Decreased prolactin responsiveness to thyrotrophin-releasing hormone and metoclopramide in hyperthyroidism

To investigate whether prolactin (Prl) responsiveness to thyrotrophin-releasing hormone (TRH) differs in thyrotoxic and normal individuals, serum Prl was determined before and after iv injection of 200 micrograms TRH in 10 patients with untreated thyrotoxicosis and also in 9 normal subjects. Both the maximal Prl increment after TRH and the total Prl response, represented by the Prl incremental area, were significantly larger in the normal subjects compared with the thyrotoxic (max Prl increment 56 +/- 11 vs 15 +/- 3 ng/ml, P less than 0.001; Prl incremental area 3071 +/- 522 vs 579 +/- 171, P less than 0.001; mean +/- SEM). The maximal Prl increase after 15 mg oral metoclopramide (MET) was also significantly larger in the normal (125 +/- 13 ng/ml) than in the thyrotoxic subjects (60 +/- 13 ng/ml, P less than 0.01). When 200 micrograms TRH was injected iv 90 min after oral administration of 15 mg MET, an additional Prl increase was observed in normal individuals (21 +/- 6 ng/ml, P less than 0.01). In thyrotoxic patients, however, iv TRH failed to induce a significant increase in Prl after oral priming with MET (0 +/- 3 ng/ml). When 7 thyrotoxic patients, made euthyroid by 125I-treatment, were investigated according to the same protocol as the one mentioned above, they displayed normal Prl responses to iv TRH and to oral MET. Furthermore, they showed a significant Prl response to iv TRH after oral priming with MET (20 +/- 8 ng/ml, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

DOPAMINE IS A PHYSIOLOGICAL REGULATOR OF THYROTROPHIN (TSH) SECRETION IN NORMAL MAN

Using a sensitive and precise radioimmunoassay for human TSH we have demonstrated significant elevations in serum TSH levels in euthyroid volunteers following administration of the dopamine receptor blocking drug metoclopramide when compared with placebo. The degree of TSH response is significantly greater in females than in males and is sustained over a 3-hour period after a single oral 10 mg dose of metoclopramide. The degree of TSH release after metoclopramide is inversely related to the basal TSH level suggesting that dopamine is a determinant of low daytime TSH levels and is thus implicated in the circadian rhythm of TSH secretion. Pretreatment with 10 mg of metoclopramide orally, one hour before TRH administration leads to significant enhancement of the TSH response to TRH. Our findings provide further evidence for the physiological inhibitory role of dopamine in the control of TSH secretion in normal man. The possible mode of action of dopamine and the clinical implications of this neuroregulatory pathway are discussed.     

THE INTERRELATIONSHIPS BETWEEN PROLACTIN AND THYROTROPHIN SECRETION FOLLOWING DOPAMINERGIC BLOCKAGE IN PATIENTS WITH MILD HYPERPROLACTINAEMIA WITHOUT ANY DEMONSTRABLE PITUITARY TUMOUR

PRL, TSH and gonadotrophin responses to the dopaminergic antagonist, metoclopramide, were studied in mildly hyperprolactinaemic patients with normal sella radiology and CT scan. Eleven female patients with basal PRL levels ranging from 23 to 124 ng/ml were challenged with intravenous metoclopramide (10 mg) and on subsequent occasions with TRH (200 micrograms) and LHRH (100 micrograms). On the basis of the PRL secretory pattern following metoclopramide and TRH stimulation, the patients were divided into two groups. Group I comprised six subjects who were PRL non-responsive to TRH and metoclopramide. Group II (five subjects) demonstrated PRL responses to TRH and metoclopramide indistinguishable from female controls. Mean +/- SD basal PRL levels were 68.5 +/- 29.9 ng/ml in Group I and not different in Group II (40.6 +/- 12.0 ng/ml). Basal LH levels were increased in Group II, whereas FSH was increased in Group I. Basal TSH levels were lower in Group I than the controls. Following metoclopramide, Group I patients had an increase in TSH from a basal of 2.4 +/- 0.7 microU/ml to a peak of 5.9 +/- 2.7 microU/ml (P less than 0.005) which occurred at 30 min. TSH values were increased above basal at all time intervals following metoclopramide. In contrast, TSH levels did not change in Group II patients or the controls after metoclopramide administration. Both patient groups had TSH responses to TRH similar to the controls. Following LHRH, the LH increase was greater in Group II and the FSH in Group I. In neither group nor the controls did gonadotrophin levels change after metoclopramide. In Group II females, PRL responsiveness to metoclopramide was associated with TSH non-responsiveness. In Group I females, PRL levels failed to rise, whereas TSH increased. The PRL and TSH profile in Group I females is typical of a prolactinoma. It is concluded that PRL as well as TSH determinations following metoclopramide are useful indices in the assessment of hyperprolactinaemia and may be of value in differentiating the functional state from that of a pituitary tumour.     

