[Lymphocytic hypophysitis: a reality]. / Hypophysite lymphocytaire: une réalité.

Lymphocytic hypophysitis is a rare entity; we report here three cases. This condition usually occurs in women during pregnancy or in the post-partum period. Pituitary enlargement is associated with complete or partial hypopituitarism. The difficulty in diagnosis is well illustrated by our cases and results from the similarity between the clinical and biological signs of adenoma and hypophysitis. Circulating antipituitary antibodies are not constantly found and are nonspecific, evidence only of the autoimmune nature of hypophysitis. Thus the diagnosis has to be undertaken in all suspected cases in pregnant women or during the post-partum period. The clinical course may be very long, emphasizing the need for rigorous long-term observation. The pituitary gland is commonly enlarged and homogenous in lymphocytic hypophysitis, but in our third case the enlargement was heterogeneous with associated cyst formation. We suggest that the inflammatory process could have been maintained by the presence of cysts. Finally, corticosteroids are the therapy of choice in the inflammatory stage and should be undertaken as soon as the diagnosis has been established. Regular surveillance is required.

Pharmacokinetic study and effects on growth hormone secretion in healthy volunteers of the new somatostatin analogue BIM 23014.

We have studied the pharmacokinetics and the effects of BIM 23,014 (BIM), a new, long-acting octapeptide somatostatin analogue, on basal and stimulated GH secretion in normal men. BIM 250 micrograms sc significantly reduced a GHRH-induced increase in plasma GH. The continuous sc administration of BIM for 24 h dramatically blunted spontaneous GH secretion; 2000 and 3000 micrograms daily reduced GH secretion to a greater extent than 1000 micrograms daily. During these experiments a significant negative correlation (r - 0.66) was found between plasma GH and BIM levels. Acute sc administration of 1000 micrograms BIM significantly reduced the rise in plasma GH observed in the second part of the oral glucose tolerance test. Plasma BIM levels peaked around 30 min, and the elimination half life was 90 min. Plasma BIM levels were below 1 ng/ml 6 h after the injection of 1000 micrograms BIM, and at that time GH started to rise again. We conclude that BIM 23,014 250 to 1000 micrograms sc is able to reduce the plasma GH response to GHRH or to the fall in glucose following an oral glucose tolerance test; a constant infusion of BIM, in doses 1000 micrograms daily, dramatically suppresses spontaneous GH secretion; 2000 micrograms/day by chronic subcutaneous infusion was the most effective dose of BIM in the suppression of GH secretion, and was associated only with minor adverse effects.

Effects of the new somatostatin analogue (BIM 23014) on blood glucose homeostasis in normal men.

Changes in blood glucose homeostasis induced by the new somatostatin analogue BIM 23014 (BIM) were studied. Eight normal men (study 1) received either vehicle or 1000, 2000 and 3000 micrograms BIM as a 24 h s.c. infusion. Blood glucose, plasma insulin, C-peptide, glucagon and growth hormone (GH) were measured before treatment and then hourly for 24 h. In five normal men (study 2) an oral glucose tolerance test (OGTT) was performed during vehicle infusion and then on days 1 and 7 of a continuous s.c. infusion of 2000 micrograms BIM daily for 7 days. The same biological parameters as in study 1 were measured before OGTT and then twice-hourly for 5 h. Dose-dependent and transient glucose intolerance was observed in the first half of study 1. Except for glucagon, BIM significantly (P < 0.01) reduced plasma insulin, C-peptide and GH levels. In study 2 BIM infusion induced glucose intolerance and a drop in plasma insulin and C-peptide on day 1 which disappeared on day 7 of infusion. Higher on day 7 than on day 1, plasma GH secretion was significantly (P < 0.01) reduced throughout BIM infusion. In contrast plasma glucagon levels were not modified at any time. Side-effects were abdominal cramps and diarrhoea which were observed in most subjects when increasing BIM daily dose. In conclusion, BIM infusion induced transient changes in glucose homeostasis and insulin secretion in normal men. By contrast, plasma GH levels remained reduced throughout the treatment. BIM appears to be a useful tool to selectively inhibit GH secretion.

[Influence of dose and modalities of administration of BIM 23014 on growth hormone secretion in patients with acromegaly]. / Influence de la dose et des modalités d'administration du BIM 23014 sur la sécrétion d'hormone de croissance de l'acromégale.

