TSH Pulse Research Articles

TSH Pulses Finely Tune Thyroid Hormone Release and TSH Receptor Transduction.

Detection of circulating TSH is a first-line test of thyroid dysfunction, a major health problem (affecting about 5% of the population) that, if untreated, can lead to a significant deterioration of quality of life and adverse effects on multiple organ systems. Human TSH levels display both pulsatile and (nonpulsatile) basal TSH secretion patterns; however, the importance of these in regulating thyroid function and their decoding by the thyroid is unknown. Here, we developed a novel ultra-sensitive ELISA that allows precise detection of TSH secretion patterns with minute resolution in mouse models of health and disease. We characterized the patterns of ultradian TSH pulses in healthy, freely behaving mice over the day-night cycle. Challenge of the thyroid axis with primary hypothyroidism because of iodine deficiency, a major cause of thyroid dysfunction worldwide, results in alterations of TSH pulsatility. Induction in mouse models of sequential TSH pulses that mimic ultradian TSH profiles in periods of minutes were more efficient than sustained rises in basal TSH levels at increasing both thyroid follicle cAMP levels, as monitored with a genetically encoded cAMP sensor, and circulating thyroid hormone. Hence, this mouse TSH assay provides a powerful tool to decipher how ultradian TSH pulses encode thyroid outcomes and to uncover hidden parameters in the TSH-thyroid hormone set-point in health and disease.

Psoriatic arthritis and Hashimoto's thyroiditis in a patient presenting with major depression and subclinical hyperthyroidism: A case report

Psoriatic arthritis (PsA) is a chronic, deforming arthritis associated with psoriatic skin lesions. Numerous patients with PsA carry other co-existing chronic diseases, adding to their overall disease burden and affecting the patient’s quality of life. Depression is a common illness known to coexist in about 20% of patients with PsA. Long-term inflammation conditions can make patients more depressed and make the treatment more difficult. Cushing Syndrome (CS) is a complication of long-term treatment due to the exposure of glucocorticoids given to turn the hypothyroid condition into hyperthyroid because hypercortisolism in humans lowers TSH secretion and TSH pulse amplitude. When PsA combines with depression and CS, it will create complex conditions and treatments. The complexity is all about how we control the disease activity of PsA and the vicious circle of an inflammatory process that is difficult to control. Conventional treatment will fail, and targeted therapy with monoclonal antibodies such as anti-IL-17 Secukinumab, is needed. Secukinumab as an anti-IL-17 will block the inflammation pathway from interleukin-17, decrease the inflammation process, and improve the symptoms of PsA. We report a patient with psoriatic arthritis and Hashimoto's thyroiditis (HT) with a major depressive episode with CS and subclinical hyperthyroidism successfully treated with Secukinumab.

Thyroid autotransplantation after total thyroidectomy in multi-nodular goiter—a case series analysis

Following the success of parathyroid autotransplantation, thyroid autotransplantation was introduced, aiming to avoid or reduce the severity of post-thyroidectomy hypothyroidism in noncompliant patients. While our primary aim was to assess the survival and function of heterotopic autotransplanted thyroid tissue after total thyroidectomy, our secondary aim was to establish a relationship between autotransplanted volume and euthyroid state. We conducted a case series analysis, including 40 women diagnosed with multinodular goiter for whom total thyroidectomy was considered. Patients were randomized into two groups: group A (20 patients) who received 15 g and group B (20 patients) who received 10 g of healthy non-nodular thyroid tissue. Survival and function of heterotopic autotransplanted thyroid tissue was assessed by hormonal profile and thigh ultrasound scan (site of autotransplanted thyroid graft) 2, 6, and 12 months postoperatively. We have included 40 ladies divided into two groups: group A 50 years. There was no statistically significant difference between group A and group B regarding radioactive iodine uptake after the 2nd, 6th, and 12th months. There was a statistically significant difference between results after the 2nd, 6th, and 12th months regarding free T3 (FT3; tri-iodothyronine), free T4 (FT4; thyroxine), thyroid-stimulating hormone, and pulse (p ≤ 0.001). The study revealed a highly statistically significant difference between the 2nd, 6th, and 12th months in FT3, FT4, and TSH levels and pulse (p ≤ 0.001) as well as highly statistically significant difference between group A and group B regarding FT3 and FT4 after the 2nd, 6th, and 12th months (p ≤ 0.001) (Tables 2 and 3). Autotransplanted thyroid tissue processing and injection time range was 18–20 min, and none of the patients had immediate or delayed complications. We found the procedure to be safe, successful, and not time-consuming; we also found that better results were achieved when larger volumes were implanted in younger patients.

Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing's syndrome

The hypothalamus-pituitary-thyroid axis in Cushing's syndrome may be altered. Previous reports have shown diminished serum TSH concentration and decreased response to TRH. We analyzed serum TSH profiles in relation to cortisol profiles in patients with hypercortisolism of pituitary (n=16) or primary-adrenal origin (n=11) and after remission by pituitary surgery (n=7) in order to delineate aberrations in the hypothalamus-pituitary-thyroid system. Patients and controls (n=27) underwent a 24-h blood sampling study. Serum TSH and cortisol were measured with precise methods, and data were analyzed with a deconvolution program, approximate entropy (ApEn), and cosinor regression. Pulsatile TSH secretion and mean TSH pulse mass were diminished during hypercortisolism, independently of etiology (P<0.001). TSH secretion was increased in patients in remission only during daytime due to increased basal secretion (P<0.01). Pulse frequency and half life of TSH were similar in patients and controls. TSH ApEn (irregularity) was increased in patients with hypercortisolism (P<0.01), but was normal in cured patients. Cross-ApEn between TSH and cortisol, a measure of pattern synchrony loss, was increased in active disease, indicating (partial) loss of secretory synchrony. The TSH rhythm was phase delayed in hypercortisolemic patients, but normal in cured patients (P<0.01). Free thyroxine levels were decreased only in pituitary-dependent hypercortisolism compared with controls (P=0.003). Total 24-h TSH correlated negatively and linearly with log-transformed cortisol secretion (R=0.43, P=0.001). Cortisol excess decreases TSH secretion by diminishing pulsatile release, whereas surgically cured patients have elevated nonpulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic/annexin-1 control.

Seasonal and pulsatile dynamics of thyrotropin and leptin in mares maintained under a constant energy balance

The objective of this study was to determine if seasonal and/or pulsatile variations occur in plasma concentrations of thyrotropin (TSH) and leptin in mares while maintaining a constant energy balance. Blood samples were collected every 20 min during a 24 h period in winter and again in summer from six Quarter Horse type mares. Plasma concentrations of TSH, leptin, and T 4 were determined by radioimmunoassay. No differences were observed in body weight between winter (388.1 ± 12.5 kg) and summer (406.2 ± 12.5 kg; P = 0.11). Plasma concentrations of TSH were greater in the summer (2.80 ± 0.07 ng/ml) when compared to winter (0.97 ± 0.07 ng/ml; P < 0.001). Pulse frequency of TSH was not different between winter (6.17 ± 0.78 pulses/24 h) and summer (5.33 ± 0.78 pulses/24 h; P = 0.49). Mean TSH pulse amplitude, pulse area, and area under the curve were all greater in summer compared to winter (3.11 ± 0.10 ng/ml versus 1.20 ± 0.10 ng/ml, 24.86 ± 0.10 ng/ml min versus 13.46 ± 1.90 ng/ml min, 3936 ± 72.93 ng/ml versus 1284 ± 72.93 ng/ml, respectively; P < 0.01). Mean concentrations of leptin were greater in summer (2.48 ± 0.17 ng/ml) compared to winter (0.65 ± 0.17 ng/ml; P < 0.001). Pulsatile secretion patterns of leptin were not observed in any horses during experimentation. Mean concentrations of T 4 were greater in winter (20.3 ± 0.4 ng/ml) compared to summer (18.2 ± 0.4 ng/ml; P < 0.001). These seasonal differences between winter and summer provide evidence of possible seasonal regulation of TSH and leptin.

