[Evaluation of the hypothalamo-hypopituitary axis after long-term inhalation corticotherapy for nasal polyposis]. / Evaluation de l'axe hypothalamo-hypophysaire après corticothérapie inhalée de longue durée pour polypose naso-sinusienne.

OBJECTIVE: To assess the hypothalamic-pituitary-adrenal (HPA) axis after long-term intranasal corticosteroid treatment in nasal polyposis. PATIENTS AND METHODS: A short synacthen test was performed in 24 patients who received the highest dose of inhaled beclomethasone among a population of 392 patients treated for nasal polyposis with inhaled corticosteroid therapy and short-term oral corticosteroids. RESULTS: Mean yearly dose of oral prednisone administered in short-term treatment was 371 mg/year. The amount of short-term oral prednisone decreased during the treatment. Mean daily dose of inhaled beclomethasone was 2861 micrograms/day, decreasing during treatment. Morning plasma cortisol was normal in all patients before and after stimulation (163 +/- 44 and 1 +/- 60 micrograms/ml respectively). Nolomethasone dose and plasma cortisol level before or after stimulation. DISCUSSION: The high dose of inhaled beclomethasone used to treat nasal polyposis does not affect the HPA axis. Some authors in the literature contest the validity of short synacthen test to detect HPA axis suppression. This test does however detect severe impairments of the HPA axis in outpatients.

Monthly intravenous pulse cyclophosphamide therapy in Wegener's granulomatosis.

OBJECTIVE: To study the long term effects of monthly intravenous cyclophosphamide therapy in Wegener's granulomatosis. METHODS: Fourteen consecutive patients with active Wegener's granulomatos treated with a first-line combination of high-dose prednisone and monthly intravenous pulse cyclophosphamide were retrospectively studied. RESULTS: One patient died from septicemia complicating severe leukopenia after the first pulse. At 8 months after instituting intravenous pulse cyclophosphamide therapy, failure was observed in 6 other patients. Between month 16 and 18, 2 other patients relapsed when the time between 2 pulses was lengthened. Five patients developed cyclophosphamide-related side-effects: infection (n = 2), amenorrhea (n = 1), alopecia (n = 2) and vomiting (n = 2). Except for one fatal infection, no major side-effect of intravenous cyclophosphamide therapy was observed. At the end of the study, all patients were off intravenous cyclophosphamide therapy with more than 6 months of followup. The 6 responders were in remission on low-dose prednisone or without treatment. CONCLUSION: A combination of high-dose prednisone and intravenous cyclophosphamide may achieve long-term remission in 42% of patients with Wegener's granulomatosis. Responders to intravenous cyclophosphamide therapy had less extensive disease than non-responders.

Urogenital manifestations of Wegener granulomatosis.

We report 8 patients with Wegener granulomatosis (WG) who suffered from symptomatic urogenital involvement including acute urinary retention related to prostatitis, orchitis, ureteral stenosis, bladder pseudotumor, and penile ulceration. Urogenital manifestations occurred as an isolated manifestation of WG in 4 patients, at the onset of the disease in 1 patient, and as the only symptom of relapse in 3. Data used to distinguish specific WG involvement from infection or cyclophosphamide urothelial toxicity are discussed. Four patients needed a surgical procedure consisting of suprapubic cystostomy for acute urinary retention, bilateral ureteral double J stents for bilateral ureteral stenosis, and prostate transurethral resection. Urogenital symptoms promptly resolved with medical therapy. High-dose corticosteroids and immunosuppressive drugs should be used as first-line therapy to avoid unnecessary surgery.

Endocrine, paracrine and autocrine control of follicular development.

Development of a single follicle during the menstrual cycle is under control of hormones stimulating follicular maturation, ovulation and luteogenesis. Several factors intervene locally to prevent other follicles from developing at the same time as dominant follicle. These other follicles remain quiescent or evaluate to atresia. Atresia results from the action of several endocrine, paracrine and autocrine mechanisms which synergistically inhibit aromatase activity. The subsequent lack of estrogens reduces granulosa cell multiplication. The oocyte will not become fertilizable before the preovulatory peak of LH, after the resumption of meiosis and after reaching metaphase of the second meiotic division. Several factors are involved in the inhibition of spontaneous resumption of meiosis: cyclic nucleotides, sex steroids, somatostatin and oocyte maturation inhibitor(s) (OMI). Ovulation is related to breakdown of connective tissue synthesized by granulosa cells under the influence of FSH. Connective tissue lysis is dependent on proteolytic enzymes which are released and activated by FSH, LH and relaxin. A paracrine control could be involved in ovulation: LH induces the production of prostaglandin and relaxin by theca cells which, in turn, stimulate collagenase and proteoglycanase secretion by granulosa cells.