Somatostatin analogs, with prolonged half-lives have been proposed for the treatment of acromegalics. The aim of the study was to evaluate the short term efficacy of different doses and modalities of administration of the new somatostatin analog, BIM 23014 (BIM), on GH secretion in acromegalics. Ten acromegalics, with evolutive disease, who previously had had transsphenoidal surgery (and pituitary radiotherapy in 8) were evaluated in a three step study. The first part included four patients who received in a random order either vehicle or 500, 1000 and 1500 micrograms BIM for a day as a continuous s.c. infusion using programmable pumps at one-week interval for 24 hours to measure plasma GH levels. The second part included six patients who received in a random order either vehicle or 1500 micrograms/24h BIM as 500 micrograms x 3 s.c. injections, 750 micrograms x 2 s.c. injections and a continuous s.c. infusion using programmable pumps at one-week interval. During each period of the study blood was sampled at 4 hour intervals for 24 hours in order to measure plasma GH and BIM levels by radioimmunoassays. The third part of the study included the same 6 patients as the second part, who received 30 mg IM of a long acting formulation of BIM. Blood was sampled before and thereafter on days 1, 3, 6, 9, 12, 15, 18 and 21 following the injection for measurement of plasma GH and BIM levels. In first group 500 micrograms BIM slightly decreased plasma GH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ovarian tumors located in the hilus. Analysis of 126 publications of the literature]. / Tumeurs ovariennes de siège hilaire. Analyse des 126 publications de la littérature.

One hundred and twenty six reported cases of ovarian tumors located in the hilus (OTLH) are analyzed. They represent a special sub group of ovarian steroid cell tumors (former "lipid cell tumors"). A number of these neoplasms are Leydig-Berger cell tumors (LBCT), which are characterized by the presence of the crystal of Reinke, a specific proteinaceous inclusion, whose detection may be improved by new available methods. Crystal-free steroid cell tumors located in the hilus are in most cases true leydigoma of the ovary whose features are indiscernible from LBCT's. They are revealed after years of evolution by signs of hyperandrogeny or post menopausal bleeding. Plasma testosterone levels are always elevated while urinary 17 keto steroid cytoplasmic values are normal in 50% of cases. Three main features distinguish ovarian tumors located in the hilus from others ovarian steroid cell tumors: the occurrence in aged women, the small size of the tumors, and the excellent prognosis.

Peripheral antiglucocorticoid action of RU 486 in man.

In order to evaluate the peripheral antiglucocorticoid activity of RU 486 in man we examined its ability to antagonize the effects of acutely administered glucocorticoids on blood leukocyte counts. The study was performed on eight normal male subjects. They were given 400 mg RU 486 (or placebo) orally at 0730 h and 1 mg dexamethasone (or placebo) orally at 0830 h, using a double-blind, cross-over, latin-square design with a one week interval between each of the four different treatments. Circulating eosinophils, lymphocytes, and neutrophils were counted at 0730 h and 1330 h, and their variations (1330 h counts/0730 h counts x 100) were compared under each treatment. For each cell type, dexamethasone induced variations (eosinophil and lymphocyte drop, neutrophil rise) which were significantly (P less than 0.05) different from those under the three other treatments; these latter treatments (placebo, RU 486, and RU 486 + dexamethasone) were equivalent to each other, inducing no variations of leucocyte counts. These data show that RU 486 inhibits dexamethasone induced leukocyte changes; this simple test provides a useful means to further analyse the peripheral antiglucocorticoid activity of RU 486 in man.

[Location of an insulinoma by transhepatic phlebography with staged insulin assays (author's transl)]. / Localisation d'un insulinome par phlébographie transhépatique avec dosages étagés de l'insulinémie.

Insulinoma was easily diagnosed in a 73-year-old woman who had organic hypoglycaemia associated with hyperinsulinism, but the tumour could not be located by echotomography and computerized tomography. The state of the patient's arteries precluded arteriography. Pancreatic phlebography was carried out by the portal transhepatic route and blood was collected at different levels for plasma insulin assays. A very high gradient at the pancreatic isthmus indicated the site of the tumour, which was found on surgery to be precisely there and could be enucleated. This technique cannot be used systematically to locate insulinomas, but it is unquestionably helpful when the tumour cannot be located by other methods or when these are contra-indicated.