TSH Pulse Frequency Research Articles

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.

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.

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.

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.

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.

Pulsatile thyrotropin secretion in nonthyroidal illness.

Pulsatile and nocturnal TSH secretion was investigated in 16 healthy controls (group A) and 21 patients with nonthyroidal illness (NTI; group B). Ten patients had normal plasma T3 and T4 values (group B1), and 11 patients had decreased plasma T3 with normal or low plasma T4 (group B2). Mean 24-h TSH secretion in NTI patients was higher than that in controls (3.1 +/- 0.7 vs. 1.7 +/- 0.7 mU/L; P < 0.01; mean +/- SD). This was associated with an increased TSH pulse amplitude in NTI patients relative to controls [Desade, 0.79 +/- 0.46 vs. 0.44 +/- 0.20 mU/L (P < 0.01); Cluster, 0.64 +/- 0.42 vs. 0.39 +/- 0.20 mU/L (P < 0.05)]. There was no difference in TSH pulse amplitude between subgroups B1 and B2. TSH pulse frequency was not different between NTI patients and controls (approximately 10 pulses/24 h). The mean 24-h TSH concentration was significantly related to the mean 24-h TSH pulse amplitude but not to the mean 24-h TSH pulse frequency. The absolute nocturnal TSH surge in NTI patients was lower than that in controls (0.6 +/- 0.6 vs. 1.0 +/- 0.6 mU/L; P < 0.05). The lower nocturnal TSH surge in patients with decreased plasma T3 (group B2) was associated with a loss of the usual nocturnal increase of TSH pulse amplitude; the usual nocturnal increase in TSH pulse frequency was preserved. This was also observed in the six patients (two in group B1 and four in group B2) in whom the nocturnal TSH surge was completely absent. The changes in nocturnal TSH secretion in NTI resemble those found in central hypothyroidism, suggesting that features of central hypothyroidism are involved in the euthyroid sick syndrome.

Pulsatile thyrotropin release in patients with untreated pituitary disease.

Pulsatile and nocturnal TSH secretion was investigated in 16 healthy controls (group A) and 19 patients with untreated pituitary disease [7 were euthyroid without suprasellar extension (group B), 6 were euthyroid with suprasellar extension (group C) of pituitary lesions, and 6 were hypothyroid with or without suprasellar extension (group D)]. Pulse analysis was performed using Desade and Cluster algorithms. No changes were observed among groups A-D in mean 24-h TSH pulse amplitude [values given as mean +/- SD; Desade, 0.4 +/- 0.2 vs. 0.7 +/- 0.4 vs. 0.6 +/- 0.4 vs. 0.5 +/- 0.2 mU/L (P = NS); Cluster, 0.4 +/- 0.2 vs. 0.7 +/- 0.4 vs. 0.5 +/- 0.3 vs. 0.4 +/- 0.2 mU/L (P = NS)] or in the mean 24-h TSH pulse frequency (approximately 10 pulses/24 h). The mean 24-h TSH concentration was highly correlated to the mean 24-h TSH pulse amplitude in controls (r = 0.93; P < 0.001) and patients (r = 0.63; P < 0.01), but not to the mean 24-h TSH pulse frequency. The nocturnal TSH surge was similar in controls and euthyroid patients without suprasellar extension (group A, 1.0 +/- 0.6; group B, 1.3 +/- 1.3 mU/L; P = NS), but was decreased in euthyroid patients with suprasellar extension (group C, 0.3 +/- 1.0 mU/L; P < 0.05) and hypothyroid patients (group D, 0.4 +/- 0.4 mU/L; P < 0.05). The decreased nocturnal TSH surge was associated with a loss of the usual nocturnal increase in TSH pulse amplitude, whereas the usual nocturnal increase in TSH pulse frequency was maintained. In conclusion, 1) mean 24-h TSH pulse amplitude and frequency are unchanged in untreated patients with pituitary disease; and 2) patients with central hypothyroidism as well as euthyroid patients with suprasellar extension of pituitary lesions had a decreased nocturnal TSH surge associated with a loss of the usual nocturnal increase in TSH amplitude, but not TSH pulse frequency.

Circadian changes in pulsatile TSH release in primary hypothyroidism.

