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Biomedical subjects

G Sassolas

Publications and source records attributed to G Sassolas.

At least 55 records · Page 3Linked to original sources

[Idiopathic giant cell granulomas of the pituitary gland. Apropos of 2 cases].

Two cases are reported of two women who had developed progressive hypopituitarism without visual disturbances. Pituitary tumors were evoked by radiological findings. The patients underwent surgical removal of invasive intrasellar tumor by transphenoidal route. Giant-cell granuloma was histologically demonstrated with negative special staining for tuberculosis acid-fast bacilli, bacteria and fungi. Secondary granuloma due to tuberculosis, brucellosis or neurosarcoidosis was ruled out by serological grounds. The prognosis was discusses through a follow-up of 7 years in the first case and 7 months in the second one. The appropriately documented 31 cases collected from the literature were compared with our two cases.

Adult↗

Assay of growth hormone levels in human plasma using commercial kits: analysis of some factors influencing the results.

The reliability of growth hormone (GH) assays, performed in 39 different laboratories, using five different immunoassay kits was evaluated. It was found that the variability in GH levels measured by different commercial assay kits may be due to human factors, as well as differences between the kits. The influence of the variation in amount of circulating GH, during provocative testing and spontaneous secretory episodes, on the results of GH assay was also evaluated. It was found that large molecular weight forms of GH may be underestimated by some assay kits.

Child↗

Neurophysins as markers of vasopressin and oxytocin release. A study in carcinoma of the lung.

Vasopressin-neurophysin (hNpI), oxytocin-neurophysin (hNpII) and blood osmolality were assayed before any treatment in basal conditions in 35 patients suffering from lung carcinoma (20 oat cell, 6 undifferentiated and 9 well-differentiated epidermoid cell carcinomas). Plasma vasopressin (antidiuretic hormone, ADH) was also assayed in 7 of the 20 patients suffering from oat cell carcinoma. We found a close correlation (r = 0.98) between plasma ADH and hNpI levels in the 7 patients. Further, hNpI was elevated in 13 out of the 20 oat cell carcinoma patients and in none of the epidermoid-cell carcinoma group; however, searching for an abnormality of ADH secretion as reflected by a detectable plasma hNpI level together with subnormal plasma osmolality revealed 2 additional positive results in the oat cell carcinoma group, and 2 out of the 6 in the undifferentiated-cell carcinoma group. hNpII was increased together with an increase in hNpI in 6 oat cell carcinoma patients; it was specifically increased without hNpI increment in 2 additional oat cell carcinoma patients and in 2 patients of the undifferentiated-cell carcinoma group (different from the 2 positive for the hNpI-osmolality ratio). hNpI and hNpII were normal in the majority of undifferentiated and all of the differentiated epidermoid-cell carcinoma group. Hence, our results show that simultaneous measurements of hNpI, hNpII, and blood osmolality could detect abnormalities in 17 out of 20 oat cell carcinoma patients, in 4 of the 9 undifferentiated-cell carcinoma patients, but in none of the differentiated epidermoid-cell carcinoma patients, suggesting that the neurophysin assay can be used for the early detection of oat cell- and possibly other neuroendocrine-derived carcinomas.

Biomarkers, Tumor↗

Effects of a new prolactin inhibitor, CV 205-502, in the treatment of human macroprolactinomas.

The effects of a new PRL inhibitor, CV 205-502 (CV), on human macroprolactinomas were studied in nine patients according to a prospective protocol. Five patients had undergone surgery leaving tumor remnants and persistent hyperprolactinemia. The four others were de novo patients, two of whom had received short term treatment with Parlodel. Plasma PRL levels ranged from 235-6050 micrograms/L before treatment. The doses of CV used in this trial ranged from 0.075-0.600 mg. Plasma PRL normalized in eight of the nine patients during treatment with CV. The time to normalize varied from 2 weeks to 9 months, and the doses from 0.075-0.450 mg. A tumor volume reduction of more than 50% was obtained in all four patients who had not been operated on before CV treatment. Only one of the five patients with postoperative tumor remnants had no reduction in tumor size. The drug was generally well tolerated, and no patient interrupted the treatment. Slight and short-lasting gastrointestinal symptoms were noted in several patients, and a single episode of fainting occurred in one patient when the drug was not taken at bedtime as instructed. A noticeable and persistent weight loss with anorexia was noted in two patients. Since CV 205-502, administered in a single daily dose, has tolerable side-effects and is effective in reducing PRL secretion and tumor size, it can be considered to be a useful treatment for macroprolactinomas.

