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P Chanson

Publications and source records attributed to P Chanson.

At least 73 records · Page 4Linked to original sources
PubMed1995

The prevalence of colonic polyps in acromegaly: a colonoscopic and pathological study in 103 patients.

Patients with acromegaly are reported to be at risk of developing adenomatous colonic polyps, which are considered to be preneoplastic lesions. This assumption is, however, usually drawn from results obtained in rather small series of patients or without a control group. We, therefore, undertook a prospective colonoscopic and pathological study comprising 103 acromegalic patients and 138 nonacromegalic control subjects referred for irritable bowel syndrome. The prevalence of adenomatous colonic polyps was significantly increased in acromegalic patients compared to that in control subjects (22.3% vs. 8.0%; P = 0.0024). The significance was similarly present in male acromegalic patients (28.6% vs. 5.5% in male control subjects; P = 0.0026), but was absent in female acromegalic patients. The prevalence of colonic polyps was also significantly increased in the group of acromegalic patients under 55 yr of age (20.0% vs. 3.0% in the control group of the same age; P = 0.0026). Other characteristics of adenomatous colonic polyps in acromegaly were the multiplicity and the presence proximal to the splenic flexure. No difference in the duration of acromegaly was found between patients with or without adenomatous polyps. The prevalence of hyperplastic colonic polyps was also significantly increased to 24.3% in acromegalic patients vs 4.4% in control subjects (P < 0.001). In conclusion, in view of the increased incidence of adenomatous colonic polyps, colonoscopy should be part of the follow-up examination in acromegaly.

Acromegaly↗
PubMed1995

Even after priming with ovarian steroids or pulsatile gonadotropin-releasing hormone administration, naltrexone is unable to induce ovulation in women with functional hypothalamic amenorrhea.

In functional hypothalamic amenorrhea (HA), it has been reported that administration of opioid receptor antagonists restores gonadotropin secretion and ovarian function. However, endogenous opioids may modulate gonadotropin secretion only in the presence of ovarian steroids. To further study these conflicting results, a group of nine women with secondary functional HA who wished to become pregnant were studied. The opiate antagonist naltrexone (Nal; 100 mg/day) was administered for two 30-day periods, starting on either day 22 (Nal 1) of a well characterized replacement regimen with estradiol (E2) and progesterone (P), or on day 22 (Nal 2) of the luteal phase induced by exogenous pulsatile GnRH administration (10 micrograms/pulse, iv, every 90 min). Plasma LH and FSH were measured every 10 min for 8 h before treatment and on day 12 of each treatment period (Nal 1, pulsatile GnRH, and Nal 2). Ovulation was monitored during each treatment. Plasma E2 levels were measured on days 12 and 22, and P levels on day 22 of each treatment. During exogenous E2 and P administration, plasma steroid levels reached luteal phase levels. However, during Nal 1, plasma E2 levels fell to prestudy levels and remained low. No follicular growth occurred, and the pulsatile study showed pretreatment frequency, amplitude, and mean plasma levels of LH. On day 12 of pulsatile GnRH administration, plasma E2 levels increased, and LH and FSH pulses followed each GnRH pulse during the frequent sampling study. Ovulation occurred in all women during pulsatile GnRH treatment. During Nal 2 treatment, plasma E2 levels returned to prestudy levels without follicular growth, and the pulsatile study was similar to those prior treatment and during Nal 1 administration. In conclusion, Nal, started during priming either with exogenous E2 and P treatment or gonadotropin stimulation induced by pulsatile GnRH administration, was unable when continued alone to initiate or maintain gonadotropin secretion in women with HA. Thus, the exclusive role of opioids in HA and the effect of Nal even in the presence of ovarian steroids are questionable.

Adult↗
PubMed1995

The cyclic adenosine 3',5'-monophosphate-responsive factor CREB is constitutively activated in human somatotroph adenomas.

Oncogenic gsp proteins appear to stimulate the transformation of pituitary somatotrophs by inducing the constitutive activation of adenyl cyclase. Previous work implicating the cAMP-responsive transcription factor CREB as a biochemical intermediate in the proliferative response to cAMP led us to examine whether CREB activity was correspondingly elevated in human somatotroph adenomas. In a series of 15 human GH-secreting tumors, we found that each of these contained elevated levels of Ser133-phosphorylated and, hence, activated CREB compared with nonfunctioning pituitary tumors. Four of the GH-secreting adenomas contained an oncogenic gsp gene by polymerase chain reaction analysis, and two additional adenomas expressed wild-type G alpha s protein at 5- to 10-fold higher levels than nonfunctioning pituitary tumors. As both oncogenic gsp and overexpressed G alpha s proteins can induce Ser133 phosphorylation and cAMP-responsive gene expression in transfected GC somatotroph cells, our studies indicate that these proteins may promote somatotroph transformation in part by inducing the transcription of specific CREB-dependent target genes.

