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E Ciccarelli

Publications and source records attributed to E Ciccarelli.

At least 19 recordsLinked to original sources
PubMed2006

Clinical characterization of familial isolated pituitary adenomas.

CONTEXT: Familial pituitary adenomas occur rarely in the absence of multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). OBJECTIVE: Our objective was to characterize the clinical and genealogical features of non-MEN1/CNC familial isolated pituitary adenomas (FIPA). DESIGN AND SETTING: We conducted a retrospective study of clinical and genealogical characteristics of FIPA cases and performed a comparison with a sporadic population at 22 university hospitals in Belgium, Italy, France, and The Netherlands. RESULTS: Sixty-four FIPA families including 138 affected individuals were identified [55 prolactinomas, 47 somatotropinomas, 28 nonsecreting adenomas (NS), and eight ACTH-secreting tumors]. Cases were MEN1/PRKAR1A-mutation negative. First-degree relationships predominated (75.6%) among affected individuals. A single tumor phenotype occurred in 30 families (homogeneous), and heterogeneous phenotypes occurred in 34 families. FIPA cases were younger at diagnosis than sporadic cases (P = 0.015); tumors were diagnosed earlier in the first vs. the second generation of multigenerational families. Macroadenomas were more frequent in heterogeneous vs. homogeneous FIPA families (P = 0.036). Prolactinomas from heterogeneous families were larger and had more frequent suprasellar extension (P = 0.004) than sporadic cases. Somatotropinomas occurred as isolated familial somatotropinoma cases and within heterogeneous FIPA families; isolated familial somatotropinoma cases represented 18% of FIPA cases and were younger at diagnosis than patients with sporadic somatotropinomas. Familial NS cases were younger at diagnosis (P = 0.03) and had more frequently invasive tumors (P = 0.024) than sporadic cases. CONCLUSIONS: Homogeneous and heterogeneous expression of prolactinomas, somatotropinomas, NS, and Cushing's disease can occur within families in the absence of MEN1/CNC. FIPA and sporadic cases have differing clinical characteristics. FIPA may represent a novel endocrine neoplasia classification that requires further genetic characterization.

Adenoma↗
PubMed2003

Three-hour spontaneous GH secretion profile is as reliable as oral glucose tolerance test for the diagnosis of acromegaly.

The diagnosis of acromegaly, in an appropriate clinical context, usually relies on lack of GH suppression below 1 microg/l during OGTT coupled with elevated IGF-I levels. On the other hand, in normal subjects glucose-induced inhibition of GH secretory bursts without any further decrease of interpulse GH levels had already been shown. Based on the foregoing, we aimed to compare the diagnostic reliability of OGTT-induced GH nadir with that recorded during 3-h spontaneous GH secretion. In 59 acromegalic patients (17 male and 42 female, age, mean +/- SE 51.5 +/- 1.9, range 21-76 yr) and in 82 normal subjects (43 male and 39 female, age, mean +/- SE 35.7 +/- 1.5, range 15-72 yr) GH secretion was evaluated every 30 min from 0 to 180 min during slow saline infusion or OGTT (75 g at 0 min). A nadir GH concentration below 1 microg/l was recorded in all normal subjects either during OGTT or saline infusion if GH secretion was evaluated over 180 min. In contrast in acromegalic patients a nadir GH concentration below 1 microg/l never occurred in both conditions. This study shows that a 3-h spontaneous GH profile is as reliable as OGTT in the diagnosis of active acromegaly.

Acromegaly↗
PubMed2001

Effects of octreotide treatment on the proliferation and apoptotic index of GH-secreting pituitary adenomas.

