Adaptation of ghrelin and the GH/IGF axis to high altitude.

OBJECTIVE: High altitude (HA) provokes a variety of endocrine adaptive processes. We investigated the impact of HA on ghrelin levels and the GH/IGF axis. DESIGN: Observational study as part of a medical multidisciplinary project in a mountainous environment. METHODS: Thirty-three probands (12 females) were investigated at three timepoints during ascent to HA (A: d -42, 120 m; B: d +4, 3440 m; C: d +14, 5050 m). The following parameters were obtained: ghrelin; GH; GH-binding protein (GHBP); IGF1; IGF2; IGF-binding proteins (IGFBPs) -1, -2, and -3; acid-labile subunit (ALS); and insulin. Weight was monitored and general well being assessed using the Lake Louise acute mountain sickness (AMS) score. RESULTS: Ghrelin (150 VS 111PG/ML; P0.01) and GH (3.4 VS 1.7G/L; P0.01) were significantly higher at timepoint C compared with A whereas GHBP, IGF1, IGF2, IGFBP3, ALS, and insulin levels did not change. IGFBP1 (58 VS 47G/L; P0.05) and, even more pronounced, IGFBP2 (1141 VS 615G/L; P0.001) increased significantly. No correlation, neither sex-specific nor in the total group, between individual weight loss (females: -2.1 kg; males: -5.1 kg) and rise in ghrelin was found. Five of the subjects did not reach investigation point C due to AMS. CONCLUSIONS: After 14 days of exposure to HA, we observed a significant ghrelin and GH increase without changes in GHBP, IGF1, IGF2, IGFBP3, ALS, and insulin. Higher GH seems to be needed for acute metabolic effects rather than IGF/IGFBP3 generation. Increased IGFBP1 and -2 may reflect effects from HA on IGF bioavailability.

Pediatric reference intervals for thyroid hormone levels from birth to adulthood: a retrospective study.

BACKGROUND: Age- and sex-specific reference intervals are an important prerequisite for interpreting thyroid hormone measurements in children. However, only few studies have reported age- and sex-specific pediatric reference values for TSHbasal (TSH), free T3 (fT3), and free T4 (fT4) so far. Reference intervals are known to be method- and population-dependent. The aim of our study was to establish reference intervals for serum TSH, fT3, and fT4 from birth to 18 years and to assess sex differences. METHODS: 2,194 thyroid hormone tests obtained from a hospital-based pediatric population were included into our retrospective analysis. Individuals with diagnoses or medications likely to affect thyroid function were primarily excluded, as well as the diagnostic groups, if different from the purely healthy subgroup (n = 414). Age groups were ranging from 1 day to 1 month, 1 - 12 months, and 1 - 5, 6 - 10, 11 - 14, and 15 - 18 years, respectively. Levels of fT3, fT4 and TSH were measured on Advia(R) Centaur automated immunoassay system. RESULTS: The final sample size for reference data creation was 1,209 for TSH, 1,395 for fT3, and 1,229 for fT4. Median and 2.5/10/25/75/90/97.5 percentiles were calculated for each age group. Males had greater mean fT3 concentrations than females (p < 0.001). No sex-differences were found for TSH and fT4 between age-matched serum samples. Median concentrations of fT3, fT4 and TSH were greatest during the first month of life, followed by a continuous decline with age. CONCLUSION: Our results corroborate those of previous studies showing that thyroid hormone levels change markedly during childhood, and that adult reference intervals are not universally applicable to children. Moreover, differences of our reference intervals compared to previous studies were observed, likely caused by different antibody characteristics of various analytical methods, different populations or undefined geographic covariates, e.g. iodine and selenium status.

Increase in 6-hydroxymelatonin excretion in humans during ascent to high altitudes.

Melatonin (MLT), the pineal gland hormone involved in the regulation of circadian rhythms, shows characteristic diurnal variation. Its physiological role in humans is not clear. Exposure to high altitudes may disrupt the circadian rhythm and lead to various endocrine changes. MLT in humans has not been studied under these conditions. Urinary 6-hydroxy-MLT sulfate (aMT6s) excretion was analyzed during the day (0700-2200 h) and night (2200-0700 h) phases. A cohort of 33 healthy volunteers, aged 19-65 yr, was studied during an ascent to a high altitude in the Himalayas on three occasions (at a lower altitude, at 3400 m, and after reaching maximal altitudes of 5600-6100 m). aMT6s excretion during the daytime remained unchanged during exposure to high altitudes. As expected, nocturnal values were higher than diurnal values at each point in time. However, there was a significant increase in nocturnal MLT excretion after the ascent to high altitudes. Ascent to high altitudes is associated with increased nocturnal excretion of aMT6s. The mechanism and physiological significance of this MLT increase are unclear.