Pituitary reactivity, androgens and catecholamines in obstructive sleep apnoea. Effects of continuous positive airway pressure treatment (CPAP).

We studied the effects of chronic nocturnal hypoxaemia due to obstructive sleep apnoea syndrome (OSAS) on the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-testicular axes and on catecholamine and cortisol secretion. We investigated whether hormones other than catecholamines may serve as markers for chronic hypoxic stress and the possible effects of nasal continuous positive airway pressure (nCPAP) treatment on endocrine status. Nocturnal oximetry was performed in 16 male patients with OSAS diagnosed by polysomnography, immediately before nCPAP treatment and in 11 of the patients the oximetry was repeated after 7 months of nCPAP therapy. Plasma and urinary catecholamines, luteinizing hormone (LH) testosterone, cortisol, thyroid stimulating hormone (TSH), prolactin (PRL), and the response of TSH and PRL to a thyroid releasing hormone (TRH) challenge test were measured immediately before and after 7 months of nCPAP treatment. Subnormal LH and TSH and elevated serum cortisol as well as increased nocturnal urinary norepinephrine levels were found in patients prior to treatment; otherwise endocrine values were normal. There was a significant correlation between low pretreatment nocturnal arterial oxygen saturation and high plasma and urinary norepinephrine levels. The nCPAP treatment caused significant reduction in serum prolactin and TSH, and significant reduction in plasma epinephrine and urinary norepinephrine. The reduction in serum TSH and urinary norepinephrine was most pronounced in the subjects with the worst pretreatment nocturnal hypoxaemia. No other significant changes were found in basal hormone levels. The response to TRH challenge was normal before and after treatment and was not influenced by CPAP therapy. OSAS is associated with elevated catecholamine and cortisol and decreased TSH and LH levels but a normal response to TRH challenge and a normal androgen status. Apart from catecholamines, none of the hormones studied is likely to serve as a specific marker for chronic hypoxic stress.     

THE EFFECT OF LISURIDE HYDROGEN MALEATE, AN ERGOT DERIVATIVE ON ANTERIOR PITUITARY HORMONE SECRETION IN MAN

The effects of single oral doses of 0.2 mg of lisuride hydrogen maleate, a semisynthetic ergot derivative, on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol and blood glucose were studied in six normal males. Lisuride effectively inhibited basal PRL secretion as well as the PRL response to TRH given 3 h later. In addition, the drug raised basal GH levels and decreased basal and TRH stimulated TSH secretion. No significant differences between lisuride and control were observed in basal LH and FSH, LHRH stimulated gonadotrophins or in cortisol. Drowsiness was noted by all subjects, one became nauseated and another vomited, 60 and 90 min respectively after administration of lisuride. No changes were seen in pulse rate and blood pressure. The endocrine effects of lisuride were attenuated by the prior administration of the dopamine antagonist metoclopramide. These results suggest that lisuride acts as a long-acting dopamine agonist and that therefore this drug could be of therapeutic use in hyperprolactinaemic states and acromegaly.     

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.     

Abnormal Growth Hormone Responsiveness to Stimuli in Women with Active Celiac Sprue

Baseline somatomedin C (Sm-C) and responses of growth hormone (GH), prolactin (PRL), and thyrotropin (TSH) to TSH-releasing hormone (TRH) and to L-dopa were evaluated in 10 untreated and nine treated women with celiac sprue, and in 10 normal women. Mean basal Sm-C, GH, PRL, and TSH levels were similar in all groups of subjects. In all subjects, L-dopa decreased PRL levels, without affecting TSH, and TRH increased PRL and TSH levels. In both controls and treated patients, TRH did not influence GH secretion, whereas L-dopa significantly increased GH levels. In untreated patients, GH levels paradoxically increased after TRH (8/10) but were unaffected by L-dopa (7/10). Because L-dopa would stimulate hypothalamic GH-releasing hormone (GHRH) secretion, four untreated patients, unresponsive to L-dopa, received GHRH, and GH levels rose markedly. These data suggest that, in untreated celiac sprue patients, hypothalamic control of GH secretion is reversibly impaired.     

