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Biomedical subjects

P Chanson

Publications and source records attributed to P Chanson.

At least 91 records · Page 5Linked to original sources
PubMed1993

Octreotide therapy for thyroid-stimulating hormone-secreting pituitary adenomas. A follow-up of 52 patients.

OBJECTIVE: To evaluate the efficacy of octreotide in the treatment of pituitary thyroid-stimulating hormone (TSH)-secreting adenomas. DATA SOURCES: Combination of review and original data. Review data included information supplied by Sandoz Pharmaceuticals from patient case report forms and information from abstracts and articles published in the French or English language between 1987 and 1991. Original data included follow-up data on 15 of 37 previously reported cases and data on 15 new cases provided by 11 investigators. STUDY SELECTION: Fifty-two cases from 24 medical centers in nine countries reported between 1987 and 1991. DATA EXTRACTION: Chief clinical characteristics of the patients; dose and duration of octreotide treatment; serum TSH, thyroid hormone, and free alpha-subunit levels before and during treatment; serial anatomic evaluation of the pituitary gland by either computed tomographic scanning or magnetic resonance imaging; and side effects. DATA SYNTHESIS: After the first octreotide dose (50 to 100 micrograms), TSH levels decreased in all but 2 patients (mean decrease for the whole group, 55.8% +/- 27%). Levels of alpha-subunit decreased in 15 of the 19 patients who had alpha-subunit assessments (mean decrease, 37.5% +/- 24%). Reduction of TSH levels after short-term treatment (50 or 100 micrograms two or three times daily) was observed in 30 to 33 patients (mean decrease, 74.1%). Thyroid hormone levels were reduced in all patients and returned to normal in 73%. Despite an initial response to therapy, thyroid hormone levels continued to rise ("true escape") in 2 patients receiving short-term therapy and in 3 patients receiving long-term therapy. Partial shrinkage of the adenoma occurred in 11 patients. CONCLUSIONS: Octreotide is an effective treatment for TSH-secreting adenomas. Thyroid-stimulating hormone levels almost always decreased, and thyroid hormone levels reverted to normal in about three quarters of patients. Partial tumor shrinkage was observed in one third of patients receiving long-term octreotide treatment.

Adenoma↗
PubMed1993

[Diabetic thoracoabdominal neuropathy. Clinical and electrophysiological study with evaluation of the autonomic nervous system].

We report on eight patients with diabetic thoracoabdominal neuropathy in whom careful evaluation of peripheral and autonomic nervous system function was performed. All patients had non insulin-dependent diabetes mellitus of 10.5 +/- 6.7 years mean (+/- SD) known duration with poor glycemic control. Thoracic (n = 7) or abdominal (n = 1) pain of sudden onset involved several adjacent dermatomal segments and was bilateral and asymmetrical in 7/8 patients. Four patients had hypoesthesia in the painful zone and six presented with significant weight loss (6.2 +/- 4.3 kg) which reversed after the relief of pain. Truncal electromyogram was abnormal in 7/7 patients. Nerve damage was not limited to thoracic nerves since electrophysiological studies evidenced distal polyneuropathy in all patients. The autonomic nervous system was also involved. Sympathetic skin response was abnormal in 7/7 patients and autonomic cardiovascular function tests demonstrated cardiac denervation in 5/5 patients. In 4/4 patients a marked relief of pain was noted within one week with amitriptyline treatment. This report confirms the characteristic clinical presentation of diabetic thoracoabdominal neuropathy. Moreover, it suggests that this neuropathy is part of a diffuse damage that also involves peripheral nerves of the limbs and autonomic nervous system.

Abdominal Pain↗
PubMed1993

Inhibin and follicle-stimulating hormone levels in gonadotroph adenomas: evidence of a positive correlation with tumour volume in men.