Thyrotropin secretion in thyrotoxic and thyroxine-treated patients: assessment by a sensitive immunoenzymometric assay

A new TSH immunoenzymometric assay was found to be capable of discriminating between the serum TSH values of normal subjects [2.28 +/- 1.02 (+/-SD); range, 0.6-6.5 microU/ml] and those of clinically euthyroid, antithyroid drug-treated (n = 22) or clinically thyrotoxic (n = 34) patients. While a wide spectrum of basal TSH values was found in the antithyroid drug group [ranging from undetectable (less than 0.05 microU/ml: 57%) to 17.9 microU/ml], all clinically thyrotoxic patients had undetectable values. In 33 patients receiving chronic oral T4 therapy for treatment of goiter (n = 15) or thyroid cancer (n = 18), 48% (6 of 33) had undetectable basal TSH levels and no TSH response to TRH stimulation. Detectable TSH levels were found in 42% (14 of 33), and TRH responsiveness was found in 52% (17 of 33). The TSH response to TRH stimulation was less than 2.0 microU/ml in 7 patients. Serum free T4 index, free T3 index, and free T4 levels and oral T4 dosage were inferior predictors of TRH responsiveness compared to the basal TSH value. No patient receiving more than 0.2 mg T4 daily or having a free T4 index above 18, a free T3 index above 205 or a free T4 level above 3.0 ng/dl had a TSH response to TRH. Seventy-six percent (16 of 21) of the patients, when reevaluated 1-6 weeks after increased oral T4 dosage, had a significant reduction in their serum thyroglobulin level. This was true of both patients with initially detectable (11 of 14) as well as undetectable (5 of 7) basal serum TSH levels. These findings support the concept that subnormal and, for that matter, as yet undetectable levels of circulating TSH may exert stimulatory effects on thyroid tissue.     

DISSOCIATION BETWEEN TSH AND PROLACTIN DYNAMICS IN TREATED THYROTOXICOSIS

TSH and prolactin secretory patterns in thyroid disease have generally been reported as concordant. We studied TSH and prolactin responses to TRH infusion (500 mug) in euthyroid individuals previously treated for thyrotoxicosis with 131I or antithyroid drugs. The 131I-treated group (seven men, twenty women) had been clinically and biochemically euthyroid (normal serum thyroxine and triiodothyronine levels) for 6 months to 4-5 years (kappa +/- SD = 17-1 +/- 4-1 months). Based on maximal TSH increment (deltaTSH), three patient groups were identified: Group 1 [normal deltaTSH, n = 6]: delta prolactin was normal in two, blunted in one and exaggerated in three. Group 2 (exaggerated TSH response, n = 8): delta prolactin was normal in two, blunted in one and exaggerated in five. Group 3 (TSH nonresponders, n = 13): delta prolactin was normal in five, blunted in three, and exaggerated in five. Eleven patients (three men, eight women) were studied after 6 months antithyroid-drug treatment. All were clinically and biochemically euthyroid. All but one showed a blunted TRH-TSH response. All three men showed an exaggerated delta prolactin as did four of eight women. Three women showed a blunted delta prolactin and in one, delta prolactin was normal. Thus, TRH-induced TSH and prolactin response patterns in treated thyrotoxicosis are not uniformly concordant, and, while a blunted or absent TSH response commonly persists long after euthyroidism has been restored, this is most frequently accompanied by a normal or exaggerated prolactin response.     

