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Biomedical subjects

A Liuzzi

Publications and source records attributed to A Liuzzi.

At least 73 records · Page 4Linked to original sources

Serum type III procollagen propeptide levels in acromegalic patients.

Serum type III procollagen propeptide (PIIIP) is a reliable index of tissue collagen synthesis. Since in acromegaly there is increased collagen production, we measured serum PIIIP in acromegalic patients before any treatment (basal), during medical treatment with the somatostatin analog SMS 201-995, and after pituitary adenomectomy. In all patients, serum GH and plasma somatomedin-C (SmC) levels were also measured. Basal serum PIIIP levels were significantly (P less than 0.01) higher in acromegalic patients (mean +/- SEM, 22.7 +/- 2.1 ng/ml) than in normal subjects (n = 30; 9.7 +/- 0.5 ng/ml), and they were significantly correlated with plasma SmC values (r = 0.31; P less than 0.05). A significant (P less than 0.01) reduction in PIIIP levels occurred in patients treated with SMS 201-995 or surgery (from 24.3 +/- 2.7 to 12.4 +/- 1 ng/ml) as well as in GH and SmC levels. The maximum percent decrease in serum PIIIP was significantly correlated with those in GH (r = 0.65; P less than 0.01) and SmC (r = 0.60; P less than 0.01). Serum PIIIP levels did not change in those patients in whom neither GH nor SmC were decreased by treatment. In conclusion, serum PIIIP levels are elevated in acromegalic patients, and they decline in parallel with GH and SmC during medical or surgical treatment. Serum PIIIP measurements may be useful in the evaluation of acromegalic patients to gain information on the biological activity of GH and in monitoring the course of the disease.

Acromegaly↗

Low doses of dopamine agonists in the long-term treatment of macroprolactinomas.

To evaluate the long-term effects of dopamine agonists in the treatment of macroprolactinoma, we studied prolactin levels and tumor size for 30 to 88 months (57 +/- 14, mean +/- S.D.) in 38 patients treated with bromocriptine or lisuride. Elevated prolactin levels became normal in 30 patients, and the tumor shrank in 29. After two years of treatment, we attempted to reduce the maintenance dose (5 to 20 mg of bromocriptine per day or 0.4 to 0.8 mg of lisuride per day); in 21 patients no changes in prolactin levels or tumor size were observed over 6 to 52 months with 0.625 to 10 mg of bromocriptine per day or 0.05 mg of lisuride per day. However, it was possible to withdraw the drug in only one patient. We conclude that dopamine agonists are usually effective treatments for macroprolactinoma and that after a response has been obtained, it can be maintained in many patients with a greatly reduced dose.

Adenoma↗

Effect of chronic bromocriptine administration on tumor size in patients with "nonsecreting" pituitary adenomas.

The effect of chronic bromocriptine administration (7.5-20 mg/day for 1-32 months) on the size of "nonsecreting" pituitary adenomas (NPA) was studied in 20 patients. Brain computed tomography showed a marked reduction of the adenoma in one patient after 1 month of treatment (7.5 mg/day); further scans taken 2 and 15 months later, under the same bromocriptine dose, did not show any other variations in the tumoral mass. In the remaining 19 patients, no changes in tumor size were documented by CT during the treatment. Four patients had a worsening of visual fields during bromocriptine administration and they were referred for neurosurgery. In conclusion, bromocriptine was ineffective in reducing tumor size in all but one patient with NPA and, in some cases, it did not prevent tumor growth as is suggested by the worsening of visual fields. Thus, bromocriptine treatment, at least at the doses capable of shrinking macroprolactinomas, seems to be of limited value in patients with NPA.

Adenoma↗

Effect of the new ergot derivative terguride on plasma PRL and GH levels in patients with pathological hyperprolactinemia or acromegaly.

Terguride, a derivative of lisuride, has been shown to possess a mixed dopaminergic-antidopaminergic activity in experimental models. We have studied the effects on PRL and GH levels of 0.2 mg po of terguride in 8 normal subjects, in 15 patients with pathological hyperprolactinemia (PHP) and in 17 patients with active acromegaly. In PHP, PRL levels were significantly reduced up to 300 min after terguride with a nadir (45 +/- 4.0% SE) significantly lower (p less than 0.05) than the one observed in the 8 normal subjects (72 +/- 3.5%). There was no significant difference in plasma PRL levels after 0.2 mg terguride or lisuride in 7 out of 15 patients tested with both drugs. Terguride did not significantly modify GH levels in PHP and in normals but when considering basal and peak (occurring between 60 and 150 min) GH values, a significant difference was found (p less than 0.01). Mean peak of GH did not differ significantly between PHP (5.0 +/- 1.1 ng/ml) and normals (6.8 +/- 1.7 ng/ml). Plasma GH levels of 17 acromegalics were not modified by 0.2 mg of terguride but were significantly reduced by 2.5 mg of bromocriptine. Terguride and bromocriptine reduced PRL levels in acromegalics (p less than 0.01) without any significant difference between the two drug. 0.2 mg terguride bid given for 15 days to 7 healthy volunteers significantly reduced both basal and sulpiride (25 mg im)-stimulated PRL levels. Side effects were observed only in 4 out of 47 subjects tested with terguride and in 8 out of 34 tested with bromocriptine.