Adenoma↗
PubMed1995

[Screening of multiple endocrine neoplasias type 1. Reflexions of the Study Group on Multiple Endocrine Neoplasias type 1].

The "Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1 (GENEM 1)" is a French group involved in a comprehensive multicentre study of Multiple Endocrine Neoplasia type 1 syndrome (NEM 1). The objectives of this group are to define diagnostic and therapeutic protocols and to carry out genetic research on NEM1. The first aim of physicians is to recognize the syndrome and to determine the appropriate screening especially into two circumstances: 1 degree In case of isolated and sporadic glandular disease -i-e-parathyroid glands, endocrine pancreas, antehypophysis, adrenal glands and neuroendocrine tumors? 2 degrees In case of very high probability of NEM 1 syndrome? This paper answers these two questions, based on the analysis of the first 150 cases collected by the GENEM 1.

Adenoma↗
PubMed1994

[Dysthyroidism in patients treated with interferon alpha].

In addition to their initially recognized antiviral activity, interferons are known to have a number of effects on the immune system. The role of alpha-interferon (alpha-IFN) has been evaluated in 8 studies, including 573 patients, aimed at determining the prevalence, clinical course and predictive factors of autoimmune dysthyroidism in patients treated with alpha-IFN. Two major categories of patients were treated with alpha-IFN: those with cancer and those with chronic viral hepatitis. Two types of interferon were used: human leukocyte IFN and recombinant IFN. Among the 542 patients in which thyroid function was evaluated, 47 (8.7%) had clinical or biological dysthyroidism: hypothyroidism in 25 (53%), hyperthyroidism in 13 (28%) and biphasic hyper-hypothyroidism in 9 (19%). The delay to onset was known in 44 patients (mean 9 months, range 1.5 to 23 months). Dysthyroidism was temporary in certain patients and did not require treatment, but antithyroid drugs were required in others. The prevalence of antithyroglobulin and/or antimicrosomal antibodies varied from 0 to 20% (mean 13.7%). The prevalence of antithyroid stimulating hormone receptor antibodies appeared to be lower than that of antithyroid antibodies. The pathogenic mechanism of dysthyroidism in patients given alpha-IFN remains unknown, but could result from the induction of antithyroid antibodies or an increase in pre-existing levels. Abherent expression of HLA-DR antigens on the surface of the thyrocytes has been proposed as a possible factor, although gamma-IFN and not alpha-IFN leads to the expression of class II antigens. It has also been shown that alpha-IFN induces the expression of class I antigens on thyrocytes, indicating that the observed dysthyroidism might result from an over-expression of class I antigens which would facilitate direct activation of cytotoxic T cells. In summary, alpha-IFN can induce dysthyroidism in about 1 out of 10 patients, probably by the induction or stimulation of autoimmune phenomena. The positive predictive value of antithyroid antibodies is modest, about 60%, but the negative predictive value is high at 93%. Thyroid function should be monitored closely in patients given alpha-interferon.

Breast Neoplasms↗
PubMed1994

Effects of octreotide on biliary lipid composition and occurrence of cholesterol crystals in patients with acromegaly. A prospective study.

Treatment with the somatostatin analog octreotide is associated with increased gallstone formation. The mechanism of formation of these stones is unclear. The purpose of this study was to examine the effect of a three-month treatment with octreotide on biliary lipid composition and the occurrence of cholesterol crystals in patients with acromegaly. Thirteen patients with active acromegaly, aged 24-76 years, received octreotide (100 micrograms three times daily) for three months. Fasting gallbladder bile was obtained during upper gastrointestinal endoscopy after ceruletide stimulation. Bile was studied before and at the end of the treatment period (N = 7), only before (N = 4), or only at the end of treatment (N = 2). Before treatment, all bile samples but one were supersaturated with cholesterol. However, none contained cholesterol crystals on microscopic examination. At the end of the treatment period, all but two samples were supersaturated with cholesterol. Three of nine samples contained cholesterol crystals, a proportion significantly higher than before treatment. The relative proportions of bile acids, cholesterol, and phospholipids, and the mean cholesterol saturation index were not different before and during treatment. Follow-up ultrasonography showed the occurrence of gallstones in four patients, including the three patients who had cholesterol crystals. We conclude that: (1) fasting gallbladder bile of patients with acromegaly is frequently supersaturated with cholesterol; (2) treatment with octreotide does not increase cholesterol saturation index, but may induce the occurrence of cholesterol crystals. The data are consistent with the view that gallstones induced by octreotide are cholesterol stones and suggest that the drug may impair gallbladder motility and/or decrease cholesterol nucleation time.