Prolactin Suppresses GnRH but Not TSH Secretion

Background/Aims: In animal models, prolactin increases tuberoinfundibular dopamine turnover, which has been demonstrated to suppress both hypothalamic GnRH and pituitary TSH secretion. To test the hypothesis that prolactin suppresses GnRH and TSH secretion in women, as preliminary evidence that a short-feedback dopamine loop also operates in the human, the effect of hyperprolactinemia on GnRH and TSH secretion was examined. Methods: Subjects (n = 6) underwent blood sampling every 10 min in the follicular phase of a control cycle and during a 12-hour recombinant human prolactin (r-hPRL) infusion preceded by 7 days of twice-daily subcutaneous r-hPRL injections. LH and TSH pulse patterns and menstrual cycle parameters were measured. Results: During the 7 days of r-hPRL administration, baseline prolactin increased from 16.0 ± 3.0 to 101.6 ± 11.6 µg/l, with a further increase to 253.7 ± 27.7 µg/l during the 12-hour infusion. LH pulse frequency decreased (8.7 ± 1.0 to 6.0 ± 1.0 pulses/12 h; p < 0.05) with r-hPRL administration, but there were no changes in LH pulse amplitude or mean LH levels. There were also no changes in TSH pulse frequency, mean or peak TSH. The decreased LH pulse frequency did not affect estradiol, inhibin A or B concentrations, or menstrual cycle length. Conclusion: These studies demonstrate that hyperprolactinemia suppresses pulsatile LH secretion but not TSH secretion and suggest that GnRH secretion is sensitive to hyperprolactinemia, but that TSH secretion is not. These data further suggest that the degree of GnRH disruption after 7 days of hyperprolactinemia is insufficient to disrupt menstrual cyclicity.

THYROTROPIC FEEDBACK CONTROL: EVIDENCE FOR AN ADDITIONAL ULTRASHORT FEEDBACK LOOP FROM FRACTAL ANALYSIS

More than 70 years after the discovery of the pituitary–thyroid feedback control mechanism, a classical endocrine regulation system, most of its parameters have been identified. However, the regulation of its central component in the pituitary gland, probably responsible for pulsatile release of thyrotropin (TSH), remains obscure. In order to infer its structure from the system's behavior, four different pituitary models were created and compared regarding their fractal properties. Based on the simplest model showing noncompetitive inhibition of TSH release by thyroid hormones—a physiologically plausible correlation—one alternative model added stochastic stimulation by central signals and another added an additional intrapituitary feedback loop, whereas the fourth model combined both effects. This latter model combining noncompetitive inhibition with the two additional effects showed the same fractal dimensions as in vivo time series, whereas the simpler models yielded significantly lower time-series complexity. These results suggest that both stochastic stimulation and ultrashort loop feedback are involved in the generation of TSH pulses in the human pituitary.

Effects of variations in physiological cortisol levels on thyrotropin secretion in subjects with adrenal insufficiency: a clinical research center study.

Although pharmacological doses of glucocorticoids suppress TSH secretion, less is known regarding the effects of physiological variations in cortisol levels on TSH. To study this issue, seven subjects with primary adrenal insufficiency each underwent four studies. In the first study subjects received infusions of saline for 48 h (baseline study). In the second study subjects received infusions of hydrocortisone for 48 h in a pulsatile and diurnal pattern that replicated serum cortisol levels in healthy subjects (physiological study). In most cases, the dose of hydrocortisone was 19 mg/24 h, but this was adjusted as necessary until the resulting serum cortisol levels reproduced those seen in healthy, nonstressed control subjects. In the third study subjects received the same total dose of hydrocortisone as in the physiological study, but with pulses of equal magnitude spaced evenly throughout the time period (constant study). In the fourth study subjects received the same total dose of hydrocortisone, but with the diurnal pattern shifted 12 h from the physiological infusion (reversed study). TSH levels were measured every 15 min during the final 24 h of each study. During the baseline study, the 24-h mean TSH level was 2.87 +/- 0.56 mU/L and did not exhibit any diurnal variation. During the physiological study, daytime TSH levels decreased 39% compared to those during the baseline study due to decreased TSH pulse amplitude, and the normal TSH diurnal rhythm was reestablished. The constant and reversed studies did not lead to significant changes in serum TSH levels compared to baseline. These results suggest that the normal circadian variation in endogenous cortisol levels may control TSH secretion, with maximal TSH suppression seen during the time when cortisol levels are highest. However, changing the diurnal pattern of hydrocortisone infusion did not lead to reciprocal changes in TSH levels, and the specific nature of the interactions between cortisol and TSH within the physiological range remains to be fully elucidated.

