PRL Normalization Research Articles

Chronic Treatment With Parlodel LAR® of Patients With Prolactin-Secreting Tumours

UNLABELLED Forty-one patients with prolactinoma (25 micro-, 16 macroprolactinomas) were treated with a long-acting injectable preparation of bromocriptine (Parlodel LAR, Sandoz), 25-100 mg (mostly 50 mg) in every 4-8 weeks for as long as 43 months (median 19 months). The first injection caused a prompt fall of plasma PRL which reached its nadir value after 3 days. Thereafter, hormone levels remained well below initial values for 4 weeks or longer, though with the tendency, more pronounced in microprolactinoma patients, to rise again toward baseline. The prevalence of PRL normalization was greater in the macro- than in the microprolactinoma group. By repeated injections plasma PRL could be kept close to or within the normal limits in most of the patients. However, the extent of PRL inhibition was significantly greater in macro- than in microprolactinoma patients (p less than 0.01). Clinical improvement occurred in the majority of the patients, shrinkage of the tumour in 50% of them. Adverse reactions were generally mild or of moderate severity and subsided spontaneously in 24 h. They were less frequent (NS) and less severe (p less than 0.05) in macro- than in microprolactinoma patients. IN CONCLUSION a. injectable bromocriptine (Parlodel LAR) is a highly effective preparation particularly suitable for the long-term treatment of tumourous hyperprolactinemia; b. patients with macroprolactinoma exhibit, compared with microprolactinoma patients, better responsiveness and better tolerability to injectable bromocriptine.

Clinical management of prolactinomas: a ten-year experience.

A ten-year experience on 36 patients bearing macroprolactinomas (MP) and 86 others bearing microprolactinomas (mP) is reported in this study. Different therapeutical approaches were used: 1) trans-sphenoidal surgery in 24 patients with MP and in 25 with mP; 2) medical therapy with the oral form of bromocriptine (BRC) in all the 24 patients with MP previously subjected to surgery, in 48 patients with mP ab initio, and in 16 out of 25 patients with mP previously subjected to surgery; 3) medical therapy with the long-acting injectable forms of BRC in 12 MP- and 13 mP-bearing patients, and 4) conventional radiotherapy in 12 of the 24 patients with MP previously subjected to surgery. The follow-up, performed five years after surgery, showed that: a) all the 24 patients with MP but one had normal PRL levels during BRC administration, with a rebound of hyperprolactinemia in all cases after withdrawal; b) during the treatment BRC caused normalization of PRL in 15 of the 16 mP-bearing patients surgically treated and in all the 48 mP-bearing patients only treated with BRC; c) in 20 of the 25 patients the treatment with injectable retard BRC caused the normalization of plasma PRL and the shrinkage of the tumor mass in all the patients with MP but one, as revealed by seriate CT scans. In conclusion, the surgical treatment of prolactinomas was ineffective to normalize plasma PRL levels in most patients whereas BRC, in standard or in retard forms, was able to normalize plasma PRL levels, reduce the tumoral mass and preserve the pituitary residual tissue. BRC should be, therefore, used as first choice therapy both for MP and mP.

Modifications of thymulin titers in patients affected with prolonged low or high zinc circulating levels are independent of patients' age