Acromegaly↗
PubMed1994

Responses to gonadotropin releasing hormone agonist and antagonist administration in patients with gonadotroph cell adenomas.

As they are clinically silent, gonadotroph cell pituitary adenomas are usually diagnosed only when pituitary enlargement causes visual impairment or hypopituitarism. In postmenopausal women presenting with pituitary tumors it can be difficult to determine whether gonadotropin hypersecretion is due to adenomatous or normal gonadotrophs prior to surgery. The usual GnRH dependency of gonadotropin secretion may be of diagnostic and therapeutic value. We therefore evaluated responses to the GnRH antagonist Nal-Glu-GnRH and to the long-acting GnRH agonist D-Trp6 (3.75 mg IM) in 9 and 4 patients with FSH- and/or alpha-subunit-secreting adenomas, respectively. Six of the 7 patients with FSH-secreting adenomas and one of the 2 patients with pure alpha subunit-secreting adenomas were studied postoperatively. In these patients postoperative FSH and/or alpha-subunit levels remained elevated and pituitary imaging by CT-scan and/or MRI disclosed tumoral residues. In the 2 remaining patients testing was performed preoperatively. A single administration of 5 mg Nal-Glu to the 7 patients with FSH-secreting adenomas produced a slight but significant fall in above-normal FSH levels from 24.4 +/- 15.4 IU/l to a nadir of 20.3 +/- 11.9 IU/l (-17%, p < 0.05) 20 h following the injection. LH levels fell markedly in the 6 patients with normal basal serum LH concentrations to those observed in hypophysectomized patients, while mean alpha-subunit levels were not modified. Alpha-subunit levels were not modified by Nal-Glu administration in the 2 patients with alpha-subunit-secreting adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1994

The diagnostic value of fine-needle aspiration biopsy under ultrasonography in nonfunctional thyroid nodules: a prospective study comparing cytologic and histologic findings.

Fine-needle aspiration biopsy (FNAB) of thyroid nodules has been proposed as a preoperative screening method to reduce the number of patients with benign nodules referred for surgery. Only a few previously published studies have compared cytologic results with a systematic surgical control; furthermore, the role of ultrasound guidance for FNAB in obtaining representative material has been poorly evaluated. The authors tried to assess the diagnostic value of FNAB performed under ultrasonography in a series of patients with a cold nodule and a systematic surgical control. This prospective study included 132 consecutive patients, 19 men and 113 women, aged from 18 to 82 years. The rate of carcinomas was 13.8%. A very high rate of adequate material was obtained (96.2%). Sensitivity, specificity, and global accuracy were 95%, 87.7%, and 89%, respectively. These results, which are equivalent to those previously published but associated with a low level of insufficient material, emphasize the diagnostic value of thyroid FNAB.

Adult↗
PubMed1994

Calcitonin genes (I and II) expression in human nervous and medullary thyroid carcinoma tissues.

The calcitonin gene family comprises two main genes: CALC I which encodes for calcitonin (CT) mRNA in thyroid and calcitonin gene-related peptide I (CGRP I) mRNA in neuronal tissues and CALC II gene which encodes for CGRP II mRNA only. Recently, in normal thyroid and in medullary thyroid carcinoma (MTC), we detected an additional splicing pathway involving the splicing of exon 4 to exon 5 and leading to the expression of a third CALC I mRNA: CT mRNA II. In the present study, we analyzed by polymerase chain reaction the expression of CT mRNAs I and II, CGRP I and II mRNAs in MTC and in human tumors of the nervous system (3 pituitary adenomas, 3 astrocytomas, 2 schwanomas). In pituitary tissues, CGRP II expression was constant and easily detectable in comparison to other tissues. CT mRNA II signal was very low, but clearly detectable after a reamplification indicating that the factors responsible for the splicing of exon 4 to exon 5 are poorly operative in neuronal tissues.

Adenoma↗
PubMed1994

Glycoprotein hormone alpha-subunit secretion in prolactinomas and in non-functioning adenomas: relation with the tumour size.