Effect of acute levodopa load on blood prolactin concentration in patients with thyroid diseases

In 14 thyrotoxic patients and 5 persons with endemic euthyroid goiter the blood plasma prolactin content was studied under the action of an acute oral load of levodopa in a dose of 0.5 g. It was found that the basal prolactin level was significantly higher in the blood of patients of both sexes with thyrotoxicosis and endemic euthyroid goiter than that in the control group (10 healthy humans). The blood plasma prolactin content markedly decreased in thyrotoxic patients under levodopa effect, regardless of the sex, whereas in patients with endemic euthyroid goiter the drug exhibited no considerable action on the prolactin level. A possible mechanism of hyperprolactinemia in the thyroid hyperfunction is discussed.     

Increased plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide concentration in clinically euthyroid women with suppressed plasma thyrotropin levels: further evidence for generalized tissue overexposure to thyroid hormones in these subjects.

It has been reported that plasma levels of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (ADG) are increased in thyrotoxic patients. The present study was carried out to determine whether in clinically euthyroid subjects with suppressed TSH levels, ADG plasma levels would also be increased, suggesting a more generalized tissue overexposure to thyroid hormones. The latter has been suggested from increased sex hormone-binding globulin levels (SHBG) in these subjects. ADG and SHBG levels were measured in a group of 20 euthyroid postmenopausal women, 20 postmenopausal women with clinically evident thyrotoxicosis, and 16 euthyroid postmenopausal women with suppressed TSH levels. The mean ADG level in the thyrotoxic group was 4 times the mean level in the control group, whereas in the group with isolated TSH suppression the mean level was about twice the level in the control group. As levels of dehydroepiandrosterone sulfate, the major precursor of plasma ADG, were not significantly increased in these subjects, these data suggest an increased conversion of dehydroepiandrosterone sulfate to ADG. Together with the increased SHBG levels observed in both thyrotoxic and euthyroid subjects with suppressed serum TSH concentrations, these data support the concept that the TSH-suppressed euthyroid subjects have generalized increased thyroid hormone effects on peripheral tissues.     

Effect of prolonged oral administration of TRH on plasma levels of thyrotrophin and prolactin in normal individuals and in patients with primary hypothyroidism.

Forty mg TRH/day was given orally for 3 weeks to 10 euthyroid women and 10 women with primary hypothyroidism on low replacement doses of thyroxine. Once weekly oral TRH was replaced by an iv TRH-test (0.4 mg) with measurement of serum concentration of TSH, prolactin (PRL), thyroxine (T4), triiodothyronine (T3) and cholesterol. In the normal group, mean serum T4 concentration increased after one week and remained elevated. Serum TSH concentration showed a slight tendency to decline. Maximal rise in TSH concentration after iv TRH (deltaTSH) fell from a mean of 4.0 ng/ml to 1.4 ng/ml within one week and stayed low. T3, cholesterol, PRL and deltaprl were normal and unchanged throughout. In the hypothyroid group T4, T3, cholesterol, PRL and deltaPRL were not influenced by the TRH administration. In 2 patients (with the highest serum T4 concentrations) serum TSH concentration was normal and resistant to iv TRH. Of the 8 patients with elevated TSH, basal level and deltaTSH did not change in 2 (with subnormal T4 levels and the highest TSH levels). In the other 6 (with intermediate T4 levels) basal TSH fell from a mean of 10.1 ng/ml to 4.2 ng/ml, and deltaTSH from 10.0 ng/ml to 3.3 ng/ml after three weeks. It is concluded that in addition to feed-back effect of thyroid hormones, the pituitary response to long-term administration of TRH is determined by other factors. Among these may be reduced pituitary TRH receptor capacity and the activity of the TSH producing cells.     