OBJECTIVE: Gonadotroph adenomas are generally revealed by symptoms of mass effect at the stage of macroadenoma. Most of them hypersecrete FSH and/or gonadotrophin subunits. Rarely they hypersecrete LH, which could induce endocrinological symptoms. As the glycoprotein inhibin is secreted by the gonads under FSH control, we have evaluated whether high immunoreactive inhibin (iINH) levels correlated with FSH hypersecretion and whether iINH and FSH levels were related to tumour volume in subjects with gonadotroph adenomas. PATIENTS: Forty-five patients (30 men, 15 women) were retrospectively selected on the basis of immunostaining technique using specific antibodies raised against FSH-beta, LH-beta and glycoprotein alpha-subunit. MEASUREMENTS: Immunoreactive inhibin (iINH) was measured by radioimmunoassay using antiserum 1989 raised to bovine inhibin. Tumour volume index was the product in cm3 of length, width and height of the adenoma as assessed by computerized tomography. RESULTS: In men (age 21-61 years), iINH levels were positively correlated with FSH levels (Spearman's r = 0.67, P < 0.001), and both iINH and FSH levels were significantly correlated with tumour volume index (Spearman's r = 0.38, P < 0.05 and r = 0.39, P < 0.05 respectively). In the subgroup of men with normal FSH levels (n = 17), the correlation of FSH with tumour volume index was high: Spearman's r = 0.56, P < 0.05. In the post-menopausal women (n = 8, age > 55 years), iINH levels were undetectable or below the follicular phase range regardless of FSH values. In the premenopausal women (n = 7, age 22-49 years, follicular phase or amenorrhoea) iINH levels were above follicular phase range in three women including one who had very high FSH levels. CONCLUSIONS: These data show that in men with gonadotroph adenoma FSH levels are related to tumour mass and suggest that a significant part of circulating FSH in patients with normal FSH levels arises from the tumour. The significant correlation between iINH and FSH levels demonstrates that tumoral FSH is bioactive and that high iINH levels do not exert any feedback control on tumoral FSH secretion. Therefore the coexistence of high FSH levels with high iINH levels is strongly suggestive of a gonadotroph adenoma. Gonadotroph adenomas seem to represent a unique model of long-term FSH stimulation of inhibin-producing cells, in some way analogous to that created by repetitive administration of exogenous FSH.

Adenoma↗
PubMed1993

Somatostatin receptors, adenylate cyclase activity, and growth hormone (GH) response to octreotide in GH-secreting adenomas.

To determine the cellular mechanism(s) of the variability in GH responsiveness to octreotide in acromegaly, somatostatin (SRIH) receptor status was studied in 37 GH-secreting adenomas. SRIH receptor binding was always present in all GH-secreting adenomas either in membrane preparations (Exp A; n = 17) or by quantitative autoradiography (Exp B; n = 20). In membranes, maximal binding capacities ranged from 83-2331 fmol/mg protein; affinity was in the nanomolar range (Kd, 1.3 +/- 0.2 nmol/L). By quantitative autoradiography, SRIH-14 and octreotide were equally active in displacing [125I]SRIH binding in tumors (Spearman correlation rho = 0.92). IC50 values ranged from 3-22 nmol/L (mean +/- SE, 8.0 +/- 1.3 nmol/L). In Exp A, basal adenylate cyclase (AC) activity was high in 7 tumors (841 +/- 306 pmol/L cAMP x 30 min/mg protein) compared to that in the other 10 (252 +/- 92 pmol/L cAMP x 30 min/mg protein). In these 7 tumors, GH-releasing hormone (0.1 mumol/L) stimulation of AC was lower (53 +/- 11% vs. 297 +/- 48%), whereas SRIH (1 mumol/L) inhibition was higher (52 +/- 5% vs. 34 +/- 5%). Similar results were obtained with Exp B tumors. In both experiments, no correlation was apparent between SRIH-binding capacity and inhibition of AC. In Exp B, a variable decrease in mean plasma GH levels was observed (> or = 80% in 5 patients, between 50-80% in 8 patients, and < or = 50% in 5 patients) after a single sc injection of octreotide (100 micrograms). A modest correlation was found between the GH response to octreotide and SRIH-binding capacity (rho = 0.48) or SRIH inhibition of AC (rho = 0.61). The IC50 values to displace SRIH binding were lower in poorly responsive patients than in highly responsive ones (IC50, 4.6 +/- 1.9 and 13.9 +/- 2.7 nmol/L, respectively). These data indicate that an absence of SRIH receptors cannot account for the weak response to SRIH therapy in 20-30% of acromegalic patients. Alternatively, the weak correlation between either SRIH binding or SRIH inhibition of AC with octreotide inhibition of plasma GH levels might reflect the heterogeneity of SRIH receptor subtypes in GH-secreting adenomas.