Adult↗

Long term effect of incremental doses of the somatostatin analog SMS 201-995 in 58 acromegalic patients. French SMS 201-995 approximately equal to Acromegaly Study Group.

Fifty-eight acromegalic patients were included in a multicenter prospective study of increasing doses (300-1500 micrograms) of SMS 201-995 (octreotide, Sandostatin) administered 3 times daily, sc, during 6 months to determine its effect on signs and symptoms of GH hypersecretion. Subsequently, 34 of the patients were maintained for 12-26 months on the minimal efficacious dose, determined from the previous dose-response study. Some adverse effects were frequently encountered, mostly at the initiation of treatment, and disappeared with time. Asymptomatic gallstones occurred in 5 patients. Minimal changes in carbohydrate tolerance, consisting of a rise in blood glucose and a transient decrease in plasma insulin level after meals, were noted. GH normalized in 22% of the patients, improved in 56%, and remained unchanged in 22% regardless of the dose. The optimal daily dose was 300 micrograms in 50% of the patients and 1500 micrograms in 20%. Pituitary tumor size reduction occurred in 47% of the patients harboring large tumors or tumor remnants. No additional improvement or escape from being controlled occurred with time. These data indicate that SMS 201-995 is an effective treatment for refractory acromegaly and for some de novo patients for whom surgical therapy is not advisable.

Acromegaly↗

Dose-effect study of intranasal administration of growth hormone-releasing hormone-44-NH2 in healthy subjects.

Intranasal (in) administration of GH-releasing hormone-40- (GHRH-40) has been demonstrated to be efficient in stimulating GH secretion at doses equal to or higher than 30 micrograms/kg in man. We performed a dose-response study with GHRH-44-NH2 (GHRH) given by nasal spray and closely monitored local tolerance. Twelve normal young men were given 5 GNRH doses (125, 250, 500, 750, and 1000 micrograms) and placebo in random order according to a latin square design. Mild symptoms of local intolerance, subjective, objective, or both, were noted in the first 20 min after spray in 30 of 72 tests, and a significant difference (P = 0.003) was obtained in their frequency between the group placebo plus the lowest dose and the group of the other doses. The areas under the GH curves were significantly different between the subjects and the doses (by analysis of variance, P = 0.001 and P = 0.025, respectively). Multiple comparison tests showed a significant difference between the 3 highest doses and the placebo (P = 0.005, P = 0.05, and P = 0.02, respectively) and a significant difference between the highest dose and the 2 lowest doses (P = 0.005). By weighted linear regression between GH areas under the curve and GHRH doses the dose-response relationship was established as: y = 1.226x + 457. The magnitude of the GH peaks induced by in GHRH was significantly lower than that induced by iv GHRH. We conclude that in the normal young men tested, who were high responders to GHRH (as demonstrated by iv test), a 500-micrograms dose is sufficient to elicit GH secretion. Local tolerance, although imperfect, appears satisfactory to permit a clinical trial in children.

Administration, Intranasal↗

[Normal and tumorous human gonadotropic cells].

Gonadotropic cells are scattered in the anterior and tuberal lobes and make up 10 to 20% of the anterior pituitary cells. Having a morphofunctional plasticity, they secrete FSH and LH, most often simultaneously. These hormones are stored together in the granulations. In addition, under the action of regulating factors, especially GnRH, the cells can secrete one hormone or the other, or even the alpha subunit. Gonadotropic adenomas range third in frequency among operated pituitary adenomas (12% in our series). The diagnosis is based on the presence of at least 5% of immunoreactive cells with specific antibodies to gonadotropic hormones. These adenomas are distributed into 3 major types: FSH-LH adenoma, the most frequent one, FSH adenoma and alpha-subunit adenoma. The LH adenoma and the beta FSH and beta LH adenomas are very rare. Tumoral gonadotropic cells lose their morphofunctional differentiation. They also lose, to an extent varying according to the cases, their control mechanisms as well as their capacity of synthesis and excretion of both subunits. The alpha subunit, the oldest one in ontogeny, remains the most often and longest-secreted substance. There is a continuum from the gonadotropic adenoma with high plasma gonadotropins levels to the non-functioning adenoma.