The influence of thyroid disorders on the dopaminergic regulation of prolactin, thyrotropin and growth hormone

In order to clarify if hyper- and hypothyroidism change by feed-back mechanisms the dopaminergic controlled release of PRL, TSH and GH, the serum values of these hormones were measured before and following iv administration of 5 mg metoclopramide in 10 hyperthyroid, 11 euthyroid and 10 primary hypothyroid age-matched females, all consecutively investigated. The secretion pattern, as well as the quantitated response (area under the curve - AUC) of PRL were identical for the three groups, and uninfluenced by thyroid status. By contrast the TSH responses (AUC) were significantly and positively correlated to the basal TSH, suggesting that the effect of metoclopramide was dependent on the secretory capacity of the thyrotropic cells. The serum GH level was found to decrease in all three groups following metoclopramide, probably due to the inhibition of release. Stimulation of the same subjects with 200 micrograms TRH iv resulted in response curves of serum PRL and TSH, which were significantly and positively correlated to the basal serum TSH. The serum values of GH increased following TRH in the hypothyroid group, while the values of the hyperthyroid were depressed and unchanged. The present results suggest that the dopaminergic tonus on PRL, TSH and GH secretion is unaffected by thyroid feed-back mechanisms. The TRH-induced release of each of the three hormones is, however, dependent on thyroid status.     

BROMOCRIPTINE SUPPRESSION OF TRH-STIMULATED PROLACTIN AND THYROTROPHIN RELEASE AND ACCOMPANYING INHIBITION OF BROMOCRIPTINE INDUCED GROWTH HORMONE RELEASE BY TRH IN NORMAL MAN

Six normal fasting males received on four separate occasions in random order (1) a placebo tablet followed 60 min later by 200 microgram of TRH intravenously (2) bromocriptine 2.5 mg orally followed by TRH intravenously (3) bromocriptine 2.5 mg orally followed by a placebo injection and (4) placebo tablet followed by placebo injection. Plasma prolactin and TSH responses to TRH were decreased following bromocriptine pretreatment. The rise of plasma growth hormone after bromocriptine was inhibited by TRH. The rise in plasma FSH seen after TRH injection was not influenced by bromocriptine pretreatment. Circulating LH and insulin concentrations were unaffected by any drug administration. These results suggest a dopaminergic influence on prolactin and TSH release in normal men, an inhibitory effect of TRH on bromocriptine stimulated growth hormone secretion, and no dopaminergic modulation of basal insulin secretion.     

Effect of Pyridostigmine on the Thyroid-Stimulating Hormone Response to Thyrotropin-Releasing Hormone in Abstinent Alcoholics

Alcoholism is sometimes associated with a blunted thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH; peak minus baseline < 5 mlU/liter), despite basal TSH and thyroid hormone levels within the normal range. In light of the inhibitory effect of somatostatin on TSH secretion, we examined whether this condition is caused by an increased hypothalamic somatostatinergic tone in alcoholic subjects. To answer this question, 16 euthyroid male alcoholics (aged 38 to 50 years) with normal [ n = 8; normal responder alcoholics (NRAs)] or blunted [ n = 8; low responder alcoholics (LRAs)] TSH response to TRH were selected in a preliminary TRH test (200 μg in an intravenous bolus). In addition, 8 age- and weight-matched normal men were tested with TRH and used as normal controls (NCs). NCs and alcoholic patients showed similar basal serum TSH, free triiodothyronine, and free thyroxine levels. All subjects were tested again with TRH, 60 min after treatment with 180 mg of pyridostigmine orally. According to selection criteria, NCs and NRA groups showed similar TSH responses to TRH, whereas TRH-induced TSH rise was strikingly lower in LRAs than in NCs and the NRA group. Pyridostigmine did not change the basal levels of TSH in any group, whereas it enhanced in a similar manner the TRH-induced TSH rise in the NC and NRA groups. No significant change in the TSH response to TRH was observed in LRA patients after pyridostigmine treatment. These data argue against the possibility that an enhanced somatostatinergic tone is responsible for the blunted TSH response to TRH observed in some alcoholic patients. This phenomenon might be attributed to alcohol-related defects of stimulated pituitary thyrotroph secretory capacity in some individuals, possibly due to genetic vulnerability and/or the toxic effects of prolonged alcohol abuse.     