OBJECTIVE: Free glycoprotein hormone alpha-subunit plasma levels have been reported to be increased in glycoprotein hormone-secreting adenomas and in acromegaly, but rarely in prolactinomas and in only two cases of Cushing's disease. The prevalence of elevated plasma alpha-subunit levels in patients with non-functioning adenomas is still unclear. In addition, no previous work has described plasma alpha-subunit levels in a comprehensive series of adenomas characterized by in-vivo secretion and/or immunocytochemistry. PATIENTS: Thirty-seven patients with definite prolactinomas and 48 with non-functioning tumours characterized by immunocytochemistry were studied, from a series of 145 consecutive patients including 33 acromegalics, 18 patients with glycoprotein hormone-secreting adenomas and 9 with Cushing's disease. MEASUREMENTS: Plasma free alpha-subunit was measured by radioimmunoassay in all patients and in a large sample of normal subjects to establish normal ranges according to sex, age and menstrual status. Tumour volume index was the product in cm3 of length, width and height of the adenoma as assessed by computerized tomography or magnetic resonance imaging. RESULTS: Twelve of the 37 (32%) patients with prolactinomas had increased plasma alpha-subunit levels; their tumours were significantly larger with significantly higher plasma PRL levels than those of patients without increased plasma alpha-subunit levels (P < 0.02). All prolactinomas above 50 cm3 were associated with alpha-subunit secretion, whereas only 6 of 29 smaller tumours were similarly associated. Twelve of the 48 'non-functioning' adenomas actually secreted alpha-subunit in vivo: 8 gonadotrophin-secreting, 2 'pure' alpha-secreting, one with negative immunocytochemistry and one necrotic adenoma. Their volumes were significantly higher than those of adenomas without increased plasma alpha-subunit levels (P < 0.04). Plasma alpha-subunit levels were increased in the 6 patients with TSH-secreting adenomas, 8 of 12 with FSH-secreting adenomas, 11 of 33 acromegalics and none of those with Cushing's disease. CONCLUSION: Plasma free alpha-subunit levels were increased in 49 of 145 patients (34%). For prolactinomas and 'non-functioning' adenomas, alpha-subunit hypersecretion was seen more often with larger tumours. Half of the cases with increased free alpha-subunit in this series were patients harbouring an adenoma which did not stain for an intact glycoprotein hormone.

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↗
PubMed1994

Thyrotropin-releasing hormone (TRH) binding sites and thyrotropin response to TRH are regulated by thyroid hormones in human thyrotropic adenomas.

In order to see whether, in thyrotropic adenomas with thyrotoxicosis, plasma thyroid hormones regulate the thyrotropin-releasing hormone (TRH) binding sites and the thyrotropin (TSH) response to TRH, we investigated: the presence of TRH binding sites in two cases of thyrotropic adenomas associated with hyperthyroidism and in one case of thyrotropic adenoma secondary to thyroid failure: and the in vitro effect, in a perifusion system, of triiodothyronine (T3) on the response of TSH to TRH in three cases of TSH-secreting adenomas associated with hyperthyroidism. The TRH binding sites were absent in the adenomas associated with high levels of circulating thyroid hormones, whereas they were present in the adenoma secondary to primary thyroid failure (Kd = 47 nmol/l, Bmax = 40 nmol/kg membrane proteins). In vitro, the three adenomas spontaneously released TSH in the perifusion medium (1.49 +/- 0.06 (mean +/- SEM), 7.25 +/- 0.12 and 16.73 +/- 0.36 mIU.l-1 x 10(6) cells-1 x 2 min-1) and exhibited an ample TSH response to 10(-7) mol/l TRH pulses. In two cases, tumoral secretion of fragments was compared with those of fragments maintained since the time of surgical removal in the presence of 10(-8) mol/lT3. The TSH responses to TRH were abolished in the presence of T3 in these two cases. We conclude that thyrotropic adenomas associated with hyperthyroidism are still controlled in vivo by T3. In particular, T3 regulates the TSH response to TRH, probably via a down-regulation of the TRH binding sites.

Adenoma↗
PubMed1994

McCune-Albright syndrome and acromegaly: clinical studies and responses to treatment in five cases.