Acromegaly↗

Free thyroid hormone levels and TSH response to TRH in patients with autonomous thyroid adenomata and normal T3 and T4.

Free thyroid hormone levels together with basal and TRH stimulated TSH levels, have been determined in 50 patients with autonomous thyroid adenomata, who had normal serum total T3 and T4 values. Similar measurements were made in 33 healthy subjects. FT3 and FT4 plasma levels were significantly higher (P less than 0.01 and P less than 0.05 respectively), and basal and TRH stimulated TSH were significantly lower (P less than 0.05 and P less than 0.001 respectively) in the patients than in the controls. The TSH response to TRH was decreased in spite of normal free thyroid hormones in 25 patients and in a further ten both the delta TSH after TRH and the free fractions were normal. Eighteen patients were studied over periods from 4 37 months by repeating thyroid hormone levels and TRH tests. In six of them a change of these parameters toward toxicity was observed. The data obtained in the longitudinal study indicate that the values of free thyroid hormones and the result of the TRH test obtained by a single determination may represent different steps in the evolution of autonomous thyroid adenomata rather than a distinct pathophysiological condition.

Adenoma↗

Changes in growth hormone (GH) secretion induced by human pancreatic GH releasing hormone-44 in acromegaly: a comparison with thyrotropin-releasing hormone and bromocriptine.

We studied the effects of 100 micrograms human pancreatic GH releasing hormone-44 (GRH) in 35 acromegalic patients. Plasma GH levels significantly increased [basal, 30 +/- 10 (SE) ng/ml; peak, 82 +/- 21 ng/ml; P less than 0.01], but a wide intersubject variability of the responses was found (range, 20-1602%). No relationship was found between the percentage GH increase after GRH and basal values of GH, PRL, or somatomedin-C. All patients also underwent an acute test with bromocriptine (2.5 mg orally) and TRH (200 micrograms iv). When dividing the patients according to their GH responsiveness to bromocriptine (Br), an inverse correlation (r = -0.42, P less than 0.05) was found between percentage of GH changes after GRH and after Br; moreover Br responder patients had a lesser (P less than 0.001) GH increase after GRH (124 +/- 27%) than nonresponders (562 +/- 116%). No relationship was found between the GH response to TRH and GRH, and no differences were found between the percentage GH increase after TRH (513 +/- 117%) and after GRH (349 +/- 71%). We conclude that the tumoral somatotrophs are sensitive to their specific releasing hormone and we suggest that the presence in the adenoma of cells with surface membrane receptors similar to those on the lactotropes may explain the lower sensitivity to GRH of Br responders compared to nonresponders.

Acromegaly↗

Cushing's disease and marked hyperprolactinemia in a patient with a pituitary macroadenoma: effectiveness of bromocriptine treatment.

The case of a young boy bearing a pituitary PRL secreting adenoma (20-30,000 ng/ml) with the unusual association of clinical and endocrinological features of Cushing's disease successfully treated with bromocriptine is described. Brain computed tomography evidenced a huge pituitary adenoma leading to visual field defects and raised intracranial pressure. Due to the very large size of the tumor, which rendered the complete neurosurgical removal unlikely, medical treatment with bromocriptine (10 mg/day) was started. Follow-up for more than six months demonstrated an impressive reduction of tumor size, the lowering of prolactin levels into the normal range, the normalization of visual field, and the regression of both clinical and biochemical signs of hypercortisolism.

Adenoma↗

Dopaminergic treatment of acromegaly: different effects on hormone secretion and tumor size.