Adenoma↗
PubMed1993

Non-responsiveness of serum gonadotropins and testosterone to pulsatile GnRH in hemochromatosis suggesting a pituitary defect.

We investigated the potential pituitary origin of gonadal insufficiency in hemochromatosis. Gonadotropin secretion was studied in seven patients with hemochromatosis and hypogonadism, before and after chronic pulsatile GnRH therapy. Pulsatile LH secretion was studied before (sampling every 10 min for 6 h) and after 15-30 days of chronic pulsatile GnRH therapy (10-12 micrograms per pulse). Prior to GnRH therapy, all the patients had low serum testosterone, FSH and LH levels. LH secretion was non-pulsatile in four patients, while a single pulse was detected in the remaining three. Chronic pulsatile GnRH administration did not increase serum testosterone levels; similarly, serum LH levels remained low: neither pulse frequency nor pulse amplitude was modified. We conclude that hypogonadism in hemochromatosis is due to pituitary lesions.

Adolescent↗
PubMed1993

Hyperfunctioning unilateral adrenal macronodule in three patients with Cushing's disease: hormonal and imaging characterization.

We aimed to investigate the dynamics of adrenocorticotropin (ACTH) and cortisol secretion in pituitary-dependent Cushing's syndrome with bilateral macronodular adrenal hyperplasia presenting as a single adrenal macronodule, and to determine the imaging characteristics of this syndrome. Three female patients were studied. Plasma ACTH and serum cortisol secretion were studied by determining their rhythmicity and pulsatility and their responses to the administration of ovine corticotropin-releasing factor, thyrotropin-releasing hormone, metyrapone, tetracosactrin, insulin and dexamethasone. Techniques used to localize the anatomical lesion were bilateral simultaneous inferior petrosal sinus sampling, magnetic resonance examination of the pituitary, computed tomography (CT) scanning and [75Se]cholesterol scintigraphy of the adrenal glands. Plasma ACTH and serum cortisol levels were measured using a commercial radioimmunoassay and an immunoradiometric assay. The ACTH and cortisol pulse number and amplitude were calculated using established computer software. In all three patients ACTH and cortisol secretory dynamics fulfilled the requirements for diagnosis of pituitary-dependent Cushing's syndrome. A close relationship between ACTH and cortisol pulses also favored a pituitary dependency. Study of the amplitude of cortisol pulses classified two patients in the group of hypopulsatile Cushing's disease. Adrenal CT scanning demonstrated the presence of a large single nodule. [75Se]Cholesterol scintigraphy showed bilateral radionuclide uptake, although mostly localized over the adrenal nodule. All patients underwent successful trans-sphenoidal hypophysectomy. Over a period of 1 year, a slow shrinkage of the adrenal nodule was observed in two patients, while no change in volume was observed in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1993

Clinical pharmacokinetics of octreotide. Therapeutic applications in patients with pituitary tumours.

