other factors must also have an influence.
The cold that occurs at high altitudes is probably not relevant or only of limited relevance because, due to good clothing, any relevant exposure to cold is mainly achieved via respiratory air. An effect of the increased physical burden at altitude due to hypobaric hypoxia is conceivable.
The effect of disturbed sleep due to periodic breathing at high altitudes would also be conceivable in terms of the change in stress axes Insomnia and shortened sleep leads to significantly higher cortisol levels, even at low altitudes 17 , Because of this, it can be assumed that several height-dependent factors such as hypoxia, cold, physical stress, disturbed sleep, etc. The question also arises if these endocrine changes might have a substantial effect on the health of humans living at high altitude for a long time.
Insomnia leads to increased cortisol concentrations and to increased blood pressure and the risk for cardiovascular diseases In line with this, patients with adverse cardiovascular events had higher median levels of cortisol Clinical and subclinical hyperthyroidism is associated with different kinds of cardiovascular diseases These effects might clinically be relevant as even a mild increase of blood pressure has an impact on mortality Therefore, in our view, the hypothesis is acceptable that the endocrine system might play a role in the fact that human beings cannot live long term at very high altitude.
The endocrine changes found at higher altitude might contribute to the physical degradation and thereby to the incapability of humans to live permanently at very high altitude. The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
M v W and J P H designed the study, participated in the expedition, analysed the data and prepared the manuscript. M T prepared the samples and performed the analysis. C T N performed the statistical analysis. Baker , Penn State University , in the Department of Anthropology also conducted a considerable amount of research into human adaptation to high altitudes, and mentored students who continued this research. Scientists started to notice the extraordinary physical performance of Tibetans since the beginning of Himalayan climbing era in the early 20th century.
The hypothesis of a possible evolutionary genetic adaptation makes sense. The Tibetans, who have been living in this region for 3, years, do not exhibit the elevated haemoglobin concentrations to cope with oxygen deficiency as observed in other populations who have moved temporarily or permanently at high altitudes. Instead, the Tibetans inhale more air with each breath and breathe more rapidly than either sea-level populations or Andeans.
Tibetans have better oxygenation at birth, enlarged lung volumes throughout life, and a higher capacity for exercise. They show a sustained increase in cerebral blood flow, lower haemoglobin concentration, and less susceptibility to chronic mountain sickness than other populations, due to their longer history of high-altitude habitation.
General people can develop short-term tolerance with careful physical preparation and systematic monitoring of movements, but the biological changes are quite temporary and reversible when they return to lowlands. In addition, they have high levels mostly double of nitric oxide in their blood, when compared to lowlanders, and this probably helps their blood vessels dilate for enhanced blood circulation.
Everest base camp in two weeks. Even when they climbed the highest summits like Mt. Everest, they showed regular oxygen uptake, greater ventilation, more brisk hypoxic ventilatory responses, larger lung volumes, greater diffusing capacities, constant body weight and a better quality of sleep, compared to people from the lowland. In contrast to the Tibetans, the Andean highlanders, who have been living at high-altitudes for no more than 11, years, show different pattern of haemoglobin adaptation.
Their haemoglobin concentration is higher compared to those of lowlander population, which also happens to lowlanders moving to high altitude.
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When they spend some weeks in the lowland their haemoglobin drops to average of other people. This shows only temporary and reversible acclimatisation. However, in contrast to lowland people, they do have increased oxygen level in their haemoglobin, that is, more oxygen per blood volume than other people.
This confers an ability to carry more oxygen in each red blood cell, making a more effective transport of oxygen in their body, while their breathing is essentially at the same rate. The Andean highlanders are known from the 16th-century missionaries that their reproduction had always been normal, without any effect in the giving birth or the risk for early pregnancy loss, which are common to hypoxic stress.
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Though the physical growth in body size is delayed , growth in lung volumes is accelerated. Among the Quechua people of the Altiplano , there is a significant variation in NOS3 the gene encoding endothelial nitric oxide synthase , eNOS , which is associated with higher levels of nitric oxide in high altitude. Blood profile comparisons show that among the Andeans, Aymaran highlanders are better adapted to highlands than the Quechuas. The intrapopulation genetic variation was relatively less among the Aymara people.
For example, among four quantitative features, such as are resting ventilation, hypoxic ventilatory response, oxygen saturation, and haemoglobin concentration, the levels of variations are significantly different between the Tibetans and the Aymaras. The underlying molecular evolution of high-altitude adaptation has been explored and understood fairly recently. For example, Tibetan adaptations became prevalent in the past 3, years, a rapid example of recent human evolution.