We studied the effects of long term treatment with bromocriptine (Br) or lisuride (L) on GH secretion and tumor size in 19 acromegalic patients with large pituitary adenomas. In 22 additional patients with smaller adenomas, only plasma GH levels were monitored during treatment. All patients underwent an acute test with 2.5 mg Br or 0.3 mg L and, on the basis of GH changes, were classified as responders, i.e. reduction in circulating GH concentrations by at least 50% below baseline, or as nonresponders. The chronic treatment was 5-20 mg/day Br in 26 patients or 0.3-2.0 mg/day L in 15 patients. Treatment was given for 4-26 months (mean +/- SE, 13.3 +/- 2.8 months). Plasma GH levels (baseline, 46.3 +/- 8.3 ng/ml) were significantly lower in the group as a whole (22.7 +/- 3.6 ng/ml; P less than 0.01) after the first month of treatment with dopamine agonist agents. GH levels decreased significantly in those acromegalic patients who responded to the acute test (P less than 0.001), but were unchanged in the nonresponders. In addition, there was a significant correlation between the maximal percent GH decrease in the acute test and the response during chronic treatment (r = 0.73; P less than 0.01). Computed tomography failed to show any tumor size changes in any of the GH nonresponders who had a macroadenoma . However, in two patients in the acute responder group with macroadenomas, chronic dopamine agonist therapy resulted in reduction of the extrasellar portion of the tumor (-30% and -40% of tumor area, respectively). These data show that although dopaminergic drugs lower GH levels and reverse signs and symptoms of active disease in those acromegalic patients who are responsive to an acute challenge, tumor size reduction occurred in a minority of such patients.

Acromegaly↗

Reenlargement of macroprolactinomas during bromocriptine treatment: report of two cases.

We report two cases with macroprolactinoma who during medical treatment with bromocriptine showed a normalization of PRL levels and a reduction of tumor size as documented by computed tomography. After a few months of therapy both patients suddenly complained of worsening of their visual fields and a computed tomography demonstrated a reenlargement of the tumor mass; whereas in one patient PRL levels remained always within normal range, in the other patient, who was taking spiramycin for an intercurrent illness, there was also an escape of the hormonal secretion from the inhibitory effect of bromocriptine. The first patient underwent surgery, whereas in the second patient continuation of bromocriptine and interruption of antibiotic treatment resulted in progressive improvement in visual fields and a reduction of tumor size again. We want to stress that in patients with macroprolactinomas responsive to the medical treatment both in terms of PRL secretion and of tumor size reduction, an escape from the effects of bromocriptine, although infrequently, may occur.

Adult↗

The role of prolactin in the inhibitory action of bromocriptine on growth hormone secretion in acromegaly.

UNLABELLED: Bromocriptine treatment results in clinical improvement and inhibition of plasma GH levels in only part of the acromegalic patients. The possible role of the simultaneous presence of Prl and GH in GH-secreting pituitary adenomas was investigated with regard to the inhibitory action of bromocriptine on GH secretion and the paradoxical increase of GH release in reaction to TRH. Surgically obtained pituitary tumour tissue from 35 consecutive acromegalic patients was studied immunohistochemically. In 21 patients no Prl was present in the tumour tissue. These patients had normal plasma Prl levels. In the other 14 patients Prl was present in the tumour tissue. Hyperprolactinaemia was found in 10 of these 14 patient. Plasma GH levels from 2 till 10 h after the administration of 2.5 mg bromocriptine measured before operation were significantly more suppressed in the patients with mixed GH/Prl-containing than in those with pure GH-containing pituitary adenomas, being 38 +/- 4% and 65 +/- 4% of basal values, respectively (P less than 0.01). The response of GH to TRH, however, did not differ significantly between the two groups. CONCLUSIONS: 1. In about 70% of patients with 'mixed' GH/Prl containing adenomas, hyperprolactinaemia is present. 2. The simultaneous presence of Prl and GH in a GH-secreting pituitary tumour increases the sensitivity of GH secretion to bromocriptine. 3. The plasma Prl level is of value to predict which patients with acromegaly are likely to respond to bromocriptine with an inhibition of GH secretion.

Acromegaly↗

Treatment of hyperprolactinemic states with different drugs: a study with bromocriptine, metergoline, and lisuride.

One hundred ninety-one hyperprolactinemic patients (78 women and 13 men; 54 with pituitary macroadenoma, 53 with microadenoma, and 84 with idiopathic disease) were treated for 2 to 48 months with one or two of the following prolactin (PRL)-lowering drugs: bromocriptine, metergoline, and lisuride. All of the three drugs used were highly effective in lowering PRL levels and restoring gonadal function both in females and in males in the majority of patients with either idiopathic or tumorous disease. In poorly responsive patients, increasing the drug doses resulted in further PRL lowering for all the three drugs. Mild side effects were frequently encountered with initiation of drug treatment but spontaneously subsided in most cases; severe side effects, necessitating stopping of the treatment, occurred in only 12 instances, but changing of the drug allowed PRL-lowering treatment to be continued in 11 of them.