We report here five new patients with McCune-Albright syndrome and acromegaly. In the five patients studied (three males and two females aged 18-42 years), acromegaly began before the age of 20 years and was recognized after the diagnosis of fibrous dysplasia, which was polyostotic in three cases and monostotic in two. Bone fibrous dysplasia always involved the base of the skull and in four patients prevented surgical removal of the pituitary adenoma, which was visualized easily by magnetic resonance imaging. Serum growth hormone (GH) levels ranged between 20 and 48 micrograms/l and were not suppressed by an oral glucose load. Thyrotropin-releasing hormone administration produced a paradoxical increase in serum GH levels in all the patients. Four of the five patients had hyperprolactinemia (43-670 micrograms/l). In the sole patient who could be operated on, a typical adenoma with positive immunostaining for GH was incompletely removed and postoperative radiation therapy failed to cure the acromegaly. In two patients, medical therapy with bromocriptine and/or octreotide was partially or totally ineffective whatever the dose (up to 1.5 mg per day) and duration (2-4 years) of octreotide treatment.

Acromegaly↗
PubMed1994

Remission of proteinuria following correction of hyperlipidemia in NIDDM patients with nondiabetic glomerulopathy.

OBJECTIVE: Animal studies suggest that hyperlipidemia may play a direct role in glomerular damage. In patients with non-insulin-dependent diabetes mellitus (NIDDM), dyslipidemia occurs early in the course of nephropathy and may be involved in the progression of renal disease. CASES: We report on two young NIDDM patients with marked hyperlipidemia and proteinuria, in whom renal biopsy demonstrated nondiabetic glomerulopathy. In both cases, the decrease in blood lipid levels was associated with a major decrease in proteinuria. Episodes of hyperlipidemia were associated with a resumption of heavy proteinuria in one patient with serum triglyceride levels and proteinuria being closely correlated. CONCLUSIONS: These two cases suggest that hyperlipidemia has an important role in the pathogenesis of glomerular disease.

Adult↗
PubMed1994

[Treatment of acromegaly with a new slow release somatostatin analog, lanreotide].

Treatment of Acromegaly has been improved by the development of the somatostatin analogs characterized by an increased specificity and longer duration of action. One of these analogs-Lanreotide- (Somatuline) is supplied under a slow release formulation and does not require several daily injections like other analogs presently available. The clinical pharmacodynamic studies that have been conducted in healthy and acromegalic patients show that the i.m. injection of a single dose of this slow-release formulation leads to a significant decrease of the plasma GH and IGF-1 levels. This effect lasts at least 14 days. The Lanreotide slow-release formulation has been used to treat 123 acromegalic patients who presented with a still evolutive disease after conventional therapy. The product was given at a 30 mg-dose every 10 or 14 days during a 3-to 24-month period. This treatment led to a reduction of the symptoms and to a decrease of GH hypersecretion. GH and IGF-1 levels have been normalized respectively in 46% and 32% of the patients. The observed results allow to conclude to an immediate efficacy of the treatment (without escape sign). The adverse drug events are minor and transitory. The antitumor effects are modest and inconstant. The slow release formulation seems to provide the patients with a better quality of life, as compared to the several daily injections.

Acromegaly↗
PubMed1993

[Octreotide, analog of somatostatin. Pharmacological properties and therapeutic applications in pituitary endocrine tumors].

Octreotide, the first somatostatin analogue developed, has pharmacological properties (it inhibits pituitary GH and TSH secretion, pancreatic and digestive tract endocrine secretion and various gastrointestinal functions) which are qualitatively similar to those of the natural 14 amino acids peptide. Enzymatic structural modification had resulted in a peptide which is very resistant to degradation and has a 90-110 min half-life permitting subcutaneous administration. Following a subcutaneous injection of 50 to 100 micrograms, absorption is rapid and complete. The peak plasma concentration is obtained within 20 to 30 minutes. The drug is degraded mostly in the liver. Among pituitary tumours, GH- and TSH-secreting adenomas constitute the primary indication. Octreotide has been widely tested in the treatment of acromegaly; 50 to 80 percent of patients with that disease respond to a discontinuous administration (usually 3 subcutaneous injections per day), and the IGF1 level is normalized in 50 percent of the cases. No long-term desensitization and no rebound phenomenon after drug withdrawal have been observed. Clinical improvement is obvious, even in cases with partial response to treatment. The dose required to obtain maximum response may vary from one patient to another, and resistance to the peptide has been observed in a few patients. This resistance does not seem to be related solely to the absence of somatostatin receptors on the tumours. The principal side-effect of octreotide treatment is the occurrence of gallstones. In some patients, continuous subcutaneous injection gives a better result with a lower dose. Other ways of administration (nasal or oral) have been tested or are being evaluated.

Acromegaly↗