Multiple abnormalities of anterior pituitary hormone secretion in association with pseudohypoparathyroidism

A male with pseudohypoparathyroidism presented with several hormonal abnormalities. He was clinically euthyroid with no palpable goiter, His serum T4, total T3, T3 Sephadex retention, and 131I uptake were normal. However, elevated basal TSH levels and exaggerated TSH responses to TRH which normalized during the administration of thyroid extract suggested reduced thyroidal reserve. Despite these finding the 131I uptake increased after exogeneous TSH, and the T3 level rose after TRH. Basal testosterone levels and response to hCG were normal however, gonadotropins were elevated and there was an exaggerated response after LRH treatment. Both LH and FSH levels were suppressed by testosterone propionate. The patient demonstrated intermittent basal hyperprolactinemia and impaired PRL responsiveness after metolopramide, chlorpromazine, and insulin administration. There was, however, an intact response to TRH. Basal PRL, TSH, and LH levels decreased after the administration of L-dopa and bromocriptine. Although the precise mechanism underlying these finding is unknown, the elevated basal levels of TSH, LH, and FSH and the exaggerated responses to their respective releasing hormones suggest the presence of partial degree of end-organ resistance to these pituitary trophic hormones. Together with the resistance to PTH, this may imply a common defect, presumably at a postreceptor level. However, hyporesponsiveness of PRL to metoclopramide and chlorpromazine and normal responsiveness to TRH suggest that an abnormality of dopamine tone also exists in pseudohypoparathyroidism.     

PROTEIN-A PURIFIED HUMAN IMMUNOGLOBULINS: A COMPARISON OF THYROID STIMULATING AND THYROTROPHIN RECEPTOR BINDING ACTIVITIES IN THYROTOXICOSIS

Protein-A purified human thyroid stimulating immunoglobulins (TSIg) and thyrotrophin binding inhibiting immunoglobulins (TBIIg) were measured in euthyroid subjects and thyrotoxic patients by bioassay and TSH radioligand receptor assay respectively. Unextracted sera from euthyroid and thyrotoxic subjects inhibited both basal and TSH stimulated iodide uptake in the bioassay, which was based on iodide uptake in porcine thyrocytes. Similar effects were seen with Ig and TSIg extracted from sera using either polyethylene glycol or ammonium sulphate. However IgG and TSIg prepared using Protein-A Sepharose CL-4B from sera of euthyroid subjects had little effect in this system. The majority of Protein-A purified TSIg preparations from sera of thyrotoxic patients stimulated iodide uptake in procine thyrocytes in a dose-dependent manner and most (85%) diluted parallel to both bovine and human TSH. TSIg and TBIIg from 73 patients with thyrotoxicosis were assessed using the bioassay and receptor assay and compared to a control group of 35 euthyroid subjects. The median (and range) values for TSIg and TBIIg in the euthyroid group were 4.35 (0.8 to 7.5, % stimulation over control) and 2.7 (-9.3 to 8.6, TBII index) for the bioassay and radioreceptor assay respectively. A value of greater than 10.0 in both assays was taken as a positive result. Of the thyrotoxic patients 61 out of 73 were positive in the bioassay (83.6%) compared to 60 in the radioreceptor assay (82.2%). There was a positive correlation between the two assays (r = 0.821, P less than 0.001). Of the 73 thyrotoxic patients 40 were untreated, 18 had received carbimazole and 15 had been previously treated with iodine-131. TSIg levels in the untreated thyrotoxics were similar to those in either group of treated patients. However they were higher (P less than 0.05) in the iodine-131 group than in the patients treated with carbimazole. Similar results were obtained for TBIIg. The coupling of a specific extraction method for human serum IgG with a bioassay for TSIg has demonstrated a high prevalence of these immunoglobulins in patients with thyrotoxicosis. The agreement between this assay and a radioreceptor assay was good, indicating that TSH displacing and thyroid stimulating activities of these immunoglobulins are closely related.     