To investigate the effects of octreotide administration on the growth rate of GH-secreting pituitary adenomas, we measured both the Ki-67 labeling index (LI) and the apoptotic index in tumor specimens from octreotide-treated or matched untreated acromegalic patients. Thirty-nine patients who received octreotide until the day of or the day before surgery and 39 untreated patients matched for sex, age, tumor size, extension, and invasiveness were studied. Immunocytochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick endlabeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. The Ki-67 LI and apoptosis were counted on separate slides in at least 1000 evaluable cells. Octreotide-treated patients showed a lower Ki-67 LI (1.8 +/- 0.3%) than untreated controls (3.8 +/- 0.7%; P < 0.02). Overall, the mean Ki-67 LI of treated patients was 53% lower than that in untreated patients. The antiproliferative effect of octreotide occurred independently of tumor extension and invasiveness. Octreotide-treated and untreated patients showed similar apoptotic indexes (0.6 +/- 0.2% and 0.8 +/- 0.3%, respectively). There was a positive correlation between the Ki-67 LI and the apoptotic index (r = 0.29; P < 0.03). Our study demonstrates that acromegalic patients receiving chronic octreotide treatment have a lower value of the proliferation marker Ki-67, but no significant difference in the apoptotic index compared with matched untreated patients. The antiproliferative effect of octreotide on GH-secreting adenomas should imply a lower risk of tumor growth during long-term chronic treatment with the drug.

Acromegaly↗
PubMed2001

Hyperprolactinaemia and prolactin binding in benign intracranial tumours.

BACKGROUND: Meningiomas have been found to have receptors for several hormones, such as oestrogen, progesterone, somatostatin, dopamine and recently also for prolactin. METHODS: To investigate any possible role of prolactin in the growth of those tumours we detected the presence of prolactin-receptors (PRL-R) in 22 meningiomas and we correlated these data with PRL serum levels in patients before surgery. We also studied 13 patients with schwannomas and 7 with other cerebral tumours (4 glioblastomas, 2 ependymomas and 1 astrocytoma). RESULTS: Increased prolactin binding was present in 10 (45.4 percent;) meningiomas, 9 (69.2 percent;) schwannomas and in the patient with astrocytoma. The presence of high PRL levels was present in 6 (27.2 percent;) patients with meningiomas, 8 (61.5 percent;) with schwannomas and in 3 (42.8 percent;) with other tumours. No direct correlation was present between serum PRL levels and PRL binding in all groups. CONCLUSIONS: In conclusion we confirmed the presence of PRL receptors in patients with meningiomas and we have also shown the presence of PRL receptors also in schwannomas. Moreover increased serum PRL were shown in some patients with different tumours of nervous tissue before surgery. Our data could suggest that PRL might have a role in the growth of meningiomas and schwannomas.

Adult↗
PubMed2000

Two-year follow-up of acromegalic patients treated with slow release lanreotide (30 mg).

Pharmacotherapy of acromegaly has been improved in recent years as new long-acting somatostatin analogs have became available; they have been suggested as an alternative treatment to pituitary surgery and radiotherapy. To avoid the inconvenience of multiple daily injections during long-term therapy, a slow release formulation of lanreotide (LAN), to be administered im at a dose of 30 mg every 7-14 days, has been introduced in the therapeutic management. The suppressive effects of a short-term LAN treatment on GH and insulin-like growth factor I (IGF-I) hypersecretion were shown to be similar to those obtained with sc octreotide. However, scant data have been reported concerning a long-term treatment with this drug. In the present study the efficacy and tolerability of a 24-month LAN treatment were evaluated in 118 active acromegalic patients; 71 had been previously operated on and treated with s.c. octreotide (operated patients), 24 previously operated on had been irradiated and treated with s.c. octreotide (irradiated patients), and the remaining 23 were newly diagnosed (de novo patients). The efficacy was considered on the basis of controlled GH (fasting, <7.5 mU/L; glucose-suppressed, <3.0 mU/L) and IGF-I (age-adjusted normal values) secretion. In the 118 patients as a whole, circulating GH and IGF-I levels were significantly decreased during the 24-month LAN treatment (P < 0.0005 at all time points vs. basal value). After 24 months of therapy, controlled GH and IGF-I levels were achieved in 64%, 37%, and 78% and in 51%, 37%, and 70% of operated, irradiated, and de novo patients, respectively. A reduction in tumor size was documented in 5 of 23 de novo patients (22%). Among the 84 operated/irradiated with evident tumor remnant, significant shrinkage was documented in 5 patients (5.9%). Treatment was well tolerated by the majority of patients. Only 2 patients (1.7%) withdrew from LAN treatment due to severe side effects. In conclusion, a 24-month treatment with slow release lanreotide (30 mg) is effective in reducing GH and IGF-I levels; furthermore, in de novo patients it induces disease control in 70% of patients and causes tumor shrinkage in 22% of them, with excellent compliance. These data suggest that LAN can be used in long-term treatment of acromegalic patients.

