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Biomedical subjects

I Morange

Publications and source records attributed to I Morange.

15 recordsLinked to original sources
PubMed2007

Gamma knife radiosurgery is a successful adjunctive treatment in Cushing's disease.

OBJECTIVE: Though transsphenoidal surgery remains the first-line treatment of Cushing's disease, recurrence occurs frequently. Conventional radiotherapy and anticortisolic drugs both have adverse effects. Stereotactic radiosurgery needs to be evaluated more precisely. The aim of this study was to determine long-term hormonal effects and tolerance of gamma knife (GK) radiosurgery in Cushing's disease. DESIGN: Forty patients with Cushing's disease treated by GK were prospectively studied over a decade, with a mean follow-up of 54.7 months. Eleven of them were treated with GK as a primary treatment. METHODS: Radiosurgery was performed at the Department of Functional Neurosurgery of Marseille, France, using the Leksell Gamma Unit B and C models. Median margin dose was 29.5 Gy. Patients were considered in remission if they had normalized 24-h free urinary cortisol and suppression of plasma cortisol after low-dose dexamethasone suppression test. RESULTS: Seventeen patients (42.5%) were in remission after a mean of 22 months (range 12-48 months). The two groups did not differ in terms of initial hormonal levels. Target volume was significantly higher in uncured than in remission group (909.8 vs 443 mm(3), P = 0.038). We found a significant difference between patients who were on or off anticortisolic drugs at the time of GK (20 vs 48% patients in remission respectively, P = 0.02). CONCLUSION: With 42% of patients in remission after a median follow-up of 54 months, GK stereotactic radiosurgery, especially as an adjunctive treatment to surgery, may represent an alternative to other therapeutic options in view of their adverse effects.

Adolescent↗
PubMed2000

Efficacy of quinagolide in resistance to dopamine agonists: results of a multicenter study. Club de l'Hypophyse.

OBJECTIVE: A retrospective French multicenter analysis was carried out to assess changes in tumor volume and plasma prolactin concentration in order to evaluate the efficacy of quinagolide (Norprolac) in patients with prolactinoma resistant to ergot dopamine agonists. PATIENTS AND METHODS: One hundred seven patients (46 men and 61 women) from 27 centers were included in the statistical analysis. All had previously been treated with a dopamine agonist (bromocriptine). Fifty-five patients had undergone surgery before being administered quinagolide: 17 of the patients had also received radiotherapy (before and after the initiation of treatment with quinagolide in 14 and 3 cases respectively). Quinagolide was given at doses ranging from 75 to 750 microg daily and continued for more than one year for 84 patients. RESULTS: The prolactin level returned to normal after a mean interval of 9.8 1.6 months (1-48) in 47 of the 107 patients (44%) using a mean dose of quinagolide of 259 32.7 microg/d (75-750). The plasma prolactin concentration had already been normalized using bromocriptine in three patients. The variation in tumor volume was assessed in 82 patients since 8 had no residual tumor post-operatively and 17 had received radiotherapy: at least partial regression of the tumor was noted in 25 (30.8%), including 16 (19.5%) with a more than 50% decrease in the remaining tumor. The mean time taken to observe the anti-tumoral effect was 16.8 3.1 months (3-78) using a mean dose of quinagolide of 255.4 37.8 microg/d d (75-750). The following predictive indicators were identified concerning the efficacy of quinagolide: a pre-quinagolide prolactin level of<300 ng/ml in the group of patients whose plasma prolactin concentration was normalized, and a mean decrease in prolactin of 619 ng/ml in the group of patients showing a reduction in tumor volume treated with quinagolide for 3 months. Side effects (nausea, vomiting, hypotension) were generally mild and were observed in 51 patients (47.6%). Only 11 (10.2%) of patients had to discontinue treatment because of adverse reactions. CONCLUSION: An anti-tumoral effect was noted in 30.8% of patients and occurred within an interval of less than 2 years in 80% of cases at a dose of 300 microg/d. Normalization of the plasma prolactin concentration was obtained in 44% of cases and occurred in less than one year in 80% of patients at a dose of 300 microg/d. Quinagolide is a useful drug and from now on should be prescribed as first-line treatment for patients presenting with bromocriptine-resistant prolactinoma.