Adenoma↗

Experience of a six-month treatment with sandostatin at increasing doses in acromegaly.

The French Sandostatin/Acromegaly Study Group performed a multicentric, prospective, open-label trial of incremental doses with the aim of obtaining the best antisecretory effect. Forty-two patients (24 women, 18 men) aged 22-71 years were involved, either after unsuccessful surgery and/or radiotherapy (30 patients), or as primary treatment (12 patients). Doses were increased from 3 x 100 to 3 x 500 micrograms/day, according to the results of hormonal investigations (GH profiles and Sm-C) performed each month and for each dose, and tolerability. Four patients dropped out because of major digestive troubles. Recurrent pain at the injection site and minor gastrointestinal disorders were noted in some patients. Asymptomatic gallstones appeared in 4 patients. Carbohydrate tolerance and insulin secretion (determined by diurnal plasma glucose and insulin profiles) were not significantly altered by the various SMS doses. Clinical improvement was determined by the scoring of the symptoms. Mean plasma GH concentrations were significantly reduced for each SMS dose, compared to pretreatment values. Fifteen patients obtained 75% of GH values less than or equal to 2 micrograms/l. In 9 patients the highest dose failed to bring GH below 10 micrograms/l. Sm-C normalized in 17/31 patients. After 6 months of treatment a tumor reduction of 20-50% was found in 7 patients and greater than 50% in 5 patients. We conclude that (1) the tolerability of SMS is compatible with long-term treatments; (2) clinical improvement and biological criteria of efficacy are obtained in 3/4 acromegalic patients treated by SMS, and that (3) some patients are resistant to SMS and the increase in the dose does not improve the result.

Acromegaly↗

Effects of the somatostatin analog BIM 23014 on the secretion of growth hormone, thyrotropin, and digestive peptides in normal men.

BIM 23014 (BIM) is a long-acting octapeptide somatostatin analog. We studied the effects of this analog on the secretion of GH, TSH, and gastroenteropancreatic hormones [secretin, motilin, and pancreatic polypeptide (PP)] in normal men. In the first protocol three BIM doses (125, 250, and 500 micrograms) and vehicle were administered sc in random order at 2000 h to eight normal young men. Plasma GH concentrations decreased during the first part of the night only after the highest dose (P less than 0.05). Plasma secretin levels did not change, while plasma motilin decreased after the 250- and 500-micrograms doses (P = 0.05 and P = 0.02, respectively), and plasma PP decreased after all three doses (P less than 0.05, P less than 0.01, and P less than 0.01, respectively) during the first part of the night. In the second protocol, eight men received BIM, administered by constant sc infusion during the night in a dose of 2 mg/12 h, or vehicle, either alone or in association with a 10 ng/kg.min iv GHRH or vehicle infusion. Nocturnal GH secretion was suppressed by the BIM infusion (P less than 0.001). GH secretion, stimulated by GHRH infusion (P less than 0.001), was reduced by concomitant BIM infusion (P less than 0.001) and was pulsatile during the combined infusions. BIM infusion suppressed the physiological nighttime rise in plasma TSH levels. Plasma motilin and PP levels were reduced by BIM, when administered either alone or in combination with GHRH. We conclude that: 1) BIM is capable of reducing GH secretion when administered sc in a dose of 500 micrograms and of abolishing nocturnal GH secretion when constantly infused at a dose of 2 mg/12 h; 2) BIM, constantly infused, reduces the nocturnal rise in TSH secretion; and 3) motilin and PP secretion are more sensitive than that of GH to BIM, as they are reduced by a lower dose.

Adult↗

[Pituitary adenoma treated with a somatostatin analog].

