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Biomedical subjects

P Caron

Publications and source records attributed to P Caron.

At least 55 records · Page 3Linked to original sources

Three year follow-up of acromegalic patients treated with intramuscular slow-release lanreotide.

Somatostatin analogs are an alternative treatment to pituitary surgery and radiotherapy in acromegalic patients. Recently, a depot long-lasting formulation of slow release (SR) lanreotide has been shown to be effective in the short-term control of GH hypersecretion in acromegalic patients. We report the long-term follow-up of a cohort of 22 acromegalic patients treated with SR lanreotide during 1-3 yr. Thirteen females and 9 males, age 51 +/- 3 yr, presented with macroadenomas (n = 12), microadenomas (n = 8), or empty sella (n = 2). Seven patients previously had undergone a partial surgical removal of their adenomas, and 21 of them had mean plasma GH levels less than 5 micrograms/L during a previous octreotide treatment. According to GH values recorded after 3 months of twice monthly 30 mg SR lanreotide im injection, SR lanreotide was administered every 14 days (n = 13) or every 10 days (n = 9). At the 6-month visit, mean GH values were 5 micrograms/L or less in 68% and 2.5 micrograms/L or less in 27% of patients, and these results remained unchanged during the 1-3 yr follow-up period. During SR lanreotide treatment, the mean insulin-like growth factor I (IGF-I) concentrations remained in the normal range in 63% of patients. No escape from the treatment occurred in any of the cases. A significant decrease of the pituitary tumor volume was observed in 3 (13%) patients. The main side effect consisted of minor digestive problems during 48 h after each injection and was reported by 13 patients. Biannual gallbladder echographies revealed the occurrence of gallstones in 4 (18%) patients. In conclusion, these data confirm the efficacy and the tolerance of the long-term SR lanreotide administration (30 mg im every 10-14 days) in the control of acromegaly.

Acromegaly↗

Expression of somatostatin receptor SST4 in human placenta and absence of octreotide effect on human placental growth hormone concentration during pregnancy.

In pregnancy, the human placenta GH acts as a growth-promoting hormone and appears to be the main stimulator of insulin-like growth factor I (IGF-I) secretion. In a woman with a TSH-secreting macroadenoma, successful treatment with the somatostatin analog octreotide was conducted during the first month and the second half of pregnancy without side-effects on placental and fetal development. As observed in normal pregnancy, both serum placental GH and IGF-I levels increased throughout pregnancy and dropped sharply after delivery. In placental membranes from both treated and healthy untreated patients, we demonstrated the presence of high affinity binding sites for somatostatin-14 (Kd, 4.6 and 5.3 nmol/L; binding capacity, 1.53 and 1.35 pmol/mg protein, respectively). These receptors displayed low affinity for octreotide (IC50, 1.2-2 mumol/L), suggesting the presence of SST1 and/or SST4 receptors. We found that messenger ribonucleic acids of these two subtypes were expressed in both human placental tissue and purified human cytotrophoblast cells. Finally, the SST1-selective analog, des-AA1,2,5[D-Trp8,IAmp9]S-14 had low affinity for placental somatostatin receptors. These results argue in favor of the presence of the SST4 subtype in human placenta. At the doses administered, octreotide did not bind to placental somatostatin receptors. Our results may explain the absence of changes in both human placental GH and IGF-I concentrations that we observed during octreotide treatment.

Adenoma↗

Interest of routine measurement of serum calcitonin: study in a large series of thyroidectomized patients. The French Medullary Study Group.