Pyridostigmine and metoclopramide do not restore the TSH response to TRH inhibited by L-thyroxine treatment in children with goiter

To define the role of somatostatin and dopamine in TSH suppression induced by L-thyroxine, 16 children (12 F, 4 M) on suppressive doses of L-thyroxine (3-4 microg/kg/day) for endemic goiter were studied. Firstly a conventional TRH test was performed in all subjects, in order to evaluate TSH, PRL and GH (basal study). A week later a second TRH test was carried out; one hour before the test, however, group A (9 patients) was given 60 mg pyridostigmine bromide po (pyridostigmine study) and group B (7 patients) 10 mg metoclopramide po (metoclopramide study). In the basal study, TSH was suppressed in both groups and levels did not increase following TRH administration, while PRL increased significantly and GH levels remained stable. In the pyridostigmine study, TSH levels did not increase following TRH administration, while PRL and GH levels were both significantly raised. In the metoclopramide study, TSH and GH levels were not raised following TRH administration, while a significantly greater increase of PRL was observed. In conclusion, suppressive doses of L-thyroxine inhibit the TSH response to TRH, while they do not seem to affect GH and PRL secretion. Somatostatin and/or dopamine do not seem to play a significant role in the L-thyroxine-induced TSH suppression.     

The Effect of Long-Term Cimetidine Treatment on PRL and TSH Response Capacity to TRH in Male Patients with Duodenal Ulcer

ABSTRACT. The effect of long-term cimetidine treatment for 6 months on basal and thyrotropin-releasing hormone (TRH)-stimulated prolactin (PRL) and thyroid-stimulating hormone (TSH) secretion was studied in eight male patients with duodenal ulcer. They received 1000 mg cimetidine orally per day until ulcer healing and thereafter 400 mg daily for the remaining period. TRH perturbation tests were performed before and after the 6 months of treatment. A significant reduction in the pituitary TSH response capacity was found. No significant changes in basal and TRH-stimulated PRL, basal TSH, thyroxine and triiodothyronine were found. It is uncertain if the reduction in pituitary TSH response capacity has any clinical implications in euthyroid patients.     

INAPPROPRIATE THYROTROPHIN SECRETION, INCREASED DOPAMINERGIC TONE AND PRESERVATION OF THE DIURNAL RHYTHM IN SERUM TSH

A patient presented with mild hyperthyroidism, elevated serum T4 and T3, and an inappropriately raised serum thyrotrophin (TSH). There was no evidence of pituitary tumour (alpha-subunit secretion and CT scan of the pituitary were normal). The TSH response to TRH was greater than normal. The elevated TSH was suppressed by oral triiodothyronine (100 micrograms daily for 10 d). The normal diurnal variation of TSH was preserved. Intravenous injection of the dopamine receptor blocking agent domperidone led to a greater than normal elevation in TSH (maximum increments 18-20 mU/l). This increased dopaminergic tone was similar in studies carried out in the morning and late evening. The dopamine agonist bromocriptine (2.5 mg twice daily) failed to suppress serum TSH either acutely or over 6 weeks. The circadian rhythm was unaltered by this treatment. Basal serum prolactin levels were normal, and responded appropriately to TRH, domperidone and bromocriptine. These observations indicate that dopamine does not control the diurnal variation of TSH in nontumoral TSH-mediated hyperthyroidism. The increased dopaminergic tone demonstrated may be secondary to the primary failure of pituitary-thyroid feedback in the condition.     

Are fasting-induced effects on thyrotropin and prolactin secretion mediated by dopamine?

