Variation Of TSH Research Articles

Effect of methadone on TSH and thyroid hormone secretion.

The hypothalamus-pituitary-thyroid function was studied in 15 male patients on chronic methadone treatment (40 mg/day). No significant variations of TSH, T4, T3 and rT3 levels were documented, either in basal conditions or after TRH stimulation; however a reduced TSH pituitary response was recorded in some patients (6 out of 15).

A longitudinal study of serum TSH, and total and free iodothyronines during normal pregnancy.

Serum T4, T3, rT3, free T4, free T3 and TSH were measured during and after normal pregnancy in 20 women. Special methodological precautions were taken to avoid interference of other hormones and protein alterations in the assays. Serum T4 and T3 were steadily increasing during the last part of the 1st trimester, and remained high and nearly stable during the 2nd and 3rd trimester of the gestation period. The high levels were approximately 1.5 times the values measured 10 weeks post-partum. Serum rT3 was elevated already during the last part of the 1st trimester and remained high throughout pregnancy, compared to the post-partum value. Serum free T4 and free T3 were slightly elevated in early pregnancy. The values decreased gradually during pregnancy and were slightly depressed during the 3rd trimester. A gradual increase in serum TSH was observed during pregnancy and the 2nd and 3rd trimester values were significantly higher than the post-partum value. The mean values for serum TSH, free T4 and free T3 remained always well within the normal range. Thus small variations in serum free iodothyronines and TSH occur during normal pregnancy, the alterations observed in the last trimester of the gestation period resembling those of a slight thyroid insufficiency. These trends in variation of the reference values are worth to remember in the diagnosis of borderline hypo- or hyperthyroidism and in the balanced treatment of pregnant women with thyroid dysfunction.

Effects of starvation on circadian variations of plasma TSH in rats.

Diurnal fluctuations of plasma TSH were investigated in ad libitum fed rats as well as after a 3 day starvation period in order to study the relationship between the circadian pattern of TSH secretion and nutritional status. Our study showed the persistence of a circadian TSH rhythm after a 3-day starvation without any change in the amplitude of plasma TSH variations. However, the 24 h average plasma TSH levels were significantly lower. A suggestive acrophase occurred at the same period of the day in starved and fed rats. Our results suggest that the control of plasma TSH concentrations and nycthemeral rhythm are not closely related and may even possibly be independent of one another.

Diurnal variations of plasma thyrotropin, thyroxine, and triiodothyronine in female rats are phase shifted after inversion of the photoperiod.

The present study examined plasma TSH, T4, and T3 concentrations in rats throughout the day to determine if diurnal variations of these hormones occurred. Female rats on a 12-h light, 12-h dark cycle (onset of light, 0730 h) were sampled by cardiac puncture at 2-h intervals throughout the day on 2 days, 1 week apart. Significant diurnal variations of plasma TSH, T4, and T3 were detected (P less than 0.01), Peak TSH concentrations occurred soon after the onset of light, whereas T4 and T3 concentrations peaked 3-4 h later. After these variations were detected, the effect of inverting the photoperiod was examined. Female rats were placed on 12-h light,, 12-h dark cycles, with the onset of light at 0730 h (LD) or 1930 h (DL). After 3 weeks, rats from each group were killed by decapitation at 4-h intervals throughout the day, and trunk blood was collected. Diurnal variations in plasma TSH, T4, and T3 (P less than 0.01) were similar to those found with 2-h sampling intervals in the previous experiment, and plasma corticosterone and PRL rhythms peaked near the onset of darkness (P less than 0.05). Inversion of the photoperiod phase shifted all diurnal variations, such that they maintained a similar phase relationship to the light-dark cycle on both LD and DL photoperiods. These results indicated that diurnal variations of plasma TSH, T4, and T3 concentrations could be repeatedly detected with different sampling protocols. These variations were phase shifted by inverting the photoperiod, which indicated that some aspect of the light-dark cycle can act to set the phase of these diurnal variations in the pituitary-thyroid axis.

