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T Brue

Publications and source records attributed to T Brue.

51 records · Page 3Linked to original sources

Effects of the dopamine agonist CV 205-502 in human prolactinomas resistant to bromocriptine.

In 21 patients with prolactinomas resistant to bromocriptine, we studied the effects of CV 205-502 on PRL hypersecretion and tumor mass, as assessed by consecutive computed tomography examinations. Cell culture studies were performed in 9 of such tumors. In 11 patients (group I; 52%) with a mean baseline plasma PRL level of 468 +/- 160 micrograms/L (+/- SE), normal PRL values were achieved after 1-6 months of treatment with 0.1-0.5 mg/day CV 205-502. Tumor size was reduced by 25% or more in 6 of 11 patients. In group II (n = 10), PRL levels (948 +/- 538 micrograms/L at baseline) were reduced by 48% after treatment with 0.1 mg/day CV 205-502. A progressive increase in the daily dose up to 0.5 mg did not further improve the partial reduction of PRL. No reduction in tumor size was observed in this group. The cell culture studies showed that 1) a brief exposure to both drugs provoked PRL suppression lasting 3 days; 2) in group I, CV 205-502 suppressed PRL release more efficiently than bromocriptine, with a maximal inhibition of 72% at 10(-9) mol/L; and 3) in group II, CV 205-502 only achieved a 26% inhibition of PRL release at 10(-8) mol/L, superimposable to that of bromocriptine. These data indicate that in at least half of such adenomas resistant to bromocriptine, CV 205-502, probably due to its higher affinity toward the D2 dopamine receptor, can overcome such resistance.

Adult↗

Somatostatin receptors on thyrotropin-secreting pituitary adenomas: comparison with the inhibitory effects of octreotide upon in vivo and in vitro hormonal secretions.

The in vivo and in vitro inhibitory effects of a somatostatin (SRIH) analog, octreotide, upon TSH, alpha-subunit, GH, and PRL have been studied, as well as SRIH receptors and their coupling to adenylate cyclase, in nine TSH-secreting pituitary adenomas. From in vivo and cell culture studies, the TSH- and alpha-subunit-secreting adenomas appeared heterogeneous, with four out of the nine tumors cosecreting GH and/or PRL. A single sc injection of octreotide (100 micrograms) lowered plasma concentration of TSH by 40 +/- 5% (mean +/- SE of 5), of alpha-subunit by 27 +/- 9% (n = 5), of GH by 60 +/- 5% (n = 4), and of PRL by 27 +/- 9% (n = 4). In cells cultures, octreotide (10(-8) mol/L) inhibited equally TSH, alpha-subunit, and GH release. 125I-Tyr0-DTrp8-SRIH binding sites were measurable in the nine TSH-secreting adenomas either on membrane preparations (n = 6; Bmax: 152 +/- 73 fmol/mg protein) or on frozen sections by radioautography (n = 3). Their density was variable among TSH adenomas and was lower than that measured in GH-secreting adenomas but higher than in nonfunctioning tumors. Two out of three TSH-secreting adenoma displayed an heterogeneous distribution of 125I-Tyr0-DTrp8-SRIH binding sites. 125I-Tyr0-DTrp8-SRIH specific binding was inhibited by guanosine triphosphate (GTP: 10(-4) mol/L). SRIH inhibited adenylate cyclase in 5/5 TSH-secreting adenomas and a good correlation (r = 0.92, P less than 0.02) was found between 125I-Tyr0-DTrp8-SRIH binding capacity (Bmax) and maximal adenylate cyclase inhibition by SRIH. These results demonstrate in vivo and in vitro inhibition of TSH, alpha-subunit, PRL, and GH secretion by octreotide in TSH-secreting pituitary adenomas. Functional SRIH receptors are present on these tumors and the effect of SRIH on hormonal secretion could be mediated, at least in part, by inhibition of adenylate cyclase. These findings support the medical treatment of this rare type of tumors by SRIH analogs.