We studied for over 7 months the use of SMS 201-995, in 1 woman with pituitary adenoma. Eight years after surgical and irradiation therapy, adenoma relapsed with hyperthyroidism (T4 L = 71pmol/l, TSH = 5.3 mU/l, subunit: 309 micrograms/l) and was complicated by meningitis. It was invasive and removed only partly. SMS therapy, 100 micrograms SC q 8 h, allowed partial reduction of clinical hyperthyroidism and decreased TSH and alpha subunit of 47%. Increased dosage and changing route of administration did not increase efficacy. A modest decrease of adenoma was probably caused by several reasons. In summary in an adenoma unusual by the extremely high value of alpha subunit in contrast with modest value of TSH, SMS therapy allowed partial control only.

Adenoma↗

The TSH secretion in the human pituitary adenomas.

TSH secretion by a pituitary tumor is very rare (2%) and it is often associated with another hormone: GH or PRL essentially. We present here nine tumors in which the TSH secretion was proved by immunocytochemistry (ICC) and by RIA in the tumor extracts, in the serum and in the culture medium. Four tumors secreted TSH only. Five tumors secreted TSH and GH predominantly. In 3 of them traces of other hormones (PRL and FSH) were also detected. The "pure" TSH adenomas were monomorphous with typical ultrastructural and immunocytochemical features. Plurihormonal TSH adenomas were bimorphous with different cells secreting GH and TSH or monomorphous with one type of cell which secreted TSH or GH or both TSH and GH. In a majority of the cases, the tumoral TSH secretion induced hyperthyroidism but in 2 patients with TSH adenoma there was euthyroidism and in another with TSH-GH adenoma there was no sign of acromegaly and GH serum levels were normal.

Adenoma↗

Plasma alpha-subunit levels during the treatment of pituitary adenomas with the somatostatin analog (SMS 201-995).

The effect os SMS 201-995 (Sandostatin), a long-acting somatostatin analog, on different types of pituitary adenomas including alpha-subunit elevation is illustrated in this report. Treatment induced a fall in hCG levels in a woman with a pituitary adenoma producing only alpha-subunit. In 3 acromegalic patients, there was only a partial drop in GH and alpha-hCG. The same effect was observed in a woman with menopausal FSH and LH levels. SMS reduced plasma TSH and alpha-hCG in a case of thyrotropic adenoma. Two patients exhibiting FSH- and alpha-hCG-secreting adenomas did not respond to acute administration of SMS 201-995. More patients have to be treated before a definitive statement can be made on the usefulness of somatostatin analogs in the management of different types of pituitary adenomas.

Adenoma↗

Gonadotropin-releasing hormone agonists are unsuccessful in reducing tumoral gonadotropin secretion in two patients with gonadotropin-secreting pituitary adenomas.

Whether GnRH agonist treatment leads to reduced gonadotropin secretion and tumor volume in patients with gonadotropin-secreting pituitary adenomas is controversial. We studied the effect of GnRH analog treatment in two such patients, one with a recurrent FSH- and LH-secreting pituitary adenoma (patient 1) and one with a recurrent FSH- and alpha-subunit-secreting pituitary adenoma (patient 2). Patient 1 was treated with 200 micrograms Buserelin daily for 65 days, and patient 2 received three injections of 3 mg [D-Trp6]-LHRH formulated in microcapsules at 21-day intervals. In both patients, plasma FSH, LH (RIA), and alpha-subunit concentrations increased initially and remained above the pretreatment values throughout the treatment period. Plasma LH, measured by immunoradiometric assay, remained well above the detection limit. Plasma bioactive LH and testosterone became undetectable in patient 2, but did not change in patient 1. In neither patient did pituitary tumor size (determined by computed tomographic scan) change during treatment. We conclude that 1) the overall effect of GnRH analogs in patients with gonadotroph cell adenomas is stimulation of gonadotropin release by the tumor, although LH release varies according to how plasma LH is measured, possibly related to the origin of the hormone (normal or tumor gonadotroph cells), and 2) GnRH analog treatment does not reduce tumor size.

Adenoma↗

[Hypothalamic insufficiency following irradiation. Late, subacute and curable dementia].

A 31 year-old patient suffered from a subacute and major dementia, sixty months after whole brain irradiation with 54 grays for a pinealoma. Clinical features and biological investigations led to a diagnosis of hypothalamic insufficiency. A dramatic clinical recovery followed therapy with hydrocortisone and thyroxine. An hypothalamic radionecrosis and a vascular mechanism are presumed.

Adult↗