The aim of our study was to assess the ability of routine calcitonin (CT) measurement to improve the preoperative diagnosis of medullary thyroid carcinoma (MTC) in nodular thyroid diseases. We systematically determined basal CT in 1167 patients before thyroid surgery and performed a pentagastrin (Pg) CT stimulation test in 121 of these patients whose basal CT level was normal. Sixteen MTC (1.37%) were found on histopathological examination of surgical specimens: 14 in the 34 patients (41.1%) with abnormal basal CT levels and 2 in the 1133 patients with normal basal CT levels (0.17%). An abnormal increase in Pg-stimulated CT was observed in 7 of the 121 patients tested and was related to microscopic MTC in 2 cases. Among 1167 thyroidectomized patients with nodular thyroid diseases, the prevalence of MTC was 1.37% and reached 41.1% when the basal CT level was abnormal (3% of the patients). CT evaluation detected MTC, whereas other procedures, such as fine needle aspiration cytology, failed, thus allowing early radical surgery. CT measurement should thus become a routine part of the diagnostic evaluation of nodular thyroid diseases.

Adolescent↗

Thyroid volume and urinary iodine in European schoolchildren: standardization of values for assessment of iodine deficiency.

Up to 1992, most European countries used to be moderately to severely iodine deficient. The present study aimed at evaluating possible changes in the status of iodine nutrition in 12 European countries during the past few years. Thyroid volume was measured by ultrasonography in 7599 schoolchildren aged 7-15 years in one to fifteen sites in The Netherlands. Belgium, Luxemburg, France, Germany, Austria, Italy, Poland, the Czech and Slovak Republics, Hungary and Romania. The concentrations of urinary iodine were measured in 5709 of them. A mobile unit (ThyroMobil van) equipped with a sonographic device and facilities for the collection of urine samples visited all sites in the 12 countries. All ultrasounds and all urinary iodine assays were performed by the same investigators. The status of iodine nutrition in schoolchildren has markedly improved in many European countries and is presently normal in The Netherlands, France and Slovakia. It remains unchanged in other countries such as Belgium. There is an inverse relationship between urinary iodine and thyroid volume in schoolchildren in Europe. Goiter occurs as soon as the urinary iodine is below a critical threshold of 10 micrograms/dl. Its prevalence is up to 10 to 40% in some remote European areas. This work produced updated recommendations for the normal volume of the thyroid measured by ultrasonography as a function of age, sex and body surface area in iodine-replete schoolchildren in Europe. This study proposes a method for a standardized evaluation of iodine nutrition on a continental basis, which could be used in other continents.

Adolescent↗

Osteoporotic vertebral fractures in a man under high-dose inhaled glucocorticoid therapy. A case-report with a review of the literature.

A 65-year-old man had surgery in June 1995 for femoral neuralgia. The plain films of the spine were normal at the time. In September of the same year, when he was beginning to walk gradually longer distances, he started experiencing back pain. Crush fractures of T8 and L2 were seen on plain films. His pain worsened, and he was admitted in December 1995. A third set of plain films disclosed fractures of all the vertebral bodies from T8 through L5, with increased density of the endplates of the same vertebras. Serum and urinary levels of calcium and phosphate were normal. Dual-energy X-ray absorptiometry demonstrated osteoporosis predominating in the trabecular bone. Evidence of increased bone resorption was seen on the histomorphometric study. Large amounts of dihydroxypyridinoline were found in the urine. Investigations for the classical causes of osteoporosis in males were unrewarding. Careful questioning revealed that the patient had been taking inhaled beclomethasone for seven years to treat chronic obstructive lung disease. Serum levels of cortisol and ACTH were low, consistent with a diagnosis of treatment-induced hypercorticism. To our knowledge, this is the first reported case of osteoporotic vertebral fractures in a male due to inhaled glucocorticoid therapy. Inhaled glucocorticoids are generally believed to induce only minimal systemic effects. However, decreased serum osteocalcin levels and increased urinary excretion of bone resorption markers have been reported in patients under inhaled beclomethasone therapy. Low spinal bone mineral density values correlated with the degree of pituitary-adrenal gland suppression as evaluated using the ACTH test have also been found in several groups of patients treated with inhaled glucocorticoids.

Administration, Inhalation↗

Successful pregnancy in an infertile woman with a thyrotropin-secreting macroadenoma treated with somatostatin analog (octreotide).

