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Original Studies |
Divisions of Clinical Chemistry (C.A., H.G.), Pathology (C.A.), Allergological and Immunological Diseases (A.H.), and Haematology (K.P.), Inselspital, University of Bern, CH-3010 Bern; and Swiss Federal Office of Public Health (M.H., B.Z.), CH-3003 Bern, Switzerland
Address correspondence and requests for reprints to: Claudine Als, M.D., Division of Clinical Chemistry, Inselspital, University of Bern, CH-3010 Bern, Switzerland.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResults and Statistical AnalysisDiscussionReferences |
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Forty-two subjects (18 males and 24 females, including 13 children) collected 3023 urine spots between May 1996 and May 1998, at a rate of three to five samples per month, at any time of the day. The results show that circadian rhythmicity of UI in adults and children was found independent of the individual subject, age, gender, and season. Lowest UI levels were found between 8–11 h. A curve increasing progressively between 12 and 24 h was obtained. UI returned to base-line levels between 21 and 22 h in children only. UI peaks occurred 4–5 h after main meals; children’s peaks occurred later than that of adults.
Although the existence of a circadian rhythm of UI is probably universal, its profile, however, depends on alimentation. Because nadir of UI is represented by morning spots, this might seem an appropriate collecting period. In view of the significant circadian rhythmicity of UI, studies with restriction of sampling time to morning hours, for example, cannot be directly compared with studies in which urine is sampled all over the day.
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResults and Statistical AnalysisDiscussionReferences |
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In the present study, our aim was to determine whether a relation between UI and the spot sampling hour exists in adults and children. Is the hour of spot urine sampling a significant factor to be considered in the design of epidemiologic studies and in the interpretation of own data on UI?
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResults and Statistical AnalysisDiscussionReferences |
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This ongoing prospective study, approved by the Ethical
Commission of the University Hospital of Bern, is patronized by the
Swiss National Foundation for Scientific Research (number 32-49424.96).
An informed consent was signed by all study subjects. The subjects in
the present study were 42 healthy volunteers: 18 males and 24 females
(aged 4–60 yr at the beginning of the study in May 1996), including 13
children (Table 1
). Of a total of 50
subjects at the beginning of the study, 8 subjects aged 47–75 yr had
been excluded because of: 1) long-lasting iodine exposure by oral
ingestion of oligoelements (n = 4) or percutaneous application of
betadine (n = 1); 2) lack of compliance (n = 2); and 3)
incomplete age category with only one 66-yr-old subject left after
exclusion of the other subjects more than 60 years of age.
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Between May 1996 and May 1998, a total of 3023 urine spots were collected at a rate of three to five samples per month, at any time of the day, as convenient. The urines were immediately frozen. The subjects recorded the sampling hour, but not the hour of meals. The main meals were breakfast, lunch, and supper; some subjects moreover took small meals in-between. Due to the long-time study design aimed primarily at monitoring a potential increase of UI in Switzerland, no special emphasis had been laid on sampling during late night. As a consequence, only few spot samples were collected between 1 and 5 h in the morning. Therefore, those hours were left out from statistical analysis.
Laboratory analyses
The laboratory analyses of all 3023 spots, primarily frozen at -30 C, were realized in a continuous run-through between May and September 1998 in the laboratory of the Swiss Federal Office of Public Health. Urinary iodine was measured according to a new method: inductively coupled plasma mass spectrometry (ICP-MS) (2). ICP-MS allows the direct determination of iodine in urine. The application of isotope dilution analysis by using the long-lived radioisotope of iodine I-129 as a spike offered possibilities for automatic and accurate measurement.
Because of extremely high values between 2500–6000 µg I/L, 5 samples were excluded from the calculations, as also were 67 samples collected between 1 and 5 h in the morning. Results were expressed as I/volume (µg/L). The relation between daytime of spot urine sampling and UI was evaluated.
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Results and Statistical Analysis |
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TopAbstractIntroductionSubjects and MethodsResults and Statistical AnalysisDiscussionReferences |
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were subtracted from
the respective yi values for each subject to center the
data around zero: zi = yi - .
Accordingly, the transformed UI data (zi) were evaluated by
ANOVA. Thereby, the effects of season (summer, winter) and sampling
hour were significant (P < 0.001), whereas the effects
of individual subject, gender, and age were not (P >
0.9). A fully factorial ANOVA of the transformed UI data
(zi) with the factors sampling hour (P <
0.001) and season (P < 0.001) was next calculated and
revealed that interaction between the two categorical variables did not
occur (P = 0.84). Consequently, it was assumed that the
factor sampling hour was not modified by seasonal variations.
Most urine spots were sampled in the morning (6–10 h, n =
191–390/h). Less specimens were obtained in the evening (19–23 h,
n = 106–262/h) and between 11–18 h (n = 95–140/h); for
obvious reasons, even less at 24 h (n = 20/h) and between 1
and 5 h (n = 2–11/h, n = 67 samples omitted in Fig. 1).
