Effect of oral zinc administration on prolactin and thymulin circulating levels in patients with chronic renal failure.

High serum PRL and low zinc (Zn) levels are common findings in patients with chronic renal failure (CRF); in such patients serum Zn concentrations have been reported to be inversely correlated to serum PRL levels. Moreover, Zn regulates both thymus growth and the biological activity of the thymic hormone thymulin, and PRL-thymic interrelationships have been described. To determine whether hypozincemia alters serum PRL and plasma thymulin concentrations in CRF, 9 men with CRF treated by chronic hemodialysis were given 400 mg/day Zn sulfate, orally (4.96 meq/day Zn), for 6 months. Before treatment, serum PRL levels were significantly higher (P less than 0.001) in these patients than in normal men [mean, 28.7 +/- 20.7 (+/-SD) vs. 7.5 +/- 3.7 micrograms/L], and their serum PRL response to TRH (200 micrograms, iv) was impaired (mean maximal percent increase, 38.2 +/- 10.9 vs. 641 +/- 335; P less than 0.001). The plasma Zn-bound bioactive thymulin titer (1.3 +/- 0.7 1/log2), total thymulin titer (Zn-bound plus Zn-unbound forms, 2.1 +/- 0.8 1/log2), and serum Zn (13.1 +/- 2.4 mumol/L) were lower (P less than 0.001) in men with CRF than in normal men. Zn therapy did not induce any significant change in basal and TRH-stimulated serum PRL levels, while serum Zn levels significantly increased, reaching the normal range after the first week of treatment (17.8 +/- 6.3 mumol/L). Plasma total thymulin increased rapidly, reaching normal levels after 1 week, but Zn-bound thymulin increased modestly during the first month of treatment and more after 3 and 6 months of treatment. There was no age-related difference in plasma thymulin levels during therapy. We conclude that oral Zn administration in patients with CRF significantly increases both total and Zn-bound thymulin, but does not modify basal and TRH-stimulated serum PRL levels. The observation that Zn supplementation markedly increased plasma thymulin levels in uremic patients suggests that Zn is a potent stimulus for thymic hormone synthesis, and it can reverse the age-related diminution of thymic activity in CRF patients.

Increase of OKT4+ cells during treatment with thymostimulin in parenteral drug addicts with persistent generalized lymphadenopathy.

Thymostimulin (TP-1), a parenterally administered calf thymus extract, has induced a significant increase of OKT4+ peripheral cells in 9 drug addicts with persistent generalized lymphadenopathy; OKT4+ lymphocytes decreased gradually after withdrawal of treatment. In a control group, a spontaneous decrease occurred in the same period of observation. A more prolonged treatment should be undertaken to assess the effectiveness of the drug on the evolution of the disease.

Bromocriptine treatment of microprolactinomas: evidence of stable prolactin decrease after drug withdrawal.

Thirty-six women with PRL-secreting pituitary microadenomas [mean PRL, 114 +/- 12.5 (+/- SE) ng/ml] were treated with bromocriptine (BRC; 2.5-10 mg/day) for 12 months. During BRC treatment, serum PRL decreased in all patients. After termination of treatment, mean serum PRL levels, evaluated at 15, 30, and 45 days, were significantly decreased (-41.6%, -43.0%, and -40.2%, respectively) compared to pretreatment values. The patients were arbitrarily divided into 3 groups: 12 responders, in whom the PRL persistent posttreatment decrease was greater than 50%, 8 hyporesponders, in whom the PRL decrease was between 30% and 50%, and 16 nonresponders with absent or negligible PRL decrease. Four patients had normal PRL levels and clinical remission for 14-30 months after BRC withdrawal. In 18 women, BRC treatment was repeated for another 12 months. After termination of treatment, 11 patients were responders, 1 was a hyporesponder, and 6 were nonresponders. Four of these 18 patients still had normal PRL levels 8-28 months after drug discontinuation. The responses of PRL to TRH and domperidone were compared before and after termination of treatment at 30 and 45 days, respectively. Both mean peak values of PRL and absolute increases after TRH treatment were similar before and after BRC administration; however, a PRL response to TRH was present in 15% of 26 patients before treatment and in 42% after treatment. The mean peak values after domperidone were similar before and after BRC treatment, but the absolute increase over the basal value was much higher after BRC; PRL response to domperidone was present in 16% of 19 patients before BRC treatment and in 74% after BRC. These data suggest that BRC is effective in the treatment of some microprolactinomas; BRC effectiveness improves after prolonged periods of administration. The variations in PRL responses to TRH and domperidone suggest profound modification of PRL secretion after BRC treatment.

Effect of bromocriptine and metergoline in the treatment of hyperprolactinaemic states.