We evaluated pulsatile and circadian TSH secretion in primary hypothyroidism. In a prospective study, blood was sampled every 10 minutes during 24 hours for assay of TSH (IRMA). Thyroid hormones and TSH responsiveness to TRH were then measured. Nine patients with overt primary hypothyroidism, seven patients with subclinical hypothyroidism and 16 healthy controls. Computer-assisted analysis by the Desade and Cluster programs. Both computer-assisted programs revealed an increased TSH pulse amplitude in both overt and subclinical hypothyroidism versus controls (Desade: 36.9 +/- 31.4 (mean +/- SD) (P < 0.001) and 2.8 +/- 1.9 (P < 0.001) vs 0.4 +/- 0.2 mU/l; Cluster: 25.6 +/- 25.1 (P < 0.001) and 2.4 +/- 1.4 (P < 0.001) vs 0.4 +/- 0.2 mU/l). TSH pulse frequency remained unchanged with approximately 10 pulses/24 hours. A highly significant correlation was found between the mean 24-hour TSH concentration and the TSH pulse amplitude in all controls and patients but not to TSH pulse frequency. The nocturnal TSH surge was absent in six out of nine patients with overt primary hypothyroidism. The deficient nocturnal rise of TSH in primary hypothyroidism vs controls (22 +/- 51 vs 82 +/- 41%, P < 0.001), was associated with a loss of the usual nocturnal increase in TSH pulse amplitude and frequency. Mean 24-hour TSH pulse amplitude is increased in primary hypothyroidism, but TSH pulse frequency remains unchanged. The decrease of the nocturnal TSH increase in primary hypothyroidism is associated with a loss of the usual nocturnal increase in TSH pulse amplitude and frequency.

Effects of dopamine and somatostatin on pulsatile pituitary glycoprotein secretion.

The hypothalamic factors dopamine (DA) and somatostatin (SRIH) inhibit pituitary glycoprotein secretion, but little is known regarding the effects of these factors on glycoprotein pulses. To address this question, 12 healthy volunteers underwent frequent blood sampling over 12 h at baseline and during 12-h infusions of DA and/or SRIH. TSH, LH, FSH, and alpha-subunit (alpha) levels were measured in all samples, and hormone pulses were located by Cluster analysis. Both DA and SRIH suppressed TSH pulse amplitude by 70%, while SRIH decreased TSH pulse frequency as well. Both infusions decreased LH pulse amplitude by 30-35%, but had no effect on pulse frequency. In contrast, neither infusion significantly altered FSH pulse parameters, although mean FSH levels declined 15%. DA had no effect on pulsatile alpha secretion, while SRIH decreased alpha pulse frequency. Serum thyroid hormone levels declined during both infusions, but there were no major changes in serum sex steroid levels. Thus, the hypothalamic inhibitory factors DA and SRIH had divergent effects on glycoprotein hormone pulses. The major effects on pulse amplitude, rather than frequency, imply that these factors do not play major roles in the generation of glycoprotein pulses, although SRIH may directly affect the TSH and alpha pulse generators.

Unaltered pulsatile and circadian TSH release in euthyroid patients with endemic goitre

To evaluate the pathophysiological role of TSH in goitrogenesis we investigated pulsatile TSH secretion in 11 patients with a non-toxic goitre and in 11 healthy controls. Thyroid volume was 40 +/- 10 ml in the goitre group and 15 +/- 4 ml in the controls as measured by ultrasound. Blood was sampled continuously via an indwelling venous catheter at 10-min intervals over 24 h. Neither the mean 24-h serum TSH levels (goitre 1.1 +/- 0.5 vs controls 0.9 +/- 0.4 mU/l) nor the nocturnal surge of TSH were significantly different between the two groups. The average of the TSH pulse frequency (goitre 10.8 +/- 3.7 vs controls 9.6 +/- 3.5 pulses/24-h) and of the TSH pulse amplitude (goitre 0.4 +/- 0.2 vs controls 0.3 +/- 0.1 mU TSH/l) as analysed by DESADE programme (detection of secretory activity by discrete deconvolution) did not differ in the two groups. Furthermore, there was no correlation between the volume of the thyroid gland and the dynamics of the TSH secretion. We conclude that our data do not suggest a relevant pathophysiological role of TSH secretion in the development of non-toxic goitre in man.