Adenoma↗

The value of plasma prolactin levels in the prediction of the responsiveness of growth hormone secretion to bromocriptine and TRH in acromegaly.

UNLABELLED: The mechanism of the inhibition of growth hormone secretion in response to bromocriptine and the ability of thyrotropin releasing hormone to stimulate growth secretion in acromegaly is unknown. In the present study the relationship between the plasma prolactin concentration of untreated acromegalic patients and the reaction of growth hormone to thyrotropin releasing hormone and bromocriptine was investigated. Plasma prolactin levels were elevated in thirty-three (42%) of seventy-nine untreated acromegalic patients. Seventeen patients had mildly elevated prolactin levels, but in sixteen the plasma prolactin concentration was higher than 30 ng/ml. Bromocriptine (2.5 mg) inhibited growth hormone secretion by more than 50% in 22% of the normoprolactinaemic, in 53% of the mild hyperprolactinaemic and in 88% of the patients with a prolactin level above 30 ng/ml (P less than 0.01 v. normoprolactinaemic; P less than 0.01 v. mildly elevated prolactin levels). An increase of growth hormone secretion by more than 100% of the basal value in response to thyrotropin releasing hormone was observed in 44% of the normoprolactinaemic, in 59% of the mildly hyperprolactinaemic and in 75% of the clearly hyperprolactinaemic patients; (P less than 0.01 v. normo- and mildly hyperprolactinaemic patients). CONCLUSION: An increased plasma prolactin concentration in patients with acromegaly is accompanied in most patients by a higher sensitivity of growth hormone secretion to bromocriptine.

Acromegaly↗

Effects of nomifensine on growth hormone and prolactin secretion in normal subjects and in pathological hyperprolactinemia.

We have studied the effect of the oral administration of 200 mg nomifensine (nom), a drug which activates the dopaminergic system, on GH and PRL secretion in 15 normal subjects, 18 patients with idiopathic hyperprolactinemia, and 17 patients with tumoral hyperprolactinemia. GH levels increased significantly after nom in normal subjects (basal, 0.96 +/- 0.76 ng/ml; peak 4.6 +/- 0.61 ng/ml; P less than 0.01) and patients with hyperprolactinemia, both idiopathic (basal, 1.0 +/- 0.38 ng/ml; peak, 4.2 +/- 1.0 ng/ml; P less than 0.05) and tumoral (basal 0.88 +/- 0.3 ng/ml, peak 6.68 +/- 1.2 ng/ml; P less than 0.01). Peak GH levels higher than 5 ng/ml were observed in 8 of 15 normal subjects, 6 of 18 patients with idiopathic hyperprolactinemia, and 8 of 17 patients with tumoral hyperprolactinemia. PRL levels decreased in response to nom in normal subjects, but not in patients with idiopathic or tumoral hyperprolactinemia. A reduction in plasma PRL levels of at least 30% below the baseline was observed only in two patients with idiopathic hyperprolactinemia and in none of the patients with tumoral hyperprolactinemia. These results demonstrate that nom does not discriminate between idiopathic and tumoral hyperprolactinemia. Since nom probably requires a hypothalamic pool of dopamine to bring about its GH stimulatory effect, the suggestion that the lack of a PRL-lowering effect of the drug is attributable to a dopamine deficiency is not supported by our data.

Adult↗

Size reduction of macroprolactinomas by bromocriptine or lisuride treatment.

We have administered to 29 patients with macroprolactinoma the dopamine agonists bromocriptine and lisuride for 1-50 months (mean +/- SE, 12.7 +/- 1.8) in order to assess the effects of these drugs on tumor size. Fourteen patients were treated with bromocriptine (dose range, 7.5-20 mg/day), 12 patients were treated with lisuride (0.6-2 mg/day), and 3 patients were given both drugs. Computed tomography performed before and during treatment showed the occurrence of tumor shrinkage in 18 patients (62%), but in no case was a complete disappearance of the tumor observed. In 5 of these patients, it was even possible to document tumor shrinkage within the first month of treatment with low doses of the dopamine agonists, whereas in other patients, tumors shrank only after prolonged treatment with higher doses. Visual field and acuity improved or normalized in 8 of the 13 patients with visual defects; in some cases, the improvement was reported as early as 2 days after the treatment was started. Plasma PRL levels fell in all patients who showed a reduction in tumor size; in 2 other patients, PRL levels were only poorly suppressed, and tumor size remained unchanged. In the remaining patients, PRL levels were lowered without convincing evidence of tumor shrinkage. In considering the high percentage of patients showing tumor shrinkage under medical treatment, we propose a course with dopamine agonists as the first step in the management of patients with macroprolactinomas regardless of the presence of visual impairments.

Adolescent↗