Among somatostatin analogues, octreotide is the most extensively studied. Its pharmacodynamic properties are similar to those of somatostatin, with a wide spectrum of inhibitory effects on anterior pituitary function, pancreas and gut endocrine secretions, and gastrointestinal functions. Compared with the somatostatin, octreotide is highly resistant to enzymatic degradation and has a prolonged plasma half-life of about 100 minutes in humans, allowing its use in the long term treatment of various pathological conditions. Differential effects of octreotide on endocrine secretions such as growth hormone (GH) and insulin in healthy volunteers, as well as variable efficacy in the treatment of endocrine tumours, may relate to the distribution of somatostatin receptor subtypes. The volume of distribution of octreotide ranges from 18 to 30L. Calculated serum distribution half-life ranges from 72 to 98 minutes. In blood, octreotide is mainly distributed in the plasma, 65% being bound to lipoproteins. After subcutaneous injection, absorption appears rapid and complete and bioavailability is about 100%. Mean peak plasma concentrations are between 2 and 4 micrograms/L in patients receiving 50 to 100 micrograms. Peak concentrations are reached within 20 to 30 minutes and are 20 to 40% of corresponding values after intravenous injection. Peak concentrations and values for areas under the plasma concentration-time curve linearly correlate with the dosage. The elimination half-life is about 90 to 110 minutes. Total clearance in healthy individuals is about 160 ml/min (9.6 L/h). Hepatic metabolism of octreotide is extensive (30 to 40%) and about 11 to 20% of the dose is excreted unchanged in the urine. Among pituitary tumours, GH- and thyrotrophin-secreting adenomas are the most sensitive to octreotide. Octreotide has been widely used in the treatment of acromegaly. 50 to 80% of the patients respond to daily multiple subcutaneous injections with insulin-like growth factor-1 (IGF1) levels being normalised in about 40 to 50% of them. Neither desensitisation with long term therapy nor rebound phenomena after octreotide withdrawal have been noticed in these studies. Even in patients with partial response, clinical symptoms improved. Octreotide daily dosages needed to achieve optimum responses may vary greatly from one patient to another. In a minority of patients complete resistance to octreotide was observed and was not always related to the absence of somatostatin receptors in the tumour. The wide spectrum of effects of octreotide in humans accounts for adverse effects seen during long term treatment, primarily cholelithiasis. Other modes of administration are efficient.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1992

[Diabetes in elderly subjects].

Problems raised by diabetes in subjects above 65 years of age are of three kinds: diagnostic, therapeutic and social. Passed the age of 40, there is a regular physiological increase of glycaemia, and this must be taken into account to diagnose diabetes and to set the threshold for therapeutic intervention. The treatment of elderly people has its specific imperatives, due to feeding habits and age-related changes in hepatic and renal functions. The presence of complications, sometimes multiple, explains that the patient often takes several drugs, which increases the risk of interaction between these drugs and oral antidiabetics. The therapeutic objectives must be adjusted to these imperatives, and neither the diabetic... nor his doctor must be afraid of insulin. The social status of elderly patients must not be neglected: the help of private nurses and the training in diabetology of the patient's entourage often permit to postpone the date of institutionalization.

Aged↗
PubMed1992

Treatment of thyroid-stimulating hormone-secreting adenomas with octreotide.

From data collected in the literature, the effects of octreotide therapy in 37 patients with thyroid-stimulating hormone (TSH)-secreting adenomas who received short-term (1 to 2 weeks, n = 23) and long-term treatment (3 to 36 months) are reviewed. In 20 of 21 patients studied, short-term administration of octreotide (50 or 100 micrograms subcutaneously [SC] produced a 25% to 100% (mean +/- SD, 55.3% +/- 29%) decrease in TSH levels, with the nadir being obtained between the third and sixth hour following injection. After 1 to 2 weeks therapy with 50 to 100 micrograms twice or three times a day, 21 of 23 patients studied demonstrated a 66% (+/- 30%) decrease in TSH levels and 14 of 16 showed a 64% (+/- 27%) decrease in alpha-subunit levels. In approximately two thirds of the patients, the response was better than after short-term administration. The effect of octreotide on clinical and biological thyroid status was significant in all patients studied. After 1 week or 1 month of treatment, thyroid hormone levels were reduced in all patients and were normalized in 78%. Response to therapy was similar whether TSH secretion was pure or mixed (growth hormone [GH]-TSH adenomas). Fourteen patients received long-term treatment (3 to 36 months; mean, 12 +/- 10) with daily doses ranging from 200 to 1,500 micrograms. The response was better than or similar to that with short-term treatment. An escape occurred in TSH levels in two patients and in thyroid hormone levels in three patients, leading to an adjustment of dose or frequency of injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1992

Effects of octreotide on lipid metabolism in acromegaly.

