Pegvisomant and cabergoline combination therapy in acromegaly.

Combination with cabergoline may offer additional benefits to acromegalic patients on pegvisomant monotherapy. We evaluated the safety and efficacy profile of this combination and investigated the determinants of response. An observational, retrospective, cross-sectional study. Fourteen acromegalic patients (9 females), who were partially resistant to somatostatin analogs and on pegvisomant monotherapy. Cabergoline was added because of the presence of persistent mildly increased IGF-I. The mean follow-up time was 18.3 ± 10.4 months. The efficacy and safety profile was assessed. The influence of clinical and biochemical characteristics on treatment efficacy was studied. IGF-I levels returned to normal in 4 patients (28%) at the end of the study. In addition, some decline in IGF-I levels was observed in a further 5 patients. The % IGF-I decreased from 158 ± 64% to 124 ± 44% (p = 0.001). The average change in IGF-I was -18 ± 27% (range -67 to +24%). Lower baseline IGF-I (p = 0.007), female gender (p = 0.013), lower body weight (p = 0.031), and higher prolactin (PRL) levels (p = 0.007) were associated with a better response to combination therapy. There were no significant severe adverse events. Significant tumour shrinkage was observed in 1 patient. Combination therapy with pegvisomant and cabergoline could provide better control of IGF-I in some patients with acromegaly. Baseline IGF-I levels, female gender, body weight, and PRL levels affect the response to this combination therapy.

Somatotroph tumor progression during pegvisomant therapy: a clinical and molecular study.

CONTEXT: There is concern that pegvisomant could be associated with a higher risk of tumor growth. The rate and possible determinants of this tumor growth are unknown. OBJECTIVE: The objective of the study was to investigate the clinical, immunohistological, and molecular factors conditioning tumor growth in patients taking pegvisomant. DESIGN AND SETTING: This was a cross-sectional study performed from 2004 to 2010 in four university hospitals in Spain. PATIENTS: Seventy-five acromegalic patients with active disease resistant to somatostatin analogs treated with pegvisomant were followed up for a mean of 29 ± 20 months. MAIN OUTCOME MEASURES: Magnetic resonance images before initiation of pegvisomant, at 6 months, and then yearly were examined in all patients. Immunohistological and molecular studies were performed in tumors that grew. RESULTS: A significant increase in tumor size was observed in five patients (6.7%). Absence of previous irradiation (P = 0.014) and shorter duration of prepegvisomant somatostatin analog therapy (P < 0.001) were associated with an increased risk of tumor growth. A stepwise multivariate linear regression analysis (R(2) = 0.334, P < 0.001) identified the duration of somatostatin analog therapy prior to pegvisomant (beta = -4.509, P = 0.014) as the only significant predictor of tumor growth. In those tumors that grew, GH expression and insulin receptor expression were higher (P = 0.033 in both cases) than in the control group. CONCLUSIONS: No previous radiotherapy, shorter duration of prepegvisomant somatostatin analog therapy, and higher tumor expression of GH and insulin receptor could be risk factors for tumor growth during pegvisomant therapy.

[Induction of labor with misoprostol]. / Inducción del trabajo de parto con misoprostol.

The results obtained with the induction of labor with a synthetic analogue of prostaglandin E1: misoprostol, are presented. We reviewed 149 cases of patients admitted to this hospital (The "Policlínico Escuela Eva Perón") for induction of labor throughout a 13-month period of time since 06/01/92 until 06/30/93. All patients had a medical indication for induction of labor, a single pregnancy, cephalic - vertex presentation, no previous surgical scars on uterus, no contraindications for vaginal delivery, Bishop score below 7, gestational age over 37 weeks, and a reactive NST (Non Stress Test). Misoprostol was used intravaginally in the posterior fornix, in one dose of 100 mcg. In those patients where the spontaneous rupture of membranes was not the cause of induction itself, these were artificially ruptured at the moment of admission if possible depending on obstetric conditions, or no longer than 2 hours afterward. All patients underwent continuous fetal hart rate monitoring, during the active phase of labor. There were no failures of induction since all patients reached the active phase of labor without using oxytocin. There was an extremely high percentage of vaginal deliveries being this figure 96.6%. Only 5 patients had to undergo a cesarean section, 2 because of arrest of labor and 3 because acute fetal distress. Four cases of acute intrauterine fetal distress were registered but none of them were caused by tachysystole or hypercontractility. The mean time from the beginning of induction to delivery was 5 hours and 20 minutes (+/- 2 hs, 40') 70.5% of patients giving birth before 6 hours since admittance.(ABSTRACT TRUNCATED AT 250 WORDS)