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ARTICLES Table of Contents   
Year : 2002  |  Volume : 5  |  Issue : 17  |  Page : 47-52
Excretion of Cortisol under Nocturnal Noise and Differences due to Analytic Techniques

Robert Koch-Institute, Federal Institute for Infectious and Noninfectious Diseases, Section: Environmental related disorders, Berlin, Germany

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The measurement of urinary free cortisol is an established index for the diagnosis of disorders involving glucocorticoids (see Braun et al. 1999) but the amount of free cortisol in urine samples is dependent on the analytic-technology. Competitive binding assays and radioimmuno assays, the methods used most commonly in routine laboratories, missestimate the amount of free cortisol because of interference by strongly cross-reacting substances in urine (Schoneshofer et al. 1986b). The specificity of these tests is too low to distinguish between free cortisol and near metabolites. The revision of the long-term study by "online" liquid chromatography (HPLC) suggestes that immuno assay technique produce doubtful results, particulary when free cortisol and metabolites react in different ways. This is of particular importance, since several studies containing indications, that an acute demand leads particularly to alterations of free Cortisol and a chronic demand essentially to alterations of metabolites. Schoneshofer pointed out already in 1986 that by additional measuring of the 20α-Dihydrocortisol and Cortisone it may be possible to differentiate chronic hypercorticoidism from the acute state. In connection with the findings of the present comparison it is urgently required to standardize both the data collection and the data analysis to get comparable results. Therefore, it has to be concluded from today's point of view, that free cortisol and metabolites must be investigated with HPLC if urine samples are used.

Keywords: Nocturnal aircraft noise, cortisol excretion, metabolites, comparability, analytic techniques, data collection, harmonisation.

How to cite this article:
Maschke C. Excretion of Cortisol under Nocturnal Noise and Differences due to Analytic Techniques. Noise Health 2002;5:47-52

How to cite this URL:
Maschke C. Excretion of Cortisol under Nocturnal Noise and Differences due to Analytic Techniques. Noise Health [serial online] 2002 [cited 2023 Nov 28];5:47-52. Available from: https://www.noiseandhealth.org/text.asp?2002/5/17/47/31835

  Introduction Top

A total of 16 residents living near the airport (Hamburg-Fuhlsbuttel) were studied over a period of 40 nights. The test persons slept in their own apartments and were exposed to additional nocturnal aircraft noise. This was possible because at Hamburg-Fuhlsbuttel airport there are nearly no starts or landings during the night. For the first 2 nights there was no additional nocturnal flight noise. During the further 38 nights, 32 takeoffs and landings with sound levels of L max = 65 dB(A) were simulated electro-acoustically each night using a computer controlled system. The simulation began at 23 p.m. and stopped at 6 a.m. During this time the flight events were spread stochastically. The 8 hour L eq of all the events was 42dB(A) and the duration of each noise signal was between 30s and 65s. The night urine excretion was collected each morning and analysed for the amount of free cortisol by enzyme immunoassay technique as well as by HPLC for the amount of free cortisol and cortisol metabolites technique, since the measurement of free cortisol is related with uncertainties

  Differences due to analytic techniques Top

Immunologic assays of cortisol in urine are known to strongly overestimate true cortisol concentrations due to the presence of large amounts of other cortisol-immunoreactive substances. These substances are cross-reacting metabolites of cortisol, which are present in much higher concentrations than the cortisol molecule itself. The contribution of these cortisol-immunoreactive substances is triggered by different metabolic or hormonal influences. Thus, immunologic cortisol estimates may only poorly correlate to the adrenal, glucocorticoid activity and to the bioactive, non-protein bound serum cortisol concentration. The latter one is known to be better monitored by the urinary excretion of the unmetabolized cortisol molecule itself. High performance liquid chromatographic (HPLC) techniques are able to specifically estimate urinary cortisol concentrations. To evaluate the impact of analytical techniques we therefore assessed urinary cortisol both by an immunologic assay and by an HPLC- technique (Schoneshofer et al. 1985, 1986a). Beside cortisol itself, the HPLC- technique additionally produced the estimates of 20α-Dihydrocortisol, the metabolic product of the 20-oxidoreductase, and of cortisone, the metabolic product of 11 B­Hydroxysteroiddehydrogenase. The ratio of cortisol to 20α-Dihydrocortisol reflects states of chronically elevated glucocorticoid activity (Schoneshofer et al. 1986b), whereas the ratio of cortisol to cortisone more reflects acute corticotrophic stimulation of adrenal activity (Schoneshofer et al. 1986b).