24h variation of T4, FT4, T3 and TSH after a single oral dose of l-T4 in congenital hypothyroidism

Knowledge of plasma variation of thyroid parameters is important for blood sampling during evaluation of 1-T4 treatment. 11 children, aged 2 to 12 months, treated with a single oral dose of 1-T4 at 8 am (5 to 8 μg/kg) were studied for 24h. TSH was expressed as % of basal 8 am values (m ± SD). No significant variation was observed for plasma T4 or T3. A significant plasma TSH decrease was shown 4 to 8h after drug administration. Preliminary data on serum FT4 indicate a significant increase at + 2 and + 4h (n = 6). In conclusion : due to lack of plasma T4 variations, there is no special timing for plasma sampling and T4 determination. The transient TSH decrease may underestimate plasma value if blood is taken 4 to 8h after medication. This may be due to FT4 elevation related to 1-T4 absorption.

Plasma immunoreactive TRH (IR-TRH) in normal and anencephalic neonates and their mothers

To further investigate neonatal thyroid function IR-TRH was studied by RIA after plasma chacoal extraction. TSH and IR-TRH were measured in paired maternal cord samples and in 40 min and 24 h old neonates. IR-TRH was higher in cord than in maternal plasma (p<0.001) and remained constant during the first 24h of life. No correlation with TSH was observed. IR-TRH was undetectable in 3 to 6 months old normal infants. In 2 anencephalics, cord IR-TRH was 15 and 8 pg/ml and no acute variation of TSH was observed during the first 2 h of life. In conclusion : High plasma IR-TRH was observed in human neonates at birth. Low values in anencephalic babies is in favour of the hypothalamic origin of this material.

Suppression of the night increase in serum TSH during development of ketosis in diabetic patients.

The alterations in metabolic parameters, circulating iodothyronines and serum TSH were studied during a 21 h period of insulin withdrawal in 6 young patients with juvenile type diabetes mellitus. Concomitant with the derangement of metabolic state a significant fall in serum T3 (in average 27%), serum free T3 (28%), and T4 (12%) was observed. SErum free T4 remained unchanged. Before and after the period of ketosis the normal diurnal pattern of high serum TSH at night and low levels during the daytime period was observed. During the period of ketosis the night level of serum TSH was significantly depressed (46 +/- 9% lower at 23.00 h, p less than 0.01) while no significant alterations occurred in daytime TSH. Both the variations in T3, reverse T3 (rT3) and night TSH were correlated to the increase in blood-3-hydroxybutyrate. The depression of the night surge in serum TSH may be of importance for the fall in circulating levels of active iodothyronines during the initial phase of illness, together with the well known inhibition of T4 deiodination to T3 in peripheral tissues occurring in acute illness.

Circadian variations of plasma TSH in patients with severe hypothyroidism.

Five patients with severe hypothyroidism were studied to determine diurnal variations in serum TSH and thyroid hormones. The results were based on blood samples withdrawn at 1-h intervals during a 24-h period. A statistically significant circadian rhythm in TSH was detected with the acrophase at 23(30); no significant diurnal periodicity was observed for serum T3. The TSH pattern was similar to that observed in normal and midly hypothyroid subjects, with low levels during the day and higher levels at night. The findings are consistent with the following concepts: a. the TSH circadian rhythm is retained in patients with severe hypothyroidism; b. the abnormality in thyroid function does not effect the regulation of the TSH periodicity.

Effect of propylthiouracil on nycthemeral and sex related variation of plasma TSH in rats.

Studies of the effect on feedback mechanisms in nycthemeral fluctuation of plasma TSH and of its sex-related variation were carried out on normally fed (Purina) and propylthiouracil (PTU) treated rats. Plasma TSH concentration of purina fed rat was significantly higher in males than in females (M = 96 +/- 14, F = 49 +/- 3 microunits/ml, P less than 0.01). Plasma T4 concentration also showed a high tendency in males compared to females (M = 7.4 +/- 0.5, F = 5.8 +/- 1.0 micrograms/dl, 0.05 less than P less than 0.1) but the statistical difference was not significant. Plasma TSH demonstrated a typical periodicity characterized by a zenith at 1200 hr and a nadir at 1800 hr as in the previous reports. Plasma TSH concentrations rose apparently after the diet was switched to the one containing 0.15% of PTU. On the other hand, plasma T4 concentrations decreased to the very low levels following PTU administration. Concerning to the nycthemeral fluctuation and its sex related variation following PTU administration, nycthemeral fluctuation in male rats disappeared rapidly, whereas it was preserved in female rats. These facts showed that it kept more persistent fluctuation in female rats than in male rats under the high plasma TSH levels. Furthermore, female rats showed higher concentration of plasma TSH after PTU treatment compared to male rats. These results suggest that the nycthemeral fluctuation of plasma TSH was abolished or masked by the feedback mechanism of hypothalamo-pituitary-thyroid axis and there was a sex-related difference.