Acromegaly↗
PubMed2000

Gonadotroph cell pituitary adenomas in males.

BACKGROUND: Considered exceptional in the past, gonadotroph cell pituitary adenomas account for 3.5-6.4% of total surgically excised pituitary adenomas when examined with immunospecific staining. The aim of this study was to describe the clinical, hormonal, radiological and immunohistochemical features, the management and the follow-up of our patients with gonadotroph adenoma. METHODS: In this retrospective study we describe 14 male subjects aged 19-70 yrs affected by gonadotroph cell pituitary adenomas; the patients were studied by hormonal, radiological and immunohistochemical investigations and followed up for 3-13 yrs by ambulatory and/or hospitalized care. RESULTS: Visual impairment and/or decreased libido and erectile dysfunction were the symptoms at presentation. Increased serum gonadotropin concentrations were shown in 3 patients. Reduced levels of testosterone were present in 9 patients, and normal in the remainder. At diagnosis all patients had pituitary macroadenomas, with wide extrasellar extension in 12. All patients underwent trans-sphenoidal surgery and immunohistochemical staining of surgically excised specimens showed the presence of gonadotroph and alpha-subunit cells in all pituitary adenomas. After surgery 3 patients had clear radiological evidence of normal pituitary; in the others a doubtful MRI picture or a residual adenomatous tissue were present. In the patients who did not undergo radiotherapy immediately after surgery, a regrowth of tumoral tissue was shown in 1-10 yrs. CONCLUSIONS: We stress the importance of a close follow-up of patients with gonadotroph adenomas after surgery, and we raise the question of whether radiotherapy may be useful for avoiding any further adenomatous regrowth.

Adenoma↗
PubMed1999

Comparison of six months therapy with octreotide versus lanreotide in acromegalic patients: a retrospective study.

OBJECTIVE: We analysed the effects of 6-months' treatment with octreotide s.c. and lanreotide-SR on circulating GH and IGF-I levels in acromegaly. DESIGN: Open retrospective study. PATIENTS: Thirty-eight patients with active acromegaly (plasma IGF-I levels greater than 2 standard deviations for age-matched controls and increased serum GH levels not suppressible by oral glucose load) were studied. All patients received s.c. octreotide at a dose of 150-600 microg/day for six months as first therapy and subsequently, lanreotide i.m., 30-60 mg either at 14 or 10 day intervals, for 6 months. A 3 months' washout was applied before starting lanreotide treatment. MEASUREMENTS: Mean serum GH levels (from three samples), IGF-I, and clinical examination were performed before and 30, 60, 90 and 180 days after octreotide and lanreotide treatments. Safety tests, HbA1c and, thyroid function were evaluated every three months. RESULTS: Circulating GH and IGF-I levels were significantly reduced (P < 0.001) after one, three and six months of both octreotide and lanreotide treatment. The absolute values were lower and the percent decrease in serum GH levels obtained after octreotide treatment was significantly greater, at all scheduled assessments, than after lanreotide (P < 0.01). Serum IGF-I levels during octreotide were significantly lower only after the first month of therapy (P < 0.01). CONCLUSIONS: Our study shows that octreotide s.c. is able to induce an earlier reduction in IGF-I levels and a more marked reduction in GH levels than lanreotide. However, after six months of therapy the number of patients with safe GH levels and normal IGF-I age-matched levels, was similar with both drugs. Therefore we suggest that octreotide treatment be preferentially used in the short-term presurgical treatment, while lanreotide can be used in chronic therapy when better compliance is necessary.

Acromegaly↗
PubMed1997

Reduction of the somatotrope responsiveness to GHRH and Hexarelin but not to arginine plus GHRH in hyperprolactinemic patients.