Secretion pattern of thyroid-stimulating hormone in dogs during euthyroidism and hypothyroidism

In as many as one third of dogs with primary hypothyroidism a plasma thyrotropin (TSH) concentration within the reference range for euthyroid dogs is found. To determine whether this is due to fluctuations in the release of TSH, the plasma profiles of TSH were analyzed in 7 beagle bitches by collecting blood samples every 10 min for 6 hr, both before and after induction of primary hypothyroidism. After induction of primary hypothyroidism, a 37-fold increase in mean basal plasma TSH concentration and a 34-fold increase in mean area under the curve for TSH were found. Analysis by the Pulsar program demonstrated pulsatile secretion of TSH in the hypothyroid state, characterized by relatively low amplitude pulses (mean [±SEM]) amplitude 41 ± 3% of basal plasma TSH level) and a mean pulse frequency of 2.0 ± 0.5 pulses/6 hr. In the euthyroid state, significant TSH pulses were identified in only 2 dogs. The mean basal plasma TSH level correlated positively (r = 0.84) with the mean amplitude of the TSH pulses, and correlated negatively (r = −0.88) with the TSH pulse frequency. The results of this study demonstrate pulsatile secretion of TSH in dogs during hypothyroidism and only small fluctuations in plasma TSH concentrations during euthyroidism. The findings also suggest that the low TSH values occasionally found in dogs with spontaneous primary hypothyroidism may in some cases in part be the result of ultradian fluctuations.

Abnormal circadian rhythm and increased non-pulsatile secretion of thyrotrophin in Sheehan's syndrome.

It has previously been shown that patients with postpartum pituitary necrosis (Sheehan's syndrome, SS) have paradoxically increased TSH levels and loss of the nocturnal TSH surge. This study sought to determine the circadian and pulsatile characteristics of TSH secretion underlying those abnormalities. Chronobiological and cluster analyses of 24-h TSH profiles were performed in nine SS patients (43-61 years, median = 52 years) and nine healthy female controls (33-47 years, median = 42 years). Serum concentrations of T3, T4, free T4 (fT4) and cortisol were measured by radioimmunoassay; TSH, GH, PRL and LH were determined by immunometric assays. All patients and controls showed significant circadian TSH rhythms, but the percentage amplitude was decreased (7.5% vs. 21.3%, P < 0.0001) and the acrophase was markedly displaced in SS patients, occurring between 0315 h and 1515 h in seven/nine patients and in two/nine controls (P = 0.057). Patients showed increased total 24-h TSH secretion (6054 +/- 2293 vs. 2193 +/- 340 mU/l/min, mean +/- SE, P = 0.04) due to increased non-pulsatile or tonic 24-h TSH secretion (5631 +/- 2105 vs. 1925 +/- 301 mU/l/min, P = 0.026), but no difference was detected in pulsatile secretion (424 +/- 191 vs. 268 +/- 41, P = 0.82). The contribution of non-pulsatile to total TSH secretion was also increased in SS patients (93.8% vs. 87.6%, P = 0. 002). No significant changes were found in TSH pulse frequency, amplitude, duration or interpeak interval. When cluster parameters were individually analysed in two distinctive 12-h periods corresponding to acrophase and nadir, patients showed increased non-pulsatile TSH secretion in both periods, but no differences were found in pulsatile TSH secretion, pulse frequency or amplitude. The increment of TSH secretion during the acrophase in SS patients was exclusively due to increased non-pulsatile TSH secretion, as opposed to controls who displayed significant increments in both non-pulsatile and pulsatile TSH secretions. Sheehan's syndrome patients have increased total TSH secretion due to increased tonic TSH secretion. A circadian TSH rhythm is still present in these patients, but shows decreased magnitude and markedly displaced acrophase.