Adenoma↗

Immunoradiometric analysis of circulating human glycosylated and nonglycosylated prolactin forms: spontaneous and stimulated secretions.

The monoclonal antibodies (MAbs) obtained in mice immunized with human PRL coupled to an anti-PRL MAb were screened for their ability to distinguish the glycosylated (G-) and nonglycosylated (NG-) forms of PRL. The 431-29 MAb exhibited high affinity binding for NG-PRL but little or no cross-reactivity to G-PRL. Using this antibody in conjunction with other MAbs which equally recognized both forms, we developed 2 immunoradiometric assays which were used to determine the amount of G- and NG-PRL in plasma. In 85 normal subjects, NG-PRL baseline levels averaged 6.6 +/- 3 micrograms/L, and represented 76 +/- 8% of the total PRL immunoreactivity. In 74 pregnant women, this proportion was significantly higher during the last 2 trimesters (84 +/- 4% and 85 +/- 6%), as compared to the first trimester (76 +/- 7%). In 6 healthy volunteers studied over 24 h, 79% of the NG-PRL peaks detected using the cluster algorithm occurred concomitantly to a G-PRL peak. The mean NG-PRL/PRL ratio was significantly higher during NG-PRL pulses (81 +/- 9%) than during valleys (71 +/- 12%). Similarly, this ratio was significantly increased during TRH or metoclopramide stimulated PRL secretion (to 88 +/- 7% and 86 +/- 6%, respectively). We conclude that 1) NG-PRL is the predominant immunoassayable form of PRL in plasma; 2) both G- and NG-PRL are cosecreted but NG-PRL is the main PRL form released during spontaneous or pharmacologically induced PRL secretion.

Adult↗

[Value of alpha subunit assay in pituitary pathology].

We evaluated serum alpha-subunit concentrations in 72 patients bearing pituitary adenomas. We conclude that: 1) alpha-subunit hypersecretion is found in all patients with TSH secreting pituitary adenoma (n = 10). Two patients have a predominant secretion of alpha-subunit as compared to TSH secretion. 2) As concerns gonadotropin secreting pituitary adenomas (n = 3), all patient have elevated serum alpha-subunit levels with increased FSH and LT concentrations in 2 cases and 1 case respectively. 3) In prolactinomas (n = 14), alpha-subunit concentrations are not significantly different from that of normal subjects. 4) In 11 acromegalic patients, alpha-subunit hypersecretion is found in 2 patients only with GH-alpha and GH-PRL-alpha secreting pituitary adenomas. 5) Among 34 patients with nonsecreting adenomas, 8 have elevated alpha-subunit concentrations (24%). Positive immunocytochemical staining is found in 70% most often with gonadotropins (55%). Only a few pituitary tumors with positive alpha-subunit immunocytochemical staining have elevated serum alpha-subunit levels. At least, the measurement of basal circulating alpha-subunit levels is very useful in the follow-up of patients with nonsecreting adenomas. In our study, medical treatments including bromocriptine and somatostatin analogues have been found effective in patients with alpha-subunit hypersecretion. Further investigations are necessary to prove if such treatments could control tumoral growth and could prevent recurrences.

Acromegaly↗

[Serum human growth hormone assay. Comparison of six assay kits].

Measurements of human growth hormone (hGH) plasma levels using mono or polyclonal antibodies based on kits are often highly variable depending upon the kit used. We compared six kits commercially available: one based on polyclonal antiserum, five based on monoclonal antisera. We measured 695 sera obtained in short stature children (GH deficiency or normal GH secretory) and adults (normal, hypopituitarism or acromegaly). Our results confirm the variability between the assays. The maximal variation was obtained with SBhGH kit which showed mean results 1.7 fold higher than those obtained with hGH Coatria. Using the OMS 80.205 standard with the six kits, we found a good correlation between the six kits indicating that the standard used in each case was not responsible for the observed variations. This suggest that the different antibodies used in these kits may recognize different isoforms of circulating hGH. In addition variations in reagents used in the different kits may also explain these discrepancies. The variations observed using these six commercially available kits may have important clinical repercussion and especially may impede the diagnosis in hGH deficiency in children.