  The temporal course of the cortisol excretion Top

One of the important results of the 40-day longitudinal study (Harder et al. 1998) was the observation of rhythmic fluctuations of the cortisol values by using the enzyme immuno assay technique. An analysis of variance confirmed significant differences within the nights (p = 0,016) with two significant temporal trend-components. One trend-component was a weekly rhythm (p < 0,001) and the second component a 2nd order trend (p = 0,033) (Maschke et al. 2002).

In contrast to [Figure - 2] in "Stress hormone changes in Persons exposed to simulated night noise" the average excretion of free cortisol by using "online" liquid chromatography (HPLC) is given in the first figure for this paper. Included in the figure are both the HPLC measured cortisol excretion and the significant trend components. The dominating trend-component (dotted line) is a season factor (p < 0,000) in form of a weekly rhythm and the less striking component is a 3rd order trend (p = 0,024).

The cortisol excretion increases from Monday to Friday night, but unlike the immuno assay results, on Wednesday night there is a light break-in. Furthermore, in agreement with the immuno assay results, an increasing cortisol excretion phase (sensitizing phase) follows a phase of decreasing cortisol excretion. However, there was a clear difference to the findings of the immuno assay technique for the trend within the first days.

Similar time courses arose also for the cortisol-metabolites Cortisone and 20a-Dihydrocortisol. The average excretion of Cortisone by using "online" liquid chromatography (HPLC) is presented on the second figure together with the significant trend components. The fluctuations show exactly the same weekly rhythm as the excretion of free cortisol. There is an additional 3rd order trend to observe, which is only slightly different from the less striking trend component of the free cortisol secretion.

The averaged excretion of 20α-Dihydrocortisol by using "online" liquid chromatography (HPLC) is presented in the third figure together with the significant trend components. A weekly rhythm dominates, also in 20α-Dihydrocortisol, which is hardly different from the others. The same applies to the less striking 3rd order trend component.

  Different Cortisol secretion by women and men Top

Another important result by using immuno assay analysis was the observation of a sex specific reaction of the cortisol excretion under night time noise exposure. Both the initial reaction and the cortisol secretion trend was significantly different for men and women. The statistical analysis shows a significant interaction between weekly excretion and sex (p = 0,002) and the initial reaction for men was significantly higher than for women (p = 0,038) (Maschke et al. 2002). Such differences between the sexes could be observed in free Cortisol and Cortisone when the analysis was carried out with "online" liquid chromatography (HPLC).

For the initial reaction, the course of the free cortisol seems different, but the values are statistically only borderline significant (p = 0,069). The further course of the free Cortisol secretions (weekly excretion) is statistically not different for women and men (p = 0,238).

In agreement with the results of the immuno assay technique, the Cortisone excretion appears significantly different in the initial reaction (p = 0,015) as well as in the interaction between sex and weekly excretion (p = 0,045).

For 20(x-Dihydrocortisol no significant differences could be determined between women and men (initial reaction p = 0,408; interaction p = 0,913), if HPLC-analysis was carried out.

  Summary Top

The presenting method comparison points out, that analytic's independent effects as well as analytic's dependent effects exist.

The weekly rhythm of the Cortisol secretions exist independent of the analytic technology (Eickmann 2002) and must be taken into account in every study-designs. The fluctuations within the weekly-rhythm amount to 35-50% of the weekly mean values and therefore can not be neglected. To compensate for the weekly rhythm, the sampling may be carried out over 7 days or same days must be compared. Cross­section studies, in which the weekly rhythm was not taken into account, are therefore not very meaningful. Findings derived from medical sleep research may probably give a better access to endocrine secretion. A raised minimum level of cortisol can in fact be regarded as an essential marker substance of chronic stress [Born et al. 2000]. This has been confirmed by studies with depressive patients [Deuschle et al. 1997]. The cortisol low point (nadir) occurs in the first half of the night as a result of the circadian rhythm whereas its release in plasma is around the factor 10 higher in the morning [Born et al. 2000]. This is why the greatest likelihood of detecting endocrine changes is in the first half of the night. Therefore the difficulties of inter individual differences and circaseptan rhythms can be minimized when a cortisol quotient is used. The quotient of free cortisol excretion during the first half of the night, divided by the cortisol excretion in the second half of the night, show at an undisturbed sleep a stable value of approximately 0.2.

First investigations on the effects of traffic noise confirming that this cortisol quotient represents a sensitive indicator for the nightly noise load (see Ising et al. 2002a, 2002b).

