Shrinking of a growth hormone-producing pituitary tumor by continuous subcutaneous infusion of the somatostatin analog SMS 201-995.

SMS 201-995, a long-acting somatostatin analog, was given as the initial treatment to an acromegalic patient. SMS 201-995 (200 micrograms, sc, three times daily) reduced, but did not normalize, serum GH levels. Complete and prolonged control of GH secretion was obtained with a 600-micrograms daily continuous sc infusion (CSI), and the patient was treated in this way for 6 months. Rapid improvement of clinical signs and symptoms of acromegaly occurred, as did major tumor shrinkage. The other pituitary functions did not change. After 6 months, the daily SMS 201-995 dose was progressively reduced; GH secretion remained suppressed. After 12 months of treatment, GH secretion was controlled with a CSI of 100 micrograms SMS 201-995 daily, but not with two daily sc 100-micrograms injections. Further significant reduction in tumor size occurred. We conclude that CSI of SMS 201-995 resulted in constant GH normalization and marked clinical and morphological improvement. This form of treatment should be considered as an alternative to ablative treatment of acromegaly.

Paradoxical ovarian stimulations in the use of LHRH analogs.

In the case of in vitro fertilization, LHRH analogs are used to induce a hypophysial blockage before the phase of stimulation, via administration of exogenous gonadotropin. During in vitro fertilization attempts using LHRH analogs, the blockage is controlled after 14 days of treatment by measuring plasmatic estradiol and by pelvic ultrasonography. In this retrospective study, which concerned 1075 in vitro fertilization cycles, a paradoxical ovarian stimulation with LHRH analogs was observed in 93 cases (8.7%) with high estradiol levels and follicular growth (detected by ultrasonography), in spite of low FSH and LH levels. In 4 cases, a follicular puncture was performed, which made it possible to collect oocytes from which embryos were obtained, thus confirming the observed follicular growth and maturation. The most probable hypothesis explaining this phenomenon seems to be direct ovarian stimulation effectuated in vivo by LHRH analogs. This stimulation is only observed in certain patients, and, more frequently it seems, with certain LHRH analogs, which is probably due to a variation in the expression of ovarian LHRH receptors.

Paradoxical ovarian stimulations in the use of LHRH analogs.

In the case of in vitro fertilization, LHRH analogs are used to induce an hypophysary blockage, before the phase of stimulation, via administration of exogenous gonadotropin. During in vitro fertilization attempts using LHRH analogs, the blockage is controlled after 14 days of treatment through measurement of the plasmatic estradiol and pelvic ultra-sonography. In this retrospective study, which concerned 1075 in vitro fertilization cycles, a paradoxical ovarian stimulation with LHRH analogs was observed in 93 cases (8.7%), with high estradiol levels and follicular growth (detected by ultra-sonography), in spite of low FSH and LH levels. In 4 cases, a follicular puncture was performed, which allowed to collect oocytes from which embryos were obtained, thus confirming the observed follicular growth and maturation. The most probable hypothesis explaining this phenomenon seems to be a direct ovarian stimulation, effectuated in vivo by LHRH analogs. This stimulation is only observed in certain patients, and apparently more frequently, with certain LHRH analogs, probably through a variation in the expression of ovarian LHRH receptors.