Aim of the present study was to verify the maximal secretory capacity of somatotrope cells in patients with pathological hyperprolactinemia (HPRL) comparing it with that in normal age-matched women (NW). To this goal in 12 HPRL normal weight patients (age 28.6 +/- 2.6 yr, BMI 23.1 +/- 1.1 kg/m2) and 8 NW (27.2 +/- 0.8 yr, 22.8 +/- 0.8 kg/m2) we studied the GH response to GHRH (1 microgram/kg i.v.), GHRH plus arginine (ARG, 0.5 g/kg i.v.), an amino acid probably acting at the hypothalamic level inhibiting somatostatin release, and Hexarelin (HEX, 2 micrograms/kg i.v.), a synthetic hexapeptide belonging to GHRP family, which acts concomitantly at the pituitary and the hypothalamic level. IGF-I levels in HPRL were similar to those in NW (179.2 +/- 16.5 micrograms/l and 218.5 +/- 30.8 micrograms/l). In NW the GH response to GHRH (AUC: 1299.5 +/- 186.9 micrograms 90 min/l) was lower (p < 0.02) than those to GHRH + ARG (5252.7 +/- 846.3 micrograms 90 min/l) and HEX 3216.6 +/- 462.3 micrograms 90 min/l) which, in turn, were similar. In HPRL the GH response to GHRH (894.7 +/- 242.4 micrograms 90 min/l) was lower (p < 0.03) than that to HEX (1586.5 +/- 251.3 micrograms 90 min/l) and both were lower (p < 0.03) than that to GHRH + ARG (4468.8 +/- 941.7 micrograms 90 min/l). In HPRL the GH responses to GHRH and HEX were lower than those that in NW (p < 0.03) while that to GHRH + ARG was similar in both groups. These results demonstrate that the somatotrope responsiveness to GHRH and HEX is clearly reduced in patients with pathological hyperprolactinemia. On the other hand, in this condition the GH response to GHRH + ARG is normal. As arginine likely acts via inhibition of hypothalamic somatostatin release, these findings show that the maximal secretory capacity of somatotrope cells in hyperprolactinemia is preserved and indicate that partial refractoriness of somatotrope cells to GHRH and HEX could be due to somatostatinergic hyperactivity.

Adenoma↗
PubMed1997

Long-term treatment with cabergoline, a new long-lasting ergoline derivate, in idiopathic or tumorous hyperprolactinaemia and outcome of drug-induced pregnancy.

Cabergoline (CAB), a new long-acting ergoline derivative, was shown to be very effective in reducing PRL levels in normal volunteers and in hyperprolactinemic patients. We evaluated the hormonal changes after discontinuation of long-term therapy with CAB as well as the safety of drug exposure during pregnancy both for mothers and babies. We therefore studied 48 patients (47 females and one male) with pathological hyperprolactinaemia (mean +/- SE, 117.2 +/- 15.2: median 73.2 micrograms/l), treated for 1-82 months (mean +/- SE, 28.3 +/- 3; median 18). After long-term treatment, CAB was withdrawn in 11 patients and PRL levels were persistently normal for almost 15 days and significantly lower (p < 0.05) than basal at 30, 45, 60, 90, 120 days. Three patients had normal PRL levels still at 45 days after treatment discontinuation. Nine patients became pregnant after 1-37 months (mean 12.4) of therapy. In two patients the pregnancy was interrupted spontaneously in one case and voluntarily in the other. In all but one patients after delivery or three-month breast feeding, PRL levels trended towards reduction. In two cases (one with microadenoma and one with idiopathic hyperprolactinaemia) PRL remained in the normal levels for 1-3 years after delivery. In conclusion CAB is able to inhibit plasma PRL levels for long time (up to 120 days) after withdrawal in patients with pathological hyperprolactinaemia treated with long-term therapy.

Adenoma↗
PubMed1997

Treatment of macroprolactinoma with cabergoline: a study of 85 patients.