The initial reaction and the other temporal trend components of the cortisol excretion seems dependent by the different analytic methods. Therefore urine examinations with different analytic methods could be compared with each other only restrictedly and the interpretation of the results is restricted as well. Furthermore, several clinical studies suggest, that an acute demand leads particularly to alterations of free Cortisol and a chronic demand essentially to alterations of metabolites. Therefore only analytic procedures which are able to distinguish between free cortisol and near metabolites should be used and the metabolites must be included in the examination, if the study deals with chronic stress situations.

  Conclusions Top

The presented comparison shows that studies into noise induced endocrine reactions are comparable with each other only when the same analytic techniques are used. Therefore, it has to be concluded from today's point of view, that free cortisol and well-chosen metabolites must be investigated with HPLC from urine samples, to get legitimate results. On the other hand it is urgently required that we understand the complex endocrine noise-reaction better than we do today. To accomplish this goal more interdisciplinary cooperation and studies are necessary.

Furthermore, the first step is to standardize both the urine sampling and the analytic techniques. Regarding the present scientific knowledge the following points have to be highlighted.

  • Harmonization of the urine collection, because the fluctuations within the weekly­rhythm amount to 35-50% of the weekly mean values.
  • Harmonization of the analytic techniques, because different analytic technologies lead to different findings.
  • Selection of appropriate indicators for the description of the complex hormonal reaction, because with the complex reaction it may be possible to differentiate chronic hypercorticoidism from the acute state.
  • Use of longitudinal studies with durations of at least 6 weeks, because during prolonged noise load the endocrine excretion may increases again after a phase of diminishing.[11]

  References Top

1.Born J., H.L. Fehm (2000): The neuroendocrine recovery function of sleep. Noise & Health 7, 25-37  Back to cited text no. 1    
2.Braun, C. (1999): Chronische Cortisolerhohung bei nachtlicher Verkehrslarmbelastung, Dissertation, Freie Universitat Berlin  Back to cited text no. 2    
3.Deuschle M., U. Schweiger, B. Weber, U. Gotthardt, A. Korner, J. Schmider, H. Standhardt, C.H. Lammers, I. Heuser (1997): Diurnal activity and pulsatility of the hypothalamus-pituitary-adrenal system in male depressed patients and healthy controls. J. Clin. Endocrinol. Metab. 82, 234-238  Back to cited text no. 3    
4.Eikmann, T.; C. Herr, H. Seitz (2002): Entwurf der Machbarkeitstudie; Teilprojekt 1b. Regionales Dialogforum zum Ausbau des Flughafens Frankfurt am Main.  Back to cited text no. 4    
5.Harder J., Maschke C., Ising H. (1998): Langsschnittstudie zum Verlauf von Stressreaktionen unter Einfluss von nachtlichem Fluglarm. Berlin, Umweltbundesamt; Forschungsbericht FKZ 506 01 003  Back to cited text no. 5    
6.Ising H. and M. Ising (2002a): Chronic Cortisol increases in the first half of the night caused by road traffic noise. Noise & Health, 4; 16, 13-21  Back to cited text no. 6    
7.Ising H., H. Lange-Asschenfeldt, Lieber, Weinhold and M. Eilts (2002b): Auswirkungen langfristiger Expositionen gegenuber Straβenverkehrs-Immissionen auf die Entwicklung von Haut- und Atemwegserkrankungen bei Kindern (Effects of long-term exposures of traffic emissions on the development of skin and respiratory tract diseases with children). Bundesgesundheitsblatt 2002 (in press)  Back to cited text no. 7    
8.Maschke et al. (2002): Stress hormone changes in persons exposed to chronic night noise. Noise & Health, 5; 17, 47­53  Back to cited text no. 8    
9.Schoneshofer M., A. Kage, B. Weber, I. Lenz, E. Kottgen (1985): Determination of urinary free cortisol by „on-line" liquid chromatography. Clinical Chemistry Vol. 31, No. 4, 564-568  Back to cited text no. 9    
10.Schoneshofer M., A. Kage, B. Eisenschmid, P. Heilmann, T.K. Dhar, B. Weber (1986b): Automated liquid chromatographic determination of the 20-Dihydro isomers of cortisol and cortisone in human urine. Journal of Chromatography, 380, 267-274  Back to cited text no. 10    
11.Schoneshofer M., B. Weber, W. Oelkers, K. Nahoul, F. Mantero (1986b): Measurement of urinary free 20­Dihydrocortisol in biochemical diagnosis of chronic hypercorticoidism. Clinical Chemistry Vol. 32, No. 5, 808-­810  Back to cited text no. 11    

Correspondence Address:
Christian Maschke
Müller-BBM GmbH, Robert-Koch-Str. 11, 82152 Planegg bei München
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Source of Support: None, Conflict of Interest: None

PMID: 12537834

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  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]

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