Apoplexy of a pituitary macroadenoma with reversible third, fourth and sixth cranial nerve palsies following administration of hypothalamic releasing hormones: MR features.

Pituitary apoplexy in patients with pituitary macroadenomas can occur either spontaneously or following various interventions. We present a case of a 71-year-old woman who developed third, fourth, and sixth cranial nerve palsies following administration of the four hypothalamic releasing hormones for routine preoperative testing of pituitary function. The MR examination showed interval tumor growth with impression of the floor of the third ventricle. There were also changes in signal intensity characteristics of the mass, suggestive of intratumoral bleeding. A transsphenoidal surgery with subtotal resection of the pituitary adenoma was performed. Microscopical examination revealed large areas of necrosis and blood surrounded by adenomatous tissue. Third, fourth, and sixth cranial nerve palsies completely resolved within 4 months. We conclude that MR imaging is useful in the demonstration of pituitary apoplexy following preoperative stimulation tests, but we suggest that these tests should be abandoned in patients with pituitary macroadenomas.

Efectos de los agonistas de GnRH sobre la supresión hormonal, menstrual y endometrial en endometriosis. Revisión / Effects of GnRH agonists on hormonal supression menstrual and endometrial in endometriosis

La síntesis de análogos de hormona liberadora de gonadotropinas (GnRH) ha permitido manipular, de manera segura y eficaz, el estado hormonal de las mujeres con endometriosis y crear un estado hipoestrogénico reversible, que ocasiona reducción en los implantes endometriósicos y mejoría de la sintomatología, sin los efectos adversos que se observan con el danazol

Follicle cysts after menstrual versus midluteal administration of gonadotropin-releasing hormone analog in in vitro fertilization.

The incidence and behavior of follicle cysts after different timing of gonadotropin-releasing hormone analog (GnRH-a) administration was studied in 321 in vitro fertilization (IVF) cycles. Group M included 198 cycles in which GnRH-a was injected at menstruation. Of these, 171 (88.6%) were without cysts (group M1) and 27 (13.6%) with cysts (group M2). Group L comprised of 123 cycles in which GnRH-a was administered in the midluteal phase. Of them, 70 (56.9%) were without cystic finding (group L1), 19 (15.4%) with follicle cysts (group L2), and 34 cases (27.6%) with visible corpus luteum at the time of GnRH-a initiation (group L3). Both groups with follicle cysts demonstrated a higher luteinizing hormone peak and continuous elevated estradiol (E2) levels. In group M2, the E2 rise and the cysts persisted longer compared with group L2. Gonadotropin treatment was accordingly postponed until the cysts regressed spontaneously. Only two cases of group M2 required aspiration of the cysts. Follicle cyst formation is not related to the timing of GnRH-a administration and their occurrence did not have adverse effects on IVF outcome.

[Increased incidence of ovarian hyperstimulation syndrome following combined GnRH agonist/hMG therapy]. / Erhöhte Inzidenz des ovariellen Uberstimulationssyndroms nach kombinierter GnRH-Agonist/hMG-Therapie.

In the present paper we examined, whether the combined GnRH-agonist/hMG therapy implies an increased risk of the ovarian hyperstimulation syndrome (OHS). In a retrospective analysis, 525 GnRH-a/hMG cycles were compared with 643 cycles of hMG stimulation, which were simultaneously performed at the Department of Gynecology and Obstetrics of the University of Hamburg. Two different GnRH-agonists were used: Buserelin (Hoechst) given intranasally (410 cycles) and Triptorelin (Ferring) intramuscularly (115 cycles). The clinical results of hMG "only"-therapy revealed an OHS incidence of 7% for grade II and 0.2% for grade III. In contrast, significantly higher incidences were observed after GnRH-a/hMG treatment. In Buserelin/hMG cycles in 23% OHS grade II and in 1.0% OHS grade III occurred, in Triptorelin/hMG cycles in 40% OHS II and in 5.2% OHS III, respectively. The increased incidence of OHS correlated with higher ovarian estrogen production as well as a higher number of follicles following the GnRH-a/hMG stimulation. Furthermore, in GnRH-a/hMG cycles a prolonged duration of follicular maturation occurred due to an increase of the active phase; in addition the amount of hMG-ampoules needed for ovarian stimulation was higher. After GnRH-a/hMG treatment, an endogenous LH-surge was not detected, whereas in 34% of hMG stimulated cycles irregular LH-fluctuations were observed. There was a higher pregnancy rate in GnRH-a/hMG cycles (15%/525 cycles), as compared to hMG stimulation (8%/643 cycles), but the abortion rate was similar (23%, GnRH-a/hMG, versus 13%, hMG). The demonstration of an increased ovarian response leading to better pregnancy rates but also higher risks of OHS is well known from earlier data of hMG stimulation in patients with hypogonadotropic amenorrhoea (WHO group I). This implies that GnRH-agonist pre-treatment shows similar endocrine conditions in normogonadotropic patients.

Hypersensitivity reaction with intravenous GnRH after pulsatile subcutaneous GnRH treatment in male hypogonadotrophic hypogonadism.