The effects of bromocriptine or metergoline treatment were evaluated in 80 hyperprolactinaemic patients (62 women and 18 men). The patients were subdivided into 4 groups: group A) 16 women with idiopathic hyperprolactinaemia; group B) 19 women with untreated Prl-secreting microadenomas; group C) 27 women with unsuccessfully operated prolactinomas; group D) 18 men with unsuccessfully treated macroprolactinomas. Sixty-eight patients were given bromocriptine (2.5-20 mg/day) for 3-58 months and 33 patients were given metergoline (4-16 mg/day) for 3-19 months. Bromocriptine and metergoline were equally effective in the treatment of functional hyperprolactinaemia and of untreated microadenomas, while bromocriptine showed a more potent Prl-lowering effect than metergoline in patients with higher Prl levels and large prolactinomas; both drugs restored the gonadal function to a similar extent, though metergoline was effective in some cases, even in the absence of full Prl suppression. Bromocriptine seems to exert an antitumoral effect, as documented by CT scan in some patients with macroadenomas, but the precise role of both drugs with respect to dose, length of treatment and effectiveness after withdrawal needs to be evaluated further.

Hypothalamic-pituitary-testicular function in men with PRL-secreting tumors.

We studied the hypothalamic-pituitary-gonadal system in 33 men with PRL-secreting tumors to determine at which level(s) high PRL levels interfere with testicular function. In basal conditions serum PRL levels ranged between 24-4500 ng/ml, serum LH and FSH concentrations were lower than normal in 61% and 39% of patients; low testosterone (T) levels and sexual impotence appeared more common (85% and 88%) than that we expected on the basis of gonadotropin deficiency. Mean T increase after hCG in 14 patients with prolactinomas was significantly less than in normals (3.3 +/- 0.7) ng/Ml vs 7.3 +/- 0.5 ng/ml; p less than 0.025); a significantly higher T response to hCG was obtained in 5 cases retested after PRL levels had been reduced by therapy. GnRH test induced a normal LH rise in 45% of patients, Mean serum LH increase after clomiphene administration did not differ from that in normals, though 4 out of 10 patients showed an impared response. Metoclopramide injection did not cause a rise of LH in 11 patients so tested. These data, while not excluding a central influence of PRL on LHRH, suggest that in men the antigonadotropic effects of PRL are mainly exerted at the gonadal levels.

Evaluation of two inhibitory tests (nomifensine and L-dopa + carbidopa) for the diagnosis of hyperprolactinaemic states.

It has been reported that administration of nomifensine (Nom) or of L-dopa + carbidopa (L-dopa + Carb) potentiates central dopaminergic tonus, resulting in decreased prolactin (PRL) secretion. It has been proposed that these drugs would help to discriminate patients with PRL-secreting pituitary tumours from those with so-called 'functional' hyperprolactinaemia. In this study, oral Nom (200 mg) was given to forty-three hyperprolactinaemic patients and L-dopa + Carb (50 mg Carb every 6 h for four doses followed by L-dopa 100 mg and Carb 35 mg) to thirty of them and both treatment to ten normal subjects. The hyperprolactinaemic patients were divided into four clinical groups. Group A, twenty patients with proven PRL-secreting pituitary tumours; Group B, thirteen women with elevated PRL levels (less than 100 ng/ml) without any radiological evidence of a pituitary tumour (hyperprolactinaemia of unknown aetiology or 'functional' hyperprolactinaemia); Group C, four women with polycystic ovarian disease and mildly elevated serum PRL; Group D, six patients with various other disorders associated with hyperprolactinaemia. PRL levels decreased in the normal controls below the basal values by 61.3% +/- 6.2 (SEM) after Nom and 77.6% +/- 4.2 after L-dopa + Carb. Decreases in serum PRL of at least 50% (in three consecutive determinations) were found in group A in 20% of patients after Nom and in 25% after L-dopa + Carb; in group B in 15% and 40% of cases; in most of the hyperprolactinaemic women in group C; and some in group D. In conclusion, these two treatments did not discriminate between tumorous and non-tumorous cases of PRL hypersecretion.

Effects of serotonin antagonists in sexually impotent men.

Thirty-one men affected with sexual impotence were studied. Since sexual function in the male seems to be controlled by both dopaminergic stimulatory and serotoninergic inhibitory mechanisms, the patients were treated with serotonin antagonists. In basal conditions mean serum LH, FSH, PRL and testosterone did not significantly differ from those found in normal subjects; no significant variations, except for PRL reduction, were observed after treatment. Both methysergide, in association with bromocriptine or mesterolone, and metergoline, either alone or in association with mesterolone, were ineffective in significantly improving sexual activity.