Adolescent↗

[Pituitary tumor syndrome and hyperprolactinemia in peripheral hypothyroidism].

We studied 7 women with primary hypothyroidism who were suspected to harbor a prolactinoma on the basis of a pituitary gland enlargement associated with hyperprolactinemia. The diagnosis of prolactinoma was confirmed in 1 case only, which was treated surgically. In the remaining 6 patients the serum prolactin levels fell to normal on thyroxine replacement therapy and reduction in size of the pituitary gland was demonstrated by neuroradiological imaging in the 3 documented cases. This study underlines the fact that hyperprolactinemia associated with pituitary hyperplasia is secondary to hypothyroidism and that thyroid function tests should be obtained in all hyperprolactinemic patients even those with pituitary enlargement.

Adult↗

[Evaluation of nuclear magnetic resonance imaging in tridimensional acquisition in the investigation of prolactin microadenoma].

Twenty one patients with suspected prolactin-secreting microadenoma were evaluated with MRI. MRI is the most sensitive means for detecting focal microadenomas. In these patients who were clinically and endocrinologically considered to harbor a microadenoma, MR detected a focal pituitary signal abnormality in 100% when the patients had not previously taken bromocriptine therapy. On the other hand MR demonstrated a focal abnormality in only 30% of cases when the patients had been on dopamine agonist therapy: the MRI findings in the group of bromocriptine treated patients are not affected by neither the duration and dosage of the therapy or the delay between MR examination and the bromocriptine therapy discontinuation. Among the 9 cases in which MRI did not demonstrate a focal abnormality, MRI was strictly normal in 3 cases only; MR showed a localized expansion of the subarachnoid space in two cases; the pituitary gland was large and round, and had a homogeneous signal in one case; the pituitary gland had a heterogeneous signal in 3 cases. In our study the microadenoma had a high signal intensity on the precontrast T1 weighted sequence in 5 cases. The focal abnormality was not seen on the precontrast MR images in 2 cases. The microadenoma enhanced in 3 cases on the postcontrast three dimensional MR images. This MR technique allows thin section slices (1 mm) and therefore the detection of small focal abnormality of the pituitary gland (2.5 x 3 mm). Thus three points have to the emphasized: a) MRI always detected a microadenoma when the patients had never received a bromocriptine therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A long-acting repeatable form of bromocriptine as long-term treatment of prolactin-secreting macroadenomas: a multicenter study.

OBJECTIVE: To assess the efficacy and tolerability of monthly injections of the long-acting repeatable bromocriptine in patients with macroprolactinomas. DESIGN: Open and prospective trial. SETTING: This multicenter trial was carried out in seven university hospitals. PATIENTS: Forty-two patients with prolactin (PRL)-secreting macroadenomas. INTERVENTIONS: Fifty to 200 mg of the drug were administered intragluteally every 28 days for 6 to 24 months. MAIN OUTCOME MEASURES: The efficacy was assessed by repetitive plasma PRL measurements, visual field determinations, and computed tomography scan examinations. RESULTS: After the first 50-mg injection, the mean percentage decrease of PRL levels was 71% from baseline on day 14; between days 1 and 28, PRL levels were suppressed to normal in nine cases, and a clear tumor shrinkage was documented in 21% of the patients. Normalization of PRL secretion was obtained in 62%, and a clear-cut reduction in tumor size in 50% of the patients after 6 months of treatment. CONCLUSIONS: The long-acting repeatable form of bromocriptine was a well tolerated and quickly effective treatment in most of these patients with macroprolactinomas.

Adenoma↗

Severe fibromyalgia after hypophysectomy for Cushing's disease.