Central Nervous System Control of Thyrotropin Secretion during Sleep and Wakefulness

Thyrotropin (TSH) is a pulsatile secreted hormone with a pronounced circadian rhythmicity and a characteristic nightly surge based on an augmentation of pulsatile release. A number of physiological factors influence TSH secretion via an alteration in the amount of pulsatile released hormone. An increase in somatostatinergic tone during fasting appears to decrease TSH pulse amplitude and sequentially mean TSH serum levels. In contrast, blockade of dopaminergic tone by metoclopramide infusion when circulating TSH levels are low during the afternoon hours increase TSH pulse amplitude to levels comparable to the nightly TSH surge suggesting a physiological dampening of TSH pulse amplitude by dopamine during the daytime.

Ultradian rhythms in pituitary and adrenal hormones: their relations to sleep.

Sleep and circadian rhythmicity both influence the 24-h profiles of the main pituitary and adrenal hormones. From studies using experimental strategies including complete and partial sleep deprivation, acute and chronic shifts in the sleep period, or complete sleep-wake reversal as occurs with transmeridian travel or shift-work, it appears that prolactin (PRL) and growth hormone (GH) profiles are mainly sleep related, while cortisol profile is mainly controlled by the circadian clock with a weak influence of sleep processes. Thyrotropin (TSH) profile is under the dual influence of sleep and circadian rhythmicity. Recent studies, in which we used spectral analysis of sleep electroencephalogram (EEG) rather than visual scoring of sleep stages, have evaluated the temporal associations between pulsatile hormonal release and the variations in sleep EEG activity. Pulses in PRL and in GH are positively linked to increases in delta wave activity, whereas TSH and cortisol pulses are related to decreases in delta wave activity. It is yet not clear whether sleep influences endocrine secretion, or conversely, whether hormone secretion affects sleep structure. These well-defined relationships raise the question of their physiological significance and of their clinical implications.

Effects of Metoclopramide on Fasting-Induced TSH Suppression

Short-term caloric deprivation leads to suppression of TSH secretion in healthy subjects, but the mechanism of this effect is unknown. Since dopamine inhibits TSH secretion at physiologic levels, increased endogenous dopamine activity may cause the TSH suppression observed during fasting. To test this hypothesis, 11 healthy subjects underwent four studies: (1) Baseline-subjects were allowed ad libitum food. (2) MCP-subjects were allowed ad libitum food and received iv metoclopramide (MCP) at 30 micrograms/kg/h over 48 h. (3) Fasting-subjects received no caloric intake for 56 h. (4) Fasting+MCP-subjects fasted for 56 h, and received iv MCP during the final 48 h of the study. Serum TSH levels were measured every 15 min during the final 24 h of each study, and a TRH stimulation test was performed at the conclusion of each study: 56 h of fasting decreased 24 h mean TSH levels and TSH pulse amplitude by 40%, with blunting of the TSH response to TRH. MCP infusions increased 24 h mean TSH levels and TSH pulse amplitude 26-34%, with no differences between the fasting and nonfasting studies. MCP infusions did not normalize TSH levels, TSH responses to TRH, or serum T3 levels during fasting. These data suggest that endogenous dopaminergic activity does not play a major role in fasting-induced TSH suppression in healthy subjects.

Differential effects of short-term fasting on pulsatile thyrotropin, gonadotropin, and alpha-subunit secretion in healthy men--a clinical research center study.

In healthy subjects, short term fasting suppresses the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal (HPG) axes, with decreased serum levels of TSH and LH. However, effects of fasting on pulsatile release of TSH, LH, FSH, and alpha-subunit are less clear. Eleven healthy young men each underwent two 2-day studies: a baseline study during normal caloric intake and a fasting study during 56 h of caloric deprivation. During the final 24 h of each study, blood samples were drawn every 15 min for measurement of serum TSH, LH, FSH, and alpha-subunit pulses. Fifty-six hours of fasting caused a 50% suppression of mean TSH levels and TSH pulse amplitude, without altering TSH pulse frequency. Nocturnal TSH pulse amplitude decreased by 60%, with abolition of the usual nocturnal TSH surge. Fasting suppressed mean LH levels and LH pulse amplitude by 30%, without affecting LH pulse frequency. In contrast, mean FSH levels only decreased by 13%, without changes in FSH pulse parameters, whereas mean alpha-subunit levels and pulse amplitude decreased by 20%. These data show that short term fasting has a greater suppressive effect on the hypothalamic-pituitary-thyroid axis than on the HPG axis. Within the HPG axis, FSH is more resistant to fasting-induced suppression than LH, implying discordant regulation of the two gonadotropins during nutritional deprivation. alpha-Subunit suppression during fasting appears to parallel that seen for LH.