Somatostatin analogs are an alternative medical treatment in patients with TSH-secreting pituitary adenoma. A 31-yr-old infertile woman with a TSH-secreting macroadenoma was treated with continuous sc infusion of 300 micrograms octreotide/day. After 3 months, euthyroid status was restored, and pituitary magnetic resonance imaging showed a reduction of the macroadenoma. Subsequently, the patient was found to be pregnant, and octreotide was stopped after 1 month of gestation. Serum TSH and free thyroid hormone concentrations returned to pretreatment values. At 6 months of pregnancy, a visual field examination was abnormal, and a magnetic resonance imaging scan showed an enlargement of the pituitary adenoma. Reinstitution of octreotide treatment was associated with normalization of TSH and free thyroid hormone concentrations, a rapid improvement of visual fields, and a new reduction in the size of pituitary macroadenoma. Octreotide treatment was continued until an elective cesarean section was performed at 8 months gestation. Despite the presence of immunoreactive octreotide in the umbilical cord, neonatal thyroid parameters were normal, and a physiological rise in TSH with the increase in thyroid hormone concentrations occurred in the neonate. In conclusion, 1) octreotide treatment is effective in controlling TSH-secreting macroadenoma during pregnancy; 2) despite the transplacental passage of immunoreactive octreotide, physiological changes in thyroid parameters occur in the neonate, and 3) exposure of the fetus to octreotide during the first month as well as the last trimester of gestation did not induce any malformation or affect fetal development.

Adenoma↗

Expression of the cell death-inducing gene bax in carcinomas developed from the follicular cells of the thyroid gland.

The expression of apoptosis-regulating proteins, Bcl-2, Bax, Mcl-1, and Bcl-X, was evaluated by immunohistochemical methods in 39 cases of thyroid carcinomas. Normal thyroid tissues showed a consistent expression of Bcl-2 and Mcl-1 whereas Bax and Bcl-X proteins were essentially absent from most follicular thyroid cells. Bax expression was observed in all papillary carcinomas (n = 23) and in 8 of 10 follicular carcinomas. The intensity of Bcl-2 immunostaining was generally higher in follicular tumors (n = 10) than in papillary carcinomas (n = 21 of 23). However, in undifferentiated tumors, both Bax and Bcl-2 were weakly expressed. Mcl-1 protein expression was similar to that of Bax in papillary and follicular tumors, but was also frequently detectable in undifferentiated tumors. Bcl-X immunostaining was seen in all undifferentiated tumors (n = 6), in 22 of 23 papillary tumors, and in 5 of 10 follicular tumors. Our findings show that the regulation of bcl-2 family gene expression is different in normal thyroid tissue compared to that of its neoplastic counterpart and varies with the tumor subtype. In particular, unlike normal thyroid epithelium, the apoptosis-blocking gene bcl-X and the apoptosis-inducing gene bax are frequently expressed in thyroid carcinomas derived from the follicular cells. Thus, alterations in the expression of these bcl-2 family genes may contribute to the pathogenesis of thyroid carcinomas.

Adenocarcinoma, Follicular↗

C618R mutation in exon 10 of the RET proto-oncogene in a kindred with multiple endocrine neoplasia type 2A and Hirschsprung's disease.

The cosegregation of multiple endocrine neoplasia (MEN) type 2A with Hirschsprung's disease (HSCR), two diseases associated with mutation of the RET proto-oncogene, is infrequent. A 30-yr-old man was referred for screening of MEN 2A. Surgery for HSCR was performed at 4 yr of age. Basal and pentagastrin-stimulated calcitonin levels were abnormal. Histological examination of the thyroid confirmed bilateral medullary thyroid carcinoma. Screening of family members revealed six subjects with medullary thyroid carcinoma or abnormal pentagastrin-stimulated calcitonin test; one had an unilateral pheochromocytoma and two were affected with HSCR. DNA sequence analysis showed a heterozygote C618R mutation in exon 10 of the RET proto-oncogene in the proband and his mother, as well as in second-degree relatives with MEN 2A phenotype or HSCR. In this study, we report on a novel kindred with MEN 2A and HSCR phenotype associated with a point mutation (C618R) in one of the cysteine codons at the extracellular domain of the RET proto-oncogene.