Age-related alterations in pulsatile secretion of TSH: role of dopaminergic regulation

To investigate the influence of aging on dopaminergic modulation of pulsatile thyrotropin (TSH) secretion, we examined changes in circulating TSH levels during the day and night, with and without a dopamine antagonist metoclopramide, in healthy young (20-35 yr old) and old (69-83 yr old) subjects, with the use of cluster analysis. Baseline thyroid function tests including serum thyroxine, 3,5,3'-triiodothyronine (T3), T3 resin uptake, and TSH and the response of TSH to thyrotropin-releasing hormone were within normal limits in young and old subjects, and antimicrosomal and anti-thyroglobulin antibodies were absent in all participants. Pulsatile TSH secretion was identified in all subjects, and as a group there were significant increases in nocturnal peak height (P less than 0.01), amplitude (P less than 0.01), and mean TSH (P less than 0.001). TSH pulse amplitude increased 160% (P less than 0.05) at night compared with day in the young but was unchanged at night in the old. After the administration of metoclopramide there was a significant increase in peak height (P less than 0.01), amplitude (P less than 0.01), and mean TSH (P less than 0.01). However, the effect of metoclopramide was different in young and old subjects. In the young, daytime administration of metoclopramide increased TSH pulse height (P less than 0.02) and mean TSH (P less than 0.05); pulse parameters remained unchanged at night. In comparison, in old subjects after metoclopramide, pulse parameters were unchanged during the day but pulse amplitude significantly (P less than 0.01) increased at night. TSH pulse frequency remained stable with age and was unaltered after metoclopramide.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsatile Secretion of Thyrotropin during Fasting: A Decrease of Thyrotropin Pulse Amplitude*

The effect of fasting on circadian and pulsatile TSH secretion was investigated in eight healthy subjects (four men and four women in the follicular phase). Each subject was studied twice, once during 24 h with normal food intake and once during the last 24 h of a 60-h fast. Blood was sampled every 10 min during 24 h for measurement of TSH by a sensitive immunoradiometric assay. Fasting induced a decrease in plasma T3 [1.73 +/- 0.06 vs. 1.36 +/- 0.04 nmol/L; P less than 0.01 (mean +/- SE), control period vs. fasting] and thyroglobulin (52 +/- 8 vs. 35 +/- 7 pmol/L; P less than 0.001) and an increase in plasma rT3 (0.30 +/- 0.06 vs. 0.44 +/- 0.09 nmol/L; P less than 0.02). Plasma T4, thyroid hormone binding index, and free T4 were not statistically different in both periods. The mean plasma 24-h TSH concentration was lower during fasting than in the control period (2.0 +/- 0.3 vs. 1.0 +/- 0.2 mU/L; P less than 0.005). This was associated with a decrease in mean TSH pulse amplitude during fasting (Desade program: 0.6 +/- 0.1 vs. 0.3 +/- 0.1 mU/L; P less than 0.01; Cluster program: 0.5 +/- 0.1 vs. 0.2 +/- 0.1 mU/L; P less than 0.05), whereas TSH pulse frequency during fasting was unchanged (Desade program: 8.4 +/- 0.9 vs. 9.8 +/- 0.8 pulses/24 h; Cluster program: 9.5 +/- 0.5 vs. 7.9 +/- 0.9 pulses/24 h). There was a highly significant correlation between the mean 24-h TSH concentration and the mean TSH pulse amplitude during both the control period and fasting. Although the decrease in TSH concentration during fasting was evident over 24 h, fasting especially decreased the absolute (1.3 +/- 0.3 vs. 0.4 +/- 0.1 mU/L, P less than 0.02) and the relative (101 +/- 18% vs. 40 +/- 14%; P less than 0.02) nocturnal TSH surge (mean TSH 0000-0400 h vs. mean TSH 1500-1900 h). The decreased nocturnal TSH surge during fasting was associated with a significantly decreased TSH pulse amplitude, but with an unaltered number of TSH pulses between 2000-0400 h. In conclusion, fasting decreases 24-h TSH secretion and the nocturnal TSH surge in the absence of a change in plasma T4 concentration. This is associated with a decreased TSH pulse amplitude, whereas TSH pulse frequency remains unchanged.