Effect of a single dose of glucocorticoid on the diurnal variations of TSH, thyroxine, 3,5,3'-triiodothyronine, 3,3'5'-triiodothyronine and cortisol in normal men.

Plasma thyrotropin (TSH) and cortisol concentrations were suppressed immediately after an intravenous bolus dose of 8 mg betamethasone in 6 male subjects. The circadian variations of these hormones disappeared for 40 hr (TSH) and 44 hr (cortisol). Plasma thyroxine (T4), 3, 5, 3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3) levels did not show diurnal variations before betamethasone administration. Plasma T3 levels decreased to 66% of the basal levels 20 hr after batamethasone administration, whereas plasma reverse T3 levels increased to 163% of the basal levels at 24 hr. These changes were reversed by 3 to 5 days after betamethasone. The earlier recovery of the diurnal rhythm of TSH than that of cortisol suggests that the TSH rhythm is not under the direct control of circulating cortisol.

Circadian and 30 minutes variations in serum TSH and thyroid hormones in normal subjects.

Ten normal young males were investigated in order to examine diurnal and short-term variations in serum TSH and serum thyroid hormones. In five subjects blood samples were obtained every 30 min during a 24 h period of daily life. A synchronous diurnal rhythm was found for free T3 and serum TSH with low levels in the day-time and higher levels at night. The mean increase from day to night was 15 and 140 per cent, respectively. There was a tendency to a similar rhythm in free T4, but the increase of 7 per cent fell short of statistical significance. In the other five men blood samples were obtained every 5 min in a 6 to 7 h period starting within the interval from 19.15 to 22.00 h. A significant regular variation with a cycle-length of half an hour was found in TSH, free T3 and free T4. This rhythm accounted for a significant part of the total variation in the levels of TSH, free T3 and free T4. The mean amplitude of the short-term variation is 13, 15 and 11 per cent of the mean level of the respective hormones. The data suggest a pulsatile release of hormones from the thyroid gland governed by a pulsatile TSH secretion.

Disturbed circadian variation of serum thyrotropin in patients with endogenous depression.

The relationship between the degree of depression and the circadian variation of serum TSH, T3 and T4 was investigated in 19 endogenously depressed patients. The difference between the hormone concentrations at 2 p.m. and at 12 p.m. was taken as an estimate of the magnitude of circadian variation. It was found that the circadian variation in serum TSH was inversely related to the degree of endogenous depression. This was mainly due to a diminution or absence of the night increase of TSH in severely depressed patients. A circadian variation of serum free T3 was found in the less depressed patients whereas no diurnal change was found in serum free T4. In severely depressed patients there were no significant diurnal changes in free thyroid hormone concentrations. The results indicate a hypothalamic dysfunction in manic-depressive psychosis.

Effect of normal and reversed sleep-wake cycles upon nyctohemeral rhythmicity of plasma thyrotropin: evidence suggestive of an inhibitory influence in sleep.

