Circannual and Within-Individual Variation of Thyroid Function Tests in Normal Subjects

Abstract

SUMMARY.Blood was taken from normal subjects at monthly intervals over a period of one year for subsequent determination of serum thyroid hormone concentrations. Thyroid-stimulating hormone (TSH) responses to TSH-releasing hormone were performed at 3-monthly intervals. This study provided data on within-individual variation and on seasonally-related changes of these thyroid function tests.The results showed that, within an individual, thyroid hormone concentrations are maintained within narrow limits. For both thyroxine and triiodothyronine the component contribution of within-individual variation to the population-based variation (the latter also termed the 'reference interval', or colloquially the 'normal range') was small. This high degree of individuality implies that rigorous comparison of thyroid hormone results against a population-based 'normal range' can be potentially misleading.Despite the limited within-individual variation, seasonally-related changes in thryoid hormone concentrations were apparent, with higher thyroxine and triiodothyronine values seen in winter months. A tendency to a greater TSH response to TSH-releasing hormone was also noted at this time. Conceivably these changes could reflect a centrally-mediated response of the hypothalamic-pituitarythyroid axis to environmental temperature.Laboratory 'normal ranges' are usually based on results from a group of healthy subjects and, for data showing a Gaussian distribution, conventionally embrace values extending to two standard deviations from the mean value. It is well recognised, however, that withinindividual variation of many biochemical tests is considerably less than the population-based reference interval (usually referred to as the 'normal range').l-4 We have studied withinindividual variation of serum thyroid hormone concentrations over a 13-month period; in addition, this investigation has allowed us to determine the extent of any seasonal influence on thyroid hormone values. Thyroid-stimulating-hormone-releasing hormone (TRH) tests were performed at intervals during the study. MethodsSix normal subjects (three male, three female) took part. Blood was taken without venous stasis" from each subject, who was seated quietly at the time of venepuncture. The samples were taken during the first 10 days of each calendar month for 13 months (OctoberOctober), and from each subject at the same time of day. Sera were stored at -20°C until the end of the study and those from each subject were assayed in a single batch to eliminate between-assay variation. Studies in this laboratory have confirmed other reports": 7 that serum thyroid hormones are stable under these conditions for at least one year. TRH tests were conducted using a 200 J.lg bolus intravenous injection (TRH, Roche Products Ltd) and blood was taken before and at 10, 20, 30, 45 and 60 min after TRH; these tests were performed every three months at 0, 3, 6 and 12 months of the study. An exceptionally cold period occurred between 2 and 3 months after the conclusion of the study and t...

Variation in thyroid function in subclinical hypothyroidism: importance of clinical follow-up and therapy

“…The intra-individual variation of thyroid function tests has been studied in individuals with normal thyroid function (28)(29)(30)(31)(32)(33)(34)(35)(36)(37). This has revealed both a considerable circadian rhythm and a small seasonal variation in TSH secretion, but over time TSH in an individual varies within a range of only half of a population-based reference range.…”

The pituitary-thyroid axis in healthy men living under subarctic climatological conditions

“…Other studies have, however, led to opposite results. In healthy subjects serum total T 4 levels were similar during all seasons, but the serum thyrotrophin (TSH) response to TSH-releasing hormone (TRH) was greater in winter than in summer (Konno 1978, Harrop et al 1985. In hypothyroid subjects, lower serum T 4 levels and higher serum TSH levels and TSH responses to TRH were found in winter rather than in summer (Konno & Morikawa 1982).…”

“…Japanese subjects living in unheated dwellings had higher serum total triiodothyronine (T 3 ) levels in winter than in summer, but subjects working outdoors showed no differences in serum T 3 or thyroxine (T 4 ) between summer and winter (Nagata et al 1976). High serum total T 3 and T 4 levels in winter were also found in laboratory workers in the Netherlands (Smals et al 1977) and the UK (Harrop et al 1985). This would indicate that the pituitary-thyroid axis becomes directly activated during the cold season.…”

Pilot study on the assessment of the setpoint of the hypothalamus–pituitary–thyroid axis in healthy volunteers

“…There is a considerable variation in serum TSH and thyroid hormone concentrations in healthy subjects, in whom the inter-individual variability is much greater than the intra-individual variability (5)(6)(7)(8)(9)(10)(11)(12). It looks like every individual has his/her own peculiar combination of TSH and FT 4 , which is determined by genetic and environmental factors (13).…”