Thymulin (FTS) is a thymic hormone, the bioactivity of which depends on zinc (Zn) incorporation in its molecule (FTS bioactive form: Zn-FTS). Many hormones (T3, GH, PRL, Gn-RH 6-endorphin) and Zn are able to increase thymus trophism and Zn-FTS circulating levels, even in old animals, suggesting that age dependent thymic involution is a reversible phenomenon. FTS circulating levels and thymus trophism are age-dependent. In fact, the decrease of Zn-FTS starts from the age of 10-20 years and proceeds progressively. In 19 uremic patients on hemodialysis (mean age +/- SD: 44.7+/-11.7, range 29-60 years) and 58 patients with prolactinoma (mean age 31+/-7; range 18-58) we found low Zn-FTS levels (expressed as scalar dilution in form of 1/log(2)): 1.5+/-0.5 and 2.1+/-0.7, respectively, vs normal age and sex matched controls: 2.9+/-0.4 and 3.6+/-0.3, respectively; p<0.01. On the contrary, in 41 acromegalic patients (mean age 43+/-12; range 20-63 years) Zn-FTS levels were elevated (4.5+/-0.7 vs controls: 2.8+/-0.3, p<0.01). In all these patients, age-related differences of Zn-FTS circulating levels were lost and Zn-FTS titers were homogeneously low or high according to Zn levels. In fact, in uremic patients and in patients with prolactinoma, Zn levels were low (79+/-26 microg/dl and 82+/-23 microg/dl, respectively, vs control levels: 114+/-12 microg/dl, p<0.01), while They were high in acromegalic patients (141+/-44 microg/dl vs control levels: 112+/-11 microg/dl, p<0.01). After ZnSO(4) administration (400 mg per os/day) for six months. Zn levels increased over the normal range, both in patients with uremia and in patients with prolactinoma (136+/-15 microg/dl and 138+/-18 microg/dl, respectively; p<0.01). Also Zn-FTS levels increased homogeneously independently of age (5.2+/-0.7 and 5.3+/-0.8, respectively); p<0.01, both vs basal and control values; PRL circulating levels did not change. In 20 patients affected with prolactinoma and in 10 acromegalic patients, Zn and Zn-FTS decreased to the normal range, 6, or 12 months after surgical or pharmacological normalization of high PRL and GH circulating levels. In these patients, age-related titers of Zn-FTS were found, such as in controls. (i) Reduced Zn-FTS levels in patients affected with uremia or prolactinoma and the increased Zn-FTS titers present in acromegalic patients are related to low and high Zn circulating levels, respectively, underlining the importance of Zn in regulating thymulin secretion. (ii) When spontaneous (or induced) hyper- or hypo-zincemia occurs, age-related differences of Zn-FTS titers are lost, suggesting that Zn may overcome the effect of age on thymic function.

Chronic treatment with Parlodel LAR® of patients with prolactin-secreting tumours. Different responsiveness of micro- and macroprolactinomas

Forty-one patients with prolactinoma (25 micro-, 16 macroprolactinomas) were treated with a long-acting injectable preparation of bromocriptine (Parlodel LAR, Sandoz), 25-100 mg (mostly 50 mg) in every 4-8 weeks for as long as 43 months (median 19 months). The first injection caused a prompt fall of plasma PRL which reached its nadir value after 3 days. Thereafter, hormone levels remained well below initial values for 4 weeks or longer, though with the tendency, more pronounced in microprolactinoma patients, to rise again toward baseline. The prevalence of PRL normalization was greater in the macro- than in the microprolactinoma group. By repeated injections plasma PRL could be kept close to or within the normal limits in most of the patients. However, the extent of PRL inhibition was significantly greater in macro- than in microprolactinoma patients (p less than 0.01). Clinical improvement occurred in the majority of the patients, shrinkage of the tumour in 50% of them. Adverse reactions were generally mild or of moderate severity and subsided spontaneously in 24 h. They were less frequent (NS) and less severe (p less than 0.05) in macro- than in microprolactinoma patients. a. injectable bromocriptine (Parlodel LAR) is a highly effective preparation particularly suitable for the long-term treatment of tumourous hyperprolactinemia; b. patients with macroprolactinoma exhibit, compared with microprolactinoma patients, better responsiveness and better tolerability to injectable bromocriptine.