Hypertriglyceridemia is the most frequent modification of lipid metabolism observed in acromegaly. The somatostatin analog, octreotide (Sandostatin), widely used in the treatment of acromegaly, is able to produce a decrease in levels of growth hormone (GH), insulin, and Insulin-like Growth Factor 1 (IGF1). We have attempted to evaluate the influence of this treatment on the lipid status of acromegalic patients. Seventeen patients with active acromegaly were treated with octreotide, 100 to 500 micrograms/injection subcutaneously three times daily. The levels of fasting serum triglycerides (TG), total cholesterol, High Density Lipoprotein (HDL) cholesterol and IGF1, as well as mean plasma GH and insulin levels during a diurnal profile, were evaluated before and after three months of octreotide therapy. GH, insulin and IGF1 decreased by 61%, 42% and 36% respectively (p less than 0.05). Mean levels (+/- SEM) of TG and total cholesterol fell from 2.2 +/- 0.4 mmol/l to 1.6 +/- 0.3 mmol/l (p less than 0.05) and 6.4 +/- 0.39 mmol/l to 5.6 +/- 0.27 mmol/l (p greater than 0.05), respectively. There was no correlation between triglyceride decrease and hormonal changes or clinical status (BMI, age, sex). In conclusion, the administration of octreotide over a three month period to acromegalic patients is associated with a decrease in TG levels.

Acromegaly↗
PubMed1992

Resistance to somatostatin (SRIH) analog therapy in acromegaly. Re-evaluation of the correlation between the SRIH receptor status of the pituitary tumor and the in vivo inhibition of GH secretion in response to SRIH analog.

The development of a long-acting somatostatin (SRIH) analog (octreotide, Sandoz) has been a major breakthrough in the treatment of acromegaly. However, in 20-30% of the patients, growth hormone (GH) plasma levels remain elevated (> 10 micrograms/l) despite treatment with octreotide. This raised the concept of resistance to SRIH analog therapy in acromegaly. Indeed, in vivo response to SRIH analogs varies greatly among acromegalic patients. According to the reviews in the literature and our own autoradiographic data, no direct correlation can be established between the GH response to octreotide and the number or affinity of the SRIH receptors located on the tumor. In our series a greater density of SRIH receptors is present on tumors from patients very sensitive to the SRIH agonist. A subset of patients resistant to octreotide could result from a very low density of SRIH receptor although this type of GH-secreting tumor constitutes certainly a rare case. A subset of GH-secreting pituitary tumors can be characterized by a mutation on the alpha subunit of the guanine nucleotide-dependent protein coupled to the stimulation of adenylate cyclase (G alpha s). This mutation results in a high basal adenylate cyclase activity and a low GHRH-stimulated activity. However, when the adenomas are separated according to their basal adenylate cyclase activity, SRIH is able to decrease cAMP levels in both types of tumor. In addition, in our series no direct correlation is observed between the SRIH inhibition of adenylate cyclase and the amount of SRIH-binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1992

Growth hormone and insulin-like growth factor-I stimulate hormonal function and proliferation of thymic epithelial cells.

We have investigated the role of GH and insulin-like growth factor-I (IGF-I) in controlling the secretion of thymulin, a hormone produced by thymic epithelial cells (TEC). Thymulin plasma concentrations (mean +/- SD) were increased in 21 patients with acromegaly compared to those in 30 controls, as assessed by bioassay (4.24 +/- 0.97 vs. 2.67 +/- 0.87; P less than 0.001) and RIA (561 +/- 241 vs. 315 +/- 113 pg/L; P less than 0.01). Good correlations were observed between plasma levels of thymulin and IGF-I (P less than 0.001). In vitro experiments demonstrated that both recombinant human GH and IGF-I significantly increased thymulin production in culture supernatants of normal human TEC and a rat TEC line. In parallel, IGF-I also significantly stimulated the proliferation of human TEC, as measured by bromodeoxyuridine incorporation. Additionally, the stimulatory effect of GH on thymulin production was abrogated by both an anti-IGF-I antibody and an anti-IGF-I receptor antibody. These results support a role for GH and IGF-I in the control of thymic hormonal function in man and suggest that the effect of GH may be mediated by local secretion of IGF-I within the thymus.