[Indications and results of pituitary radiotherapy after microsurgery in acromegaly. 15 cases]. / Indications et résultats de la radiothérapie hypophysaire après microchirurgie dans l'acromégalie. Quinze cas.

The present treatment of acromegaly consists of selective adenomectomy followed, when unsuccessful, by pituitary gland irradiation. Fifteen acromegalic patients were evaluated after adenomectomy, then radiotherapy. Growth hormone assays were performed after carbohydrate load and administration of thyroid stimulating hormone. Somatomedins were measured by radiocompetition using the vector protein. Cure was obtained with adenomectomy alone in 3 of the 15 patients (mean follow-up 39 months). The remaining 12 patients were all cured by subsequent irradiation at the cost of pituitary insufficiency in one-third of them. Post-surgical cure of acromegaly can only be asserted from range of strict criteria. The best indicators of persisting activity are high levels of growth hormone and/or somatomedins. A solitary somatotropic dysregulation does not necessarily herald a relapse.

[Endocrine, paracrine and autocrine mechanisms involved in follicular development]. / Mécanismes endocriniens, paracrines et autocrines du développement folliculaire.

Development of a single follicle during the menstrual cycle is under control of hormones stimulating follicular maturation, ovulation and luteogenesis. Several factors intervene locally to avoid other follicles developing at the same time as the dominant follicle. These other follicles remain quiescent or go on to atresia. Atresia results from the action of several endocrine, paracrine and autocrine mechanisms which synergistically inhibit aromatase activity. The subsequent lack of oestrogens reduces granulosa cell multiplication. The oocyte will not become fertilizable before the preovulatory peak of LH, after the resumption of meiosis and after reaching the metaphase of the second meiotic division. Several factors are involved in this inhibition of spontaneous resumption of meiosis: cyclic nucleotides, sex steroids, somatostatin, oocyte maturation inhibitor(s) (OMI). Ovulation is related to breakdown of connective tissue synthesized by granulosa cells under the influence of FSH. Connective tissue lysis is dependent on proteolytic enzymes which are released and activated by FSH, LH and relaxin. A paracrine control could be involved in ovulation: LH induces the production of prostaglandin and relaxin by theca cells which, in turn, stimulate collagenase and proteoglycanase secretion by granulosa cells.

[Influence of gonadotropins on inhibin secretion]. / Influence des gonadotrophines sur la sécrétion d'inhibine.

Inhibin is produced by Sertoli cells in the male and by granulosa cells in the female. Follicular-stimulating hormone acts directly to stimulate production whereas luteinizing hormone exerts an indirect effect by stimulating production of androgens which themselves activate synthesis and release of inhibin. Prolactin has no effect on inhibin. These interpretations, derived from numerous in vivo and in vitro studies, explain why inhibin is not secreted in the hypophysectomized animal. Interruption of spermatogenesis by ligature of deferens canals, by experimental cryptorchidism in the rat, and in human primary azoospermias, provokes a reduction in production of inhibin and an increased secretion of FSH. The second must be the consequence of the first. Restoration of normal spermatogenesis results in normal production of inhibin. Biochemical mechanisms linking spermatogenesis and inhibin production are still unknown.

[Precocious pseudo-puberty due to HCG-secreting androblastoma of the ovary. One case (author's transl)]. / Pseudo-puberté précoce par androblastome ovarien avec sécrétion d'alpha et de bêta HCG. Une observation.

A case of ovarian androblastoma (arrhenoblastoma) of the intermediate differentiation type in a 5-year old girl is reported. The clinical features were precocious isosexual puberty with secondary masculinization. The tumour was removed but relapsed 26 months later, requiring ovariectomy and salpingectomy. The patient, who has now been followed up for 7 years and 6 months, is definitely cured. Biochemically, the androblastoma was accompanied by high plasma levels of oestrogens, androgens and, quite exceptionally, human chorionic ganodotropin, alpha HCG and beta HCG. Light and electron microscope examination failed to differentiale Sertoli cells from granulosa cells and Leyding cells from luteinized ovarian stroma cells. Areas resembling syncytiotrophoblastic cells were very limited and could not be seen under the electron microscope. Some cells looked like undifferentiated germ cells. The HCG secreted was biologically active on rabbit ovaries (Reiprich's reaction) but inactive on the girl's contralateral ovary, which was found on two biopsies to be unstimulated and prepubertal.