CV 205-502—effectiveness, tolerability, and safety over 24-month study

Twenty hyperprolactinemic women (median prolactin [PRL] 2,989 mU/L, range 1,149 to 11,910 mU/L), previously unsuccessfully treated with bromocriptine, were treated in a prospective study, for 3 to 24 months with the new, nonergot, long-acting, dopamine agonist, CV 205-502. Treatment resulted in normalization of PRL in 14 patients, in one daily dose of 0.075 to 0.150 mg of the drug. Three patients were treated in doses above 0.150 mg up to 0.300 mg, but PRL was not normalized during the study. Menstrual function was restored in 15 of 18 amenorrheic patients. Galactorrhea, present in 7 patients, disappeared in 5. Four patients became pregnant and gave birth to healthy children. In conclusion, we found CV 205-502 effective in one daily dose, with good tolerability; it is safe and provides a valuable alternative to the dopamine agonist drugs in use today.

Effects of a new long-acting form of bromocriptine on tumorous hyperprolactinemia.

Recently, a new long-acting form of bromocriptine (Parlodel LA, Sandoz) has been developed and it has already been found to be effective in lowering plasma PRL levels in normal volunteers and postpartum women. This work reports the clinical, hormonal and radiological effects of a single 50 mg dose of long-acting bromocriptine in 10 patients with tumorous hyperprolactinemia (2 microprolactinomas, 6 macroprolactinomas, 1 acromegaly and 1 nonsecreting macroadenoma). A rapid and long-lasting (28 days) normalization of PRL levels was observed in patients with microprolactinoma, acromegaly and nonsecreting adenoma. None of the 6 patients with macroprolactinoma underwent normalization of plasma PRL, but the latter was markedly reduced (61-80% of basal levels). A second injection of the drug in 5 macroprolactinoma patients induced a further reduction of plasma PRL levels in 2 of them. No changes in the tumor size were observed either after the first or the second injection of long-acting bromocriptine in any of the patients. This injectable form of bromocriptine induced nausea and/or mild hypotension lasting a few h in 4 of the 10 patients and was better tolerated than the oral form as regards both the duration and intensity of the side effects. Thus, as this drug has proved to be efficacious and well tolerated by the patients, this long-acting form of bromocriptine may be a valid therapeutical approach for initiating medical treatment of patients with prolactinoma.

Serum gonadotrophin pulsatile secretion in men with Prl-secreting and non-secreting pituitary tumours.

In order to investigate the possible influence of prolactin (Prl) at the hypothalamic level, serum LH and FSH pulsatility was studied in 16 male patients with prolactinomas, normally LH responders to GnRH (group A): 8 of them were untreated (group A1) and 8 had undergone previous unsuccessful pituitary treatments (group A2). In 7 patients the study was repeated when serum Prl was normalized by bromocriptine treatment (group B). For comparison the secretory pattern of LH and FSH was studied in 6 male patients with non-secreting pituitary tumours (group C). All parameters of LH pulsatile secretion (i.e. arithmetic mean of the single concentration, coefficient of variation from the mean value, frequency of peaks, amplitude of pulses expressed as either absolute or per cent value) were significantly lower in patients of groups A1, A2 and C than in normal subjects and no difference was found between the three groups. Furthermore the 7 patients with prolactinomas studied both before and after bromocriptine-induced Prl normalization showed no difference in all the parameters of LH pulsatility in both conditions. No significant abnormalities of FSH secretory pattern were found in the patients of groups A1, A2, B and C in comparison to normal subjects. In all groups of patients mean serum testosterone basal levels were significantly lower than in normals, while the mean oestradiol-17 beta basal concentration was normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Somatomedin A increments are diminished in acromegaly with concomitant hyperprolactinaemia.