The relation of nyctohemeral variation in plasma TSH to sleep-wake cycles was examined in 10 normal young men who had their sleep polygraphically monitored and their blood sampled every 20 min for 24,36, or 48 h periods. Studies of normal sleepwake cycles in which sleep was allowed from the usual bedtime to 0630 h totalled 21 nights (night = 1840-0620 h) and their corresponding 16 days. TSH was measured by a sensitive RIA. On 17 nights, the mean nightly TSH significantly exceeded that of the day's and, on 18 nights, clear nyctohemerally maximal peaks in TSH were seen in the 2100-0100 h interval. Greater amplitude, duration and rhythmic repetition over several nights distinguished 2100-0100 h maxima from a background of persistent briefly episodic release. These nyctohemeral peaks were pre-sleep maxima, as rises uniformly began, and on 15 nights, the peaks occurred prior to the onset of sleep. The peaks clustered within the 30 min just before (12 nights) or after (3 nights) entry into sleep. TSH release then declined across sleep. Other evidence suggestive of an inhibitory influence in sleep upon TSH release was that sleep began early on the 3 nights without clear 2100-0100 h TSH maxima and that the mean 2100-0100 h TSH peak was significantly reduced when sleep began prior to the usual 2300-0000 h interval and significantly increased when the onset of sleep was delayed or postponed. After a 24 h baseline, 4 men underwent phase-reversal of their sleep-wake cycles for 48 h, in which sleep was shifted to the 1100-1830 h interval. On the first wakeful night of reversal, the 2100-0100 h peak began normally, but, in the absence of sleep, the enhanced TSH release then simply continued across this night, delaying achievement of the nyctohemeral maxima. On the second wakeful night of reversal, the maximum in mean TSH lay in the same 0400-0600 h interval as that of first reversal night, and the mean 2100-0100 h peak was no longer evident. The TSH of the second 24 h of reversal also was significantly reduced, suggestive of a negative feedback effect of enhanced release of the first reversal day. No shift of basal pre-sleep TSH peaks to the 0900-1300 h interval or of sleep-enhanced TSH release was seen during reversal. Thus, despite the persistence of TSH's nyctohemeral rhythmicity across acute sleep-wake reversal, its pattern changed significantly in relation to shifts in sleep. We currently view these results as consistent with the origin of TSH's nyctohemeral rhythmicity in a circadian mechanism whose expression is subject to modulation by the inhibitory influences of feedback and sleep.

Diurnal TSH Variations in Hypothyroidism

There is a circadian variation in serum TSH in euthyroid subjects. A similar diurnal variation has been demonstrated in patients with hypothyroidism. In the present study the 24-hour pattern of serum TSH was investigated in eight patients with hypothyroidism of varying severity and in five hypothyroid patients treated with thyroxine (T4). There was a circadian variation in serum TSH in patients with hypothyroidism of moderate degree, and in patients treated for severe hypothyrodism with thyroxine. The pattern was similar to that found in normal subjects, i.e., low TSH levels in the daytime and higher levels at night. In severely hypothyroid patients, no diurnal variation in serum TSH was observed. A practical consequence is that blood samples for TSH measurements in patients with moderately elevated TSH levels are best taken after 1100 h, when the low day levels are reached.

Thyrotrophin estimation in diagnosis and treatment of childhood thyroid disorders.

Serum thyrotrophin (TSH) was estimated by double-antibody radioimmunoassay in 200 children aged 2 months to 16 years with normal thyroid function. There was no apparent variation in TSH with age or sex and only 4 children had TSH levels greater than 5 muU/ml. High TSH values were obtained in 9 children with primary hypothyroidism, in 3 children with thyroiditis, and in one girl with a lingual thyroid. Moderately raised TSH was found in 3 girls with thyroiditis, 2 brothers with goitres due to enzyme defect, and a girl with an ectopic thyroid. In one girl with a defect of iodine organification and in 3 boys with thyroxine binding globulin deficiency the TSH levels were normal despite very low serum thyroxine values. Serum TSH was also estimated in 20 children during treatment for primary hypothyroidism. 3 of these children showed slightly raised TSH levels despite apparently adequate replacement therapy with L-thyroxine. One girl showed a very high TSH level 3 weeks after treatment had been temporarily withdrawn.

Effects of Oral Contraceptive Therapy on the Orcadian Patterns of Cortisol and Thyrotropin (TSH)