Adult↗

[Bcl-2 proto-oncogene expression in neoplastic and non neoplastic thyroid tissue].

bcl-2 protein which protects cells from apoptosis is found to be expressed in several neoplastic and non neoplastic tissues. bcl-2 is consistently expressed in normal thyroid tissue but the regulation of its expression in thyroid tumors derived from the follicular cells remains to be discovered. In this study, we have assessed bcl-2 expression in different samples of non neoplastic and neoplastic thyroid tissues. Sixteen papillary carcinomas (including four papillary carcinomas of follicular variant), eight follicular carcinomas and five undifferentiated carcinomas were selected for this study. The tissues were routinely fixed and paraffin embedded. Four cases of normal thyroid tissue, four cases of Hashimoto's thyroiditis and five cases of thyroid tissue with Graves' disease were also investigated. Immunohistochemistry was performed with an anti-bcl-2 monoclonal antibody on paraffin sections. bcl-2 was highly expressed in normal follicular cells but also in follicles of Hashimoto's thyroiditis and Graves' disease while its expression appeared to be downregulated in papillary (14 cases on 16), in follicular (five cases on eight) and undifferentiated (five cases on five) carcinomas. However, in five carcinoma cases (one papillary, one papillary follicular variant, three of follicular type), bcl-2 expression was similar or higher than in normal tissue. The highest expression of bcl-2 was observed in one case of follicular carcinoma with large amounts of atypical cells. bcl-2 protein seems to play a more important role in non-neoplastic thyroid cells rather than in carcinoma cells. The heterogeneity of its expression in thyroid neoplasms opens the question as to whether bcl-2 detection could serve as a prognostic factor in such tumors. This question could be answered on large series of cases with concomitant analysis of clinical data.

Apoptosis↗

[Iodine consumption in France. National results of the Thyromobile project in a population of schoolchildren aged 6-14 years].

The "Thyromobile" project was initiated to update information on iodine supply in school-children aged 6-14 years in Europe. It involved 4 places in France: Lorraine, Rhône-Alpes, Languedoc-Roussillon, Midi-Pyrénées. Schools of the three former places had been investigated in 1986 during the Mornex's study whereas in the latter they had never been investigated in the past. With a mobile unit, all children (n = 1522) had a thyroid echography performed by the same trained investigator, and urinary iodine concentration was determined in 1458 of them. The mean +/- SD of urinary iodine concentration was 13.0 +/- 7.4 micrograms/dl, but 38% of urinary iodine concentrations were below 10 micrograms/dl and 10% were under 5 micrograms/dl. The prevalence of goitre was 4.1% in boys and 3.1% in girls. There was a negative correlation between urinary iodine concentration and thyroid volume (p < 0.001). Therefore, the results of the "Thyromobile" project show that the places, investigated in France, are not in an area of endemic goitre due to iodine deficiency. However, other epidemiological studies must be done to provide further information about iodine supply in all parts of France.

Adolescent↗

[Effects of amiodarone on thyroid function].

Amiodarone has been used in cardiology for more than 20 years as an anti-angina and anti-arrhythmia agent. In the seventies, variations in thyroid hormone and TSH concentrations were described in treated patients. Only recently, however the pathogenic mechanisms leading to dysthyroidism in long-term treatment have been described. Today, the gravity of amiodarone-induced hyperthyroidism has been greatly reduced due to a better understanding of the underlying mechanisms and better surveillance of thyroid function. In clinical practice, the following attitude can be proposed. Thyroid exploration should be completed before prescribing amiodarone: clinical examination should emphasize personal or familial history in search of dysthyroidism or goitre; hormone assays (TSH, free T4) are needed to eliminate any latent thyroid dysfunction, particularly hyperthyroidism with little or no clinical manifestation but sometimes the causal factor in cardiac symptomatology; search for a significant level of anti-thyroperoxidase antibodies can reveal underlying chronic thyroiditis. After prescription, clinical surveillance and TSH assay should be performed at 3 months then every 6 months during treatment. After withdrawal, surveillance should be continued with check-ups at 6 and 12 months.