OBJECTIVE: Cabergoline is now established as an effective and well-tolerated treatment for prolactinoma. However, there are relatively few published data on the treatment of macro-, as opposed to micro-, prolactinoma. We have therefore reviewed the efficiency and safety of cabergoline in the treatment of patients with prolactin-secreting macroadenomas treated on a compassionate basis. STUDY DESIGN AND PATIENTS: Eighty-five patients with prolactin-secreting macroadenomas were treated with cabergoline 0.25 to 10.5 mg per week (median 1 mg) given to one to seven doses. Treatment durations ranged between 3 months and 8 years. Sixty-five patients (32 intolerant, 16 resistant) had been treated previously with other dopamine agonists. Pretreatment prolactin levels ranged between 80 and 8300 micrograms/I and tumour maximum diameters were between 11 and 42 mm. MEASUREMENTS: Serum prolactin, visual fields if initially abnormal, occurrence of menses or return of libido and potency, blood chemistry and adverse events were assessed at 1 month and then at 3-month intervals during treatment. Pituitary computed tomography or magnetic resonance imaging was usually repeated at 3 months and 1 year, then yearly, in most patients (n = 62). RESULTS: Normalization of prolactin levels was achieved in 52 patients (61.2%) and a prolactin decrease of at least 75% of pretreatment values occurred in 24 others (28.2%). Of the 20 de novo patients, 17 had prolactin normalized and the remainder had at least 75% reduction. Disappearance of tumour image was found in eight of 62 evaluable patients (12.9%) and reduction of the largest diameter by at least 25% in another 33 (53.2%), with an overall success rate of 66.1%; among the 17 evaluable de novo patients the success rate was 82.3%. Fifteen of 21 patients who failed to show tumour shrinkage had previously demonstrated resistance/intolerance to other prolactin-lowering treatments. Of the 12 patients with visual field defects at baseline, six normalized and two showed an improvement. Menses resumed during cabergoline treatment in 79.5% of premenopausal women. Restoration of potency was reported by seven of eight evaluable men. Adverse events were recorded in 24.7% of cases, four of whom (4.7%) discontinued treatment. CONCLUSIONS: Although the present data were not obtained in a formal study we conclude that cabergoline is an effective and well-tolerated treatment for macroprolactinoma patients.

Adolescent↗
PubMed1997

Clinical results of long-term slow-release lanreotide treatment of acromegaly.

Medical therapy is frequently needed to normalize growth hormone/insulin-like growth factor I secretion in acromegaly. The aim of this study was to determine the long-term effects of the slow-release (SR) somatostatin analogue lanreotide in 57 acromegalic patients. SR lanreotide (30 mg) was given every 14 days for 12 months. In 33% of patients, the drug dosage was raised to 60 mg and/or the time interval was shortened to 10 days. Two months of clinical evaluation followed drug discontinuation in 47 out of 48 (84%) patients who completed the 12-month period. A drug-related decrease in GH/IGF-I levels was observed. Basal GH/IGF-I levels were significantly (P < 0.001) reduced at 12 months, IGF-I was normalized in 35% of patients and GH levels were < 5 micrograms L-1 in 54%. There was a clinical improvement in patients complaining of joint pain, rachialgias, headache, digital paraesthesias and hyperhidrosis. Soft-tissue changes were documented by significant (P < 0.001) decreases in finger size. In 52 (91%) patients without overt diabetes, a slight but significant increase in integrated glycaemia (P < 0.001) was noted, while integrated insulin levels were reduced (P < 0.001). Of 33 (58%) patients with normal basal ultrasound examination of the gall bladder, three (9%) had developed asymptomatic gall stones or biliary sludge after 12 months. Adverse events were generally mild. They frequently (52%) occurred after the first SR lanreotide administration; only 28% were recurrent and 20% appeared for the first time during therapy. SR lanreotide is an effective treatment in most unselected acromegalic patients. Tolerance towards the drug is high. Subjective benefits seem to override the simple biochemical control of the disease. Glucose homeostasis more than the incidence of gall stones seems to require monitoring on therapy. SR lanreotide is clearly advantageous in improving patient compliance with medical treatment for acromegaly.

Acromegaly↗
PubMed1997

Prolactin receptors in human meningiomas: characterization and biological role.