Temporal link between plasma thyrotropin levels and electroencephalographic activity in man

Plasma thyrotropin (TSH) levels have been previously shown to be associated with the internal sleep structure determined by conventional scoring of sleep stages. This temporal relationship was re-evaluated using spectral analysis of the sleep electroencephalogram (EEG). Eight healthy male subjects underwent two randomized night studies after having received either placebo or 5 mg ritanserin, a selective 5-HT 2 receptor antagonist known to increase slow-wave sleep. Delta relative power and TSH levels, determined at 10 min intervals, were found to be inversely related with an average cross-correlation coefficient highly significant ( P < 0.0001) in both experimental conditions. Alpha slow-wave index, an estimator of awakenings, and TSH pulses exhibited a significant temporal association in both conditions. These results demonstrate that TSH fluctuations are linked to the sleep EEG activity in man.

Pulsatile thyrotropin secretion in patients with Cushing's syndrome

Pulsatile and circadian thyrotropin (TSH) secretion were studied in 16 healthy controls and in three patients with Cushing's syndrome who were studied twice (before and after treatment). Blood was sampled every 10 minutes over 24 hours for TSH (immunoradiometric assay [IRMA]). Mean 24-hour TSH in Cushing's syndrome was lower than in controls (0.4 ± 0.2 v 1.7 ± 0.7 mU/L, P < .001), related to a lower mean 24-hour TSH pulse amplitude (Desade: 0.16 ± 0.15 v 0.44 ± 0.20 mU/L, P < .001; Cluster: 0.17 ± 0.14 v 0.39 ± 0.20 mU/L, P < .001; mean ± SD). TSH pulse frequency was unchanged with approximately 10 pulses 24 h . The nocturnal TSH surge was diminished relative to controls (median-0, range-−0.03 to 0.2 mU/L v 0.9 and 0.3 to 2.5 mU/L, respectively), related to a loss of the usual nocturnal increase in TSH pulse amplitude, but not of TSH pulse frequency. In the eucorticoid state, there was an increase of mean 24-hour TSH to 1.3 ± 0.8 mU/L ( P < .001) under normalization of the mean 24-hour TSH pulse amplitude. The nocturnal TSH surge also increased (median, 0.21; range, 0.15 to 0.4 mU/L) under restoration of the usual nocturnal increase in TSH pulse amplitude. In conclusion, Cushing's syndrome is associated with a decrease of mean 24-hour plasma TSH, related to a decrease of TSH pulse amplitude (not of TSH pulse frequency). The nocturnal TSH surge is decreased in Cushing's syndrome associated with a loss of the usual nocturnal increase of TSH pulse amplitude. The changes in pulsatile TSH release disappear upon restoration of the eucorticoid state.

Effects of naloxone infusions on pulsatile thyrotropin secretion.

Endogenous opioids are known to modulate the secretion of some anterior pituitary hormones, but they are not thought to have significant effects on TSH secretion. However, dynamic TSH secretion has not been characterized during naloxone infusions. Therefore, we measured TSH levels every 15 min over 24 h in nine healthy young men at baseline and during infusions of naloxone at 2 mg/h. A TRH test was performed after each study. TSH pulses were located by Cluster analysis. Naloxone infusions decreased 24-h mean TSH levels by 28%, from 1.68 +/- 0.20 to 1.21 +/- 0.19 mU/L. Mean daytime TSH levels did not change, but nocturnal TSH levels were decreased by 39%, from 2.21 +/- 0.30 to 1.35 +/- 0.21 mU/L. There were no changes in TSH pulse frequency, but naloxone infusions decreased 24-h TSH pulse amplitude by 32%, from 2.02 +/- 0.26 to 1.37 +/- 0.21 mU/L. Daytime TSH pulse amplitude was relatively unaffected (1.27 +/- 0.15 vs. 1.16 +/- 0.21 mU/L), whereas nocturnal TSH pulse amplitude was decreased by 42%, from 2.72 +/- 0.40 to 1.57 +/- 0.23 mU/L. TSH responses to acute TRH administration were decreased after naloxone infusions (12.38 +/- 1.93 vs. 9.17 +/- 1.36 mU/L). Serum T3 levels fell by 21% during naloxone infusions, from 1.9 +/- 0.1 to 1.5 +/- 0.1 nmol/L, whereas other thyroid hormone levels and cortisol levels were unchanged. These findings suggest that endogenous opioids have significant stimulatory effects on TSH secretion, predominantly during the nocturnal TSH surge.

