Acute mountain sickness is related to nocturnal hypoxemia but not to hypoventilation. P. Erba, S. Anastasi, O. Senn, M. Maggiorini, K.E. Bloch. #ERS Journals Ltd 2004. ABSTRACT: The purpose of the study was to investigate determinants of acute mountain sickness after rapid ascent to high altitude.A total of 21 climbers were studied ascending from v1,200 m to Capanna Regina Margherita, a hut in the Alps at 4,559 m, within v24 h. During their overnight stay at 4,559 m, breathing patterns and ventilation were recorded by calibrated respiratory inductive plethysmography along with pulse oximetry. In the following morning, acute mountain sickness was assessed.Altogether, 11 mountaineers developed pronounced symptoms of acute mountain sickness (Lake Louise score o5) and 10 did not (controls). Compared to controls, subjects with acute mountain sickness had lower nocturnal oxygen saturation (mean¡SD 59¡13% versus 73¡6%), higher minute ventilation (7.94¡2.35 versus 6.06¡ 1.34 L?min -1 ), and greater mean inspiratory flow, a measure of respiratory centre drive (0.29¡0.09 versus 0.22¡0.05 L?s -1 ). Periodic respiration was prevalent but not significantly different among the two groups (apnoea/hypopnea index 60.1¡34.6 versus 47.1¡42.6 events per h).The data suggest that pronounced nocturnal hypoxemia, which was not related to hypoventilation, may have promoted acute mountain sickness. Periodic breathing seems not to play a predominant role in the pathogenesis of acute mountain sickness. Otherwise healthy subjects ascending rapidly to altitudes w2,500 m often develop acute mountain sickness (AMS), a condition characterised by insomnia, headache, dizziness, loss of appetite, nausea and vomiting [1]. In the Alps, symptoms and signs of AMS sufficiently severe to force a reduction in activity were found in 6-8% of climbers examined at altitudes between 2,850 and 3,650 m, and in 30% of climbers at 4,559 m [2]. AMS is promoted by a rapid ascent rate, depends on the altitude reached, and on acclimatisation [3]. It occurs in both sexes, at all ages, and athletic fitness does not protect against it [1,4,5].Despite its high prevalence, the pathophysiology of AMS is incompletely understood. Hypoxia seems to play an important role [3,6,7]. A reduced ventilatory response to hypoxia, and impaired pulmonary gas exchange related to pulmonary fluid accumulation, and water and salt retention have been implicated in development of exaggerated hypoxemia in subjects with AMS [8][9][10]. As AMS often develops or worsens over the night, when periodic breathing and repetitive oxygen desaturation are also prevalent, a causal relationship or a common pathophysiological pathway have been evaluated [11,12]. However, the results of these earlier studies were inconclusive due to the small number of subjects with AMS enrolled, and the lack of quantitative estimation of ventilation during sleep.Therefore, the purpose of the current study was to further explore the potential role of periodic respiration, and other characteristics of breathing patterns, in p...

IntroductionIGF-1 deficiency in TM patients in children and adolescents has been attributed to chronic anemia and hypoxia, chronic liver disease, iron overload and other associated endocrinopathies, e.g. growth hormone deficiency (GHD). Few data are available in the literature regarding adult TM patients and growth disorders. The aim of this study was to measure IGF-1 values and other clinical data in a large number of adult patients with TM to evaluate the possible relationships between them.Patients and MethodsA cohort of 120 adult patients with TM was studied for plasma levels of IGF-1. Plasma total IGF-1 was determined by chemiluminescent immunometric assay (CLIA) method. In eleven patients (3 females) the GH response during glucagon stimulation test (GST) was also evaluated.ResultsFifty percent of patients (33 males and 27 females) had IGF-1 levels <- 2 SDs below normative values for healthy subjects matched for age and sex. In these patients endocrine complications and elevations of aminotransferases (ALT) were more common compared to TM patients with IGF1 > -2SDs. In multivariate regression analyses, height, weight, BMI, serum ferritin, ALT, HCV serology and left ventricular ejection fraction (LVEF) were not significantly related to IGF-1, but a significant correlation was found in females between HCV-RNA positivity and IGF-1, ALT and serum ferritin. AGHD was diagnosed in 6 (4 males) out of 11 patients (54.5%) who had glucagon stimulation tests and in 5 out of 8 (62.5%) with IGF-1 <-2SD. The mean age of patients with GHD was 39.3 years (range: 25–49 years, median: 39 years) versus 35.8 years (range: 27–45 years, median: 37.5 years) in non-GHD patients. A positive correlation between GH peak after GST and IGF-1 level was found (r: 0.6409; p: < 0.05).ConclusionsIn 50% of TM patients the IGF-1 levels were 2SDs below average values for healthy individuals. IGF-1 deficiency was more common in TM patients with associated endocrine complications, and a significant correlation was found in HCV-RNA positive females among IGF-1, ALT, and serum ferritin. Further data in a larger group of patients are needed to confirm whether IGF-1 level <-2 SDs may be a potential criterion for additional studies in TM patients. This datum could avoid performing GH stimulation tests in the majority of them.

BackgroundMulti-transfused thalassemia major (TM) patients frequently develop severe endocrine complications, mainly due to iron overload, anemia, and chronic liver disease, which require prompt diagnosis, treatment and follow-up by specialists.The most common endocrine complication documented is hypogonadotropic hypogonadism which increases with age and associated comorbidities. It is thus important for physicians to have a clear understanding of the pathophysiology and management of this disorder. Also to be aware of the side effects, contraindications and monitoring of sex steroid therapy. In this paper, practical ICET-A recommendations for the management of hypogonadism in adult females with TM are addressed.MethodsIn March 2015, the Coordinator of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) conducted a two-step survey to assess the attitudes and practices of doctors in the ICET-A network taking care of adult female TM patients with hypogonadism. They were clinically characterized by the absence of pubertal development or discontinuation or regression of the maturation of secondary sex characteristics, and biochemically by persistent low FSH, LH and estradiol levels. Recently a supplementary survey on adult female hypogonadism in TM was undertaken within the ICET-A network.ResultsThe completed questionnaires were returned by 16 of 27 specialists (59.2%) following 590 female TM patients over the age of 18 years; 315 patients (53.3%) had hypogonadism, and only 245 (74.6%) were on hormone replacement therapy (HRT). Contraceptive oral pills (COC) were the first treatment choice in 11 centers (68.7%). A wide range of COCs was used with different progestin contents. In general, the patients’ compliance to treatment was reported as good in 81.2 % of centers. The frequency of required tests for follow-up HRT, in addition to the regular check-up for thalassemia, was variable in the participating centers.ConclusionsDoctors taking care of TM patients should have sound knowledge of the pathophysiology of hypogonadism in adult females with TM. They should know the potential effects of HRT including advantages and disadvantages of estrogen and progestins. Moreover, they should keep in consideration the emotional needs of these patients dreaming of attaining a full pubertal development.

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Children with thalassemia are living longer due to better care. Physicians dealing with this group of patients now have to contend with new challenges resulting from iron overload. Endocrine complications represent the most common morbidities encountered. To provide a better quality of life, these complications have to be addressed in a consistent way. For this purpose, we have compiled a set of recommendations to help physicians provide the best care possible to these patients.