Sixty cerebral meningioma specimens obtained at surgery from 34 female and 26 male patients were examined for the presence of prolactin (PRL) receptors. These were compared with normal arachnoid tissue from which these tumours arise. PRL receptors were detected in 61.7% of meningiomas whereas no PRL binding was found in samples of normal arachnoid tissue. No relationship was found when sex or histological findings were compared with the presence of PRL receptors. Receptor-positive tumours had saturable and high-affinity (Kd, 4.8 +/- 0.5 ng/ml) receptors with hormonal specificity for human PRL (hPRL) resembling that of other target tissues of PRL in man. The biological role of these receptors was investigated in primary cell cultures derived from meningioma tissue characterized for PRL receptor. When human PRL was added to the culture medium, in doses ranging from 1 to 200 ng/ml, a dose-dependent stimulation of 3H-thymidine incorporation was observed only in PRL-receptor positive tumours. The PRL concentrations required to produce a half-maximal effect ranged from 11 to 20 ng/ml and were quite close to the dissociation constant (Kd) of binding of PRL to its receptors. PRL also caused an increase of cell number compared with control with a significant effect after 3 and 4 days of culture. In conclusion, these findings indicate that a large number of human meningiomas express specific and functional receptors for PRL which are involved in mediating its proliferative effects.

Adult↗
PubMed1996

Galanin positively modulates prolactin secretion in normal women.

It is widely accepted that, in man, galanin, a neuropeptide, has a clear GH-releasing effect while its stimulatory influence on PRL secretion is matter of debate. To clarify this point, in 6 normal young women (23-35 yr) in their early follicular phase, we studied the effect of galanin (pGAL, 80 pmol/kg. min infused i.v. over 60 min) on both basal and arginine (ARG, 0.5 g/kg i.v. in 30 min), TRH (400 micrograms i.v. as a bolus at 0 min) or metoclopramide (MCP, 10 mg i.v. as a bolus at 0 min)-stimulated PRL secretion. GAL infusion failed to significantly increase basal PRL levels (peak vs baseline: 12.2 +/- 3.6 vs 8.7 +/- 1.2 micrograms/L) but counteracted the spontaneous PRL decrease observed during saline infusion (AUC: 1216.6 +/- 282.1 vs 672.0 +/- 94.5 micrograms.min/L; p < 0.05). GAL infusion clearly enhanced the PRL response to TRH (AUC: 5806.3 +/- 743.0 vs 3952.1 +/- 423.9 micrograms.min/L, p < 0.05) and ARG (AUC: 3676.8 +/- 382.6 vs 2638.9 +/- 287.0 micrograms.min/L, p < 0.05), respectively. On the other hand, GAL failed to modify the MCP-induced PRL response (AUC: 15409.5 +/- 2085.3 vs 14,787.9 +/- 2045.5 micrograms.min/L). The PRL response to MCP was higher than that to TRH (p < 0.01) which, in turn, was higher than that to ARG (p < 0.01). During GAL infusion, the PRL response to TRH or ARG remained lower (p < 0.01) than that after MCP administration. Thus, in conclusion, present data demonstrate that in normal women galanin enhances the PRL response to ARG and TRH but fails to modify that induced by dopamine receptor blockade with metoclopramide. Based on evidence that the inhibition of central dopaminergic activity inhibits the lactotrope responsiveness to dopaminergic antagonists or TRH, it is unlikely that galanin influences PRL secretion via inhibition of dopaminergic tone.

Adult↗
PubMed1996

Effect of bromocriptine on insulin, growth hormone and prolactin responses to arginine in obesity.