Aminoquinolines↗
PubMed1997

[Macroprolactinemia, a variety of hyperprolactinemia. Apropos of 5 cases].

Macroprolactinemia, due to increased circulating levels of large molecular weight forms of prolactin, results in elevated level of immuno-reactive prolactin. The big variants have only weak biological activity; thus macroprolactinemia appears as a case of hyperprolactinemia without clinical significance as demonstrated by the five patients described. The diagnosis is based upon chromatography which separates the hormone and its variants. This disorder produces a pitfall in the diagnostic evaluation of hyperprolactinemia.

Adult↗
PubMed1996

[Acromegaly].

The diagnosis of acromegaly, in more than 95% linked to a pituitary adenoma, is essentially a clinical dysmorphic syndrome. Because of its low evolution, the illness is too often diagnosed when complications (cardio-respiratory, diabetes...) occur. The biological diagnosis is based on high insulin growth factor 1 (IGF1) and growth hormone (GH) levels which are not suppressed under an oral glucose load. The treatment is mainly surgical (transsphenoidal selective adenomectomy) at first intention. Irradiation and medical treatment (dopaminergic or somatostatinergic drugs) are used in case of surgical failure.

Acromegaly↗
PubMed1996

[Prolactin-secreting adenoma].

Prolactinoma, a benign tumor originating from the lactotroph cells of the anterior pituitary, is responsible for signs and symptoms related to both hypersecretion of prolactin and tumor mass. Hyperprolactinemia frequently causes menstrual cycle disturbances, galactorrhea and infertility in women, sexual disorders in men. Microadenomas, characterized by a largest diameter less than 10 mm, may induce frontal headaches, and macroadenomas (more than 10 mm in diameter) may also impair visual function through chiasma compression. Treatment modalities include dopamine agonist therapy such as bromocriptine which allows normalization of prolactin levels, restoration of gonadal functions and tumor shrinkage in most cases. In microadenomas a definitive cure may be achieved by transsphenoidal total selective adenomectomy.

Bromocriptine↗
PubMed1996

Prolactinomas resistant to bromocriptine: long-term efficacy of quinagolide and outcome of pregnancy.

Resistance to bromocriptine, defined as the absence of normalization of prolactin (PRL) levels despite a 15-30 mg daily dose of bromocriptine during at least 6 months, has been observed in 5-17% of the prolactinomas according to the literature. The recent availability of a new potent dopamine agonist, quinagolide, prompted us to analyze its long-term therapeutic effects in 28 patients with prolactinomas resistant to bromocriptine. Before bromocriptine, their PRL levels were 520 +/- 185 micrograms/l (mean +/- SEM) and decreased to 291 +/- 154 micrograms/l after a 6-21 month period of bromocriptine treatment. All the women (N = 20) remained amenorrheic and hypogonadism was not improved in men (N = 8). Subsequently, after 1 year of 150-300 micrograms/day quinagolide, 12/28 patients of the present series recovered normal gonadal function and their initial mean baseline PRL value (404 +/- 180 micrograms/l) was 16 +/- 2 micrograms/l after 1 year of treatment. A significant tumor shrinkage was observed in 5/8 macroadenomas (62%). During the 3-year follow-up period under quinagolide, a similar good control was achieved in these patients, with the exception of one man presenting with a secondary rise of PRL under quinagolide. In contrast, 15 other patients (one patient interrupted quinagolide at 6 months because of poor tolerance) were not normalized under 150-450 micrograms/day quinagolide. Their initial PRL levels (606 +/- 298 micrograms/l) were reduced to 343 +/- 187 micrograms/l (versus 463 +/- 265 micrograms/l under bromocriptine after the same duration of treatment). Despite such a partial inhibitory effect of quinagolide, 7/12 women resumed menstrual cycles and three pregnancies occurred. In no case was any tumor shrinkage noticed during the 3-4-year follow-up. Three patients even presented, after 2 years of quinagolide treatment, with a secondary rise of PRL values associated with a further tumor growth in two patients. During the 3-year follow-up period, nine pregnancies occurred in seven women. In five women, after quinagolide withdrawal, the plasma PRL baseline values ranged from 52 to 158 micrograms/l and from 65 to 192 micrograms/l, respectively, at the first trimester and at the end of uneventful pregnancies. In contrast, in two women a rapid increase of PRL (240-400 micrograms/l) correlated with tumor growth during the first trimester. Such a tumor progression was blocked by quinagolide treatment but not by bromocriptine. These data, although observed in a limited series, justify the careful follow-up of pregnancies in this subclass of patients at risk. Finally, in the whole population, long-term control of hyperprolactinemia by quinagolide was obtained in 11/28 patients (39%) previously resistant to bromocriptine, and 15/20 women (75%) resumed normal gonadal function with a quinagolide daily dose of 300 micrograms in most of them.