Pulsatile secretion of thyrotropin in children.

To examine pulsatile TSH secretion, serum TSH was determined every 30 min for 24 h in eight short normal prepubertal children (3 males and 5 females, age 4.0-12.6 yr). All children exhibited a clear circadian pattern of TSH secretion. Pulsatile TSH secretion was identified in all subjects with a mean (+/- SD) TSH pulse frequency of 6.9 +/- 1.2 pulses/24 h. The group mean TSH pulse amplitude was 1.4 +/- 0.3 mU/L. Mean TSH concentration was higher during the night hours (2.1 +/- 0.8 mU/L) than during the day hours (1.3 +/- 0.4 mU/L, p < 0.005), and significantly more pulses were detected during the night (mean 4.7 +/- 1.4) than during the day hours (2.1 +/- 0.6, p < 0.005). On average, 62 to 68% of the peaks were detected in the night hours. Mean TSH pulse amplitude during the night hours was not significantly different from that during the day hours. Our findings indicate that, as previously shown in adults, a pulsatile pattern of TSH secretion is present in children. In our study group, the nocturnal TSH surge is associated with an increase in pulse frequency but not amplitude.

Nycthemeral patterns of thyroid hormones and their relationships with thyrotropin variations and sleep structure

In order to precise the relationships between TSH, FT3, and FT4 nycthemeral variations and the relationships between thyroid hormone variations and sleep, 8 healthy young males were studied twice, once during a 24-h experiment with normal nocturnal sleep, and once during a night of sleep deprivation. The subjects received continuous enteral nutrition and remained supine during the whole experiment. Blood was sampled every 10 min for TSH, FT3, and FT4 measurements. Thyroid hormones exhibited small oscillations which were not systematically related to TSH pulses, and there was no evidence of a nycthemeral rhythm. SWS was associated with TSH declining phases, whereas awakenings were strongly associated with ascending phases of TSH variations. There was no association between sleep structure or awakenings and thyroid hormones. Sleep deprivation led to increased TSH and FT3 levels, without any variation in FT4 levels. These results demonstrate that short-term thyroid hormone variations do not only depend on the effect of TSH on thyroid secretion but also on a possible role of TSH on peripheral FT4 to FT3 conversion. Conversely, the relationships between TSH and SWS or awakenings are not mediated by thyroid hormones.

Effects of hydrocortisone on pulsatile pituitary glycoprotein secretion.

During states of stress, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal function can be suppressed. One putative mediator of this stress response may be glucocorticoids, which have widespread effects on thyroid and gonadal function. To characterize dynamic pituitary glycoprotein secretion during glucocorticoid administration, 24-h TSH, LH, FSH, and alpha-subunit pulses were measured in 10 healthy young subjects on 3 occasions: 1) at baseline, 2) during infusions of 100 mg hydrocortisone (HC) over 24 h, and 3) during infusions of 300 mg HC over 24 h. These HC infusions led to serum cortisol levels similar to the endogenous cortisol levels seen in moderate and severe stress. Both HC infusions had profound rapid effects on TSH levels, decreasing TSH pulse amplitude by 60% and abolishing the nocturnal TSH surge. However, TSH pulse frequency was unaltered. In contrast, HC infusions did not change mean or pulsatile LH, FSH, or alpha-subunit secretion. These results suggest that stress levels of cortisol acutely suppress TSH secretion at the pituitary level, with little effect on the TSH pulse generator. On the other hand, the effects of stress and/or hypercortisolism on the gonadal axis may require higher cortisol levels, more prolonged exposure, or other mediators of the stress response.