Amiodarone↗

Intramuscular injections of slow-release lanreotide (BIM 23014) in acromegalic patients previously treated with continuous subcutaneous infusion of octreotide (SMS 201-995).

Nine acromegalic patients (five females and four males), mean age 50 +/- 4 years, presented macroadenomas (N = 7), microadenoma (N = 1) or normal computed tomography scans (N = 1). Patients were treated with continuous subcutaneous infusion of octreotide (range 200-600 micrograms/day). Following a washout period of 7 days, the patients were injected im with 30 mg slow-release lanreotide every 10 days for the first month and then twice monthly. In case of elevated growth hormone (GH) levels at 3 months, the patients were injected every 10 days for the next three months. Plasma GH and insulin-like growth factor I (IGH-I) decreased in all patients during octreotide treatment. After 6 months of octreotide treatment, seven patients were considered as well controlled (mean 8 h GH < 5 micrograms/l, IGF-I normal) whereas in two patients the mean 8-h GH and/or IGF-I levels remained increased. Serum GH and IGH-I increased after octreotide withdrawal. In one patient, serum GH and IGF-I increased during slow-release lanreotide administration and injections were stopped after 45 days. After 3 months of lanreotide, three patients were well controlled while in five patients GH or IGF-I levels were not normalized. At 6 months, five patients were injected twice monthly and three patients had one injection every 10 days. Six patients were well controlled and in two patients the mean 8-h GH level remained increased. The pituitary tumor volume decreased by 20-30% in two patients during octreotide, as well as in one other during slow-release lanreotide therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

[Use of a gonadoliberin agonist with or without gonadoliberin pulses for ovulation induction in ovarian dystrophies].

OBJECTIVES: Determine whether ovulation in dystrophic ovaries treated with GnRH agonist followed by GnRH pulses is due to the GnRH pulse or is patient-dependent. SITE. Endocrinology department, CHU Purpan, Toulouse, France. METHODS: Fifteen infertile patients, age range 22 to 35 years, with ovarian dystrophy were given GnRH agonist (Decapeptyl, 3.75 mg IM on day 3 of the cycle). In 5 patients, an IV pulse of GnRH was then given (6 micrograms/90 min). STATISTICAL ANALYSIS: Mann-Whitney U test, corrected chi 2 test. RESULTS: Ovulation was achieved in 8/15 cases (3/5 with and 5/10 without pulsatile GnRH p = NS) and 3 pregnancies (without pulsatile GnRH). Before treatment LH was higher in patients who had an ovulation. CONCLUSION: Ovulation can be achieved after GnRH agonist treatment in patients with dystrophic ovaries, with or without pulsatile GnRH, particularly if the initial LH levels are high.

Adult↗

[Hyperthyroidism caused by inappropriate secretion of TSH. Apropos of 2 new cases].

Hyperthyroidism due to inappropriate secretion of TSH is rare. It may be due to either TSH-secreting pituitary adenomas (n = 15) or selective pituitary resistance to thyroid hormone action (n = 31). The recognition of these patients is of great clinical importance since they should be treated differently than patients with more common forms of hyperthyroidism (Graves' disease, autonomous thyroid nodule).

Adult↗

Cutaneous metastasis from follicular carcinoma of the thyroid gland.

A 65-year-old man with a history of malignant melanoma presented a reddish nodule on the left temporal region of the scalp. Histologic features and immunoperoxidase staining on the skin biopsy specimen confirmed the diagnosis of metastatic thyroid follicular carcinoma. The patient presented recurrences of metastatic skin nodules, lung and bone metastases, and died after a 3-year follow-up.

Adenocarcinoma, Follicular↗