Chronic pulsatile subcutaneous administration of low doses of gonadotrophin releasing hormone (GnRH) is an effective therapy for men with hypogonadotrophic hypogonadism. Hypersensitivity reactions to GnRH are rare. We wish to report hypersensitivity reactions with intravenous GnRH after low dose subcutaneous pulsatile GnRH treatment in two men with hypogonadotrophic hypogonadism due to suprasellar disease.

The theory and practice of ovulation induction with gonadotropin-releasing hormone.

Gonadotropin-releasing hormone therapy has undergone sufficient basic and clinical investigation as a tool for ovulation induction that it should now be considered a safe and effective infertility therapy for office practice. Nevertheless, there remains sufficient mystique about patient selection, optimal dosage and route of delivery, and apprehension on the part of both physicians and patients about cost and inconvenience of medication pumps that gonadotropin-releasing hormone therapy has not enjoyed the widespread acceptance it deserves. This article presents straightforward guidelines for therapy that are based on a detailed review of current literature, together with new information about evolving pump technologic characteristics, that should offer reassurance to the practitioner considering use of gonadotropin-releasing hormone therapy in her/his practice.

GnRH agonists in the treatment of endometriosis.

GnRH agonists, synthetic peptide analogs of GnRH, desensitize pituitary receptors for the native molecule, thus causing reversible hypogonadotropic hypogonadism. Numerous clinical studies have suggested that these compounds are efficacious in the treatment of endometriosis, but it is not clear whether they are superior to the other drugs used in treatment of this disease. The frequency of recurrence of pain symptoms at the end of treatment is high and the data on recovery of fertility are conflicting. Long-term administration of GnRH agonists is a safe and well tolerated treatment but its role in the management of endometriosis is still not well defined.

Urticaria associated with antigonadotropin-releasing hormone antibody in a female Kallman's syndrome patient being treated with long-term pulsatile gonadotropin-releasing hormone.

The administration of pulsatile gonadotropin-releasing hormone (GnRH) has received increasing attention as a method of inducing ovulation or initiating puberty. Few side effects have been reported, although urticarial allergic reactions have been reported in the male. An 18-year-old female with hypogonadotropic hypogonadism and anosmia due to lack of endogenous GnRH was treated for 230 days using subcutaneous GnRH in an attempt to induce physiologic puberty. Just before anticipated menarche, therapy was discontinued because of the appearance of an urticarial reaction at the injection site as well as at previous injection sites. The presence of immunoglobulin G (IgG) antibodies against GnRH were subsequently identified in the patient's serum. These results further confirm the potential for antibody production to this small natural peptide in the female not previously exposed to GnRH. Some practical considerations for this form of therapy are highlighted.

Treatment of prostatic cancer. Newer forms of androgen deprivation.

The hope of providing a safe alternative to bilateral orchiectomy for patients with prostatic cancer has spurred the development in recent years of various agents capable of reducing androgen level. Another reason for intensifying these efforts relates to the hope held by many clinicians that earlier initiation of androgen deprivation for patients with regional or distant metastases will improve the patient's course. Finally, attempts to provide a more complete androgen blockade hold the hope of delaying or preventing relapse, which usually occurs with continued androgen deprivation.

Pituitary stimulation by combined administration of four hypothalamic releasing hormones in normal men and patients.

Ten normal young men (22-28 yr of age), within 10% of their ideal body weight, were given the four releasing hormones (TRH, 200 micrograms; GnRH, 100 micrograms; ovine corticotropin-releasing hormone, 50 micrograms; GH-releasing hormone, 80 micrograms) iv on separate days and then in combination on the same day. Plasma TSH, PRL, FSH, LH, cortisol, ACTH, and GH were measured by RIA in samples collected from 20 min before to 120 min after injection. There were no significant differences in responses to the separate and combined tests for FSH, LH, cortisol, ACTH, and GH. The plasma TSH (0.001 less than P less than 0.01) and PRL (P less than 0.001) responses were significantly higher after the combined test. The tolerance was identical to that of TRH alone. In eight patients studied after pituitary surgery, combined administration provided results comparable to those obtained after separate administration of TRH, GnRH, and insulin.

Ovarian hyperstimulation with exogenous pulsatile gonadotropin releasing hormone therapy.

Two cases are reported of women with hypothalamic amenorrhea who had sonographic and biochemical evidence of ovarian hyperstimulation during the first cycle of exogenous pulsatile gonadotropin releasing hormone (GnRH) therapy. In one case, it was demonstrated that, with early detection, decrease in the dosage of GnRH may stabilize the condition and prevent further progression of the hyperstimulation. Therefore, the authors suggest that sonographic monitoring should be performed at least in the initial ovulatory cycle so that adjustment of the dosage of GnRH can be made with early detection of hyperstimulation.

Ovarian hyperstimulation due to long-term pulsatile intravenous GnRH treatment.

Pulsatile long-term gonadotropin releasing hormone (GnRH) therapy with an average dosage of 8 micrograms/pulse i.v. in intervals of 90 min induced in a patient with hypothalamic amenorrhea the development of multiple ovarian cysts as visualized by ultrasonography. Estradiol (E2) plasma concentration reached values of 5000 pg/ml. These findings indicate that pulsatile GnRH application can induce ovarian hyperstimulation.