Hypothalamic regulation of pulsatile thyrotopin secretion.

To determine the mechanism underlying pulsatile TSH secretion, 24-h serum TSH levels were measured in three groups of five healthy volunteers by sampling blood every 10 min. The influence of an 8-h infusion of dopamine (200 mg), somatostatin (500 micrograms), or nifedipine (5 mg) on the pulsatile release of TSH was tested using a cross-over design. The amount of TSH released per pulse was significantly lowered by these drugs, resulting in significantly decreased mean basal TSH serum levels. However, pulses of TSH were still detectable at all times. The TSH response to TRH (200 micrograms) tested in separate experiments was significantly lowered after 3 h of nifedipine infusion compared to the saline control value. Nifedipine treatment did not alter basal, pulsatile, or TRH-stimulated PRL secretion. The persistence of TSH pulses under dopamine and somatostatin treatment and the blunted TSH responses to nifedipine infusion support the hypothesis that pulsatile TSH secretion is under the control of hypothalamic TRH. The 24-h TSH secretion pattern achieved under stimulation with exogenous TRH in two patients with hypothalamic destruction through surgical removal of a craniopharyngioma provided further circumstantial evidence for this assumption. No TSH pulses and low basal TSH secretion were observed under basal conditions (1700-2400 h), whereas subsequent repetitive TRH challenge (25 micrograms/2 h to 50 micrograms/1 h) led to a pulsatile release of TSH with fusion of TSH pulses, resulting in a TSH secretion pattern strikingly similar to the circadian variation. These data suggest that pulsatile and circadian TSH secretions are predominantly controlled by TRH.     

EFFECTS OF ORAL AND INTRAVENOUS TRH AND METOCLOPRAMIDE ON PRL AND TSH SECRETION IN WOMEN

Pituitary secretion of PRL and TSH is under the control of inhibitory dopaminergic and stimulatory TRH-mediated mechanisms. To evaluate the relationships between these regulatory systems, ten healthy women were treated with oral TRH (20 mg twice daily), a dopamine blocking drug, metoclopramide (MC) (10 mg t.d.s.) or placebo for 1 week (from 8th to 14th cycle day). Serum concentrations of PRL, TSH, T3 and T4 were determined before, at the end, and 3 days after the treatments. In addition, PRL and TSH responses to i.v. TRH (200 μg) or MC (10 mg) were studied at the end of the oral treatments. Oral TRH treatment was accompanied by increases in basal T3 and T4 concentrations, no change in PRL, and a decrease in TSH 3 days after the end of treatment. Oral TRH did not modify the PRL response to i.v. MC while it eliminated the TSH response to i.v. MC, possibly because of elevated concentrations of thyroid hormones. Oral MC treatment raised the concentrations of PRL, T3 and T4, and also potentiated the PRL response to i.v. TRH, whereas the TSH response remained unaltered. These results demonstrate that dopaminergic and TRH-mediated mechanisms are related in the control of PRL and TSH secretions, perhaps directly or through thyroid hormones.     

Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion

To determine how arginine (Arg) stimulates GH secretion, we investigated its interaction with GHRH in vivo and in vitro. Six normal men were studied on four occasions: 1) Arg-TRH, 30 g arginine were administered in 500 mL saline in 30 min, followed by an injection of 200 micrograms TRH; 2) GHRH-Arg-TRH, 100 micrograms GHRH-(1-44) were given iv as a bolus immediately before the Arg infusion, followed by 200 micrograms TRH, iv; 3) GHRH test, 100 micrograms GHRH were given as an iv bolus; and 4) TRH test, 200 micrograms TRH were given iv as a bolus dose. Blood samples were collected at 15-min intervals for 30 min before and 120 min after the start of each infusion. Anterior pituitary cells from rats were coincubated with Arg (3, 6, 15, 30, and 60 mg/mL) and GHRH (0.05, 1, 5, and 10 nmol/L) for a period of 3 h. Rat GH was measured in the medium. After Arg-TRH the mean serum GH concentration increased significantly from 0.6 to 23.3 +/- 7.3 (+/- SE) micrograms/L at 60 min. TRH increased serum TSH and PRL significantly (maximum TSH, 11.1 +/- 1.8 mU/L; maximum PRL, 74.6 +/- 8.4 micrograms/L). After GHRH-Arg-TRH, the maximal serum GH level was significantly higher (72.7 +/- 13.4 micrograms/L) than that after Arg-TRH alone, whereas serum TSH and PRL increased to comparable levels (TSH, 10.2 +/- 3.0 mU/L; PRL, 64.4 +/- 13.6 micrograms/L). GHRH alone increased serum GH to 44.9 +/- 9.8 micrograms/L, significantly less than when GHRH, Arg, and TRH were given. TRH alone increased serum TSH to 6.6 +/- 0.6 mU/L, significantly less than the TSH response to Arg-TRH. The PRL increase after TRH only also was lower (47.2 +/- 6.8 micrograms/L) than the PRL response after Arg-TRH. In vitro Arg had no effect on basal and GHRH-stimulated GH secretion. Our results indicate that Arg administered with GHRH led to higher serum GH levels than did a maximally stimulatory dose of GHRH or Arg alone. The serum TSH response to Arg-TRH also was greater than that to TRH alone. We conclude that the stimulatory effects of Arg are mediated by suppression of endogenous somatostatin secretion.     

Effect of long-term androgen treatment on the function of hypothalamo-hypophysial and -adrenal axes in transsexual agonadal women

The study was aimed at assessing the influence of prolonged (18-24 months) androgen treatment of 11 agonadal transsexual women on basal concentrations of LH, FSH, testosterone (T), estradiol (E2), progesterone (P) and SHBG, on the hypothalamic-hypophysial (GH, PRL, ACTH) and hypothalamic-adrenal (cortisol) response in insulin test and TSH and PRL response after TRH administration. Fifteen healthy women in follicular phase of menstrual cycle and 15 men served as controls. In TS women basal concentrations of E2 were comparable with those in healthy women in follicular phase and the lowered T value showed negative correlation with SHBG. In most TS women the stimulated secretion of GH, PRL, ACTH and cortisol in insulin test was diminished. Basal values of these hormones oscillated within normal range except ACTH levels which were higher as compared with control values. In most cases the PRL response to TRH was diminished, but in three patients excessive secretion of PRL was found. Long-term priming with androgen was found to produce a dramatic change in the patterns of hormonal response to post-insulin hypoglycaemia and TRH in female-to-male transsexuals. It was concluded that in prolonged treatment of agonadal transsexual women the doses of testosterone preparations should be adjusted to individual patients in order to monitor steroid and gonadotropin hormone values, as well as the response of pituitary hormones, particularly that of PRL, to stimuli.     

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.     

Effects of thyrotropin-releasing hormone in vitro on thyrotropin and prolactin release from the turtle pituitary

Effects of synthetic thyrotropin-releasing hormone (TRH) on thyrotropin (TSH) and prolactin (PRL) release by hemipituitaries of adult turtles, Chrysemys picta, were studied in an in vitro superfusion system. Significant increases in the rates of secretion of both immuno-reactive TSH and PRL occurred at doses between 0.01 and 10 ng/ml TRH. TSH secretion increased acutely by two-, to sixfold over nonstimulated secretion levels; responses tended to decline after many hours of continual stimulation, but output remained elevated above baseline in most cases. PRL secretion increased, parallel to TSH secretion during TRH stimulation. No significant difference was found in secretion rates between males and females, and no clear relationship between TRH responsiveness and reproductive stage was evident. These data provide the first direct evidence for the stimulation of TSH secretion by TRH in a reptile and confirm earlier reports that TRH stimulates the release of PRL in the turtle. Although previous in vivo studies indicated that TSH secretion was not affected by TRH in turtles, the present data indicate that the dose sensitivity of the chelonian gland is comparable with that of mammalian and avian pituitaries. Evidence for the role of TRH in endogenous TSH regulation is still lacking in reptiles but the present data provide evidence for functional TRH receptors on the chelonian thyrotrope and, hence, argue against the hypothesis that TSH stimulating activity of TRH evolved relatively recently in association with endothermy.     