Aminoquinolines↗
PubMed1995

Glycosylated and non-glycosylated prolactin forms are increased after opioid administration as part of surgical anaesthesia.

OBJECTIVE: Previous studies have shown that non-glycosylated prolactin (NG-PRL) increased more markedly than glycosylated hormone (G-PRL) after TRH or metoclopramide stimulation. The aim of the present study was to determine whether such results could be extended to opioid-induced PRL stimulation. DESIGN: Open and prospective study. Using a newly developed IRMA specific for NG-PRL, we determined G-PRL and NG-PRL immunoreactivities after administration of 0.8-1.2 mg of the opioid drug phenoperidine as part of an anaesthesia. PATIENTS: Ten male patients anaesthetized for surgical treatment of a prolapsed lumbar intervertebral disc. MEASUREMENTS: Samples were obtained hourly pre and post-operatively, and every 15 minutes during operation for determination of plasma PRL, NG-PRL and G-PRL. Plasma cortisol, ACTH and GH levels were measured in an attempt to differentiate the respective roles of stress and opiate agonists in the variations of PRL levels during surgery. RESULTS: A dramatic increase in PRL levels was observed in all patients from an average of 300 +/- 90 to 1200 +/- 330 mU/l (mean + SEM) 30 minutes after drug administration. The proportion of G-PRL immunoreactivity was not significantly different when basal (25.2%) and stimulated (27%) values were compared (P > 0.05), and when mean increments of NG-PRL and G-PRL were compared (345 and 348%, respectively). The opioid drug induced a significant decrease in cortisol levels after injection and during operation (from 585 +/- 63 to 99 +/- 51 nmol/l) with a concomitant decrease in ACTH levels. GH levels were not significantly altered during anaesthesia but were significantly greater (P < 0.05) after than before surgery (5.0 +/- 1.3 vs 0.98 +/- 0.54 mU/l, respectively). CONCLUSIONS: We conclude from the present and from previous data that opioid induced anaesthesia is accompanied by an increase in both glycosylated and non-glycosylated PRL and that different PRL secretagogues may induce distinct responses in terms of PRL molecular forms.

Adult↗
PubMed1994

Decreased expression of the two D2 dopamine receptor isoforms in bromocriptine-resistant prolactinomas.

Bromocriptine or other dopamine agonists are usually effective for the treatment of prolactin-secreting adenomas. Five to 18% of prolactinomas, however, do not respond to such therapy. We have shown previously that such resistance to bromocriptine correlates with reduced binding to the D2 receptor subtype of dopamine, the major PRL inhibiting factor. In the present work, we demonstrated that reduced binding actually corresponds to decreased expression of the gene coding for the D2 receptor in the pituitary from bromocriptine-resistant patients, as shown by 4-fold lower levels of the corresponding mRNAs compared to those coding for actin. The existence of two D2 receptor isoforms, D2S and D2L generated by alternative splicing, has been described in several tissues, including the pituitary. Both are negatively coupled to adenylyl cyclase and inhibit prolactin secretion, but, in addition, the shortest one (D2S) is more efficiently coupled to phospholipase C. Consequently, we also investigated whether expression of a particular D2 receptor isoform was preferentially affected in resistant adenomas. The proportion of messengers corresponding to the short receptor isoform (D2S) was lower in resistant compared to responsive adenomas: D2S/D2L = 0.74 +/- 0.08 and 1.00 +/- 0.07, respectively. In parallel, much lower levels of D2 receptor mRNAs were found in growth hormone-secreting adenomas, with a D2S/D2L ratio comparable to those of both normal human pituitary and bromocriptine-sensitive prolactinomas (1.05 +/- 0.11). Thus, resistance to bromocriptine therapy seems to involve defects in D2 dopamine receptor expression and possibly in posttranscriptional splicing.