We report a case of fibromyalgia occurring after hypophysectomy for Cushing's disease. Clinical examination revealed tender points at 12 of the 18 tender point sites described in the American College of Rheumatology 1990 criteria for the classification of fibromyalgia. The cause of fibromyalgia remains unknown. In our patient, hypophysectomy may have played a role by disturbing endorphin secretion and pain modulation.

Cushing Syndrome↗

[Short-term effect of delayed-action injectable bromocriptine in macroprolactinoma. French multicenter study].

In this prospective multicenter trial, 61 patients presenting with a macroprolactinoma were studied over a 1 month-period following a single 50 mg intragluteal injection of the long-acting repeatable (L.A.R.) form of bromocriptine. The effects of the drug were evaluated mainly by repetitive plasma prolactin measurements on days 1, 3, 7, 14 and 28 after injection, and by repeated visual-field and computed tomography scanning examinations. Normalization of PRL levels was obtained in 23% of patients during the first month following injection. In 6 patients (9.8%), PRL values remained within normal range on day 28 after injection. In these latter patients, PRL levels were significantly lower than in the patients whose PRL values were not normal on day 28 (312 +/- 111 vs 2454 +/- 484 ng/ml [m +/- SEM]). The mean lowest PRL levels were achieved on day 3. The mean percent maximal decrease in PRL levels ranged between 70 and 72% from days 3 to 14 but constantly remained below 50% in 6 patients. An improvement in visual field was observed by day 7 in 45% of patients presenting initially with visual field defects. In particular, in half of the patients with bilateral quadranopsia or hemianopsia, such visual impairments had disappeared after 1 month of treatment. Computed tomography scanning examinations showed in 11% of the patients a more than 20% reduction in tumor mass by day 7 following injection. On day 28, the percent reduction in tumor size was 20-40% in 28% and above 40% in 10% of the patients. Most adverse effects (digestive symptoms, dizziness, postural hypotension) were observed during the first 24 hours of treatment. Local and systemic tolerability was in general good. In macroprolactinoma patients, a single 50 mg injection of bromocriptine LAR was thus able to achieve in the short-term a clear cut reduction in tumor size in 2/5 patients and normalization of PRL levels in 1/10 of patients. A study of the effects of monthly administration of bromocriptine LAR is currently under progress to assess the long-term efficacy of this drug.

Adult↗

Enlarged adenomectomy for enclosed prolactinomas: a preliminary study of 26 cases.

Preliminary results obtained from 26 cases of prolactinomas less than 20 mm in diameter after treatment by enlarged adenomectomy are described. The operation consisted in removal of the adenoma, a layer of normal pituitary at the outer edge of the tumour and the pituitary capsule in contact with the sellar meninges. 24 women and 2 men were involved whose prolactin levels (PRL) were less than 200 ng/ml. All presented abnormal PRL responses to Thyrotropin releasing hormone (TRH) and Metoclopramide (MCP) tests and an absence of a nocturnal rise in the sleep cycle study. Postoperatively, three patients developed transitory diabetes insipidus and five transitory adrenal insufficiency. Gonadotropin reserve was always found normal. All 24 women resumed normal menstrual cycles and two became pregnant within one year. From a serological viewpoint, after surgery 100% of patients were found to be normal for levels of prolactin but only 85% turned to normal dynamic tests. The results of this small series of enlarged adenomectomies seem better than those obtained using selective adenomectomy, but must be confirmed with time.

Adolescent↗

[Pseudohypoxemia and a myeloproliferative syndrome].

In the interval between the sampling of blood and analysis of the blood gas composition, the partial pressure of oxygen falls. The rate of fall depends on the temperature, initial level of partial pressure of oxygen in arterial blood, white cell and platelet count. Pseudohypoxaemia secondary to leukaemia and thrombocytosis can be recognized if the arterial blood sample is kept in ice until analysis can be carried out.

Aged↗