The dissociation of the exaggerated prolactin and thyrotropin responses in seminiferous tubule failure following the administration of a double-pulse of thyrotropin-releasing hormone

PRL and TSH secretion has been evaluated in 11 patients with seminiferous tubule failure and 9 controls. When compared to the controls, the patients had increased basal FSH, TSH and PRL levels. However, LH, E2, T and thyroid hormone levels were similar to the controls. Both groups were given two pulses of TRH (200 micrograms) at 30 min intervals. Following the initial pulse of TRH, the patients demonstrated exaggerated TSH and PRL responses. The administration of a second pulse of TRH led to a further increment of TSH secretion in the patients. There was, however, no PRL response to the second TRH pulse in either patients or controls although mean PRL levels remained significantly greater in the patients.     

Prolactin response to growth hormone-releasing hormone during chronic thyrotropin-releasing hormone infusion in the treatment of amyotrophic lateral sclerosis

In six patients suffering from amyotrophic lateral sclerosis we evaluated changes of T4, T3, TSH, PRL, and GH during treatment by continuous iv infusion of TRH for at least 15 days. No clinical improvement was detected. A significant rise of thyroid hormone levels was observed, as well as an upward trend of basal TSH levels and no change of basal PRL and GH levels. TRH acute test-induced TSH and PRL responses became blunted. Treatment provoked also the onset of a responsiveness of PRL to GHRH. The reduced TSH and PRL responses to acute TRH test during treatment could be explained by a down-regulation of TRH pituitary receptors. On the contrary, the onset of PRL responsiveness to GHRH is at present without a satisfactory explanation.     

Primary hypothyroidism and galactorrhea.

Ten of 16 women with primary hypothyroidism and high thyrotropin (TSH) concentrations had high serum prolactin (PRL) concentrations. A positive correlation was observed between the basal TSH and PRL levels in the hypothyroid patients. Five of these patients complained of persistent galactorrhea after delivery. After treatment with triiodothyronine (T3), the elevated TSH and PRL levels fell to within normal ranges, and the galactorrhea disappeared. It is suggested that the elevated serum PRL levels of patients with primary hypothyroidism are mediated by feedback-induced thyrotropin-releasing hormone (TRH) secretion or an enhanced response to endogenous TRH, and that the combination of delivery and the PRL excess may induce persistent galactorrhea in patients with primary hypothyroidism.     

Growth hormone response to thyrotropin-releasing hormone in diabetes

The effect of TRH on GH secretion was assessed in 13 insulin-dependent diabetics. PRL and TSH responses to TRH were also determined. Glycosylated hemoglobin levels and serial fasting glucose concentrations indicated that all but 1 of the patients had a period of poor diabetic control for several months before the study. Peak PRL and TSH levels after TRH injection in these diabetic patients did not differ significantly from values observed in nondiabetic individuals. Six of the patients responded to TRH with a significant rise in GH levels; basal GH concentrations were also elevated in these patients. Five of the 6 responders and none of the nonresponders had proliferative diabetic retinopathy. The results suggest that diabetics with elevated basal GH levels hyperrespond to TRH, and that nonspecific secretion of GH in response to TRH occurs in some patients with proliferative diabetic retinopathy. Chronic hyperglycemia does not appear to be the critical factor in determining this response.     

Evidence for a thyrotropin inhibitory effect of histamine in man.