EFFECT OF DOPAMINE AND A DOPAMINE D‐1 RECEPTOR AGONIST ON PULSATILE THYROTROPHIN SECRETION IN NORMAL WOMEN

The inhibitory effect of a pharmacological dose of dopamine and the specific dopamine D-1 receptor agonist fenoldopam on basal and pulsatile TSH secretion was investigated in normal women. The TSH response to fenoldopam and subsequent releasing hormone administration was also studied. Six women received placebo or dopamine infusion (4.0 micrograms/kg min) for 17 h. After 9 h, blood samples were collected every 10 min between 0800 and 1600 h for measurement of TSH. Eight women received 8-h (0900-1700 h) infusions of either fenoldopam (0.5 micrograms/kg min) or placebo. After 7 h of infusion 10 micrograms TRH, 5 micrograms GnRH and 25 micrograms CRF was given i.v. Blood samples were collected every 10 min. Dopamine infusion as well as fenoldopam infusion significantly reduced both mean basal TSH secretion and TSH pulse frequency compared with corresponding control infusions (P less than 0.05). However, while the effect on TSH pulsatility was comparable (P greater than 0.05), the percentage decrease in basal TSH levels after 16 h of dopamine infusion was 51 +/- 16% (mean +/- SD) and after 7 h of fenoldopam infusion 19 +/- 12% (P less than 0.05). Neither of the drugs affected TSH pulse amplitude and fenoldopam did not influence TRH-stimulated TSH release (P greater than 0.05). The results suggest that dopamine D-1 receptors are involved in modulation of TSH pulsatility probably at the hypothalamic level. It is argued that dopaminergic inhibition of basal TSH secretion and TSH pulsatility is predominantly regulated through dopamine D-2 receptors at the pituitary level, and through D-1 receptors at the hypothalamic level, respectively.

Patterns of Pulsatile Pituitary Glycoprotein Secretion in Central Hypothyroidism and Hypogonadism*

Five patients with central hypothyroidism and hypogonadism due to mass or infiltrative lesions of the pituitary and hypothalamus were studied to determine pulsatile pituitary glycoprotein secretion patterns. Blood samples were obtained every 15 min over 24 h, and TSH, LH and FSH were measured by immunoradiometric assays. Hormone pulses were located by cluster analysis, and pulse patterns were compared to those in normal subjects. Three patients had unmeasurable LH levels, while two had a normal number of low amplitude pulses. In contrast, all patients had normal FSH pulse frequency, and only one had low pulse amplitude. Three patients had normal 24-h TSH pulse frequency and amplitude, while two had slightly decreased pulse parameters. However, all failed to show normal nocturnal increases in TSH pulse amplitude. Thus, anatomical hypothalamic-pituitary lesions disrupt pulsatile glycoprotein secretion in a discordant fashion. LH is most severely affected, with abnormal pulse patterns similar to those in idiopathic central hypogonadism. FSH and TSH pulses are relatively preserved, but loss of the usual nocturnal increase in TSH pulse amplitude is sufficient to cause clinical hypothyroidism. Whether these defects reflect intrinsic pituitary disease or impaired hypothalamic releasing factor function remains to be determined.

Pulsatile secretion of thyrotropin in man.

To examine pulsatile TSH secretion, serum TSH was determined every 10 min for 24 h in 6 normal subjects and every 15 min in 10 euthyroid patients with underlying thyroid disease. Serum T4, T3, and PRL were simultaneously measured in the 10 patients. Pulsatile TSH secretion was identified in all individuals. There was a highly significant correlation between the mean 24-h TSH concentration and pulse amplitude (P less than 0.001). There was a highly significant inverse correlation between the mean 24-h TSH concentration and pulse frequency (P = 0.002) and between the pulse amplitude and frequency (P = 0.002). The mean serum TSH level at night (1800-0600 h) was significantly higher than that during the day (P less than 0.001) and was associated with increases in pulse amplitude (P = 0.008) and frequency (P = 0.007). TSH pulses did not correlate with serum T4 or T3, but did correlate with serum PRL (P = 0.03) in patients with thyroid disease. We conclude that TSH pulsations can be identified in normal subjects and patients with thyroid disease; elevations in serum TSH levels correlate with an increase in pulse amplitude and a decrease in pulse frequency; the nocturnal rise in serum TSH is associated with increases in both pulse amplitude and frequency; and peripheral serum T4 or T3 concentrations are not closely associated with pulsatile TSH secretion.