Dopaminergic system seems to influence the regulation of insulin secretion, although in man conflicting data are reported. Furthermore, bromocriptine (BRC), a dopaminergic agonist, has been recently found to inhibit the seasonally occurring hyperinsulinemia and the increase in body weight in the hamster. On this basis, we investigated the effect of BRC on spontaneous and stimulated insulin secretion in human obesity. Six obese (BMI: 33.2 +/- 1.6 Kg/m2) underwent the administration of: 1) arginine (ARG, 0.5 g/Kg iv in 30 min), 2) BRC (2.5 mg po), 3) ARG+BRC. In each test plasma glucose and serum insulin, growth hormone (GH) and prolactin levels were determined. BRC did not significantly reduce spontaneous and ARG-induced insulin release. Baseline and stimulated glucose levels were also unchanged. BRC determined an increase in GH levels (3.7 +/- 1.3 vs 0.5 +/- 0.3 microgram/l, p < 0.05), but failed to modify the somatotrope responsiveness to ARG. On the other hand, both spontaneous and stimulated PRL secretion were reduced by BRC (2.5 +/- 0.4 vs 6.7 +/- 1.1 micrograms/l, p < 0.05 and 0.8 +/- 1.9 vs 11.0 +/- 2.1 micrograms/l, p < 0.05, respectively). Our results show that in obese patients the acute activation of dopaminergic receptors by bromocriptine fails to modify both basal and ARG-induced insulin release, while inhibits spontaneous and stimulated PRL secretion. Our data also show that the low GH response to arginine in obesity is not improved by the coadministration of bromocriptine, in agreement with the hypothesis that both substances act by the same mechanism, i.e. inhibition of endogenous somatostatin release.

Adolescent↗
PubMed1996

Hexarelin, a synthetic growth hormone releasing peptide, stimulates prolactin secretion in acromegalic but not in hyperprolactinaemic patients.

OBJECTIVE: In man, new synthetic peptides such as hexarelin have been shown to have a potent and dose dependent GH releasing activity. Furthermore, a significant PRL releasing activity has also been demonstrated, but this has been investigated in less detail. We have therefore evaluated the effect of hexarelin on PRL and GH secretion in patients with active acromegaly or pathological hyperprolactinaemia. DESIGN: Hexarelin (2 micrograms/kg i.v.), a modified derivative of GHRP-6 of the following structure: His-2-Me-D-Trp-Ala-Trp-D-Phe-Lys-NH2, or placebo, was administered in random order on two separate occasions. PATIENTS: Eight patients with active acromegaly (ACRO, 6 F and 2 M, mean age 61.7 years, range 56-73), 6 with macroadenomas and 2 without radiological signs of tumour, and 6 female patients with pathological hyperprolactinaemia (HPRL, mean age 31.2 years, range 18-47) 5 with microadenomas and 1 with empty sella, were studied. Fourteen normal subjects (NS, 8 F and 6 M, 27.1 years, 24-30) were studied as controls. MEASUREMENTS: GH and PRL levels were evaluated every 15 minutes for 2 hours after hexarelin or placebo. Both hormones were measured using commercial IRMA kits. Basal IGF-I was measured in all subjects using an RIA following acid-ethanol extraction. RESULTS: Hexarelin induced a significant increase in PRL levels in NS (median, range, delta peak HEX vs placebo: 150 (-14-402) vs 10 (-34-24) mU/l; delta AUC HEX vs placebo: 7710 (2,100-3 2540) vs 30 (-2,566-2,040) mU min/l, P < 0.01) and in ACRO (190 (-10-496) vs 6 (-100-34) mU/l; 10,170 (-5,310-51,436) vs -82 (-6,030-1,410) mU min/l, P < 0.02), but not in HPRL (10 (-180-80) vs 50 (-100-240) mU/l; -600 (-16,996-10,140) vs -1,950 (-8,540-14,160) mU min/l). Hexarelin also induced a lower increase of GH in HPRL (60 (30-82) vs 1.8 (-0.2-2.2) mU/l; 2,853 (1,477.6-4,372.6 vs 91.6 (-160.6-174) mU min/l, P < 0.05) than in NS (90.8 (50.6-181) vs 0.8 (-1.2-6.8) mU/l; 6642 (2,004-13,252.6 vs 42 (456-900) mU min/l, P < 0.01) or in ACRO (117.2 (21.2-420.6 vs 3.8 (-2.2-18) mU/l; 6645 (1,554-22,138.6 vs 334.6 (-324-1,065) mU min/l, P < 0.02). CONCLUSIONS: Our data show that the PRL releasing effect of hexarelin is preserved in acromegaly but lost in pathological hyperprolactinaemia. In contrast with acromegaly, the GH releasing effect of hexarelin is also blunted in hyperprolactinaemic patients. These data demonstrate that patients with pathological hyperprolactinaemia are partially refractory to the activity of hexarelin.

Acromegaly↗