Because of certain side effects of cimetidine therapy which may be hormonally mediated (e.g. gynecomastia), there has been recent interest in the possible endocrine effects of this H2 histamine receptor-blocking agent used in the treatment of peptic ulcer disease. Accordingly, the effect of chronic cimetidine therapy on anterior pituitary function was examined in 12 adult men with mild peptic ulcer disease. TRH and insulin-hypolycemic stimulation tests were performed by standard methods. Serum for TSH and PRL RIA was obtained after TRH; serum for GH, cortisol, and PRL RIA was obtained after insulin-induced hypoglycemia. In addition, serum for LH, FSH, testosterone, and PRL was obtained every 4 h for 24 h. After these baseline studies, 300 mg cimetidine were administered orally 4 times a day for 4--8 weeks and the studies were repeated as before. Chronic treatment with cimetidine caused a significant increase in the peak TSH response to TRH at 30 min (mean peak TSH value before cimetidine, 7.0 microU/ml; after cimetidine, 10.2 microU/ml; P less than 0.05) as well as a significant increase in the TSH area under the curve. There was no statistically significant effect of cimetidine on basal TSH or basal or stimulated PRL secretion. Cimetidine had no effect on the GH, PRL, or cortisol response to insulin-induced hypolycemia or the 24-h secretion of LH, FSH, testosterone, or PRL.     

THYROTROPHIN, PROLACTIN AND GROWTH HORMONE RESPONSES TO TRH IN BARBITURATE COMA AND IN DEPRESSION

The effects of 200 microgram thyrotrophin-releasing hormone (TRH) i.v. on thyrotrophin (TSH), prolactin (PRL), growth hormone (GH) and triiodothyronine (T3) were studied in eight patients with barbiturate coma due to attempted suicide, in the same patients after recovery, in eight depressive patients and in eight normal controls. The patients with barbiturate coma presented normal basal TSH and PRL, elevated basal GH and normal PRL but blunted TSH responses to TRH; their GH concentrations varied widely without consistent relation to TRH administration. The same patients after recovery from coma presented normal TSH and PRL, slightly elevated basal GH, and normal PRL but blunted TSH responses to TRH; in four of these patients, a clear-cut rise in GH (i.e. more than 10 ng/ml) occurred after TRH administration. The depressive patients presented normal basal TSH and PRL, slightly elevated basal GH, and normal PRL but blunted TSH responses to TRH; in four of these patients, a moderated rise in GH (less than 10 ng/ml) occurred after TRH administration. The increment in T3 concentrations 120 min after TRH was found reduced in the comatose patients only. Basal cortisol was measured in all the subjects and found elevated in the comatose patients only. It is concluded that the abnormal TSH and GH responses to TRH observed in patients with barbiturate coma are more likely related to depressive illness than to an effect of barbiturates at the pituitary level. Barbiturates might affect thyroid secretion.     

Different prolactin, thyrotropin, and thyroxine responses after prolonged intermittent or continuous infusions of thyrotropin-releasing hormone in rhesus monkeys

Serum PRL, TSH, and T4 secretion during prolonged continuous or intermittent iv infusions of TRH were studied in 14 adult ovariectomized rhesus monkeys (Macaca mulatta). For 9 days, TRH was administered intermittently at 0.33 or 3.3 micrograms/min for 6 of every 60 min and continuously at 0.33 micrograms/min. With both modes, the PRL levels and responsiveness to TRH simulation peaked on day 1 and then fell to levels that were still higher than the preinfusion values; levels for the intermittently treated group on days 3-9 were 2- to 4-fold above prestimulation levels and significantly (P less than 0.01) higher than levels for the continuously treated group. Elevated basal levels and PRL responses to TRH pulses were similar during the 0.33 and 3.3 micrograms/min pulses of the 9-day treatment period. For both TRH modes, TSH levels were elevated significantly (P less than 0.001) on day 1 [this increase was higher with continuous infusion (P less than 0.001)] and then fell to preinfusion levels by day 3. Serum T4 also increased during both continuous and intermittent TRH stimulations. However, serum T4 levels were significantly lower (P less than 0.01) after intermittent TRH (both 0.33 and 3.3 micrograms/min) than after continuous (0.33 micrograms) TRH (8 +/- 1.1 and 10 +/- 1.8 micrograms T4/dl vs. 18 +/- 3.1 micrograms, respectively). These PRL and T4 responses were replicated when the mode of administering 0.33 micrograms/min TRH was reversed after 9 days. An iv bolus of TRH (20 micrograms) after 9 days of continuous or intermittent TRH infusion caused significant release of PRL and TSH, an indication that neither mode of administration resulted in pituitary depletion of releasable hormone. We have concluded that intermittent TRH is more effective in elevating serum PRL, and continuous TRH is more effective in raising TSH and T4 levels. Thus, the manner of TRH secretion by the hypothalamus may determine its relative physiological importance in the stimulation of lactotropes and thyrotropes.     

