CIRCADIAN VARIATIONS OF SERUM THYROTROPIN LEVELS IN MAN¹

Abstract

The existence of circadian variations in serum TSH levels was investigated in 8 normal subjects. The analysis of the data indicated the presence of 2 different reproducible phenomena, a circadian rhythm characterized by an important acrophase and lower amplitude higher frequency variations, with period between 1 and 3 hours. It is suggested that neural mechanisms are at the origin of both the high., frequency variations and the circadian phenomenon, this latter being related to the sleep-wake cycle. A significant difference, between nocturnal and diurnal mean TSH levels was observed in women, but not in men.The existence of circadian rhythmic variations in the secretion pattern of different human pituitary hormones (ACTH and consequently cortisol (1,2), GH (3), FSH (4))has been demonstrated. Until now such a rhythmic pattern could not be demonstrated for TSH secretion (5,6,7,8). However, Nicoloff et al. (9) have suggested the existence of circadian variations of serum TSH levels with a maximum between midnight and 4 a.m., and a minimum around 6 p.m.; these data supported a negative regulation of TSH levels by hydrocortisone.The present study reports more extensive observations of the circadian variations of serum TSH levels in normal man.PATIENTS AND METHODS.. Eight human volunteers (5 males and 3 females), aged 22 to 65 years, clinically and biologically euthyroid, were submitted to blood sampling, every 30 min during 24 hr, through a plastic indwelling needle frequently rinsed with saline. Three of the 5 male volunteers, hospitalized patients for benign non-endocrine diseases, were confined in bed during the observation period, while the other subjects kept their usual life schedule. Their night sleep was rarely interrupted. Three of them were submitted to a second experiment 3 weeks later.Serum TSH was measured by a slightly modified double antibody radioimmunoassay (10,11) and the results were expressed in yU per ml in terms of the international reference standard A preparation (N.M.R.C., Mill-Hill, England); 200 yl TSH-free human serum were added in each tube of the standard curve. In order to avoid the interassay error, all the samples for a given subject were measured in the same assay. Under these conditions the coefficient of variation for several determinations of the same sample fell generally below 2.5 %. Serum total proteins were estimated by the Biuret technique adapted to the Technicon autoanalyser.Statistical analysis of the data included the detection of the possible periodicities by the periodogram method (12,13). RESULTS.Important changes in serum TSH levels were observed during the 24-hours span. Analysis of the data showed two kinds of variations. First, a circadian rhythm characterized by the presence of a peak (acrophase) of TSH levels between 4 a.m. and 6 a.m.; this pediodicity was confirmed by the periodogram analysis and was detected in all subjects except one. Secondly, significant high frequency variations,

A Case of The Syndrome of Inappropriate Secretion of TSH

“…The main features of the patient described herein are the advanced body height and skeletal growth for her age, the goiter with the elevated thyroid hormone level, the high nocturnal peak of TSH (Vanhaelet et al, 1972) and PRL (Parker et al, 1973), and the inappropriate TSH and exaggerated PRL responsiveness to TRH. Although the patient presents no clinical signs of thyrotoxicosis, she is reasonably considered to be in the state of mild hyperthyroidism on the basis of physical and biochemical parameters.…”

Metabolic Clearance and Production Rates of Human Thyrotropin

“…Further, the assumption that the 24 h production rate of hTSH remains constant has been supported by studies showing constant blood levels of hTSH during the 24-h period (3,17,18). However, more recent studies (19,20) utilizing sensitive radioimmunoassays have demonstrated a significant small and brief rise in hTSH concentra- tion in the early morning hours, suggesting a circadian variation in TSH production. Thus the results in the present study, which assumes constant production of hTSH, may be slightly low since this method does not include the brief rise of hTSH during the early morning hours.…”

GH replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies

“…Patients with CH have a blunted nocturnal surge (84,85) in TSH circadian secretion (86)(87)(88). However, this may be found in NTI (89), in post-operative patients (90,91), during starvation (92), and in severe primary hypothyroidism (93).…”