Adenoma↗
PubMed1994

Slow release lanreotide treatment in acromegalic patients previously normalized by octreotide.

Several clinical studies reported the efficacy of the long-acting SRIH analog, octreotide (Octreotide, Sandoz) in the treatment of acromegaly. Recently, another SRIH analog (BIM 23014, Ipsen Biotech) was shown to decrease plasma GH levels in acromegalic patients. The recent availability of a long-acting formulation of BIM 23014 [slow release (SR) lanreotide] could avoid the inconveniences associated with either repeated sc injections or continuous sc infusions. In this study, we compared the clinical and biochemical efficacies of both drugs in a cohort of 19 acromegalic patients, considered initially as responsive to octreotide and sequentially treated with octreotide (3 sc injections of 100-200 micrograms/day) for 12 months and with SR lanreotide (30 mg, im, every 10 or 14 days) for 6 months. Before octreotide treatment, baseline plasma GH (mean +/- SE of 8 hourly samplings) was 29.0 +/- 10.0 micrograms/L and was lowered to 3.2 +/- .2 micrograms/L during the first 7 h after the first 100-micrograms sc octreotide administration. After 12 months of treatment with octreotide, 14 of 19 patients (74%) were considered normalized, as their mean individual GH profiles and insulin-like growth factor-I (IGF-I) values were within the normal range. After octreotide withdrawal for 1 week, plasma GH and IGF-I levels rose to 18.3 +/- 4.8 and 4.1 +/- 0.4 U/mL, respectively. The first 30-mg SR lanreotide im injection produced an acute suppression of plasma GH levels (mean GH value during the 7 h after the injection, 3.0 +/- 0.4 micrograms/L), not different from results previously observed after the first octreotide injection. After 3 months of treatment with 30 mg SR lanreotide every 14 days, normalization of baseline GH and IGF1 levels was achieved in 6 of 19 patients. Ten patients, who did not achieve normal GH levels, subsequently received a 30-mg SR lanreotide injection every 10 days. Among them, normalization of GH and IGF-I levels occurred in 7 of 10 patients after 3 months of such a regimen. After 6 months of SR lanreotide treatment, 13 of 19 patients (68%) were considered normalized, with mean GH and IGF-I values, respectively, of 3.1 +/- 0.4 micrograms/L and 1.5 +/- 0.1 U/mL. The overall tolerance of both drugs (glucose homeostasis and gallstone formation) was similar.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗
PubMed1992

Prolactinomas and resistance to dopamine agonists.

Among 288 patients with prolactinoma (aged 12-62 years; 242 women), 27 were diagnosed as resistant to bromocriptine as their plasma prolactin (PRL) levels remained elevated despite long-term (3 months or more) treatment at high doses (> or = 15 mg daily). These 18 women and 9 men, aged 29 +/- 9 years (mean +/- SD, range 13-50), followed-up for 8 +/- 4 years, had microadenomas (n = 6) or macroadenomas. They were treated by dopamine agonists alone (n = 6) or associated with surgical or radiation therapy. In 8 cases repetitive surgical treatments were necessary. Among the 24 patients who were treated with the nonergot dopamine agonist CV 205-502 after unsuccessful bromocriptine treatment, half of them (9 women, 3 men) resumed normal PRL levels on doses ranging from 0.15 to 0.45 mg/day. Despite daily doses of CV 205-502 from 0.3 to 0.525 mg, the remaining patients were not normalized by this drug which did not prevent tumor growth in 4 of them. Two patients died from invasive cerebral extensions of their tumor and a third had vertebral metastases with positive anti-PRL immunostaining. It is concluded that bromocriptine-resistant prolactinomas represent the most severe aspect of this disease and that a more powerful dopamine agonist like CV 205-502 is effective in only a fraction of these patients.

Adolescent↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

[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↗