Modulation of pituitary thyrotropin releasing hormone receptor levels by estrogens and thyroid hormones.

The effect of estradiol and thyroid hormone treatment on pituitary TRH binding and TSH and PRL responses to the neurohormone was studied. A significant increase in the number of pituitary TRH binding sites was observed between 2 and 4 days after daily administration of estradiol benzoate with a plateau at 300% of control being reached at 7 days. Plasma PRL levels showed a similar early pattern of response. In animals rendered hypothyroid by a 2-month treatment with propylthiouracil or 1 month after surgical thyroidectomy, the level of pituitary TRH receptors was increased approximately 2-fold, this elevation being completely reversed by treatment with thyroid hormone. Estradiol-17beta administered with L-thyroxine partially reversed the inhibitory effect of thyroid hormone on TRH receptor levels in hypothyroid animals. The antagonism between estrogens and thyroid hormone is also apparent on the TSH response to TRH since estrogen administration can reverse the marked inhibition by thyroxine of the TSH response to TRH either partially or completely in intact and hypothyroid animals, respectively. The PRL response to TRH is 55 and 40% inhibited in hypothyroid and intact rats, respectively, by thyroid hormone when combined with estrogen treatment. The present data clearly show that estrogens and thyroid hormones can affect TSH and PRL secretion, the effect of estrogens being predominantly on PRL secretion while thyroid hormone affects mainly TSH. The close correlation observed between the level of TRH receptors and PRL and TSH responses to TRH suggests that estrogens and, to a lesser extent, thyroid hormones, exert their action by modulation of the level of receptors for the neurohormone in both thyrotrophs and mammotrophs.     

EFFECT OF SUBACUTE CABERGOLINE TREATMENT ON PROLACTIN, THYROID STIMULATING HORMONE AND GROWTH HORMONE RESPONSE TO SIMULTANEOUS ADMINISTRATION OF THYROTROPHIN-RELEASING HORMONE AND GROWTH HORMONE-RELEASING HORMONE IN HYPERPROLACTINAEMIC WOMEN

It is known that dopaminergic neurotransmission is involved in the control of PRL, TSH and GH secretion. Cabergoline (CAB) is a new ergolinic derivative with a long-acting dopaminergic activity. We evaluated 11 women with pathological hyperprolactinaemia before and during sub-acute CAB treatment (0.8-1.2 mg/p.o.; 8 weeks). Simultaneous administration of TRH (200 micrograms i.v.) and GHRH 1-44 (50 micrograms i.v.) were carried out before and after 4, 8 and 10 week intervals from the beginning of CAB treatment. Basal PRL levels (2453.5 +/- S.E. 444.5 mU/l) were significantly reduced during CAB administration (week 4: 164.5 +/- 66.5 mU/l; week 8: 168.0 +/- 66.5 mU/l; P less than 0.01) and no variations were observed 2 weeks after drug discontinuation (week 10: 210.0 +/- 98.0 mU/l). PRL percentage change after TRH was increased by CAB (P less than 0.05). No variation in basal and TRH-stimulated TSH levels was found during CAB administration. A slight increase in GH basal levels (3.0 +/- 0.6 mU/l) was found after weeks 4 (6.4 +/- 2.0 mU/l) and 10 (5.8 +/- 1.6 mU/l) (P less than 0.05). GH response to GHRH was significantly enhanced (ANOVA: P less than 0.01) during sub-acute CAB treatment. A positive correlation was found between GH secretory area and weeks of CAB therapy (P less than 0.01). Our data show that CAB is very effective in lowering PRL secretion in hyperprolactinaemia, and is able to modify PRL and GH responses after TRH and GHRH. The increasing trend in GH basal and GHRH-stimulated GH levels seems to indicate that CAB can override the central dopaminergic tone which is operative in hyperprolactinaemia.     

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.