The Effect of Diurnal Variation on Laboratory Tests

Abstract

Objective: Commonly used biochemical tests in blood samples may be measured at any time of day. This study investigated the existence and clinical significance of diurnal variations in some of routine parameters to facilitate accurate and reliable decision-making in diagnosis and follow-up. Materials and Methods: Blood samples were collected from 17 healthy volunteers who were 18-50 years of age (11 men, 6 women) on the same day at 9:00 am, 12:00 am, 3:00 pm, 6:00 pm, and 12:00 pm. Samples collected at 9:00 am were regarded as baseline. The results of 19 biochemical parameters in blood samples obtained at 12.00 am, 3.00 pm, 6.00 pm and 12.00 pm were statistically and clinically compared with the results at 9.00 am baseline sample. Results: Total protein, creatinine, aspartate transaminase, alanine transaminase, alkaline phosphatase and gamma glutamyl transferase showed no clinically significant variation within the day, but clinically significant changes were observed in levels of glucose, total cholesterol, HDL-cholesterol, triglyceride, total bilirubin (TBIL), direct bilirubin (DBIL), albumin, blood urea nitrogen, uric acid, sodium, potassium, chloride and amylase. Especially, BUN changed by maximum 20-30%, TBIL, DBIL and triglyceride maximum 40-50% within the day. Conclusion: The results of our study suggest that clinicians should consider the timing of blood sampling and the diurnal variations in BUN, TBIL, DBIL and triglyceride parameters during diagnosis and treatment follow-up. Sampling throughout the day seems to pose no problem for other tests with limited diurnal variation.

Keywords

• Diurnal rhythm
• blood urea nitrogen
• bilirubin
• triglyceride

References

1. 1. Forsman, R.W. Why Is the Laboratory an Afterthought for Managed Care Organizations? Clinical Chemistry 1996;4:813-6.
2. 2. Satish C. Kalhan, Arnab Ghosh. Dietary iron, circadian clock, and hepatic gluconeogenesis. Diabetes 2015;64:1091-3.
3. 3. Sturgess I, Thomas SH, Pennell DJ, Mitchell D, Croft DN. Diurnal variation in TSH and free thyroid hormones in patients on thyroxine replacement. Acta Endocrinol (Cophenh) 1989;121(5):674-6.
4. 4. Eriksson L, Eden S, Holst J, Lindstedt G, Von Schoultz B. Diurnal variations in thyrotropin, prolactin and cortisol during human pregnancy. Gynecol Obstet Invest 1989;27(2):78-83.
5. 5. Dibner C, Schibler U, Albrecht U. The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol 2010;72:517-49.
6. 6. Clinical Laboratory Standards Institute. Procedures for the collection of diagnostic blood specimens by venipuncture. CLSI H3-A6 document. 6th ed. Wayne, PA: Clinical Laboratory Standards Institute; 2007.
7. 7. Simundic AM, Cornes MP, Grankvist K, Lippi G, Nybo M. Standardization of collection requirements for fasting samples: For the Working Group on Preanalytical Phase (WGPA) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM). Clin Chim Acta 2014;432:33-7.
8. 8. Miller R. Simultaneous Statistical Inference, 2d Ed. New York: Springer-Verlag. 1981.

9. 9. Ricos C, Alvarez V, Cava F, Garcia-Lario JV, Hernandez A, Jimenez CV, et al. "Current databases on biologic variation: pros, cons and progress." Scand J Clin Lab Invest 1999; 59:491-500. This database was most recently updated in 2017.
10. 10. College of American Pathologists (CAP). Available at: https://datainnovations.com/allowable-total-error-table.
11. 11. Pocock SJ, Ashby D, Shaper AG, Walker M, Broughton PM. Diürnal variations in serum biochemical and haematological measurements. J Clin Pathol 1989;42:172-9.
12. 12. Sennels HP, Jørgensen HL, Fahrenkrug J. Diurnal changes of biochemical metabolic markers in healthy young males - the Bispebjerg study of diurnal variations. Scand J Clin Lab Invest 2015;75(8):686-92.
13. 13. Muller EE, Locatelli V, Cocchi D. Neuroendocrine Control of Growth Hormone Secretion. Physiol Rev 1999;79(2):511–607.
14. 14. Karpe F, Steiner G, Uffelman K, Olivecrona T, Hamsten A. Postprandial lipoproteins and progression of coronary atherosclerosis. Atherosclerosis1994;106(1):83-92.
15. 15. Miettunen TA. Diurnal variation of LDL and HDL cholesterol. Ann Clin Res 1980;12(6):295-8.
16. 16. Sennels HP, Jorgensen HL, Goetze JP, FahrenkrugJ. Rhythmic 24-hour variations of frequently used clinical biochemical parameters in healthy young males–the Bispebjerg study of diürnal variations. Scand J Clin Lab Invest 2012;72(4):287-295.
17. 17. Morrison B, Shenkin A, McLelland A, Robertson DA, Barrowman M, Graham S, Wuga G, Cunningham KJ. Intra-individual variation in commonly analyzed serum constituents. Clin Chem 1979; 25(10):1799-805.
18. 18. Barrett PVD. Hyperbilirubinemia of fasting. JAMA 1971;217(10):1349-53.
19. 19. Rejnmark L, Lauridsen AL, Vestergaard P, Heickendorff L, Andreasen F, Mosekilde L. Diurnal rhythm of plasma 1,25-dihydroxyvitamin D and vitamin D-binding protein in postmenopausal women: Relationship to plasma parathyroid hormone and calcium and phosphate metabolism. Eur J Endocrinol 2002;146(5):635-42.
20. 20. Kanabrocki EL, Sothern RB, Scheving LE, Vesely DL, Tsai TH, Shelstad J, et al. Reference values for circadian rhythms of 98 variables in clinically healthy men in the fifth decade of life. Chronobiol Int 1990;7(5-6):445-61.
21. 21. Statland BE, Winkel P, Bokelund H. Factors contributing to intra-individual variation of serum constituents: 1. Within day variation of serum constituents in healthy subjects. Clin Chem 1973;19(12):1374-9.
22. 22. Melchart D, Martin P, Hallek M, Holzmann M, Jurcic X, Wagner H. Circadian variation of the phagocytic activity of polymorphonuclear leukocytes and of various other parameters in 13 healthy male adults. Chronobiol Int 1992;9(1):35-45.
23. 23. Touitou Y, Touitou C, Bogdan A, Reinberg A, Motohashi Y, Auzeby A, et al. Circadian and seasonal variations of electrolytes in aging humans. Clin Chim Acta 1989;180(3):245-54.
24. 24. Winkel P, Statland BE, Bokelund H. The effects of time of venipuncture on variation of serum constituents. Consideration of within-day and day-to-day changes in a group of healthy young men. Am J Clin Pathol 1975; 64(4):433-47.
25. 25. Kanabrocki EL, Sothern RB, Scheving LE, Halberg F, Pauly JE, Greco J, Nemchausky BA, et al. Ten-year-replicated circadian profiles for 36 physiological, serological and urinary variables in healthy men. Chronobiol Int 1988;5(3):237-84.
26. 26. Böning D, Schweigart U, Kunze M. Diurnal variations of protein and electrolyte concentrations and of acid-base status in plasma and red cells of normal man. Eur J Appl Physiol Occup Physiol1974;32(3):239-250.
27. 27. Keller J, Layer P. Circadian pancreatic enzyme pattern and relationship between secretory and motor activity in fasting humans. J Appl Physiol 2002;93(2):592-600.