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, a curve of UI increasing progressively
between 12 and 24 h was obtained with significant differences
between the mean values of the sampling hours (P <
0.001). Although the effect of age was not significant, the circadian
rhythm is given separately for both children and adults to point out
the differences. There was no return of UI to base-line levels between
12 and 24 h, except for children between 21 and 22 h. After
midnight, however, the return took place progressively over about
12 h in adults and children (i.e. lowest levels were
found in the morning, between 8–11 h). UI "peaks" appeared
around 13–14 h, around 16–17 h, and most pronounced around 22–23 h.
The child’s first UI peak between 12–14 h was relatively higher than
the corresponding adult peak; each child’s peak was found delayed as
compared to the corresponding adult’s peak. |
Discussion |
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TopAbstractIntroductionSubjects and MethodsResults and Statistical AnalysisDiscussionReferences |
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Although the existence of a circadian rhythm of UI is most probably universal (nadir in the morning, followed by a progressive increase until about 24 h), its profile seems to depend on alimentary peculiarities. As UI peaks followed the three main meals by 4–5 h, the profile of the circadian rhythm suggests a short-timed relation to alimentary iodine intakes. Compared to an UI peak at about 20 h in 193 Romanian children (4), the third peak at 22–23 h in our study is possibly due to later intakes of qualitatively different suppers. In analogy, the different shape of the first peak in our children and adults, respectively, may be related to qualitatively different breakfasts. In this context, it has been shown that in Switzerland milk is an important provider of iodine, especially during the winter months, when cows are fed in the stables with industrially prepared animal foods (5). In our study, indeed, the reported milk intake at breakfast of participating children was high: 0.2–0.6 L. On the contrary, adults consumed much less milk at breakfast: 0–0.15 L. The abundant consumption of milk at breakfast by our child subjects should, thus, be considered an important provider of iodine, mirrored by the children’s first peak of UI between 12 and 14 h.
In analogy to the circadian rhythmicity of UI described herein, other 24-h rhythmic profiles (i.e., of serum TSH and T3) have been described in young and elderly men, aged 20–27 and 67–84 yr, respectively (1). The chronobiological modulation of TSH and of T3 is preserved in the elderly compared with young men, even if the amplitude of the overall normal TSH secretion over 24 h is decreased in the elderly. However, in contrast to our findings of a nadir of UI between 8 and 11 h both in adults and children, the nadir of serum TSH was found in the afternoon, both in young and elderly men. Moreover, the acrophases of UI between 13 and 14 h, 16 and 17 h, and 22 and 23 h anticipate (or follow!) the acrophase of serum TSH found between 0 and 8 h. Thus, thyroid economy underlies a chronobiological rhythmicity of several of its main parameters. To find out whether or not relations between circadian rhythmicity of UI and of plasma TSH or T3 exist is beyond the scope of this study. Future studies should deal with this question.
As the significant interaction between daytime and UI had to, our knowledge, not been known as such up to now, it is not astonishing that in virtually all reviews and studies, including ours, dealing on epidemiological or methodological aspects of iodine in urine, this point was not systematically addressed. On the contrary, spot urine sampling was often random [i.e. untimed (6, 7, 8, 9, 10, 11, 12, 13, 14, 15); Brander, L., C. Als, H. Buess, F. Haldimann, M. Harder, W. Hanggi, U. Hermann, K. Lauber, U. Niederer, H. Odermatt, E. Schürch, T. Zürcher, U. Bürgi, and H. Gerber, submitted for publication]. The question remains open whether randomized sampling compared to early morning sampling leads to significantly different results of UI. However, only the integral of daily iodine excretion really counts. Indeed, complete urine collections of 24 h, albeit very difficult to obtain in field conditions, represent without doubt the most precise marker of daily iodine intake.
For a feasible and adequate assessment of a population’s iodine status, however, the WHO and others (3) have recommended early morning, respectively, fasting urine samples. Our results show that spots taken in the morning or 8–12 h after the last meal represent the nadir of UI; hence, this might seem a sensitive collecting period. In view of the pronounced circadian rhythmicity of UI, studies with exclusive urine spot collections in the morning (i.e. in the nadir of UI), cannot be directly compared with studies in which urine spots are sampled all over the day (i.e. including the peaks that may not reflect real iodine intake). Our data are useful for standardization of the methodology of surveys assessing iodine intake of a population.
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Acknowledgments |
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Footnotes |
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Received July 9, 1999.
Revised December 1, 1999.
Accepted December 9, 1999.
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References |
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This article has been cited by other articles:
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  C. Als, P. Gedeon, H. Rosler, C. Minder, P. Netzer, and J. A. Laissue Survival Analysis of 19 Patients with Toxic Thyroid Carcinoma J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4122 - 4127. [Abstract] [Full Text] [PDF]
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