Abstract. The daily variation of serum cortisol and thyrotropin (TSH) has been simultaneously recorded every 30‐min. in 4 women taking the same oral contraceptive containing oestrogens and progestogens and in 4 control women. The circadian rhythm of cortisol persisted under contraceptive therapy with about a 2.5 fold elevation of the mean level and amplitude of the basal rhythm. Theoretical equilibrium calculations of the circadian variations of the free, transcortin‐bound and albumin‐bound cortisol fractions showed that these elevations are explained qualitatively and quantitatively by an oestrogen‐induced increase of the same order of the transcortin cortisol‐binding sites. As a consequence of the already high saturation of transcortin in normal conditions, the magnitude of the variation of free cortisol level resulting from a burst in cortisol secretion varies with the time of day. The role of albumin as a buffer is thereby emphasized. The early morning maximum, characterizing the normal TSH daily pattern, appeared to be considerably enhanced in women under contraceptive therapy. If the circadian variations of TSH are driven by thyrotropir releasing hormone (TRH), these higher morning peaks probably reflect a higher burst of TRH secretion rather than an increased responsiveness of the pituitary to TRH secretion induced by contraceptive therapy. Finall these results do not support the hypothesis of a regulation of TSH circadian variations by an inhibiotry action of cortisol. Contraceptive therapy does not appear to play a role at the level of the central clock or on the resetting mechanism.

Effects of oral contraceptive therapy on the circadian patterns of cortisol and thyrotropin (TSH).

The daily variation of serum cortisol and thyrotropin (TSH) has been simultaneously recorded every 30-min. in 4 women taking the same oral contraceptive containing oestrogens and progestogens and in 4 control women. The circadian rhythm of cortisol persisted under contraceptive therapy with about a 2.5 fold elevation of the mean level and amplitude of the basal rhythm. Theoretical equilibrium calculations of the circadian variations of the free, transcortin-bound and albumin-bound cortisol fractions showed that these elevations are explained qualitatively and quantitatively by an oestrogen-induced increase of the same order of the transcortin cortisol-binding sites. As a consequence of the already high saturation of transcortin in normal conditions, the magnitude of the variation of free cortisol level resulting from a burst in cortisol secretion varies with the time of day. The role of albumin as a buffer is thereby emphasized. The early morning maximum, characterizing the normal TSH daily pattern, appeared to be considerably enhanced in women under contraceptive therapy. If the circadian variations of TSH are driven by thyrotropin releasing hormone (TRH), these higher morning peaks probably reflect a higher burst of TRH secretion rather than an increased responsiveness of the pituitary to TRH secretion induced by contraceptive therapy. Finally these results do not support the hypothesis of a regulation of TSH circadian variations by an inhibiotry action of cortisol. Contraceptive therapy does not appear to play a role at the level of the central clock or on the resetting mechanism.

Thyrotropin secretion and metabolism in rats during propylthiouracil treatment.

The action of propylthiouracil (PTU; 0.01% in drinking water) on the development of goiter, thyroid hormone synthesis, plasma and pituitary TSH levels determined by radioimmunoassay, and on pituitary TSH secretion rate, has been studied in the normal rat. It has been found that PTU acts first on the peripheral metabolism of thyroxine and later on the thyroid hormone synthesis, both actions inducing a rapid increase in the plasma TSH concentration during the first week of treatment after which time the plasma TSH level returns to the normal range in all animals treated for 17 days. Then, it increases regularly up to the end of treatment (6 months). The pituitary TSH concentration diminishes immediately (24 hr) after the beginning of PTU treatment and remains low for three weeks. It reaches the initial level only after one month. In spite of these important pituitary and plasma TSH variations, the thyroid gland increases regularly. Study of the pituitary TSH secretion rate has shown that it increases during the first week of PTU treatment and returns to normal between the 17th day and one month. After two months of treatment, the secretion rate of TSH is four times higher than normal. The intrathyroid iodine concentration is decreased by PTU treatment and is about 30 times lower after one month. It is possible that this low iodine content may play a role on the TSH regulation of the thyroid. The half—time of disappearance of the injected 131I—bTSH is prolonged in all groups of PTU—treated rats. (Endocrinology92: 166, 1973)

Absence of diurnal variation of serum TSH.

Frequent sampling of blood throughout the day and night has been carried out in normal subjects and in patients with mild or severe primary myxedema. Measurements of TSH (by radioimmunoassay) and plasma cortisol have been made on each blood sample. Apart from what appear to be very occasional random, but significant variations in serum TSH concentration, no convincing pattern of circadian or other mode of variation of TSH secretion could be identified. On the contrary, our observations indicate that in most subjects, normal or hypothyroid, serum TSH levels remain remarkably constant, being unaffected by activity, sleep or eating.