Acromegaly↗
PubMed1992

Lipoprotein(a) in diabetic patients with and without chronic renal failure.

OBJECTIVE: To examine the distribution of Lp(a) plasma levels in patients with IDDM and NIDDM, and in nondiabetic and IDDM patients with chronic renal failure. RESEARCH DESIGN AND METHODS: Cross-sectional study of Lp(a) plasma levels in a population of diabetic patients with stable metabolic control, with simultaneous determination of plasma lipids, fasting plasma glucose, and HbA1. Thirty-six patients with IDDM, 90 with NIDDM, and 41 with chronic renal failure (20 IDDM, 21 nondiabetic) were compared with 78 control subjects. RESULTS: Lp(a) plasma levels were significantly higher in IDDM and NIDDM patients, as well as in nondiabetic and IDDM patients with chronic renal failure compared with control subjects. No correlation was observed between Lp(a) and lipid plasma levels, fasting plasma glucose, and HbA1. CONCLUSIONS: Lp(a) may contribute to the increased prevalence of atherosclerotic disease in diabetic patients and patients with chronic renal failure, especially in IDDM patients whose lipoprotein pattern was not different from that of the control group.

Adult↗
PubMed1991

Effect of the new dopaminergic agonist CV 205-502 on plasma prolactin levels and tumour size in bromocriptine-resistant prolactinomas.

Bromocriptine is currently and successfully used for the treatment of pituitary prolactinomas. However, bromocriptine appears unable to normalize plasma prolactin levels in about 10% and to reduce tumour size in one-third of cases. The lack of normalization of plasma prolactin levels in spite of a daily dose of bromocriptine equal to or higher than 15 mg suggests a bromocriptine resistance. We compared the long-term effects of bromocriptine and CV 205-502 (a non-ergot derivative D2 dopamine agonist) on plasma prolactin levels and tumour size in seven bromocriptine-resistant prolactinomas. Bromocriptine reduced significantly (P less than 0.001) plasma prolactin levels (from 2307 +/- 518 to 568 +/- 279 micrograms/l) (conversion to Sl units: 1 microgram/l = 20 mU/l). Visual field defects observed in five patients improved in four. However, CT scan analysis showed a decrease in tumour size in only three patients. Except for transient and minor side-effects at the beginning of the treatment, CV 205-502 was well tolerated in five of seven patients. In the remaining two patients nausea and vertigo occurred with high dosages of CV 205-502 and it was necessary to reduce the daily dose. CV 205-502 lowered plasma prolactin to levels similar to those obtained after bromocriptine therapy in four cases. In the three remaining patients, CV 205-502 was more potent than bromocriptine as demonstrated by the further 90% reduction in plasma levels obtained in one case and by the normalization of plasma prolactin levels in the two other cases. One woman became pregnant during CV 205-502 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Shrinkage of a primary thyrotropin-secreting pituitary adenoma treated with the long-acting somatostatin analogue octreotide (SMS 201-995).

The long-acting somatostatin agonist octreotide can control TSH hypersecretion from most thyrotropic adenomas. Octreotide therapy has even been shown to improve chiasmal dysfunction. We report another patient in whom octreotide therapy was associated with gradual suppression of TSH hypersecretion, which escaped partially, dramatic and very rapid and sustained improvement of chiasm compression, and dramatic and sustained shrinkage of an unresectable TSH-secreting pituitary tumour. Unusual and prolonged gastrointestinal adverse reactions eventually disappeared except for steatorrhea. In conclusion, octreotide may be considered as first line treatment in patients with unresectable thyrotropic adenomas.

Adenoma↗