To investigate whether total caloric deprivation influences TSH and/or PRL responsiveness, seven healthy volunteers fasted overnight (8 h) and were injected iv with a small dose (25 micrograms) of TRH and 30 min later with 40 mg cimetidine (CIM). This combined TRH-CIM test was repeated in the same individuals after a fasting period of 56 h. The TRH-stimulated mean maximal TSH increment fell from 5.1 +/- 1.2 to 1.2 +/- 0.6 microU/ml (P less than 0.01) during fasting. In contrast, both the TRH- and CIM-induced PRL responses were unaffected. To exclude methodologic errors on this reduced TSH responsiveness, an additional four normal subjects fasted for 56 h and then were given TRH alone. Two days later the TRH test was repeated after a fasting period of only 8 h. This experimental design also resulted in a significantly lower TSH response after the longer fasting period than after the shorter period, thus demonstrating that prolonged fasting inhibits TSH responsiveness regardless of whether the starvation period precedes or follows the TRH injection, and regardless of whether the pituitary thyrotrophs are stimulated with TRH plus CIM, or with TRH alone. In an additional seven healthy subjects injected with TRH plus CIM before and after a fasting period of 56 h, a dopamine D-2 receptor blocking agent, metoclopramide (MET), was given orally 90 min before the second TRH-CIM load. This priming with MET failed to restore normal TSH responsiveness in the fasting subjects, thus indicating that the suppressed TSH secretion could not have been mediated through dopamine D-2 receptors. However, since oral pretreatment with MET completely abolished the CIM-elicited PRL response in the fasting subjects, it is reasonable to assume that CIM stimulates PRL release via a reduced dopaminergic inhibition of the pituitary lactotrophs.     

The blunting of the thyrotropin response to repeated thyrotropin-releasing hormone administration is reduced by dopaminergic blockade both at normal and elevated serum levels of thyroid hormones

Fifteen premenopausal women were investigated in the follicular phase of the menstrual cycle with two TRH tests within an interval of 48 to 96 h. Ninety min before each TRH test either 10 mg metoclopramide or saline was injected iv in randomized order. The same procedure was repeated in the following menstrual cycle after pretreatment with T4 (0.5 mg daily for 6-14 days). At least 2 months later the same procedure was repeated with T3 pretreatment (60-120 micrograms for 6-8 days) in 9 of them. A multiple regression analysis was used in modelling the relationships between TSH release and serum free T3, T4 and estradiol levels, adjusting for the presence of metoclopramide and the order of the test. No correlation was found between the TSH response to TRH and the serum estradiol level. The TSH response to the second TRH test was approximately half the first one, both in the control situation and after treatment with T4 or T3. The blunting of the TSH response to the second TRH administration was significantly reduced by metoclopramide, both at normal and elevated thyroid hormone levels, suggesting that a dopaminergic mechanism takes part in the blunting.     

Prolactin and TSH response to TRH and metoclopramide before and after l-thyroxine therapy in subclinical hypothyroidism

The effects of the dopamine (DA) receptor antagonist metoclopramide on the plasma thyroid stimulating hormone (TSH) and prolactin (PRL) levels were studied in 8 patients with subclinical hypothyroidism (defined as absence of clinical signs of hypothyroidism with normal thyroid hormone levels, normal or slightly increased basal plasma TSH levels and increased and long-lasting TSH response to TRH) before and after l-thyroxine replacement therapy. Metoclopramide induced a significant (p less than 0.01) TSH release in the subclinical hypothyroid patients. Two weeks after l-thyroxine replacement therapy (50 micrograms/day), the TSH response to metoclopramide was completely blunted in subclinical hypothyroidism. In these patients a significant (p less than 0.01) inhibition of TSH response to intravenous thyrotropin-releasing hormone (TRH) was also observed after treatment with thyroid hormone. In analogy to the TSH behavior, plasma PRL secretion in response to metoclopramide and TRH administration was significantly (p less than 0.05) inhibited in the subclinical hypothyroid patients after l-thyroxine replacement therapy.     

Prolactin level in thyroid diseases and its reaction to thyroliberin

Prolactin content was determined before and after thyroliberin (TRH) injection in 15 healthy subjects and 136 patients. Basal levels of prolactin were increased in initial hypothyrosis, decreased in nodular euthyroid goitre, thyroid cancer and close to normal in thyrotoxicosis. TRH assay is more informative than the study of prolactin basal level. Prolactin hypophyseal content is decreased in diffuse toxic goitre, nodular euthyroid goitre, particularly, in cancer, being within normal in toxic adenoma and sharply increased in initial hypothyrosis. Hypothyrosis treatment produces a decrease in prolactin basal and stimulated levels down to normal. The treatment of diffuse toxic goitre leads to a slight rise only in the stimulated level of prolactin. Indices of TRH assays remained unchanged after surgical treatment of toxic adenoma.