The influence of prolactin (Prl) on growth hormone (GH) regulated somatomedin A (SMA) levels was studied in 30 patients with acromegaly before and after transsphenoidal pituitary surgery. Pre-operative GH levels were elevated in all patients and SMA levels in all but one patient. Eleven patients (33%) showed hyperprolactinaemia. There was no correlation between GH and SMA levels. Plasma GH did not differ in patients with GH and Prl producing adenomas compared to those with isolated GH hypersecretion. SMA levels, however, were significantly lower in patients with hyperprolactinaemia than in those with normal serum prolactin (P less than 0.001). After surgery GH decreased in all and SMA levels in all but one patient. Despite similar post-operative GH levels SMA decreased to significantly lower levels in patients with combined hypersecretion of GH and Prl compared to patients with normal prolactin levels (P less than 0.05). Nine of the 11 patients with hyperprolactinaemia showed normal Prl after surgery. The SMA levels in patients with acromegaly seem to be suppressed in patients with pre-operatively concomitant hyperprolactinaemia before as well as after adenomectomy regardless of the normalization of Prl. Our findings offer one explanation of the lack of correlation between SMA and GH levels in acromegaly.

Treatment of hyperprolactinaemic patients with pergolide.

Eighteen hyperprolactinaemic patients were orally treated for up to 16 months with pergolide mesylate, a new potent long-lasting dopaminergic ergot derivative. In all cases, Prl normalization (less than 25 ng/ml) was achieved at a once-a-day dose of 50-300 micrograms. All women recovered and/or exhibited normal menstrual function. Among the 6 women wishing to become pregnant, 4 of them conceived within 4 months; there were other causes for infertility than hyperprolactinaemia in the 2 other couples. A macroprolactinoma man experienced important improvement in well-being as well as objective regression of his visual fields defect. This suggests a shrinkage effect of pergolide on the tumoural process. Another man regained normal potency and normal testosterone within 2 weeks. While 10 patients were completely free of any side effect, 7 experienced transiently mild gastro-intestinal side effects or postural hypotension. Only one patient discontinued her treatment because of dizziness. The present study demonstrates the high potency, the good tolerance and the excellent efficacy of pergolide in the treatment of hyperprolactinaemia.

Hypothalamic-pituitary-ovarian function in hyperprolactinemic women.

Hypothalamic-pituitary-ovarian function, as well as other pituitary tropic hormone secretions, was examined in 27 hyperprolactinemic patients (17 with PRL-secreting tumor and 10 with so called functional hyperprolactinemia). Serum PRL levels ranged between 39 and 108 ng/ml in functional cases and between 34 and 2500 ng/ml in patients with pituitary adenoma. Basal serum LH, FSH and 17 β-estradiol levels did not differ from those recorded between days −14 and −10 in normally cycling women in functional cases, and were lowered in patients with pituitary tumor. LH response to GnRH (25μg iv) was normal in 7, impaired in 1 and exaggerated in 2 functional cases, and appeared normal in 9 and impaired in 8 tumoral cases. Two exaggerated FSH responses were seen in functional patients and 4 in patients with pituitary tumor. Estradiol benzoate administration (1 mg im) caused a significant fall in serum FSH and LH within 24 hr, but failed to induce serum LH increase within 96 hr in 11 out of 12 examined patients while a definite LH peak occurred within 48–72 hr in 7 patients retested after serum PRL normalization. Clomiphene citrate (100 mg/day for 5 days) administration caused a normal rise in serum LH, FSH and 17β-estradiol in 5 functional cases and in 1 case with pituitary tumor out of 9 patients tested. Normal pulsatility of serum LH was observed in 3 examined patients. In 3 normogonadotropic patients with PRL-secreting tumor, hCG + hMG administration (5000 + 150 IU im for 3 days) did not cause any significant increase in plasma 17β-estradiol while inducing a sharp rise in the same patients retested after serum PRL normalization. No abnormal changes in TSH, GH and ACTH secretion both in the basal state and after provocative stimuli were observed in patients with functional hyperprolactinemia, whereas in patients with pituitary tumors TSH secretion was impaired in 53% of cases, GH secretion in 71% and ACTH secretion in 29%. The present data along with previous reports in the literature suggest that high serum PRL can induce anovulation and amenorrhea by acting at both hypothalamic and ovarian levels.